19 results on '"Onyamboko, M"'
Search Results
2. A randomised controlled trial of 3 versus 5 days artemether-lumefantrine regimen for uncomplicated Plasmodium falciparum treatment in pregnancy in Africa
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Onyamboko, M, Hoglund, R, Lee, S, Kabedi, C, Kayembe, D, Badjanga, B, Turner, G, Jackson, N, Tarning, J, McGready, R, Nosten, F, White, N, Day, N, and Fanello, C
- Abstract
Artemether-lumefantrine antimalarial efficacy in pregnancy could be compromised by reduced drug exposure. Population-based simulations suggested that therapeutic efficacy would be improved if the treatment duration was increased. We assessed the efficacy, tolerability and pharmacokinetics of an extended 5-day regimen of artemether-lumefantrine compared to the standard 3-day treatment in 48 pregnant women and 48 non-pregnant women with uncomplicated falciparum malaria in an open-label, randomized clinical trial. Babies were assessed at birth, 1, 3, 6 and 12 months. Nonlinear mixed-effects modelling was used to characterise the plasma concentration-time profiles of artemether and lumefantrine and their metabolites. Both regimens were highly efficacious (100% PCR-corrected cure rates) and well tolerated. Babies followed up to 1 year had normal development. Parasite clearance half-lives were longer in pregnant women (median [range]: 3.30 [1.39-7.83] hours) compared to non-pregnant women (2.43 [1.05-6.00] hours), p=0.005. Pregnant women had lower exposures to artemether and dihydroartemisinin compared to non-pregnant women, resulting in 1.2% decreased exposure for each additional week of gestational age. By term, these exposures were reduced by 48% compared to non-pregnant patients. The overall exposure to lumefantrine was improved with the extended regimen, with no significant differences in exposures to lumefantrine or desbutyl-lumefantrine between pregnant and non-pregnant women. The extended artemether-lumefantrine regimen was well tolerated and safe and increased the overall antimalarial drug exposure, and so could be a promising treatment option in pregnancy in areas with lower malaria transmission and/or emerging drug resistance (http://www.clinicalTrials.gov/;NCT01916954).
- Published
- 2019
3. Treatment of Plasmodium falciparum malaria in the Democratic Republic of the Congo
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Onyamboko, M, Day, N, and Fanello, C
- Abstract
Despite international efforts, the malaria burden remains high worldwide with half of all malaria-attributable deaths occurring in the Democratic Republic of Congo and Nigeria. Children under five and pregnant women bear the heaviest burden. New treatment options for falciparum malaria are urgently needed due to potential wide spreading plasmodium resistance to artemisinin derivatives. In the first study, amodiaquine-artesunate, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) were assessed in 684 Congolese children under 5. The efficacy was good and comparable for all combinations. The short parasitaemia clearance half-life suggested that the local parasite populations are still susceptible to the artemisinin derivatives. DHA-PQ provided the greatest prophylactic effect making it a good candidate for Intermittent Preventive Treatment in pregnancy. Plasma level of piperaquine and lumefantrine in small children at day 7 was however suboptimal indicating the necessity of adjusting the current dosage. Artemether-lumefantrine is the most recommended ACT for malaria treatment in pregnancy although its pharmacokinetics properties are altered in this group. In the second study, the PK, efficacy, safety and tolerability of a 5 days regimen of AL were tested in a group of 48 pregnant women and a control group of 48 non-pregnant women with uncomplicated falciparum malaria versus the standard 3 day regimen. The day 42 PCR corrected efficacy was 100% in both treatment arms. Pregnancy was associated with reduced exposure to both lumefantrine and dihydroartemisinin. The extended regimen improved the exposure to lumefantrine, artemether and DHA in pregnancy. The QTc duration remained normal, but transient hematological or biochemical changes were observed in both groups. Babies born from the women treated in the study displayed a normal physical and neurological development in the first 12 months of life. At delivery 38% of women had placental malaria. The extended AL regimen is a promising option for those areas with emerging artemisinin resistance.
- Published
- 2016
4. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance
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Mok, S, Ashley, E, Ferreira, P, Zhu, L, Lin, Z, Yeo, T, Chotivanich, K, Imwong, M, Pukrittayakamee, S, Dhorda, M, Nguon, C, Lim, P, Amaratunga, C, Suon, S, Hien, T, Htut, Y, Faiz, M, Onyamboko, M, Mayxay, M, Newton, P, Tripura, R, Woodrow, C, Miotto, O, Kwiatkowski, D, and Nosten, F
- Abstract
Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion.
