Prevalence of G6PD deficiency and diagnostic accuracy of a G6PD point-of-care test among a population at risk of malaria in Myanmar.

BACKGROUND: Over the past decade, the incidence of malaria has steadily declined in Myanmar, with Plasmodium vivax becoming predominant. The resilience of P. vivax to malaria control is attributed to the parasite's ability to form hypnozoites in the host's liver, which can cause relapse. Primaquine is used to eliminate hypnozoites but can cause haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. It is thus necessary to estimate the frequency and variant types of G6PD deficiency in areas where primaquine will be widely used for P. vivax elimination. METHODS: In this study, a descriptive cross-sectional survey was conducted to determine the prevalence of G6PD deficiency in a population residing in Nay Pyi Taw, Myanmar, using a standard spectrophotometric assay, a rapid diagnostic test (RDT), Biosensor, and by genotyping G6PD variants. RESULTS: G6PD enzyme activity was determined from 772 leukocyte-depleted samples, with an adjusted male median G6PD activity value of 6.3 U/g haemoglobin. Using a cut-off value of 30% enzyme activity, the overall prevalence of G6PD deficiency was 10.8%. Genotyping of G6PD variants was performed for 536 samples, of which 131 contained mutations. The Mahidol variant comprised the majority, and males with the Mahidol variant showed lower G6PD enzyme activity. The G6PD Andalus variant, which has not been reported in Myanmar before, was also identified in this study. CONCLUSION: This study provides a G6PD enzyme activity reference value for the Myanmar population and further information on the prevalence and variants of G6PD deficiency among the Myanmar population; it also evaluates the feasibility of G6PD deficiency tests.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION: This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING: National Health and Medical Research Council of Australia.

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm).

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.

Uptake of routine viral load testing among people living with HIV and its implementation challenges in Yangon region of Myanmar: a mixed-methods study.

OBJECTIVES: In 2017, Myanmar implemented routine viral load (VL) monitoring for assessing the response to antiretroviral therapy (ART) among people living with HIV (PLHIV). The performance of routine VL testing and implementation challenges has not yet assessed. We aimed to determine the uptake of VL testing and factors associated with it among PLHIV initiated on ART during 2017 in ART clinics of Yangon region and to explore the implementation challenges as perceived by the healthcare providers. DESIGN: An explanatory mixed-methods study was conducted. The quantitative component was a cohort study, and the qualitative part was a descriptive study with in-depth interviews. SETTING: Six ART clinics operated by AIDS/sexually transmitted infection teams under the National AIDS Programme. PRIMARY OUTCOME MEASURES: (1) The proportion who underwent VL testing by 30 March 2019 and the proportion with virological suppression (plasma VL <1000 copies/mL); (2) association between patient characteristics and 'not tested' was assessed using log binomial regression and (3) qualitative codes on implementation challenges. RESULTS: Of the 567 PLHIV started on ART, 498 (87.8%) retained in care for more than 6 months and were eligible for VL testing. 288 (57.8%, 95% CI: 53.3% to 62.2%) PLHIV underwent VL testing, of which 263 (91.3%, 95% CI: 87.1% to 94.4%) had virological suppression. PLHIV with WHO clinical stage 4 had significantly higher rates of 'not being tested' for VL. Collection of sample for VL testing only twice a month, difficulties in sample collection and transportation, limited trained workforce, wage loss and out-of-pocket expenditure for patients due to added visits were major implementation challenges. CONCLUSIONS: The VL test uptake was low, with only six out of ten PLHIV tested. The VL testing uptake needs to be improved by strengthening sample collection and transportation, adopting point-of-care VL tests, increasing trained workforce, providing compensation to patients for wage loss and travel costs for additional visits.

Southeast Asian Pharmacogenomics Research Network (SEAPharm): Current Status and Perspectives.

