Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.

BACKGROUND: The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed. RESULTS: Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration. CONCLUSION: Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.

The community acceptance of COVID-19 vaccines in Rakhine State: A cross-sectional study in Myanmar.

The global pandemic situation of SARS-CoV-2 (COVID-19) has been ongoing for more than 2 years with the emergence of different variants. With the rapid development of vaccines, countries including Myanmar rolled out vaccination programs to reduce the morbidity and mortality due to COVID-19 with the ultimate goal to end the pandemic. This study seeks to explore the acceptance of the general adult population towards the COVID-19 vaccines administered by the Ministry of Health, and barriers to vaccine acceptance. A quantitative cross-sectional study was conducted by adopting valid and reliable questionnaires from similar studies around the world. Simple random sampling was used to select 288 participants from 12 townships of Rakhine State, Myanmar. The interview was performed using standardized paper-based documents. While the data entry and manipulation were performed using Microsoft Excel, the data analysis process was performed using the Statistical Package for Social Science (SPSS) software. As descriptive statistics, the level of vaccine acceptance, and barriers to vaccine acceptance were calculated. Chi-square analysis and bivariate logistics regression was performed to explore the associated socio-demographic characteristics, COVID-19 and vaccine-related experience, and perceptions of participants on the health belief model (HBM) domains related to vaccine acceptance. A total of 276 participants entered the study and revealed an overall vaccine acceptance level of 91.3%. Higher level of education, working in skilled manual and sales services, monthly income of more than 200,000 MMK (111 USD), history of previous vaccination, not experiencing side effects of vaccine after previous immunization, and elements of the health belief model (HBM) were associated with higher vaccine acceptance. The barriers to vaccine acceptance were mistrust of the efficacy of vaccines and potential major adverse events of COVID-19 vaccines. The high level of vaccine acceptance among the general population in Rakhine state provides an opportunity for health authorities to achieve high vaccination coverage within the community. Nevertheless, the vaccine-related education campaigns should be targeted and conveyed frequently to the sub-groups of the population with vaccine hesitancy to obtain the highest achievable level of vaccine coverage within the community for the ultimate goal to end the pandemic.

Seroprevalence and associated risk factors of Toxoplasma gondii infection among slaughterhouse workers in Yangon Region, Myanmar: A cross-sectional study.

BACKGROUND: Toxoplasmosis, having the significant consequences affecting mortality and quality of life, is still prevalent in various places throughout the world. The major gap in surveillance for Toxoplasma gondii infection among high-risk population, slaughterhouse workers, is an obstacle for the effective policies formulation to reduce the burden of toxoplasmosis in Myanmar. Therefore, this study aimed to assess the seroprevalence of toxoplasmosis and associated factors of seropositivity among slaughterhouse workers in Yangon Region, Myanmar. METHODS: A cross-sectional study that was conducted from June to November 2020 included 139 slaughterhouse workers involving at five main slaughterhouses under Yangon City Development Committee, Myanmar. The presence of IgG and IgM anti-T. gondii antibodies in serum was detected using the OnSite Toxo IgG/IgM Combo Rapid Test. A face-to-face interview was also performed using pretested structured questionnaires to obtain the detail histories: sociodemographic characteristics, level of knowledge, occupational factors, and environmental factors related to T. gondii infection. Bivariate logistic regression was used to determine the factors associated with T. gondii infection. RESULTS: Of all participants, the overall seroprevalence of anti-T. gondii was 43.9% (95% CI: 35.5-52.5%), of whom 98.4% (95% CI: 91.2-100.0%) were reactive only for IgG antibody and 1.6% (95% CI: 0.0-8.8%) were reactive for IgG and IgM antibodies. The significant factors associated with the seropositivity of T. gondii antibodies were blood transfusion history (OR: 5.74, 95% CI: 1.17-28.09), low level of knowledge (OR: 2.91, 95% CI: 1.46-5.83), contact with animal organs, muscles or blood (OR: 14.29, 95% CI: 1.83-111.51), and animals most frequently slaughtered (cattle) (OR: 3.22, 95% CI: 1.16-8.93). CONCLUSIONS: A high seroprevalence of toxoplasmosis was detected among slaughterhouse workers in Yangon Region and it raises a significant public health concern. Therefore, providing health education regarding toxoplasmosis, enforcement of personal hygiene practices in workplaces, the establishment of training for occupational hygiene, and commencement of the risk assessment and serological screening for toxoplasmosis are crucial to curtail the prevalence of T. gondii infection among slaughterhouse workers.

