The Journal of Infectious Diseases

BackgroundTuberculosis (TB) is a leading cause of morbidity and mortality among children living with HIV (CLHIV). Poor diagnostic performance is a significant contributor. Serological assays that determine levels of Mycobacterium tuberculosis reactive antibodies inconsistently detect TB. However, antigen-specific antibody Fc receptor engagement and effector functions are promising biomarkers of TB disease. MethodsThis study evaluated serum from a well-characterized cohort of Kenyan CLHIV via tw...

ObjectiveSevere tuberculosis (TB) is a major cause of critical illness and death in people living with HIV (PLWH) worldwide. Despite this, the immunopathology of severe HIV-associated TB (HIV/TB) is poorly understood. We aimed to identify an immunopathologic signature of severe HIV/TB in sub-Saharan Africa. Design and SettingWe analyzed proteomic data from two prospective observational cohorts of adults hospitalized with severe undifferentiated infection in Uganda: an urban discovery cohort (En...

BackgroundSeveral Shigella vaccine candidates are in late stages of development, and the design of large Phase 3 trials in target populations is underway. Immunologic catch up by unvaccinated infants to vaccinated infants, which is determined by the trial site-specific force of infection, may modify the vaccine efficacy (VE) estimates observed in such trials. To set expectations and support optimal planning of future Shigella vaccine trials, we aimed to quantify the potential bias of VE estimate...

BackgroundMalaria transmission in southwestern Uganda is low, but persists despite ongoing control efforts. Identifying whether infections are locally sustained or imported by travelers is critical for guiding interventions. We integrated epidemiologic surveillance with parasite genomics to characterize imported malaria episodes at three health facilities in southwestern Uganda. MethodsBetween January 2023 and June 2024, we enrolled microscopy-confirmed malaria cases at three health facilities,...

BackgroundMalaria caused by Plasmodium falciparum remains a major global health challenge. Although clinical disease results from asexual blood-stage replication, transmission depends on gametocyte carriage. We characterized the seasonal dynamics of the human infectious reservoir in a rural high-transmission setting in Burkina Faso. MethodsWe conducted a 2-year cohort study (2019-2020) including 871 individuals of all ages from four villages in the Nanoro health district. Participants were acti...

BackgroundEnteric fever, caused by Salmonella Typhi or Paratyphi, is a major public health issue in low-and middle-income countries. Accurate burden estimation is hampered by limited microbiological facilities and low sensitivity of blood culture tests. Serosurveillance offers a scalable alternative to address these challenges. This study estimated the seroincidence of enteric fever in Bangladesh using cross-sectional rapid serosurveys. MethodsSchool-based surveys (January-June 2022) were condu...

BackgroundIn Bangladesh, cholera treatment focuses on acute watery diarrhea in symptomatic cases at health facilities, though asymptomatic infections are common. Understanding the role of asymptomatic infections in transmission is crucial for designing appropriate control strategies in this setting. MethodsWe utilized data from household studies conducted in Dhaka, Bangladesh during 2006-2018 where a symptomatic confirmed cholera case and their household contacts were followed for thirty days. ...

BackgroundThe number and timing of pneumococcal conjugate vaccine (PCV) primary doses can impact infant immune responses. This descriptive post hoc analysis evaluates the immunogenicity of the 20-valent PCV (PCV20) by vaccination timing in healthy infants in 2 key phase 3 trials. MethodsImmunogenicity endpoints from study B7471012 comparing PCV20 to 13-valent PCV (PCV13) in a 2+1 schedule were examined by timing of vaccination subgroup; the 2,4m subgroup (participants vaccinated at 2, 4, and 11...

BackgroundElimination of Plasmodium vivax is challenging due to its dormant liver stages (hypnozoites), which can reactivate weeks or months after the primary infection, causing relapses and ongoing transmission of the parasite. Despite these challenges, P. vivax clinical case numbers have declined over the past decade in Cambodia. We used parasite genotyping to assess whether the decline in case numbers was reflected in parasite diversity and relatedness as a proxy to transmission. MethodsGeno...

BackgroundWe previously reported that nasal SARS-CoV-2 viral loads (VL) peaked around the fourth day of symptoms in highly immune adults sampled April 2022 - April 2023, while influenza A VL peaked soon after symptom onset. We hypothesized that SARS-CoV-2 kinetics may have changed due to reduced COVID-19 incidence and altered vaccination patterns. Understanding how viral kinetics evolve over time is essential to inform testing strategies. MethodsParticipants with symptomatic upper respiratory i...

Annual influenza vaccination is the cornerstone for seasonal protection, yet antibody responses are highly variable across individuals and over time. To systematically assess the determinants of this heterogeneity, we compiled 20,449 hemagglutination inhibition and neutralization titers from 4,540 participants enrolled in 14 new vaccine studies we conducted and 50 prior studies that collectively span 2010-2023. Seasonal effects dominated, with pre- and post-vaccination titers declining steadily ...

BackgroundSerotype 3 (S3) has remained a major cause of invasive pneumococcal disease (IPD) despite its inclusion in 13-valent pneumococcal conjugate vaccine (PCV). In October 2023, a 15-valent PCV (PCV15) including S3 was introduced into the Catalan universal childhood immunization program. MethodsWe conducted a retrospective pre-post surveillance study to compare pediatric IPD incidence in Catalonia during a pre-PCV15 period (October 1, 2022-September 30, 2023) and two post-PCV15 periods (Oct...

BackgroundRespiratory syncytial virus (RSV) is a leading cause of severe acute respiratory infection in infants, young children and vulnerable adults. Despite implications for designing interventions, our understanding of RSV infection/reinfection patterns during community outbreaks is incomplete. MethodsTo characterize respiratory virus infections regardless of symptom status, we performed a prospective cohort surveillance in coastal Kenya from August 2023 to August 2024. Nasopharyngeal/oropha...

Dengue virus (DENV), comprising four distinct serotypes (DENV-1 to DENV-4), poses a major public health challenge in tropical regions. Infection with one serotype confers long-term immunity to that serotype alone, while subsequent heterologous infections are associated with increased risk of severe disease, necessitating vaccines that induce durable, balanced immunity across all serotypes. However, achieving such balance immunity remains a central challenge for dengue vaccine development. Using ...

BackgroundTuberculosis (TB) and HIV co-infection cause profound immune dysregulation. Understanding how these infections alter immune cell distribution across systemic and tissue compartments is critical for improving therapeutic and vaccine strategies. MethodsFlow cytometry was used to quantify CD4 and CD8 T cells, B cells, and tissue-resident memory (TRM) T and B cells in peripheral blood mononuclear cells (PBMCs), lung tissue, bronchoalveolar lavage (BAL), spleen, and lung-draining hilar lym...

BackgroundEpstein-Barr virus (EBV) establishes latency in most adults and can be reactivated under conditions of co-infection and immune dysregulation. COVID-19 has been associated with EBV reactivation, primarily in hospitalized cohorts, but EBV shedding in the oral cavity and the extent to which these dynamics trigger a systemic anti-EBV antibody response during acute COVID-19 remain poorly understood. MethodsWe conducted a nested cohort study of 69 community-based participants including 56 S...

BACKGROUNDUnderstanding SARS-CoV-2 antibody dynamics is critical for pandemic preparedness, particularly where population immunity has developed through high infection rates with minimal vaccination. Whether predominantly asymptomatic infections confer protective immunity and which biomarkers best predict protection in resource-limited settings remain unclear. METHODSWe conducted a household cohort study in The Gambia over 15 months (March 2021-June 2022) during Delta and Omicron waves, with we...

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)-and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting a...

To evaluate the impact of sex on acute SARS-CoV-2 infection, 668 participants from the ACTIV-2/A5401 study were followed over a 28-day period. A primary analysis was performed on the 469 participants who had quantifiable viral loads at baseline. Male and female participants had comparable nasal SARS-CoV-2 RNA levels at study entry and throughout follow-up. However, sex-specific differences in viral shedding emerged when stratified by duration of symptoms. In the first three days from symptom ons...

In nonsuppressible HIV viremia (NSV), individuals have persistently detectable viral load despite adherence to [≥]2 fully active antiretroviral drugs. NSV represents an area of clinical uncertainty and an opportunity to understand the mechanisms of HIV persistence. We performed in-depth virologic characterization to identify distinct NSV phenotypes. We categorized participants into those who had persistent viremia after antiretroviral therapy (ART) initiation (primary NSV) and those who had N...