Papers by Myat Thura Kyaw
Myanmar Health Sciences Research Journal, 2009
The efficacy of AntiOxidant Biofactor (AOB(R)) for the management of apparently healthy subjects ... more The efficacy of AntiOxidant Biofactor (AOB(R)) for the management of apparently healthy subjects with chronic hepatitis C infection was investigated. A total of 60 subjects (35 males, 25 females) participated in the trial. AOB was given orally in 2 packs (3g per pack) 3 times per day. 17 subjects had taken AOB for 3 years, 31 subjects up to 2 years, and 41 subjects up to one year. The initial mean (SD) serum alamine aminotransferase (ALT) level was 46.3+/-35.4IU/L, and significant (p0.05, paired t-test) reductions in the mean serum ALT levels were observed at 6 months (38.6+/-21.5IU/L), 18 months (31.9+/-18.1IU/L), 2 years (31.2+/-14.6IU/L), and 3 years (28.0+/-15.9IU/L). Those presenting with high serum ALT levels (30 subjects) demonstrated significant levels (p0.05, paired t-test) of reduction in the mean serum ALT levels at 6, 12, 18, 24, and 36 months of treatment. No side effects were observed and the AOB treatment was well tolerated by all subjects.
Infection and Immunity, 2015
Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified in human and rode... more Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified in human and rodent malaria parasites. TRAgs have been proposed as candidate antigens for potential vaccines. The Plasmodium vivax TRAg (PvTRAg) family includes 36 members. Each PvTRAg contains a tryptophan-rich (TR) domain in the C-terminal region. In this study, we recombinantly expressed all 36 PvTRAgs using a cell-free expression system, and, for the first time, profiled the IgG antibody responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40 healthy individuals using protein microarray technology. The mean seropositive rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13, PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG antibody, even in low-endemicity countries. In addition, the results of an immunofluorescence analysis suggest that PvTRAgs ...
The Southeast Asian journal of tropical medicine and public health, 1997
Malaria is one of the main health problems in the non-immune immigrant workers and army personnel... more Malaria is one of the main health problems in the non-immune immigrant workers and army personnel of the malaria endemic areas in Myanmar. Due to changes in the vector bionomics and multiresistant strains of P. falciparum, chemoprophylaxis alone is not an effective means of control of malaria in them. So it is envisaged that the combined used of personal protective measures (deltamethrin impregnated bed-nets, scalves and hand-bands) and the chemoprophylaxis will be an effective means of control of malaria in the define group of people. The study also intended to find out the side effects of the deltamethrin and feasibility and acceptability of methods by the users. The study was conducted in Theini Township, Northern Shan State, from March to November 1993. The study population consisted of all ages of both sexes 554 and 440 persons in the test and control groups respectively. At the initial phase of the study, malaria infected persons from both the groups were treated. The experime...
The Southeast Asian journal of tropical medicine and public health, 1997
The study was intended to develop a simple and reliable in vivo field test for monitoring of sens... more The study was intended to develop a simple and reliable in vivo field test for monitoring of sensitivity of P.falciparum to antimalarials. The test is to be used as a built in sustainable monitoring system and applied at regular frequencies to provide guidance in developing a country-wide antimalarial drug policy. The study was conducted as a hospital based study in Mon State in Mudon, Kamawet and Pa-auk hospitals. The criteria matched malaria patients were treated with standard dosages of chloroquine, sulfadoxine-pyrimethamine and mefloquine and blood films were taken on days 0, 2, 3, 4, 7, 14 and 28. The assessment of the in vivo drug response of P.falciparum on days 2, 3 and 4 were compared with WHO standard 28 days and 7 day tests. The following successful tests were carried out for 7 days with different antimalarials: 171 tests with chloroquine and sulfadoxine-pyrimethamine and 167 tests with mefloquine. Tests were also carried out for 28 days: 59 tests with chloroquine, 77 tes...
