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1. Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

Author: Delmas, Gilles, Delmas, Gilles, Watthanaworawit, Wanitda, McLean, Alistair, Arya, Ann, Reyes, Ann, Li, Xue, Miotto, Olivo, Soe, Kyaw, Ashley, Elizabeth, Dondorp, Arjen, White, Nicholas, Day, Nicholas, Anderson, Tim, Imwong, Mallika, Nosten, Francois, Smithuis, Frank, Thu, Aung, Phyo, Aung, Pateekhum, Chanapat, Rae, Jade, Landier, Jordi, Parker, Daniel, Delmas, Gilles, Delmas, Gilles, Watthanaworawit, Wanitda, McLean, Alistair, Arya, Ann, Reyes, Ann, Li, Xue, Miotto, Olivo, Soe, Kyaw, Ashley, Elizabeth, Dondorp, Arjen, White, Nicholas, Day, Nicholas, Anderson, Tim, Imwong, Mallika, Nosten, Francois, Smithuis, Frank, Thu, Aung, Phyo, Aung, Pateekhum, Chanapat, Rae, Jade, Landier, Jordi, and Parker, Daniel
Abstract: BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.
Published: 2024

2. Exploring the feasibility of introducing triple artemisinin-based combination therapy in the malaria treatment policy in Vietnam

Author: Cao, Van Anh Thi, Nguyen, Thieu Quang, Le Quyen, Duong, Boon, Wouter P C, Moors, Ellen H M, Dondorp, Arjen M, de Haan, Freek, Amaratunga, Chanaki, Cao, Van Anh Thi, Nguyen, Thieu Quang, Le Quyen, Duong, Boon, Wouter P C, Moors, Ellen H M, Dondorp, Arjen M, de Haan, Freek, and Amaratunga, Chanaki
Abstract: BACKGROUND: This study investigates the processes regarding changing malaria treatment policies in Vietnam. Moreover, it explores the feasibility of introducing triple artemisinin-based combination therapy (TACT) in Vietnam to support the national malaria control and elimination plan.METHODS: Data were collected via 12 in-depth interviews with key stakeholders, combined with a review of policy documents.RESULTS: TACT is considered as a useful backup strategy in case future treatment failures with current artemisinin-based combination therapy (ACT) would occur. Moreover, TACT is also considered as a promising strategy to prevent the re-establishment of malaria. However, regulatory procedures and implementation timelines for TACT were expected to be lengthy. Therefore, strategies to engage national decision-makers, regulators, and suppliers should be initiated soon, stipulating the benefits of TACT deployment. In Vietnam, a procedure to apply for an import permit without registration that has previously been applied to the introduction of artesunate-pyronaridine was proposed to accelerate the introduction of TACT. Global-level support through the World Health Organization recommendations and prequalification were considered critical for supporting the introduction of TACT in Vietnam.CONCLUSIONS: Appropriate approach strategies and early stakeholder engagement will be needed to accelerate the introduction of TACT in Vietnam.
Published: 2023

3. The impact of anti-malarial markets on artemisinin resistance: perspectives from Burkina Faso

Author: Guissou, Rosemonde M., Amaratunga, Chanaki, de Haan, Freek, Tou, Fatoumata, Cheah, Phaik Yeong, Yerbanga, R. Serge, Moors, Ellen H.M., Dhorda, Mehul, Tindana, Paulina, Boon, Wouter P.C., Dondorp, Arjen M., Ouédraogo, Jean Bosco, Guissou, Rosemonde M., Amaratunga, Chanaki, de Haan, Freek, Tou, Fatoumata, Cheah, Phaik Yeong, Yerbanga, R. Serge, Moors, Ellen H.M., Dhorda, Mehul, Tindana, Paulina, Boon, Wouter P.C., Dondorp, Arjen M., and Ouédraogo, Jean Bosco
Abstract: Background: Widespread artemisinin resistance in Africa could be catastrophic when drawing parallels with the failure of chloroquine in the 1970s and 1980s. This article explores the role of anti-malarial market characteristics in the emergence and spread of arteminisin resistance in African countries, drawing on perspectives from Burkina Faso. Methods: Data were collected through in-depth interviews and focus group discussions. A representative sample of national policy makers, regulators, public and private sector wholesalers, retailers, clinicians, nurses, and community members were purposively sampled. Additional information was also sought via review of policy publications and grey literature on anti-malarial policies and deployment practices in Burkina Faso. Results: Thirty seven in-depth interviews and 6 focus group discussions were conducted. The study reveals that the current operational mode of anti-malarial drug markets in Burkina Faso promotes arteminisin resistance emergence and spread. The factors are mainly related to the artemisinin-based combination therapy (ACT) supply chain, to ACT quality, ACT prescription monitoring and to ACT access and misuse by patients. Conclusion: Study findings highlight the urgent requirement to reform current characteristics of the anti-malarial drug market in order to delay the emergence and spread of artemisinin resistance in Burkina Faso. Four recommendations for public policy emerged during data analysis: (1) Address the suboptimal prescription of anti-malarial drugs, (2) Apply laws that prohibit the sale of anti-malarials without prescription, (3) Restrict the availability of street drugs, (4) Sensitize the population on the value of compliance regarding correct acquisition and intake of anti-malarials. Funding systems for anti-malarial drugs in terms of availability and accessibility must also be stabilized.
Published: 2023

4. Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion

Author: de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., Moors, Ellen H. M., de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., and Moors, Ellen H. M.
Abstract: Background This is a qualitative study to identify implementation challenges for deploying triple artemisinin-based combination therapy (TACT) in the Greater Mekong Subregion (GMS) of Southeast Asia and to explore strategies to overcome these challenges. Methods In-depth interviews were conducted in three countries that have repeatedly been confronted with ACT failures: Cambodia, Vietnam, and Lao PDR. Thirty-nine key stakeholders in the healthcare systems in these countries were interviewed. One participatory workshop was conducted in Cambodia, where scenarios for potential TACT deployment were discussed. Results The results section is organized around four strategic themes that emerged from the data: policy support, data and evidence, logistics and operation, and downstream engagement. The study revealed that countries in the GMS currently rely on ACT to eliminate Plasmodium falciparum malaria by 2025. TACT is, however, considered to be a useful backup strategy in case of future treatment failures and to prevent the re-establishment of malaria. The study showed that a major challenge ahead is to engage decision makers and healthcare providers into deploying TACT, given the low case incidence of falciparum malaria in the GMS. Interview respondents were also skeptical whether healthcare providers would be willing to engage in new therapies for a disease they hardly encounter anymore. Hence, elaborate information dissemination strategies were considered appropriate and these strategies should especially target village malaria workers. Respondents proposed several regulatory and programmatic strategies to anticipate the formation of TACT markets in the GMS. These strategies include early dossier submission to streamline regulatory procedures, early stakeholder engagement strategies to shorten implementation timelines, and inclusion of TACT as second-line therapy to accelerate their introduction in case they are urgently needed. Co
Published: 2023

5. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author: Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia
Abstract: Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr
Published: 2023
Full Text: View/download PDF

6. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author: Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia
Abstract: Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr
Published: 2023
Full Text: View/download PDF

7. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author: Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia
Abstract: Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr
Published: 2023
Full Text: View/download PDF

8. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author: Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia
Abstract: Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr
Published: 2023
Full Text: View/download PDF

9. Exploring the feasibility of introducing triple artemisinin-based combination therapy in the malaria treatment policy in Vietnam

Author: Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, Cao, Van Anh Thi, Nguyen, Thieu Quang, Le Quyen, Duong, Boon, Wouter P C, Moors, Ellen H M, Dondorp, Arjen M, de Haan, Freek, Amaratunga, Chanaki, Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, Cao, Van Anh Thi, Nguyen, Thieu Quang, Le Quyen, Duong, Boon, Wouter P C, Moors, Ellen H M, Dondorp, Arjen M, de Haan, Freek, and Amaratunga, Chanaki
Published: 2023

10. Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis

Author: Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., Stepniewska, Kasia, Wynberg, Elke, Commons, Robert J., Humphreys, Georgina, Ashurst, Hazel, Burrow, Rebekah, Adjei, George O., Adjuik, Martin, Anstey, Nicholas M., Anvikar, Anup, Baird, Kevin J., Barber, Bridget E., Barennes, Hubert, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Binh, Tran Quang, Borghini, Isabelle, Chu, Cindy S., Daher, Andre, D'Alessandro, Umberto, Das, Debashish, Davis, Timothy Me, de Vries, Peter J., Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Faucher, Jean-Francois F., Fogg, Carole, Gaye, Oumar, Grigg, Matthew, Hatz, Christoph, Kager, Piet A., Lacerda, Marcus, Laman, Moses, Mårtensson, Andreas, Menan, Herve Ignace Eby, Monteiro, Wuelton M., Moore, Brioni R., Nosten, Francois, Ogutu, Bernhards, Osorio, Lyda, Penali, Louis K., Pereira, Dhelio B., Rahim, Awab G., Ramharter, Michael, Sagara, Issaka, Schramm, Birgit, Seidlein, Lorenz, Siqueira, Andre M., Sirima, Sodiomon B., Starzengruber, Peter, Sutanto, Inge, Taylor, Walter R., Toure, Offianan A., Utzinger, Jurg, Valea, Innocent, Valentini, Giovanni, White, Nicholas J., William, Timothy, Woodrow, Charles J., Richmond, Caitlin L., Guerin, Philippe J., Price, Ric N., and Stepniewska, Kasia
Abstract: Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve pr
Published: 2023
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11. The impact of anti-malarial markets on artemisinin resistance: perspectives from Burkina Faso

Author: Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, Guissou, Rosemonde M., Amaratunga, Chanaki, de Haan, Freek, Tou, Fatoumata, Cheah, Phaik Yeong, Yerbanga, R. Serge, Moors, Ellen H.M., Dhorda, Mehul, Tindana, Paulina, Boon, Wouter P.C., Dondorp, Arjen M., Ouédraogo, Jean Bosco, Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, Guissou, Rosemonde M., Amaratunga, Chanaki, de Haan, Freek, Tou, Fatoumata, Cheah, Phaik Yeong, Yerbanga, R. Serge, Moors, Ellen H.M., Dhorda, Mehul, Tindana, Paulina, Boon, Wouter P.C., Dondorp, Arjen M., and Ouédraogo, Jean Bosco
Published: 2023

12. Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion

Author: Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., Moors, Ellen H. M., Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., and Moors, Ellen H. M.
Published: 2023

13. Severe falciparum malaria in pregnancy in Southeast Asia: a multi-centre retrospective cohort study

Author: MS Verloskunde, Cancer, Saito, Makoto, Phyo, Aung Pyae, Chu, Cindy, Proux, Stephane, Rijken, Marcus J, Beau, Candy, Win, Htun Htun, Archasuksan, Laypaw, Wiladphaingern, Jacher, Phu, Nguyen H, Hien, Tran T, Day, Nick P, Dondorp, Arjen M, White, Nicholas J, Nosten, François, McGready, Rose, MS Verloskunde, Cancer, Saito, Makoto, Phyo, Aung Pyae, Chu, Cindy, Proux, Stephane, Rijken, Marcus J, Beau, Candy, Win, Htun Htun, Archasuksan, Laypaw, Wiladphaingern, Jacher, Phu, Nguyen H, Hien, Tran T, Day, Nick P, Dondorp, Arjen M, White, Nicholas J, Nosten, François, and McGready, Rose
Published: 2023

14. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Abstract: BACKGROUND: Triple Artemisinin-based Combination Therapies (TACTs) are being developed as a response to artemisinin and partner drug resistance in Southeast Asia. However, the desirability, timing and practical feasibility of introducing TACTs in Southeast Asia is subject to debate. This study systematically assesses perspectives of malaria experts towards the introduction of TACTs as first-line treatment for uncomplicated falciparum malaria in Southeast Asia.METHODS: A two-round Delphi study was conducted. In the first round, 53 malaria experts answered open-ended questions on what they consider the most important advantages, disadvantages, and implementation barriers for introducing TACTs in Southeast Asia. In the second round, the expert panel rated the relevance of each statement on a 5-point Likert scale.RESULTS: Malaria experts identified 15 advantages, 15 disadvantages and 13 implementation barriers for introducing TACTs in Southeast Asia in the first round of data collection. In the second round, consensus was reached on 13 advantages (8 perceived as relevant, 5 as not-relevant), 12 disadvantages (10 relevant, 2 not-relevant), and 13 implementation barriers (all relevant). Advantages attributed highest relevance related to the clinical and epidemiological rationale of introducing TACTs. Disadvantages attributed highest relevance related to increased side-effects, unavailability of fixed-dose TACTs, and potential cost increases. Implementation barriers attributed highest relevance related to obtaining timely regulatory approval, timely availability of fixed-dose TACTs, and generating global policy support for introducing TACTs.CONCLUSIONS: The study provides a structured oversight of malaria experts' perceptions on the major advantages, disadvantages and implementation challenges for introducing TACTs in Southeast Asia, over current practices of rotating ACTs when treatment failure is observed. The findings can benefit strategic decisi
Published: 2022

15. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Published: 2022

16. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Published: 2022

17. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies.

Author: UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, Schultz, Marcus J, ERICC study investigators, LUNG SAFE study investigators, PRoVENT study investigators, PRoVENT-iMiC study investigators, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre, Dive, Alain-Michel, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, Schultz, Marcus J, ERICC study investigators, LUNG SAFE study investigators, PRoVENT study investigators, PRoVENT-iMiC study investigators, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre, and Dive, Alain-Michel
Abstract: BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). T
Published: 2022

18. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author: Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally
Abstract: Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7
Published: 2022
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19. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author: Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally
Abstract: Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7
Published: 2022
Full Text: View/download PDF

20. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author: Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally
Abstract: Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7
Published: 2022
Full Text: View/download PDF

21. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Published: 2022

22. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Published: 2022

23. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Published: 2022

24. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, Dondorp, Arjen M, Innovation and Sustainability, Innovation Studies, de Haan, Freek, Boon, Wouter P C, Amaratunga, Chanaki, and Dondorp, Arjen M
Published: 2022

25. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author: Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally
Abstract: Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7
Published: 2022
Full Text: View/download PDF

26. Anti-gametocyte antigen humoral immunity and gametocytemia during treatment of uncomplicated falciparum malaria:A multi-national study

Author: O'Flaherty, Katherine, Chan, Jo-Anne, Cutts, Julia C, Zaloumis, Sophie G, Ashley, Elizabeth A, Phyo, Aung Pyae, Drew, Damien R, Dondorp, Arjen M, Day, Nicholas P, Dhorda, Mehul, Fairhurst, Rick M, Lim, Pharath, Amaratunga, Chanaki, Pukrittayakamee, Sasithon, Hien, Tran Tinh, Htut, Ye, Mayxay, Mayfong, Faiz, M Abul, Mokuolu, Olugbenga A, Onyamboko, Marie A, Fanello, Caterina, Takashima, Eizo, Tsuboi, Takafumi, Theisen, Michael, Nosten, Francois, Beeson, James G, Simpson, Julie A, White, Nicholas J, Fowkes, Freya J I, O'Flaherty, Katherine, Chan, Jo-Anne, Cutts, Julia C, Zaloumis, Sophie G, Ashley, Elizabeth A, Phyo, Aung Pyae, Drew, Damien R, Dondorp, Arjen M, Day, Nicholas P, Dhorda, Mehul, Fairhurst, Rick M, Lim, Pharath, Amaratunga, Chanaki, Pukrittayakamee, Sasithon, Hien, Tran Tinh, Htut, Ye, Mayxay, Mayfong, Faiz, M Abul, Mokuolu, Olugbenga A, Onyamboko, Marie A, Fanello, Caterina, Takashima, Eizo, Tsuboi, Takafumi, Theisen, Michael, Nosten, Francois, Beeson, James G, Simpson, Julie A, White, Nicholas J, and Fowkes, Freya J I
Abstract: Introduction: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates.Methods: In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment.Results: Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071).Conclusion: Pfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gam
Published: 2022

27. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Author: Pisani, Luigi, Geke Algera, Anna, Serpa Neto, Ary, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, Gama de Abreu, Marcelo, Pelosi, Paolo, M Dondorp, Arjen, Bellani, Giacomo, G Laffey, John, J Schultz, Marcu, study investigators, Ericc, SAFE study investigators, Lung, study investigators, Provent, study investigators, PRoVENT-iMiC, Montini, Luca, Luca Montini (ORCID:0000-0003-4602-5134), Pisani, Luigi, Geke Algera, Anna, Serpa Neto, Ary, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, Gama de Abreu, Marcelo, Pelosi, Paolo, M Dondorp, Arjen, Bellani, Giacomo, G Laffey, John, J Schultz, Marcu, study investigators, Ericc, SAFE study investigators, Lung, study investigators, Provent, study investigators, PRoVENT-iMiC, Montini, Luca, and Luca Montini (ORCID:0000-0003-4602-5134)
Abstract: Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference –1·69 [–9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). T
Published: 2022

28. Anti-gametocyte antigen humoral immunity and gametocytemia during treatment of uncomplicated falciparum malaria:A multi-national study

Author: O'Flaherty, Katherine, Chan, Jo-Anne, Cutts, Julia C, Zaloumis, Sophie G, Ashley, Elizabeth A, Phyo, Aung Pyae, Drew, Damien R, Dondorp, Arjen M, Day, Nicholas P, Dhorda, Mehul, Fairhurst, Rick M, Lim, Pharath, Amaratunga, Chanaki, Pukrittayakamee, Sasithon, Hien, Tran Tinh, Htut, Ye, Mayxay, Mayfong, Faiz, M Abul, Mokuolu, Olugbenga A, Onyamboko, Marie A, Fanello, Caterina, Takashima, Eizo, Tsuboi, Takafumi, Theisen, Michael, Nosten, Francois, Beeson, James G, Simpson, Julie A, White, Nicholas J, Fowkes, Freya J I, O'Flaherty, Katherine, Chan, Jo-Anne, Cutts, Julia C, Zaloumis, Sophie G, Ashley, Elizabeth A, Phyo, Aung Pyae, Drew, Damien R, Dondorp, Arjen M, Day, Nicholas P, Dhorda, Mehul, Fairhurst, Rick M, Lim, Pharath, Amaratunga, Chanaki, Pukrittayakamee, Sasithon, Hien, Tran Tinh, Htut, Ye, Mayxay, Mayfong, Faiz, M Abul, Mokuolu, Olugbenga A, Onyamboko, Marie A, Fanello, Caterina, Takashima, Eizo, Tsuboi, Takafumi, Theisen, Michael, Nosten, Francois, Beeson, James G, Simpson, Julie A, White, Nicholas J, and Fowkes, Freya J I
Abstract: Introduction: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates.Methods: In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment.Results: Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071).Conclusion: Pfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gam
Published: 2022

29. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Author: Pisani, L, Algera, A, Neto, A, Azevedo, L, Pham, T, Paulus, F, de Abreu, M, Pelosi, P, Dondorp, A, Bellani, G, Laffey, J, Schultz, M, Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, Schultz, Marcus J, Pisani, L, Algera, A, Neto, A, Azevedo, L, Pham, T, Paulus, F, de Abreu, M, Pelosi, P, Dondorp, A, Bellani, G, Laffey, J, Schultz, M, Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, and Schultz, Marcus J
Abstract: Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference –1·69 [–9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). T
Published: 2022

30. Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Author: Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Roper, Cally, Mansoor, Rashid, Commons, Robert J., Douglas, Nicholas M., Abuaku, Benjamin, Achan, Jane, Adam, Ishag, Adjei, George O., Adjuik, Martin, Alemayehu, Bereket H., Allan, Richard, Allen, Elizabeth N., Anvikar, Anupkumar R., Arinaitwe, Emmanuel, Ashley, Elizabeth A., Ashurst, Hazel, Asih, Puji B. S., Bakyaita, Nathan, Barennes, Hubert, Barnes, Karen, I, Basco, Leonardo, Bassat, Quique, Baudin, Elisabeth, Bell, David J., Bethell, Delia, Bjorkman, Anders, Boulton, Caroline, Bousema, Teun, Brasseur, Philippe, Bukirwa, Hasifa, Burrow, Rebekah, Carrara, Verena, I, Cot, Michel, D'Alessandro, Umberto, Das, Debashish, Das, Sabyasachi, Davis, Timothy M. E., Desai, Meghna, Djimde, Abdoulaye A., Dondorp, Arjen M., Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Espie, Emmanuelle, Etard, Jean-Francois, Falade, Catherine, Faucher, Jean Francois, Filler, Scott, Fogg, Carole, Fukuda, Mark, Gaye, Oumar, Genton, Blaise, Rahim, Awab Ghulam, Gilayeneh, Julius, Gonzalez, Raquel, Grais, Rebecca F., Grandesso, Francesco, Greenwood, Brian, Grivoyannis, Anastasia, Hatz, Christoph, Hodel, Eva Maria, Humphreys, Georgina S., Hwang, Jimee, Ishengoma, Deus, Juma, Elizabeth, Kachur, S. Patrick, Kager, Piet A., Kamugisha, Erasmus, Kamya, Moses R., Karema, Corine, Kayentao, Kassoum, Kazienga, Adama, Kiechel, Jean-Rene, Kofoed, Poul-Erik, Koram, Kwadwo, Kremsner, Peter G., Lalloo, David G., Laman, Moses, Lee, Sue J., Lell, Bertrand, Maiga, Amelia W., Mårtensson, Andreas, Mayxay, Mayfong, Mbacham, Wilfred, McGready, Rose, Menan, Herve, Menard, Didier, Mockenhaupt, Frank, Moore, Brioni R., Muller, Olaf, Nahum, Alain, Ndiaye, Jean-Louis, Newton, Paul N., Ngasala, Billy E., Nikiema, Frederic, Nji, Akindeh M., Noedl, Harald, Nosten, Francois, Ogutu, Bernhards R., Ojurongbe, Olusola, Osorio, Lyda, Ouedraogo, Jean-Bosco, Owusu-Agyei, Seth, Pareek, Anil, Penali, Louis K., Piola, Patrice, Plucinski, Mateusz, Premji, Zul, Ramharter, Michael, Richmond, Caitlin L., Rombo, Lars, Rosenthal, Philip J., Salman, Sam, Same-Ekobo, Albert, Sibley, Carol, Sirima, Sodiomon B., Smithuis, Frank M., Some, Fabrice A., Staedke, Sarah G., Starzengruber, Peter, Strub-Wourgaft, Nathalie, Sutanto, Inge, Swarthout, Todd D., Syafruddin, Din, Talisuna, Ambrose O., Taylor, Walter R., Temu, Emmanuel A., Thwing, Julie, I, Tinto, Halidou, Tjitra, Emiliana, Toure, Offianan A., Tran, T. Hien, Ursing, Johan, Valea, Innocent, Valentini, Giovanni, van Vugt, Michele, von Seidlein, Lorenz, Ward, Stephen A., Were, Vincent, White, Nicholas J., Woodrow, Charles J., Yavo, William, Yeka, Adoke, Zongo, Issaka, Simpson, Julie A., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., and Roper, Cally
Abstract: Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.7
Published: 2022
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31. To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies?

