Carl Morrow

Nutrient concentration ratios and co-limitation in South African grasslands

*Assessing plant nutrient limitation is a fundamental part of understanding grassland dynamics. The ratio of concentrations of nitrogen (N) and phosphorus (P) in vegetation has been proposed as an index of the relative limitation of biomass production by N and P, but its utility has not been tested well in grasslands. *At five sites in Kruger National Park, South Africa, across soil and precipitation contrasts, N and P were added in a factorial design to grass-dominated plots. *Although the N:P ratio of unfertilized vegetation across all sites (5.8) would have indicated that production was N-limited, aboveground production was consistently co-limited by N and P. Aboveground production was still greater in plots fertilized with N and P than in those fertilized with just N, but the N:P ratio did not exceed standard thresholds for P limitation in N-fertilized vegetation. Comparisons among sites showed little pattern between site N:P ratio and relative responses to N and P. *When combined with results from other grassland fertilization studies, these data suggest that the N:P ratio of grasses has little ability to predict limitation in upland grasslands. Co-limitation between N and P appears to be much more widespread than would be predicted from simple assumptions of vegetative N:P ratios.

Molecular Epidemiology of Mycobacterium tuberculosis in a South African Community with High HIV Prevalence

To explore the relationship between human immunodeficiency virus (HIV) and Mycobacterium tuberculosis genotypes, we performed IS6110-based restriction fragment-length polymorphism analysis on M. tuberculosis culture specimens from patients with smear-positive tuberculosis in a periurban community in South Africa from 2001 through 2005. Among 151 isolates, 95 strains were identified within 26 families, with 54% clustering. HIV status was associated with W-Beijing strains (P = .009) but not with clustering per se. The high frequency of clustering suggests ongoing transmission in both HIV-negative and HIV-positive individuals in this community. The strong association between W-Beijing and HIV infection may have important implications for tuberculosis control.

Social Mixing Patterns Within a South African Township Community: Implications for Respiratory Disease Transmission and Control

A prospective survey of social mixing patterns relevant to respiratory disease transmission by large droplets (e.g., influenza) or small droplet nuclei (e.g., tuberculosis) was performed in a South African township in 2010. A total of 571 randomly selected participants recorded the numbers, times, and locations of close contacts (physical/nonphysical) and indoor casual contacts met daily. The median number of physical contacts was 12 (interquartile range (IQR), 7-18), the median number of close contacts was 20 (IQR, 13-29), and the total number of indoor contacts was 30 (IQR, 12-54). Physical and close contacts were most frequent and age-associative in youths aged 5-19 years. Numbers of close contacts were 40% higher than in corresponding populations in industrialized countries (P < 0.001). This may put township communities at higher risk for epidemics of acute respiratory illnesses. Simulations of an acute influenza epidemic predominantly involved adolescents and young adults, indicating that control strategies should be directed toward these age groups. Of all contacts, 86.2% occurred indoors with potential exposure to respiratory droplet nuclei, of which 27.2%, 20.1%, 20.0%, and 8.0% were in transport, own household, crèche/school, and work locations, respectively. Indoor contact time was long in households and short during transport. High numbers of indoor contacts and intergenerational mixing in households and transport may contribute to exceptionally high rates of tuberculosis transmission reported in the community.

Antiretroviral therapy and TB notification rates in a high HIV prevalence South African community.

Background: Antiretroviral therapy (ART) has been proposed as an intervention for reducing tuberculosis (TB) burdens in areas with high HIV prevalence. However, little data is available on the impact of ART on population-level TB. Methods: Trends in adult TB case fatality and notifications were assessed before and during increasing ART coverage in a well-defined periurban community, from 1997 to 2008. Mean changes in TB rates were measured using linear autoregression models. ART coverage increased from 1% in 2003 to 5%, 13%, and 21% of HIV-infected population in 2004, 2005, and 2008, respectively. Results: From 1997 to end of 2004 TB notification rates increased by an average of 187 cases/100,000/year (P < 0.001), reaching a peak of 2536/100,000 in 2005. From 2005 to 2008, TB notification rates declined by approximately 202 cases/100,000/year (P < 0.001). TB rates were initially stable in HIV-uninfected individuals, but declined moderately from 2005. TB rates declined in HIV-infected adults from 6513/100,000 in 2005 to 4741/100,000 in 2008. The predominant decline in TB notifications occurred among HIV-infected patients receiving ART (1156 cases/100,000/year) and was less marked in those not receiving ART (416cases/100,000/year). Similarly, TB case fatality was constant for HIV-uninfected individuals, but declined in HIV-infected individuals from 23% in 2002 to 8% in 2008 (P = 0.01). Conclusions: In this community heavily affected by both HIV and TB epidemics, rapid and high ART coverage was associated with significant reductions in TB notifications and TB-associated case fatality.

