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Malaria causes nearly half a million deaths worldwide every year. Ninety percent of them are in sub-Saharan Africa, where poor infrastructure limits delivery of drugs. But now there is worry that those drugs are losing effectiveness as disease strains become resistant. PBS News Hour special correspondent Fred de Sam Lazaro reports from Cambodia, where scientists are researching and tracking new outbreaks.
Defining the hidden burden of disease in rural communities in Bangladesh, Cambodia and Thailand: a cross-sectional household health survey protocol
IntroductionIn low-income and middle-income countries in Southeast Asia, the burden of diseases among rural population remains poorly understood, posing a challenge for effective healthcare prioritisation and resource allocation. Addressing this knowledge gap, the South and Southeast Asia Community-based Trials Network (SEACTN) will undertake a survey that aims to determine the prevalence of a wide range of non-communicable and communicable diseases, as one of the key initiatives of its first project—the Rural Febrile Illness project (RFI). This survey, alongside other RFI studies that explore fever aetiology, leading causes of mortality, and establishing village and health facility maps and profiles, will provide an updated epidemiological background of the rural areas where the network is operational.Methods and analysisDuring 2022–2023, a cross-sectional household survey will be conducted across three SEACTN sites in Bangladesh, Cambodia and Thailand. Using a two-stage cluster-sampling approach, we will employ a probability-proportional-to-size sample method for village, and a simple random sample for household, selection, enrolling all members from the selected households. Approximately 1500 participants will be enrolled per country. Participants will undergo questionnaire interview, physical examination and haemoglobin point-of-care testing. Blood samples will be collected and sent to central laboratories to test for chronic and acute infections, and biomarkers associated with cardiovascular disease, and diabetes. Prevalences will be presented as an overall estimate by country, and stratified and compared across sites and participants’ sociodemographic characteristics. Associations between disease status, risk factors and other characteristics will be explored.Ethics and disseminationThis study protocol has been approved by the Oxford Tropical Research Ethics Committee, National Research Ethics Committee of Bangladesh Medical Research Council, the Cambodian National Ethics Committee for Health Research, the Chiang Rai Provincial Public Health Research Ethical Committee. The results will be disseminated via the local health authorities and partners, peer-reviewed journals and conference presentations.Trial registration numberNCT05389540.
Field evaluation of a novel semi-quantitative point-of-care diagnostic for G6PD deficiency in Indonesia.
BackgroundThe WHO recommends routine testing of G6PD activity to guide radical cure in patients with Plasmodium vivax malaria. Females may have intermediate G6PD enzyme activity and to date, only complex diagnostics are able to reliably identify them. The semi-quantitative G6PD diagnostic "One Step G6PD Test" (Humasis, RoK; "RDT") is a lateral flow assay that can distinguish deficient, intermediate, and normal G6PD status and offers a simpler diagnostic alternative.MethodsG6PD status of participants enrolled in Malinau and Nunukan Regencies and the capital Jakarta was assessed with the RDT, and G6PD activity was measured in duplicate by reference spectrophotometry. The adjusted male median (AMM) of the spectrophotometry measurements was defined as 100% activity; 70% and 30% of the AMM were defined as thresholds for intermediate and deficient G6PD status, respectively. Results were compared to those derived from spectrophotometry at the clinically relevant G6PD activity thresholds of 30% and 70%.ResultsOf the 161 participants enrolled, 10 (6.2%) were G6PD deficient and 12 (7.5%) had intermediate G6PD activity by spectrophotometry. At the 30% threshold, the sensitivity of the RDT was 10.0% (95%CI: 0.3-44.5%) with a specificity of 99.3% (95%CI: 96.4-100.0%); the positive predictive value was 50.0% (95%CI: 1.3-98.7%) and the negative predictive value 94.3% (95%CI: 89.5-97.4%). The corresponding figures at the 70% threshold were 22.7% (95%CI: 7.8-45.4%), 100.0% (95%CI: 97.4-100.0%), 100.0% (95%CI: 47.8-100.0%) and 89.1% (95%CI: 83.1-93.5%), respectively.ConclusionWhile there is a dire need for an easy-to-use, economical, semi-quantitative diagnostic for the point of care, the observed performance of the "One Step G6PD Test" in its current form was insufficient to guide antimalarial treatment.
Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings
Abstract Background In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. Methods We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. Results In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72–0.74) and calibration (calibration slopes: 1.01–1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. Conclusions We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
Temporal changes in SARS-CoV-2 clearance kinetics and the optimal design of antiviral pharmacodynamic studies: an individual patient data meta-analysis of a randomised, controlled, adaptive platform study (PLATCOV).
BackgroundEffective antiviral drugs prevent hospitalisation and death from COVID-19. Antiviral efficacy can be efficiently assessed in vivo by measuring rates of SARS-CoV-2 clearance estimated from serial viral genome densities quantitated in nasopharyngeal or oropharyngeal swab eluates. We conducted an individual patient data meta-analysis of unblinded arms in the PLATCOV platform trial to characterise changes in viral clearance kinetics and infer optimal design and interpretation of antiviral pharmacometric evaluations.MethodsSerial viral density data were analysed from symptomatic, previously healthy, adult patients (within 4 days of symptom onset) enrolled in a large multicentre, randomised, adaptive, pharmacodynamic, platform trial (PLATCOV) comparing antiviral interventions for SARS-CoV-2. Viral clearance rates over 1 week were estimated under a hierarchical Bayesian linear model with B-splines used to characterise temporal changes in enrolment viral densities and clearance rates. Bootstrap re-sampling was used to assess the optimal duration of follow-up for pharmacometric assessment, where optimal was defined as maximising the expected Z score when comparing effective antivirals with no treatment. PLATCOV is registered at ClinicalTrials.gov, NCT05041907.FindingsBetween Sept 29, 2021, and Oct 20, 2023, 1262 patients were randomly assigned in the PLATCOV trial. Unblinded data were available from 800 patients (who provided 16 818 oropharyngeal viral quantitative PCR [qPCR] measurements), of whom 504 (63%) were female. 783 (98%) patients had received at least one vaccine dose and 703 (88%) were fully vaccinated. SARS-CoV-2 viral clearance was biphasic (bi-exponential). The first phase (α) was accelerated by effective interventions. For all the effective interventions studied, maximum discriminative power (maximum expected Z score) was obtained when evaluating serial data from the first 5 days after enrolment. Over the 2-year period studied, median viral clearance half-lives estimated over 7 days shortened from 16·6 h (IQR 15·3 to 18·2) in September, 2021, to 9·2 h (8·0 to 10·6) in October, 2023, in patients receiving no antiviral drugs, equivalent to a relative reduction of 44% (95% credible interval [CrI] 19 to 64). A parallel reduction in viral clearance half-lives over time was observed in patients receiving antiviral drugs. For example, in the 158 patients assigned to ritonavir-boosted nirmatrelvir (3380 qPCR measurements), the median viral clearance half-life reduced from 6·4 h (IQR 5·7 to 7·3) in June, 2022, to 4·8 h (4·2 to 5·5) in October, 2023, a relative reduction of 26% (95% CrI -4 to 42).InterpretationSARS-CoV-2 viral clearance kinetics in symptomatic, vaccinated individuals accelerated substantially over 2 years of the pandemic, necessitating a change to how new SARS-CoV-2 antivirals are compared (ie, shortening the period of pharmacodynamic assessment). As of writing (October, 2023), antiviral efficacy in COVID-19 can be efficiently assessed in vivo using serial qPCRs from duplicate oropharyngeal swab eluates taken daily for 5 days after drug administration.FundingWellcome Trust.
Exploring the pediatric nasopharyngeal bacterial microbiota with culture-based MALDI-TOF mass spectrometry and targeted metagenomic sequencing.
