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

Malaria incidence in Myanmar 2005–2014: steady but fragile progress towards elimination

Abstract Background There has been an impressive recent reduction in the global incidence of malaria, but the development of artemisinin resistance in the Greater Mekong Region threatens this progress. Increasing artemisinin resistance is particularly important in Myanmar, as it is the country in the Greater Mekong Region with the greatest malaria burden. If malaria is to be eliminated in the region, it is essential to define the spatial and temporal epidemiology of the disease in Myanmar to inform control strategies optimally. Results Between the years 2005 and 2014 there was an 81.1 % decline in the reported annual incidence of malaria in Myanmar (1341.8 cases per 100,000 population to 253.3 cases per 100,000 population). In the same period, there was a 93.5 % decline in reported annual mortality from malaria (3.79 deaths per 100,000 population to 0.25 deaths per 100,000 population) and a 87.2 % decline in the proportion of hospitalizations due to malaria (7.8 to 1.0 %). Chin State had the highest reported malaria incidence and mortality at the end of the study period, although socio-economic and geographical factors appear a more likely explanation for this finding than artemisinin resistance. The reduced malaria burden coincided with significant upscaling of disease control measures by the national government with support from international partners. These programmes included the training and deployment of over 40,000 community health care workers, the coverage of over 60 % of the at-risk population with insecticide-treated bed nets and significant efforts to improve access to artemesinin-based combination treatment. Beyond these malaria-specific programmes, increased general investment in the health sector, changing population demographics and deforestation are also likely to have contributed to the decline in malaria incidence seen over this time. Conclusions There has been a dramatic fall in the burden of malaria in Myanmar since 2005. However, with the rise of artemisinin resistance, continued political, financial and scientific commitment is required if the ambitious goal of malaria elimination in the country is to be realized

A Deficiency of Ceramide Biosynthesis Causes Cerebellar Purkinje Cell Neurodegeneration and Lipofuscin Accumulation

Sphingolipids, lipids with a common sphingoid base (also termed long chain base) backbone, play essential cellular structural and signaling functions. Alterations of sphingolipid levels have been implicated in many diseases, including neurodegenerative disorders. However, it remains largely unclear whether sphingolipid changes in these diseases are pathological events or homeostatic responses. Furthermore, how changes in sphingolipid homeostasis shape the progression of aging and neurodegeneration remains to be clarified. We identified two mouse strains, flincher (fln) and toppler (to), with spontaneous recessive mutations that cause cerebellar ataxia and Purkinje cell degeneration. Positional cloning demonstrated that these mutations reside in the Lass1 gene. Lass1 encodes (dihydro)ceramide synthase 1 (CerS1), which is highly expressed in neurons. Both fln and to mutations caused complete loss of CerS1 catalytic activity, which resulted in a reduction in sphingolipid biosynthesis in the brain and dramatic changes in steady-state levels of sphingolipids and sphingoid bases. In addition to Purkinje cell death, deficiency of CerS1 function also induced accumulation of lipofuscin with ubiquitylated proteins in many brain regions. Our results demonstrate clearly that ceramide biosynthesis deficiency can cause neurodegeneration and suggest a novel mechanism of lipofuscin formation, a common phenomenon that occurs during normal aging and in some neurodegenerative diseases

Prevalence of plasmodium falciparum in active conflict areas of eastern Burma: a summary of cross-sectional data

BACKGROUND: Burma records the highest number of malaria deaths in southeast Asia and may represent a reservoir of infection for its neighbors, but the burden of disease and magnitude of transmission among border populations of Burma remains unknown. METHODS: Plasmodium falciparum (Pf) parasitemia was detected using a HRP-II antigen based rapid test (Paracheck-Pf(R)). Pf prevalence was estimated from screenings conducted in 49 villages participating in a malaria control program, and four retrospective mortality cluster surveys encompassing a sampling frame of more than 220,000. Crude odds ratios were calculated to evaluate Pf prevalence by age, sex, and dry vs. rainy season. RESULTS: 9,796 rapid tests were performed among 28,410 villagers in malaria program areas through four years (2003: 8.4%, 95% CI: 8.3 - 8.6; 2004: 7.1%, 95% CI: 6.9 - 7.3; 2005:10.5%, 95% CI: 9.3 - 11.8 and 2006: 9.3%, 95% CI: 8.2 - 10.6). Children under 5 (OR = 1.99; 95% CI: 1.93 - 2.06) and those 5 to 14 years (OR = 2.24, 95% CI: 2.18 - 2.29) were more likely to be positive than adults. Prevalence was slightly higher among females (OR = 1.04, 95% CI: 1.02 - 1.06) and in the rainy season (OR = 1.48, 95% CI: 1.16 - 1.88). Among 5,538 rapid tests conducted in four cluster surveys, 10.2% were positive (range 6.3%, 95% CI: 3.9 - 8.8; to 12.4%, 95% CI: 9.4 - 15.4). CONCLUSION: Prevalence of plasmodium falciparum in conflict areas of eastern Burma is higher than rates reported among populations in neighboring Thailand, particularly among children. This population serves as a large reservoir of infection that contributes to a high disease burden within Burma and likely constitutes a source of infection for neighboring regions

