Kyaw Zin Thant

Myanmar dengue outbreak associated with displacement of serotypes 2, 3, and 4 by dengue 1.

In 2001, Myanmar (Burma) had its largest outbreak of dengue—15,361 reported cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), including 192 deaths. That year, 95% of dengue viruses isolated from patients were serotype 1 viruses belonging to two lineages that had diverged from an earlier, now extinct, lineage sometime before 1998. The ratio of DHF to DSS cases in 2001 was not significantly different from that in 2000, when 1,816 cases of DHF/DSS were reported and dengue 1 also was the most frequently isolated serotype. However, the 2001 ratio was significantly higher than that in 1998 (also an outbreak year) and in 1999, when all four serotypes were detected and serotypes 1, 2, and 3 were recovered in similar numbers. The large number of clinical cases in 2001 may have been due, in part, to a preponderance of infections with dengue 1 viruses.

Co-occurrence of Point Mutations in the Voltage-Gated Sodium Channel of Pyrethroid-Resistant Aedes aegypti Populations in Myanmar

Background Single amino acid substitutions in the voltage-gated sodium channel associated with pyrethroid resistance constitute one of the main causative factors of knockdown resistance in insects. The kdr gene has been observed in several mosquito species; however, point mutations in the para gene of Aedes aegypti populations in Myanmar have not been fully characterized. The aim of the present study was to determine the types and frequencies of mutations in the para gene of Aedes aegypti collected from used tires in Yangon City, Myanmar. Methodology/Principal Findings We determined high pyrethroid resistance in Aedes aegypti larvae at all collection sites in Yangon City, by using a simplified knockdown bioassay. We showed that V1016G and S989P mutations were widely distributed, with high frequencies (84.4% and 78.8%, respectively). By contrast, we were unable to detect I1011M (or I1011V) or L1014F mutations. F1534C mutations were also widely distributed, but with a lower frequency than the V1016G mutation (21.2%). High percentage of co-occurrence of the homozygous V1016G/S989P mutations was detected (65.7%). Additionally, co-occurrence of homozygous V1016G/F1534C mutations (2.9%) and homozygous V1016G/F1534C/S989P mutations (0.98%) were detected in the present study. Conclusions/Significance Pyrethroid insecticides were first used for malaria control in 1992, and have since been constantly used in Myanmar. This intensive use may explain the strong selection pressure toward Aedes aegypti, because this mosquito is generally a domestic and endophagic species with a preference for indoor breeding. Extensive use of DDT for malaria control before the use of this chemical was banned may also explain the development of pyrethroid resistance in Aedes aegypti.

Whole genomic analysis of human G12P[6] and G12P[8] rotavirus strains that have emerged in Myanmar

G12 rotaviruses are emerging rotavirus strains causing severe diarrhea in infants and young children worldwide. However, the whole genomes of only a few G12 strains have been fully sequenced and analyzed. In this study, we sequenced and characterized the complete genomes of six G12 strains (RVA/Human-tc/MMR/A14/2011/G12P[8], RVA/Human-tc/MMR/A23/2011/G12P[6], RVA/Human-tc/MMR/A25/2011/G12P[8], RVA/Human-tc/MMR/P02/2011/G12P[8], RVA/Human-tc/MMR/P39/2011/G12P[8], and RVA/Human-tc/MMR/P43/2011/G12P[8]) detected in six stool samples from children with acute gastroenteritis in Myanmar. On whole genomic analysis, all six Myanmarese G12 strains were found to have a Wa-like genetic backbone: G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 for strains A14, A25, P02, P39, and P43, and G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 for strain A23. Phylogenetic analysis showed that most genes of the six strains examined in this study were genetically related to globally circulating human G1, G3, G9, and G12 strains. Of note is that the NSP4 gene of strain A23 exhibited the closest relationship with the cognate genes of human-like bovine strains as well as human strains, suggesting the occurrence of reassortment between human and bovine strains. Furthermore, strains A14, A25, P02, P39, and P43 were very closely related to one another in all the 11 gene segments, indicating derivation of the five strains from a common origin. On the other hand, strain A23 consistently formed distinct clusters as to all the 11 gene segments, indicating a distinct origin of strain A23 from that of strains A14, A25, P02, P39, and P43. To our knowledge, this is the first report on whole genome-based characterization of G12 strains that have emerged in Myanmar. Our observations will provide important insights into the evolutionary dynamics of spreading G12 rotaviruses in Asia.

Validation of G6PD Point-of-Care Tests among Healthy Volunteers in Yangon, Myanmar.