Author: de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., Amaratunga, Chanaki, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., and Amaratunga, Chanaki
Abstract: Introduction Triple artemisinin-based combination therapies (TACTs) are being developed as a response to artemisinin and partner drug resistance in the treatment of falciparum malaria in Southeast Asia. In African countries, where current artemisinin-based combination therapies (ACTs) are still effective, TACTs have the potential to benefit the larger community and future patients by mitigating the risk of drug resistance. This study explores the extent to which the antimalarial drug markets in African countries are ready for a transition to TACTs. Methods A qualitative study was conducted in Nigeria and Burkina Faso and comprised in-depth interviews (n = 68) and focus group discussions (n = 11) with key actor groups in the innovation system of antimalarial therapies. Results Evidence of ACT failure in African countries and explicit support for TACTs by the World Health Organization (WHO) and international funders were perceived important determinants for the market prospects of TACTs in Nigeria and Burkina Faso. At the country level, slow regulatory and implementation procedures were identified as potential barriers towards rapid TACTs deployment. Integrating TACTs in public sector distribution channels was considered relatively straightforward. More challenges were expected for integrating TACTs in private sector distribution channels, which are characterized by patient demand and profit motives. Finally, several affordability and acceptability issues were raised for which ACTs were suggested as a benchmark. Conclusion The market prospects of TACTs in Nigeria and Burkina Faso will depend on the demonstration of the added value of TACTs over ACTs, their advocacy by the WHO, the inclusion of TACTs in financial and regulatory arrangements, and their alignment with current distribution and deployment practices. Further clinical, health-economic and feasibility studies are required to inform decision makers about the broader implications of a transition to TACTs in Afr
Published: 2021

32. Market Formation in a Global Health Transition

Author: de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., Boon, Wouter P.C., de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., and Boon, Wouter P.C.
Abstract: Transition studies have started to focus on market formation in innovation systems. This article investigates market formation in a global health transition that was instigated by drug-resistant malaria. We explore how markets for Artemisinin-based Combination Therapies (ACT) in the Greater Mekong Subregion (GMS) were formed at multiple geographical scales and locations. The study reveals the role of public institutes, academia and partnerships in early innovation system development. It demonstrates how transnational organizations created a supportive global landscape for ACT development and deployment. It then reveals how these advancements led to the formation of public-sector and private-sector ACT markets in the GMS. We illustrate how market formation activities took place on global, national and local scales and how structural couplings enabled the functioning of this global innovation system. The lessons learned are particularly relevant now that drug-resistant malaria has once more emerged in the GMS, urgently calling for new therapies and associated end-user markets.
Published: 2021

33. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination.

Author: Jacob, Christopher G, Jacob, Christopher G, Thuy-Nhien, Nguyen, Mayxay, Mayfong, Maude, Richard J, Quang, Huynh Hong, Hongvanthong, Bouasy, Vanisaveth, Viengxay, Ngo Duc, Thang, Rekol, Huy, van der Pluijm, Rob, von Seidlein, Lorenz, Fairhurst, Rick, Nosten, François, Hossain, Md Amir, Park, Naomi, Goodwin, Scott, Ringwald, Pascal, Chindavongsa, Keobouphaphone, Newton, Paul, Ashley, Elizabeth, Phalivong, Sonexay, Maude, Rapeephan, Leang, Rithea, Huch, Cheah, Dong, Le Thanh, Nguyen, Kim-Tuyen, Nhat, Tran Minh, Hien, Tran Tinh, Nguyen, Hoa, Zdrojewski, Nicole, Canavati, Sara, Sayeed, Abdullah Abu, Uddin, Didar, Buckee, Caroline, Fanello, Caterina I, Onyamboko, Marie, Peto, Thomas, Tripura, Rupam, Amaratunga, Chanaki, Myint Thu, Aung, Delmas, Gilles, Landier, Jordi, Parker, Daniel M, Chau, Nguyen Hoang, Lek, Dysoley, Suon, Seila, Callery, James, Jittamala, Podjanee, Hanboonkunupakarn, Borimas, Pukrittayakamee, Sasithon, Phyo, Aung Pyae, Smithuis, Frank, Lin, Khin, Thant, Myo, Hlaing, Tin Maung, Satpathi, Parthasarathi, Satpathi, Sanghamitra, Behera, Prativa K, Tripura, Amar, Baidya, Subrata, Valecha, Neena, Anvikar, Anupkumar R, Ul Islam, Akhter, Faiz, Abul, Kunasol, Chanon, Drury, Eleanor, Kekre, Mihir, Ali, Mozam, Love, Katie, Rajatileka, Shavanthi, Jeffreys, Anna E, Rowlands, Kate, Hubbart, Christina S, Dhorda, Mehul, Vongpromek, Ranitha, Kotanan, Namfon, Wongnak, Phrutsamon, Almagro Garcia, Jacob, Pearson, Richard D, Ariani, Cristina V, Chookajorn, Thanat, Malangone, Cinzia, Nguyen, T, Stalker, Jim, Jeffery, Ben, Keatley, Jonathan, Johnson, Kimberly J, Muddyman, Dawn, Chan, Xin Hui S, Sillitoe, John, Amato, Roberto, Simpson, Victoria, Gonçalves, Sonia, Rockett, Kirk, Day, Nicholas P, Dondorp, Arjen M, Kwiatkowski, Dominic P, Miotto, Olivo, Jacob, Christopher G, Jacob, Christopher G, Thuy-Nhien, Nguyen, Mayxay, Mayfong, Maude, Richard J, Quang, Huynh Hong, Hongvanthong, Bouasy, Vanisaveth, Viengxay, Ngo Duc, Thang, Rekol, Huy, van der Pluijm, Rob, von Seidlein, Lorenz, Fairhurst, Rick, Nosten, François, Hossain, Md Amir, Park, Naomi, Goodwin, Scott, Ringwald, Pascal, Chindavongsa, Keobouphaphone, Newton, Paul, Ashley, Elizabeth, Phalivong, Sonexay, Maude, Rapeephan, Leang, Rithea, Huch, Cheah, Dong, Le Thanh, Nguyen, Kim-Tuyen, Nhat, Tran Minh, Hien, Tran Tinh, Nguyen, Hoa, Zdrojewski, Nicole, Canavati, Sara, Sayeed, Abdullah Abu, Uddin, Didar, Buckee, Caroline, Fanello, Caterina I, Onyamboko, Marie, Peto, Thomas, Tripura, Rupam, Amaratunga, Chanaki, Myint Thu, Aung, Delmas, Gilles, Landier, Jordi, Parker, Daniel M, Chau, Nguyen Hoang, Lek, Dysoley, Suon, Seila, Callery, James, Jittamala, Podjanee, Hanboonkunupakarn, Borimas, Pukrittayakamee, Sasithon, Phyo, Aung Pyae, Smithuis, Frank, Lin, Khin, Thant, Myo, Hlaing, Tin Maung, Satpathi, Parthasarathi, Satpathi, Sanghamitra, Behera, Prativa K, Tripura, Amar, Baidya, Subrata, Valecha, Neena, Anvikar, Anupkumar R, Ul Islam, Akhter, Faiz, Abul, Kunasol, Chanon, Drury, Eleanor, Kekre, Mihir, Ali, Mozam, Love, Katie, Rajatileka, Shavanthi, Jeffreys, Anna E, Rowlands, Kate, Hubbart, Christina S, Dhorda, Mehul, Vongpromek, Ranitha, Kotanan, Namfon, Wongnak, Phrutsamon, Almagro Garcia, Jacob, Pearson, Richard D, Ariani, Cristina V, Chookajorn, Thanat, Malangone, Cinzia, Nguyen, T, Stalker, Jim, Jeffery, Ben, Keatley, Jonathan, Johnson, Kimberly J, Muddyman, Dawn, Chan, Xin Hui S, Sillitoe, John, Amato, Roberto, Simpson, Victoria, Gonçalves, Sonia, Rockett, Kirk, Day, Nicholas P, Dondorp, Arjen M, Kwiatkowski, Dominic P, and Miotto, Olivo
Abstract: BackgroundNational Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.MethodsSamples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs.ResultsGenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs.ConclusionsGenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community.FundingThe GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the
Published: 2021

34. Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection.