UNLABELLED: The nasopharynx is an important reservoir of disease-associated and antimicrobial-resistant bacterial species. This proof-of-concept study assessed the utility of a combined culture, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and targeted metagenomic sequencing workflow for the study of the pediatric nasopharyngeal bacterial microbiota. Nasopharyngeal swabs and clinical metadata were collected from Cambodian children during a hospital outpatient visit and then biweekly for 12 weeks. Swabs were cultured on chocolate and blood-gentamicin agar, and all colony morphotypes were identified by MALDI-TOF MS. Metagenomic sequencing was done on a scrape of all colonies from a chocolate agar culture and processed using the mSWEEP pipeline. One hundred one children were enrolled, yielding 620 swabs. MALDI-TOF MS identified 106 bacterial species/40 genera: 20 species accounted for 88.5% (2,190/2,474) of isolates. Colonization by Moraxella catarrhalis (92.1% of children on ≥1 swab), Haemophilus influenzae (87.1%), and Streptococcus pneumoniae (83.2%) was particularly common. In S. pneumoniae-colonized children, a median of two serotypes [inter-quartile range (IQR) 1-2, range 1-4] was detected. For the 21 bacterial species included in the mSWEEP database and identifiable by MALDI-TOF, detection by culture + MALDI-TOF MS and culture + mSWEEP was highly concordant with a median species-level agreement of 96.9% (IQR 86.8%-98.8%). mSWEEP revealed highly dynamic lineage-level colonization patterns for S. pneumoniae which were quite different to those for S. aureus. A combined culture, MALDI-TOF MS, targeted metagenomic sequencing approach for the exploration of the young child nasopharyngeal microbiome was technically feasible, and each component yielded complementary data. IMPORTANCE: The human upper respiratory tract is an important source of disease-causing and antibiotic-resistant bacteria. However, understanding the interactions and stability of these bacterial populations is technically challenging. We used a combination of approaches to determine colonization patterns over a 3-month period in 101 Cambodian children. The combined approach was feasible to implement, and each component gave complementary data to enable a better understanding of the complex patterns of bacterial colonization.
Determination of ivermectin in plasma and whole blood using LC-MS/MS
Background Ivermectin is the most widely used drug for the treatment of helminthiasis worldwide, and it has also shown promise for malaria elimination through its potent mosquito-lethal activity. The objective of this study was to develop and validate a high-throughput and sensitive method to quantify ivermectin in plasma and whole blood samples, using automated sample extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods Phospholipids were removed in patient whole blood (100 µl) and plasma (100 µl) samples using a 96-well plate Hybrid-solid phase extraction technique. Ivermectin and its isotope-labelled internal standard (ivermectin-D2) were separated on an Agilent Poroshell 120 EC-C18 50mm × 3.0mm I.D. 2.7µm, using a mobile phase of acetonitrile: ammonium formate 2 mM containing 0.5% formic acid (90: 10, v/v). Detection was performed using a triple quadrupole mass spectrometer in the positive ionization mode. Results The method was validated in the concentration range 0.970 - 384 ng/ml in both plasma and whole blood matrices. Intra- and inter-batch precisions during the validation were below 15%. There was no carryover or matrix effects detected. Ivermectin is a stable compound and results showed no degradation in the different stability tests. Conclusions The validated method proved to have high sensitivity and precision, good selectivity and to be suitable for clinical application or laboratory quantification of ivermectin in plasma or whole blood samples.
CamTrapAsia: A dataset of tropical forest vertebrate communities from 239 camera trapping studies.
Information on tropical Asian vertebrates has traditionally been sparse, particularly when it comes to cryptic species inhabiting the dense forests of the region. Vertebrate populations are declining globally due to land-use change and hunting, the latter frequently referred as "defaunation." This is especially true in tropical Asia where there is extensive land-use change and high human densities. Robust monitoring requires that large volumes of vertebrate population data be made available for use by the scientific and applied communities. Camera traps have emerged as an effective, non-invasive, widespread, and common approach to surveying vertebrates in their natural habitats. However, camera-derived datasets remain scattered across a wide array of sources, including published scientific literature, gray literature, and unpublished works, making it challenging for researchers to harness the full potential of cameras for ecology, conservation, and management. In response, we collated and standardized observations from 239 camera trap studies conducted in tropical Asia. There were 278,260 independent records of 371 distinct species, comprising 232 mammals, 132 birds, and seven reptiles. The total trapping effort accumulated in this data paper consisted of 876,606 trap nights, distributed among Indonesia, Singapore, Malaysia, Bhutan, Thailand, Myanmar, Cambodia, Laos, Vietnam, Nepal, and far eastern India. The relatively standardized deployment methods in the region provide a consistent, reliable, and rich count data set relative to other large-scale pressence-only data sets, such as the Global Biodiversity Information Facility (GBIF) or citizen science repositories (e.g., iNaturalist), and is thus most similar to eBird. To facilitate the use of these data, we also provide mammalian species trait information and 13 environmental covariates calculated at three spatial scales around the camera survey centroids (within 10-, 20-, and 30-km buffers). We will update the dataset to include broader coverage of temperate Asia and add newer surveys and covariates as they become available. This dataset unlocks immense opportunities for single-species ecological or conservation studies as well as applied ecology, community ecology, and macroecology investigations. The data are fully available to the public for utilization and research. Please cite this data paper when utilizing the data.
Understanding hospital antimicrobial prescribing decisions and determinants of uptake of new local antimicrobial prescribing guidelines in the Laos
Background Antimicrobial use in the Laos is among the highest in the Southeast Asia region. The first Lao comprehensive antimicrobial prescribing guidelines have been available since 2021. This study explored the determinants of antibiotic prescribing decisions and how the new prescribing guidelines were being used. Methods In August 2022, in-depth interviews were conducted with 16 Lao prescribers from two hospitals. Participants were questioned about their prescribing behaviours, attitudes to guidelines, how they learned about the guidelines and factors influencing their uptake. The interviews were audio-recorded, transcribed, and translated into English. Thematic analysis of the transcripts was conducted. Results Lao prescribers considered multiple factors before deciding to prescribe antibiotics to their patients. The most common factor was based on the clinical judgement of the prescribers. Lack of certain antibiotics and turnaround times of laboratory results were the main challenges to prescribing antibiotics appropriately. The majority of participants were satisfied with the guidelines, regarding them as comprehensive, simple and convenient. However, most participants admitted that they did not access the guidelines very often. The main reason was that they could remember the treatment recommendations because they treat similar diseases on a daily basis. Improving antibiotic knowledge was the most common recommendation in order to improve the appropriate use of antibiotics. Raising awareness of the guidelines and promoting their use should also be considered. In addition, heads of the wards, and policy and implementation leaders, should support, monitor and feedback their use to encourage all prescribers to follow the guidelines. Conclusions Several factors contribute to enhancing appropriate antibiotic prescription. Key factors for improving antibiotic prescription include enhancing prescribers' clinical knowledge, ensuring access to essential antibiotics, utilizing point-of-care diagnostics while waiting for culture and susceptibility testing results, and updating guidelines regularly. Health leaders must get involved to promote their use.
Comparison of perinatal outcome and mode of birth of twin and singleton pregnancies in migrant and refugee populations on the Thai Myanmar border: A population cohort
Background In low- and middle-income countries twin births have a high risk of complications partly due to barriers to accessing hospital care. This study compares pregnancy outcomes, maternal and neonatal morbidity and mortality of twin to singleton pregnancy in refugee and migrant clinics on the Thai Myanmar border. Methods A retrospective review of medical records of all singleton and twin pregnancies delivered or followed at antenatal clinics of the Shoklo Malaria Research Unit from 1986 to 2020, with a known outcome and estimated gestational age. Logistic regression was done to compare the odds of maternal and neonatal outcomes between twin and singleton pregnancies. Results Between 1986 and 2020 this unstable and migratory population had a recorded outcome of pregnancy of 28 weeks or more for 597 twin births and 59,005 singleton births. Twinning rate was low and stable (<9 per 1,000) over 30 years. Three-quarters (446/597) of the twin pregnancies and 96% (56,626/59,005) of singletons birthed vaginally. During pregnancy, a significantly higher proportion of twin pregnancies compared to singleton had pre-eclampsia (7.0% versus 1.7%), gestational hypertension (9.9% versus 3.9%) and eclampsia (1.0% versus 0.2%). The stillbirth rate of twin 1 and twin 2 was higher compared to singletons: twin 1 25 per 1,000 (15/595), twin 2 64 per 1,000 (38/595) and singletons 12 per 1,000 (680/ 58,781). The estimated odds ratio (95% confidence interval (CI)) for stillbirth of twin 1 and twin 2 compared to singletons was 2.2 (95% CI 1.3-3.6) and 5.8 (95% CI 4.1-8.1); and maternal death 2.0 (0.95-11.4), respectively, As expected most perinatal deaths were 28 to <32 week gestation. Conclusion In this fragile setting where access to hospital care is difficult, three in four twins birthed vaginally. Twin pregnancies have a higher maternal morbidity and perinatal mortality, especially the second twin, compared to singleton pregnancies.
Stable isotope ratio analysis: an emerging tool to trace the origin of falsified medicines
Falsified medicines pose a serious threat to global public health. Over the past few decades, the number of public health issues and seizures of falsified medicines has dramatically increased across the world. The development of new analytical techniques for the identification and traceability of these products hold great promise for innovation to help curtail the high number of deaths caused by the lack of adequate treatments and in combating the criminals responsible for manufacturing these products. This review presents the main approaches, based on stable isotope ratios of the bio-elements, mainly Isotope Ratio Mass Spectrometry and Site-specific Natural Isotopic Fractionation by Nuclear Magnetic Resonance, that can contribute to identifying the origin of these products, both in terms of geographical origin and raw materials employed as well as for the batch controls by the producers.
Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match.
BACKGROUND: The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines. METHODS: Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed. RESULTS: COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index. DISCUSSION: Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines.
High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection.
Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.
Factors influencing Thai university students' decisions to take COVID-19 vaccine booster doses: a cross-sectional survey.
BACKGROUND: We aimed to describe the acceptance of COVID-19 vaccine booster doses and factors influencing this among Thai university students. METHODS: A cross-sectional survey was conducted between July and September 2022. All university students in Thailand were eligible to participate. We explored the acceptance rate of COVID-19 vaccine booster doses and regular vaccines (if available) among university students. Associations between factors influencing the acceptance of vaccination were analyzed by multiple logistic regression analysis. RESULTS: A total of 322 participants were surveyed (78.9% female, age 18 to 49 years (mean = 22.6, standard deviation = 5.47)). Most participants (85.7%) were undergraduate students (Bachelor level), and a proportion (84.8%) had a background in health sciences studies. The proportions who accepted booster doses and regular vaccines were 52.8% and 69.3%, respectively. Vaccine accessibility was found to be significantly associated with the acceptance of booster doses (adjusted odds ratio (AOR) = 2.77, 95% confidence interval (CI) = 1.10-6.97), while the availability of scientific evidence (AOR = 3.44, 95% CI = 1.21-9.77) was significantly associated with the acceptance of regular vaccines. CONCLUSIONS: This study contributes to addressing the knowledge gap regarding acceptance of COVID-19 vaccine booster doses among university students in Thailand. Our findings revealed that vaccine accessibility and the availability of scientific evidence, as well as vaccination costs, influenced individuals' decisions around accepting vaccine booster doses. Further research should focus on the dynamics of vaccine acceptance to facilitate the development of targeted strategies and support vaccination policymaking in Thailand.