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- 2016
5. Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine
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Fanello, C., primary, Onyamboko, M., additional, Lee, S. J., additional, Woodrow, C., additional, Setaphan, S., additional, Chotivanich, K., additional, Buffet, P., additional, Jauréguiberry, S., additional, Rockett, K., additional, Stepniewska, K., additional, Day, N. P. J., additional, White, N. J., additional, and Dondorp, A. M., additional
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- 2017
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6. Genomic epidemiology of artemisinin resistant malaria
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Amato, R., Miotto, O., Woodrow, C.J., Almagro-Garcia, J., Sinha, I., Campino, S., Mead, D., Drury, E., Kekre, M., Sanders, M., Amambua-Ngwa, A., Amaratunga, C., Amenga-Etego, L., Andrianaranjaka, V., Apinjoh, T., Ashley, E., Auburn, S., Awandare, G.A., Baraka, V., Barry, Alyssa, Boni, M.F., Borrmann, S., Bousema, T., Branch, O., Bull, P.C., Chotivanich, K., Conway, D.J., Craig, A., Day, N.P., Djimdé, A., Dolecek, C., Dondorp, A.M., Drakeley, C., Duffy, P., Echeverry, D.F., Egwang, T.G., Fairhurst, R.M., Faiz, A., Fanello, C.I., Hien, T.T., Hodgson, A., Imwong, M., Ishengoma, D., Lim, P., Lon, C., Marfurt, J., Marsh, K., Mayxay, M., Michon, P., Mobegi, V., Mokuolu, O.A., Montgomery, J., Mueller, I., Kyaw, M.P., Newton, P.N., Nosten, F., Noviyanti, R., Nzila, A., Ocholla, H., Oduro, A., Onyamboko, M., Ouedraogo, J.B., Phyo, A.P.P., Plowe, C., Price, R.N., Pukrittayakamee, S., Randrianarivelojosia, M., Ringwald, P., Ruiz, L., Saunders, D., Shayo, A., Siba, P., Takala-Harrison, S., Thanh, T.N.N., Thathy, V., Verra, F., Wendler, J., White, N.J., Ye, H., Cornelius, V.J., Giacomantonio, R., Muddyman, D., Henrichs, C., Malangone, C., Jyothi, D., Pearson, R.D., Rayner, J.C., McVean, G., Rockett, K.A., Miles, A., Vauterin, P., Jeffery, B., Manske, M., Stalker, J., Macinnis, B., Kwiatkowski, D.P., Amato, R., Miotto, O., Woodrow, C.J., Almagro-Garcia, J., Sinha, I., Campino, S., Mead, D., Drury, E., Kekre, M., Sanders, M., Amambua-Ngwa, A., Amaratunga, C., Amenga-Etego, L., Andrianaranjaka, V., Apinjoh, T., Ashley, E., Auburn, S., Awandare, G.A., Baraka, V., Barry, Alyssa, Boni, M.F., Borrmann, S., Bousema, T., Branch, O., Bull, P.C., Chotivanich, K., Conway, D.J., Craig, A., Day, N.P., Djimdé, A., Dolecek, C., Dondorp, A.M., Drakeley, C., Duffy, P., Echeverry, D.F., Egwang, T.G., Fairhurst, R.M., Faiz, A., Fanello, C.I., Hien, T.T., Hodgson, A., Imwong, M., Ishengoma, D., Lim, P., Lon, C., Marfurt, J., Marsh, K., Mayxay, M., Michon, P., Mobegi, V., Mokuolu, O.A., Montgomery, J., Mueller, I., Kyaw, M.P., Newton, P.N., Nosten, F., Noviyanti, R., Nzila, A., Ocholla, H., Oduro, A., Onyamboko, M., Ouedraogo, J.B., Phyo, A.P.P., Plowe, C., Price, R.N., Pukrittayakamee, S., Randrianarivelojosia, M., Ringwald, P., Ruiz, L., Saunders, D., Shayo, A., Siba, P., Takala-Harrison, S., Thanh, T.N.N., Thathy, V., Verra, F., Wendler, J., White, N.J., Ye, H., Cornelius, V.J., Giacomantonio, R., Muddyman, D., Henrichs, C., Malangone, C., Jyothi, D., Pearson, R.D., Rayner, J.C., McVean, G., Rockett, K.A., Miles, A., Vauterin, P., Jeffery, B., Manske, M., Stalker, J., Macinnis, B., and Kwiatkowski, D.P.