Author: Mukaka, Mavuto, Mukaka, Mavuto, Peerawaranun, Pimnara, Parker, Daniel M, Kajeechiwa, Ladda, Nosten, Francois H, Nguyen, Thuy-Nhien, Hien, Tran Tinh, Tripura, Rupam, Peto, Thomas J, Phommasone, Koukeo, Mayxay, Mayfong, Newton, Paul N, Imwong, Mallika, Day, Nicholas PJ, Dondorp, Arjen M, White, Nicholas J, von Seidlein, Lorenz, Mukaka, Mavuto, Mukaka, Mavuto, Peerawaranun, Pimnara, Parker, Daniel M, Kajeechiwa, Ladda, Nosten, Francois H, Nguyen, Thuy-Nhien, Hien, Tran Tinh, Tripura, Rupam, Peto, Thomas J, Phommasone, Koukeo, Mayxay, Mayfong, Newton, Paul N, Imwong, Mallika, Day, Nicholas PJ, Dondorp, Arjen M, White, Nicholas J, and von Seidlein, Lorenz
Abstract: BackgroundMalaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources.MethodsData from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL).ResultsAt baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek tre
Published: 2021

35. Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure : Guidance from an International Group of Healthcare Workers

Author: Stilma, Willemke, Åkerman, Eva, Artigas, Antonio, Bentley, Andrew, Bos, Lieuwe D., Bosman, Thomas J. C., de Bruin, Hendrik, Brummaier, Tobias, Buiteman-Kruizinga, Laura A., Carcò, Francesco, Chesney, Gregg, Chu, Cindy, Dark, Paul, Dondorp, Arjen M., Gijsbers, Harm J. H., Gilder, Mary Ellen, Grieco, Domenico L., Inglis, Rebecca, Laffey, John G., Landoni, Giovanni, Lu, Weihua, Maduro, Lisa M. N., McGready, Rose, McNicholas, Bairbre, de Mendoza, Diego, Morales-Quinteros, Luis, Nosten, Francois, Papali, Alfred, Paternoster, Gianluca, Paulus, Frederique, Pisani, Luigi, Prud'homme, Eloi, Ricard, Jean-Damien, Roca, Oriol, Sartini, Chiara, Scaravilli, Vittorio, Schultz, Marcus J., Sivakorn, Chaisith, Spronk, Peter E., Sztajnbok, Jaques, Trigui, Youssef, Vollman, Kathleen M., van der Woude, Margaretha C. E., Stilma, Willemke, Åkerman, Eva, Artigas, Antonio, Bentley, Andrew, Bos, Lieuwe D., Bosman, Thomas J. C., de Bruin, Hendrik, Brummaier, Tobias, Buiteman-Kruizinga, Laura A., Carcò, Francesco, Chesney, Gregg, Chu, Cindy, Dark, Paul, Dondorp, Arjen M., Gijsbers, Harm J. H., Gilder, Mary Ellen, Grieco, Domenico L., Inglis, Rebecca, Laffey, John G., Landoni, Giovanni, Lu, Weihua, Maduro, Lisa M. N., McGready, Rose, McNicholas, Bairbre, de Mendoza, Diego, Morales-Quinteros, Luis, Nosten, Francois, Papali, Alfred, Paternoster, Gianluca, Paulus, Frederique, Pisani, Luigi, Prud'homme, Eloi, Ricard, Jean-Damien, Roca, Oriol, Sartini, Chiara, Scaravilli, Vittorio, Schultz, Marcus J., Sivakorn, Chaisith, Spronk, Peter E., Sztajnbok, Jaques, Trigui, Youssef, Vollman, Kathleen M., and van der Woude, Margaretha C. E.
Abstract: Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
Published: 2021

36. To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies?

Author: Innovation Studies, Innovation and Sustainability, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., Amaratunga, Chanaki, Innovation Studies, Innovation and Sustainability, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., and Amaratunga, Chanaki
Published: 2021

37. Market Formation in a Global Health Transition

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., Boon, Wouter P.C., Innovation and Sustainability, Innovation Studies, de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., and Boon, Wouter P.C.
Published: 2021

38. An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples

Author: Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amato, Roberto, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim JC, Andrianaranjaka, Voahangy, Apinjoh, Tobias, Ariani, Cristina, Ashley, Elizabeth A, Auburn, Sarah, Awandare, Gordon, Ba, Hampdate, Baraka, Vito, Barry, Alyssa E, Bejon, Philip, Bertin, Gwladys I, Boni, Maciej F, Borrmann, Steffen, Bousema, Teun, Branch, Oralee, Bull, Peter C, Busby, George BJ, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David, Craig, Alister, D'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas PJ, Denis, Brigitte, Diakite, Mahamadou, Djimdé, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen M, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego F, Egwang, Thomas G, Erko, Berhanu, Fairhurst, Rick M, Faiz, Abdul, Fanello, Caterina A, Fukuda, Mark M, Gamboa, Dionica, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Hamilton, William L, Harrison, GL Abby, Hart, Lee, Henrichs, Christa, Hien, Tran Tinh, Hill, Catherine A, Hodgson, Abraham, Hubbart, Christina, Imwong, Mallika, Ishengoma, Deus S, Jackson, Scott A, Jacob, Chris G, Jeffery, Ben, Jeffreys, Anna E, Johnson, Kimberly J, Jyothi, Dushyanth, Kamaliddin, Claire, Kamau, Edwin, Kekre, Mihir, Kluczynski, Krzysztof, Kochakarn, Theerarat, Konaté, Abibatou, Kwiatkowski, Dominic P, Kyaw, Myat Phone, Lim, Pharath, Lon, Chanthap, Loua, Kovana M, Maïga-Ascofaré, Oumou, Malangone, Cinzia, Manske, Magnus, Marfurt, Jutta, Marsh, Kevin, Mayxay, Mayfong, Miles, Alistair, Miotto, Olivo, Mobegi, Victor, Mokuolu, Olugbenga A, Montgomery, Jacqui, Mueller, Ivo, Newton, Paul N, Nguyen, Thuy, Nguyen, Thuy-Nhien, Noedl, Harald, Nosten, Francois, Noviyanti, Rintis, Nzila, Alexis, Ochola-Oyier, Lynette I, Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amato, Roberto, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim JC, Andrianaranjaka, Voahangy, Apinjoh, Tobias, Ariani, Cristina, Ashley, Elizabeth A, Auburn, Sarah, Awandare, Gordon, Ba, Hampdate, Baraka, Vito, Barry, Alyssa E, Bejon, Philip, Bertin, Gwladys I, Boni, Maciej F, Borrmann, Steffen, Bousema, Teun, Branch, Oralee, Bull, Peter C, Busby, George BJ, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David, Craig, Alister, D'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas PJ, Denis, Brigitte, Diakite, Mahamadou, Djimdé, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen M, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego F, Egwang, Thomas G, Erko, Berhanu, Fairhurst, Rick M, Faiz, Abdul, Fanello, Caterina A, Fukuda, Mark M, Gamboa, Dionica, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Hamilton, William L, Harrison, GL Abby, Hart, Lee, Henrichs, Christa, Hien, Tran Tinh, Hill, Catherine A, Hodgson, Abraham, Hubbart, Christina, Imwong, Mallika, Ishengoma, Deus S, Jackson, Scott A, Jacob, Chris G, Jeffery, Ben, Jeffreys, Anna E, Johnson, Kimberly J, Jyothi, Dushyanth, Kamaliddin, Claire, Kamau, Edwin, Kekre, Mihir, Kluczynski, Krzysztof, Kochakarn, Theerarat, Konaté, Abibatou, Kwiatkowski, Dominic P, Kyaw, Myat Phone, Lim, Pharath, Lon, Chanthap, Loua, Kovana M, Maïga-Ascofaré, Oumou, Malangone, Cinzia, Manske, Magnus, Marfurt, Jutta, Marsh, Kevin, Mayxay, Mayfong, Miles, Alistair, Miotto, Olivo, Mobegi, Victor, Mokuolu, Olugbenga A, Montgomery, Jacqui, Mueller, Ivo, Newton, Paul N, Nguyen, Thuy, Nguyen, Thuy-Nhien, Noedl, Harald, Nosten, Francois, Noviyanti, Rintis, Nzila, Alexis, and Ochola-Oyier, Lynette I
Abstract: MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
Published: 2021

39. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination.