Parkinson's Disease: Basic Pathomechanisms and a Clinical Overview

PD is a common and a debilitating degenerative movement disorder. The number of patients is increasing worldwide and as yet there is no cure for the disease. The majority of existing treatments target motor symptom control. Over the last two decades the impact of the genetic contribution to PD has been appreciated. Significant discoveries have been made, which have advanced our understanding of the pathophysiological and molecular basis of PD. In this chapter we outline current knowledge of the clinical aspects of PD and the basic mechanistic understanding

A cross-sectional survey of soil-transmitted helminthiases in two Myanmar villages receiving mass drug administration: epidemiology of infection with a focus on adults

Background: Soil-transmitted helminths (STH) are still highly prevalent in southeast Asia. The country of Myanmar has had ongoing mass drug administration (MDA) programmes since 2003 in an attempt to control STH and reduce STH-related morbidities. Whilst the MDA programmes have reported high nationwide coverage, there have been no epidemiological surveys that included measurements from adults. This paper details three cross-sectional surveys that took place over the course of a year in two villages endemic for STH and receiving MDA in lower Myanmar. Results: At baseline, 27.81% of participants were infected with at least one type of STH. The most prevalent STH was Trichuris trichiura (18.12%) followed by hookworm (8.71%) and Ascaris lumbricoides (5.34%). Most infections were of low intensity, measured by eggs per gram of faeces (EPG). Gender stratification revealed that A. lumbricoides prevalence was significantly higher in females, whereas hookworm prevalence was significantly higher in males. The distribution of EPG in the study sample was highly overdispersed, suggesting that most people release few eggs whereas a few people release many eggs. Adults harbour a major proportion of the overall STH burden; 65.15% of STH infections were harboured by adults. Conclusions: STH infection remains at medium prevalence in the study villages despite past and recent MDA. Recorded prevalence of STH in school-aged children has not substantially decreased since the last monitoring and evaluation activities in Myanmar in 2013. Analyses suggest that adults are a major contributor to the total STH prevalence and EPG burden, probably perpetuating transmission

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

Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling.

Silent information regulator T1 (SirT1) is linked to longevity and negatively controls NF-κB signaling, a crucial mediator of survival and regulator of both osteoclasts and osteoblasts. Here we show that NF-κB repression by SirT1 in both osteoclasts and osteoblasts is necessary for proper bone remodeling and may contribute to the mechanisms linking aging and bone loss. Osteoclast- or osteoblast-specific SirT1 deletion using the Sirt(flox/flox) mice crossed to lysozyme M-cre and the 2.3 kb col1a1-cre transgenic mice, respectively, resulted in decreased bone mass caused by increased resorption and reduced bone formation. In osteoclasts, lack of SirT1 promoted osteoclastogenesis in vitro and activated NF-κB by increasing acetylation of Lysine 310. Importantly, this increase in osteoclastogenesis was blocked by pharmacological inhibition of NF-κB. In osteoblasts, decreased SirT1 reduced osteoblast differentiation, which could also be rescued by inhibition of NF-κB. In further support of the critical role of NF-κB signaling in bone remodeling, elevated NF-κB activity in IκBα(+/-) mice uncoupled bone resorption and formation, leading to reduced bone mass. These findings support the notion that SirT1 is a genetic determinant of bone mass, acting in a cell-autonomous manner in both osteoblasts and osteoclasts, through control of NF-κB and bone cell differentiation