- Published
- 2016
7. Genomic epidemiology of artemisinin resistant malaria
- Author
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Amato, R, Miotto, O, Woodrow, CJ, Almagro-Garcia, J, Sinha, I, Campino, S, Mead, D, Drury, E, Kekre, M, Sanders, M, Amambua-Ngwa, A, Amaratunga, C, Amenga-Etego, L, Andrianaranjaka, V, Apinjoh, T, Ashley, E, Auburn, S, Awandare, GA, Baraka, V, Barry, A, Boni, MF, Borrmann, S, Bousema, T, Branch, O, Bull, PC, Chotivanich, K, Conway, DJ, Craig, A, Day, NP, Djimde, A, Dolecek, C, Dondorp, AM, Drakeley, C, Duffy, P, Echeverry, DF, Egwang, TG, Fairhurst, RM, Faiz, MA, Fanello, CI, Tran, TH, Hodgson, A, Imwong, M, Ishengoma, D, Lim, P, Lon, C, Marfurt, J, Marsh, K, Mayxay, M, Michon, P, Mobegi, V, Mokuolu, OA, Montgomery, J, Mueller, I, Kyaw, MP, Newton, PN, Nosten, F, Noviyanti, R, Nzila, A, Ocholla, H, Oduro, A, Onyamboko, M, Ouedraogo, J-B, Phyo, APP, Plowe, C, Price, RN, Pukrittayakamee, S, Randrianarivelojosia, M, Ringwald, P, Ruiz, L, Saunders, D, Shayo, A, Siba, P, Takala-Harrison, S, Thanh, T-NN, Thathy, V, Verra, F, Wendler, J, White, NJ, Ye, H, Cornelius, VJ, Giacomantonio, R, Muddyman, D, Henrichs, C, Malangone, C, Jyothi, D, Pearson, RD, Rayner, JC, McVean, G, Rockett, KA, Miles, A, Vauterin, P, Jeffery, B, Manske, M, Stalker, J, Maclnnis, B, Kwiatkowski, DP, Amato, R, Miotto, O, Woodrow, CJ, Almagro-Garcia, J, Sinha, I, Campino, S, Mead, D, Drury, E, Kekre, M, Sanders, M, Amambua-Ngwa, A, Amaratunga, C, Amenga-Etego, L, Andrianaranjaka, V, Apinjoh, T, Ashley, E, Auburn, S, Awandare, GA, Baraka, V, Barry, A, Boni, MF, Borrmann, S, Bousema, T, Branch, O, Bull, PC, Chotivanich, K, Conway, DJ, Craig, A, Day, NP, Djimde, A, Dolecek, C, Dondorp, AM, Drakeley, C, Duffy, P, Echeverry, DF, Egwang, TG, Fairhurst, RM, Faiz, MA, Fanello, CI, Tran, TH, Hodgson, A, Imwong, M, Ishengoma, D, Lim, P, Lon, C, Marfurt, J, Marsh, K, Mayxay, M, Michon, P, Mobegi, V, Mokuolu, OA, Montgomery, J, Mueller, I, Kyaw, MP, Newton, PN, Nosten, F, Noviyanti, R, Nzila, A, Ocholla, H, Oduro, A, Onyamboko, M, Ouedraogo, J-B, Phyo, APP, Plowe, C, Price, RN, Pukrittayakamee, S, Randrianarivelojosia, M, Ringwald, P, Ruiz, L, Saunders, D, Shayo, A, Siba, P, Takala-Harrison, S, Thanh, T-NN, Thathy, V, Verra, F, Wendler, J, White, NJ, Ye, H, Cornelius, VJ, Giacomantonio, R, Muddyman, D, Henrichs, C, Malangone, C, Jyothi, D, Pearson, RD, Rayner, JC, McVean, G, Rockett, KA, Miles, A, Vauterin, P, Jeffery, B, Manske, M, Stalker, J, Maclnnis, B, and Kwiatkowski, DP
- Abstract
The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.