Trajectory of confirmed cases and deaths: fourth wave of COVID-19 epidemic in Myanmar.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has affected day-to-day life worldwide and presents an unprecedented challenge to public health. Many countries performed mitigation measures to contain the disease spread and break the exponential curve. Omicron had already become a dominant variant in Myanmar and then, the fourth wave of the COVID-19 epidemic started on 28th January 2022. Myanmar performed the main community mitigation measures such as strict quarantine for the people who came back from foreign countries, expansion of testing capacity, enforcement of non-pharmaceutical interventions, and improvement of COVID-19 vaccination coverage. Although decreasing the number of COVID-19 cases and deaths, Myanmar is facing the challenges such as human resource shortages in the health sector, community trust for vaccine safety, and inequitable vaccine demand. This communication intends to give insights on what should be considered as the proper mitigation measures to contain the disease spread through the community and as the challenges that occur in implementing public health and social measures.

Involvement of high school teachers in Health Promoting School program in selected township, Yangon Region, Myanmar: A cross-sectional mixed methods study.

BACKGROUND: Schools provide a big opportunity for promoting the student's health, life skill, and behavior. Teachers play a fundamental role in the promotion and successful implementation of school health services. This study aimed to assess the level of involvement in the Health Promoting School program and its associated factors and to explore the benefits and barriers to involvement among high school teachers in Myanmar. METHODS: A mixed methods explanatory sequential study was conducted among 194 high school teachers in Thanlyin Township, Yangon Region, Myanmar, from June to August 2020. Quantitative data were collected with the pretested structural questionnaire and analyzed by Chi-square tests and Fisher's exact tests. A qualitative strand was added by conducting in-depth interviews (n = 15, five teachers from each level of involvement: poor, medium, and good), analyzed by thematic content analysis. RESULTS: Of the 194 teachers, 23.7% had a good level of involvement in the Health Promoting School program. The factor associated with involvement in Health Promoting School program were age (p value < 0.001), duration of services (p value = 0.001), and a number of accomplished training-related school health (p value = 0.008). Qualitative data revealed that improvement of the health knowledge and awareness on health problems, the progress of healthy behaviors, development of physical and mental health, prevention of the disease spread, achievement of healthy and productive learning environment, and development of academic achievement were major benefits of teachers' involvement. Moreover, the main barriers to involvement were insufficient materials and human resources, time constraints, incompetence of the teachers, poor cooperation of school health partnerships, and insufficient awareness of parents. CONCLUSIONS: The proportion of good involvement in the Health Promoting School program among high school teachers was low in this study area. Providing sufficient human resources and material, conducting the on-the-job and refresher training, enhancing parent-teacher cooperation, and strengthening the community partnerships were crucial to improve the level of involvement and reduced the barriers for the achievement of the Health Promoting School program.

Impact of containment measures on community mobility, daily confirmed cases, and mortality in the third wave of COVID-19 epidemic in Myanmar.

In Myanmar, third wave of COVID-19 epidemic began with a surge of confirmed cases in the last week of May 2021. The laboratory-confirmed cases and deaths distinctly increased within 9 weeks. The government and the Ministry of Health adopted containment measures to flatten the peak of the epidemic and to suppress the disease transmission. The strictly containment measures: stay-at-home restrictions, school closure, and office closure have reduced the community mobility, confirmed cases and mortality. Therefore, the timely containment measures implemented by the government were important to reduce the transmission as observed in the third wave of COVID-19 epidemic in Myanmar.

