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Invasive fungal infections are an increasing global health concern, particularly in low-resource settings where diagnostic capacity is limited. In The Gambia, where tuberculosis is highly prevalent, fungal infections may be misdiagnosed as mycobacterial disease due to overlapping clinical symptoms and limited access to fungal testing. This study aimed to determine the presence of three priority fungal pathogens by the World Health Organization (WHO) classification system-Aspergillus species (spp.), Histoplasma spp., and Pneumocystis jirovecii-in patients with symptoms suggestive of tuberculosis, and to develop a molecular tool to support future surveillance. A multiplex quantitative polymerase chain reaction assay was developed and validated for simultaneous detection of Aspergillus spp., Histoplasma spp., and Pneumocystis jirovecii DNA in human sputum. The assay was applied to 273 stored sputum samples collected from adult patients presenting with respiratory symptoms concerning for tuberculosis in The Gambia. The multiplex assay demonstrated high sensitivity and specificity, detecting as few as ten DNA copies per reaction for each target. Among the 273 sputum samples analyzed, Aspergillus DNA was identified in five samples (1.8%), Pneumocystis jirovecii DNA in three samples (1.1%), and no samples were positive for Histoplasma. Cough and weight loss were the most frequently reported symptoms among participants with positive results. This study represents the first molecular detection of Aspergillus spp. and Pneumocystis jirovecii in adults in The Gambia. These findings suggest that fungal colonization or infection may occur in a small proportion of patients presenting with tuberculosis-like symptoms. The multiplex molecular platform developed here provides an accessible approach for fungal surveillance and may improve diagnosis and management of fungal infections in resource-limited settings.

Background Malaria is a major public health concern in The Gambia. There is limited data on the clinical manifestation and outcome of severe malaria in adult patients in The Gambia. The study therefore assessed the clinical manifestations and outcome of severe malaria in adult patients admitted at the Edward Francis Small Teaching Hospital. Methods The study retrospectively reviewed the records of all malaria patients admitted from 18th October 2020 to 2nd February 2022. Demographic data, clinical features, investigations, treatment, and outcomes were recorded. Results A total of 131 confirmed malaria patients were recruited into the study. The median age was 21 yrs, range (15–90) and most of them were within the youth age group (15–24yrs) 85 (64.9%). The majority of the patients were also male 88 (67.2%) with a male to female ratio of 2:1. The most common symptom at presentation was fever 119 (90.8%) and the most common sign was pallor 48 (36.6%). Seventy-six patients (58.1%) and 55 (41.9%) patients met the criteria for severe malaria and uncomplicated malaria diagnosis, respectively. The most common clinical feature amongst patients with severe malaria were impaired consciousness 34 (44.7%), severe anaemia 26 (34.2%) and acute kidney injury 20 (26.3%). Patients with severe malaria were younger with mean age of 22.9 vs. 29 yrs (p = 0.004), more likely to be referred from a lower-level health facility 62 (81.6%) vs. 34 (61.8%) (p = 0.012), to have a longer duration of admission (p = 0.024) and to die 13 (17.1%) vs. 0 (0%) (p = 0.001) as compared to patients with uncomplicated malaria. The total mortality was 13 (9.9%) and all the patients who died had severe malaria. Mortality was higher in patients with impaired consciousness 9 (26.5%) and there was a significant relationship between death and impaired consciousness 9 (69.3%) vs. 25 (21.4%) p = 0.001. Conclusion Severe malaria still affects young adults in an endemic area with significant mortality. This suggests the need for targeted malaria prevention, surveillance, case management and control strategies in this population group in The Gambia to help reduce morbidity and mortality of malaria.

Significant selection pressure has been exerted on the genomes of human populations exposed to Plasmodium falciparum infection, resulting in the acquisition of mechanisms of resistance against severe malarial disease. Many host genetic factors, including sickle cell trait, have been associated with reduced risk of developing severe malaria, but do not account for all of the observed phenotypic variation. Identification of novel inherited risk factors relies upon high-resolution genome-wide association studies (GWAS). We present findings of a GWAS of severe malaria performed in a Tanzanian population (n = 914, 15.2 million SNPs). Beyond the expected association with the sickle cell HbS variant, we identify protective associations within two interleukin receptors (IL-23R and IL-12RBR2) and the kelch-like protein KLHL3 (all P<10-6), as well as near significant effects for Major Histocompatibility Complex (MHC) haplotypes. Complementary analyses, based on detecting extended haplotype homozygosity, identified SYNJ2BP, GCLC and MHC as potential loci under recent positive selection. Through whole genome sequencing of an independent Tanzanian cohort (parent-child trios n = 247), we confirm the allele frequencies of common polymorphisms underlying associations and selection, as well as the presence of multiple structural variants that could be in linkage with these SNPs. Imputation of structural variants in a region encompassing the glycophorin genes on chromosome 4, led to the characterisation of more than 50 rare variants, and individually no strong evidence of associations with severe malaria in our primary dataset (P>0.3). Our approach demonstrates the potential of a joint genotyping-sequencing strategy to identify as-yet unknown susceptibility loci in an African population with well-characterised malaria phenotypes. The regions encompassing these loci are potential targets for the design of much needed interventions for preventing or treating malarial disease.

