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International Journal of Infectious Diseases

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match International Journal of Infectious Diseases's content profile, based on 126 papers previously published here. The average preprint has a 0.10% match score for this journal, so anything above that is already an above-average fit.

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Impact and cost of scaling up TB screening and diagnostics in Asias ten high-burden countries: a modelling analysis

Mandal, S.; Rade, K.; Singh, A.; Nair, S. A.; Sahu, S.

2026-04-19 infectious diseases 10.64898/2026.04.16.26351072 medRxiv
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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.

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Empiric tuberculosis treatment and 12-month mortality among sputum GeneXpert-negative adults living with HIV in Uganda in the era of widespread Antiretroviral therapy: A prospective cohort study

Nakiyingi, L.; Kikaire, B.; Nakayenga, S.; Kamulegeya, L.; Nakabugo, E.; Asio, J. N.; Bagaya, B.; Ssengooba, W.; Mayanja-Kizza, H.; Manabe, Y. C.

2026-04-06 hiv aids 10.64898/2026.04.04.26350152 medRxiv
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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.

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Differences in tuberculosis prevalence among people living with and without HIV in low-and-middle-income countries: A systematic review and meta-analysis

Swartwood, N.; Can, M. H.; Mortazavi, S. A.; Cui, H.; Singh, N.; Ryuk, D. K.; Horton, K.; MacPherson, P.; Menzies, N. A.

2026-04-22 infectious diseases 10.64898/2026.04.20.26351343 medRxiv
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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.

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ICU admission and mortality in adult patients with influenza A/H1N1-related pneumonia in Vietnam since the 2009 H1N1 pandemic: a 10-year cohort study

Ho, M. Q.; Duong, T. B.; Nguyen, T. L. N.; Tri, N. S.; Bui, T.; Thai, T. T.; Muscatello, D. J.; Sunjaya, A. J.; Chen, S.; Nguyen, N. T.; Nguyen, T. M.; Nguyen, A. T. K.; Duong, C. M.

2026-04-20 infectious diseases 10.64898/2026.04.18.26351156 medRxiv
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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.

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Attitudes towards new tuberculosis vaccines among adults, adolescents and their caregivers in southern Mozambique, 2024

Lima, A.; Campos, I.; Kim, D.; Shiiba, M.; Cranmer, L. M.; Acacio, S.; Garcia-Basteiro, A. L.; Vasudevan, L.; Nelson, K. N. B.

2026-04-01 infectious diseases 10.64898/2026.03.30.26349798 medRxiv
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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.

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Diagnostic Accuracy and Potential Resource Savings of Pooled Sputum Testing with Xpert MTB/RIF Ultra for Tuberculosis among adults in Vietnam: A Cross-Sectional Study

Nguyen, H. T.; Codlin, A. J.; Vo, L.; Nguyen, N.; Forse, R.; Dang, H.; Nguyen, L. H.; Hoa, N. B.; Dinh, L. V.; Doan, H. T.; Nguyen Van, H.; Creswell, J.; Garg, T.; Cubas Atienzar, A. I.; Byrne, R. L.; Iem, V.; Squire, B.; Forsman, L. D.; Wingfield, T.

2026-04-01 infectious diseases 10.64898/2026.03.31.26349825 medRxiv
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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.

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Prevalence and Risk Factors of Respiratory Tract Infections Following Medically-Attended-Diarrhea in Children Aged 6-35 Months: Enterics for Global Health (EFGH)-Shigella Surveillance Study, 2022-2024.

Conteh, B.; Galagan, S. R.; Badji, H.; Secka, O.; Bar, B. T.; Rao, S. I.; Atlas, H.; Omore, R.; Ochieng, J. B.; Tapia, M.; Cornick, J.; Cunliffe, N.; Zegarra Paredes, L. F.; Colston, J.; Islam, M. T.; Mosharraf, M. P.; Qamar, F. N.; Fatima, I.; Pavlinac, P. B.; Hossain, M. J.

2026-04-20 infectious diseases 10.64898/2026.04.17.26351078 medRxiv
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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.