Pharmacogenomics (PGx) is increasingly being recognized as a potential tool for improving the efficacy and safety of drug therapy. Therefore, several efforts have been undertaken globally to facilitate the implementation process of PGx into routine clinical practice. Part of these efforts include the formation of PGx working groups working on PGx research, synthesis, and dissemination of PGx data and creation of PGx implementation strategies. In Asia, the Southeast Asian Pharmacogenomics Research Network (SEAPharm) is established to enable and strengthen PGx research among the various PGx communities within but not limited to countries in SEA; with the ultimate goal to support PGx implementation in the region. From the perspective of SEAPharm member countries, there are several key elements essential for PGx implementation at the national level. They include pharmacovigilance database, PGx research, health economics research, dedicated laboratory to support PGx testing for both research and clinical use, structured PGx education, and supportive national health policy. The status of these essential elements is presented here to provide a broad picture of the readiness for PGx implementation among the SEAPharm member countries, and to strengthen the PGx research network and practice in this region.

Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns.

Estimates of Plasmodium falciparum migration may inform strategies for malaria elimination. Here we elucidate fine-scale parasite population structure and infer recent migration across Southeast Asia using identity-by-descent (IBD) approaches based on genome-wide single nucleotide polymorphisms called in 1722 samples from 54 districts. IBD estimates are consistent with isolation-by-distance. We observe greater sharing of larger IBD segments between artemisinin-resistant parasites versus sensitive parasites, which is consistent with the recent spread of drug resistance. Our IBD analyses reveal actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination, as well as asymmetrical migration identifying potential sources and sinks of migrating parasites.

Dawn of Theranostics in Myanmar (Dream, Reality, and Constraint).

Prostate cancer is third common malignancy in men of old age (average 65 years) in Myanmar. Currently, serum PSA and bone scan are the markers of choice. Because of the evidence-based, promising success of 68Ga-PSMA PET-CT and 177Lu-PSMA theranostics in prostate cancer worldwide, 99mTc-PSMA SPECT-CT imaging and 177Lu-PSMA therapy has launched as a stepping-stone of theranostics in Myanmar with the available facilities. Twelve cases of prostate cancer patients were imaged with 600 MBq of 99mTc-PSMA I+S SPECT-CT. Four metastatic castration resistant prostate cancer (MCRPC) patients with abnormal result were treated with 177Lu-PSMA. The protocol consists of 6-8 GBq of 177Lu-PSMA, three successive doses at interval of 4-6 weeks. Post-therapy SPECT-CT imaging was done. All treated patients were improved by free of bone pain, and fall/rise in serum PSA level. Two patients with extensive skeletal metastases succumbed to complications. The results are well documented and present at the multidisciplinary conferences for clinical awareness. Theranostics in prostate cancer with available facilities is an additional boon to our health care professionals to upgrade cancer management in Myanmar. This paper provides the technology with cost effectiveness and benefit to prostate cancer patients of Myanmar.

Neuroblastoma involving urinary bladder: A rare type of tumor with diagnostic ambiguity.

INTRODUCTION: Neuroblastoma of urinary tract is an extremely rare type of tumor and only a few cases have been reported worldwide. CASE PRESENTATION: We presented an adult case of neuroblastoma involving urinary bladder. Patient was a 24-year-old man with a history of repeated attack of hematuria. Patient underwent cystoscopy and transuretheral resection of bladder tumor. Biopsy result was "Blastema cell (suggestive of neuroblastoma) with immature ganglion cells." Immunohistochemistry workup was continued and neuron-specific enolase and S100 staining were positive. Patient lost to further follow-up visit. CONCLUSION: Although neuroblastoma of skin and peripheral nerve is not a rare disease entity, involvement of deeper structures (especially urinary bladder) is exceptional.

Delay in diagnosis and treatment among adult multidrug resistant tuberculosis patients in Yangon Regional Tuberculosis Center, Myanmar: a cross-sectional study.

