Prevalence, incidence and determinants of QuantiFERONTM positivity in South African schoolchildren.

BACKGROUND: TB control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town, South Africa. METHODS: We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB burden communities. Prevalent infection was defined as QuantiFERON™-TB Gold Plus (QFT-Plus) positivity as assessed at baseline. Subsequent conversion to QFT-Plus positivity was measured 3 years later among those QFT-Plus-negative at baseline. Multivariable logistic regression models examined factors associated with TB infection. RESULTS: QuantiFERON-positivity at baseline (prevalence: 22.6%, 95% CI 20.9-24.4), was independently associated with increasing age (aOR 1.24 per additional year, 95% CI 1.15-1.34) and household exposure to TB during the participant's lifetime (aOR 1.87, 95% CI 1.46-2.40). QFT-Plus conversion at year 3 (12.2%, 95% CI 10.5-14.0; annual infection rate: 3.95%) was associated with household exposure to an index TB case (aOR 2.74, 95% CI 1.05-7.18). CONCLUSION: Rates of QFT-diagnosed TB infection remain high in this population. The strong association with household TB exposure reinforces the importance of contact tracing, preventative treatment and early treatment of infectious disease to reduce community transmission.

CONTEXTE: La lutte contre la TB nécessite la compréhension et la perturbation de la transmission de la TB. Nous décrivons la prévalence, l'incidence et les facteurs de risque associés à l'infection tuberculeuse infantile au Cap, en Afrique du Sud. MÉTHODES: Nous rapportons des données transversales de référence et d'incidence prospective provenant d'un vaste essai mené auprès d'enfants d'écoles primaires vivant dans des communautés à forte charge de morbidité tuberculeuse. La prévalence de l'infection a été définie comme la positivité au QuantiFERON™-TB Gold Plus (QFT-Plus) telle qu'évaluée au départ. La conversion subséquente en QFT-Plus positif a été mesurée 3 ans plus tard chez les QFT-Plus négatifs au départ. Des modèles de régression logistique multivariée ont examiné les facteurs associés à l'infection tuberculeuse. RÉSULTATS: La positivité QuantiFERON-au départ (prévalence : 22,6%, IC à 95% 20,9­24,4), était indépendamment associée à l'augmentation de l'âge (aOR 1,24 par année supplémentaire, IC à 95% 1,15­1,34) et à l'exposition du ménage à la TB au cours de la vie du participant (aOR 1,87 ; IC à 95% 1,46­2,40). La conversion QFT-Plus à l'année 3 (12,2%, IC à 95% 10,5­14,0 ; taux d'infection annuel : 3,95%) était associée à l'exposition du ménage à un cas de tuberculose index (aOR 2,74 ; IC à 95% 1,05­7,18). CONCLUSION: Les taux d'infection tuberculeuse diagnostiquée par QFT restent élevés dans cette population. La forte association avec l'exposition à la TB dans les ménages renforce l'importance de la recherche des contacts, du traitement préventif et du traitement précoce des maladies infectieuses pour réduire la transmission communautaire.

Importance of ventilation and occupancy to Mycobacterium tuberculosis transmission rates in congregate settings.

BACKGROUND: Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings. METHODS: We collected carbon dioxide concentration and occupancy data in congregate locations and public transport on 88 occasions, in Cape Town, South Africa. For each location, we estimated ventilation rates and the relative rate of infection, accounting for ventilation rates and occupancy. RESULTS: We show that the estimated potential transmission rate in congregate settings and public transport varies greatly between different settings. Overall, in the community we studied, estimated infection risk was higher in minibus taxis and trains than in salons, bars, and shops. Despite good levels of ventilation, infection risk could be high in the clinic due to high occupancy levels. CONCLUSION: Public transport in particular may be promising targets for infection prevention and control interventions in this setting, both to reduce Mtb transmission, but also to reduce the transmission of other airborne pathogens such as measles and SARS-CoV-2.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation.