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Seroprevalence of chikungunya virus in Colombo, Sri Lanka before the 2025 outbreak and implications for population susceptibility

Danasekara, S.; Jeewandara, C.; Jayamali, J.; Ramu, S. T.; Gomes, L.; Peranantharajah, D.; Colambage, H. S.; Karunananda, M. V.; Chathurangika, P. H.; Aberathna, S.; Ranasinghe, T.; Dissanayake, M.; Kuruppu, H.; Perera, L.; Jayadas, T.; Bary, F.; Ranatunga, C.; Guruge, D.; Prathapan, S.; Rathnawardana, G.; Nawaratne, S.; Liyanage, E.; Senathilaka, N.; Wickramanayake, R.; Warnakulasuriya, N.; Madusanka, S.; Dissanayake, C.; Yatiwella, S.; Wijayamuni, R.; Malavige, G. N.

2026-04-06 infectious diseases 10.64898/2026.04.04.26350157 medRxiv
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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.

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Global Burden, Temporal Trends, and Health Inequalities of Early-Onset Group B Streptococcus Infection in Neonates, 1990-2021: A Systematic Analysis of the Global Burden of Disease Study 2021

Wen, Q.; Wang, X.; Wu, Y.; Jiang, Y.; Xu, Z.

2026-04-04 infectious diseases 10.64898/2026.04.02.26350022 medRxiv
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Objectives: Group B Streptococcus (GBS) is a leading cause of neonatal mortality worldwide. However, the global burden of early-onset GBS disease (EOD-GBS) has not been fully elucidated. We aimed to describe the geographical distribution and epidemiological characteristics of the EOD-GBS burden, and analyze its association with socio-economic development and universal health coverage. Methods: We used data from the Global Burden of Disease Study 2021 and the Universal Health Coverage Service Coverage Index (UHC-SCI) to calculate estimated annual percentage changes (EAPCs) of EOD-GBS mortality. Sex differences were analyzed using the conservative overlap assessment. The geographical distribution of EOD-GBS clinical presentations and mortality was mapped. Health inequality analysis was conducted to evaluate the relationship between the sociodemographic index (SDI), UHC-SCI, and EOD-GBS burden. Results: Global EOD-GBS mortality decreased by nearly 50% from 1990 (693.41 per 100,000) to 2021 (348.80 per 100,000). However, the decline was not uniform: the most significant decrease occurred in high-middle SDI regions (EAPC: -7.17%), and the slowest in low SDI regions (EAPC: -2.23%). Male neonates accounted for the most EOD-GBS deaths, particularly in high SDI regions. Lower respiratory infections were common in Asia and Oceania; meningitis was more prominent in Europe. Inequality analysis revealed a phenomenon of "absolute convergence but relative differentiation": as social development and universal health coverage improves, the absolute mortality gap between countries narrowed, but relative burden concentrated increasingly among the poorest populations. Conclusions: The global burden of EOD-GBS has decreased substantially, but there are marked differences among countries. Continued socioeconomic development and expanded universal health coverage are critical to further reduce neonatal mortality.

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Streptococcus agalactiae, a frequent but not so well-known cause of bone and joint infections: a Multicentric observational study 2014-23

Jamard, S.; Le Moal, g.; Plouzeau-Jayle, c.; Arvieux, C.; Ressier, S.; Lecomte, r.; Corvec, S.; Ansart, S.; Lamoureux, C.; Abgueguen, P.; Chenouard, R.; Lartigue, M. F.; Lemaignen, A.

2026-03-31 infectious diseases 10.64898/2026.03.30.26349534 medRxiv
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Abstract Introduction: Streptococcus is the second genus involved in bone and joint infections (BJIs) after Staphylococcus. Streptococcus agalactiae is the predominant Streptococcus species implicated in BJIs. However, unlike Staphylococcus-related BJIs, data on S. agalactiae infections remain scarce. Methods: We conducted a retrospective cohort study from the West Region cohort of the CRIOAc registry among six university hospitals including all microbiologically confirmed streptococcal BJI in adults between 2014 and 2023. Results: 1454 patients were included, with a median age of 67 years and 65% male. S. agalactiae was the predominant streptococcal species involved 423/1454(29%). The most prevalent comorbidities identified were obesity (378/1454;26%) and diabetes mellitus (343/1454;24%). Prosthetic joint infections (PJIs) were the most common (653/1454;45%), although diabetic foot osteitis was less prevalent overall, it was significantly more associated with S. agalactiae infections (48/423;11% versus 70/1031;7%, p=0.05). S. agalactiae BJIs were more frequently lower-limb infections and chronic infections (240/423;57% versus 502/1031;49%, p=0.04). Half of the cohort had a polymicrobial infection and were slightly more frequent with S. agalactiae BJIs (235/423;56% versus 498/1031;48%, p=0.1). These results were consistent with a sensitivity analysis excluding diabetic foot related osteitis. Logistic regression analysis identified arteriopathy (OR: 4.16; IC95:1.64-11.24, p=0.003), and obesity (OR: 2.57; IC95: 1.41-4.78, p=0.002) as specific risk factors for S. agalactiae BJIs. Conclusion: S. agalactiae emerges as a prominent and distinct pathogen in complex streptococcal BJIs, with specific risk factors such as arteriopathy, obesity and diabetes mellitus, and more chronic infections.

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Tongue swab Xpert MTB/RIF Ultra testing for tuberculosis in adolescents: a cross-sectional study of diagnostic accuracy and acceptability

MacLean, E. L.; Ma, T. T.; Chuong, L. H.; Minh, K. H.; Hoddinott, G.; Pham, Y. N.; Tiep, H. T.; Nguyen, T.-A.; Fox, G.; Nguyen, N. T.

2026-04-25 infectious diseases 10.64898/2026.04.17.26351119 medRxiv
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Introduction Improved diagnostics are needed for people at risk of tuberculosis, especially adolescents. Tongue swab (TS) molecular testing has emerged as a promising strategy for tuberculosis diagnosis. We evaluated diagnostic accuracy and acceptability of Xpert MTB/RIF Ultra (Xpert) using TS samples for tuberculosis detection among adolescents. Methods We conducted a cross-sectional diagnostic accuracy study with consecutive recruitment in Vietnam. Adolescents aged 10-19 who were recommended to undergo investigation for tuberculosis and had not received tuberculosis treatment in the past years were eligible. Participants provided TS and sputum samples and completed a structured survey regarding sampling experiences. TS was tested on Xpert, with sputum tested on Xpert and liquid culture. We utilised a composite reference standard of a positive result on sputum Xpert or sputum culture to define disease status. Sensitivity, specificity, and diagnostic yield were calculated for TS Xpert. Results From July to December 2025, we enrolled 225 adolescents from Can Tho and An Giang provinces in southern Vietnam. Fewer than half (96/225, 43%) the participants exhibited a tuberculosis -like symptom, and the majority (157/225, 70%) were close contacts of a person recently diagnosed with tuberculosis. TS were collected from all adolescents, while 116 (52%) could provide mucopurulent sputum. Tuberculosis prevalence was relatively low (12/225, 5.3%). TS Xpert sensitivity (90% CI) and specificity (90% CI) were 58.3% (35.6, 78.0) and 99.5% (97.9, 99.9), respectively. Diagnostic yield among all diagnosed was 58.3% (7/12). TS sampling was highly acceptable to adolescents; the short time and simplicity of collecting TS were considered favourably. Conclusions The sensitivity and diagnostic yield of TS Xpert was relatively low among adolescents recommended for tuberculosis investigation, which includes asymptomatic individuals who may not provide high quality sputum. Specificity was excellent, and everyone could provide a TS. TS high acceptability indicates it remains a promising sample for diagnostic algorithms.

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Quantitative interferon gamma responses to Mycobacterium tuberculosis in a community-based survey of adolescents and adults in Blantyre, Malawi

Phiri, M. D.; Rickman, H. M.; Mandalasi, C.; Chirambo, A.; Jambo, K. C.; Mwandumba, H. C.; Corbett, E. L.; Horton, K. C.; Henrion, M. Y. R.; MacPherson, P.

2026-04-04 infectious diseases 10.64898/2026.04.02.26349931 medRxiv
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Background: Binary interpretation of Mycobacterium tuberculosis (Mtb) interferon gamma release assay (IGRA) results discards information about recency of exposure and disease risk. We analysed quantitative IGRA responses to Mtb in a community--based survey to investigate associations with response magnitude and inform understanding of transmission dynamics. Methods: We included QuantiFERON--TB Gold Plus (QFT--Plus) results from 2,895 participants (10--40 years old) in Blantyre, Malawi. Bayesian regression models assessed the probability of a positive response ([&ge;]0.35 IU/mL), response magnitude, and associated factors. We also investigated associations with a TB2-TB1 differential >0.6 IU/mL (proposed to reflect recent transmission), and how hypothetical alternative IGRA positivity thresholds affected inference about age-- and sex--specific transmission. Results: 17.4% (503/2,895) of participants had positive TB1 or TB2 responses at the QFT--Plus positivity threshold (0.35 IU/mL). The distributions of TB1 and TB2 responses, among participants with positive QFT--Plus, were similar across age and sex. A TB2-TB1 differential >0.6 IU/mL occurred in 3.8% (109/2,895) of participants and was not associated with age or sex. However, participants with HIV had reduced odds of TB2-TB1>0.6 IU/mL (adjusted odds ratio 0.37 [0.14--0.93]). At higher hypothetical positivity thresholds, the mean predicted Mtb immunoreactivity prevalence among males exceeded that in females at an earlier age: at 19 years, predicted immunoreactivity prevalence ratios were 0.90 (0.83--0.99) and 1.02 (0.89--1.15) at 0.1 IU/mL and 0.5 IU/mL thresholds, respectively. Conclusions: Quantitative IGRA responses offer information about age-- and sex--specific immunoreactivity and transmission risks that dichotomisation obscures. In high-burden settings, quantitative IGRA responses may clarify Mtb transmission patterns and guide targeted public health strategies.

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Incidence, Clinical Features, and Outcomes of Acute Kidney Injury in Adults and Children Admitted with Dengue Infection in Jamaica

Wilson, T.; Walker, J.; Thomas-Chen, R.; Fisher, L. A.

2026-03-28 infectious diseases 10.64898/2026.03.26.26349368 medRxiv
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Background: The global burden of dengue infection has rising, yet limited data exists on its impact in the Caribbean. We describe the incidence and associates of acute kidney injury in adults and children with dengue at a teaching hospital in Jamaica. Methods: A single-centre retrospective cohort study of admissions with laboratory confirmed dengue infection at University Hospital of the West Indies, Mona Jamaica between January 2023 to November 2024. AKI was defined using Kidney Disease Improving Global Outcomes definitions. Patients were included if aged >1year and had at least 2 creatinine values. Clinical, demographic and laboratory data were abstracted by chart review. Summary statistics were used to describe continuous and categorical data, and logistic regression to determine AKI associations. Stratified analysis was performed by age-group (adults-aged [&ge;] 16, and paediatric-aged <16 years). Results: Analyses included 167 persons, 62% (103) were male, mean age was 26.1{+/-}19.5 years. AKI occurred in 25.8%, 65.1% were KDIGO stage 1. AKI incidence was 30.2% and 18.0% among adults and children respectively. There were 3 in-hospital deaths. People with AKI were older 32{+/-}21.4 vs 24 {+/-}18.4 (p=0.021), and had longer duration of stay [6 vs 4 days (p <0.001)]. Male sex [OR 2.09 (95% CI:0.96-4.59), p=0.064], age per year [OR 1.02 (95% CI:1.01-1.04), p=0.015] symptom duration [OR1.11 (CI 0.99-1.24), p = 0.058], admission bilirubin [OR 1.02 (CI: 1.00-1.04), p = 0.022], NLR [OR 1.09 (CI 1.00-1.18), p = 0.037] were associated with AKI. In adults admission potassium was inversely associated with AKI [OR 0.46 (95% CI 0.21-1.01), p 0.056], while in children admission potassium [OR 3.00 (95% CI 0.88-10.6), p 0.088] was associated with AKI. Conclusion: AKI in dengue hospitalizations is higher than most reports at 25.8%. Targeted public health policy on vector control and early symptom recognition may be needed to improve outcomes.

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Tracking cross-border transmission of Rwandas successful dominant rifampicin-resistant Mycobacterium tuberculosis clone using genomic markers

Cuella-Martin, I.; Mulders, W.; Keysers, J.; Hakizayezu, F.; Niyompano, H.; Runyambo, D.; de Rijk, W.-B.; Phelan, J.; Mucyo Habimana, Y.; Migambi, P.; Sawadogo, M.; Mambo Muvunyi, C.; C. de Jong, B.; Ngabonziza, J. C. S.; Rigouts, L.; Meehan, C.

2026-03-31 infectious diseases 10.64898/2026.03.29.26349652 medRxiv
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Background: In Rwanda, genomic surveillance identified a dominant multidrug-resistant tuberculosis (MDR-TB) strain, the R3clone, responsible for approximately 70% of rifampicin-resistant TB cases. Its presence beyond Rwanda remains unexplored. Methods: Unique genetic signatures of the R3clone were defined using whole-genome sequencing of MDR-TB isolates from Rwanda. We developed a targeted qPCR assay detecting a clone-specific single-nucleotide polymorphism. With these tools, we screened isolates from neighbouring countries and public genomic repositories. Results: We identified 375 R3clone isolates, including 264 from historical Rwandan collections (1991-2021), 49 from recent Rwandan diagnostic routine (2021-2024), 25 from historical Burundi isolates (2002-2013), and 37 among public repositories from several countries. The R3clone-specific qPCR showed 100% specificity in distinguishing the R3clone from other MTBC (sub-)lineages. Transmission analysis revealed cross-border transmission of the R3clone within the Great Lakes Region. Conclusion: This study comprehensively assesses cross-border transmission of a dominant MDR-TB strain, highlighting the need for coordinated international surveillance.

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Comparative Evaluation of CLIA and ELISA Serological Assays for HSV-1 IgG with Western Blot Confirmation in a Clinical Cohort

Issa, F.; Trad, F.; Zein, N.; Abunasser, S.; Nizamuddin, P. B.; Salameh, I.; Ayoub, H.; Al-Abbadi, B.; Al-Hiary, M.; Abou-Nouar, Z.; Al-Subeihi, O.; Al-Zubi, Y.; Al-Manaseer, A.; Al-Jaloudi, A.; Nasrallah, D.; Younes, S.; Younes, N.; Abdallah, M.; Pieri, M.; Nicolai, E.; YASSINE, H. M.; Abu-Raddad, L. J.; Nasrallah, G.

2026-04-15 infectious diseases 10.64898/2026.04.14.26350849 medRxiv
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Introduction: Herpes simplex virus type 1 (HSV-1) is highly prevalent worldwide, making accurate serological testing essential for both clinical diagnosis and epidemiological surveillance. Automated chemiluminescent immunoassays (CLIAs) offer operational advantages over enzyme-linked immunosorbent assays (ELISAs); however, their diagnostic performance relative to Western blot (WB) confirmation in high-prevalence settings remains insufficiently characterized. Hypothesis/Gap Statement: The comparative diagnostic accuracy of CLIA- and ELISA-based assays for HSV-1 IgG detection, when benchmarked against a WB reference standard in endemic populations, remains unclear. Aim: This study aimed to evaluate HSV-1 IgG seroprevalence and diagnostic performance of one CLIA and two ELISA platforms using Western blot as the reference method. Methodology: Four hundred archived serum samples from adult male craft and manual workers in Qatar were tested using the Mindray CL-900i CLIA, HerpeSelect ELISA, NovaLisa ELISA, and Euroimmun Western blot. Seroprevalence, diagnostic accuracy, and interassay agreement were assessed using WB as the reference standard, with equivocal and indeterminate results excluded from analysis. Results: HSV-1 IgG seroprevalence estimates were comparable across assays: HerpeSelect 72.5%, Mindray 70.5%, NovaLisa 66.3%, and Western blot 66.5%, with no statistically significant differences (all p > 0.05). The Mindray CLIA demonstrated the highest diagnostic performance (sensitivity 95.7%, specificity 88.9%, accuracy 93.4%) and strong agreement with Western blot ({kappa} = 0.85). HerpeSelect showed substantial agreement ({kappa} = 0.81), while NovaLisa exhibited lower specificity. Conclusion: CLIA- and ELISA-based assays produced comparable HSV-1 seroprevalence estimates in this high-prevalence population; however, diagnostic accuracy varied across platforms. The CLIA platform demonstrated the strongest agreement with Western blot, supporting its use in high-throughput settings, while confirmatory testing remains important to minimize misclassification.

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Improving estimation of vaccine effectiveness during outbreaks in low-resource settings: A case study of oral cholera vaccination during the 2022-2023 cholera outbreak in Malawi

Ndeketa, L.; Hungerford, D.; Pitzer, V. E.; Jere, K. C.; Jambo, K. C.; Mseka, U. L.; Kumwenda, N.; Banda, C.; Kagoli, M.; Chibwe, I.; Musicha, P.; Cunliffe, N. A.; French, N.; Dodd, P. J.

2026-03-31 infectious diseases 10.64898/2026.03.29.26349659 medRxiv
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Background Use of oral cholera vaccine (OCV) is globally recommended as a public health response to cholera outbreaks, alongside water, sanitation and hygiene (WASH) interventions. Estimating vaccine effectiveness during emergencies in low-and middle-income countries is challenging because vaccination campaigns are often implemented over short time frames, while individual-level data are frequently incomplete due to constraints in infrastructure, resources and data systems. There is a need for pragmatic approaches that can generate timely, policy-relevant evidence using routinely collected data. Methods We analysed routine surveillance data from a large 2022-2023 cholera outbreak in Blantyre District, Malawi. The EpiEstim framework was used to generate estimates of the time-varying reproduction number (Rt) from line-listed case data. We modelled changes in Rt as a function of cumulative OCV coverage using a log-linear framework and propagated uncertainty through posterior sampling. Lagged WASH exposure variables were incorporated in the model to generate adjusted vaccine effectiveness estimates and to explore potential interaction effects. Sensitivity analyses assessed robustness to alternative lag structures. Findings The Blantyre outbreak was characterised by an initial period of low-level transmission followed by a sharp increase in cases from late November 2022, after which transmission declined steadily through April 2023. This decline coincided with the implementation of a reactive OCV campaign. The majority of the cases were among middle-aged men living in urban Blantyre. The unadjusted vaccine-associated reduction in transmission was estimated at 53.52% (95% credible interval (CrI):42.5-64.1%). After adjusting for a 7-day rolling average WASH activity, total vaccine effectiveness increased to 62.1% (95% CrI: 49.3-74.9%). Sensitivity analyses using alternative lag structures for WASH exposure produced comparable adjusted estimates. Interpretation Implementation of OCV contributed to a substantial reduction in cholera transmission during the outbreak. This study demonstrates a feasible approach for estimating vaccine-attributable impact whilst accounting for public health and social measures, such as WASH interventions. The methods described will be useful in outbreaks where classical observational designs are not possible, providing actionable evidence to policy makers for outbreak response in resource-limited settings.

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Uptake and retention in HIV care among pregnant and postpartum women living with HIV under different eras of vertical transmission prevention policies in sub-Saharan Africa: a systematic review and meta-analysis

Jinga, N. N.; Hwang, C.; Rossouw, L.; Clouse, K.; Nattey, C.; Mbwele, B.; Ngcobo, N. B.; Beestrum, M.; Huffman, M. D.; Fox, M. P.; Maskew, M.

2026-04-08 epidemiology 10.64898/2026.04.02.26350030 medRxiv
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Objectives: This systematic review and meta-analysis (2010 - 2025) examines changes in uptake and retention rates among pregnant and postpartum women with HIV in sub-Saharan Africa as countries adopted Option B+ for preventing vertical transmission. Design and data sources: We searched PubMed, Embase, Cochrane Library, Scopus, and African Index Medicus from 10/2021 - 05/2025 for eligible studies that measured HIV care uptake or retention for pregnant/postpartum women under prevention policies before or during Option B+. Study designs were limited to cohort, case-control, cross-sectional, or interventional studies. Exclusions were white papers, commentaries, modeling, cost-effectiveness, and qualitative studies. Data extraction and synthesis: Outcomes were (i) HIV care uptake defined as initiation of ART during pregnancy or prior to initial antenatal care (ANC) visit and (ii) proportion of women retained in HIV care as defined by study authors after ART initiation (or entry to antenatal care). These were synthesized in meta-analyses stratified by policy era (pre-Option B+ vs. Option B+) at different times for different countries. Comparisons between policy eras were made using relative risk with a 95% confidence interval. Pooled retention estimates at 6- and 12-months post ART initiation used crude relative risks (RR) with 95% confidence intervals (CI). Results: Among 4,752 articles, 82 from 17 countries were included; 60 reported HIV care uptake, 31 reported retention outcomes. Pooled HIV uptake rose by 8% (RR=1.08; 95% CI:1.06-1.09) and pooled retention in HIV care rose by 46% (RR=1.46; 95% CI:1.41-1.51) after Option B+ implementation. Pooled estimates of retention in care were 36.9% (95% CI: 13.9%, 59.9%) at 6 months post ART initiation before the implementation of Option B+ and 72.7% (95% CI: 66.3%, 79.1%) after implementation. Conclusion: HIV care uptake and retention improved after Option B+ implementation in 15 countries reporting results, but retention remains suboptimal for meeting UNAIDS 95-95-95 targets.

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Assessing the impact of a gender-neutral approach to HPV vaccination on vaccination coverage for nine-year-old girls in Cameroon: a retrospective, cross-sectional study

Griffith, B. C.; Iliassu, S.; Mbanga, C.; Ngenge, B. M.; Patel, S.; Graves, J. C.; Singh, N.; Ndoula, S.; Njoh, A. A.; Gisele, E.; Mngemane, S.; Ajayi, T.; Zultak, L. A.; Saidu, Y.

2026-04-11 public and global health 10.64898/2026.04.09.26350560 medRxiv
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Cameroon introduced Human papilloma virus vaccine (HPVV) into the routine immunization schedule in October 2020. By the end of 2022, coverage remained low. To increase coverage, Cameroon switched to a country-wide, gender-neutral vaccination (GNV) approach in 2023, coupled with a revamped delivery strategy consisting of Community Dialogues (CDs) and Periodic Intensification of Routine Immunization (PIRIs) activities in selected health districts (HDs). We assessed the impact of these programmatic changes, notably the GNV approach, on HPVV coverage. This retrospective, cross-sectional study measured the effect of GNV and CDs + PIRIs on HPVV coverage among 9-year-old girls in Cameroon (2022-2023). Data on HPVV coverage from all 203 HDs were extracted from DHIS2, and coverage was calculated at the HD level, based on the estimated population eligible of 9-year-old girls. Descriptive statistics and multiple regression models were employed to assess the impact of GNV on vaccination coverage while adjusting for CDs + PIRIs and urban/rural status. In 2023, of the 203 HDs, 115 (56.7%) conducted GNV only, 74 (36.5%) implemented GNV & CDs + PIRIs, and 75.9% (154) were classified as rural. Among age-eligible girls, there was an overall increase in HPV vaccination coverage, with coverage rising 39.2 percentage points from 2022 to 2023. Following multiple linear regression, there was a significant increase in HPVV coverage in HDs with GNV & CDs + PIRIs compared to those with no GNV and no CDs + PIRIs ({beta}:55.5%, 95%CI: 38.7, 72.3, p=0.000). Furthermore, there was a significant increase in HPVV coverage in HDs with GNV only compared to those with no GNV or no CDs + PIRIs ({beta}:28.7%, 95%CI: 12.5, 45.0 p=0.001). Overall, the GNV approach increased HPVV coverage for girls significantly, particularly when implemented alongside CDs + PIRIs.

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Time-to-Tuberculosis disease diagnosis after completion of Tuberculosis preventive therapy among people living with HIV on Antiretroviral Therapy in Eastern Uganda: A retrospective cohort study

Esele, B. A.; Oryokot, B.; Ssentongo, S. M.; Mulongo, M.; Akanyo, J.; Bongomin, F.

2026-04-13 hiv aids 10.64898/2026.04.08.26350451 medRxiv
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BackgroundTuberculosis (TB) remains a leading cause of morbidity and mortality among people living with HIV (PLHIV), who face a 12-fold higher risk of active TB reactivation than HIV-negative individuals. TB preventive therapy (TPT) is an effective intervention, yet TB/HIV co-infection persists at 40-45%, raising questions about the durability of a single course of TPT. This study assessed the time from TPT completion to TB diagnosis and predictors of early TB reactivation. MethodsWe conducted a retrospective case-only cohort study using routine data from Ugandas electronic medical record system, TB registers, and patient files at three TASO Centres of Excellence (Soroti, Mbale, Tororo). PLHIV on antiretroviral therapy (ART) diagnosed with TB after completing TPT between 2022-2024 were included. Participant characteristics and time to TB diagnosis were summarised descriptively; predictors of early TB were identified using logistic regression. ResultsAmong 670 participants, most were female (464, 69.3%) with mean age 51.6 years (SD 14.5). Newly diagnosed TB accounted for 638 (95.2%), including bacteriologically confirmed pulmonary TB (535, 79.9%), clinically diagnosed TB (123, 18.4%), and extrapulmonary TB (12, 1.8%). Overall, 548 (82.8%) participants were virally suppressed, with most on Dolutegravir-based regimens (641, 95.7%). Early TB occurred in 144 (21.5%), with average time to diagnosis 2.6 years. Multivariable analysis showed care at TASO Soroti was protective (aOR = 0.104, p < 0.001), while clinically diagnosed TB (aOR = 1.91, p = 0.007), shorter ART duration (<5 years: aOR = 3.07, p = 0.001; 5-10 years: aOR = 1.74, p = 0.018), and viral suppression (aOR = 1.87, p = 0.014) increased odds of early TB. ConclusionsTB can occur soon after TPT completion, with one in five PLHIV developing early disease particularly those with shorter ART duration despite viral suppression. Strengthening TB screening, continuous monitoring, and repeat TPT for high-risk groups may improve prevention.

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Real world data on Solitary Plasmacytoma from eastern India- highlighting favorable trends in outcome

Podder, D.; Sonowal, H.; Saha, S.; Shah, B.; Ghosh, S.; Kumar, J.; Nag, A.; Chattyopadhyay, D.; Javed, R.; Rath, A.; Chakraborty, S.; Parihar, M.; Zameer, L.; Achari, R. B.; Nair, R.

2026-04-17 hematology 10.64898/2026.04.15.26350956 medRxiv
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Introduction: Solitary plasmacytomas (SP) are rare neoplasm of localised proliferation of clonal plasma cells. It can be classified based on site of involvement and bone marrow involvement. It is an indolent disease in the majority of patients. Primary modality of treatment is radiotherapy and surgical excision. Materials and methods: This was a retrospective audit of SP who were treated and followed up at a tertiary care center in eastern India from January 2012 to December 2025. Patients who has solitary plasma cytoma with more than 10% plasma cells, POEMS syndrome, have been excluded from analysis. Results: We identified 46 patients of SP. The median age of the studied population was 53 years (23-75 years). Males were more commonly affected than females (M:F=2.2:1). Most common chief complaints were bony pain (67.4%). SBP was seen in 39 (84.8%) cases whereas SEP was seen in 7 (15.2%) cases. Vertebra was the most common site of involvement (61.4%). Median M band concentration 0.24 g/dL (0.1 to 1.95 gm/dL). IgG was the most common isotype accounting for 60.6% cases. Six cases (13%) had minimal bone marrow involvement. The majority of the patients received local radiotherapy (89.1%). With a median follow up of 5.4 years (95% CI: 1.8 - 9.0), median OS was not reached, median PFS was 9.22 years (95% CI: 5.8-12.6), median time to next treatment (TTNT) was 9.86 years (95% CI: 6.8 - 12.9). Conclusion: Solitary plasmacytoma commonly affects young males. Bones are more commonly affected than extramedullary sites. SP has a lower rate of progression and excellent prognosis when treated with local radiotherapy.