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- 2016
8. Randomized Comparison of the Efficacies and Tolerabilities of Three Artemisinin-Based Combination Treatments for Children with Acute Plasmodium falciparum Malaria in the Democratic Republic of the Congo
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Onyamboko, M. A., primary, Fanello, C. I., additional, Wongsaen, K., additional, Tarning, J., additional, Cheah, P. Y., additional, Tshefu, K. A., additional, Dondorp, A. M., additional, Nosten, F., additional, White, N. J., additional, and Day, N. P. J., additional
- Published
- 2014
- Full Text
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9. Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial
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von Seidlein, L., primary, Olaosebikan, R., additional, Hendriksen, I. C. E., additional, Lee, S. J., additional, Adedoyin, O. T., additional, Agbenyega, T., additional, Nguah, S. B., additional, Bojang, K., additional, Deen, J. L., additional, Evans, J., additional, Fanello, C. I., additional, Gomes, E., additional, Pedro, A. J., additional, Kahabuka, C., additional, Karema, C., additional, Kivaya, E., additional, Maitland, K., additional, Mokuolu, O. A., additional, Mtove, G., additional, Mwanga-Amumpaire, J., additional, Nadjm, B., additional, Nansumba, M., additional, Ngum, W. P., additional, Onyamboko, M. A., additional, Reyburn, H., additional, Sakulthaew, T., additional, Silamut, K., additional, Tshefu, A. K., additional, Umulisa, N., additional, Gesase, S., additional, Day, N. P. J., additional, White, N. J., additional, and Dondorp, A. M., additional
- Published
- 2012
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10. Randomized Comparison of the Efficacies and Tolerabilities of Three Artemisinin-Based Combination Treatments for Children with Acute Plasmodium falciparumMalaria in the Democratic Republic of the Congo
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Onyamboko, M. A., Fanello, C. I., Wongsaen, K., Tarning, J., Cheah, P. Y., Tshefu, K. A., Dondorp, A. M., Nosten, F., White, N. J., and Day, N. P. J.
- Abstract
ABSTRACTAn open-label, randomized controlled trial was carried out in 2011–2012 in the Democratic Republic of the Congo to test the efficacy, safety, and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate, and artemether-lumefantrine. Six hundred eighty-four children aged 3 to 59 months with uncomplicated Plasmodium falciparummalaria were randomly allocated to each study arm. Children were hospitalized for 3 days, given supervised treatment, and followed up weekly for 42 days. All regimens were well tolerated and rapidly effective. The median parasitemia clearance half-life was 2.2 h, and half-lives were similar between arms (P= 0.19). The PCR-uncorrected cure rates by day 42 were 73.0% for amodiaquine-artesunate, 70.2% for artemether-lumefantrine, and 86.3% for dihydroartemisinin-piperaquine (P= 0.001). Early treatment failure occurred in three patients (0.5%), one in each arm. The PCR-corrected cure rates were 93.4% for amodiaquine-artesunate, 92.7% for artemether-lumefantrine, and 94.3% for dihydroartemisinin-piperaquine (P= 0.78). The last provided a longer posttreatment prophylactic effect than did the other two treatments. The day 7 plasma concentration of piperaquine was below 30 ng/ml in 47% of the children treated with dihydroartemisinin-piperaquine, and the day 7 lumefantrine concentration was below 280 ng/ml in 37.0% of children who received artemether-lumefantrine. Thus, although cure rates were all satisfactory, they could be improved by increasing the dose. (This study has been registered with the International Standard Randomized Controlled Trial Number Register [www.isrctn.org] under registration no. ISRCTN20984426.)
- Published
- 2014
- Full Text
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11. Prevalence and Risk Factors of Neonatal Hyperbilirubinemia in a Semi-Rural Area of the Democratic Republic of Congo: A Cohort Study.
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Fanello C, Lee SJ, Bancone G, Kayembe D, Ndjowo P, Badjanga B, Gornsawun G, Chotthanawathit P, Waithira N, White NJ, and Onyamboko M
- Subjects
- Humans, Democratic Republic of the Congo epidemiology, Infant, Newborn, Risk Factors, Female, Prevalence, Adult, Male, Glucosephosphate Dehydrogenase Deficiency epidemiology, Glucosephosphate Dehydrogenase Deficiency blood, Cohort Studies, Young Adult, Pregnancy, Hyperbilirubinemia, Neonatal epidemiology, Hyperbilirubinemia, Neonatal etiology, Hyperbilirubinemia, Neonatal blood, Rural Population
- Abstract
Neonatal hyperbilirubinemia (NH) is a frequent condition that, if left untreated, can lead to neurological disability and death. We assessed the prevalence of NH and associated neonatal and maternal risk factors in 362 mothers and 365 newborns in a semi-rural area of the Democratic Republic of Congo. In addition, we explored the knowledge and practices of mothers regarding this condition. We collected demographic data, anthropometric data, and obstetric and medical anamneses. We examined newborns at birth and at 24, 48, and 72 hours and measured bilirubin at birth in umbilical cord and capillary blood and thereafter in capillary blood. Hemoglobin, hematocrit, ABO group, Rhesus factor, glucose-6-phosphate dehydrogenase (G6PD) deficiency, Hemoglobin S (HbS), and malaria were assessed in mothers and newborns. Among 296 newborns (all time points available), 5.7% developed NH (95% CI: 3.4-9.0) between 24 and 72 hours according to National Institute for Health and Care Excellence (NICE) UK guidelines. There was a significantly higher risk in newborns with G6PD deficiency (homo- and hemizygous adjusted Odd Ratio [aOR]: 21.0, 95% CI: 4.1-105.9), preterm births (aOR: 6.1, 95% CI: 1.4-26.9), newborns with excessive birth weight loss (aOR: 5.8, 95% CI: 1.4-23.2), and hyperbilirubinemia at birth (aOR: 14.8, 95% CI: 2.7-79.6). Newborns with feto-maternal ABO incompatibility and G6PD deficiency had significantly higher bilirubin at birth than others. More than 60% of mothers had adequate knowledge of NH, but compliance with phototherapy in the absence of symptoms was low. Although risk factors for NH are common in this area, prevalence was not high, suggesting a need for better case definition. Implementation of point-of-care devices for diagnosis and awareness programs on risk prevention could help reduce neonatal morbidity and mortality associated with hyperbilirubinemia in these areas.