Malaria journal, Jan 5, 2015
A community-based malaria intervention was introduced through fixed and mobile clinics in rural M... more A community-based malaria intervention was introduced through fixed and mobile clinics in rural Myanmar. This study attempted to identify treatment-seeking behaviour of caregivers for children under five and the determinants of appropriate treatment-seeking behaviour in mobile clinic villages (MV) and non-mobile clinic villages (NMV) in malaria-endemic rural areas in Myanmar. A cross-sectional study was conducted in 23 MV and 25 NMV in Ingapu Township, Myanmar. Appropriate treatment-seeking behaviour was operationally defined as seeking treatment from trained personnel or at a health facility within 24 hours after the onset of fever. Multiple logistic regression analyses were conducted to identify the determinants of appropriate treatment-seeking behaviour. Among the 597 participants in both types of villages, 166 (35.3%) caregivers sought appropriate treatment. No significant difference in appropriate treatment-seeking behaviour was found between the two types of villages (adjusted...
Pathogens and Global Health, 2013
Plasma levels of pro-and anti-inflammatory cytokines of Plasmodium falciparum-infected patients w... more Plasma levels of pro-and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n562) and uncomplicated malaria (UM; n569) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P,0.01), IL-6 (P,0.01), and IL-10 (P,0.05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n514) were significantly higher than those of the UM patients (P,0.001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n534) and SM (n534) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNFalpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P,0.05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.
The Lancet Infectious Diseases, 2015
Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the gl... more Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. Methods We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. Findings Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 diff erent mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations. Interpretation Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided. Funding Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.
Malaria Journal, 2015
Background: Data collected in clinical trials have been used to develop scoring systems that iden... more Background: Data collected in clinical trials have been used to develop scoring systems that identify adults with malaria at greatest risk of death. One of these, the RCAM score, can be simply determined by measuring a patient's Glasgow Coma Score and respiratory rate on admission to hospital. However the safety of using the RCAM score to define high-risk patients has not been assessed outside of the clinical trial setting. Methods: A retrospective audit of medical records of all adults admitted with a diagnosis of malaria to two tertiary referral hospitals in Lower Myanmar in 2013 was undertaken. An RCAM score was calculated in all patients and related to their subsequent clinical course. Results: The recent decline in malaria hospitalizations at both sites continued in 2013. During the year 90 adults were hospitalized with malaria; 62 (69%) had Plasmodium falciparum mono-infection, 11 (12%) had Plasmodium vivax mono-infection, 17 (19%) had mixed infection. All seven (7.7%) deaths occurred in patients infected with P. falciparum. An admission RCAM score <2 identified all the patients that would survive to discharge (positive predictive value (95% confidence interval (CI)) 100% (94.9-100%) and also predicted a requirement for less supportive care: 9/70 (13%) patients with an admission RCAM score <2 required supportive care (blood transfusion, vasopressor support or oxygen supplementation) during their hospitalization compared with 12/20 (60%) patients with an admission RCAM score ≥2 (p < 0.0001). No patient with P. vivax mono-infection required supportive care during their hospitalization. Patients with an oxygen saturation ≤95% on room air on admission were more likely to die before discharge (odds ratio 17.3 (95% CI: 2.9-101.2) than patients with a higher oxygen saturation (p = 0.002). Conclusions: Even outside a clinical trial setting the RCAM score reliably identifies adults with malaria who are at greatest risk of death and can be safely used in the initial triage and management of these patients.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, Jan 13, 2014
Multiple transcontinental waves of drug resistance in Plasmodium falciparum have originated in So... more Multiple transcontinental waves of drug resistance in Plasmodium falciparum have originated in Southeast Asia before spreading westward, first into the rest of Asia and then to sub-Saharan Africa. In vitro studies have suggested that hypermutator P. falciparum parasites may exist in Southeast Asia and that an increased rate of acquisition of new mutations in these parasites may explain the repeated emergence of drug resistance in Southeast Asia. This study is the first to test the hypermutator hypothesis using field isolates. Using genome-wide SNP data from human P. falciparum infections in Southeast Asia and West Africa and a test for relative rate differences we found no evidence of increased relative substitution rates in P. falciparum isolates from Southeast Asia. Instead, we found significantly increased substitution rates in Mali and Bangladesh populations relative to those in populations from Southeast Asia. Additionally we found no association between increased relative subs...