Antimicrobial use is associated with emergence of antimicrobial resistance. We report hospital antimicrobial procurement, as a surrogate for consumption in humans, expenditure and prices in public hospitals in Vietnam, a lower middle-income country with a high burden of drug resistant infections. Data on antimicrobial procurement were obtained from tender-winning bids from provincial health authorities and public hospitals with detailed bids representing 28.7% (1.68 / 5.85 billion US $) of total hospital medication spend in Vietnam. Antimicrobials were classified using the Anatomical Therapeutic Chemical (ATC) Index and the 2019 WHO Access, Watch, Reserve (AWaRe) groups. Volume was measured in number of Defined Daily Doses (DDD). Antimicrobial prices were presented per DDD. Expenditure on systemic antibacterials and antifungals accounted for 28.6% (US $482.6 million/US $1.68 billion) of the total drug bids. 83% of antibacterials (572,698,014 DDDs) by volume (accounting for 45.5% of the antibacterials spend) were domestically supplied. Overall, the most procured antibacterials by DDD were second generation cephalosporins, combinations of penicillins and beta-lactamase inhibitors, and penicillins with extended spectrum. For parenteral antibacterials this was third generation cephalosporins. The average price for antibacterials was US $15.6, US $0.86, US $0.4 and US $11.7 per DDD for Reserve, Watch, Access and non-recommended/unclassified group antibacterials, respectively. Antimicrobials accounted for a substantial proportion of the funds spent for medication in public hospitals in Vietnam. The pattern of antibacterial consumption was similar to other countries. The high prices of Reserve group and non-recommended/unclassified antibacterials suggests a need for a combination of national pricing and antimicrobial stewardship policies to ensure appropriate accessibility.

Background As in many other low and middle income countries (LIMCs), Vietnam has experienced a major growth in the pharmaceutical industry, with large numbers of pharmacies and drug stores, and increasing drug expenditure per capita over the past decade. Despite regulatory frameworks that have been introduced to control the dispensing and use of prescription-only drugs, including antibiotics, compliance has been reported to be strikingly low particularly in rural parts of Vietnam. This qualitative study aimed to understand antibiotic access and use practices in the community from both supplier and consumer perspectives in order to support the identification and development of future interventions. Methods This qualitative study was part of a project on community antibiotic access and use (ABACUS) in six LMICs. The focus was Ba Vi district of Hanoi capital city, where we conducted 16 indepth interviews (IDIs) with drug suppliers, and 16 IDIs and 6 focus group discussions (FGDs) with community members. Drug suppliers were sampled based on mapping of all informal and formal antibiotic purchase or dispensing points in the study area. Community members were identified through local networks and relationships with the field collaborators. All IDIs and FGDs were audio-taped, transcribed and analysed using content analysis. Results We identified a large number of antibiotic suppliers in the locality with widespread infringements of regulatory requirements. Established reciprocal relationships between suppliers and consumers in drug transactions were noted, as was the consumers’ trust in the knowledge and services provided by the suppliers. In addition, antibiotic use has become a habitual choice in most illness conditions, driven by both suppliers and consumers. Conclusions This study presents an analysis of the practices of antibiotic access and use in a rural Vietnamese setting. It highlights the interactions between antibiotic suppliers and consumers in the community and identifies possible targets for interventions.

Background Tuberculosis (TB) is a major global health burden, with an estimated quarter of the world’s population being infected. The World Health Organization (WHO) launched the “End TB Strategy” in 2014 emphasising knowing the epidemic. WHO ranks Vietnam 12th in the world of high burden countries. TB spatial and temporal patterns have been observed globally with evidence of Vitamin D playing a role in seasonality. We explored the presence of temporal and spatial clustering of TB in Vietnam and their determinants to aid public health measures. Methods Data were collected by the National TB program of Vietnam from 2010 to 2015 and linked to the following datasets: socio-demographic characteristics; climatic variables; influenza-like-illness (ILI) incidence; geospatial data. The TB dataset was aggregated by province and quarter. Descriptive time series analyses using LOESS regression were completed per province to determine seasonality and trend. Harmonic regression was used to determine the amplitude of seasonality by province. A mixed-effect linear model was used with province and year as random effects and all other variables as fixed effects. Results There were 610,676 cases of TB notified between 2010 and 2015 in Vietnam. Heat maps of TB incidence per quarter per province showed substantial temporal and geospatial variation. Time series analysis demonstrated seasonality throughout the country, with peaks in spring/summer and troughs in autumn/winter. Incidence was consistently higher in the south, the three provinces with the highest incidence per 100,000 population were Tay Ninh, An Giang and Ho Chi Minh City. However, relative seasonal amplitude was more pronounced in the north. Mixed-effect linear model confirmed that TB incidence was associated with time and latitude. Of the demographic, socio-economic and health related variables, population density, percentage of those under 15 years of age, and HIV infection prevalence per province were associated with TB incidence. Of the climate variables, absolute humidity, average temperature and sunlight were associated with TB incidence. Conclusion Preventative public health measures should be focused in the south of Viet Nam where incidence is highest. Vitamin D is unlikely to be a strong driver of seasonality but supplementation may play a role in a package of interventions.