Primaquine and other 8-amnoquinoline based anti-malarials can cause haemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Correct diagnosis of G6PD status in patients is crucial for safe treatment of both relapsing stages of Plasmodium vivax and transmitting forms of Plasmodium falciparum. Lack of suitable point-of-care tests has hampered a much needed wide use of primaquine for malaria elimination. In this study we have assessed the performances of two qualitative tests, the fluorescent spot test (FST) and the G6PD CareStart test (CST), against the gold standard quantitative spectrophotometric assay in a population of 1000 random adult healthy volunteers living in Yangon, Myanmar. The prevalence of G6PD deficiency in the Bamar, Karen and in the whole sample set was 6.6% (10.1% in males), 9.2% (21.0% in males) and 6.8% (11.1% in males) respectively. The FST and CST showed comparable performances with sensitivity over 95% and specificity over 90%, however for cases with severe G6PD activity the FTS had improved performance. If used with a conservative interpretation of the signal, the CareStart test has the potential to be used in the field and, by allowing a wider use of primaquine, to help malaria elimination.

Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review

The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed.

High Prevalence of G12 Human Rotaviruses in Children with Gastroenteritis in Myanmar.

Human rotavirus samples from 54 children with acute gastroenteritis in Myanmar in 2011 were subjected to reverse transcription-PCR to determine their G and P types. On G typing, G2 (24/54; 44.4%) was found to be the most prevalent, followed by G12 (17/54; 31.5%) and G1 (1/54; 1.9%). Mixed cases with G2 and G12 were found in 12 of the 54 (22.2%) samples. On P typing, P[4] was found to be the most predominant (29/54; 53.7%), followed by P[8] (17/54; 31.5%) and P[6] (4/54; 7.4%). Mixed cases with P[4] and P[8] were detected in 4 of 54 (7.4%) samples. Thus, occurrence of G2 and unusual G12 in high proportions was characteristic of human rotaviruses in Myanmar in this study setting.

Genetic diversity of merozoite surface protein-1 C-terminal 42 kDa of Plasmodium falciparum (PfMSP-1 42 ) may be greater than previously known in global isolates

BackgroundThe C-terminal 42 kDa region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-142) is the target of an immune response. It has been recognised as one of the promising candidate antigens for a blood-stage malaria vaccine. Genetic structure of PfMSP-142 has been considered to be largely conserved in the P. falciparum population. However, only limited information is currently available. This study aimed to analyse genetic diversity and the effect of natural selection on PfMSP-142 among the Myanmar P. falciparum population and compare them with publicly available PfMSP-142 from global P. falciparum populations.MethodsA total of 69 P. falciparum clinical isolates collected from Myanmar malaria patients in Upper Myanmar in 2015 were used. The PfMSP-142 region was amplified by polymerase chain reaction, cloned and sequenced. Genetic structure and natural selection of this region were analysed using MEGA4 and DnaSP programs. Polymorphic nature and natural selection in global PfMSP-142 were also investigated.ResultsAll three allele types (MAD20, K1, and RO33) of PfMSP-142 were identified in Myanmar isolates of P. falciparum. Myanmar PfMSP-142 displayed genetic diversity. Most polymorphisms were scattered in blocks 16 and 17. Polymorphisms observed in Myanmar PfMSP-142 showed a similar pattern to those of global PfMSP-142; however, they were not identical to each other. Genetic diversity of Myanmar PfMSP-142 was relatively lower than that of PfMSP-142 from different geographical regions. Evidence of natural selection and recombination were found. Comparative analysis of genetic polymorphism and natural selection in the global PfMSP-142 population suggested that this region was not tightly conserved in global PfMSP-142 as previously thought and is under the complicated influence of natural selection and recombination.ConclusionsGlobal PfMSP-142 revealed limited, but non-negligible, genetic diversity by allele types and geographical origins. Complicated natural selection and potential recombination might have occurred in global PfMSP-142. Comprehensive monitoring of genetic diversity for global PfMSP-142 would be needed to better understand the polymorphic nature and evolutionary aspect of PfMSP-142 in the global P. falciparum population. More thought would be necessary for designing a vaccine based on PfMSP-142.

Effectiveness of a novel long-lasting pyriproxyfen larvicide (SumiLarv®2MR) against Aedes mosquitoes in schools in Yangon, Myanmar

BackgroundMosquito-borne diseases are prevalent in Myanmar, with the number of dengue cases showing a significant increase in recent years. Dengue vectors have developed resistance to insecticides and currently used larvicides show only short-term effectiveness. As a result, an alternative larvicide is urgently needed. The present study evaluated the larvicidal effectiveness of long-lasting pyriproxyfen resin discs (SumiLarv®2MR) against dengue virus vectors in schools in Hlaing Thar Yar Township, Yangon.ResultsThe proportion of Aedes mosquito-infested containers was significantly reduced in the schools applied with the larvicide (OR: 0.24, 95% CI: 0.12–0.48) while there was little reduction noted in the control schools (OR: 0.97, 95% CI: 0.55–1.72). The density of infested containers was also significantly reduced in the intervention schools (Beta: -1.50, 95% CI: -1.98–xa0-1.04), but there was no significant reduction in density in the control schools (Beta: -0.19, 95% CI: -0.53–0.14). The proportion of adult emergence was less than 20% in the treated water collected from the intervention schools for six months, while the proportion was over 90% in the untreated water. In addition, eight-month-old SumiLarv®2MR resin discs were still 100% effective when tested in the laboratory. More than 50% of the discs disappeared from treated containers within two months of intervention.ConclusionsSumiLarv®2MR was effective in reducing Aedes-infested containers at least six months after its application in schools. This new pyriproxyfen formulation has great potential for improving the current dengue vector control program in Myanmar.

Pilot Study on the Application of Telemedicine as a Tool for a Population-Based Cancer Registry in Hlegu Township, Yangon Region, Myanmar

Abstract 57PurposeThe cancer burden is rising and threatens the social and economic development of low- and middle-income countries, including Myanmar, in the ASEAN region. A quality cancer registry plays a unique role in planning, the evaluation of cancer control program, treatment, and palliative care. To date, there is a paucity of studies in Myanmar that have focused on the implementation of a population-based cancer registry. In addition, the concept of telemedicine with the use of information technology applications as appropriate during implementation needs to be introduced. Such an approach may be beneficial to those working at the grassroots level for the overall improvement of the processes of community reporting, confirmation of diagnoses, effective referral for palliative care, and the establishment of cancer registries.MethodsA pilot study was therefore carried out to formulate the strategic approach for establishing a population-based cancer registry in Hlegu Township in Northern Yangon Dist...

Sentinel surveillance for rotavirus in children <5 years of age admitted for Diarrheal illness to Yangon Children’s Hospital, Myanmar, 2009–2014

BACKGROUNDnRotavirus is the leading cause of severe acute gastroenteritis (AGE) in children <5u202fyears of age in Myanmar. The purpose of this analysis is to report from the sentinel surveillance system for rotavirus gastroenteritis (RVGE), which collects information on the epidemiology and circulating genotypes to assess the disease burden and support vaccine introduction in Myanmar.nnnMETHODSnProspective, active surveillance for RVGE-associated hospitalizations was conducted during 2009 -2014 at Yangon Childrens Hospital. Stool samples collected from children <5u202fyears of age admitted for AGE were screened for rotavirus antigen by ELISA (ProSpecT™ Rotavirus, OXOID-UK). G and P genotyping was performed by reverse transcription polymerase chain reaction.nnnRESULTSnOverall, 1860/3724 (49.9%) of stool samples tested positive for rotavirus, ranging from 42-56% of hospitalized AGE cases each year. RVGE was predominant in the 6-11u202fmonths age group 889/1860 (47.8%) as compared with 12-23u202fmonths 633/1860 (34.0%), 0-5 months 226/1860 (12.2 %) and 24-59u202fmonths 112/1860 (6.0%). RVGE occurred in a seasonal cycle with peak occurrence in the cold and dry months (November to February), accounting for 65.3% (1151/1763) among enrolled AGE cases. Vomiting (84.1% Vs 67.9%; Pu202f<u202f.01), fever (84.5% Vs 75.6%; Pu202f<u202f.01) and dehydration (78% Vs 69%; Pu202f<u202f.01) were more frequently observed in RVGE than non-RVGE. Genotyping revealed that G1P[8] was predominant from January to June 2009, G12P[8] was predominant throughout 2009-2012 which was replaced in 2012-2013 by G2P[4] and changed again to G1P[8] in 2013-2014 and G9P[8] in late 2014.nnnCONCLUSIONSnRotavirus is accounting for approximately half of AGE-associated hospitalizations among children <5u202fyears of age in Myanmar. There is immense diversity of rotavirus strains similar to that reported previously for other countries in the region. Information gained from this surveillance system highlights consideration of rotavirus vaccine introduction into this target population.