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Abstract Targeted mass primaquine treatment (TPT) might be an effective intervention to facilitate elimination of vivax malaria in Myanmar by 2030. In this study, we explored the factors hindering coverage of a TPT campaign conducted in a malarious township of northern Myanmar. From August 2019 to July 2020, a cross-sectional exploratory design including quantitative and qualitative data was conducted in five villages with high P. vivax prevalence following a TPT campaign. Among a targeted population of 2322; 1973 (85.0%) participated in the baseline mass blood survey (MBS) and only 52.0% of the total targeted population (1208, 91.9% of total eligible population) completed the TPT. G6PD deficiency was found among 13.5% of total MBS participants and those were excluded from TPT. Of 1315 eligible samples, farmers and gold miners, males, and those aged 15 to 45 years had higher percentages of non-participation in TPT. Qualitative findings showed that most of the non-participation groups were outside the villages during TPT because of time-sensitive agricultural and other occupational or education-related purposes. In addition to mitigating of some inclusion criteria (i.e. including young children or offering weekly PQ treatment to G6PD deficient individuals), strengthening community awareness and increasing engagement should be pursued to increase community participation.

Abstract Background Myanmar bears the heaviest malaria burden in the Greater Mekong Subregion (GMS). This study assessed the spatio-temporal dynamics and environmental predictors of Plasmodium falciparum and Plasmodium vivax malaria in Myanmar. Methods Monthly reports of malaria cases at primary health centers during 2011–2017 were analyzed to describe malaria distribution across Myanmar at the township and state/region levels by spatial autocorrelation (Moran index) and spatio-temporal clustering. Negative binomial generalized additive models identified environmental predictors for falciparum and vivax malaria, respectively. Results From 2011 to 2017, there was an apparent reduction in malaria incidence in Myanmar. Malaria incidence peaked in June each year. There were significant spatial autocorrelation and clustering with extreme spatial heterogeneity in malaria cases and test positivity across the nation (P

Abstract Background 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. Methods 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. Results 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. Conclusions 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. Graphical abstract

Purpose – Malaria still remains a significant public health problem in Myanmar and it has a complex epidemiology. Evidence-based community awareness raising interventions are also particularly needed. This cross-sectional study was organized to explore the basic characteristics associated with knowledge, attitude and practice (KAP) regarding malaria among people living in the most malaria-endemic villages of the Banmauk Township, Sagaing Region, Myanmar. The paper aims to discuss these issues. Design/methodology/approach – The Banmauk, one of the most malaria-endemic townships, was selected purposively in order to represent the survey results for people living in malaria hotspots. During the peak malaria season (July 2018), 250 household leaders were invited to be interviewed with structured questionnaires. In addition to descriptive data, the associations were determined by χ2-test and correlation. Findings – Overall KAP indicated considerably low percentages of good levels, especially in practice, only 21.6 percent showed good practice, 38.4 percent had good knowledge and 56.8 percent had good attitude. Age (p=0.022) and annual family income (p

Abstract Background Interventions to raise community awareness about malaria prevention and treatment have used various approaches with little evidence on their efficacy. This study aimed to determine the effectiveness of loudspeaker announcements regarding malaria care and prevention practices among people living in the malaria endemic villages of Banmauk Township, Sagaing Region, Myanmar. Methods Four villages among the most malaria-burdened areas were randomly selected: two villages were assigned as the intervention group, and two as the control. Prior to the peak transmission season of malaria in June 2018, a baseline questionnaire was administered to 270 participants from randomly selected households in the control and intervention villages. The loudspeaker announcements broadcasted health messages on malaria care and prevention practices regularly at 7:00 pm every other day. The same questionnaire was administered at 6-month post intervention to both groups. Descriptive statistics, Chi-square, and the t-test were utilized to assess differences between and within groups. Results Participants across the control and intervention groups showed similar socio-economic characteristics; the baseline knowledge, attitude and practice mean scores were not significantly different between the groups. Six months after the intervention, improvements in scores were observed at p-value

