International Journal of Infectious Diseases

Gout is the most common inflammatory arthritis worldwide, traditionally associated with older males (2024c, 2025). However, many studies focus on the elderly, leaving a gap in understanding the burden of gout among working-age individuals. We aimed to quantify the global burden of gout in the working-age population (WAP, 15-64 years) and characterise trends, inequalities, and future projections, using Global Burden of Disease (GBD) 2021 data. We extracted GBD 2021 estimates for gout in 204 countries and territories from 1990 to 2021 for ages 15-64. Disease burden was assessed through incidence, prevalence, and years lived with disability (YLDs), along with corresponding age-standardised rates (per 100,000). Trend analysis included calculating the estimated annual percentage change (EAPC) of age-standardised rates and using join point regression to detect inflexion points. We quantified contributions of demographic drivers (population growth and ageing) versus epidemiologic changes in gout rates using decomposition analysis. Cross-national inequalities were evaluated with the Slope Index of Inequality (SII) and concentration index for gout metrics across the socio-demographic spectrum. A forecasting model (based on GBD data and a mixed-effects temporal model) projected gout burden in WAP through 2045. Globally in 2021, there were 6.08 million (95% UI: [~]5.5-6.6) new gout cases and 32.7 million (UI: [~]30-35) prevalent gout cases among people aged 15-64 years. The age-standardised incidence rate (ASIR) was approximately 105 per 100,000, and the age-standardised prevalence rate (ASPR) was about 510 per 100,000 in 2021. These rates rose modestly since 1990 (EAPCs [~]0.5-0.8%/year), reflecting a gradual upward trend. No major joinpoints were indicated to have sudden trend shifts over the 1990-2021 period. Males in the working-age group had about 3-fold higher gout prevalence than females, mirroring known sex disparities. High-income regions (e.g., Australasia and North America) exhibited the highest WAP gout rates. In contrast, some low-income areas (e.g., parts of sub-Saharan Africa and Latin America) had the lowest. A moderate positive correlation between national gout burden and Socio-demographic Index (SDI) was observed. Health disparities widened over time: the gout concentration index increased, indicating the disease became more unequally distributed, disproportionately affecting higher-SDI populations by 2021. From 1990 to 2021, the total number of WAP gout cases increased substantially. Decomposition analysis revealed that population growth accounted for [~]54.4% of this increase, with population ageing and rising age-specific gout prevalence contributing [~]20% and [~]25%, respectively (Table 1). We project that by 2045, the number of working-age gout cases will rise to [~]45 million, a 40% increase from 2021. Despite growing absolute cases, age-standardised rates are expected to stabilise or increase only slightly in the coming decades, assuming current trends hold. The burden of gout in working-age adults has increased globally over the past three decades and is expected to continue growing due to demographic expansion. This first comprehensive analysis of the working-age population reveals that gout is not merely a disease of the elderly - a majority of global cases occur before the age of 65, with significant implications for productivity and healthcare systems. Urgent, age-targeted prevention strategies (e.g. obesity and metabolic syndrome management) and improved access to care for younger gout patients are warranted to curb the rising burden and reduce future disability.

Recent studies suggested that human cytomegalovirus (HCMV) exposure may increase tuberculosis (TB) disease risk. We assessed the association between active HCMV infection and recent HCMV exposure with tuberculosis (TB) disease among TB-presumptive South African adults. This was a nested case-control analysis that utilized stored plasma and serum samples collected from adults ([≥]18 years) with presumptive TB self-presenting to primary care clinics in in the Kraaifontein District in Cape Town, South Africa. Cases (n=98) and HIV status frequency matched controls (n=199) basing on mycobacterial culture and or GeneXpert Ultra were included in the study. HCMV DNAemia was detected by qPCR well as current HCMV reactivation or reinfection and recent HCMV infection, reactivation or reinfection were categorized using PCR and serology (IgM and IgG avidity ELISA) results. The median age of all participants was 37 years (IQR 29-47), 164 (55.2%) were male and 119 (40.1%) had previous TB treatment. Overall, 21 (7.1%) had HCMV DNAemia, 19 (6.4%) had positive HCMV IgM and 2 (0.7%) had low HCMV avidity. In a logistic regression model adjusting for age, gender, HIV status and BMI, TB disease was associated with current HCMV reactivation or reinfection [adjusted odds ratio (aOR) 4.88, 95%CI 1.59-16.31, p=0.007]. There was no association with recent HCMV infection, reactivation or reinfection. Unlike recent HCMV infection, reactivation or reinfection, active HCMV replication although not frequent was associated with TB disease which suggests that TB disease or an underlying common factor reactivates HCMV replication in this population.

