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Background: The Magude Project assessed the feasibility of eliminating malaria in Magude district, a low transmission setting in southern Mozambique, using a package of interventions, including long-lasting insecticidal nets (LLINs). As the efficacy of LLINs depends in part on their physical integrity, this metric was quantified for Olyset® Nets post mass-distribution, in addition to net use, care and handling practices and other risk factors associated with net physical integrity., Methods: Nets were collected during a cross-sectional net evaluation, nine months after the Magude project commenced, which was 2 years after the nets were distributed by the National Malaria Control Programme (NMCP). The physical integrity of the nets was assessed by counting and sizing the holes at different positions on each net. A structured questionnaire was administered to assess how the selected net was used and treated (care, wash and repair). Net bio-efficacy was assessed following the standard World Health Organization (WHO) cone bioassay procedures., Results: Out of the 170 Olyset® Nets included in the analysis, 63.5% had been used the night before. The main reason for not using a net was the notion that there were no mosquitoes present. The average number of people using each net was 1.79. Two thirds of the nets had only been washed once or twice since distribution. Most nets (80.9%) were holed and 18% were torn, but none of the risk factors were significantly associated with net integrity, except for presence of mice in the household. Less than half of the participants noticed holes in holed nets, and of those only 38.6% attempted to repair those. None of the six nets that were tested for bio-efficacy passed the WHO threshold of 80% mosquito mortality., Conclusion: Overall the majority of Olyset® Nets were in serviceable condition two years post-distribution, but their insecticidal effect may have been lost. This study-together with previous evidence on suboptimal access to and use of LLINs in Magude district-highlights that LLINs as an intervention could have been optimized during the Magude project to achieve maximum intervention impact., (© 2024. The Author(s).)

Background: Although the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin in Plasmodium falciparum on the continent is troubling, given the lack of alternative treatments., Methods: In this study, we used data from drug-efficacy studies conducted between 2016 and 2019 that evaluated 3-day courses of artemisinin-based combination therapy (artesunate-amodiaquine or artemether-lumefantrine) for uncomplicated malaria in Eritrea to estimate the percentage of patients with day-3 positivity (i.e., persistent P. falciparum parasitemia 3 days after the initiation of therapy). We also assayed parasites for mutations in Pfkelch13 as predictive markers of partial resistance to artemisinin and screened for deletions in hrp2 and hrp3 that result in variable performance of histidine rich protein 2 (HRP2)-based rapid diagnostic tests for malaria., Results: We noted an increase in the percentage of patients with day-3 positivity from 0.4% (1 of 273) in 2016 to 1.9% (4 of 209) in 2017 and 4.2% (15 of 359) in 2019. An increase was also noted in the prevalence of the Pfkelch13 R622I mutation, which was detected in 109 of 818 isolates before treatment, from 8.6% (24 of 278) in 2016 to 21.0% (69 of 329) in 2019. The odds of day-3 positivity increased by a factor of 6.2 (95% confidence interval, 2.5 to 15.5) among the patients with Pfkelch13 622I variant parasites. Partial resistance to artemisinin, as defined by the World Health Organization, was observed in Eritrea. More than 5% of the patients younger than 15 years of age with day-3 positivity also had parasites that carried Pfkelch13 R622I. In vitro, the R622I mutation conferred a low level of resistance to artemisinin when edited into NF54 and Dd2 parasite lines. Deletions in both hrp2 and hrp3 were identified in 16.9% of the parasites that carried the Pfkelch13 R622I mutation, which made them potentially undetectable by HRP2-based rapid diagnostic tests., Conclusions: The emergence and spread of P. falciparum lineages with both Pfkelch13 -mediated partial resistance to artemisinin and deletions in hrp2 and hrp3 in Eritrea threaten to compromise regional malaria control and elimination campaigns. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry numbers, ACTRN12618001223224, ACTRN12618000353291, and ACTRN12619000859189.)., (Copyright © 2023 Massachusetts Medical Society.)

Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Importance: The war in Tigray, Ethiopia, has disrupted the health care system of the region. However, its association with health care services disruption for chronic diseases has not been well documented., Objective: To assess the association of the war with the utilization of health care services for patients with chronic diseases., Design, Setting, and Participants: Of 135 primary health care facilities, a registry-based cross-sectional study was conducted on 44 rural and semiurban facilities of Tigray. Data on health services utilization were extracted for patients with tuberculosis, HIV, diabetes, hypertension, and psychiatric disorders in the prewar period (September 1, to October 31, 2020) and during the first phase of the war period (November 4, 2020, to June 30, 2021)., Main Outcomes and Measures: Records on the number of follow-up, laboratory tests, and patients undergoing treatment of the aforementioned chronic diseases were counted during the prewar and war periods., Results: Of 4645 records of patients with chronic diseases undergoing treatment during the prewar period, 998 records (21%) indicated having treatment during the war period. Compared with the prewar period, 59 of 180 individuals (33%; 95% CI, 26%-40%) had tuberculosis, 522 of 2211 (24%; 95% CI, 22%-26%) had HIV, 228 of 1195 (19%; 95% CI, 17%-21%) had hypertension, 123 of 632 (20%; 95% CI, 16%-22%) had psychiatric disorders, and 66 of 427 (15%; 95% CI, 12%-18%) had type 2 diabetes records, which revealed continued treatment during the war period. Of 174 records of patients with type 1 diabetes in the prewar period, at 2 to 3 months into the war, the numbers dropped to 10 with 94% decline compared with prewar observations., Conclusions and Relevance: This study found that the war in Tigray has resulted in critical health care service disruption and high loss to follow-up for patients with chronic disease, likely leading to increased morbidity and mortality. Local, national, and global policymakers must understand the extent and impact of the service disruption and urge their efforts toward restoration of those services.

Introduction: Sexual and gender-based violence (SGBV) during armed conflicts has serious ramifications with women and girls disproportionally affected. The impact of the conflict that erupted in November 2020 in Tigray on SGBV is not well documented. This study is aimed at assessing war-related SGBV in war-affected Tigray, Ethiopia., Methods: A community-based survey was conducted in 52 (out of 84) districts of Tigray, excluding its western zone and some districts bordering Eritrea due to security reasons. Using a two-stage multistage cluster sampling technique, a total of 5171 women of reproductive age (15-49 years) were randomly selected and included in the study. Analysis used weighted descriptive statistics, regression modelling and tests of associations., Results: Overall, 43.3% (2241/5171) of women experienced at least one type of gender-based violence. The incidents of sexual, physical and psychological violence, and rape among women of reproductive age were found to be 9.7% (500/5171), 28.6% (1480/5171), 40.4% (2090/5171) and 7.9% (411/5171), respectively. Of the sexual violence survivors, rape accounted for 82.2% (411/500) cases, of which 68.4% (247) reported being gang raped. Young women (aged 15-24 years) were the most affected by sexual violence, 29.2% (146/500). Commonly reported SGBV-related issues were physical trauma, 23.8% (533/2241), sexually transmitted infections, 16.5% (68/411), HIV infection, 2.7% (11/411), unwanted pregnancy, 9.5% (39/411) and depression 19.2% (431/2241). Most survivors (89.7%) did not receive any postviolence medical or psychological support., Conclusions: Systemic war-related SGBV was prevalent in Tigray, with gang-rape as the most common form of sexual violence. Immediate medical and psychological care, and long-term rehabilitation and community support for survivors are urgently needed and recommended., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: COVID-19 is a deadly pandemic caused by an RNA virus that belongs to the family of CORONA virus. To counter the COVID-19 pandemic in resource limited settings, it is essential to identify the risk factors of COVID-19 mortality. This study was conducted to identify the social and clinical determinants of mortality in COVID-19 patients hospitalized in four treatment centers of Tigray, Northern Ethiopia., Methods: We reviewed data from 6,637 COVID-19 positive cases that were reported from May 7, 2020 to October 28, 2020. Among these, 925 were admitted to the treatment centers because of their severity and retrospectively analyzed. The data were entered into STATA 16 version for analysis. The descriptive analysis such as median, interquartile range, frequency distribution and percentage were used. Binary logistic regression model was fitted to identify the potential risk factors of mortality of COVID-19 patients. The adjusted odds ratio (AOR) with 95% confidence interval was used to determine the magnitude of the association between the outcome and predictor variables., Results: The median age of the patients was 30 years (IQR, 25-44) and about 70% were male patients. The patients in the non-survivor group were much older than those in the survivor group (median 57.5 years versus 30 years, p-value < 0.001). The overall case fatality rate was 6.1% (95% CI: 4.5% - 7.6%) and was increased to 40.3% (95% CI: 32.2% - 48.4%) among patients with critical and severe illness. The proportions of severe and critical illness in the non-survivor group were significantly higher than those in the survivor group (19.6% versus 5.1% for severe illness and 80.4% versus 4.5% for critical illness, all p-value < 0.001). One or more pre-existing comorbidities were present in 12.5% of the patients: cardiovascular diseases (42.2%), diabetes mellitus (25.0%) and respiratory diseases (16.4%) being the most common comorbidities. The comorbidity rate in the non-survivor group (44.6%) was higher than in the survivor group (10.5%). The results from the multivariable binary regression showed that the odds of mortality was higher for patients who had cardiovascular diseases (AOR = 2.49, 95% CI: 1.03-6.03), shortness of breath (AOR = 9.71, 95% CI: 4.73-19.93) and body weakness (AOR = 3.04, 95% CI: 1.50-6.18). Moreover, the estimated odds of mortality significantly increased with patient's age., Conclusions: Age, cardiovascular diseases, shortness of breath and body weakness were the predictors for mortality of COVID-19 patients. Knowledge of these could lead to better identification of high risk COVID-19 patients and thus allow prioritization to prevent mortality., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: None declared.

