Malaria volunteers (MVs) play an essential role in resolving malaria problems by delivering greater access to diagnosis and treatment services, mainly for the underserved community residing in hard-to-reach rural areas. The Karen Department of Health and Welfare (KDHW) has implemented community-based malaria control activities among the ethnic minorities in southeastern Myanmar by promoting the roles of MVs. This study aimed to explore the factors influencing the performance of MVs regarding malaria control activities in the area. From July to August 2019, a cross-sectional study was conducted in 12 townships of southeastern Myanmar under the umbrella of the KDHW malaria project. A total of 140 MVs were employed as study participants. Data were collected through face-to-face interviews using a structured questionnaire. For data analyses, descriptive statistics, chi-squared tests, and logistics regression models were applied. More than half of the MVs perceived a good level of performance on malaria control activities. A higher level of performance has been observed among the MVs who had another job (AOR: 1.9, 95% CI: 1.2–3.9), those experienced in health-related fields (AOR: 1.9, 95% CI: 1.4–4.9), who received good community support (AOR: 2.1, 95% CI: 1.3–10.9), who were volunteers beyond three years (AOR: 4.0, 95% CI: 2.8–9.2), and whose family income totaled over 500,000 MMK (AOR: 2.8, 95% CI: 1.6–4.2). The results mentioned the characteristics which should be prioritized in recruiting MVs. MV network and their workforce need to be nurtured by encouraging community support. For performance sustainability, attractive incentive schemes or a salary should be subsidized in support of their livelihoods.
Sexual stage surface antigens are potential targets of transmission-blocking vaccines (TBVs). The gametocyte and gamete surface antigen P230, a leading TBV candidate, is critical for red blood cell binding during exflagellation and subsequent oocyst development. Here, the genetic diversity of Pvs230 was studied in Plasmodium vivax parasite isolates from the China-Myanmar border (CMB) and central Myanmar.Plasmodium vivax isolates were collected in clinics from malaria-endemic areas of the CMB (143 samples) and Myanmar (23 samples). The interspecies variable part (IVP, nucleotides 1-807) and interspecies conserved part (ICP, 808-2862) of Pvs230 were amplified by PCR and sequenced. Molecular evolution studies were conducted to evaluate the genetic diversity, signature of selection, population differentiation, haplotype network, and population structure of the study parasite populations and publicly available Pvs230 sequences from six global P. vivax populations.Limited genetic diversity was observed for the CMB (π = 0.002) and Myanmar (π = 0.001) isolates. Most amino acid substitutions were located in the IVP and cysteine-rich domain of Pvs230. Evidence of positive selection was observed for IVP and purifying selection for ICP. Codon-based tests identified specific codons under natural selection in both IVP and ICP. The fixation index (FST) showed low genetic differentiation between East and Southeast Asian populations, with FST ranging from 0.018 to 0.119. The highest FST value (FST = 0.503) was detected between the Turkey and Papua New Guinea populations. A total of 92 haplotypes were identified in global isolates, with the major haplotypes 2 and 9 being the most abundant and circulating in East and Southeast Asia populations. Several detected non-synonymous substitutions were mapped in the predicted structure and B-cell epitopes of Pvs230.We detected low levels of genetic diversity of Pvs230 in global P. vivax populations. Geographically specific haplotypes were identified for Pvs230. Some mutations are located within a potential B-cell epitope region and need to be considered in future TBV designs.
Additional file 3: Table S3. The variables used for each isolate input in the ClustVis online program. Column A indicaes the all variables of each gene. Second row indicates the samples used and Third raw indicates the groups. The reference and alternate allele is shown by 0 and 1, respectively.
Abstract Background Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). HAP2/GCS1, a TBV candidate, is critical for fertilization in Plasmodium . Here, the genetic diversity of PvHAP2 was studied in Plasmodium vivax parasite populations from the Greater Mekong Subregion (GMS). Methods Plasmodium vivax clinical isolates were collected in clinics from the China-Myanmar border region (135 samples), western Thailand (41 samples) and western Myanmar (51 samples). Near full-length Pvhap2 (nucleotides 13–2574) was amplified and sequenced from these isolates. Molecular evolution studies were conducted to evaluate the genetic diversity, selection and population differentiation. Results Sequencing of the pvhap2 gene for a total of 227 samples from the three P. vivax populations revealed limited genetic diversity of this gene in the GMS (π = 0.00036 ± 0.00003), with the highest π value observed in Myanmar (0.00053 ± 0.00009). Y133S was the dominant mutation in the China-Myanmar border (99.26%), Myanmar (100%) and Thailand (95.12%). Results of all neutrality tests were negative for all the three populations, suggesting the possible action of purifying selection. Codon-based tests identified specific codons which are under purifying or positive selections. Wright’s fixation index showed low to moderate genetic differentiation of P. vivax populations in the GMS, with F ST ranging from 0.04077 to 0.24833, whereas high levels of genetic differentiation were detected between the China-Myanmar border and Iran populations ( F ST = 0.60266), and between Thailand and Iran populations ( F ST = 0.44161). A total of 20 haplotypes were identified, with H2 being the abundant haplotype in China-Myanmar border, Myanmar and Thailand populations. Epitope mapping prediction of Pvhap2 antigen showed that high-score B-cell epitopes are located in the S307-G324, L429-P453 and V623-D637 regions. The E317K and D637N mutations located within S307-G324 and V623-D637 epitopes slightly reduced the predicted score for potential epitopes. Conclusions The present study showed a very low level of genetic diversity of pvhap2 gene among P. vivax populations in the Greater Mekong Subregion. The relative conservation of pvhap2 supports further evaluation of a Pvhap2-based TBV.