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- 2023
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12. Stopping prereferral rectal artesunate - a grave error.
- Author
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Watson JA, Warsame M, Peto TJ, Onyamboko M, Fanello C, Dondorp AM, and White N
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- Artesunate therapeutic use, Humans, Referral and Consultation, Antimalarials therapeutic use, Malaria
- Abstract
Competing Interests: Competing interests: MW, TJP and NW were investigators on study 13 (reference 6). The authors declare no competing interests.
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- 2022
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13. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination.
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Jacob CG, Thuy-Nhien N, Mayxay M, Maude RJ, Quang HH, Hongvanthong B, Vanisaveth V, Ngo Duc T, Rekol H, van der Pluijm R, von Seidlein L, Fairhurst R, Nosten F, Hossain MA, Park N, Goodwin S, Ringwald P, Chindavongsa K, Newton P, Ashley E, Phalivong S, Maude R, Leang R, Huch C, Dong LT, Nguyen KT, Nhat TM, Hien TT, Nguyen H, Zdrojewski N, Canavati S, Sayeed AA, Uddin D, Buckee C, Fanello CI, Onyamboko M, Peto T, Tripura R, Amaratunga C, Myint Thu A, Delmas G, Landier J, Parker DM, Chau NH, Lek D, Suon S, Callery J, Jittamala P, Hanboonkunupakarn B, Pukrittayakamee S, Phyo AP, Smithuis F, Lin K, Thant M, Hlaing TM, Satpathi P, Satpathi S, Behera PK, Tripura A, Baidya S, Valecha N, Anvikar AR, Ul Islam A, Faiz A, Kunasol C, Drury E, Kekre M, Ali M, Love K, Rajatileka S, Jeffreys AE, Rowlands K, Hubbart CS, Dhorda M, Vongpromek R, Kotanan N, Wongnak P, Almagro Garcia J, Pearson RD, Ariani CV, Chookajorn T, Malangone C, Nguyen T, Stalker J, Jeffery B, Keatley J, Johnson KJ, Muddyman D, Chan XHS, Sillitoe J, Amato R, Simpson V, Gonçalves S, Rockett K, Day NP, Dondorp AM, Kwiatkowski DP, and Miotto O
- Subjects
- Animals, Asia, Southeastern, Bangladesh, Democratic Republic of the Congo, India, Plasmodium drug effects, Communicable Disease Control statistics & numerical data, Disease Eradication statistics & numerical data, Drug Resistance genetics, Malaria prevention & control, Plasmodium genetics
- Abstract
Background: National 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., Methods: Samples 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., Results: GenRe-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., Conclusions: GenRe-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., Funding: The 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 National Institute of Allergy and Infectious Diseases., Competing Interests: CJ, NT, MM, RM, HQ, BH, VV, TN, HR, Rv, Lv, RF, FN, MH, NP, SG, PR, KC, PN, EA, SP, RM, RL, CH, LD, KN, TN, TH, AS, DU, CB, CF, MO, TP, RT, CA, AM, GD, JL, DP, NC, DL, SS, JC, PJ, BH, SP, AP, FS, KL, MT, TH, PS, SS, PB, AT, SB, NV, AA, AU, AF, CK, ED, MK, MA, KL, SR, AJ, KR, CH, MD, RV, NK, PW, JA, RP, CA, TC, CM, TN, JS, BJ, JK, KJ, DM, XC, JS, RA, VS, SG, KR, ND, AD, DK, OM No competing interests declared, HN, NZ, SC is an employee of Vysnova Partners Inc
- Published
- 2021
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14. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.
