Browsing by Author "Morrow, Carl"

Now showing 1 - 8 of 8
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    Childhood tuberculosis infection and disease: A spatial and temporal transmission analysis in a South African township
    (2009) Middelkoop, Keren; Bekker, Linda-Gail; Morrow, Carl; Zwane, Eugene; Wood, Robin
    Background. Tuberculosis (TB) remains a leading cause of South African mortality and morbidity. While adult TB arises from both recent and prior infection, childhood TB results from recent infection and reflects ongoing transmission occurring despite current TB control strategies. Setting. A South African community with high rates of TB and HIV disease. Outcomes. A Geographic Information System was used to spatially and temporally define the relationships between TB exposure, infection and disease in children <15 years of age, with exposure to adult HIV-positive and HIV-negative TB disease on residential plots between 1997 and 2007. Results. During the study period the annual adult TB notification rate increased from 629 to 2106/100,000 and <15yrs TB notification rate ranged between 664/100,000 and 1044/100,000. The mean exposure to adult TB for uninfected children, TB-infected, TB cases was 5.1%, 5.4% and 33% per annum and the mean number of adult smear-positive cases per exposed child was 1.0, 1.6 and 1.9 respectively. Acquisition of TB infection was not associated with HIV status of adult exposure TB case and 36% of child TB cases were diagnosed prior to the temporally closest adult case on their plot. Conclusions. Childhood infection and disease were quantitatively linked to infectious adult TB prevalence in an immediate social network. Childhood infection should be monitored in high burden settings as a marker of ongoing TB transmission. Improved knowledge of township childhood and adult social networks may also facilitate targeted active case finding, which may provide an adjunct to presently failing TB control strategies.
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    Decreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township
    (BioMed Central Ltd, 2014) Middelkoop, Keren; Bekker, Linda-Gail; Morrow, Carl; Lee, Namee; Wood, Robin
    BACKGROUND: Tuberculosis (TB) transmission rates are exceptionally high in endemic TB settings. Adolescence represents a period of increasing TB infection and disease but little is known as to where adolescents acquire TB infection. We explored the relationship between residential exposure to adult TB cases and infection in children and adolescents in a South African community with high burdens of TB and HIV. METHODS: TB infection data were obtained from community, school-based tuberculin skin test (TST) surveys performed in 2006, 2007 and 2009. A subset of 2007 participants received a repeat TST in 2009, among which incident TB infections were identified. Using residential address, all adult TB cases notified by the community clinic between 1996 and 2009 were cross-referenced with childhood and adolescent TST results. Demographic and clinic data including HIV status were abstracted for TB cases. Multivariate logistic regression models examined the association of adult TB exposure with childhood and adolescent prevalent and incident TB infection. RESULTS: Of 1,100 children and adolescents included in the prevalent TB infection analysis, 480 (44%) were TST positive and 651 (59%) were exposed to an adult TB case on their residential plot. Prevalent TB infection in children aged 5-9 and 10-14 years was positively associated with residential exposure to an adult TB case (odds ratio [OR]:2.0; 95% confidence interval [CI]: 1.1-3.6 and OR:1.5; 95% CI: 1.0-2.3 respectively), but no association was found in adolescents [greater than or equal to]15years (OR:1.4; 95% CI: 0.9-2.0). HIV status of adult TB cases was not associated with TB infection (p=0.62). Of 67 previously TST negative children, 16 (24%) converted to a positive TST in 2009. These incident infections were not associated with residential exposure to an adult TB case (OR: 1.9; 95% CI: 0.5-7.3). CONCLUSIONS: TB infection among young children was strongly associated with residential exposure to an adult TB case, but prevalent and incident TB infection in adolescents was not associated with residential exposure. The HIV-status of adult TB cases was not a risk factor for transmission. The high rates of TB infection and disease among adolescents underscore the importance of identifying where infection occurs in this age group.
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    Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township
    (BioMed Central Ltd, 2011) Lawn, Stephen; Campbell, Lucy; Kaplan, Richard; Little, Francesca; Morrow, Carl; Wood, Robin; IeDEA-Southern Africa
    BACKGROUND: Delays in the initiation of antiretroviral therapy (ART) in patients with HIV-associated tuberculosis (TB) are associated with increased mortality risk. We examined the timing of ART among patients receiving care provided by non-integrated TB and ART services in Cape Town, South Africa. METHODS: In an observational cohort study, we determined the overall time delay between starting treatment for TB and starting ART in patients treated in Gugulethu township between 2002 and 2008. For patients referred from TB clinics to the separate ART clinic, we quantified and identified risk factors associated with the two component delays between starting TB treatment, enrolment in the ART clinic and subsequent initiation of ART. RESULTS: Among 893 TB patients studied (median CD4 count, 81 cells/muL), the delay between starting TB treatment and starting ART was prolonged (median, 95 days; IQR = 49-155). Delays were shorter in more recent calendar periods and among those with lower CD4 cell counts. However, the median delay was almost three-fold longer for patients referred from separate TB clinics compared to patients whose TB was diagnosed in the ART clinic (116 days versus 41 days, respectively; P < 0.001). In the most recent calendar period, the proportions of patients with CD4 cell counts < 50 cells/muL who started ART within 4 weeks of TB diagnosis were 11.1% for patients referred from TB clinics compared to 54.6% of patients with TB diagnosed in the ART service (P < 0.001). CONCLUSIONS: Delays in starting ART were prolonged, especially for patients referred from separate TB clinics. Non-integration of TB and ART services is likely to be a substantial obstacle to timely initiation of ART.