BACKGROUND: Delays in diagnosis and treatment initiation may allow the emergence of new cases by transmission to the community, and is one of the challenges facing programme management of drug resistance in Myanmar. This study aimed to explore delays in diagnosis and treatment initiation, and associated factors among patients with multidrug-resistant tuberculosis. METHODS: A cross-sectional study was conducted at Yangon Regional Tuberculosis Centre, Myanmar. Data were collected by face-to-face interviews and treatment-card reviews of all adult patients who had registered and started treatment with the standard regimen from May to November, 2017. Delay time was categorized by using median cut-off and analyzed using SPSS version 23.0. Logistic regression analysis was performed to assess the relative impact of predictor variables on diagnosis and treatment delays. RESULTS: A total of 210 patients participated in this study. The median diagnosis delay was 9 days, IQR 3 (8-11) and 58.6% of the patients experienced a long diagnosis delay. Below middle school education (adjusted odds ratio [AOR] = 2.75, 95% CI = 1.22-6.21), non-permanent salaried employment (AOR = 3.03, 95% CI = 1.32-6.95), co-existing diabetes mellitus (AOR = 5.06, 95% CI = 1.97-13.01) and poor awareness (AOR = 2.99, 95% CI = 1.29-6.92) were independent predictors of long diagnosis delay. The median treatment delay was 13 days, IQR 9 (8-17) and 51% of the patients experienced long treatment delay. Age 31-50 years (AOR = 4.50, 95% CI = 1.47-13.97) and age > 50 years (AOR = 9.40, 95% CI = 2.55-34.83), history with MDR-TB patient (AOR = 3.16, 95% CI = 1.29-7.69), > 20 km away from a Regional TB Centre (AOR = 14.33, 95% CI = 1.91-107.64) and poor awareness (AOR = 4.62, 95% CI = 1.56-13.67) were independent predictors of long treatment delay. CONCLUSIONS: Strengthening comprehensive health education, enhancing treatment adherence counseling, providing more Xpert MTB/RIF machines, expanding decentralized MDR-TB treatment centers, ensuring timely sputum transportation, provision of a patient support package immediately after confirmation, and strengthening contact-tracing for all household contacts with MDR-TB patients and active tuberculosis screening were the most effective ways to shorten delays in MDR-TB diagnosis and treatment initiation.

Bayesian spatiotemporal analysis of malaria infection along an international border: Hlaingbwe Township in Myanmar and Tha-Song-Yang District in Thailand.

BACKGROUND: One challenge in moving towards malaria elimination is cross-border malaria infection. The implemented measures to prevent and control malaria re-introduction across the demarcation line between two countries require intensive analyses and interpretation of data from both sides, particularly in border areas, to make correct and timely decisions. Reliable maps of projected malaria distribution can help to direct intervention strategies. In this study, a Bayesian spatiotemporal analytic model was proposed for analysing and generating aggregated malaria risk maps based on the exceedance probability of malaria infection in the township-district adjacent to the border between Myanmar and Thailand. Data of individual malaria cases in Hlaingbwe Township and Tha-Song-Yang District during 2016 were extracted from routine malaria surveillance databases. Bayesian zero-inflated Poisson model was developed to identify spatial and temporal distributions and associations between malaria infections and risk factors. Maps of the descriptive statistics and posterior distribution of predicted malaria infections were also developed. RESULTS: A similar seasonal pattern of malaria was observed in both Hlaingbwe Township and Tha-Song-Yang District during the rainy season. The analytic model indicated more cases of malaria among males and individuals aged ≥ 15 years. Mapping of aggregated risk revealed consistently high or low probabilities of malaria infection in certain village tracts or villages in interior parts of each country, with higher probability in village tracts/villages adjacent to the border in places where it could easily be crossed; some border locations with high mountains or dense forests appeared to have fewer malaria cases. The probability of becoming a hotspot cluster varied among village tracts/villages over the year, and some had close to no cases all year. CONCLUSIONS: The analytic model developed in this study could be used for assessing the probability of hotspot cluster, which would be beneficial for setting priorities and timely preventive actions in such hotspot cluster areas. This approach might help to accelerate reaching the common goal of malaria elimination in the two countries.

Microbiome dataset from the upper respiratory tract of patients living with HIV, HIV/TB and TB from Myanmar.

This article contains microbiome data from the upper respiratory tract of patients living with HIV/TB, HIV and TB from Meiktila, a town in Myanmar where there is a high incidence of HIV and TB. Microbiomes were compared for HIV/TB infected and healthy adults from the same population. We collected nasopharyngeal and oropharyngeal swabs from a total of 33 participants (Healthy {5}, HIV/TB {8}, HIV {14}, and TB {6}). DNA was extracted from the swabs and subjected to custom single step 16s rRNA sequencing on an Illumina MiSeq platform. The sequencing data is available via http://www.ncbi.nlm.nih.gov/bioproject/ PRJNA432583.