Author: Jacob, Christopher G, Jacob, Christopher G, Thuy-Nhien, Nguyen, Mayxay, Mayfong, Maude, Richard J, Quang, Huynh Hong, Hongvanthong, Bouasy, Vanisaveth, Viengxay, Ngo Duc, Thang, Rekol, Huy, van der Pluijm, Rob, von Seidlein, Lorenz, Fairhurst, Rick, Nosten, François, Hossain, Md Amir, Park, Naomi, Goodwin, Scott, Ringwald, Pascal, Chindavongsa, Keobouphaphone, Newton, Paul, Ashley, Elizabeth, Phalivong, Sonexay, Maude, Rapeephan, Leang, Rithea, Huch, Cheah, Dong, Le Thanh, Nguyen, Kim-Tuyen, Nhat, Tran Minh, Hien, Tran Tinh, Nguyen, Hoa, Zdrojewski, Nicole, Canavati, Sara, Sayeed, Abdullah Abu, Uddin, Didar, Buckee, Caroline, Fanello, Caterina I, Onyamboko, Marie, Peto, Thomas, Tripura, Rupam, Amaratunga, Chanaki, Myint Thu, Aung, Delmas, Gilles, Landier, Jordi, Parker, Daniel M, Chau, Nguyen Hoang, Lek, Dysoley, Suon, Seila, Callery, James, Jittamala, Podjanee, Hanboonkunupakarn, Borimas, Pukrittayakamee, Sasithon, Phyo, Aung Pyae, Smithuis, Frank, Lin, Khin, Thant, Myo, Hlaing, Tin Maung, Satpathi, Parthasarathi, Satpathi, Sanghamitra, Behera, Prativa K, Tripura, Amar, Baidya, Subrata, Valecha, Neena, Anvikar, Anupkumar R, Ul Islam, Akhter, Faiz, Abul, Kunasol, Chanon, Drury, Eleanor, Kekre, Mihir, Ali, Mozam, Love, Katie, Rajatileka, Shavanthi, Jeffreys, Anna E, Rowlands, Kate, Hubbart, Christina S, Dhorda, Mehul, Vongpromek, Ranitha, Kotanan, Namfon, Wongnak, Phrutsamon, Almagro Garcia, Jacob, Pearson, Richard D, Ariani, Cristina V, Chookajorn, Thanat, Malangone, Cinzia, Nguyen, T, Stalker, Jim, Jeffery, Ben, Keatley, Jonathan, Johnson, Kimberly J, Muddyman, Dawn, Chan, Xin Hui S, Sillitoe, John, Amato, Roberto, Simpson, Victoria, Gonçalves, Sonia, Rockett, Kirk, Day, Nicholas P, Dondorp, Arjen M, Kwiatkowski, Dominic P, Miotto, Olivo, Jacob, Christopher G, Jacob, Christopher G, Thuy-Nhien, Nguyen, Mayxay, Mayfong, Maude, Richard J, Quang, Huynh Hong, Hongvanthong, Bouasy, Vanisaveth, Viengxay, Ngo Duc, Thang, Rekol, Huy, van der Pluijm, Rob, von Seidlein, Lorenz, Fairhurst, Rick, Nosten, François, Hossain, Md Amir, Park, Naomi, Goodwin, Scott, Ringwald, Pascal, Chindavongsa, Keobouphaphone, Newton, Paul, Ashley, Elizabeth, Phalivong, Sonexay, Maude, Rapeephan, Leang, Rithea, Huch, Cheah, Dong, Le Thanh, Nguyen, Kim-Tuyen, Nhat, Tran Minh, Hien, Tran Tinh, Nguyen, Hoa, Zdrojewski, Nicole, Canavati, Sara, Sayeed, Abdullah Abu, Uddin, Didar, Buckee, Caroline, Fanello, Caterina I, Onyamboko, Marie, Peto, Thomas, Tripura, Rupam, Amaratunga, Chanaki, Myint Thu, Aung, Delmas, Gilles, Landier, Jordi, Parker, Daniel M, Chau, Nguyen Hoang, Lek, Dysoley, Suon, Seila, Callery, James, Jittamala, Podjanee, Hanboonkunupakarn, Borimas, Pukrittayakamee, Sasithon, Phyo, Aung Pyae, Smithuis, Frank, Lin, Khin, Thant, Myo, Hlaing, Tin Maung, Satpathi, Parthasarathi, Satpathi, Sanghamitra, Behera, Prativa K, Tripura, Amar, Baidya, Subrata, Valecha, Neena, Anvikar, Anupkumar R, Ul Islam, Akhter, Faiz, Abul, Kunasol, Chanon, Drury, Eleanor, Kekre, Mihir, Ali, Mozam, Love, Katie, Rajatileka, Shavanthi, Jeffreys, Anna E, Rowlands, Kate, Hubbart, Christina S, Dhorda, Mehul, Vongpromek, Ranitha, Kotanan, Namfon, Wongnak, Phrutsamon, Almagro Garcia, Jacob, Pearson, Richard D, Ariani, Cristina V, Chookajorn, Thanat, Malangone, Cinzia, Nguyen, T, Stalker, Jim, Jeffery, Ben, Keatley, Jonathan, Johnson, Kimberly J, Muddyman, Dawn, Chan, Xin Hui S, Sillitoe, John, Amato, Roberto, Simpson, Victoria, Gonçalves, Sonia, Rockett, Kirk, Day, Nicholas P, Dondorp, Arjen M, Kwiatkowski, Dominic P, and Miotto, Olivo
Abstract: BackgroundNational Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.MethodsSamples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs.ResultsGenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs.ConclusionsGenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community.FundingThe GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the
Published: 2021

40. Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection.

Author: Mukaka, Mavuto, Mukaka, Mavuto, Peerawaranun, Pimnara, Parker, Daniel M, Kajeechiwa, Ladda, Nosten, Francois H, Nguyen, Thuy-Nhien, Hien, Tran Tinh, Tripura, Rupam, Peto, Thomas J, Phommasone, Koukeo, Mayxay, Mayfong, Newton, Paul N, Imwong, Mallika, Day, Nicholas PJ, Dondorp, Arjen M, White, Nicholas J, von Seidlein, Lorenz, Mukaka, Mavuto, Mukaka, Mavuto, Peerawaranun, Pimnara, Parker, Daniel M, Kajeechiwa, Ladda, Nosten, Francois H, Nguyen, Thuy-Nhien, Hien, Tran Tinh, Tripura, Rupam, Peto, Thomas J, Phommasone, Koukeo, Mayxay, Mayfong, Newton, Paul N, Imwong, Mallika, Day, Nicholas PJ, Dondorp, Arjen M, White, Nicholas J, and von Seidlein, Lorenz
Abstract: BackgroundMalaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources.MethodsData from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL).ResultsAt baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek tre
Published: 2021

41. Market Formation in a Global Health Transition

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., Boon, Wouter P.C., Innovation and Sustainability, Innovation Studies, de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., and Boon, Wouter P.C.
Published: 2021

42. To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies?

Author: Innovation Studies, Innovation and Sustainability, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., Amaratunga, Chanaki, Innovation Studies, Innovation and Sustainability, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., and Amaratunga, Chanaki
Published: 2021

43. To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies?

Author: Innovation Studies, Innovation and Sustainability, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., Amaratunga, Chanaki, Innovation Studies, Innovation and Sustainability, de Haan, Freek, Bolarinwa, Oladimeji Akeem, Guissou, Rosemonde, Tou, Fatoumata, Tindana, Paulina, Boon, Wouter P. C., Moors, Ellen H. M., Cheah, Phaik Yeong, Dhorda, Mehul, Dondorp, Arjen M., Ouedraogo, Jean Bosco, Mokuolu, Olugbenga A., and Amaratunga, Chanaki
Published: 2021

44. Market Formation in a Global Health Transition

Author: Innovation and Sustainability, Innovation Studies, de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., Boon, Wouter P.C., Innovation and Sustainability, Innovation Studies, de Haan, Freek, Moors, Ellen H.M., Dondorp, Arjen M., and Boon, Wouter P.C.
Published: 2021

45. Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials.

