Malaria epidemiology in central Myanmar: identification of a multi-species asymptomatic reservoir of infection.

BACKGROUND: The spread of artemisinin-resistant Plasmodium falciparum is a global health concern. Myanmar stands at the frontier of artemisinin-resistant P. falciparum. Myanmar also has the highest reported malaria burden in Southeast Asia; it is integral in the World Health Organization's plan to eliminate malaria in Southeast Asia, yet few epidemiological data exist for the general population in Myanmar. METHODS: This cross-sectional, probability household survey was conducted in Phyu township, Bago Region (central Myanmar), during the wet season of 2013. Interviewers collected clinical and behavioural data, recorded tympanic temperature and obtained dried blood spots for malaria PCR and serology. Plasmodium falciparum positive samples were tested for genetic mutations in the K13 region that may confer artemisinin resistance. Estimated type-specific malaria PCR prevalence and seroprevalence were calculated, with regression analysis to identify risk factors for seropositivity to P. falciparum. Data were weighted to account for unequal selection probabilities. RESULTS: 1638 participants were sampled (500 households). Weighted PCR prevalence was low (n = 41, 2.5%) and most cases were afebrile (93%). Plasmodium falciparum was the most common species (n = 19. 1.1%) and five (26%) P. falciparum samples harboured K13 mutations. Plasmodium knowlesi was detected in 1.0% (n = 16) and Plasmodium vivax was detected in 0.4% (n = 7). Seroprevalence was 9.4% for P. falciparum and 3.1% for P. vivax. Seroconversion to P. falciparum was 0.003/year in the whole population, but 16-fold higher in men over 23 years old (LR test p = 0.016). DISCUSSION: This is the first population-based seroprevalence study from central Myanmar. Low overall prevalence was discovered. However, these data suggest endemic transmission continues, probably associated with behavioural risk factors amongst working-age men. Genetic mutations associated with P. falciparum artemisinin resistance, the presence of P. knowlesi and discrete demographic risk groups present opportunities and challenges for malaria control. Responses targeted to working-age men, capable of detecting sub-clinical infections, and considering all species will facilitate malaria elimination in this setting.

Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar.

To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.

Genetic Diversity of CMY Beta-Lactamase Genes in Clinical Isolates of Escherichia coli in Myanmar: Identification of Three Novel Types and Updated Phylogenetic Classification of blaCMY.

The dissemination of CMY-type enzymes, one of the plasmid-mediated AmpC beta-lactamases, among Enterobacteriaceae has become an important public health concern. In this study, genetic diversity of CMY beta-lactamase genes was investigated for 50 blaCMY-positive isolates detected from 426 clinical isolates of Escherichia coli in Yangon, Myanmar. CMY genes were differentiated into 9 types, with blaCMY-42 being predominant (22 isolates, 44%), followed by blaCMY-2, blaCMY-6, blaCMY-146, and included three novel types (CMY-156, CMY-158, CMY-159). Among E. coli harboring blaCMY, phylogenetic group D-sequence type (ST)405 and A-ST410 were the most common genotypes, and blaCTX-M-15 was detected in 72% (36/50) of isolates. blaCMY-42 was distributed to phylogenetic groups A, B1, and D E. coli with 11 STs, which included 10 isolates harboring carbapenemase genes (blaNDM-4, blaNDM-5, or blaNDM-7). Phylogenetic analysis of all the blaCMY genes reported to date, including the three novel types in the present study, revealed the presence of at least four distinct genetic groups, that is, CMY-1, CMY-2, CMY-70, and CMY-98 group, showing less than 91% nucleotide sequence identities among different groups. CMY-2 group beta-lactamase genes, which contained by far the largest number of CMY types (89.7%) with extensive diversity, were divided into two clusters (I and II). While eight CMY types identified in the present study were classified into CMY-2 group cluster I, novel type CMY-159 was assigned into CMY-98 group with a Citrobacter freundii strain in Thailand.

The Influence of HIV Status on the Burden and Clinical Manifestations of Gastrointestinal Pathogens in Yangon, Myanmar.

The impact of HIV infection on the burden of gastrointestinal pathogens in Myanmar is poorly defined. Stools of 103 HIV-infected and 105 HIV-uninfected adult outpatients at a tertiary referral hospital in Yangon were examined microscopically. Stool antigen tests for Helicobacter pylori infection were positive in 63/103 (61%) HIV-infected and 61/105 (58%) HIV-uninfected patients (P = 0.65). Soil-transmitted helminth infections were much less common, occurring in 9/103 (9%) HIV-infected and 13/103 (13%) HIV-uninfected patients (P = 0.50). One HIV-uninfected patient had Giardia duodenalis, but there were no cases of Strongyloides stercoralis, Entamoeba histolytica, Capillaria philippinensis, Isospora, Cyclospora, or Schistosoma infection in the entire cohort. Despite the high prevalence of H. pylori, only 1/208 (0.5%) had ever received eradication, compared with 159/208 (76%) who had ever been dewormed. Helicobacter pylori appears to be an underappreciated pathogen in Myanmar. Its strong association with gastric cancer and peptic ulcer disease necessitates a more aggressive approach to its management.