Abstract Background The malaria burden of Myanmar still remains high within the Greater Mekong Subregion of Southeast Asia. An important indicator of progress towards malaria elimination is the prevalence of parasite infections in endemic populations. Information about malaria epidemiology is mostly derived from reports of confirmed acute malaria cases through passive case detection, whereas the prevalence of baseline subclinical malaria infections is much less known. Methods In this study, cross-sectional surveys were conducted during the rainy season of 2017 in four townships (Bilin, Thabeikkyin, Banmauk and Paletwa) of Myanmar with divergent annual malaria incidences. A total of 1991 volunteers were recruited from local villages and Plasmodium subclinical infections were estimated by light microscopy (LM), rapid diagnostic tests (RDTs) and nested PCR. The nested PCR analysis was performed with a modified pooling strategy that was optimized based on an initial estimate the infection prevalence. Results The overall malaria infection prevalence based on all methods was 13.9% (277/1991) and it differed drastically among the townships, with Paletwa in the western border having the highest infection rate (22.9%) and Thabeikkyin in central Myanmar having the lowest (3.9%). As expected, nested PCR was the most sensitive and identified 226 (11.4%) individuals with parasite infections. Among the parasite species, Plasmodium vivax was the most prevalent in all locations, while Plasmodium falciparum also accounted for 32% of infections in the western township Paletwa. Two RDTs based on the detection of the hrp2 antigen detected a total of 103 P. falciparum infections, and the ultrasensitive RDT detected 20% more P. falciparum infections than the conventional RDT. In contrast, LM missed the majority of the subclinical infections and only identified 14 Plasmodium infections. Conclusions Cross-sectional surveys identified considerable levels of asymptomatic Plasmodium infections in endemic populations of Myanmar with P. vivax becoming the predominant parasite species. Geographical heterogeneity of subclinical infections calls for active surveillance of parasite infections in endemic areas. The pooling scheme designed for nested PCR analysis offers a more practical strategy for large-scale epidemiological studies of parasite prevalence. Such information is important for decision-makers to put forward a more realistic action plan for malaria elimination.

Abstract Background Malaria is a major public health problem in Myanmar with reported artemisinin resistance. Myanmar promotes the use of insecticide-treated nets (ITNs) through the free delivery of long-lasting insecticide nets (LLINs) with target coverage of at least 80% in moderate and high-risk areas by 2014. Migrant people are at greater risk of malaria. They have significant barriers to health care services for febrile illness and malaria. Thus, a community-based survey was conducted among the migrant population to assess the ownership and utilization of bed nets (ITN/LLINs) for malaria. Methods The study analyzed secondary data from a community-based malaria survey conducted in 2014 among migrant population in 30 randomly selected townships out of 52 Regional Artemisinin Resistance Initiative (RAI) townships. In each township, five migrant sites were randomly selected (total of 150 migrant sites). A total of 3933 households (approximately 125 households from each township) were selected. Results Of 3923 households assessed, 97% had access to at least one bed net (any type), but only half had access to ITN/LLINs. Only 24% of households had adequate ITN/LLIN access (at least one ITN/LLIN per two persons). In terms of household utilization, 94.3% slept under a bed net (any type) the previous night. Only 43.4% slept under an ITN/LLIN. ITN/LLIN utilization in children under 5 years and pregnant women (high-malaria risk groups) was 45.3 and 46.6%, respectively. Of all nets, 31.3% had holes or had already undergone repairs. In terms of insecticide treatment status, 52.9% of bed nets were untreated and 35.9% of ITNs had not been treated with insecticide for more than a year. Conclusion This study highlights poor access and high utilization of ITN/LLINs among migrant population, particularly among children and pregnant women. It highlights the need for improving bed net coverage and access to ITN/LLINs through bed net distributions and/or social marketing with the focus on migrant population and targeting of households with children and pregnant women.