(1) Background: Laboratory-based molecular assays are the gold standard to detect SARS-CoV-2. In resource-limited settings, the implementation of these assays has been hampered by operational challenges and long turnaround times. Rapid antigen detection tests are an attractive alternative. Our aim is to evaluate the clinical performance of two SARS-CoV-2 rapid antigen tests during a high transmission period. (2) Methods: A total of 1277 patients seeking SARS-CoV-2 diagnosis were enrolled at four health facilities. Nasopharyngeal swabs for rapid antigen and real time PCR testing were collected for each patient. Sensitivity, specificity, positive and negative predictive values, misclassification rate, and agreement were determined. (3) Results: The overall sensitivity of Panbio COVID-19 was 41.3% (95% CI: 34.6-48.4%) and the specificity was 98.2% (95% CI: 96.2-99.3%). The Standard Q had an overall sensitivity and specificity of 45.0% (95% CI: 39.9-50.2%) and 97.6% (95% CI: 95.3-99.0%), respectively. The positive predictive value of a positive test was 93.3% and 95.4% for the Panbio and Standard Q Ag-RDTs, respectively. A higher sensitivity of 43.2% and 49.4% was observed in symptomatic cases for the Panbio and Standard Q Ag-RDTs, respectively. (4) Conclusions: Despite the overall low sensitivity, the two evaluated rapid tests are useful to improve the diagnosis of symptomatic SARS-CoV-2 infections during high transmission periods.

Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix ® ) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction.