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    Indoor social networks in a South African township: potential contribution of location to tuberculosis transmission
    (Public Library of Science, 2012) Wood, Robin; Racow, Kimberly; Bekker, Linda-Gail; Morrow, Carl; Middelkoop, Keren; Mark, Daniella; Lawn, Stephen D
    BACKGROUND: 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.
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    Quantification of shared air: a social and environmental determinant of airborne disease transmission
    (Public Library of Science, 2014) Wood, Robin; Morrow, Carl; Ginsberg, Samuel; Piccoli, Elizabeth; Kalil, Darryl; Sassi, Angelina; Walensky, Rochelle P; Andrews, Jason R
    BACKGROUND: Tuberculosis is endemic in Cape Town, South Africa where a majority of the population become tuberculosis infected before adulthood. While social contact patterns impacting tuberculosis and other respiratory disease spread have been studied, the environmental determinants driving airborne transmission have not been quantified. METHODS: Indoor carbon dioxide levels above outdoor levels reflect the balance of exhaled breath by room occupants and ventilation. We developed a portable monitor to continuously sample carbon dioxide levels, which were combined with social contact diary records to estimate daily rebreathed litres. A pilot study established the practicality of monitor use up to 48-hours. We then estimated the daily volumes of air rebreathed by adolescents living in a crowded township. RESULTS: One hundred eight daily records were obtained from 63 adolescents aged between 12- and 20-years. Forty-five lived in wooden shacks and 18 in brick-built homes with a median household of 4 members (range 2-9). Mean daily volume of rebreathed air was 120.6 (standard error: 8.0) litres/day, with location contributions from household (48%), school (44%), visited households (4%), transport (0.5%) and other locations (3.4%). Independent predictors of daily rebreathed volumes included household type (p = 0.002), number of household occupants (p = 0.021), number of sleeping space occupants (p = 0.022) and winter season (p<0.001). CONCLUSIONS: We demonstrated the practical measurement of carbon dioxide levels to which individuals are exposed in a sequence of non-steady state indoor environments. A novel metric of rebreathed air volume reflects social and environmental factors associated with airborne infection and can identify locations with high transmission potential.
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    Real-time investigation of tuberculosis transmission: developing the Respiratory Aerosol Sampling Chamber (RASC)
    (Public Library of Science, 2016) Wood, Robin; Morrow, Carl; III, Clifton E Barry; Bryden, Wayne A; Call, Charles J; Hickey, Anthony J; Rodes, Charles E; Scriba, Thomas J; Blackburn, Jonathan; Issarow, Chacha; Mulder, Nicola; Woodward, Jeremy; Moosa, Atica; Singh, Vinayak; Mizrahi, Valerie; Warner, Digby F
    Knowledge of the airborne nature of respiratory disease transmission owes much to the pioneering experiments of Wells and Riley over half a century ago. However, the mechanical, physiological, and immunopathological processes which drive the production of infectious aerosols by a diseased host remain poorly understood. Similarly, very little is known about the specific physiological, metabolic and morphological adaptations which enable pathogens such as Mycobacterium tuberculosis ( Mtb ) to exit the infected host, survive exposure to the external environment during airborne carriage, and adopt a form that is able to enter the respiratory tract of a new host, avoiding innate immune and physical defenses to establish a nascent infection. As a first step towards addressing these fundamental knowledge gaps which are central to any efforts to interrupt disease transmission, we developed and characterized a small personal clean room comprising an array of sampling devices which enable isolation and representative sampling of airborne particles and organic matter from tuberculosis (TB) patients. The complete unit, termed the Respiratory Aerosol Sampling Chamber (RASC), is instrumented to provide real-time information about the particulate output of a single patient, and to capture samples via a suite of particulate impingers, impactors and filters. Applying the RASC in a clinical setting, we demonstrate that a combination of molecular and microbiological assays, as well as imaging by fluorescence and scanning electron microscopy, can be applied to investigate the identity, viability, and morphology of isolated aerosolized particles. Importantly, from a preliminary panel of active TB patients, we observed the real-time production of large numbers of airborne particles including Mtb , as confirmed by microbiological culture and polymerase chain reaction (PCR) genotyping. Moreover, direct imaging of captured samples revealed the presence of multiple rod-like Mtb organisms whose physical dimensions suggested the capacity for travel deep into the alveolar spaces of the human lung.