- Author
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van der Pluijm RW, Tripura R, Hoglund RM, Pyae Phyo A, Lek D, Ul Islam A, Anvikar AR, Satpathi P, Satpathi S, Behera PK, Tripura A, Baidya S, Onyamboko M, Chau NH, Sovann Y, Suon S, Sreng S, Mao S, Oun S, Yen S, Amaratunga C, Chutasmit K, Saelow C, Runcharern R, Kaewmok W, Hoa NT, Thanh NV, Hanboonkunupakarn B, Callery JJ, Mohanty AK, Heaton J, Thant M, Gantait K, Ghosh T, Amato R, Pearson RD, Jacob CG, Gonçalves S, Mukaka M, Waithira N, Woodrow CJ, Grobusch MP, van Vugt M, Fairhurst RM, Cheah PY, Peto TJ, von Seidlein L, Dhorda M, Maude RJ, Winterberg M, Thuy-Nhien NT, Kwiatkowski DP, Imwong M, Jittamala P, Lin K, Hlaing TM, Chotivanich K, Huy R, Fanello C, Ashley E, Mayxay M, Newton PN, Hien TT, Valecha N, Smithuis F, Pukrittayakamee S, Faiz A, Miotto O, Tarning J, Day NPJ, White NJ, and Dondorp AM
- Subjects
- Adolescent, Adult, Amodiaquine administration & dosage, Amodiaquine therapeutic use, Anthraquinones administration & dosage, Anthraquinones therapeutic use, Antimalarials administration & dosage, Artemether, Lumefantrine Drug Combination administration & dosage, Artemether, Lumefantrine Drug Combination therapeutic use, Artemisinins administration & dosage, Drug Resistance, Drug Therapy, Combination, Female, Humans, Male, Mefloquine administration & dosage, Mefloquine therapeutic use, Plasmodium falciparum drug effects, Polymerase Chain Reaction, Quinolines administration & dosage, Quinolines therapeutic use, Treatment Outcome, Young Adult, Antimalarials therapeutic use, Artemisinins therapeutic use, Malaria, Falciparum drug therapy
- Abstract
Background: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance., Methods: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2-65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin-piperaquine or dihydroartemisinin-piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate-mefloquine or dihydroartemisinin-piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether-lumefantrine or artemether-lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete., Findings: Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin-piperaquine (183 [17%]), dihydroartemisinin-piperaquine plus mefloquine (269 [24%]), artesunate-mefloquine (73 [7%]), artemether-lumefantrine (289 [26%]), or artemether-lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin-piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin-piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p<0·0001). Efficacy of dihydroartemisinin-piperaquine plus mefloquine in the three sites in Myanmar was 91% (42 of 46; 95% CI 79 to 98) versus 100% (42 of 42; 95% CI 92 to 100) after dihydroartemisinin-piperaquine (risk difference 9%, 95% CI 1 to 17; p=0·12). The 42-day PCR corrected efficacy of dihydroartemisinin-piperaquine plus mefloquine (96% [68 of 71; 95% CI 88 to 99]) was non-inferior to that of artesunate-mefloquine (95% [69 of 73; 95% CI 87 to 99]) in three sites in Cambodia (risk difference 1%; 95% CI -6 to 8; p=1·00). The overall 42-day PCR-corrected efficacy of artemether-lumefantrine plus amodiaquine (98% [281 of 286; 95% CI 97 to 99]) was similar to that of artemether-lumefantrine (97% [279 of 289; 95% CI 94 to 98]; risk difference 2%, 95% CI -1 to 4; p=0·30). Both TACTs were well tolerated, although early vomiting (within 1 h) was more frequent after dihydroartemisinin-piperaquine plus mefloquine (30 [3·8%] of 794) than after dihydroartemisinin-piperaquine (eight [1·5%] of 543; p=0·012). Vomiting after artemether-lumefantrine plus amodiaquine (22 [1·3%] of 1703) and artemether-lumefantrine (11 [0·6%] of 1721) was infrequent. Adding amodiaquine to artemether-lumefantrine extended the electrocardiogram corrected QT interval (mean increase at 52 h compared with baseline of 8·8 ms [SD 18·6] vs 0·9 ms [16·1]; p<0·01) but adding mefloquine to dihydroartemisinin-piperaquine did not (mean increase of 22·1 ms [SD 19·2] for dihydroartemisinin-piperaquine vs 20·8 ms [SD 17·8] for dihydroartemisinin-piperaquine plus mefloquine; p=0·50)., Interpretation: Dihydroartemisinin-piperaquine plus mefloquine and artemether-lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe treatments of uncomplicated P falciparum malaria, including in areas with artemisinin and ACT partner-drug resistance., Funding: UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and US National Institutes of Health., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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15. Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.