BACKGROUND: HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues. OBJECTIVES: To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA). METHOD: A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4. RESULTS: The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit. CONCLUSIONS: This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation

Background. HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues.Objectives. To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA).Method. A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4.Results. The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit.Conclusions. This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required

Retreatment tuberculosis in a South African community: the role of re-infection, HIV and antiretroviral treatment.

BACKGROUND: Limited data exist on the impact of human immunodeficiency virus (HIV) or antiretroviral treatment (ART) on retreatment tuberculosis (TB). METHODS: Retreatment TB episodes between 2001 and 2010 in a high HIV and TB burden community were linked to first-episode treatment outcomes, HIV status and ART use. Genotypic analysis of Mycobacterium tuberculosis isolates distinguished re-infection from reactivation TB. RESULTS: A total of 2027 TB episodes occurred in 1755 adults: 564 were retreatment cases. New patients who interrupted or failed initial treatment, were HIV-positive or were not on ART more frequently developed retreatment TB (respectively P < 0.001, P = 0.01 and P = 0.02). Time intervals between successive diagnoses were shorter in patients who interrupted/failed treatment compared to those with favourable initial treatment outcomes (P < 0.001), but did not vary by HIV status or ART use. Genotypic data were available for 40 successive diagnoses, of which 19 had matching M. tuberculosis strains. Matching strains were associated with HIV-negative status (P < 0.001), treatment interruption/failure (P = 0.04) and shorter intervals between diagnoses (P = 0.02). HIV-positive patients and patients on ART were more likely to have non-matched strains (P = 0.01 and P = 0.03). CONCLUSION: Among HIV-negative patients, retreatment TB was predominantly due to reactivation following poor initial treatment outcomes. In HIV-positive patients re-infection TB was more common, particularly among those on ART.

Changing prevalence of tuberculosis infection with increasing age in high-burden townships in South Africa.

SETTING: Crowded townships of Cape Town, South Africa, where human immunodeficiency virus (HIV) prevalence and tuberculosis (TB) notification rates are among the highest in the world. OBJECTIVES: To determine age-specific prevalence rates of latent tuberculosis infection (LTBI) among HIV-negative individuals, and the annual risk and force of infection during childhood and adolescence. DESIGN: A cross-sectional survey using a standardised tuberculin skin test (TST) in HIV-negative individuals aged 5-40 years. A TST diameter of > or =10 mm was defined as indicative of LTBI. RESULTS: Among 1061 individuals, only 4.7% had low-grade TST responses of 1-9 mm. However, the proportions of individuals with TST > or =10 mm increased from 28.0% in the 5-10 year age stratum to 88.0% in the 31-35 year age stratum. The mean annual risk of infection was 3.9% up to 5 years of age. The estimated force of infection (the rate of acquisition of LTBI among the residual pool of non-infected individuals) increased throughout childhood to a maximum of 7.9% per year at age 15 years. CONCLUSIONS: Extremely high rates of infection in childhood and adolescence result in very high LTBI prevalence rates in young adults who are most at risk of acquiring HIV infection. This may be an important factor fuelling the high rates of HIV-associated TB in southern Africa.

A qualitative assessment of perspectives on the inclusion of adolescents in HIV vaccine trials in South Africa.

Adolescents are at high risk for HIV acquisition, and thus need to be included in HIV vaccine trials. In preparation for inclusion of adolescents in HIV vaccine trials in an urban community in Cape Town with a high antenatal HIV prevalence, the study assessed the attitudes towards the inclusion of adolescents in HIV vaccine trials. A total of 18 focus group discussions were conducted using a semistructured interview guide. The participants (n = 200) were adolescents, young adults, parents and other key informants. Participants from all groups welcomed the inclusion of adolescents in HIV vaccine trials due to their high-risk status. There were, however, concerns about sexual disinhibition, fear of side-effects, fear of HIV testing and disclosure of HIV status, mistrust of nurses and clinics. The study highlighted a number of ethical and social issues that need to be addressed before the trials.