The war in Tigray region of Ethiopia that started in November 2020 and is still ongoing has brought enormous damage to the health system. This analysis provides an assessment of the health system before and during the war. Evidence of damage was compiled from November 2020 to June 2021 from various reports by the interim government of Tigray, and also by international non-governmental organisations. Comparison was made with data from the prewar calendar year. Six months into the war, only 30% of hospitals, 17% of health centres, 11.5% of ambulances and none of the 712 health posts were functional. As of June 2021, the population in need of emergency food assistance in Tigray increased from less than one million to over 5.2 million. While the prewar performance of antenatal care, supervised delivery, postnatal care and children vaccination was 64%, 73%, 63% and 73%, respectively, but none of the services were likely to be delivered in the first 90 days of the war. A conservative estimate places the number of girls and women raped in the first 5 months of the war to be 10 000. These data indicate a widespread destruction of livelihoods and a collapse of the healthcare system. The use of hunger and rape as a weapon of war and the targeting of healthcare facilities are key components of the war. To avert worsening conditions, an immediate intervention is needed to deliver food and supplies and rehabilitate the healthcare delivery system and infrastructure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cryptosporidium is a leading cause of childhood diarrhoea and associated physical and cognitive impairment in low-resource settings. Cryptosporidium -positive faecal samples ( n = 190) from children aged ≤ 5 years enrolled in the Global Enteric Multicenter Study (GEMS) in Mozambique detected by ELISA (11.5%, 430/3754) were successfully PCR-amplified and sequenced at the gp60 or ssu rRNA loci for species determination and genotyping. Three Cryptosporidium species including C. hominis (72.6%, 138/190), C. parvum (22.6%, 43/190), and C. meleagridis (4.2%, 8/190) were detected. Children ≤ 23 months were more exposed to Cryptosporidium spp. infections than older children. Both C. hominis and C. parvum were more prevalent among children with diarrhoeal disease compared to those children without it (47.6% vs. 33.3%, p = 0.007 and 23.7% vs. 11.8%, p = 0.014, respectively). A high intra-species genetic variability was observed within C. hominis (subtype families Ia, Ib, Id, Ie, and If) and C. parvum (subtype families IIb, IIc, IIe, and IIi) but not within C. meleagridis (subtype family IIIb). No association between Cryptosporidium species/genotypes and child's age was demonstrated. The predominance of C. hominis and C. parvum IIc suggests that most of the Cryptosporidium infections were anthroponotically transmitted, although zoonotic transmission events also occurred at an unknown rate. The role of livestock, poultry, and other domestic animal species as sources of environmental contamination and human cryptosporidiosis should be investigated in further molecular epidemiological studies in Mozambique.

Introduction: Since its emergence in late December 2019, COVID-19 has rapidly developed into a pandemic in mid of March with many countries suffering heavy human loss and declaring emergency conditions to contain its spread. The impact of the disease, while it has been relatively low in the sub-Saharan Africa (SSA) as of May 2020, is feared to be potentially devastating given the less developed and fragmented healthcare system in the continent. In addition, most emergency measures practised may not be effective due to their limited affordability as well as the communal way people in SSA live in relative isolation in clusters of large as well as smaller population centres., Methods: To address the acute need for estimates of the potential impacts of the disease once it sweeps through the African region, we developed a process-based model with key parameters obtained from recent studies, taking local context into consideration. We further used the model to estimate the number of infections within a year of sustained local transmissions under scenarios that cover different population sizes, urban status, effectiveness and coverage of social distancing, contact tracing and usage of cloth face mask., Results: We showed that when implemented early, 50% coverage of contact tracing and face mask, with 33% effective social distancing policies can bringing the epidemic to a manageable level for all population sizes and settings we assessed. Relaxing of social distancing in urban settings from 33% to 25% could be matched by introduction and maintenance of face mask use at 43%., Conclusions: In SSA countries with limited healthcare workforce, hospital resources and intensive care units, a robust system of social distancing, contact tracing and face mask use could yield in outcomes that prevent several millions of infections and thousands of deaths across the continent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016-2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield., Competing Interests: LM, HC, AE, SM, YL, JP, NL, QG, VU, MD, DN, DF, LM No competing interests declared, MA, JA, PR MPA, JSFA, and PR are staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the World Health Organization., (© 2020, Mathieu et al.)

Background: Neonatal sepsis is a leading cause of mortality, yet the recommended inpatient treatment options are inaccessible to most families in low-income settings. In 2015, the World Health Organization released a guideline for outpatient treatment of young infants (0-59 days of age) with possible serious bacterial infection (PSBI) with simplified antibiotic regimens when referral was not feasible. If implemented widely, this guideline could prevent many deaths. Our implementation research evaluated the feasibility and acceptability of implementing the WHO guideline through the existing health system in Malawi., Methods: A prospective cohort study was conducted in 12 first-level health facilities in Ntcheu district. Trained health workers identified and treated young infants with PSBI signs with injection gentamicin for 2 days and oral amoxicillin for 7 days, whereas those with only fast breathing were treated with oral amoxicillin for 7 days. Health Surveillance Assistants (HSAs) were trained to promote care-seeking and to conduct home visits on day 3 and 6 to assess infants under treatment, encourage treatment adherence and remind the caregiver to return for facility follow up. Infants receiving outpatient treatment were followed up at health facility on day 4 and 8. The primary outcome was proportion of outpatient cases completing treatment per protocol., Findings: A total of 358 infants received outpatient treatment (202 clinical severe infection, 156 only fast breathing) from February to September 2017. Of these, 92.7% (332/358) met criteria for treatment completion and 88.8% (318/358) completed the day 4 follow-up. Twelve (3.4%) young infants clinically failed treatment with no reported deaths in those treated at outpatient level. This treatment failure rate was lower than those reported for the simplified regimens tested in the SATT (8-10%) and AFRINEST (5-8%) equivalency trials. More than half of infants (58.1%; 208/358) received HSA follow-up visits on days 3 and 6., Conclusion: Study results demonstrate the feasibility of outpatient treatment for sick young infants when referral is not feasible in Malawi, which will inform scale-up in other parts of Malawi and countries with similar health system constraints., Competing Interests: The authors declare that no competing interests exist. Some of the authors are currently and/or were previously employed by not-for-profit organizations including: Save the Children, World Health Organization, and ActionAid. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Insecticide-treated nets are one of two core vector control interventions recommended by the World Health Organization for deployment in malaria-endemic regions around the world, especially sub-Saharan Africa. Although there are many factors that influence the type of distribution strategy chosen, among the most important considerations for the type of distribution strategy chosen is cost, both in terms of total expenditure required and in terms of relative cost-effectiveness. This research attempted to inform these decisions by conducting a systematic review and meta-analysis of the literature on the cost and cost-effectiveness of ITN distribution. The analysis compared the relative cost and cost-effectiveness of distribution strategies. Findings suggest that mass campaigns have lower average distribution costs per net compared with continuous/health facility distribution or sale/vouchers, although the relationship between distribution channel and cost were not statistically significant in the multivariate regression models. Continuous/health facility distribution channels were found to be more cost-effective than mass campaigns for averting DALYs, death, and cases of malaria. Those who design and budget for malaria programs should base decisions about distribution channels more on operational and epidemiological considerations than on cost per net, as the costs per net between distribution channels are not statistically different., Competing Interests: Declaration of Competing Interest The authors have no competing interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) have been widely used for the treatment of uncomplicated Plasmodium falciparum malaria since 2005 in Gabon. Since 2011, a rebound of malaria morbidity has been observed in this country, while no survey evaluating ACT efficacy was performed. During the same period, parasite resistance against artemisinin has been reported in Asia. The aim of this study was to assess the efficacy and tolerability of these two drugs in two sentinel sites of Gabon 10 years after their implementation., Methods: Children aged from 12 to 144 months with uncomplicated malaria were recruited at the Regional Hospital of Melen, Libreville and in the Urban Health Center of Franceville between March 2014 and September 2015. The therapeutic efficacy was evaluated according to the WHO 2008 protocol of 28-day follow-up and PCR-uncorrected/corrected treatment outcomes were assessed., Results: One hundred and eighty-five children (98 ASAQ and 89 AL) were followed up until day 28. The PCR-corrected ACPR was 98.9% for AS-AQ and 96.4% for AL. Late therapeutic failure rate was 3.6% and 1.1% for AL and AS-AQ, respectively (p = 0.2). Adverse events and serious adverse events were rarely observed with both treatments., Conclusion: AS-AQ and AL are still efficacious and well-tolerated for the treatment of uncomplicated malaria in Gabonese children.

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Background: The national treatment guidelines of Nepal have adopted Artemisinin Combination Therapies (ACTs) for the treatment of uncomplicated falciparum malaria since 2004. Emergence of Artemisinin resistance in the Greater Mekong Sub-region (GMS) and beyond may become a threat for Nepal as well. The main objective of this study was to assess the therapeutic efficacy of antimalarial drug artemether-lumefantrine in uncomplicated P. falciparum infected patients at health centers/hospitals treated over the period of 2 years (2013-2014)., Methods: Giemsa stained thick and thin smears, prepared from uncomplicated falciparum malaria patients who visited the selected sentinel sites in Nepal during 2013 to 2014 and met the inclusion criteria that included parasitemia (1000-10,000 /μL of blood), were evaluated until 28 days after ACTs treatment, following a World Health Organization (WHO) therapeutic efficacy protocol. Based on the re-occurrence of fever and resurge in parasitemia, the study patients were classified as resistant or susceptible. Blood specimens on filter papers were further analyzed by Polymerase Chain Reaction (PCR), specifically for the K13 propeller gene mutation (a recently identified molecular marker for ACT resistance)., Results: A total of 56,013 suspected malaria cases were screened for this study. Of which, 120 (0.21%) were infected with falciparum malaria. Out of 120, 28 cases of P. falciparum ( 28/120; 23.33%) were enrolled in the study, of which 24 cases completed the post-treatment follow up for 28 days. Only one case out of 24 (4%) was identified as a late treatment failure (LTF). K13 mutation, a proxy indicator for ACT resistance in parasites, was not detected on the day 1, which indicates resistance had not yet reached the molecular level., Conclusion: Only one case of late treatment failure was identified in this study. ACT combination using artemether-lumefantrine was still effective for the treatment of uncomplicated falciparum malaria in Nepal. A close monitoring and supervision for ACT resistance is essential for future malaria treatment in Nepal., Competing Interests: Ethical approval was obtained from the ethics review committee of Nepal Health Research Council (NHRC). A written informed consent was obtained from each participant for the study.Not ApplicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

After eliminating local malaria transmission and being certified as a malaria-free country, Sri Lanka is facing the challenge of imported malaria. At the same time, the country has the unique opportunity to be a case study for other countries in a similar situation by approaching this issue systematically, guided by evidence. This study demonstrates the importance of developing a mechanism to detect imported malaria and adopting an evidence-based approach to study the resistance of imported malaria to anti-malarial medicines. This is a prospective study of patients diagnosed with imported malaria in Sri Lanka and treated according to the national treatment guidelines, over 24 months (2015/2016). The clinical features, time to diagnosis, origin of the infection, infecting species, parasite density and the treatment given were recorded. All patients were followed up for 28 days, and in the case of Plasmodium vivax and P. ovale infections, the follow up period was extended to 12 months to establish treatment failures and relapses. Fifty nine uncomplicated and 15 severe imported malaria cases were reported in Sri Lanka during the study period. Most of these infections originated in either Sub-Saharan Africa or South and Southeast Asia. Having a P. vivax infection and low parasitic counts were significantly associated with relative diagnostic delay. One of the 14 uncomplicated P. falciparum patients and two of the 12 severe P. falciparum malaria patients who were followed up till day 28 had a late clinical failure. The others responded adequately to treatment both clinically and parasitologically. There was no treatment failure reported amongst any other species. This study, which is the first to assess the therapeutic response of imported malaria in Sri Lanka after elimination, demonstrates that the current antimalarial treatment policies and strategies in Sri Lanka have been effective against infections acquired overseas up until the end of year 2016.

Background: Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions., Methods: Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators., Results: Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges., Conclusions: Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.

Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded., (© The American Society of Tropical Medicine and Hygiene.)