Use of Rapid Enzyme-Linked Immunosorbent Assays for Serological Screening of Melioidosis in Myanmar.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is an important but under-recognized cause of disease in the tropics. Although first described over a century ago as a septicemic illness associated with morphine addicts in Rangoon, Burma, there is little information regarding the incidence of melioidosis in present-day Myanmar. To address this issue, we used two recently developed and validated serological assays to detect B. pseudomallei-specific antibodies in 124 serum samples obtained from febrile patients in the delta region of Myanmar. Using cutoff values derived from culture-confirmed melioidosis cases in neighboring Thailand, 3.2% of the samples exhibited reactivity profiles consistent with active B. pseudomallei infections. Collectively, these findings indicate that melioidosis likely represents a significant cause of morbidity and mortality in Myanmar and support the need for further studies to assess the true burden of disease in this country.

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar.

BACKGROUND: Myanmar has the heaviest burden of malaria in the Greater Mekong Sub-region. Asymptomatic Plasmodium spp. infections are common in this region and may represent an important reservoir of transmission that must be targeted for malaria elimination. METHODS: A mass blood survey was conducted among 485 individuals from six villages in Kayah State, an area of endemic but low transmission malaria in eastern Myanmar. Malaria infection was screened by rapid diagnostic test (RDT), light microscopy and real-time polymerase chain reaction (PCR), and its association with demographic factors was explored. RESULTS: The prevalence of asymptomatic Plasmodium spp. infection was 2.3% (11/485) by real-time PCR. Plasmodium vivax accounted for 72.7% (8/11) and Plasmodium falciparum for 27.3% (3/11) of infections. Men were at greater risk of infection by Plasmodium spp. than women. Individuals who worked as farmers or wood and bamboo cutters had an increased risk of infection. CONCLUSION: A combination of RDT, light microscopy and PCR diagnostics were used to identify asymptomatic malaria infection, providing additional information on asymptomatic cases in addition to the routine statistics on symptomatic cases, so as to determine the true burden of disease in the area. Such information and risk factors can improve malaria risk stratification and guide decision-makers towards better design and delivery of targeted interventions in small villages, representative of Kayah State.

The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study.

BACKGROUND: Evidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion. METHODS: In this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance). We collected blood spots from patients with microscopy or rapid test confirmed uncomplicated falciparum malaria. We used microsatellite genotyping to assess genetic relatedness. FINDINGS: As part of studies on the epidemiology of artemisinin-resistant malaria between Jan 1, 2008, and Dec 31, 2015, we collected 434 isolates. In 2014-15, a single long PfKelch13 C580Y haplotype (-50 to +31·5 kb) lineage, which emerged in western Cambodia in 2008, was detected in 65 of 88 isolates from northeastern Thailand, 86 of 111 isolates from southern Laos, and 14 of 14 isolates from western Cambodia, signifying a hard transnational selective sweep. Pfplasmepsin2 amplification occurred only within this lineage, and by 2015 these closely related parasites were found in ten of the 14 isolates from Cambodia and 15 of 15 isolates from northeastern Thailand. C580Y mutated parasites from Myanmar had a different genetic origin. INTERPRETATION: Our results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance. The emergence and spread of fit artemisinin-resistant P falciparum parasite lineages, which then acquire partner drug resistance across the Greater Mekong subregion, threatens regional malaria control and elimination goals. Elimination of falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective. FUNDING: The Wellcome Trust and the Bill and Melinda Gates Foundation.

Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum extends across Southeast Asia where it is associated with worsening partner drug resistance and a decline in the efficacy of frontline artemisinin-based combination therapy. Dihydroartemisinin-piperaquine (DP) is an essential component of preventive and curative treatment in the region, but its therapeutic efficacy has fallen in Cambodia. METHODS: A prospective clinical and parasitological evaluation of DP was conducted at two sites in Upper Myanmar between August 2013 and December 2014, enrolling 116 patients with acute uncomplicated falciparum malaria. Patients received DP orally for 3 days together with primaquine 0.25 mg/kg on admission. Parasite clearance half-lives based on 6 hourly blood smears, and day 42 therapeutic responses were assessed as well as parasite K13 genotypes. RESULTS: Median parasite clearance half-life was prolonged, and clearance half-life was greater than 5 h in 21% of patients. Delayed parasite clearance was significantly associated with mutations in the propeller region of the parasite k13 gene. The k13 F446I mutation was found in 25.4% of infections and was associated with a median clearance half-life of 4.7 h compared with 2.7 h for infections without k13 mutations (p < 0.001). There were no failures after 42 days of follow-up, although 18% of patients had persistent parasitaemia on day 3. CONCLUSION: The dominant k13 mutation observed in Upper Myanmar, F446I, appears to be associated with an intermediate rate of parasite clearance compared to other common mutations described elsewhere in the Greater Mekong Subregion. Discerning this phenotype requires relatively detailed clearance measurements, highlighting the importance of methodology in assessing artemisinin resistance.