ABSTRACT. In the course of malaria elimination in the Greater Mekong Subregion (GMS), malaria epidemiology has experienced drastic spatiotemporal changes with residual transmission concentrated along international borders and the rising predominance of Plasmodium vivax . The emergence of Plasmodium falciparum parasites resistant to artemisinin and partner drugs renders artemisinin-based combination therapies less effective while the potential spread of multidrug-resistant parasites elicits concern. Vector behavioral changes and insecticide resistance have reduced the effectiveness of core vector control measures. In recognition of these problems, the Southeast Asian International Center of Excellence for Malaria Research (ICEMR) has been conducting multidisciplinary research to determine how human migration, antimalarial drug resistance, vector behavior, and insecticide resistance sustain malaria transmission at international borders. These efforts allow us to comprehensively understand the ecology of border malaria transmission and develop population genomics tools to identify and track parasite introduction. In addition to employing in vivo, in vitro, and molecular approaches to monitor the emergence and spread of drug-resistant parasites, we also use genomic and genetic methods to reveal novel mechanisms of antimalarial drug resistance of parasites. We also use omics and population genetics approaches to study insecticide resistance in malaria vectors and identify changes in mosquito community structure, vectorial potential, and seasonal dynamics. Collectively, the scientific findings from the ICEMR research activities offer a systematic view of the factors sustaining residual malaria transmission and identify potential solutions to these problems to accelerate malaria elimination in the GMS.
Abstract Background Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10 , pffd and pfmdr2 . Methods A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013. Therapeutic efficacy of ACT was assessed by longitudinal follow ups. Molecular markers analysis was done on all available day 0 samples. Results True recrudescence treatment failures cases and day 3 parasite positivity were detected at only the southern Myanmar sites. Day 3 positive and k13 mutants with higher prevalence of underlying genetic foci predisposing to become k13 mutant were detected only in southern Myanmar since 2009 and comparatively fewer mutations of pfarps10, pffd , and pfmdr2 were observed in western Myanmar. K13 mutations, V127M of pfarps10 , D193Y of pffd , and T448I of pfmdr2 were significantly associated with day 3 positivity (OR: 6.48, 3.88, 2.88, and 2.52, respectively). Conclusions Apart from k13 , pfarps10, pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported. Appropriate action to eliminate the resistant parasites and surveillance on artemisinin resistance should be strengthened in Myanmar. Trial registration This study was registered with ClinicalTrials.gov, identifier NCT02792816.
The emergence and spread of drug resistance is a problem hindering malaria elimination in Southeast Asia. In this study, genetic variations in drug resistance markers of Plasmodium falciparum were determined in parasites from asymptomatic populations located in three geographically dispersed townships of Myanmar by PCR and sequencing. Mutations in dihydrofolate reductase (pfdhfr), dihydropteroate synthase (pfdhps), chloroquine resistance transporter (pfcrt), multidrug resistance protein 1 (pfmdr1), multidrug resistance-associated protein 1 (pfmrp1), and Kelch protein 13 (k13) were present in 92.3%, 97.6%, 84.0%, 98.8%, and 68.3% of the parasites, respectively. The pfcrt K76T, pfmdr1 N86Y, pfmdr1 I185K, and pfmrp1 I876V mutations were present in 82.7%, 2.5%, 87.5%, and 59.8% isolates, respectively. The most prevalent haplotypes for pfdhfr, pfdhps, pfcrt and pfmdr1 were 51I/59R/108N/164L, 436A/437G/540E/581A, 74I/75E/76T/220S/271E/326N/356T/371I, and 86N/130E/184Y/185K/1225V, respectively. In addition, 57 isolates had three different point mutations (K191T, F446I, and P574L) and three types of N-terminal insertions (N, NN, NNN) in the k13 gene. In total, 43 distinct haplotypes potentially associated with multidrug resistance were identified. These findings demonstrate a high prevalence of multidrug-resistant P. falciparum in asymptomatic infections from diverse townships in Myanmar, emphasizing the importance of targeting asymptomatic infections to prevent the spread of drug-resistant P. falciparum.
Radical cure of the Plasmodium vivax latent liver stage is required to effectively manage vivax malaria. Targeted mass treatment with primaquine may be an effective mechanism for reducing reservoirs of the disease. Since community engagement and high coverage are essential for mass treatment programs, this study aimed to determine the acceptability of mass primaquine treatment in a targeted community in a northern Myanmar township.A cross-sectional mixed-methods study was deployed among household leaders in July 2019. Face-to-face interviews using structured questionnaires and standardized qualitative guidelines were conducted to gather information. Descriptive and inferential statistics, including logistic regression models, were applied.Among 609 study respondents, > 90% agreed to participate in an upcoming targeted mass primaquine treatment (TPT) program. Factors contributing to higher odds of acceptability of the program were older age [adjusted odds ratios (aOR): 2.38, 95% confidence intervals (CI) 1.08-8.96], secondary education level (aOR: 3.99, 95% CI 1.12-20.01), having good knowledge of malaria (aOR: 2.12, 95% CI 1.04-4.76), experiencing malaria within the family (aOR: 1.92, 95% CI 1.14-5.13), and believing eliminating malaria from the village is possible (aOR: 2.83, 95% CI 1.07-4.07). Furthermore, 50 community respondents, 6 midwives, and 4 public health staff (grade II) participated in the qualitative component of the study. Many thought that TPT seemed feasible and stressed that high coverage of underserved groups and health education are needed before commencing the activity.Most respondents agreed to participate in the proposed mass treatment campaign. Older people with secondary education level and those who had experienced malaria within their families were most likely to report willingness to participate. These same individuals may be important in the community engagement process to increase community acceptance of the program.
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