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BackgroundSystematic screening is a potential tool for reducing the prevalence of tuberculosis (TB) and counteracting COVID-19-related disruptions in care. Repeated community-wide screening can also measure changes in the prevalence of TB over time.MethodsWe conducted serial, cross-sectional TB case finding campaigns in one community in Kampala, Uganda, in 2019 and 2021. Both campaigns sought sputum for TB testing (Xpert MTB/RIF Ultra) from all adolescents and adults. We estimated the prevalence of TB among screening participants in each campaign and compared characteristics of people with TB across campaigns. We simultaneously enrolled and characterised community residents who were diagnosed with TB through routine care and assessed trends in facility-based diagnosis.ResultsWe successfully screened 12 033 community residents (35% of the estimated adult/adolescent population) in 2019 and 11 595 (33%) in 2021. In 2019, 0.94% (95% CI: 0.77% to 1.13%) of participants tested Xpert positive (including trace). This proportion fell to 0.52% (95% CI: 0.40% to 0.67%) in 2021; the prevalence ratio was 0.55 (95% CI: 0.40 to 0.75)). There was no change in the age (median 26 vs 26), sex (56% vs 59% female) or prevalence of chronic cough (49% vs 54%) among those testing positive. By contrast, the rate of routine facility-based diagnosis remained steady in the 8 months before each campaign (210 (95% CI: 155 to 279) vs 240 (95% CI: 181 to 312) per 100 000 per year).ConclusionsFollowing an intensive initial case finding campaign in an urban Ugandan community in 2019, the burden of prevalent TB as measured by systematic screening had decreased by 45% in 2021, despite the intervening COVID-19 pandemic.

IMPORTANCE: In addition to illness, the COVID-19 pandemic has led to historic educational disruptions. In March 2021, the federal government allocated $10 billion for COVID-19 testing in US schools. OBJECTIVE: Costs and benefits of COVID-19 testing strategies were evaluated in the context of full-time, in-person kindergarten through eighth grade (K-8) education at different community incidence levels. DESIGN, SETTING, AND PARTICIPANTS: An updated version of a previously published agent-based network model was used to simulate transmission in elementary and middle school communities in the United States. Assuming dominance of the delta SARS-CoV-2 variant, the model simulated an elementary school (638 students in grades K-5, 60 staff) and middle school (460 students grades 6-8, 51 staff). EXPOSURES: Multiple strategies for testing students and faculty/staff, including expanded diagnostic testing (test to stay) designed to avoid symptom-based isolation and contact quarantine, screening (routinely testing asymptomatic individuals to identify infections and contain transmission), and surveillance (testing a random sample of students to identify undetected transmission and trigger additional investigation or interventions). MAIN OUTCOMES AND MEASURES: Projections included 30-day cumulative incidence of SARS-CoV-2 infection, proportion of cases detected, proportion of planned and unplanned days out of school, cost of testing programs, and childcare costs associated with different strategies. For screening policies, the cost per SARS-CoV-2 infection averted in students and staff was estimated, and for surveillance, the probability of correctly or falsely triggering an outbreak response was estimated at different incidence and attack rates. RESULTS: Compared with quarantine policies, test-to-stay policies are associated with similar model-projected transmission, with a mean of less than 0.25 student days per month of quarantine or isolation. Weekly universal screening is associated with approximately 50% less in-school transmission at one-seventh to one-half the societal cost of hybrid or remote schooling. The cost per infection averted in students and staff by weekly screening is lowest for schools with less vaccination, fewer other mitigation measures, and higher levels of community transmission. In settings where local student incidence is unknown or rapidly changing, surveillance testing may detect moderate to large in-school outbreaks with fewer resources compared with schoolwide screening. CONCLUSIONS AND RELEVANCE: In this modeling study of a simulated population of primary school students and simulated transmission of COVID-19, test-to-stay policies and/or screening tests facilitated consistent in-person school attendance with low transmission risk across a range of community incidence. Surveillance was a useful reduced-cost option for detecting outbreaks and identifying school environments that would benefit from increased mitigation.

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The current active–latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosisand an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

Barrier contraceptive methods are the oldest type of reversible contraception still available. They work by preventing the egg and the sperm coming into contact with one another, thereby preventing fertilisation. Some barrier contraceptive methods have the added benefit of preventing transmission of sexual infections. The main types of barrier contraceptives are the male and female condoms, diaphragms and cervical caps. This article aims to provide an overview of the different barrier methods for contraception, their efficacy, and advantages and disadvantages.

In May, 2016, WHO endorsed a 9 month regimen for multidrug-resistant tuberculosis that is cheaper and potentially more effective than the conventional, longer (20–24 month) therapy. We aimed to investigate the population-level implications of scaling up this new regimen.

Multidrug-resistant (MDR) tuberculosis can be acquired through de-novo mutation during tuberculosis treatment or through transmission from other individuals with active MDR tuberculosis. Understanding the balance between these two mechanisms is essential when allocating resources for MDR tuberculosis. We aimed to create a dynamic transmission model of an MDR tuberculosis epidemic to estimate the contributions of treatment-related acquisition and person-to-person transmission of resistance to incident MDR tuberculosis cases.

ABSTRACTVibrio choleraeO1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B cells of the immunoglobulin G (IgG) and IgA isotypes to V. choleraeO1 antigens, including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera infection has been demonstrated. Memory B cells of the IgM isotype may play a role in long-term protection, particularly against T-cell-independent antigens, but IgM memory has not been studied in V. choleraeO1 infection. Therefore, we assayed acute- and convalescent-phase blood samples from cholera patients for the presence of memory B cells that produce cholera antigen-specific IgM antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and antibody-secreting cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-cell-independent antigen LPS and to the T-cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM antibody-secreting cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.

Vibrio cholerae O1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B cells of the immunoglobulin G (IgG) and IgA isotypes to V. cholerae O1 antigens, including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera infection has been demonstrated. Memory B cells of the IgM isotype may play a role in long-term protection, particularly against T-cell-independent antigens, but IgM memory has not been studied in V. cholerae O1 infection. Therefore, we assayed acute- and convalescent-phase blood samples from cholera patients for the presence of memory B cells that produce cholera antigen-specific IgM antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and antibody-secreting cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-cell-independent antigen LPS and to the T-cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM antibody-secreting cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.

ABSTRACTVibrio choleraeO1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses to V. choleraeinfection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severe V. choleraeinfection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses using V. choleraeantigens, including the toxin-coregulated pilus (TcpA), a V. choleraemembrane preparation, and the V. choleraecytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses to V. choleraeantigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to other V. choleraeantigens.

Vibrio cholerae O1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses to V. cholerae infection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severe V. cholerae infection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses using V. cholerae antigens, including the toxin-coregulated pilus (TcpA), a V. cholerae membrane preparation, and the V. cholerae cytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses to V. cholerae antigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to other V. cholerae antigens.

ABSTRACTCholera, caused by Vibrio cholerae, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with V. choleraeelicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to V. choleraeinfection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with V. cholerae. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to V. choleraeprotein antigens. Such memory B cells could mediate anamnestic responses on reexposure to V. cholerae.

Cholera, caused by Vibrio cholerae, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with V. cholerae elicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to V. cholerae infection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with V. cholerae. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to V. cholerae protein antigens. Such memory B cells could mediate anamnestic responses on reexposure to V. cholerae.