Community health workers can be trained to identify patients eligible for tuberculosis preventive therapy, but encounter barriers to programme implementation in KwaZulu-Natal, South Africa.

Tuberculosis (TB) remains one of the top 10 causes of death worldwide, ranking as the leading cause of death from infectious disease, above HIV and AIDS. South Africa has the sixth highest TB incidence rate in the world and the world's largest HIV epidemic. This study sought to demonstrate the feasibility of community health workers (CHWs) contributing to the implementation of tuberculosis preventive therapy (TPT) among people living with HIV and AIDS. Twelve community health workers were trained to test for communicable and non-communicable diseases and screen for TPT eligibility. They visited a select number of homes monthly to conduct screening for HIV, TB and non-communicable diseases. We recorded screening results, rates of referral for TPT, linkage to care - defined as being seen in the clinic for TPT - and treatment initiation. Among the 1 279 community members screened, 248 were identified as living with HIV, 99 (39.9%) individuals were identified as eligible for TPT, and 46 (46.5%) were referred to care. Among those referred, the median age was 39 (IQR 30-48) and 29 (63%) linked to care; 11 (37.9%) of those linked subsequently initiated treatment. In rural South Africa, it is feasible to train CHWs to identify and refer patients eligible for TPT, but losses occurred at each step of the cascade. CHWs can facilitate TPT implementation, although further implementation research exploring and addressing barriers to TPT (on an individual, provider and systems level) should be prioritised to optimise their role in rural resource-limited settings.

Natural ventilation reduces high TB transmission risk in traditional homes in rural KwaZulu-Natal, South Africa.

BACKGROUND: Transmission of drug susceptible and drug resistant TB occurs in health care facilities, and community and households settings, particularly in highly prevalent TB and HIV areas. There is a paucity of data regarding factors that may affect TB transmission risk in household settings. We evaluated air exchange and the impact of natural ventilation on estimated TB transmission risk in traditional Zulu homes in rural South Africa. METHODS: We utilized a carbon dioxide decay technique to measure ventilation in air changes per hour (ACH). We evaluated predominant home types to determine factors affecting ACH and used the Wells-Riley equation to estimate TB transmission risk. RESULTS: Two hundred eighteen ventilation measurements were taken in 24 traditional homes. All had low ventilation at baseline when windows were closed (mean ACH = 3, SD = 3.0), with estimated TB transmission risk of 55.4% over a ten hour period of exposure to an infectious TB patient. There was significant improvement with opening windows and door, reaching a mean ACH of 20 (SD = 13.1, p < 0.0001) resulting in significant decrease in estimated TB transmission risk to 9.6% (p < 0.0001). Multivariate analysis identified factors predicting ACH, including ventilation conditions (windows/doors open) and window to volume ratio. Expanding ventilation increased the odds of achieving ≥12 ACH by 60-fold. CONCLUSIONS: There is high estimated risk of TB transmission in traditional homes of infectious TB patients in rural South Africa. Improving natural ventilation may decrease household TB transmission risk and, combined with other strategies, may enhance TB control efforts.

Integrated Tuberculosis/Human Immunodeficiency Virus Community-Based Case Finding in Rural South Africa: Implications for Tuberculosis Control Efforts.

BACKGROUND: Intensive case finding is endorsed for tuberculosis (TB) control in high-risk populations. Novel case-finding strategies are needed in hard-to-reach rural populations with high prevalence of TB and human immunodeficiency virus (HIV). METHODS: We performed community-based integrated HIV and TB intensive case finding in a rural South African subdistrict from March 2010 to June 2012. We offered TB symptom screening, sputum collection for microbiologic diagnosis, rapid fingerstick HIV testing, and phlebotomy for CD4 cell count. We recorded number of cases detected and calculated population-level rates and number needed to screen (NNS) for drug-susceptible and -resistant TB. RESULTS: Among 5615 persons screened for TB at 322 community sites, 91.2% accepted concurrent HIV testing, identifying 510 (9.9%) HIV-positive individuals with median CD4 count of 382 cells/mm3 (interquartile range = 260-552). Tuberculosis symptoms were reported by 2049 (36.4%), and sputum was provided by 1033 (18.4%). Forty-one (4.0%) cases of microbiologically confirmed TB were detected for an overall case notification rate of 730/100000 (NNS = 137); 11 (28.6%) were multidrug-resistant or extensively drug-resistant TB. Only 5 (12.2%) TB cases were HIV positive compared with an HIV coinfection rate of 64% among contemporaneously registered TB cases (P = .001). CONCLUSION: Community-based integrated intensive case finding is feasible and is high yield for drug-susceptible and -resistant TB and HIV in rural South Africa. Human immunodeficiency virus-negative tuberculosis predominated in this community sample, suggesting a distinct TB epidemiology compared with cases diagnosed in healthcare facilities. Increasing HIV/TB integrated community-based efforts and other strategies directed at both HIV-positive and HIV-negative tuberculosis may contribute to TB elimination in high TB/HIV burden regions.

What motivates use of community-based human immunodeficiency virus testing in rural South Africa?