Author: Phommasone, Koukeo, Phommasone, Koukeo, van Leth, Frank, Peto, Thomas J, Landier, Jordi, Nguyen, Thuy-Nhien, Tripura, Rupam, Pongvongsa, Tiengkham, Lwin, Khin Maung, Kajeechiwa, Ladda, Thwin, May Myo, Parker, Daniel M, Wiladphaingern, Jacher, Nosten, Suphak, Proux, Stephane, Nguon, Chea, Davoeung, Chan, Rekol, Huy, Adhikari, Bipin, Promnarate, Cholrawee, Chotivanich, Kesinee, Hanboonkunupakarn, Borimas, Jittmala, Podjanee, Cheah, Phaik Yeong, Dhorda, Mehul, Imwong, Mallika, Mukaka, Mavuto, Peerawaranun, Pimnara, Pukrittayakamee, Sasithon, Newton, Paul N, Thwaites, Guy E, Day, Nicholas PJ, Mayxay, Mayfong, Hien, Tran Tinh, Nosten, Francois H, Cobelens, Frank, Dondorp, Arjen M, White, Nicholas J, von Seidlein, Lorenz, Phommasone, Koukeo, Phommasone, Koukeo, van Leth, Frank, Peto, Thomas J, Landier, Jordi, Nguyen, Thuy-Nhien, Tripura, Rupam, Pongvongsa, Tiengkham, Lwin, Khin Maung, Kajeechiwa, Ladda, Thwin, May Myo, Parker, Daniel M, Wiladphaingern, Jacher, Nosten, Suphak, Proux, Stephane, Nguon, Chea, Davoeung, Chan, Rekol, Huy, Adhikari, Bipin, Promnarate, Cholrawee, Chotivanich, Kesinee, Hanboonkunupakarn, Borimas, Jittmala, Podjanee, Cheah, Phaik Yeong, Dhorda, Mehul, Imwong, Mallika, Mukaka, Mavuto, Peerawaranun, Pimnara, Pukrittayakamee, Sasithon, Newton, Paul N, Thwaites, Guy E, Day, Nicholas PJ, Mayxay, Mayfong, Hien, Tran Tinh, Nosten, Francois H, Cobelens, Frank, Dondorp, Arjen M, White, Nicholas J, and von Seidlein, Lorenz
Abstract: BackgroundMass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.MethodsBetween May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected based on high prevalence of P. falciparum infections. Eight of the 16 villages were randomly assigned to receive MDA consisting of three-monthly rounds of three-day courses of dihydroartemisinin-piperaquine and, except in Cambodia, a single low-dose of primaquine. Cross-sectional surveys were conducted at quarterly intervals to detect Plasmodium infections using ultrasensitive qPCR. The difference in the cumulative incidence between the groups was assessed through a discrete time survival approach, the difference in prevalence through a difference-in-difference analysis, and the difference in the number of participants with a recurrence of P. vivax infection through a mixed-effect logistic regression.Results3,790 (86%) residents in the intervention villages participated in at least one MDA round, of whom 2,520 (57%) participated in three rounds. The prevalence of P. vivax infections fell from 9.31% to 0.89% at month 3 but rebounded by six months to 5.81%. There was no evidence that the intervention reduced the cumulative incidence of P.vivax infections (95% confidence interval [CI] Odds ratio (OR): 0.29 to 1.36). Similarly, there was no evidence of MDA related reduction in the number of participants with at least one recurrent infection (OR: 0.34; 95% CI: 0.08 to 1.42).ConclusionMDA with schizontocidal drugs had a lasting effect on P. falciparum infections but only a transient effect on the prevalence of P. vivax infections. Radical cure with an 8-aminoquinoline will be needed for the rapid elimination of vivax malaria.
Published: 2020

46. Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.

Author: Stresman, Gillian, Stresman, Gillian, Sepúlveda, Nuno, Fornace, Kimberly, Grignard, Lynn, Mwesigwa, Julia, Achan, Jane, Miller, John, Bridges, Daniel J, Eisele, Thomas P, Mosha, Jacklin, Lorenzo, Pauline Joy, Macalinao, Maria Lourdes, Espino, Fe Esperanza, Tadesse, Fitsum, Stevenson, Jennifer C, Quispe, Antonio M, Siqueira, André, Lacerda, Marcus, Yeung, Shunmay, Sovannaroth, Siv, Pothin, Emilie, Gallay, Joanna, Hamre, Karen E, Young, Alyssa, Lemoine, Jean Frantz, Chang, Michelle A, Phommasone, Koukeo, Mayxay, Mayfong, Landier, Jordi, Parker, Daniel M, Von Seidlein, Lorenz, Nosten, Francois, Delmas, Gilles, Dondorp, Arjen, Cameron, Ewan, Battle, Katherine, Bousema, Teun, Gething, Peter, D'Alessandro, Umberto, Drakeley, Chris, Stresman, Gillian, Stresman, Gillian, Sepúlveda, Nuno, Fornace, Kimberly, Grignard, Lynn, Mwesigwa, Julia, Achan, Jane, Miller, John, Bridges, Daniel J, Eisele, Thomas P, Mosha, Jacklin, Lorenzo, Pauline Joy, Macalinao, Maria Lourdes, Espino, Fe Esperanza, Tadesse, Fitsum, Stevenson, Jennifer C, Quispe, Antonio M, Siqueira, André, Lacerda, Marcus, Yeung, Shunmay, Sovannaroth, Siv, Pothin, Emilie, Gallay, Joanna, Hamre, Karen E, Young, Alyssa, Lemoine, Jean Frantz, Chang, Michelle A, Phommasone, Koukeo, Mayxay, Mayfong, Landier, Jordi, Parker, Daniel M, Von Seidlein, Lorenz, Nosten, Francois, Delmas, Gilles, Dondorp, Arjen, Cameron, Ewan, Battle, Katherine, Bousema, Teun, Gething, Peter, D'Alessandro, Umberto, and Drakeley, Chris
Abstract: BackgroundPassively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings.MethodsThe proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia.FindingsThe median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity.InterpretationThe proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that i
Published: 2020

47. Towards harmonization of microscopy methods for malaria clinical research studies

Author: Dhorda, Mehul, Ba, El Hadji, Kevin Baird, J., Barnwell, John, Bell, David, Carter, Jane Y., Dondorp, Arjen, Ekawati, Lenny, Gatton, Michelle, González, Iveth, Guérin, Philippe J., Incardona, Sandra, Lilley, Ken, Menard, Didier, Nosten, François, Obare, Peter, Ogutu, Bernhards, Olliaro, Piero L., Price, Ric N., Proux, Stéphane, Ramsay, Andrew R., Reeder, John C., Silamut, Kamolrat, Sokhna, Cheikh, Dhorda, Mehul, Ba, El Hadji, Kevin Baird, J., Barnwell, John, Bell, David, Carter, Jane Y., Dondorp, Arjen, Ekawati, Lenny, Gatton, Michelle, González, Iveth, Guérin, Philippe J., Incardona, Sandra, Lilley, Ken, Menard, Didier, Nosten, François, Obare, Peter, Ogutu, Bernhards, Olliaro, Piero L., Price, Ric N., Proux, Stéphane, Ramsay, Andrew R., Reeder, John C., Silamut, Kamolrat, and Sokhna, Cheikh
Abstract: Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.
Published: 2020

48. Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials.

