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.

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.

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.

SummaryCommunity-based integrated tuberculosis(TB)/human immunodeficiency virus (HIV) case finding demonstrates high yield for TB and HIV; a high proportion with drug resistance, without prior treatment; and the majority of tuberculosis in HIV-negative individuals, potentially representing a reservoir that is perpetuating the TB epidemic.

BackgroundDrug-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 FindingsA 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/mm3 (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/SignificanceSurvival 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.

In the United States, approximately 25% of people with HIV (PWH) are co-infected with hepatitis C (HCV). Since 2014, highly effective and well-tolerated direct-acting antivirals (DAAs) have revolutionized HCV treatment. Uptake of DAAs by people with HIV/HCV co-infection has improved but remains suboptimal due to system, provider, and patient-level barriers. To explore patient-level issues by better understanding their attitudes towards DAA treatment, we conducted qualitative interviews with 21 persons with HIV/HCV co-infection who did not consent to DAA treatment or delayed treatment for at least 1 year after diagnosis. We found PWH perceived DAA treatment barriers and facilitators on multiple levels of the social-ecological environment: the individual (HCV disease and treatment literacy), interpersonal (peer influence), institutional (media and healthcare provider relationship), and structural levels (treatment cost and adherence support). Recommendations to improve DAA treatment uptake include HCV-treatment adherence support, HCV disease and treatment literacy training (particularly for substance use and DAA treatment interactions), and encouraging PWH who have successfully completed DAA treatment to speak with their peers.

Despite substantial progress in implementing human immunodeficiency virus testing, challenges remain in achieving widespread uptake particularly in rural resource-limited settings. We sought to understand motivations for human immunodeficiency virus testing in a community-based human immunodeficiency virus testing programme in rural South Africa. We conducted a questionnaire survey in participants undergoing voluntary human immunodeficiency virus testing within an ongoing community-based integrated human immunodeficiency virus/TB 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 HV 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 human immunodeficiency virus-positive with median CD4 count 346 (IQR 218–542). Community-based testing for human immunodeficiency virus is acceptable and meets the needs of community members in rural South Africa. Motivations for human immunodeficiency virus testing at the community level are complex and differ according to gender, age, site of community testing, and human immunodeficiency virus status. These differences can be utilised to improve the focus and yield of community-based human immunodeficiency virus screening.

Objectives: Highly effective direct-acting antiviral medications have made it feasible to achieve elimination of hepatis C virus (HCV), including for people with HIV and HCV coinfection. The Centers for Disease Control and Prevention offers guidance for a laboratory surveillance–based HCV viral clearance cascade, which allows public health departments to track the outcomes of people with HCV based on the following steps: ever infected, virally tested, initial infection, and cured or cleared. We examined the feasibility of this approach among people with HIV and HCV coinfection in Connecticut. Methods: We matched an HIV surveillance database, which included cases from the enhanced HIV/AIDS Reporting System as of December 31, 2019, and the HCV surveillance database, the Connecticut Electronic Disease Surveillance System, to define a cohort of coinfected people. We used HCV laboratory results obtained from January 1, 2016, through August 3, 2020, to determine HCV status. Results: Of 1361 people who were ever infected with HCV as of December 31, 2019, 1256 (92.3%) received HCV viral testing, 865 of 1256 people tested (68.9%) were HCV infected, and 336 of 865 infected people (38.8%) were cleared or cured. People who had undetectable HIV viral loads at most recent HIV test (<200 copies/mL) were more likely than those with detectable HIV viral loads to achieve HCV cure ( P = .02). Conclusions: A surveillance-based approach that includes data based on the Centers for Disease Control and Prevention HCV viral clearance cascade is feasible to implement, can help track population-level outcomes longitudinally, and can help identify gaps to inform HCV elimination strategies.