Sexual risk factors associated with volunteering for HIV vaccine research in South Africa.

There are few data on how the risk profiles of individuals who volunteer for HIV vaccine research compare to the general population from which participants are recruited. This study contrasts demographic and sexual risk behaviours among volunteers in an HIV vaccine preparedness cohort with data from a cross-sectional community survey conducted in the same peri-urban community during the same time period. For the HIV vaccine preparedness cohort, structured questionnaires were administered to 140 HIV-negative individuals aged between 16 and 40 years. A questionnaire with identical measures was self-administered in a cross-sectional community survey of 583 randomly selected individuals within the same age range. Compared to the local community sample, individuals who volunteered for the HIV vaccine preparedness cohort were younger (adjusted odds ratio = 0.48; 95% CI = 0.28-0.82), more likely to have had a sexually transmitted disease (adjusted odds ratio = 1.75; 95% CI = 1.03-2.99) and less likely to use condoms (adjusted odds ratio = 0.51; 95% CI = 0.3-0.86). Cohort participants were also more likely to perceive themselves and their partners to be at risk of HIV infection, though these associations did not persist in multivariate analysis. These findings suggest that volunteers for vaccine-related research may be at greater risk of HIV infection than the general population from which they are recruited.

Mental health and sexual risk behaviours in a South African township: a community-based cross-sectional study.

OBJECTIVES: Despite the high prevalence of both mental illness and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in developing countries, there are few data on the association between different forms of mental illness and sexual risk behaviours in resource-poor settings. The objective of this study was to examine the association between mental illness and HIV risk behaviours in a South African township. STUDY DESIGN: A cross-sectional study was performed among 645 individuals living in households selected at random. METHODS: A self-administered translated questionnaire investigated sexual risk behaviours [including sexual partners, condom use, casual sexual contacts, and sex in exchange for money, drugs or a place to stay (transactional sex)], depression (measured using the Center for Epidemiological Studies Depression Scale), alcohol abuse (from the Alcohol Use Disorders Identification Test), and post-traumatic stress disorder (based on the Life Event Checklist). RESULTS: Of the 645 individuals who completed the survey, 33% reported depression, 17% reported alcohol abuse, and 15% reported post-traumatic stress disorder. After adjusting for demographic characteristics, the presence of any of these three conditions was strongly associated with experiences of forced sex [adjusted odds ratio (AOR) 2.53; 95% confidence intervals (CI) 1.60-4.02], transactional sex (AOR 2.88; 95% CI 1.29-6.48) and increased condom use (AOR 2.07; 95% CI 1.32-3.25). CONCLUSIONS: These findings emphasize the substantial burden of mental illness in this setting, and its association with forced and transactional sex. The temporal nature of these associations is not always clear from this cross-sectional study, and additional prospective research is required. Public health interventions are needed to address the dual burden of HIV/AIDS and mental illness in this and similar settings.

Willingness to participate in HIV vaccine research in a peri-urban South African community.

Research on willingness to participate in HIV vaccine trials is important in preparations for HIV vaccine research, but there are few data from sub-Saharan Africa. We interviewed 198 individuals in a peri-urban South African community immediately after enrolment into an HIV vaccine preparedness study on their willingness to participate in hypothetical vaccine trials. Overall 23% of participants (n = 46) said that they would be willing to participate in an HIV vaccine trial. Willingness was associated with increasing age, male gender, and increasing knowledge about vaccines generally and HIV vaccines specifically. In multivariate analysis, a 1-unit increase in HIV vaccine knowledge score was associated with a 10-fold increase in willingness to participate (adjusted odds ratio, 10.72, 95% confidence intervals: 4.40-26.12). These results suggest that while willingness to participate in HIV vaccine trials is relatively low in this setting, educational campaigns may have a substantial impact on individuals' willingness to participate in research.