Genomic Tracking of SARS-CoV-2 Variants in Myanmar.

In December 2019, the COVID-19 disease started in Wuhan, China. The WHO declared a pandemic on 12 March 2020, and the disease started in Myanmar on 23 March 2020. In December 2020, different variants were brought worldwide, threatening global health. To counter those threats, Myanmar started the COVID-19 variant surveillance program in late 2020. Whole genome sequencing was done six times between January 2021 and March 2022. Among them, 83 samples with a PCR threshold cycle of less than 25 were chosen. Then, we used MiSeq FGx for sequencing and Illumina DRAGEN COVIDSeq pipeline, command line interface, GISAID, and MEGA version 7 for data analysis. In January 2021, no variant was detected. The second run, during the rise of cases in June 2021, showed Alpha, Delta, and Kappa variants. The third and the fourth runs in August and December showed only a Delta variant. Omicron and Delta variants were detected during the fifth run in January 2022. The sixth run in March 2022 showed only Omicron BA.2. Amino acid mutation at the receptor binding domain of Spike glycoprotein started since the second run coupling with high transmission, recurrence, and vaccine escape. We also found the mutation at the primer targets used in current RT-PCR platforms, but there was no mutation at the existing antiviral drug targets. The occurrence of multiple variants and mutations claimed vigilance at ports of entry and preparedness for effective control measures. Genomic surveillance with the observation of evolutionary data is required to predict imminent threats of the current disease and diagnose emerging infectious diseases.

Initial presenting symptoms, comorbidities and severity of COVID-19 patients during the second wave of epidemic in Myanmar.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by a highly contagious virus called severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019 and became a major threat to health around the world. The health experts are still learning more about the detailed knowledge of the natural course and the severity of COVID-19. The study aimed to assess the prevalence and association of severity of disease with demographic characteristics, initial presenting symptoms, and comorbidities among COVID-19 patients in treatment centers, Myanmar. METHODS: A cross-sectional study was conducted at Hmawbi and Indine treatment centers, Yangon Region, Myanmar, from November to December 2020. Data were collected by using standardized case report forms and then, a total of 222 confirmed COVID-19 inpatients were included in this study. The odds ratio with a 95% confidence interval (CI) was used as a measure of association and the independent associated factors for severity of disease were investigated using logistic regression analysis. RESULTS: In total, 81.5% were symptomatic patients and of these, the most common presenting symptoms were fever 54.1%, loss of smell 50.3%, and cough 30.9%. Among 37.8% of COVID-19 patients with comorbidities, the most common comorbidities were hypertension 58.3%, diabetes mellitus 29.8%, and heart diseases 26.2%, respectively. As a severity, 20.7% of patients had signs of severe pneumonia. The associated factors of severe pneumonia were aged 60 years and older [Adjusted odds ratio (AOR) = 2.88, 95% CI 1.14-7.29], overweight or obesity (AOR: 3.87, 95%CI 1.80-8.33), and current smoking (AOR: 6.74, 95% CI 2.72-16.75). CONCLUSIONS: In this study, one-fifth of the patients developed severe pneumonia. The COVID-19 patients who were aged 60 years and older, overweight or obesity, and current smokers should be monitored carefully during the course of treatment to reduce the disease severity.

Information and communication technology literacy, knowledge and readiness for electronic medical record system adoption among health professionals in a tertiary hospital, Myanmar: A cross-sectional study.

