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...

We longitudinally assessed P. falciparum parasite kinetics, gametocyte production and infectivity in incident infections that were naturally acquired following infection clearance and in chronic asymptomatic infections in Burkina Faso. 92% (44/48) of the incident cohort developed symptoms and were treated within 35 days, compared to 23% (14/60) of the chronic cohort. All but two individuals with chronic infection were gametocytaemic at enrollment, whereas only 35% (17/48) in the incident cohort ...

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 control in sub-Saharan Africa is typically focused on Plasmodium falciparum (Pf), but non-falciparum species like P. ovale curtisi (Poc) and P. ovale wallikeri (Pow) appear to be rising in prevalence, especially in East Africa. MethodsWe conducted polymerase chain reaction (PCR)-based screening of 7,173 asymptomatic individuals over 5 years of age in coastal Tanzania from 2018-2022, employing real-time 18S rRNA PCR assays for P. falciparum and P. ovale, followed by Poc/Pow det...

Serologic surveillance of at-risk populations can be used to directly estimate the incidence of typhoidal Salmonella infection across a variety of settings, including those without access to facility-based blood-culture surveillance. We collected paired blood samples approximately three months apart from an age-stratified random sample of healthy children and adults in Bangladesh, Malawi, and Nepal as part of the Strategic Typhoid Alliance Across Asia and Africa (STRATAA) study. We used a multip...

BackgroundAs The Gambia aims to achieve elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. MethodsWithin a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant P...

BackgroundThe first RSV vaccines for adults 60 years and older were approved prior to the 2023-2024 respiratory virus season. This study used data from adults 60 years and older, enrolled into the Community Vaccine Effectiveness (CoVE) cohort study, in Michigan, U.S.A, to evaluate RSV vaccine effectiveness (VE) and antibody correlates of protection. MethodsA Cox proportional hazards model was used to compare incidence of symptomatic / all RSV infections in those vaccinated versus unvaccinated. ...

BackgroundEmerging artemisinin resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (K13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. K13-561H was initially described at a frequency of 7.4% from Masaka in 2014-2015 but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform contro...

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...

Plasmodium falciparum malaria remains a leading cause of mortality in Angola, with emerging antimalarial resistance threatening treatment and prevention strategies. Efficacy of artemether-lumefantrine, one of the countrys preferred malaria treatments, has been reported below 90% in two provinces, underscoring the need for routine resistance surveillance and efficacy monitoring to guide policy decisions. Between March and July 2023, dried blood spots and demographic data were collected from P. f...

BackgroundTo characterize interferences between Streptococcus pneumoniae and SARS-CoV-2 we investigated the longitudinal patterns of viral infection and pneumococcal carriage in households infected with SARS-CoV-2. MethodsSARS-CoV-2 and pneumococcus were detected with quantitative molecular methods in saliva from members of eighty participating households. Samples were collected between October 2020 and January 2021 from n=197 adults and n=118 children of which n=176 adults and n=98 children ha...

BACKGROUNDCharacterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODSWe measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose bl...

BackgroundMycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays and do not develop TB. Here we report a hitherto unknown form of this phenotype: HIV-1-positive persistently TB, tuberculin and IGRA negative (HITTIN). MethodsA community-based case-control design was...

BackgroundReports of P. vivax infections among Duffy-negative hosts have begun to accumulate throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa nor population genetic analyses to determine the source of these infections have been performed. MethodsTo overcome this critical gap in knowledge, we screened nearly 18,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using sam...

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...

Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administrations (FDA) guidelines for convalescent plasma recommends target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at low (PRNT50) and high (PRNT90) stringency thresholds. We found tha...

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, could offer protective immunity, and may affect clinical outcomes of COVID-19 patients. We analyzed 625 serial plasma samples from 40 hospitalized COVID-19 patients and 170 SARS-CoV-2-infected outpatients and asymptomatic individuals. Severely ill patients developed significantly higher SARS-CoV-2-specific antibody response...

BackgroundHepatitis E virus, typically genotypes 1 and 2, is a major cause of avoidable morbidity and mortality in South Asia. Although case fatality risk among pregnant women can reach as high as 25%, a lack of population-level disease burden data has been cited as a primary factor in key global policy recommendations against the routine use of licensed hepatitis E vaccines, one of the only effective tools available for preventing disease and death. MethodsWe tested serum from a nationally-rep...