The Journal of infectious diseases, 2014
The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria... more The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia. P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently. The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10(-12)). Parasites with a mutation in any of the K13 kelc...
Nature Genetics, 2015
We report a large multicenter genome-wide association study of Plasmodium falciparum resistance t... more We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new resistance-causing mutations emerging is determined by specific predisposing genetic factors in the underlying parasite population.
Malaria Journal, 2014
Background: High coverage of the bed nets can reduce mortality and morbidity of mosquito-borne di... more Background: High coverage of the bed nets can reduce mortality and morbidity of mosquito-borne diseases including malaria. Although the migrant workers are at high risk of malaria, there are many hidden challenges in universal coverage and utilization of the insecticide-treated nets (ITNs) in this populations. Methods: Cross sectional study was conducted in 170 migrant workers in palm oil plantation sites in Tanintharyi Region and 175 in rubber plantation sites in Mon State. A multistage stratified cluster sampling was applied to select the participants. During household visit, face-to-face interviews using structured pre-coded, pre tested questionnaires and direct observation on installation of the bed nets was conducted. Two focus group discussions in each site were done by sample stratified purposive sampling method mainly focused on effective utilization of bed nets. Results: Among them, 332 (96.2%) had a bed net and 284 (82.3%) had an ITN, while 204 (59.1%) had unused extranets. Among the ITNs users, 28.9% reported problems including insecticide smell (56.9%), dizziness (20.2%), headache (12.8%) and itchiness (9.2%). More than 75% received ITNs from health authorities and NGOs free-of-charge. More than 70% wanted to buy a net but they were unaffordable for 64% of them. On observation, only five families could show no bed net, but 80% showed 1-3 ITNs. Consistent utilization in all seasons was noted in 189 (53.1%), that was higher in palm oil plantation than rubber plantation workers (p = 0.0001) due to the nature of the work at night. Perceived malaria risk was also significantly higher ITNs consistent users than non-users (p = 0.0004) and better willingness to buy an ITN by themselves (p = 0.0005). They said that effectiveness of the ITNs was reduced after 6 months and 2-3 times washing. They wished to receive more durable smooth nets with small holes in lace. Misuses of the ITNs such as use the nets for animals and fishing, were also noted. Conclusion: There should be efforts to improve effective utilization of ITNs by continuous mass free distribution, durability monitoring, surveillance of insecticide resistance of the vector and behaviour change interventions in migrant plantation workers.
BMC Public Health, 2014
Background: Mobile populations are at a high risk of malaria infection and suspected to carry and... more 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 the192 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.
PLoS ONE, 2013
Background: Plasmodium falciparum resistance to artemisinins, the first line treatment for malari... more Background: Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries. Methods: A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days) was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia), parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope), and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels. Results: The median (range) parasite clearance half-life and time were 4.8 (2.1-9.7) and 60 (24-96) hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours) in approximately 1/3 of infections. Fourteen of 52 participants (26.9%) had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics. Conclusions: A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this location from its site of origin in western Cambodia. Resistance containment efforts are underway in Myanmar.