Some developing countries are currently introducing and implementing an electronic medical record system (EMRs) for improvement in healthcare delivery services. Availability of information and communication technology (ICT), technical skillful staff, and strong resistance to change by the health professionals impacted the successful adoption of EMRs. This study aimed to assess the ICT literacy, knowledge, and readiness for EMRs adoption among health professionals in a tertiary hospital, Myanmar. A cross-sectional study was conducted among 118 health professionals involving in a tertiary hospital at Nay Pyi Taw, Myanmar from February to April 2020 using a stratified sampling method. The data were collected through face-to-face interviews using a pretested structured questionnaire after getting informed consent. Data were analyzed by using SPSS version 23.0. Chi-square test, Fisher's exact test, and logistic regression analysis were performed to assess the associated factors of ICT literacy, knowledge, and overall readiness for EMRs adoption. The prevalence of high ICT literacy and knowledge on EMRs among health professionals were 20.3% and 24.6% respectively. The factors associated with ICT literacy were professional, education, duration of service, and reported English language skills. Duration of service was associated with knowledge on EMRs. The overall readiness was 54.2% (core readiness 59.3% and engagement readiness 61.9%), and postgraduate [Adjusted Odds Ratio (AOR): 7.32, 95% Confidence Interval (CI): 2.26-23.68] and knowledge on EMRs (AOR: 1.27, 95% CI: 1.13-1.43) were the factors associated with overall readiness for EMRs adoption. Expanding infrastructure and provision of ICT development training are crucial for the improvement of ICT literacy. EMRs training program enabling hands-on experience should be implemented for improvement of knowledge on EMRs. In general, the overall readiness for EMRs adoption was found to be moderate. Enhancing the establishment of comprehensive on-the-job training and contextualization of curriculum in EMRs training program are recommended to improve the health professionals' readiness for EMRs adoption.

Assessment of depressive symptoms in patients with COVID-19 during the second wave of epidemic in Myanmar: A cross-sectional single-center study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has had a great impact on every aspect of society. All countries launched preventive measures such as quarantine, lockdown, and physical distancing to control the disease spread. These restrictions might effect on daily life and mental health. This study aimed to assess the prevalence and associated factors of depressive symptoms in patients with COVID-19 at the Treatment Center. METHODS: A cross-sectional telephone survey was carried out at Hmawbi COVID-19 Treatment Center, Myanmar from December 2020 to January 2021. A total of 142 patients with COVID-19 who met the criteria were invited to participate in the study. A pre-tested Center for Epidemiologic Studies Depression Scale (CES-D) was used as a tool for depressive symptoms assessment. Data were analyzed by using binary logistic regression to identify associated factors of depressive symptoms. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was computed to determine the level of significance with a p < 0.05. RESULTS: The prevalence of depressive symptoms in patients with COVID-19 was 38.7%, with the means (± standard deviation, SD) subscale of somatic symptom, negative effect, and anhedonia were 4.64 (±2.53), 2.51 (± 2.12), and 5.01 (± 3.26), respectively. The patients with 40 years and older (AOR: 2.99, 95% CI: 1.36-6.59), < 4 of household size (AOR: 3.45, 95% CI: 1.46-8.15), ≤ 400,000 kyats of monthly family income (AOR: 2.38, 95% CI: 1.02-5.54) and infection to family members (AOR: 4.18, 95% CI: 1.74-10.07) were significant associated factors of depressive symptoms. CONCLUSION: The high prevalence of depressive symptoms, approximately 40%, was found in patients with COVID-19 in the Treatment Center. Establishments of psychosocial supports, providing psychoeducation, enhancing the social contact with family and friends, and using credible source of information related COVID-19 would be integral parts of mental health services in COVID-19 pandemic situation.

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial.

BACKGROUND: To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin-piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. METHODS: We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50-1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin-piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. FINDINGS: Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was -10·6% (95% CI -15·1 to -6·1; p=0·0008) at month 3 and -4·5% (-10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. INTERPRETATION: In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Assessment of respiratory dust exposure and lung functions among workers in textile mill (Thamine), Myanmar: a cross-sectional study.

BACKGROUND: Airborne dusts are being potentially harmful for workers in occupational environment. Exposure to respirable dust is the most important concern in textile workers for the widespread of occupational lung diseases, especially more serious in developing countries. The aim of the study was to assess the respirable dust exposure and associated factors of lung functions among textile workers. METHODS: A cross-sectional study was carried out at a textile mill (Thamine), Yangon Region, from April to December, 2018 and a total of 207 textile workers were randomly selected by using a multistage sampling procedure. Data were collected by using a structured questionnaire for respiratory symptoms, an air sampling pump for assessment of respirable dust exposure, and a spirometer for testing the lung functions. Logistic regression analysis was performed to assess the associated factors of lung functions. Odds ratios with a 95% confidence interval were computed for strength of associations at the significance level of α ≤ 0.05. RESULTS: The mean (± standard deviation, SD) respirable dust exposure was 3.3 mg/m3 (± 0.69) and the prevalence of increased respirable dust exposure (> 3 mg/m3) was 50.7%. The level of respirable dust exposure was highest in the textile workers involving at twisting department. The means (± SD) spirometry values were FVC 82.8% (± 17.8), FEV1 83.6% (± 18.5), and FEV1/FVC 0.9 (± 0.1). Overall magnitude of reduced lung functions was 40.1%, and the prevalence of reduced FVC, FEV1, and FEV1/FVC were 36.7, 34.3 and 3.9% respectively. The current working at twisting department, > 5 years of service duration, respiratory symptoms and increased respirable dust exposure were associated with reduction in FVC and FEV1. CONCLUSIONS: The current working department, service duration, respiratory symptoms and exposure to respirable dust were predictors of lung functions in textile workers. An adequate ventilation, good work practices, hygienic workplace, safety and health training regarding potential health effects, and periodically assessment of lung functions are the critical elements for control of respirable dust exposure and reduction of occupational lung diseases.

Plasmodium vivax Relapse Rates Following Plasmodium falciparum Malaria Reflect Previous Transmission Intensity.

From 2003 through 2009, 687 of 2885 patients (23.8%) treated for Plasmodium falciparum malaria in clinical studies in Myanmar or on the Thailand-Myanmar border had recurrent Plasmodium vivax malaria within 63 days, compared with 18 of 429 patients (4.2%) from 2010 onward (risk ratio [RR], 0.176; 95% confidence interval, .112-.278; P < .0001). Corresponding data from 42 days of follow-up revealed that 820 of 3883 patients (21.1%) had recurrent P. vivax malaria before 2010, compared with 22 of 886 (2.5%) from 2010 onward (RR, 0.117; 95% CI, .077-.177; P < .0001). This 6-fold reduction suggests a recent decline in P. vivax transmission intensity and, thus, a substantial reduction in the proportion of individuals harboring hypnozoites.

Presence of Burkholderia pseudomallei in the 'Granary of Myanmar'.

Melioidosis is a frequently fatal infectious disease caused by the Gram negative bacillus Burkholderia pseudomallei. Although it was originally discovered in Myanmar, the disease disappeared from sight for many decades. This study focuses on detection of B. pseudomallei in soil in selected sampling sites in an attempt to start to fill the gaps in the current status of our knowledge of the geographical distribution of B. pseudomallei in soil in Myanmar. This cross-sectional study consists of 400 soil samples from 10 selected study townships from two major paddy growing regions. Bacterial isolation was done using a simplified method for the isolation of Burkholderia pseudomallei from soil. In this study, only 1% (4/400) of soil samples were found to be positive; two of four were found at 90 cm depth and another two positive samples were found at 30 cm and 60 cm. This survey has confirmed the presence of environmental B. pseudomallei in Myanmar indicating that the conditions are in place for melioidosis acquisition.

Melioidosis in Myanmar.

Sporadic cases of melioidosis have been diagnosed in Myanmar since the disease was first described in Yangon in 1911. Published and unpublished cases are summarized here, along with results from environmental and serosurveys. A total of 298 cases have been reported from seven states or regions between 1911 and 2018, with the majority of these occurring before 1949. Findings from soil surveys confirm the presence of Burkholderia pseudomallei in the environment in all three regions examined. The true epidemiology of the disease in Myanmar is unknown. Important factors contributing to the current gaps in knowledge are lack of awareness among clinicians and insufficient laboratory diagnostic capacity in many parts of the country. This is likely to have led to substantial under-reporting.