Abstract Background As the prevalence of the malaria has been decreasing in many endemic countries including Myanmar, malaria elimination in Greater Mekong Region was targeted not later than 2030. The relevance of molecular and serological tools to identify residual transmission remains to be established in this setting. Methods One-year cohort study was conducted and sera samples were collected in every 3 months with active and passive case detection for clinical malaria episodes by RDT, microscopy and molecular method. The sera were used to detect the malaria antibody against PfMSP1-19, PvAMA1, PvDBPII and PvMSP1-19 by protein microarray. Results Among the recruited 1182 participants, there was no RDT positive case for malaria infection although two vivax infections were detected by microscopy in initial collection. Molecular methods detected the asymptomatic cases of 28/1182 (2.37%) in first, 5/894 (0.42%) in second, 12/944 (1.02%) in third, 6/889 (0.51%) in fourth collection, respectively. Seropositivity rates against the PfMSP1-19, PvMSP1-19, PvAMA1 and PvDBPII were 73/270 (27.0%), 85/270 (31.5%), 65/270 (24.1%) and 160/270 (59.3%), respectively. PfMSP1-19 and PvMSP1-19 showed high and stable antigenicity in acute and subacute samples but declining in 1-year history samples. No cross reactivity of PfMSP1-19 and PvMSP1-19 between the two species and higher seropositivity among the asymptomatic carriers were observed. Mapping data indicated serological surveillance can detect the geographical pattern of malaria infection under low transmission setting. Conclusions These findings support that PfMSP1-19 and PvMSP1-19 are suggested for serosurveillance of the malaria especially in low transmission setting for further necessary actions have to be carried out to eliminate the malaria.

Abstract Background The genetic diversity of malaria parasites reflects the complexity and size of the parasite populations. This study was designed to explore the genetic diversity of Plasmodium falciparum populations collected from two southeastern areas (Shwekyin and Myawaddy bordering Thailand) and one western area (Kyauktaw bordering Bangladesh) of Myanmar. Methods A total of 267 blood samples collected from patients with acute P. falciparum infections during 2009 and 2010 were used for genotyping at the merozoite surface protein 1 (Msp1), Msp2 and glutamate-rich protein (Glurp) loci. Results One hundred and eighty four samples were successfully genotyped at three genes. The allelic distributions of the three genes were all significantly different among three areas. MAD20 and 3D7 were the most prevalent alleles in three areas for Msp1 and Msp2, respectively. The Glurp allele with a bin size of 700–750 bp was the most prevalent both in Shwekyin and Myawaddy, whereas two alleles with bin sizes of 800–850 bp and 900–1000 bp were the most prevalent in the western site Kyauktaw. Overall, 73.91% of samples contained multiclonal infections, resulting in a mean multiplicity of infection (MOI) of 1.94. Interestingly, the MOI level presented a rising trend with the order of Myawaddy, Kyauktaw and Shwekyin, which also paralleled with the increasing frequencies of Msp1 RO33 and Msp2 FC27 200–250 bp alleles. Msp1 and Msp2 genes displayed higher levels of diversity and higher MOI rates than Glurp. PCR revealed four samples (two from Shwekyin and two from Myawaddy) with mixed infections of P. falciparum and P. vivax. Conclusions This study genotyped parasite clinical samples from two southeast regions and one western state of Myanmar at the Msp1, Msp2 and Glurp loci, which revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations at these sites. The results indicated that malaria transmission intensity in these regions remained high and more strengthened control efforts are needed. The genotypic data provided baseline information for monitoring the impacts of malaria elimination efforts in the region.

BackgroundAntithyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of thyrotoxicosis. Agranulocytosis is a rare but lethal adverse effect of antithyroid medications. We have reported 2 cases of MMI-induced agranulocytosis with similar risk factors that likely predisposed them to this adverse reaction.Case reportCase 1 involved a 71-year-old woman, with a history of Graves disease, who presented with an altered mental status. She was recently discharged on 40 mg of MMI twice daily, and she continued this dose for 2 months. She was readmitted and found to have neutropenic fever in the setting of MMI-induced agranulocytosis. MMI was discontinued, and she was started on filgrastim. Her cell counts gradually improved, and she was subsequently discharged.Case 2 involved a 68-year-old woman, with a history of Graves disease, who presented with severe back pain, nausea, and vomiting. She was recently discharged on 10 mg of MMI twice daily, which was increased to 10 mg 3 times a day. She was readmitted to the hospital because of a septic shock in the setting of pneumonia, colitis, bacteremia, and MMI-induced agranulocytosis. A bone marrow biopsy showed a polyclonal infiltrate with up to 85% plasma cells. Despite treatment with antibiotics, filgrastim, and continuous renal replacement therapy, she ultimately passed away.DiscussionAlthough these cases had differing outcomes, they shared similar features and risk factors, including older age, female sex, and relatively higher doses of MMI.ConclusionClose follow up and awareness of risk factors, such as age, female sex, and higher doses of MMI, may decrease the risk of MMI-induced agranulocytosis and fatal outcomes.

BACKGROUND. We conducted a phase I clinical trial that infused CCR5 gene-edited [CD4.sup.+] T cells to determine how these T cells can better enable HIV cure strategies. METHODS. The aim of trial was to develop RNA-based approaches to deliver zinc finger nuclease (ZFN), evaluate the effect of CCR5 gene-edited [CD4.sup.+] T cells on the HIV-specific T cell response, test the ability of infused CCR5 gene- edited T cells to delay viral rebound during analytical treatment interruption, and determine whether individuals heterozygous for CCR5 [DELTA]32 preferentially benefit. We enrolled 14 individuals living with HIV whose viral load was well controlled by antiretroviral therapy (ART). We measured the time to viral rebound after ART withdrawal, the persistence of CCR5-edited [CD4.sup.+] T cells, and whether infusion of 10 billion CCR5-edited [CD4.sup.+] T cells augmented the HIV-specific immune response. RESULTS. Infusion of the [CD4.sup.+] T cells was well tolerated, with no serious adverse events. We observed a modest delay in the time to viral rebound relative to historical controls; however, 3 of the 14 individuals, 2 of whom were heterozygous for CCR5 [DELTA]32, showed post-viral rebound control of viremia, before ultimately losing control of viral replication. Interestingly, only these individuals had substantial restoration of HIV-specific [CD8.sup.+] T cell responses. We observed immune escape for 1 of these reinvigorated responses at viral recrudescence, illustrating a direct link between viral control and enhanced [CD8.sup.+] T cell responses. CONCLUSION. These findings demonstrate how CCR5 gene-edited [CD4.sup.+] T cell infusion could aid HIV cure strategies by augmenting preexisting HIV-specific immune responses. REGISTRATION. ClinicalTrials.gov NCT02388594. FUNDING. NIH funding (R01AI104400, UM1AI126620, U19AI149680, T32AI007632) was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). Sangamo Therapeutics also provided funding for these studies., Introduction Prolonged HIV-1 infection results in massive [CD4.sup.+] T cell loss and profound immunodeficiency (1). Even with effective antiretroviral therapy (ART), the resident [CD4.sup.+] T cell response does not fully [...]

Introduction: Global effort to increase early diagnosis and engagement in HIV care emphasize the importance of developing novel approaches to reaching those missed by traditional methods. Such needs are particularly great for men who have sex with men (MSM), transgender women (TW), and other populations who face stigma. Myanmar's HIV epidemic is concentrated among key populations and the revised National Strategy aims to reduce late diagnosis and barriers to care to curb HIV incidence among these groups. HIV self-testing (HIVST) may be one method to improve testing and diagnosis among key populations, by placing HIV testing and disclosure within the individual's control. Methods: Formative, qualitative research including in-depth interviews with adult MSM (N = 12) and TW (N = 13) and focus group discussions with MSM, TW, and community key informants (N = 35) were conducted in June-September 2015 in Yangon, Myanmar. To inform a subsequent HIV care continuum intervention, including HIVST, participants' opinions and perceptions about HIVST were elicited. Results: The confidentiality and privacy of HIVST, particularly as it related to disclosure of HIV status and sexual behaviour, was widely recognized among participants. These major advantages were further supported by the opportunity to avoid stigma, convenience of self-testing (reduced need for transportation and time to go to clinics), and the availability of a pain-free testing option. Participants weighed these benefits against perceived disadvantages of HIVST, the majority of which centred on the perception that HIVST does not include counselling. Participants were concerned that potential lack of counselling would result in poor mental health outcomes, inadequate linkage to HIV care and surveillance, and reductions in disclosure of HIV status. Participants did not view these disadvantages as an impediment, but provided suggestions for future implementation of HIVST in Myanmar. Conclusions: MSM and TW are optimistic about the confidentiality and privacy afforded by HIVST but wanted HIV counselling and linkage to appropriate services. The domestic reprioritization of HIV and opening of the country to international support has substantially increased the availability of HIV treatment and provides new opportunities, like HIVST, to potentially improve the HIV response for key populations who are at risk for HIV acquisition. Keywords: men who have sex with men; transgender women; HIV test; Myanmar, Introduction Demonstration that early antiretroviral therapy (ART) can result in up to 96% reduction in HIV transmission [1] has led to a global goal to increase early identification and engagement [...]