X-linked Glucose-6-phosphate dehydrogenase (G6PD) A- deficiency is prevalent in sub-Saharan Africa populations, and has been associated with protection from severe malaria. Whether females and/or males are protected by G6PD deficiency is uncertain, due in part to G6PD and malaria phenotypic complexity and misclassification. Almost all large association studies have genotyped a limited number of G6PD SNPs (e.g. G6PD202 / G6PD376), and this approach has been too blunt to capture the complete epidemiological picture. Here we have identified 68 G6PD polymorphisms and analysed 29 of these (i.e. those with a minor allele frequency greater than 1%) in 983 severe malaria cases and controls in Tanzania. We establish, across a number of SNPs including G6PD376, that only female heterozygotes are protected from severe malaria. Haplotype analysis reveals the G6PD locus to be under balancing selection, suggesting a mechanism of protection relying on alleles at modest frequency and avoiding fixation, where protection provided by G6PD deficiency against severe malaria is offset by increased risk of life-threatening complications. Our study also demonstrates that the much-needed large-scale studies of severe malaria and G6PD enzymatic function across African populations require the identification and analysis of the full repertoire of G6PD genetic markers.

Background Malaria remains a major public health concern in The Gambia. The study assessed the trend of malaria admissions and outcome of adult patients admitted after the start of the COVID-19 pandemic in a tertiary hospital in The Gambia. Methods This was a retrospective hospital-based study and data was collected from the 18th October 2020 to 28th February 2023. Demographic data, clinical features, investigations, treatment, and outcomes were recorded. Results A total of 499 malaria cases were admitted to the hospital over the 29 months of the study period. Data from 320 (67.2% of the total cases) adult patients admitted into the internal medicine department were analysed. The median age was 22 years, range (15–90) and 189 (59.1%) cases were youth with a youth (15–24 years) to older adult (> 24 years) ratio of 1.4:1. The majority of the patients were male 199 (62.2) with a male to female ratio of 1.6:1. The total number of malaria cases admitted into the internal medicine department increased from 103 cases in 2021 to 182 cases in 2022and admission peaked in November in both years. The total number of admitted malaria cases during the peak of the malaria season also increased from 92 patients between September 2021 and December 2021 to 132 patients from September 2022 to December 2022.There was also an increase in both severe and uncomplicated malaria during the same period. The total mortality was 31 (9.7%) and the rate was similar in 2021 9 (8.7%) and 2022 15 (8.4%). Patients with impaired consciousness were more likely to die when compared to those without impaired consciousness [19 (23.6%) vs 12 (5%), p  ≤ 0.001]. Patients with acute kidney injury were also more likely to die when compared with those without acute kidney injury [10 (20.4%) vs 15 (7.7%), p = 0.009]. Conclusion The findings show an emerging and consistent trend of malaria admissions and the outcome in the youth and older adult population after the start of the COVID-19 pandemic in The Gambia. This, therefore, suggests the need for the implementation of targeted malaria prevention interventions in this population to further prevent the spread of the disease to the more vulnerable population.

Background Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. Methods A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if >48 h. Results A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36–60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. Conclusions Enterobacteriaceae (predominantly K. pneumoniae and E. coli ) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam.

Vietnam has high rates of antibiotic use and resistance. Measuring resistance in commensal bacteria could provide an objective indicator for evaluating the impact of interventions to reduce antibiotic use and resistance. This study aimed to evaluate the feasibility, acceptability, and bacterial recovery for different sampling strategies. We conducted a cross-sectional mixed methods study in a rural community in Ha Nam Province, northern Vietnam, and collected structured interviews, samples, and in-depth interviews from households. Out of 389 households invited, 324 participated (83%), representing 1502 individuals. Samples were collected from these individuals (1498 stool, 1002 self-administered nasal swabs, and 496 HW-administered nasopharyngeal swabs). Pneumococci were recovered from 11.1% (128/1149) of the total population and 26.2% (48/183) of those under 5-years. Recovery was higher for health-worker (HW)-administered swabs (13.7%, 48/350) than self-administered swabs (10.0%, 80/799) (OR 2.06, 95% CI 1.07–3.96). Cost per swab was cheaper for self-administered ($7.26) than HW-administered ($8.63) swabs, but the overall cost for 100 positive samples was higher ($7260 and $6300 respectively). Qualitative interviews revealed that HW-administered nasopharyngeal swabs took longer to collect, caused more discomfort, and were more difficult to take from children. Factors affecting participation included sense of contribution, perceived trade-offs between benefits and effort, and peer influence. Reluctance was related to stool sampling and negative perceptions of research. This study provides important evidence for planning community-based carriage studies, including cost, logistics, and acceptability. Self-administered swabs had lower recovery, and though cheaper and quicker, this would translate to higher costs for large population-based studies. Recovery might be improved by swab-type, transport medium, and better cold-chain to lab.