Despite substantial progress in implementing HIV testing, challenges remain in achieving widespread uptake particularly in rural resource-limited settings. We sought to understand motivations for HIV testing in a community-based HIV testing programme in rural South Africa. We conducted a questionnaire survey in participants undergoing voluntary HIV testing within an ongoing community-based integrated HIV/tuberculosis intensive case finding programme at congregate rural settings. Participants responded to a six-item non-mutually exclusive motivations survey which included the topics of feeling ill, recent HIV exposure, risky lifestyle, illness in a family member, and pregnancy. Among 2068 respondents completing the survey, 1393 (67.4%) were women, median age was 40 years (IQR 19-56), and 1235 (59.7%) were first-time testers. Among all testers, 142 (6.9%) were HIV-positive with median CD4 count was 346 cells/mm(3) (IQR 218-542). Community-based testing for HIV is acceptable and meets the needs of community members in rural South Africa. Motivations for HIV testing at the community level are complex and differ according to gender, age, site of community testing, and HIV status. These differences can be utilised to improve the focus and yield of community-based HIV screening.

Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa.

The WHO recommends integrating interventions to address the devastating TB/HIV co-epidemics in South Africa, yet integration has been poorly implemented and TB/HIV control efforts need strengthening. Identifying infected individuals is particularly difficult in rural settings. We used mathematical modeling to predict the impact of community-based, integrated TB/HIV case finding and additional control strategies on South Africa's TB/HIV epidemics. We developed a model incorporating TB and HIV transmission to evaluate the effectiveness of integrating TB and HIV interventions in rural South Africa over 10 years. We modeled the impact of a novel screening program that integrates case finding for TB and HIV in the community, comparing it to status quo and recommended TB/HIV control strategies, including GeneXpert, MDR-TB treatment decentralization, improved first-line TB treatment cure rate, isoniazid preventive therapy, and expanded ART. Combining recommended interventions averted 27% of expected TB cases (95% CI 18-40%) 18% HIV (95% CI 13-24%), 60% MDR-TB (95% CI 34-83%), 69% XDR-TB (95% CI 34-90%), and 16% TB/HIV deaths (95% CI 12-29). Supplementing these interventions with annual community-based TB/HIV case finding averted a further 17% of TB cases (44% total; 95% CI 31-56%), 5% HIV (23% total; 95% CI 17-29%), 8% MDR-TB (68% total; 95% CI 40-88%), 4% XDR-TB (73% total; 95% CI 38-91%), and 8% TB/HIV deaths (24% total; 95% CI 16-39%). In addition to increasing screening frequency, we found that improving TB symptom questionnaire sensitivity, second-line TB treatment delays, default before initiating TB treatment or ART, and second-line TB drug efficacy were significantly associated with even greater reductions in TB and HIV cases. TB/HIV epidemics in South Africa were most effectively curtailed by simultaneously implementing interventions that integrated community-based TB/HIV control strategies and targeted drug-resistant TB. Strengthening existing TB and HIV treatment programs is needed to further reduce disease incidence.

Survival from XDR-TB is associated with modifiable clinical characteristics in rural South Africa.

BACKGROUND: Drug-resistant tuberculosis (TB) is a major threat to global public health. Patients with extensively drug-resistant TB (XDR-TB), particularly those with HIV-coinfection, experience high and accelerated mortality with limited available interventions. To determine modifiable factors associated with survival, we evaluated XDR-TB patients from a community-based hospital in rural South Africa where a large number of XDR-TB cases were first detected. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective case control study was conducted of XDR-TB patients diagnosed from 2005-2008. Survivors, those alive at 180 days from diagnostic sputum collection date, were compared with controls who died within 180 days. Clinical, laboratory and microbiological correlates of survival were assessed in 69 survivors (median survival 565 days [IQR 384-774] and 73 non-survivors (median survival 34 days [IQR 18-90]). Among 129 HIV+ patients, multivariate analyses of modifiable factors demonstrated that negative AFB smear (AOR 8.4, CI 1.84-38.21), a lower laboratory index of routine laboratory findings (AOR 0.48, CI 0.22-1.02), CD4>200 cells/mm(3) (AOR 11.53, 1.1-119.32), and receipt of antiretroviral therapy (AOR 20.9, CI 1.16-376.83) were independently associated with survival from XDR-TB. CONCLUSIONS/SIGNIFICANCE: Survival from XDR-TB with HIV-coinfection is associated with less advanced stages of both diseases at time of diagnosis, absence of laboratory markers indicative of multiorgan dysfunction, and provision of antiretroviral therapy. Survival can be increased by addressing these modifiable risk factors through policy changes and improved clinical management. Health planners and clinicians should develop programmes focusing on earlier case finding and integration of HIV and drug-resistant TB diagnostic, therapeutic, and preventive activities.

Robust scale-up of dead end filtration: impact of filter fouling mechanisms and flow distribution.

Robust design of a dead end filtration step and the resulting performance at manufacturing scale relies on laboratory data collected with small filter units. During process development it is important to characterize and understand the filter fouling mechanisms of the process streams so that an accurate assessment can be made of the filter area required at manufacturing scale. Successful scale-up also requires integration of the lab-scale filtration data with an understanding of flow characteristics in the full-scale filtration equipment. A case study is presented on the development and scale-up of a depth filtration step used in a 2nd generation polysaccharide vaccine manufacturing process. The effect of operating parameters on filter performance was experimentally characterized for a diverse set of process streams. Filter capacity was significantly reduced when operating at low fluxes, caused by both low filtration pressure and high stream viscosity. The effect of flux on filter capacity could be explained for a variety of diverse streams by a single mechanistic model of filter fouling. To complement the laboratory filtration data, the fluid flow and distribution characteristics in manufacturing-scale filtration equipment were carefully evaluated. This analysis identified the need for additional scale-up factors to account for non-uniform filter area usage in large-scale filter housings. This understanding proved critical to the final equipment design and depth filtration step definition, resulting in robust process performance at manufacturing scale.