Successful elimination of falciparum malaria following the introduction of community-based health workers in Eastern Myanmar: A retrospective analysis.

BACKGROUND: Myanmar has a large majority of all malaria in the Greater Mekong Subregion. In the past decade, substantial progress was made in malaria control. The residual burden of malaria is in remote areas where currently recommended malaria elimination approaches are generally not feasible. In such hard-to-reach communities in Mon state, East Myanmar, Medical Action Myanmar introduced community health workers (CHWs) to deliver early diagnosis and treatment for malaria. We conducted a retrospective analysis to assess the impact of this intervention. METHODS AND FINDINGS: This retrospective analysis involved data collected routinely from a CHW programme in Mon state conducted between 2011 and 2018. A network of 172 CHWs serving a population of 236,340 was deployed. These CHWs carried out 260,201 malaria rapid diagnostic tests (RDTs) to investigate patients with acute febrile illness. The median blood examination rate was 1.33%; interquartile range (IQR) (0.38 to 3.48%); 95% CI [1.28%, 1.36%] per month. The changes in malaria incidence and prevalence in patients presenting with fever were assessed using negative binomial regression mixed effects models fitted to the observed data. The incidence of Plasmodium falciparum malaria (including mixed infections) declined by 70%; 95% CI [65%, 75%]; p < 0.001 for each year of CHW operation. The incidence of P. vivax malaria declined by 56%; 95% CI [50%, 62%]; p < 0.001 per year. Malaria RDT positivity rates for P. falciparum and P. vivax declined by 69%; 95% CI [62%, 75%]; p < 0.001 and 53%; 95% CI [47%, 59%]; p < 0.001 per year, respectively. Between 2017 and 2018, only 1 imported P. falciparum case was detected in 54,961 RDTs. The main limitations of the study are use of retrospective data with possible unidentified confounders and uncharacterised population movement. CONCLUSIONS: The introduction of CHWs providing community-based malaria diagnosis and treatment and basic health care services in remote communities in Mon state was associated with a substantial reduction in malaria. Within 6 years, P. falciparum was eliminated and the incidence of P. vivax fell markedly.

Malaria elimination in remote communities requires integration of malaria control activities into general health care: an observational study and interrupted time series analysis in Myanmar.

BACKGROUND: Community health workers (CHWs) can provide diagnosis and treatment of malaria in remote rural areas and are therefore key to the elimination of malaria. However, as incidence declines, uptake of their services could be compromised if they only treat malaria. METHODS: We conducted a retrospective analysis of 571,286 malaria rapid diagnostic tests conducted between 2011 and 2016 by 1335 CHWs supported by Medical Action Myanmar. We assessed rates of decline in Plasmodium falciparum and Plasmodium vivax incidence and rapid diagnostic test (RDT) positivity rates using negative binomial mixed effects models. We investigated whether broadening the CHW remit to provide a basic health care (BHC) package was associated with a change in malaria blood examination rates. RESULTS: Communities with CHWs providing malaria diagnosis and treatment experienced declines in P. falciparum and P. vivax malaria incidence of 70% (95% CI 66-73%) and 64% (59-68%) respectively each year of operation. RDT positivity rates declined similarly with declines of 70% (95% CI 66-73%) for P. falciparum and 65% (95% CI 61-69%) for P. vivax with each year of CHW operation. In four cohorts studied, adding a BHC package was associated with an immediate and sustained increase in blood examination rates (step-change rate ratios 2.3 (95% CI 2.0-2.6), 5.4 (95% CI 4.0-7.3), 1.7 (95% CI 1.4-2.1), and 1.1 (95% CI 1.0.1.3)). CONCLUSIONS: CHWs have overseen dramatic declines in P. falciparum and P. vivax malaria in rural Myanmar. Expanding their remit to general health care has sustained community uptake of malaria services. In similar settings, expanding health services offered by CHWs beyond malaria testing and treatment can improve rural health care while ensuring continued progress towards the elimination of malaria.

Spatial distribution, work patterns, and perception towards malaria interventions among temporary mobile/migrant workers in artemisinin resistance containment zone.

BACKGROUND: Mobile populations are at a high risk of malaria infection and suspected to carry and spread resistant parasites. The Myanmar National Malaria Control Programme focuses on preventive interventions and vector control measures for the temporary mobile/migrant workers in Myanmar Artemisinin Resistance Containment Zones. METHODS: A prospective cross-sectional study was conducted in 2012 in Kawthaung and Bokepyin townships of Tanintharyi Region, Myanmar, covering 192 mobile/migrant aggregates. The objectives were to identify the spatial distribution of the mobile/migrant populations, and to assess knowledge, attitudes, perceptions, and practices concerning malaria prevention and control, and their preferred methods of interventions. The structure of the 192 migrant aggregates was investigated using a migrant mapping tool. Individual and household information was collected by structured interviews of 408 respondents from 39 aggregates, supplemented by 12 in-depth interviews of health care providers, authorities, volunteers, and employers. Data were analyzed by triangulating quantitative and qualitative data. RESULTS: The primary reasons for the limitation in access to formal health services for suspected malaria within 24 hours were identified to be scattered distribution of migrant aggregates, variable working hours and the lack of transportation. Only 19.6% of respondents reported working at night from dusk to dawn. Among study populations, 73% reported a perceived risk of contracting malaria and 60% reported to know how to confirm a suspected case of malaria. Moreover, only 15% was able to cite correct antimalarial drugs, and less than 10% believed that non-compliance with antimalarial treatment may be related to the risk of drug resistance. About 50% of study population reported to seeking health care from the public sector, and to sleep under ITNs/LLINs the night before the survey. There was a gap in willingness to buy ITNs/LLINs and affordability (88.5% vs. 60.2%) which may affect their sustained and consistent use. Only 32.4% across all aggregates realized the importance of community participation in effective malaria prevention and control. CONCLUSIONS: Community-based innovative approaches through strong collaboration and coordination of multi-stakeholders are desirable for relaying information on ITNs/LLINs, rapid diagnostic test, and artemisinin combination therapy and drug resistance successfully across the social and economic diversity of mobile/migrant aggregates in Myanmar.

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial.

BACKGROUND: To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin-piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. METHODS: We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50-1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin-piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. FINDINGS: Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was -10·6% (95% CI -15·1 to -6·1; p=0·0008) at month 3 and -4·5% (-10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. INTERPRETATION: In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Containing artemisinin resistance of Plasmodium falciparum in Myanmar: achievements, challenges and the way forward.

Artemisinin resistance is a major threat to global malaria control and elimination efforts. Myanmar detected the first indication of the resistance in 2009 in the eastern part of the country, bordering Thailand. Since 2010, WHO has played a vital role in ensuring that a comprehensive programme on the containment of the resistance is in place. This paper documents achievement made in terms of output, outcomes and early impact on malaria from July 2011 to December 2013. It also identifies enabling factors to success and, most importantly, challenges awaiting the national programme and its partners.

Retention and risk factors for attrition in a large public health ART program in Myanmar: a retrospective cohort analysis.

BACKGROUND: The outcomes from an antiretroviral treatment (ART) program within the public sector in Myanmar have not been reported. This study documents retention and the risk factors for attrition in a large ART public health program in Myanmar. METHODS: A retrospective analysis of a cohort of adult patients enrolled in the Integrated HIV Care (IHC) Program between June 2005 and October 2011 and followed up until April 2012 is presented. The primary outcome was attrition (death or loss-follow up); a total of 10,223 patients were included in the 5-year cumulative survival analysis. Overall 5,718 patients were analyzed for the risk factors for attrition using both logistic regression and flexible parametric survival models. RESULT: The mean age was 36 years, 61% of patients were male, and the median follow up was 13.7 months. Overall 8,564 (84%) patients were retained in ART program: 750 (7%) were lost to follow-up and 909 (9%) died. During the 3 years follow-up, 1,542 attritions occurred over 17,524 person years at risk, giving an incidence density of 8.8% per year. The retention rates of participants at 12, 24, 36, 48 and 60 months were 86, 82, 80, 77 and 74% respectively. In multivariate analysis, being male, having high WHO staging, a low CD4 count, being anaemic or having low BMI at baseline were independent risk factors for attrition; tuberculosis (TB) treatment at ART initiation, a prior ART course before program enrollment and literacy were predictors for retention in the program. CONCLUSION: High retention rate of IHC program was documented within the public sector in Myanmar. Early diagnosis of HIV, nutritional support, proper investigation and treatment for patients with low CD4 counts and for those presenting with anaemia are crucial issues towards improvement of HIV program outcomes in resource-limited settings.

Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria.

All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine+1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2+/-8.6 h and 34.6+/-14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment.