Novel two-tiered developmental screening programme for Singaporean toddlers: a quality improvement report.

Early identification of developmental delays with timely intervention, especially before the age of 3 years, can improve child development. In Singapore, however, diagnosis and intervention for developmental delays occur at a median age of 44 months. As early detection and intervention depends on an effective developmental screening programme, we aimed to improve the detection of developmental delays before the age of 3 years in a primary care setting. We did this by implementing a novel two-tiered screening programme which uses three standardised screening tools (Parents' Evaluation of Developmental Status, PEDS-Developmental Milestones and Ages and Stages Questionnaire-3). We used quality improvement methods to integrate and optimise this two-tiered programme into the existing 9-month and 18-month screening schedule, with an additional screening at 30 months to replace the pre-existing 36-month screening of the National Child Health Surveillance Programme. A total of three Plan-Do-Study-Act cycles were performed to ensure programme feasibility and sustainability. They focused on adequately training the primary care nurses, targeting an 80% screening rate and aiming for 20 min screening tool administration time per child. We assessed the proportion of children referred to the child development units after positive screening for developmental concerns under the new programme, with a pre-post and with-without intervention comparison, and reviewed the screening rates and screening tool administration time. The proportion of 18-month old children referred for developmental concerns improved from 3.5%-7.1% over a 6-month period. For those who received further assessment by developmental specialists after the two-tiered screening, 100% received a definitive diagnosis of developmental delays, similar to the situation before programme introduction. Our quality improvement efforts facilitated successful integration of the two-tiered programme into the pre-existing screening schedule with minimal impact to the clinic workflow. While we highlight challenges in implementation that need to be addressed, our findings support a potential nationwide adoption of the two-tiered programme.

Enhancing the blood safety program in Myanmar: Report on projects of global extension of medical technologies of Japan.

The National Center for Global Health and Medicine has long collaborated with the blood program in Myanmar, and the Center started a new project in 2015 to enhance blood transfusion safety as part of a new set of projects of global extension of medical technologies that aims to improve public health and medicine in developing countries under public-private partnerships. The project resulted in remarkable achievements, including maintaining a high proportion of voluntary blood donations despite a rapidly growing demand for blood, ensuring blood safety from the donor to the recipient, and creating public-private partnerships. The project supported the introduction of blood grouping using the tube method at hospital blood banks, safety measures during blood transfusions, and effective use of blood products including component blood. The project identified the need for medical devices such as leukocyte filters, serofuges, and refrigerators to store blood products. The success of the project may depend on mutual understanding and trust based on the duration of collaboration, improvement of the requirement for medical safety (including blood safety) in the country, and shifting the mindset of partner companies in public-private partnerships to create new demand by encouraging improvement of the quality of care and requiring the safety of medical care. In this era of sustainable development goals, the hopes are that these experiences will help other countries seeking to improve their public health through public-private partnerships.

Correction: Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003084.].

Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

BACKGROUND: The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. METHODS AND FINDINGS: Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. CONCLUSIONS: Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.

HIV incidence and factors associated with testing positive for HIV among men who have sex with men and transgender women in Myanmar: data from community-based HIV testing services.

INTRODUCTION: In Myanmar, men who have sex with men (MSM) and transgender women (TW) are disproportionately affected by HIV, despite national HIV program scale-up. However, limited HIV surveillance capacity prevents monitoring of epidemic trends and program impact. This study aimed to estimate HIV prevalence and incidence and explore associated sexual risk behaviours among MSM and TW clients attending HIV testing clinics in Myanmar. METHODS: An electronic data management system was implemented in two community-based, MSM and TW -tailored HIV testing clinics in Myanmar in August 2016. Unique client identifiers enabled prospective monitoring of service engagement, testing frequency and outcomes. We estimated HIV incidence and rate of HIV diagnosis at baseline testing visit among clients over a 15 month period. Correlates of HIV diagnoses were identified using multivariable logistic regression. RESULTS: 2794 MSM and TW were tested for HIV. At their baseline test, 38% of clients reported any previous testing and 93% reported being sexually active over the previous three months, with 74% reporting sex with casual male partners and 28% reporting consistent condom use with casual partners. 291 clients tested positive for HIV for the first time at baseline (10.4%; 95% CI: 9.3 to 11.6). Twelve incident cases were detected among 279 clients receiving ≥2 tests (incidence = 10.1 per 100 person-years; 95% CI: 5.73 to 17.8). HIV diagnosis at baseline was significantly associated with being a transgender woman or a non-openly disclosing man who has sex with men, age 26 to 39 years, and reporting no testing history. CONCLUSIONS: High HIV incidence and new diagnoses being associated with reporting no testing history points to undiagnosed HIV driving transmissions in Myanmar. Repeat testing was uncommon. HIV programs in Myanmar must focus on promoting frequent HIV testing alongside adequate coverage of education and primary prevention interventions among MSM and TW.

Performance of the Access Bio/CareStart rapid diagnostic test for the detection of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.

BACKGROUND: To reduce the risk of drug-induced haemolysis, all patients should be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) prior to prescribing primaquine (PQ)-based radical cure for the treatment of vivax malaria. This systematic review and individual patient meta-analysis assessed the utility of a qualitative lateral flow assay from Access Bio/CareStart (Somerset, NJ) (CareStart Screening test for G6PD deficiency) for the diagnosis of G6PDd compared to the gold standard spectrophotometry (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42019110994). METHODS AND FINDINGS: Articles published on PubMed between 1 January 2011 and 27 September 2019 were screened. Articles reporting performance of the standard CSG from venous or capillary blood samples collected prospectively and considering spectrophotometry as gold standard (using kits from Trinity Biotech PLC, Wicklow, Ireland) were included. Authors of articles fulfilling the inclusion criteria were contacted to contribute anonymized individual data. Minimal data requested were sex of the participant, CSG result, spectrophotometry result in U/gHb, and haemoglobin (Hb) reading. The adjusted male median (AMM) was calculated per site and defined as 100% G6PD activity. G6PDd was defined as an enzyme activity of less than 30%. Pooled estimates for sensitivity and specificity, unconditional negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated comparing CSG results to spectrophotometry using a random-effects bivariate model. Of 11 eligible published articles, individual data were available from 8 studies, 6 from Southeast Asia, 1 from Africa, and 1 from the Americas. A total of 5,815 individual participant data (IPD) were available, of which 5,777 results (99.3%) were considered for analysis, including data from 3,095 (53.6%) females. Overall, the CSG had a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a specificity of 0.95 (95% CI 0.92-0.96). When the prevalence of G6PDd was varied from 5% to 30%, the unconditional NPV was 0.99 (95% CI 0.94-1.00), with an LR+ and an LR- of 18.23 (95% CI 13.04-25.48) and 0.05 (95% CI 0.02-0.12), respectively. Performance was significantly better in males compared to females (p = 0.027) but did not differ significantly between samples collected from capillary or venous blood (p = 0.547). Limitations of the study include the lack of wide geographical representation of the included data and that the CSG results were generated under research conditions, and therefore may not reflect performance in routine settings. CONCLUSIONS: The CSG performed well at the 30% threshold. Its high NPV suggests that the test is suitable to guide PQ treatment, and the high LR+ and low LR- render the test suitable to confirm and exclude G6PDd. Further operational studies are needed to confirm the utility of the test in remote endemic settings.

Consumption of foods containing prohibited artificial colors among middle-school children in Nay Pyi Taw union territory, Myanmar.

BACKGROUND: Food safety control in Myanmar is regulated by the Department of Food and Drug Administration (FDA). FDA conducts food safety education programs in schools and regular market surveys of foods containing prohibited artificial colors. However, the consumption of foods containing FDA-prohibited artificial colors among school children is understudied. This study aimed to assess the consumption of foods containing FDA-prohibited artificial colors among middle-school children in Nay Pyi Taw Union Territory, Myanmar. METHODS: A cross-sectional study was conducted at eight public schools in Nay Pyi Taw Union Territory in 2017. The schools were selected using simple random sampling with a drawing method. In total, 776 students (359 boys and 417 girls) participated in face-to-face interviews using a structured questionnaire and photos of foods containing artificial color published by FDA. A multiple logistic regression was performed to estimate adjusted odds ratio (AOR) for consumption of such foods. RESULTS: In total, 519 (66.9%) children consumed foods with the FDA-prohibited colors. It was revealed that students at suburban schools were nearly five times more likely to consume foods containing FDA-prohibited artificial colors (AOR = 4.84; 95% confidence interval (CI) 2.99-7.82) compared to those at urban schools. In addition, being in the seventh grade (AOR = 3.38; 95% CI 2.30-4.98), availability of prohibited food in school canteen (AOR = 6.16; 95% CI 2.67-14.22), and having a less educated father (AOR = 1.76; 95% CI 1.06-2.92) were positively associated with consumption of the foods with the prohibited colors. CONCLUSION: More than half of the students consumed foods with the prohibited colors. Consumption was more frequent among students from suburban schools, those with unsafe foods accessible at their school canteen, seventh graders, and students with a less educated father. The findings highlighted that school food safety programs, which focus on preventing consumption of foods containing FDA-prohibited artificial colors, are urgently required. Food safety regulation is also required to ban the sale of unsafe food, especially in school canteens.

Survival rate and mortality risk factors among TB-HIV co-infected patients at an HIV-specialist hospital in Myanmar: A 12-year retrospective follow-up study.

BACKGROUND: Myanmar is listed as one of the countries with the highest burden of tuberculosis and HIV infections (TB-HIV) in the world. However, the survival rate and risk factors for mortality among TB-HIV co-infected patients in the country remain unstudied. Therefore, the purpose of this study was to examine these factors. METHODS: A 12-year retrospective follow-up study was conducted among 3598 TB-HIV co-infected patients (2452 male and 1146 female) aged 15 years and above, enrolled on antiretroviral therapy (ART) from July 1, 2005 to December 31, 2016. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Survival rates at the beginning of ART were calculated using the Kaplan-Meier method. RESULTS: A total of 494 (13.7%) patients died during this period. The survival rate of TB-HIV co-infected patients was 82.0% at 5 years and 58.1% at 10 years. The risk factors for mortality were being bedridden (adjusted hazard ratio (aHR) 2.70, 95% confidence interval (CI) 2.13-3.42), having a low baseline CD4 count (aHR 1.53, 95% CI 1.25-1.87), and being on a second-line ART regimen (aHR 8.12, 95% CI 3.56-18.54). CONCLUSIONS: Two out of five TB-HIV patients died within 10 years after ART initiation. Current HIV prevention and treatment programs should focus more on bedridden patients, those on second-line ART, and those with low baseline CD4 counts.

Myanmar language version of the Revised Hasegawa's Dementia Scale.

Reduced cognitive function among the elderly is an important issue not only in developed countries, but also in developing countries. As a test to measure cognitive function, the Revised Hasegawa's Dementia Scale (HDS-R) has been used in Asian countries including Japan, Korea, and China. Since there was no HDS-R version in Myanmar language, a questionnaire and manual for the HDS-R were developed. The translation from English to Myanmar language was done by two Myanmar researchers. Back-translation was conducted to confirm the accuracy of the translation by two other Myanmar researchers. Back-translated English was compared to the original by two Japanese researchers, and inconsistencies were discussed by all six researchers to reach consensus. Five Myanmar researchers independently read the questionnaire and manual to verify the expressions are familiar in Myanmar language. The modified points were as follows. 1) The date order in Question 2 is day/month/year. 2) The words to be memorized in Questions 4 and 7 are padauk tree, cat, and bullock cart for the first set, and tamarind tree, dog, and car for the second set. 3) The objects to be memorized in Question 8 are shown with pictures, not actual objects. 4) Like the Lao version, we introduced two new rules; a clear time definition for no reply (10 seconds), and repeating questions twice for those with hearing problems. The revised version of the HDS-R has been prepared to be an applicable standard questionnaire for use on assessment of cognitive function in suspected dementia cases in Myanmar, both in the clinical and public healthcare setting.

Assessing the operational costs of routine immunization activities at the sub-center level in Myanmar: What matters for increasing national immunization coverage?