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Taylor WR, Naw HK, Maitland K, Williams TN, Kapulu M, D'Alessandro U, Berkley JA, Bejon P, Okebe J, Achan J, Amambua AN, Affara M, Nwakanma D, van Geertruyden JP, Mavoko M, Lutumba P, Matangila J, Brasseur P, Piola P, Randremanana R, Lasry E, Fanello C, Onyamboko M, Schramm B, Yah Z, Jones J, Fairhurst RM, Diakite M, Malenga G, Molyneux M, Rwagacondo C, Obonyo C, Gadisa E, Aseffa A, Loolpapit M, Henry MC, Dorsey G, John C, Sirima SB, Barnes KI, Kremsner P, Day NP, White NJ, and Mukaka M
- Subjects
- Adolescent, Adult, Africa South of the Sahara, Age Factors, Aged, Aged, 80 and over, Antimalarials administration & dosage, Antimalarials adverse effects, Child, Child, Preschool, Clinical Protocols, Dose-Response Relationship, Drug, Female, Glucosephosphate Dehydrogenase Deficiency, Humans, Infant, Malaria, Falciparum drug therapy, Malaria, Falciparum transmission, Male, Middle Aged, Plasmodium falciparum, Primaquine administration & dosage, Primaquine adverse effects, Young Adult, Antimalarials therapeutic use, Malaria, Falciparum prevention & control, Primaquine therapeutic use
- Abstract
Background: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa., Methods: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses., Results: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively., Conclusions: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.
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- 2018
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16. Genetic architecture of artemisinin-resistant Plasmodium falciparum.
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Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, Lim P, Mead D, Oyola SO, Dhorda M, Imwong M, Woodrow C, Manske M, Stalker J, Drury E, Campino S, Amenga-Etego L, Thanh TN, Tran HT, Ringwald P, Bethell D, Nosten F, Phyo AP, Pukrittayakamee S, Chotivanich K, Chuor CM, Nguon C, Suon S, Sreng S, Newton PN, Mayxay M, Khanthavong M, Hongvanthong B, Htut Y, Han KT, Kyaw MP, Faiz MA, Fanello CI, Onyamboko M, Mokuolu OA, Jacob CG, Takala-Harrison S, Plowe CV, Day NP, Dondorp AM, Spencer CC, McVean G, Fairhurst RM, White NJ, and Kwiatkowski DP
- Subjects
- Drug Resistance genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study methods, Humans, Malaria, Falciparum drug therapy, Malaria, Falciparum parasitology, Mutation, Polymorphism, Single Nucleotide, Antimalarials pharmacology, Artemisinins pharmacology, Genome, Protozoan, Plasmodium falciparum drug effects, Plasmodium falciparum genetics
- Abstract
We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new resistance-causing mutations emerging is determined by specific predisposing genetic factors in the underlying parasite population.
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- 2015
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17. Tobacco use and secondhand smoke exposure during pregnancy in two African countries: Zambia and the Democratic Republic of the Congo.
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Chomba E, Tshefu A, Onyamboko M, Kaseba-Sata C, Moore J, McClure EM, Moss N, Goco N, Bloch M, and Goldenberg RL
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- Adult, Advertising, Cross-Sectional Studies, Democratic Republic of the Congo epidemiology, Educational Status, Female, Humans, Pregnancy, Prospective Studies, Surveys and Questionnaires, Tobacco, Smokeless, Zambia epidemiology, Health Knowledge, Attitudes, Practice, Maternal Exposure, Smoking epidemiology, Tobacco Smoke Pollution statistics & numerical data
- Abstract
Objective: To study pregnant women's knowledge, attitudes and behaviors towards tobacco use and secondhand smoke (SHS) exposure, and exposure to advertising for and against tobacco products in Zambia and the Democratic Republic of the Congo (DRC)., Design: Prospective cross-sectional survey between November 2004 and September 2005., Setting: Antenatal care clinics in Lusaka, Zambia, and Kinshasa, DRC., Population: Pregnant women in Zambia (909) and the DRC (847)., Methods: Research staff administered a structured questionnaire to pregnant women attending antenatal care clinics., Main Outcome Measures: Pregnant women's use of tobacco, exposure to SHS, knowledge of the harms of tobacco and exposure to advertising for and against tobacco products., Results: Only about 10% of pregnant women reported ever having tried cigarettes (6.6% Zambia; 14.1% DRC). However, in the DRC, 41.8% of pregnant women had tried other forms of tobacco, primarily snuff. About 10% of pregnant women and young children were frequently or always exposed to SHS. Pregnant women's knowledge of the hazards of smoking and SHS exposure was extremely limited. About 13% of pregnant women had seen or heard advertising for tobacco products in the last 30 days., Conclusions: Tobacco use and SHS exposure pose serious threats to the health of women, infants and children. In many African countries, maternal and infant health outcomes are often poor and will likely worsen if maternal tobacco use increases. Our findings suggest that a 'window of opportunity' exists to prevent increased tobacco use and SHS exposure of pregnant women in Zambia and the DRC.