Emerging pests and diseases of South-east Asian cassava: a comprehensive evaluation of geographic priorities, management options and research needs.

Cassava is a major staple, bio-energy and industrial crop in many parts of the developing world. In Southeast Asia, cassava is grown on >4 million ha by nearly 8 million (small-scale) farming households, under (climatic, biophysical) conditions that often prove unsuitable for many other crops. While SE Asian cassava has been virtually free of phytosanitary constraints for most of its history, a complex of invasive arthropod pests and plant diseases has recently come to affect local crops. We describe results from a region-wide monitoring effort in the 2014 dry season, covering 429 fields across five countries. We present geographic distribution and field-level incidence of the most prominent pest and disease invaders, introduce readily-available management options and research needs. Monitoring work reveals that several exotic mealybug and (red) mite species have effectively colonised SE Asia's main cassava-growing areas, occurring in respectively 70% and 54% of fields, at average field-level incidence of 27 ± 2% and 16 ± 2%. Cassava witches broom (CWB), a systemic phytoplasma disease, was reported from 64% of plots, at incidence levels of 32 ± 2%. Although all main pests and diseases are non-natives, we hypothesise that accelerating intensification of cropping systems, increased climate change and variability, and deficient crop husbandry are aggravating both organism activity and crop susceptibility. Future efforts need to consolidate local capacity to tackle current (and future) pest invaders, boost detection capacity, devise locally-appropriate integrated pest management (IPM) tactics, and transfer key concepts and technologies to SE Asia's cassava growers. Urgent action is needed to mobilise regional as well as international scientific support, to effectively tackle this phytosanitary emergency and thus safeguard the sustainability and profitability of one of Asia's key agricultural commodities. © 2016 Society of Chemical Industry.

An ultrasensitive reverse transcription polymerase chain reaction assay to detect asymptomatic low-density Plasmodium falciparum and Plasmodium vivax infections in small volume blood samples.

BACKGROUND: Highly sensitive, scalable diagnostic methods are needed to guide malaria elimination interventions. While traditional microscopy and rapid diagnostic tests (RDTs) are suitable for the diagnosis of symptomatic malaria infection, more sensitive tests are needed to screen for low-density, asymptomatic infections that are targeted by interventions aiming to eliminate the entire reservoir of malaria infection in humans. METHODS: A reverse transcription polymerase chain reaction (RT- PCR) was developed for multiplexed detection of the 18S ribosomal RNA gene and ribosomal RNA of Plasmodium falciparum and Plasmodium vivax. Simulated field samples stored for 14 days with sample preservation buffer were used to assess the analytical sensitivity and specificity. Additionally, 1750 field samples from Southeastern Myanmar were tested both by RDT and ultrasensitive RT-PCR. RESULTS: Limits of detection (LoD) were determined under simulated field conditions. When 0.3 mL blood samples were stored for 14 days at 28 °C and 80% humidity, the LoD was less than 16 parasites/mL for P. falciparum and 19.7 copies/µL for P. vivax (using a plasmid surrogate), about 10,000-fold lower than RDTs. Of the 1739 samples successfully evaluated by both ultrasensitive RT-PCR and RDT, only two were RDT positive while 24 were positive for P. falciparum, 108 were positive for P. vivax, and 127 were positive for either P. vivax and/or P. falciparum using ultrasensitive RT-PCR. CONCLUSIONS: This ultrasensitive RT-PCR method is a robust, field-tested screening method that is vastly more sensitive than RDTs. Further optimization may result in a truly scalable tool suitable for widespread surveillance of low-level asymptomatic P. falciparum and P. vivax parasitaemia.