PLoS ONE, 2013
The recent detection of clinical Artemisinin (ART) resistance manifested as delayed parasite clea... more The recent detection of clinical Artemisinin (ART) resistance manifested as delayed parasite clearance in the Cambodia-Thailand border area raises a serious concern. The mechanism of ART resistance is not clear; but the P. falciparum sarco/ endoplasmic reticulum Ca 2+-ATPase (PfSERCA or PfATP6) has been speculated to be the target of ARTs and thus a potential marker for ART resistance. Here we amplified and sequenced pfatp6 gene (,3.6 Kb) in 213 samples collected after 2005 from the Greater Mekong Subregion, where ART drugs have been used extensively in the past. A total of 24 single nucleotide polymorphisms (SNPs), including 8 newly found in this study and 13 nonsynonymous, were identified. However, these mutations were either uncommon or also present in other geographical regions with limited ART use. None of the mutations were suggestive of directional selection by ARTs. We further analyzed pfatp6 from a worldwide collection of 862 P. falciparum isolates in 19 populations from Asia, Africa, South America and Oceania, which include samples from regions prior to and after deployments ART drugs. A total of 71 SNPs were identified, resulting in 106 nucleotide haplotypes. Similarly, many of the mutations were continent-specific and present at frequencies below 5%. The most predominant and perhaps the ancestral haplotype occurred in 441 samples and was present in 16 populations from Asia, Africa, and Oceania. The 3D7 haplotype found in 54 samples was the second most common haplotype and present in nine populations from all four continents. Assessment of the selection strength on pfatp6 in the 19 parasite populations found that pfatp6 in most of these populations was under purifying selection with an average d N /d S ratio of 0.333. Molecular evolution analyses did not detect significant departures from neutrality in pfatp6 for most populations, challenging the suitability of this gene as a marker for monitoring ART resistance.
Malaria Journal, 2013
Background: Malaria rapid diagnostic tests (RDT) are used for diagnostic purpose in malaria-endem... more Background: Malaria rapid diagnostic tests (RDT) are used for diagnostic purpose in malaria-endemic areas where reliable microscopy is not available. Persistence of the antigenaemia causes over-diagnosis and may limit the usefulness of the RDT in monitoring treatment. In this study, the usefulness of histidine-rich protein-2 (HRP2) and pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH) in treatment monitoring of uncomplicated falciparum malaria was carried out in an endemic setting in Myanmar. Methods: A prospective longitudinal, single-arm, cohort study was done by microscopy to confirm Plasmodium falciparum mono-infected cases. After direct treatment with an artemether-lumefantrine combination, patients were followed up on day 3, 7, 14, 21, 28 and any other day of recurrent fever. Blood film examination and RDT were carried out on day 0 and all follow-up days. Results: Out of 77 recruited falciparum cases, 63 became adequate clinical and parasitological response (ACPR) cases, and 60.3% of them were still positive for HRP2 up to day 28. Eleven out of 12 treatment failure cases (91.6%) were detected by pan pLDH. The mean duration required to become negative of HRP2 was 20 days (SD ± 6.03) and that of pan pLDH was six days with or without gametocytes and 3.7 days without gametocytes. Conclusion: Although treatment monitoring cannot be performed by HRP2, it can be assessed by pan pLDH-based assay after day 3 if a gametocidal drug has been administered and after day 7 if the presence of gametocytes was not excluded. The pan pLDH-based assay was a suitable test to monitor the treatment response of uncomplicated falciparum malaria patients.
Journal of Clinical Microbiology, 2014
Asymptomatic infection is an important obstacle for controlling disease in countries where malari... more Asymptomatic infection is an important obstacle for controlling disease in countries where malaria is endemic. Because asymptomatic carriers do not seek treatment for their infections, they can have high levels of gametocytes and constitute a reservoir available for new infection. We employed a sample pooling/PCR-based molecular detection strategy for screening malaria infection in residents from areas of Myanmar where malaria is endemic. Blood samples ( n = 1,552) were collected from residents in three areas of malaria endemicity (Kayin State, Bago, and Tanintharyi regions) of Myanmar. Two nested PCR and real-time PCR assays showed that asymptomatic infection was detected in about 1.0% to 9.4% of residents from the surveyed areas. The sensitivities of the two nested PCR and real-time PCR techniques were higher than that of microscopy examination (sensitivity, 100% versus 26.4%; kappa values, 0.2 to 0.5). Among the three regions, parasite-positive samples were highly detected in sub...
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Papers by Myat Thura Kyaw