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- 2010
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18. Exposure of pregnant women to indoor air pollution: a study from nine low and middle income countries.
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Kadir MM, McClure EM, Goudar SS, Garces AL, Moore J, Onyamboko M, Kaseba C, Althabe F, Castilla EE, Freire S, Parida S, Saleem S, Wright LL, and Goldenberg RL
- Subjects
- Adult, Africa epidemiology, Air Pollution, Indoor adverse effects, Asia epidemiology, Charcoal, Cooking, Cross-Sectional Studies, Developing Countries, Female, Fires, Heating, Humans, Latin America epidemiology, Pregnancy, Prospective Studies, Tobacco Smoke Pollution statistics & numerical data, Wood, Air Pollution, Indoor statistics & numerical data, Maternal Exposure statistics & numerical data
- Abstract
Objective: We studied exposure to solid fuel and second-hand tobacco smoke among pregnant women in south Asia, Africa and Latin America., Design: Prospective cross-sectional survey., Setting: Antenatal clinics in Argentina, Brazil, Ecuador, Guatemala, Uruguay, Democratic Republic of Congo, Zambia, India and Pakistan., Sample: A total of 7,961 pregnant women in ten sites in nine countries were interviewed between October 2004 and September 2005., Methods: A standardized questionnaire on exposure to indoor air pollution (IAP) and second-hand smoke was administered to pregnant women during antenatal care., Main Outcome Measures: Exposure to IAP and second-hand tobacco smoke., Results: South Asian pregnant women commonly reported use of wood (49.1-89.7%), crop residue and animal dung as cooking and heating fuel. African pregnant women reported higher use of charcoal (85.4-93.5%). Latin American pregnant women had greater use of petroleum gas. Among south Asian women, solid fuel use and cooking on an open flame inside the home were common. There was a significant association between solid fuel use and allowing smoking within the home at the Asian sites and in Zambia (p < 0.05)., Conclusions: Pregnant women from low/middle income countries were commonly exposed to IAP secondary to use of solid fuels. Among these populations, exposure to second-hand tobacco smoke was also common. This combination of exposures likely increases the risk of poor pregnancy outcomes among the most vulnerable women. Our study highlights the importance of further research on the combined impact of IAP and second-hand tobacco smoke exposures on adverse maternal and perinatal outcomes.
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- 2010
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19. Tobacco use and secondhand smoke exposure during pregnancy: an investigative survey of women in 9 developing nations.
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Bloch M, Althabe F, Onyamboko M, Kaseba-Sata C, Castilla EE, Freire S, Garces AL, Parida S, Goudar SS, Kadir MM, Goco N, Thornberry J, Daniels M, Bartz J, Hartwell T, Moss N, and Goldenberg R
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- Adolescent, Adult, Argentina epidemiology, Brazil epidemiology, Cross-Sectional Studies, Democratic Republic of the Congo epidemiology, Ecuador epidemiology, Female, Guatemala epidemiology, Health Knowledge, Attitudes, Practice, Health Surveys, Humans, India epidemiology, Middle Aged, Pakistan epidemiology, Population Surveillance, Pregnancy, Pregnancy Complications psychology, Risk Factors, Surveys and Questionnaires, Uruguay epidemiology, Zambia epidemiology, Attitude to Health, Developing Countries statistics & numerical data, Pregnancy Complications epidemiology, Pregnant Women psychology, Tobacco Smoke Pollution statistics & numerical data
- Abstract
Objectives: We examined pregnant women's use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa., Methods: Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005., Results: At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home., Conclusions: Pregnant women's tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.
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- 2008
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