Background: Sub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency., Methodology/principal Findings: A systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified., Conclusions/significance: SM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.

Background: The Government of Ethiopia and its partners have deployed artemisinin-based combination therapies (ACT) since 2004 and long-lasting insecticidal nets (LLINs) since 2005. Malaria interventions and trends in malaria cases and deaths were assessed at hospitals in malaria transmission areas during 2001-2011., Methods: Regional LLINs distribution records were used to estimate the proportion of the population-at-risk protected by LLINs. Hospital records were reviewed to estimate ACT availability. Time-series analysis was applied to data from 41 hospitals in malaria risk areas to assess trends of malaria cases and deaths during pre-intervention (2001-2005) and post-interventions (2006-2011) periods., Findings: The proportion of the population-at-risk potentially protected by LLINs increased to 51% in 2011. The proportion of facilities with ACTs in stock exceeded 87% during 2006-2011. Among all ages, confirmed malaria cases in 2011 declined by 66% (95% confidence interval [CI], 44-79%) and SPR by 37% (CI, 20%-51%) compared to the level predicted by pre-intervention trends. In children under 5 years of age, malaria admissions and deaths fell by 81% (CI, 47%-94%) and 73% (CI, 48%-86%) respectively. Optimal breakpoint of the trendlines occurred between January and June 2006, consistent with the timing of malaria interventions. Over the same period, non-malaria cases and deaths either increased or remained unchanged, the number of malaria diagnostic tests performed reflected the decline in malaria cases, and rainfall remained at levels supportive of malaria transmission., Conclusions: Malaria cases and deaths in Ethiopian hospitals decreased substantially during 2006-2011 in conjunction with scale-up of malaria interventions. The decrease could not be accounted for by changes in hospital visits, malaria diagnostic testing or rainfall. However, given the history of variable malaria transmission in Ethiopia, more data would be required to exclude the possibility that the decrease is due to other factors.

Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7&#95;1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread., Competing Interests: The authors declare no competing financial interests. Readers are welcome to comment on the online version of the paper.

Background: An increasing number of malaria-endemic African countries are rapidly scaling up malaria prevention and treatment. To have an initial estimate of the impact of these efforts, time trends in health facility records were evaluated in selected districts in Ethiopia and Rwanda, where long-lasting insecticidal nets (LLIN) and artemisinin-based combination therapy (ACT) had been distributed nationwide by 2007., Methods: In Ethiopia, a stratified convenience sample covered four major regions where (moderately) endemic malaria occurs. In Rwanda, two districts were sampled in all five provinces, with one rural health centre and one rural hospital selected in each district. The main impact indicator was percentage change in number of in-patient malaria cases and deaths in children < 5 years old prior to (2001-2005/6) and after (2007) nationwide implementation of LLIN and ACT., Results: In-patient malaria cases and deaths in children < 5 years old in Rwanda fell by 55% and 67%, respectively, and in Ethiopia by 73% and 62%. Over this same time period, non-malaria cases and deaths generally remained stable or increased., Conclusion: Initial evidence indicated that the combination of mass distribution of LLIN to all children < 5 years or all households and nationwide distribution of ACT in the public sector was associated with substantial declines of in-patient malaria cases and deaths in Rwanda and Ethiopia. Clinic-based data was a useful tool for local monitoring of the impact of malaria programmes.

National disease burdens are often not estimated at all or are estimated using inaccurate methods, partly because the data sources for assessing disease burden-nationally representative household surveys, demographic surveillance sites, and routine health information systems-each have their limitations. An important step forward would be a more consistent quantification of the population at risk of malaria. This is most likely to be achieved by delimiting the geographical distribution of malaria transmission using routinely collected data on confirmed cases of disease. However, before routinely collected data can be used to assess trends in the incidence of clinical cases and deaths, the incompleteness of reporting and variation in the utilization of the health system must be taken into account. In the future, sentinel surveillance from public and private health facilities, selected according to risk stratification, combined with occasional household surveys and other population-based methods of surveillance, may provide better assessments of malaria trends.