Effectiveness and safety of 3 and 5 day courses of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged and spread in Southeast Asia. In areas where resistance is established longer courses of artemisinin-based combination therapy have improved cure rates. METHODS: The standard 3-day course of artemether-lumefantrine (AL) was compared with an extended 5-day regimen for the treatment of uncomplicated falciparum malaria in Kayin state in South-East Myanmar, an area of emerging artemisinin resistance. Late parasite clearance dynamics were described by microscopy and quantitative ultra-sensitive PCR. Patients were followed up for 42 days. RESULTS: Of 154 patients recruited (105 adults and 49 children < 14 years) 78 were randomized to 3 days and 76 to 5 days AL. Mutations in the P. falciparum kelch13 propeller gene (k13) were found in 46% (70/152) of infections, with F446I the most prevalent propeller mutation (29%; 20/70). Both regimens were well-tolerated. Parasite clearance profiles were biphasic with a slower submicroscopic phase which was similar in k13 wild-type and mutant infections. The cure rates were 100% (70/70) and 97% (68/70) in the 3- and 5-day arms respectively. Genotyping of the two recurrences was unsuccessful. CONCLUSION: Despite a high prevalence of k13 mutations, the current first-line treatment, AL, was still highly effective in this area of South-East Myanmar. The extended 5 day regimen was very well tolerated, and would be an option to prolong the useful therapeutic life of AL. Trial registration NCT02020330. Registered 24 December 2013, https://clinicaltrials.gov/NCT02020330.

A novel field-based molecular assay to detect validated artemisinin-resistant k13 mutants.

BACKGROUND: Given the risk of artemisinin resistance spreading from the Greater Mekong sub-region, prospective monitoring in sub-Saharan Africa should be expedited. Molecular biology techniques used for monitoring rely on the detection of k13 validated mutants by using PCR and Sanger sequencing approach, usually not available in malaria endemic areas. METHODS: A semi-automated workflow based on the easyMAG® platform and the Argene Solution® (bioMérieux, Marcy l'Etoile, France) as a field-based surveillance tool operable at national level was developed in four steps. Clinical and analytical performances of this tool detecting five of the most frequent and validated k13 mutants (Y493H, I543T, R539T, F446I and C580Y) from dried blood spots (DBS) were compared to the gold standard approach (PCR and Sanger sequencing). RESULTS: By using the ARMS (amplification-refractory mutation system) strategy, the best multiplexing options were found in 3 separate real-time PCR duplexes (IC as internal control/I543T, C580Y/Y493H and F446I/R539T) with limits of detection ranging from 50 (C580Y) to 6.25 parasites/µL (Y493H). In field conditions, using 642 clinical DBS (from symptomatic patients and asymptomatic individuals) collected from Cambodia, Myanmar and Africa (Chad), the overall sensitivity and specificity of the K13 bMx prototype assay developed by bioMérieux were ≥ 90%. Areas under the ROC curves were estimated to be > 0.90 for all k13 mutants in samples from symptomatic patients. CONCLUSION: The K13 ready-to-use bMx prototype assay, considered by the end-users as a user-friendly assay to perform (in shorter time than the K13 reference assay) and easy to interpret, was found to require less budget planning and had fewer logistical constraints. Its excellent performance qualifies the prototype as a reliable screening tool usable in malaria endemic countries recognized to be at risk of emergence or spread of validated k13 mutants. Additional multi-site studies are needed to evaluate the performances of the K13 bMx prototype assay in different epidemiological contexts such as Africa, India, or South America.

Identifying artemisinin resistance from parasite clearance half-life data with a simple Shiny web application.

The emergence of artemisinin-resistant Plasmodium falciparum malaria is a major threat to malaria elimination. New tools for supporting the surveillance of artemisinin resistance are critical for current and future malaria control and elimination strategies. We have developed an open-access, user-friendly, web-based tool to analyse parasite clearance half-life data of P. falciparum infected patients after treatment with artemisinin derivatives, so that resistance to artemisinin can be identified. The tool can be accessed at bit.ly/id_artemisinin_resistance.

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.