Background Tuberculosis (TB) remains a critical public health challenge, with two-thirds of the global TB burden in ten Asian countries. Social vulnerabilities, comorbidities, health inequity, multi-dimensional poverty, malnutrition, and barriers to healthcare access continue to fuel TB epidemic. Inability to detect asymptomatic and sub-clinical TB, combined with passive approach in service delivery and overreliance on smear microscopy, leads to delayed diagnosis, a substantial burden of undetected cases, and continuing TB transmission in the communities. In such a context, the introduction and scale-up of active case-finding approaches - including community-based TB screening using highly sensitive screening tools and novel rapid diagnostics - becomes a strategic priority to interrupt transmission. The growing availability of multiple screening and diagnostic options makes evidence-based decision-making increasingly complex. Methods To estimate the potential epidemiological impact and cost implications of scaling up TB diagnostics and community-based screening in ten high-burden Asian countries, we constructed a mathematical model and evaluated multiple intervention scenarios. We then assessed and compared four service delivery models: 1) digital ultraportable chest x-ray (UPCXR) & Xpert/Truenat in community, 2) digital UPCXR in community and Xpert/Truenat at health facilities, 3) digital UPCXR in community and near point of care (nPOC) at health facilities, 4) nPOC in community & Xpert/Truenat at health facilities - for total investment required and projected health benefits for their cost-effectiveness. Results and conclusions The modelling study indicated that strengthening health facility capacity (with enhanced TB screening, expanded molecular diagnostics, reduced loss to follow-up, private sector standard of care, leading to increased treatment coverage & quality of active disease treatment and reduced post-treatment relapse, scale-up of TB preventive treatment (TPT), and provision of nutritional support to 80% of TB patients and their household contacts) can significantly reduce TB incidence and mortality; however, community-wide mass screening remains essential to achieving TB elimination targets . Targeted screening of vulnerable populations demonstrated greater cost-effectiveness than untargeted screening approaches. Achieving the End TB goals will ultimately require an effective TB vaccine with high population-level coverage. AI-enabled digital UPCXR-based screening combined with Xpert/Truenat testing at the community level demonstrated maximum epidemiological impact potential, while the most cost-efficient model is Digital UPCXR in the community combined with nPOC testing at health facilities. An investment of USD 12.7 billion over the next five years in community-level implementation of digital UPCXR and molecular diagnostics could avert an additional 9.8 million TB cases and 1.9 million deaths across ten Asian countries over a ten-year horizon.

BackgroundAfrica continues to have a significant public health problem with mpox, where endemic transmission persists and overlaps with a high burden of other infectious diseases. Although their epidemiology and clinical impact are still poorly understood throughout the continent, coinfections with human immunodeficiency virus (HIV) and varicella-zoster virus (VZV) can affect the clinical picture, severity of the disease, and accuracy of the diagnosis. MethodsFollowing PRISMA criteria, we registered the protocol in PROSPERO (CRD420251133960) and carried out a methodical review and meta-analysis. Through searches of numerous electronic databases and grey literature up to February 27, 2025, observational studies documenting mpox coinfections with VZV and/or HIV and related clinical symptoms in Africa were searched. Pooled prevalence was calculated using random-effects models. Subgroup analyses and meta-regression were conducted to investigate heterogeneity across WHO regions, countries, study designs, settings and type of participants. ResultsA total of 27 studies carried out across African countries were included. The pooled prevalence of VZV-mpox coinfection was 10.23% (95% CI: 2.95-29.93), while HIV-mpox coinfection prevalence was 6.55% (95% CI: 2.36-16.90), both of which had significant heterogeneity. Coinfections were far more prevalent in hospital-based environments than in community-based research. The rash was nearly universal throughout all clades, but the clinical manifestations varied depending on the viral clade, with clades I and Ia linked to more severe systemic symptoms than clade II. DiscussionsHIV and VZV coinfections with mpox pose a major yet possibly underestimated burden in Africa and are linked to more severe clinical presentations, particularly in hospital environments. The necessity of including clinical, epidemiological, and genomic data into mpox monitoring systems is emphasized by the observed clinical differences between clades. Improving patient management and outbreak preparedness across the continent requires strengthening diagnostic capacity and routinely screening for coinfections.

Background: In sub-Saharan Africa where both tuberculosis (TB) and HIV are prevalent, empiric TB treatment in people living with HIV (PLHIV) persists due to limited sensitivity of sputum-based TB tests. We evaluated mortality among molecular test-negative presumptive TB adult PLHIV in a population where the majority are or have been on antiretroviral therapy (ART), comparing mortality between those who received empiric TB treatment and those who did not. Materials and Methods: From November 2017 to December 2020, Xpert-negative presumptive TB adult PLHIV were recruited at Mulago Referral Hospital and Kisenyi Health Centre-IV in Kampala, Uganda. Clinical data including TB symptoms, chest X-ray, and empiric TB treatment decision were collected. Laboratory investigations included CD4 cell count, serum cryptococcal antigen (CrAg), urine TB-lipoarabinomannan (TB-LAM), microbiological blood cultures, and sputum mycobacterial growth indicator tube (MGIT) cultures. Participants were followed monthly for 12 months to ascertain vital status. Results: Overall, 300 participants were enrolled; 61.3% inpatients, 55.7% female, median age 37 (IQR 29-45) years, 82.3% on ART, median CD4 206 cells/mm3 (IQR 36-507). Of the 300 participants, 68 (22.7%) received empiric TB treatment, of which 53 (77.9%) were inpatients. 12-month mortality was 31.0% (93/300); 91.4% among inpatients, 72% within three months post-enrolment. Mortality was higher among those who received empiric TB treatment (51.5 vs. 30.2 per 1,000 person-months; p=0.013) compared to those who did not. TB cultures were positive in 5.0% (15/300), of whom seven (46.7%) were also TB-LAM positive. CrAg was positive in 12.3% and 3.7% had positive blood culture. Conclusion: We found high mortality among Xpert-negative PLHIV, particularly those who received empiric TB treatment, despite high ART coverage. Cryptococcal antigenemia and bacteremia were not uncommon. In presence of negative Xpert results in PLHIV, clinicians should perform extensive laboratory evaluations to identify possible comorbidities or alternative non-TB diagnosis.

BackgroundEvidence emerging from Sub-Saharan Africa indicates that people living with HIV (PLHIV) on long-term antiretroviral therapy (ART) especially when the viral load is undetectable, may falsely test negative for HIV on rapid diagnostic tests. This study assessed the prevalence and factors associated with false negative rapid diagnostic HIV tests among Patients on antiretroviral therapy, with undetectable viral load levels at Kisenyi Health Center IV, Kampala, Uganda. MethodsBetween October 2023 and February 2024, a cross-sectional study was conducted among 1,248 PLHIV on ART with undetectable viral loads at Kisenyi Health Center IV. Participants were recruited consecutively, and HIV re-testing was conducted in accordance with the national serial rapid testing algorithm. The algorithm includes a screening test (Determine HIV-1/2), a confirmatory test (Stat-Pak(R)), and a tie-breaker test (SD Bioline(R)). Enzyme-linked immunosorbent assay (ELISA) was used as the final confirmatory method. Data on socio-demographics and clinical characteristics was collected using an electronic data abstraction tool. Logistic regression analysis was done to assess for factors associated with false negative results, using STATA version 14.0. ResultsThe median age of the participants was 34.0 (interquartile range 29.0-42.5 years). The prevalence of false-negative rapid test results was 3.2% (40/1248; CI:2.20-4.2). CD4 (aOR 1.001, CI:1.001-1.003) and duration on ART (aOR 0.884, CI:0.801-0.978) were significantly associated with false-negative HIV results. ConclusionFalse-negative results were observed in approximately 3 in every 100 PLHIV on ART with an undetectable viral load. Serial rapid testing alone may be suboptimal for detecting HIV infection in this population. Further confirmatory testing in individuals who test negative on rapid testing is recommended.

There is limited epidemiologic data on varicella zoster virus (VZV) infections from low- and middle-income countries including Kenya. We aimed to describe the seroepidemiology of VZV in Kilifi, Kenya, where varicella vaccine is not included in the national infant immunization program, in order to generate evidence to inform vaccine policy. We conducted a retrospective serosurvey utilizing archived plasma and serum samples from cross-sectional population-based serosurveys conducted within the Kilifi Health and Demographic Surveillance System between 2009 and 2021. We assayed immunoglobulin G (IgG) for VZV using a validated Luminex multiplex immunoassay and applied a seropositivity cutoff of [&ge;]0.26 International Units per millilitre (IU/mL), as determined by the assay developer. We calculated Bayesian-adjusted age-specific seroprevalence and tested differences in seroprevalence between groups using Chi square. We used a multivariable logistic regression model to estimate associations with VZV IgG antibody seropositivity. We fitted an age-dependent catalytic model to estimate the force of infection (FOI) in children aged 0.5-4, 5-9 and 10-14 years. A total of 2639 samples from children aged <15 years and 546 samples from persons aged [&ge;]15 years were tested. The overall population-weighted seroprevalence of VZV IgG antibodies among children aged 0-14 years was 38.4% (95%CI 27.5-49.5). Age-specific seroprevalence rose from 13.3% (95%CI 5.8-21.6) in children aged 0-4 years to 60.9% (95%CI 45.0-76.2) in those aged 10-14 years. Survey year and age were associated with VZV IgG antibody seropositivity. Children aged 5-9 years had the highest FOI (0.098; 95%CI 0.077-0.120) per susceptible year while mean age of infection was 24.3 years (95%CrI 17.6-30.1). Approximately 40% of individuals entering adulthood in Kenya remain susceptible to VZV infection, suggesting a substantial and underappreciated risk of severe VZV disease in older population including pregnant women. An infant varicella immunization program might avert disease across both paediatric and adult populations.

BackgroundStrikingly low allocation of SARS-CoV-2 vaccine to the African Continent limits its capacity to control transmission. Characterizing the trajectory of vaccination efforts and their impact on the expected burden of SARS-CoV-2 will help planning vaccine delivery strategies, and public health interventions more broadly. As the burden is strongly age-dependent, this requires an understanding of the age-structured dynamics of susceptible individuals, accounting for the combined effects of vaccination and infection induced immunity. Methods and FindingsWe illustrate with projections for diverse African LMIC demographics. To this end, we develop an age-structured mathematical model with vaccination to assess the likely time-horizon to reach target vaccine coverage of high-risk groups, and how susceptibility patterns across age will shift as a result of both infection, and the broadening of vaccination targets from a focus on risk groups to efforts to reach the general population. We base our assessment on the demography, contact patterns and public health capacity of 16 African countries with diverse age pyramids. We identify a considerable divergence in the projected horizon of expanded targeting from prioritized age groups to general vaccination, with longer time among those with higher mean age and lower vaccination capacity. We parameterize the model using realistic demographies and contact patterns to project the changing age profile of susceptibles. We demonstrate that contacts and vaccination jointly drive the early age profile; while immune duration contributes to the transition of age-susceptibility profile in the intermediate future. ConclusionsOur model framework provides a flexible and critical preparedness-tools to inform decision making against future epidemic waves and beyond Covid-19.

The world is far from achieving universal access to rapid tuberculosis (TB) diagnostics that align with World Health Organization (WHO) diagnostic standards. Although WHO-recommended molecular rapid diagnostics (mWRDs), including low-complexity automated nucleic acid amplification tests (LCaNAAT), have significantly improved TB detection, scale-up has been constrained by high capital, maintenance, and consumable costs. Recently, lower-cost, near-point-of-care nucleic acid amplification tests (NPOCs) have emerged, with attractive global-access pricing, offering the potential to expand access to rapid TB diagnosis while reducing the financial burden. To support TB program staff better understand the budget impact of using newer NPOCs as the initial TB diagnostic compared with established mWRDs, we developed a flexible cost calculator. Originally built in Microsoft Excel for Mac (version 16.91, build 24111020), it organizes key parameters in a structured input sheet using standardized labels. Separate worksheets defined diagnostic scenarios and performed calculations, with results summarized in an overview covering various costs. After validation, the model was converted into R (version 2025.09.1 + 401). The app (app.R), developed with Shiny, is now available here for free global access. Using two hypothetical country case studies, we compared current LCaNAAT- based testing strategies with scenarios in which NPOCs were implemented as the initial diagnostic test. In hypothetical Country A, there were cost savings of 43% in Scenario 1 (based on current testing trend) and 38% in Scenario 2 (based on ambitious testing goals). In hypothetical Country B, the corresponding cost differences were 55% in Scenario 1 and 40. 5% in Scenario 2. The analysis showed that countries can reach ambitious TB testing targets using NPOCs at roughly the same cost as current LCaNAAT testing. This highlights the potential of affordable molecular diagnostics to improve access to mWRDs. By reducing capital and maintenance costs, NPOCs allow TB programs to test and detect more cases within existing or slightly increased budgets, speeding up progress toward universal rapid TB diagnosis.

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) are leading causes of infectious disease deaths, with disproportionate impact in low- and middle-income countries (LMICs). Despite well-established biological relationships between these diseases, there is limited information on how TB prevalence differs between people living with and without HIV. MethodsWe conducted a systematic review and meta-analysis of TB prevalence surveys conducted in LMICs and published during January 1st 1993-October 13th 2025 (PROSPERO CRD42024503853). We extracted bacteriologically-confirmed TB prevalence estimates stratified by participant HIV status. Surveys that offered HIV testing to all, sputum-collection-eligible, or TB-positive participants were included in the primary analysis. We applied Bayesian meta-regression to estimate pooled risk ratios (RR) of bacteriologically-confirmed TB prevalence among participants living with versus without HIV. Additionally, we estimated country-level and overall TB notification-to-prevalence (N:P) ratios by HIV status. FindingsOf 10,211 potentially relevant publications, 12 TB prevalence surveys--representing 264,530 participants within nine countries in Southern and Eastern Africa--were used in the primary analysis. Reported TB prevalence was higher among participants living with versus without HIV in 11/12 surveys, with an overall pooled RR of 3{middle dot}86 (95% credible interval: 2{middle dot}41-5{middle dot}53). N:P ratios were higher among participants living with HIV in all examined countries. The overall pooled N:P ratios were 1{middle dot}74 (0{middle dot}59-4{middle dot}56) and 0{middle dot}48 (0{middle dot}17-1{middle dot}20) among participants living with versus without HIV, respectively. InterpretationIn Southern and Eastern Africa, bacteriologically-confirmed TB prevalence is three- to six-times higher among people living with HIV. Comparison of prevalence and notification data suggest higher rates of TB diagnosis for people living with versus without HIV, but also indicates substantial delays in the detection of untreated TB cases for both populations. FundingWellcome Trust, UK National Institute for Health and Care Research, UK Foreign, Commonwealth and Development Office, NIH. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is limited systematic evidence on how the prevalence of TB disease differs between people living with HIV and without HIV. Multiple observational cohorts have described substantially elevated TB incidence among populations with HIV, but disease prevalence will also be affected by differences in mortality and treatment uptake rates. We searched PubMed from inception through January 21, 2026 using the search string ((HIV AND TB) OR HIV/TB) AND (prevalence AND (systematic review OR meta-analysis)) without any restrictions on language. We also reviewed investigators personal libraries. This search yielded 506 publications; however few of these included prevalence data. An analysis conducted in 2020 synthesized HIV status-stratified data from seven national TB prevalence surveys in Africa and found that HIV prevalence was lower among prevalent TB cases than among notified cases. This study did not include subnational surveys and did not distinguish between survey participants with self-reported or test-confirmed HIV status. Added value of this studyThis study synthesized TB prevalence data, stratified by participant HIV status, from national and subnational surveys conducted in LMICs and published between January 1st 1993 and October 13th, 2025. Collated data represented 681,402 survey participants across ten countries. All but one study were conducted in Southern and Eastern Africa. We limited our primary analysis to surveys that systematically tested participants for HIV and bacteriologically-confirmed TB. The prevalence of bacteriologically-confirmed TB was estimated to be three to six times higher than among people living with versus without HIV. Ratios of TB notifications to TB prevalence were higher for people living with HIV compared to people without HIV, suggesting higher rates of TB case detection (and likely shorter duration of disease) for people living with HIV and untreated TB than those without HIV. Implications of all available evidenceFew estimates of community-representative TB prevalence stratified by participant HIV status exist. These surveys have been concentrated in Southern and Eastern Africa, despite TB-HIV burden being distributed globally. Our findings highlight the elevated burden of TB among people living with HIV in these settings, as well as the limited data on the intersection of TB and HIV epidemiology in other world regions. Furthermore, our comparison of notification and prevalence data demonstrate substantial shortfalls in TB case detection, regardless of an individuals HIV status.

The A(H1N1)pdm09 virus remains a major global health threat. This study examined the burden of ICU admission, mortality, and associated predictors among patients with A(H1N1)pdm09 pneumonia in a leading center for infectious diseases in Vietnam. Information on demographic, clinical, and laboratory characteristics, and outcomes was retrieved from medical records of adults admitted with influenza A(H1N1)pdm09 during 2009-2019. Among 729 cases, 21.7% (158/729) developed pneumonia. Among 158 pneumonia cases, 36.7% (58/158) developed moderate-to-severe acute respiratory distress syndrome (ARDS), and 15.2% (24/158) received invasive ventilation. ICU admission and mortality rates were 48.7% (77/158, 95%CI 41.1-56.5%) and 8.2% (13/158, 95%CI 4.9-13.6%), respectively. Predictors of ICU admission included being >60 years old (adjusted OR [AOR] 13.864, 95%CI 2.185-87.956, P=0.005), comorbidities (AOR 6.527, 95%CI 1.710-24.915, P=0.006), AST (AOR 1.013, 95%CI 1.001-1.025, P=0.029), and moderate-to-severe ARDS (AOR 14.027, 95%CI 4.220-46.627, P<0.001). Predictors of mortality were invasive ventilation (AOR 55.355, 95%CI 1.486-2062.375, P=0.030) and double-dose oseltamivir or combination therapy (AOR 32.625, 95%CI 1.594-667.661, P=0.024). In conclusion, mortality is not rare in A(H1N1)pdm09 infection. Monitoring of older patients and those with comorbidities, liver enzyme elevation, or moderate-to-severe ARDS is essential for the timely detection of complications requiring intensive care.

Health research priorities are generally not aligned with global disease burden. Although genome-wide association studies (GWAS) are correcting a historical bias by including samples from different demographic groups, this does not necessarily translate to improved understanding of the most important causes of disease globally. We demonstrate that while in countries with high socioeconomic development index (SDI) there is some alignment between the traits being analysed in GWAS and those that contribute most to disease burden, there is almost no such alignment in countries with low SDI. Improvement in alignment between GWAS and disease burden has been seen for countries with middle SDI over time, likely due to the contributions to disease burden changing in those regions rather than GWAS responding to the needs of those regions. Low GWAS alignment with disease burden may be partially explained by lower GWAS attention to childhood health. Improving aetiological understanding of high burden neglected conditions should be a priority for emerging biobanks in order to reduce global health inequality. Short abstractWe identify some alignment between the traits being analysed in genome-wide association studies (GWAS) and disease burden in high socioeconomic development index (SDI) countries, while there is almost no such alignment in countries with low SDI, mostly due to neglecting childhood infection. Improvement in alignment between GWAS and disease burden has been seen for countries with middle SDI over time likely due to changing disease burden.

New tuberculosis (TB) vaccines for adults and adolescents could transform TB prevention programs, but their impact depends on successful implementation. We investigated willingness to be vaccinated with a new TB vaccine in a high HIV and TB burden setting in southern Mozambique in 2024 using a mixed methods approach involving a cross-sectional survey and concurrent in-depth interviews. In 151 surveys and 23 interviews, we found that willingness to receive a new TB vaccine among adults and adolescents was 77% (148/192) overall. In multivariable analysis, adolescents were more willing to receive a new TB vaccine than adults even when adjusting for other factors which may influence vaccination decisions (adjusted OR: 5.6, 95% CI: 1.7-17.7). Personal experience with TB and greater knowledge of the disease was also linked with willingness to be vaccinated. Qualitative findings reinforced quantitative findings, further clarifying that even among those who expressed hesitancy, a safe and effective TB vaccine endorsed by healthcare workers, government agencies, and community leaders would likely have high uptake. Our findings are specific to southern Mozambique and can shape vaccine introduction efforts after a TB vaccine is licensed and approved for use in this age group.

Objectives: A pooled testing algorithm for tuberculosis (TB), in which sputum specimens from multiple individuals are tested in pools with individual testing of positive pools, can optimise diagnostic resources. This study evaluated the diagnostic accuracy and cartridge savings of pooled testing with the Xpert MTB/RIF Ultra assay (Xpert Ultra) relative to individual Xpert Ultra testing. Methods: We conducted a cross sectional study among 2,396 adults (aged above 15 years) with presumptive TB enrolled between July 2024 and February 2025, through facility based case finding (FBCF) and community based case finding (CBCF). Participants submitted two sputum specimens. The first underwent individual Xpert Ultra testing; remnant specimens were combined into four specimen pools and tested again with Xpert-Ultra. The second specimen was used to inoculate liquid culture (BACTEC MGIT). Data were used to simulate an up-front pooled testing strategy; sensitivity and specificity of this approach was estimated against culture, and cartridge use was compared with individual Xpert-Ultra testing. Results: Of 2,396 participants, 395 (16.5%) had a positive Xpert Ultra and/or culture, including 360/912 (39.5%) in FBCF and 35/1484 (2.4%) in CBCF. The pooled testing approach had sensitivity of 82.4% (95% confidence interval [CI], 77.9; 86.3) and specificity of 98.5% (97.8; 99.0) compared to culture, with lower sensitivity than individual Xpert-Ultra testing (86.5%, 82.4; 89.9) but high specificity (98.1%, 97.4; 98.7). Sensitivity of pooled testing was lower in CBCF (59.1%, 36.4; 79.3) than in FBCF (84.0%, 79.5;87%), whereas cartridge savings were greater in CBCF (69.1% vs 9.6%). The pooling strategy reduced Xpert-Ultra cartridge use by 46.5%, saving USD 14,447. Conclusions: Pooled Xpert-Ultra testing among adults appears resource-efficient for TB screening in Vietnam. As sensitivity is lower compared to individual Xpert Ultra testing, particularly for paucibacillary disease, these losses should be carefully weighed against gains in affordability and expand access to molecular testing. Careful, context-specific implementation is essential to maximise programmatic benefit while minimising missed persons with TB.

Globally, respiratory tract infections (RTI) are the main cause of morbidity, and in Low-middle-income countries (LMICs) RTI including pneumonia are a leading cause of morbidity and mortality in children <5 years. Diarrheal illness increases RTI risk in young children through micronutrient depletion, and immune stress, yet data on post-diarrhea RTI burden in LMICs are limited. We determined the prevalence and risk factors of RTI within three months following medically-attended diarrhea (MAD) in children aged 6-35 months enrolled in seven EFGH country sites in Asia, Africa and South America. The EFGH study prospectively enrolled children aged 6-35 months with MAD in selected health facilities during a 24-month period from 2022 to 2024 and followed them for three months. RTI was defined as cough or difficulty breathing and the presence of one of the following symptoms at any scheduled or unscheduled visit during follow-up: stridor; fast-breathing; oxygen saturation <90%; or chest indrawing. The period prevalence and 95% confidence intervals of RTI were calculated, and correlates of RTI were assessed using modified-Poisson regression. From June 2022 to August 2024, 9,476 children aged 6-35 months presenting with MAD in the EFGH study sites were screened: 9,116 (96.2%) included in the current study. Nearly half were female (46.7%), and median age was 15 months. Overall, 48.5% received all age-appropriate vaccines, and 87.6% received the pneumococcal vaccine, with significant variation across countries. Nearly one-quarter of children were stunted, 17.2% wasted, and 21.9% underweight. RTI occurred in 3.8% of children during the three-month follow-up, mostly within the first month. Higher prevalence of RTI occurred among children aged 12-23 months (8.7%), those undernourished (16.1%), unvaccinated (4.0%) or living in poor sanitation settings (4.1%). While children who received all age-appropriate or pneumococcal vaccinations had a lower crude prevalence of RTI, these associations were not statistically significant after adjusting for age, sex and study site. RTI was infrequently observed in the three months following MAD presentation, with significant variability by site and with the highest prevalence in Malawi. RTI risk was highest in 12-23-month-olds and among children with undernutrition, and those living in poor sanitation conditions.

The Sepsis Prevention in Neonates in Zambia (SPINZ) trial was a prospective observational cohort study conducted in the neonatal intensive care unit of the University Teaching Hospital in Lusaka, Zambia. Introduction of an infection prevention and control (IPC) bundle reduced hospital-associated mortality, total mortality, suspected sepsis, and confirmed bloodstream infections. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness in this low-resource setting. We conducted a retrospective cost analysis, using SPINZ study-related records, and expressed costs in real 2016 US dollars. We also estimated intervention cost-effectiveness using both outcomes from SPINZ (avoided deaths, confirmed infections, and suspected episodes of infection) and estimated disability-adjusted life years (DALYs) averted by the intervention. To provide data for policymakers, a future cost projection was undertaken to estimate costs of the program implemented nationally over a 10-year period in real 2025 US dollars. A total of 2,035 neonates were enrolled from September 2015 to March 2017. Total costs during implementation (introduction of the IPC bundle) (April-May 2016) and the subsequent intervention period were $17,641 and $5,265, respectively, of which most expenses were incurred during the preparation period due to travel and training. During the intervention period, the programs running cost was approximately $478 per month. The estimated cost per death, confirmed infection, and suspected episode averted was $208, $204, and $32, respectively; the estimated cost per DALY averted was $9.5. The future model was estimated to cost an average of $107,561 annually to implement nationally. The analysis indicated that the IPC bundle to prevent sepsis-related neonatal mortality was highly cost-effective. Cost reductions from task-shifting, reduced preparation (start-up) costs, and longer intervention periods would further decrease cost per death averted. IPC bundle implementation can thus be recommended for resource-constrained settings where sepsis and other nosocomial infections are associated with high neonatal mortality.

BackgroundStage at time of diagnosis and survival after diagnosis are critical parameters regarding control of any cancer in any geographical setting. In earlier research focusing on the initial years of the "Treat All" era (2016-2019), we found that HIV-associated Kaposi sarcoma (KS) in East Africa continued to be diagnosed at advanced stage of disease and conferred high mortality. Given the potential for broader implementation of "Treat All" as well as the announcement of National Comprehensive Cancer Network guidelines for cancer treatment in Africa since 2020 -- but also the countervailing influence of the COVID-19 pandemic -- we sought to provide an update on KS stage at diagnosis and survival after KS diagnosis among people living with HIV (PLWH) in East Africa. MethodsWe evaluated adult PLWH in Kenya, Tanzania and Uganda with a new diagnosis of KS identified at ambulatory and inpatient settings in four regions between September 2021 and April 2024. At time of biopsy, participants were examined to document the extent of KS. In a prospective cohort study, we followed participants to monitor vital status. ResultsAmong 493 PLWH with a new diagnosis of KS, the median (IQR) number of anatomic sites with KS lesions was 9 (4-12), and 91% had ACTG stage T1 (advanced KS). Over a median follow-up of 11 (IQR: 2.2-20) months, a total of 209 participants died, and three were lost to follow-up. Cumulative incidence of death (95% confidence interval) at months, 3, 6, 12 and 18 following KS diagnosis was 26% (22% to 30%), 32% (28%-36%), 39% (34%-43%) and 45% (40%-51%), respectively. Cumulative incidence of death was similar between countries and year of KS diagnosis. ConclusionsAmong PLWH with newly diagnosed KS in East Africa during the post-initial phase of the "Treat All" era (2021-2024), the majority had advanced disease at KS diagnosis and survival was very poor. These parameters are unchanged from the five prior years. Our findings emphasize the need for better KS control strategies in the region, including primary prevention, novel approaches for earlier detection, more timely linkage to care, and more accessible and potent anti-KS therapy.

Scrub typhus remains a persistent public health concern with strong spatial and temporal variability. This study analyses the spatio-temporal distribution, clustering patterns, and forecasting of scrub typhus across five districts, Chittoor, Ranipet, Tirupattur, Vellore, and Tiruvannamalai, using long-term surveillance data from May 2005 to May 2024. We applied spatio-temporal exploratory analysis to identify trends, seasonal behaviour, and inter-district heterogeneity in disease incidence. Hotspot analysis was conducted using the Getis-Ord Gi* statistics to detect statistically significant hotspots and coldspot clusters and examine their evolution over time. To support decision-making, we developed statistical, machine learning (ML), and deep learning (DL) based forecasting models using monthly scrub typhus and climatic features. Root mean square error (RMSE), and R-square error (R2) evaluation metrics are used to compare the performance of the prediction model. Scrub typhus shows clear and recurring seasonal peaks across all five districts, and incidence increases are associated with precipitation, dew point, relative humidity, and vegetation cover. Temperature shows a strong negative correlation, while relative humidity and normalized difference vegetation index (NDVI) show strong positive correlations in all districts. Hotspot analysis identifies Vellore and Chittoor as persistent core transmission zones, with weaker clustering in surrounding districts. Forecasting results indicate that model performance varies by location. The results reveal persistent hotspots, clear seasonal signals, and short-term forecasts across districts. This integrated spatiotemporal and forecasting framework provides actionable insights for targeted surveillance and timely intervention strategies to control scrub typhus.

BackgroundDolutegravir (DTG)-based regimens are currently the preferred first-line therapy in many HIV programs; however, the influence of baseline advanced HIV disease (AHD) on virologic outcomes in routine national data in the DTG era remains unclear. MethodsWe conducted a retrospective cohort analysis using routinely collected data from Tanzanias National AIDS, STIs, and Hepatitis Control Programme (NASHCoP) database (2017-2021). A simple random sample of 50,000 patients was drawn from the de-duplicated national dataset, yielding 49,863 patients after data processing. The analytic cohort included 4,044 patients with baseline CD4 and endpoint viral load measurements. Viral load suppression was defined as <1000 copies/mL. Associations between baseline AHD, regimen status, and suppression were assessed using risk ratios and multivariable Poisson regression models, including an interaction term between AHD and DTG. ResultsOverall viral load suppression was 89.2% (3,607/4,044). Patients with baseline AHD had lower suppression than those without AHD (81.3% vs. 91.1%; RR 0.48, 95% CI 0.40-0.57). Suppression was higher among patients receiving DTG-based regimens than among those receiving non-DTG regimens (91.5% vs. 77.2%; RR 2.67, 95% CI 2.23-3.20). In the adjusted analysis, baseline AHD remained associated with reduced suppression (aRR 0.89, 95% CI 0.86-0.92), whereas DTG use was associated with improved suppression (aRR 1.15, 95% CI 1.10-1.20). A significant interaction between AHD and DTG was observed (aRR 1.40, 95% CI 1.20-1.63), indicating that the relative benefit of DTG was greater among patients with baseline AHD. ConclusionsAlthough viral load suppression was high in this Tanzanian routine-care cohort, patients with baseline AHD had poorer outcomes. DTG-based regimens were associated with improved overall suppression, with a greater relative benefit among patients with advanced disease. These findings support the continued prioritization of DTG-based therapy and reinforce the importance of early diagnosis and targeted management of patients with AHD.

Introduction: Following a large chikungunya outbreak during 2006 to 2008, Sri Lanka did not report any outbreaks for a 16 year period until end of 2008, possibly due to population immunity. Therefore, understanding baseline immunity prior to outbreaks is crucial to inform implementation of vaccine strategies. Methods: We assessed the age stratified seroprevalence for chikungunya in an urban (n=816) and a semi urban (n=380) community in Colombo, Sri Lanka, from September to November 2024, prior to the commencement of the large chikungunya outbreak, in December 2024. Sociodemographic, socioeconomic and clinical data were collected and chikungunya specific IgG measured in serum samples. Results: Of 1196 participants, 410 (34.3%) were chikungunya IgG seropositive. Seroprevalence was significantly higher in urban populations compared with semi urban populations (39.6% vs 22.9%; p<0.001) and increased significantly with age in urban areas but not in semi-urban areas. Living in an urban area was the strongest independent risk factor of chikungunya seropositivity (aOR 7.48, 95% CI 4.05 to 13.81; p<0.001), consistent with the higher population density, poor housing conditions and overcrowding observed in that setting. The use of mosquito nets was independently associated with reduced risk of seropositivity (aOR 0.50, 95% CI 0.27 to 0.93; p=0.029). Almost no individuals aged <16 years had evidence of prior infection (0.55%), indicating minimal transmission in the preceding 16 years. In the urban cohort, seropositivity was significantly associated with diabetes, central obesity, overweight, and hypertension. Conclusions: There appears to have been minimal chikungunya transmission in the 16 years preceding the 2024 outbreak, with a large population susceptible to chikungunya. Higher seroprevalence in urban populations highlights the role of population density, overcrowding, and housing conditions as key drivers of transmission.