Indoor Social Networks in a South African Township: Potential Contribution of Location to Tuberculosis Transmission

CITATION: Wood, R. et al. 2012. Indoor social networks in a South African township : potential contribution of location to tuberculosis transmission. PLoS ONE, 7(6): e39246, doi:10.1371/journal.pone.0039246.The original publication is available at http://journals.plos.org/plosoneBackground We hypothesized that in South Africa, with a generalized tuberculosis (TB) epidemic, TB infection is predominantly acquired indoors and transmission potential is determined by the number and duration of social contacts made in locations that are conducive to TB transmission. We therefore quantified time spent and contacts met in indoor locations and public transport by residents of a South African township with a very high TB burden. Methods A diary-based community social mixing survey was performed in 2010. Randomly selected participants (n = 571) prospectively recorded numbers of contacts and time spent in specified locations over 24-hour periods. To better characterize age-related social networks, participants were stratified into ten 5-year age strata and locations were classified into 11 types. Results Five location types (own-household, other-households, transport, crèche/school, and work) contributed 97.2% of total indoor time and 80.4% of total indoor contacts. Median time spent indoors was 19.1 hours/day (IQR:14.3–22.7), which was consistent across age strata. Median daily contacts increased from 16 (IQR:9–40) in 0–4 year-olds to 40 (IQR:18–60) in 15–19 year-olds and declined to 18 (IQR:10–41) in ≥45 year-olds. Mean daily own-household contacts was 8.8 (95%CI:8.2–9.4), which decreased with increasing age. Mean crèche/school contacts increased from 6.2/day (95%CI:2.7–9.7) in 0–4 year-olds to 28.1/day (95%CI:8.1–48.1) in 15–19 year-olds. Mean transport contacts increased from 4.9/day (95%CI:1.6–8.2) in 0–4 year-olds to 25.5/day (95%CI:12.1–38.9) in 25–29 year-olds. Conclusions A limited number of location types contributed the majority of indoor social contacts in this community. Increasing numbers of social contacts occurred throughout childhood, adolescence, and young adulthood, predominantly in school and public transport. This rapid increase in non-home socialization parallels the increasing TB infection rates during childhood and young adulthood reported in this community. Further studies of the environmental conditions in schools and public transport, as potentially important locations for ongoing TB infection, are indicated.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039246Publisher's versio

Annual Risk of Tuberculous Infection Using Different Methods in Communities with a High Prevalence of TB and HIV in Zambia and South Africa

BACKGROUND: The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated. METHODOLOGY/PRINCIPAL FINDINGS: Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates. CONCLUSIONS/SIGNIFICANCE: ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded

Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area

CITATION: Chegou, N. N. et al. 2012. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE, 7(6): e38501, doi:10.1371/journal.pone.0038501.The original publication is available at http://journals.plos.org/plosoneBackground: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. © 2012 Chegou et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038501Publisher's versio

Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study

Abstract Background South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. Methods Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI Results The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0–14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01–1.05), male gender (OR = 2.70, 95 % CI = 1.55–4.70), marital status (OR = 2.00, 95 % CI = 1.31–3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04–4.31). Conclusions The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty

Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

<p>Abstract</p> <p>Background</p> <p>Interferon gamma is a major macrophage-activating cytokine during infection with <it>Mycobacterium tuberculosis</it>, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as <it>M. tuberculosis</it>. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes.</p> <p>Methods</p> <p>Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System™, capillary electrophoresis of fluorescently labelled PCR products, TaqMan^®SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses.</p> <p>Results</p> <p>A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02), but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite.</p> <p>Conclusions</p> <p>This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.</p

Working conditions and tuberculosis mortality in England and Wales, 1890-1912:a retrospective analysis of routinely collected data

BACKGROUND: Modelling studies suggest that workplaces may be important sites of Mycobacterium tuberculosis transmission in high burden countries today. Contemporary data on tuberculosis by occupation from these settings are scarce. However, historical data on tuberculosis risk in different occupations are available and may provide insight into workplace transmission. We aimed to ascertain whether, in a high burden setting, individuals working in crowded indoor environments (exposed) had greater tuberculosis mortality than individuals employed elsewhere (unexposed). METHODS: The Registrar General's Decennial Supplements from 1890-2, 1900-2 and 1910-2 contain data on mortality from tuberculosis by occupation for men in England and Wales. In these data, the association between occupational exposure to crowded indoor environments and tuberculosis mortality was assessed using an overdispersed Poisson regression model adjusting for socioeconomic position, age and decade. RESULTS: There were 23,962 deaths from tuberculosis during 14.8 million person-years of follow-up among men working in exposed occupations and 28,483 during 19.9 million person-years of follow-up among men working in unexposed occupations. We were unable to categorise a large number of occupations as exposed or unexposed. The adjusted rate ratio for death from tuberculosis was 1.34 (95 % confidence interval 1.26-1.43) comparing men working in exposed occupations to those in unexposed occupations. CONCLUSIONS: Tuberculosis mortality in England and Wales at the turn of the 20th century was associated with occupational exposure to crowded indoor environments. The association between working conditions and TB in contemporary high burden settings requires further study

The increasing burden of asthma in South African children: A call to action

Background. Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, as well as airway reversibility. The burden of asthma in children is increasing in low- and middle-income countries and remains underrecognised and poorly managed. Objectives. To quantify the burden of asthma in the South African (SA) population and identify the risk factors associated with disease severity in the local context. Methods. The SA Childhood Asthma Working Group (SACAWG) convened in January 2017 with task groups, each headed by a section leader, constituting the editorial committee on assessment of asthma epidemiology, diagnosis, control, treatments, novel treatments and self-management plans. The epidemiology task group reviewed the available scientific literature and assigned evidence according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Conclusions. Asthma in children remains a common condition, which has shown an increasing prevalence in urban and rural populations of SA. Of concern is that almost half of children in urban communities experience severe asthma symptoms, and many asthmatics lack a formal diagnosis and thus access to treatment. Exposure to tobacco smoke and living in highly polluted areas increase the severity of wheezing in young children.S Afr Med J 201

Evaluation of the central sleep apnea in asymptomatic children with Chiari 1 malformation: an open question

INTRODUCTION: Type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to intermittent brain hypertension. In symptomatic children, central sleep apneas are shown in polysomnography evaluation. A central apnea index of 1/h or more is considered abnormal, but >5/h is clearly considered pathological. Therefore, central sleep apnea evaluation in pediatric age may show great age-related variability. METHOD AND SUBJECTS: We present three patients who were assessed by polysomnography with two different scores for central sleep apneas published in the literature: the method by Scholle (2011) and the American Academy of Sleep Medicine scoring system (2012). CONCLUSIONS: We speculated that the Scholle scoring system can be more helpful in assessing children with asymptomatic Chiari 1 malformation for a closer follow-up. More studies are needed

Risk factors for infection and disease in child contacts of multidrug-resistant tuberculosis: a cross-sectional study.

BACKGROUND: Young children exposed to Mycobacterium tuberculosis have a high risk of disease progression following infection. This study aimed to determine risk factors for M. tuberculosis infection and disease in children following exposure to adults with multidrug-resistant (MDR) tuberculosis (TB). METHODS: Cross-sectional study; all children aged < 5 years, routinely referred per local guidelines to the provincial specialist MDR-TB clinic, Western Cape Province, South Africa, following identification as contacts of adult MDR-TB source cases, were eligible for enrolment from May 2010 through April 2011. Demographic, clinical and social characteristics were collected. All children underwent HIV and tuberculin skin testing. RESULTS: Of 228 children enrolled (median age: 30 months), 102 (44.7%) were classified as infected. Of these, 15 (14.7%) had TB disease at enrolment. Of 217 children tested for HIV, 8 (3.7%) were positive. In adjusted analysis, child's age (AOR: 1.43; 95% CI: 1.13-1.91; p = 0.002) and previous TB treatment history (AOR: 2.51; 95% CI: 1.22-5.17; p = 0.01) were independent risk factors for infection. Increasing age of the MDR-TB source case (AOR: 0.67; 95% CI: 0.45-1.00; p = 0.05) was protective and source case alcohol use (AOR: 2.59; 95% CI: 1.29-5.22; p = 0.007) was associated with increased odds of infection in adjusted analysis. Decreasing age of the child (p = 0.01) and positive HIV status (AOR: 25.3; 95% CI: 1.63-393; p = 0.01) were associated with prevalent TB disease. CONCLUSION: A high proportion of children exposed to MDR-TB are infected or diseased. Early contact tracing might provide opportunities to prevent the progression to TB disease in children identified as having been exposed to MDR-TB