Modeling the role of public transportation in sustaining tuberculosis transmission in South Africa.

Current tuberculosis notification rates in South Africa are among the highest ever recorded. Although the human immunodeficiency virus epidemic has been a critical factor, the density of respiratory contacts in high-risk environments may be an important and underappreciated driver. Using a modified Wells-Riley model for airborne disease transmission, we estimated the risk of tuberculosis transmission on 3 modes of public transit (minibus taxis, buses, and trains) in Cape Town, South Africa, using exhaled carbon dioxide as a natural tracer gas to evaluate air exchange. Carbon dioxide measurements were performed between October and December of 2011. Environmental risk, reflected in the rebreathed fraction of air, was highest in minibus taxis and lowest in trains; however, the average number of passengers sharing an indoor space was highest in trains and lowest in minibus taxis. Among daily commuters, the annual risk of tuberculosis infection was projected to be 3.5%-5.0% and was highest among minibus taxi commuters. Assuming a duration of infectiousness of 1 year, the basic reproductive number attributable to transportation was more than 1 in all 3 modes of transportation. Given its poor ventilation and high respiratory contact rates, public transportation may play a critical role in sustaining tuberculosis transmission in South African cities.

Childhood tuberculosis infection and disease: A spatial and temporal transmission analysis in a South African township

BACKGROUND Tuberculosis (TB) remains a leading cause of mortality and morbidity in South Africa. While adult TB results from both recent and past infection, childhood TB results from recent infection and reflects ongoing transmission 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 2 106/100 000 and the rate in children aged < 15 years ranged between 664/100 000 and 1 044/100 000. The mean number of exposures to adult TB for TB-uninfected children, latently TB-infected children and TB cases were 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 the adult TB case to which the child was exposed, and 36% of child TB cases were diagnosed before 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 could also facilitate targeted active case finding, which may provide an adjunct to currently failing TB control strategies.

Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township

BackgroundDelays 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.MethodsIn 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.ResultsAmong 893 TB patients studied (median CD4 count, 81 cells/μL), 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/μL 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).ConclusionsDelays 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.

Integrating social contact and environmental data in evaluating tuberculosis transmission in a South African township

BACKGROUND Population models of tuberculosis transmission have not accounted for social contact structure and the role of the environment in which tuberculosis is transmitted. METHODS We utilized extensions to the Wells-Riley model of tuberculosis transmission, using exhaled carbon dioxide as a tracer gas, to describe transmission patterns in an endemic community. Drawing upon social interaction data and carbon dioxide measurements from a South African township, we created an age-structured model of tuberculosis transmission in households, public transit, schools, and workplaces. We fit the model to local data on latent tuberculosis prevalence by age. RESULTS Most tuberculosis infections (84%) were estimated to occur outside of ones own household. Fifty percent of infections among young adults (ages 15-19) occurred in schools, due to high contact rates and poor ventilation. Despite lower numbers of contacts in workplaces, assortative mixing among adults with high rates of smear-positive tuberculosis contributed to transmission in this environment. Households and public transit were important sites of transmission between age groups. CONCLUSIONS Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission.

Indoor social networks in a South African township: potential contribution of location to tuberculosis transmission.

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.

Time to Initiation of Antiretroviral Therapy Among Patients With HIV-Associated Tuberculosis in Cape Town, South Africa

We studied the time interval between starting tuberculosis treatment and commencing antiretroviral treatment (ART) in HIV-infected patients (n = 1433; median CD4 count 71 cells per microliter, interquartile range: 32-132) attending 3 South African township ART services between 2002 and 2008. The overall median delay was 2.66 months (interquartile range: 1.58-4.17). In adjusted analyses, delays varied between treatment sites but were shorter for patients with lower CD4 counts and those treated in more recent calendar years. During the most recent period (2007-2008), 4.7%, 19.7%, and 51.1% of patients started ART within 2, 4, and 8 weeks of tuberculosis treatment, respectively. Operational barriers must be tackled to permit further acceleration of ART initiation as recommended by 2010 WHO ART guidelines.