Author: Phommasone, Koukeo, Diemert, David Joseph1, Phommasone, Koukeo, van Leth, Frank, Peto, Thomas J, Landier, Jordi, Nguyen, Thuy-Nhien, Tripura, Rupam, Pongvongsa, Tiengkham, Lwin, Khin Maung, Kajeechiwa, Ladda, Thwin, May Myo, Parker, Daniel M, Wiladphaingern, Jacher, Nosten, Suphak, Proux, Stephane, Nguon, Chea, Davoeung, Chan, Rekol, Huy, Adhikari, Bipin, Promnarate, Cholrawee, Chotivanich, Kesinee, Hanboonkunupakarn, Borimas, Jittmala, Podjanee, Cheah, Phaik Yeong, Dhorda, Mehul, Imwong, Mallika, Mukaka, Mavuto, Peerawaranun, Pimnara, Pukrittayakamee, Sasithon, Newton, Paul N, Thwaites, Guy E, Day, Nicholas PJ, Mayxay, Mayfong, Hien, Tran Tinh, Nosten, Francois H, Cobelens, Frank, Dondorp, Arjen M, White, Nicholas J, von Seidlein, Lorenz, Phommasone, Koukeo, Diemert, David Joseph1, Phommasone, Koukeo, van Leth, Frank, Peto, Thomas J, Landier, Jordi, Nguyen, Thuy-Nhien, Tripura, Rupam, Pongvongsa, Tiengkham, Lwin, Khin Maung, Kajeechiwa, Ladda, Thwin, May Myo, Parker, Daniel M, Wiladphaingern, Jacher, Nosten, Suphak, Proux, Stephane, Nguon, Chea, Davoeung, Chan, Rekol, Huy, Adhikari, Bipin, Promnarate, Cholrawee, Chotivanich, Kesinee, Hanboonkunupakarn, Borimas, Jittmala, Podjanee, Cheah, Phaik Yeong, Dhorda, Mehul, Imwong, Mallika, Mukaka, Mavuto, Peerawaranun, Pimnara, Pukrittayakamee, Sasithon, Newton, Paul N, Thwaites, Guy E, Day, Nicholas PJ, Mayxay, Mayfong, Hien, Tran Tinh, Nosten, Francois H, Cobelens, Frank, Dondorp, Arjen M, White, Nicholas J, and von Seidlein, Lorenz
Abstract: BackgroundMass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.MethodsBetween May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected based on high prevalence of P. falciparum infections. Eight of the 16 villages were randomly assigned to receive MDA consisting of three-monthly rounds of three-day courses of dihydroartemisinin-piperaquine and, except in Cambodia, a single low-dose of primaquine. Cross-sectional surveys were conducted at quarterly intervals to detect Plasmodium infections using ultrasensitive qPCR. The difference in the cumulative incidence between the groups was assessed through a discrete time survival approach, the difference in prevalence through a difference-in-difference analysis, and the difference in the number of participants with a recurrence of P. vivax infection through a mixed-effect logistic regression.Results3,790 (86%) residents in the intervention villages participated in at least one MDA round, of whom 2,520 (57%) participated in three rounds. The prevalence of P. vivax infections fell from 9.31% to 0.89% at month 3 but rebounded by six months to 5.81%. There was no evidence that the intervention reduced the cumulative incidence of P.vivax infections (95% confidence interval [CI] Odds ratio (OR): 0.29 to 1.36). Similarly, there was no evidence of MDA related reduction in the number of participants with at least one recurrent infection (OR: 0.34; 95% CI: 0.08 to 1.42).ConclusionMDA with schizontocidal drugs had a lasting effect on P. falciparum infections but only a transient effect on the prevalence of P. vivax infections. Radical cure with an 8-aminoquinoline will be needed for the rapid elimination of vivax malaria.
Published: 2020

49. Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data.

Author: Stresman, Gillian, Stresman, Gillian, Sepúlveda, Nuno, Fornace, Kimberly, Grignard, Lynn, Mwesigwa, Julia, Achan, Jane, Miller, John, Bridges, Daniel J, Eisele, Thomas P, Mosha, Jacklin, Lorenzo, Pauline Joy, Macalinao, Maria Lourdes, Espino, Fe Esperanza, Tadesse, Fitsum, Stevenson, Jennifer C, Quispe, Antonio M, Siqueira, André, Lacerda, Marcus, Yeung, Shunmay, Sovannaroth, Siv, Pothin, Emilie, Gallay, Joanna, Hamre, Karen E, Young, Alyssa, Lemoine, Jean Frantz, Chang, Michelle A, Phommasone, Koukeo, Mayxay, Mayfong, Landier, Jordi, Parker, Daniel M, Von Seidlein, Lorenz, Nosten, Francois, Delmas, Gilles, Dondorp, Arjen, Cameron, Ewan, Battle, Katherine, Bousema, Teun, Gething, Peter, D'Alessandro, Umberto, Drakeley, Chris, Stresman, Gillian, Stresman, Gillian, Sepúlveda, Nuno, Fornace, Kimberly, Grignard, Lynn, Mwesigwa, Julia, Achan, Jane, Miller, John, Bridges, Daniel J, Eisele, Thomas P, Mosha, Jacklin, Lorenzo, Pauline Joy, Macalinao, Maria Lourdes, Espino, Fe Esperanza, Tadesse, Fitsum, Stevenson, Jennifer C, Quispe, Antonio M, Siqueira, André, Lacerda, Marcus, Yeung, Shunmay, Sovannaroth, Siv, Pothin, Emilie, Gallay, Joanna, Hamre, Karen E, Young, Alyssa, Lemoine, Jean Frantz, Chang, Michelle A, Phommasone, Koukeo, Mayxay, Mayfong, Landier, Jordi, Parker, Daniel M, Von Seidlein, Lorenz, Nosten, Francois, Delmas, Gilles, Dondorp, Arjen, Cameron, Ewan, Battle, Katherine, Bousema, Teun, Gething, Peter, D'Alessandro, Umberto, and Drakeley, Chris
Abstract: BackgroundPassively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings.MethodsThe proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia.FindingsThe median estimated P(Detect) across all clusters was 12·5% (IQR 5·3-25·0) for P falciparum and 10·1% (5·0-18·3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0·63, 95% CI 0·57-0·69; adjusted OR for P vivax 0·52, 0·47-0·57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity.InterpretationThe proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that i
Published: 2020

50. Detecting geospatial patterns of Plasmodium falciparum parasite migration in Cambodia using optimized estimated effective migration surfaces

Author: Li, Yao, Li, Yao, Shetty, Amol C., Lon, Chanthap, Spring, Michele, Saunders, David L., Fukuda, Mark M., Hien, Tran Tinh, Pukrittayakamee, Sasithon, Fairhurst, Rick M., Dondorp, Arjen M., Plowe, Christopher V., O’Connor, Timothy D., Takala-Harrison, Shannon, Stewart, Kathleen, Li, Yao, Li, Yao, Shetty, Amol C., Lon, Chanthap, Spring, Michele, Saunders, David L., Fukuda, Mark M., Hien, Tran Tinh, Pukrittayakamee, Sasithon, Fairhurst, Rick M., Dondorp, Arjen M., Plowe, Christopher V., O’Connor, Timothy D., Takala-Harrison, Shannon, and Stewart, Kathleen
Abstract: Understanding the genetic structure of natural populations provides insight into the demographic and adaptive processes that have affected those populations. Such information, particularly when integrated with geospatial data, can have translational applications for a variety of fields, including public health. Estimated effective migration surfaces (EEMS) is an approach that allows visualization of the spatial patterns in genomic data to understand population structure and migration. In this study, we developed a workflow to optimize the resolution of spatial grids used to generate EEMS migration maps and applied this optimized workflow to estimate migration of Plasmodium falciparum in Cambodia and bordering regions of Thailand and Vietnam. The optimal density of EEMS grids was determined based on a new workflow created using density clustering to define genomic clusters and the spatial distance between genomic clusters. Topological skeletons were used to capture the spatial distribution for each genomic cluster and to determine the EEMS grid density; i.e., both genomic and spatial clustering were used to guide the optimization of EEMS grids. Model accuracy for migration estimates using the optimized workflow was tested and compared to grid resolutions selected without the optimized workflow. As a test case, the optimized workflow was applied to genomic data generated from P. falciparum sampled in Cambodia and bordering regions, and migration maps were compared to estimates of malaria endemicity, as well as geographic properties of the study area, as a means of validating observed migration patterns. Optimized grids displayed both high model accuracy and reduced computing time compared to grid densities selected in an unguided manner. In addition, EEMS migration maps generated for P. falciparum using the optimized grid corresponded to estimates of malaria endemicity and geographic properties of the study region that might be expected to impact malaria parasite migr
Published: 2020

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