BACKGROUND: Myanmar's national immunization program was launched in 1978. Routine immunization is mainly provided at sub-center level with midwives assigned as main vaccinators. The vaccinators at the sub-centers have to obtain vaccines from their designated township health department's cold room for immunization services. This study aimed to calculate the operational costs of routine immunization at sub-centers in Myanmar. METHODS: A cross-sectional study was conducted among 160 sub-centers throughout the country. Face-to-face interviews were conducted with the main vaccinator at each sub-center using a pre-tested questionnaire. The study analyzed the operational costs per facility and the associations between sub-center characteristics and operational costs. RESULTS: In Myanmar, the average operational costs of routine immunization per sub-center ranged from 434,700-990,125 MMK for rural areas and 235,875-674,250 MMK for urban areas. The operational costs increased by 8,749.50 MMK (95% CI: 6,805.79-10,693.21; p < 0.001) per mile and 5,752.50 MMK (95% CI: 914.22-10,590.79; p < 0.05) per working day. CONCLUSION: This study indicated that the operational costs at sub-centers were high and varied significantly among the different geographical areas. The operational costs could be reduced by additional support for the resources, for example, installing cold chain facilities at sub-centers and opening new sub-centers throughout the country.

Recent development of synthetic nonviral systems for sustained gene delivery.

Sustained gene delivery is of particular importance today because it circumvents the need for repeated therapeutic administration and provides spatial and temporal control of the release profile. Better understanding of the genetic basis of diseases and advances in gene therapy have propelled significant research on biocompatible gene carriers for therapeutic purposes. Varied biodegradable polymer-based architectures have been used to create new compositions with unique properties suitable for sustained gene delivery. This review presents the most recent advances in various polymeric systems: hydrogels, microspheres, nanospheres and scaffolds, having complex architectures to encapsulate and deliver functional genes. Through the recombination of different existing polymer systems, the multicomplex systems can be further endowed with new properties for better-targeted biomedical applications.

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.

Are Husbands Involving in Their Spouses' Utilization of Maternal Care Services?: A Cross-Sectional Study in Yangon, Myanmar.

INTRODUCTION: Husbands can play a crucial role in pregnancy and childbirth, especially in patriarchal societies of developing countries. In Myanmar, despite the critical influence of husbands on the health of mothers and newborns, their roles in maternal health have not been well explored. Therefore, the aim of this study was to identify the factors associated with husbands' involvement in maternal health in Myanmar. This study also examined the associations between husbands' involvement and their spouses' utilization of maternal care services during antenatal, delivery and postnatal periods. METHODS: A community-based, cross sectional study was conducted with 426 husbands in Thingangyun Township, Yangon, Myanmar. Participants were husbands aged 18 years or older who had at least one child within two years at the time of interview. Face to face interviews were conducted using a pretested structured questionnaire. Factors associated with the characteristics of husband's involvement as well as their spouses' utilization of maternal care services were analyzed by multivariable logistic regression models. RESULTS: Of 426 husbands, 64.8% accompanied their spouses for an antenatal visit more than once while 51.6% accompanied them for a postnatal visit. Husbands were major financial supporters for both antenatal (95.8%) and postnatal care (68.5%). Overall, 69.7% were involved in decision making about the place of delivery. Regarding birth preparedness, the majority of husbands prepared for skilled birth attendance (91.1%), delivery place (83.6%), and money saving (81.7%) before their spouses gave birth. In contrast, fewer planned for a potential blood donor (15.5%) and a safe delivery kit (21.1%). In the context of maternal health, predictors of husband's involvement were parity, educational level, type of marriage, decision making level in family, exposure to maternal health education and perception of risk during pregnancy and childbirth. Increased utilization of maternal health services was found among spouses of husbands who accompanied them to antenatal visits (AOR 5.82, 95% CI, 3.34-10.15) and those who had a well birth plan (AOR 2.42, 95% CI, 1.34-4.39 for antenatal visit and AOR 2.88, 95% CI, 1.52-5.47 for postnatal visit). CONCLUSION: The majority of husbands supported their spouses' maternal care services use financially; however, they were less involved in birth preparedness and postnatal care. Exposure to maternal health education and their maternal health knowledge were main predictors of their involvement. Women were more likely to use maternal care services when their husbands company them for ANC visits and had a well-birth plan in advance.

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests.

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as "radical cure"), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide.Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient's G6PD status is known before deciding to administer an 8-aminoquinoline-based drug.In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure.