Mortality from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing: a multicentre cohort study.

Background: Drug resistance threatens global tuberculosis control. We aimed to examine mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and whole-genome sequencing (WGS).

Methods: In this multicentre cohort study, we collected pulmonary isolates and clinical data from individuals with tuberculosis from antiretroviral therapy programmes and tuberculosis clinics in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, Peru, South Africa, and Thailand, stratified by HIV status and drug resistance.

Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study.

Background: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory.

Methods: This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand.

Reverse geroscience: how does exposure to early diseases accelerate the age-related decline in health?

Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the focus was on the role of aging in susceptibility to disease and disability, the other side of this relationship, which is the contribution of disease to aging, has been less explored at the molecular/cellular level.

Evaluation of tuberculosis diagnostics in children: 2. Methodological issues for conducting and reporting research evaluations of tuberculosis diagnostics for intrathoracic tuberculosis in children. Consensus from an expert panel.

Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings.

Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions.

Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research.

Apnea and its possible relationship to immunization in ex-premature infants.

This study compared the characteristics of infants hospitalized with apnea that participated in a vaccine trial compared with two control groups which consisted of 100 infants randomly selected from the same vaccine trial and 52 consecutively born very low birth weight (VLBW) infants. A total of 23 infants were admitted with apnea of whom 19 weighed <1500 g at birth and all were born at <37 weeks gestation. More of the VLBW infants in the apnea group had neonatal neurological complications compared with the VLBW control group (p=0.

Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control.

Background: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program.

Methods: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire.

Incidence of tuberculin skin test conversion among HIV-infected and -uninfected women: results of a 6-year study.

Objective: To define the incidence of tuberculin skin test (TST) conversion and to evaluate the yield of annual testing in an era of declining tuberculosis incidence rate in the United States.

Methods: Annual TSTs were performed on initially TST-negative women (HIV infected, 995; uninfected, 260) from October 1995 through March 2002.

Results: A total of 4,622 repeat TSTs were performed during 5,530 person-years.

Dose response of CRM197 and tetanus toxoid-conjugated Haemophilus influenzae type b vaccines.

High vaccine cost has limited use of conjugate vaccines in the developing world where the disease burden is greatest. Fixed fractional doses of Haemophilus influenzae type b (Hib) vaccines have been shown to be immunogenic, but dose responses of these vaccines in humans are needed to determine the lowest immunogenic dose as an option for lowering vaccine cost. We randomized children to receive one of five doses (0.

Long-term antibody levels and booster responses in South African children immunized with nonavalent pneumococcal conjugate vaccine.

Children who had initially received three doses of either a nonavalent pneumococcal conjugate vaccine containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, and 23F or placebo at 6, 10, and 14 weeks of age were bled at 9 and 18 months for determination of antibody concentrations. The children were then randomized to receive a booster dose of either the 9-valent pneumococcal conjugate vaccine or a 23-valent polysaccharide vaccine and antibody levels determined 1 month later. At 9 months, the geometric mean concentrations (GMCs) were significantly higher for all vaccine serotypes in vaccinated children compared with controls (means varied from 0.

A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection.

Background: Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa.

Methods: At 6, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo.

Antibiotic resistance and serotype distribution of Streptococcus pneumoniae colonizing rural Malawian children.

Nasopharyngeal swabs were taken from 906 Malawian children <5 years old visiting rural health clinics. Pneumococcal colonization was high, 84% among all children, and occurred early, 65% of it in children <3 months old. Among pneumococcal isolates 46% were nonsusceptible to trimethoprim-sulfamethoxazole, and 21% were nonsusceptible to penicillin.

Bacterial aetiology of non-resolving otitis media in South African children.

Little is known of the aetiology, serotypes or susceptibility of the pathogens causing non-resolving otitis media in children receiving care from specialists in private practice in developed or in developing countries. Increased access to antibiotics in the community amongst children receiving such private care in South Africa may be anticipated to lead to levels of resistance similar to those found in countries with similar models of private practice, such as the United States. This study was conducted to determine the aetiology of non-resolving otitis media in South African children receiving private care and to determine the antimicrobial resistance patterns and serotypes of the bacterial isolates.

Immunogenicity after one, two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto, South Africa.

Background: Children <6 months of age are at increased risk of pneumococcal disease. The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children.

Objectives: To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens.

Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection.

Background: Haemophilus influenzae type b (Hib) conjugate vaccines have successfully reduced the burden of invasive Hib disease in developed countries; however, their effectiveness in countries with a high incidence of pediatric HIV-1 is unknown.

Methods: The effectiveness of Hib conjugate vaccine was prospectively evaluated in South African children. The burden of invasive Hib disease in children < 1 year old was compared in 2 cohorts.

Haemophilus influenzae type b conjugate vaccine diluted tenfold in diphtheria-tetanus-whole cell pertussis vaccine: a randomized trial.

Background: Despite their proven efficacy Haemophilus influenzae type b (Hib) conjugate vaccines are not given to most children in the developing world in the face of an estimated global Hib disease burden of nearly 2 million cases per annum. A major barrier to the introduction of the vaccine would be overcome by diluting the vaccine 10-fold in diphtheria-tetanus-whole cell pertussis (DTP). We report a randomized trial comparing the use of Hib conjugate vaccine diluted in a multidose vial of DTP with that of the full Hib dose.