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.

Structural barriers to implementing recommended tuberculosis preventive treatment in primary care clinics in rural South Africa.

The World Health Organization (WHO) recommends tuberculosis preventive treatment (TPT) in people with HIV (PWH), yet implementation remains poor, especially in rural communities. We examined factors influencing TPT initiation in PWH on antiretroviral therapy (ART) in rural South Africa using the Promoting Action on Research Implementation in Health Services (PARiHS) framework to identify contextual factors and facilitation strategies to successfully implement TPT. Patient and clinical factors were extracted from medical records at two primary healthcare clinics (PHCs). Among 455 TPT eligible indivdiuals, only 263 (57.8%) initiated TPT. Patient-level characteristics (older age and symptoms of fever or weight loss) were significantly associated with TPT initiation in bivariate analysis, but PHC was the only independent correlate of TPT initiation (aOR: 2.24; 95% CI: 1.49-3.38). Clinic-level factors are crucial targets for implementing TPT to reduce the burden of HIV-associated TB. Gaps in knowledge of HCW, staff shortages, and non-integrated HIV/TB services were identified barriers to TPT implementation. Evidence-based strategies for facilitating TPT implementation that might be under-prioritized include ongoing reprioritization, expanding training for primary care providers, and quality improvement strategies (organisational changes, multidisciplinary teams, and monitoring and feedback). Addressing contextual barriers through these facilitation strategies may improve future TPT implementation in this setting.

Community-based referral for tuberculosis preventive therapy is effective for treatment completion.

Expansion of tuberculous preventive therapy (TPT) is essential to curb TB incidence and mortality among people with HIV (PWH), yet implementation has been slow. Innovative strategies to operationalize TPT are urgently needed. Here we present an evaluation of community-based identification and referral of PWH on completion of a six-month course of isoniazid in a highly prevalent region in rural South Africa. Using a community-based TB/HIV intensive case finding strategy, a team of nurses and lay workers identified community members with HIV who were without fever, night sweats, weight loss, or cough and referred them to the government primary care clinics for daily oral isoniazid, the only available TPT regimen. We measured monthly adherence and six-month treatment completion in the community-based identification and referral (CBR) group compared to those already engaged in HIV care. Adherence was measured by self-report and urine isoniazid metabolite testing. A multivariable analysis was performed to identify independent predictors of TPT completion. Among 240 participants, 81.7% were female, median age 35 years (IQR 30-44), and 24.6% had previously been treated for TB. The median CD4 count in the CBR group was 457 (IQR 301-648), significantly higher than the clinic-based comparison group median CD4 of 344 (IQR 186-495, p<0.001). Independent predictors of treatment completion included being a woman (aOR 2.41, 95% 1.02-5.72) and community-based identification and referral for TPT (aOR 2.495, 95% 1.13-5.53). Among the CBR group, treatment completion was 90.0%, an absolute 10.8% higher than the clinic-based comparison group (79.2%, p = 0.02). Adherence was significantly greater in the CBR group than the clinic-based comparison group, as measured by self-report (p = 0.02) and urine isoniazid testing (p = 0.01). Among those not on ART at baseline, 10% of eligible PWH subsequently initiated ART. Community members living with HIV in TB endemic regions identified and referred for TPT demonstrated higher treatment completion and adherence compared to PWH engaged for TPT while receiving clinic-based care. Community-based identification and referral is an innovative adjunctive strategy to facilitate implementation of TB preventive therapy in people living with HIV.

Feasibility of a community-based delivery model for HIV pre-exposure prophylaxis among bar patrons in rural South Africa.

INTRODUCTION: South Africa, home to the world's largest HIV epidemic, has made great strides in improving access to HIV services, but specific groups, particularly young men, remain difficult to engage in the HIV care cascade. Alcohol use disorder, prevalent in South Africa, further complicates engagement. Congregate settings where alcohol is served, known as shebeens, are an ideal place to engage young people for HIV testing, treatment and prevention, including pre-exposure prophylaxis (PrEP). Here, we characterize the uptake of PrEP in shebeen patrons and explore the effect of alcohol consumption on PrEP uptake by piloting a community-based delivery model. METHODS: In the rural Kwazulu-Natal province (KZN) of South Africa, a field team made up of all men offered screenings outside of shebeens at 27 events over 6 months in 2020. Screenings included rapid HIV testing and Alcohol Use Disorder Identification Test (AUDIT). Participants who tested negative for HIV were offered PrEP as once daily oral tenofovir disoproxil fumarate/emtricitabine. Short-term retention was determined. Logistic regression was performed to identify predictors of PrEP uptake, including unadjusted and adjusted odds ratios (OR) with 95% confidence interval. RESULTS: One hundred and sixty-two shebeen patrons were screened, and 136 (84%) were eligible for PrEP. Among those eligible, 37 (27%) completed clinical evaluation and initiated PrEP. Among PrEP initiators, 91.9% were men, median age was 26.0 years (interquartile range 21-31), 32.4% were employed, 18.9% had running water and 70.3% had AUDIT scores indicating hazardous drinking. Among 37 initiators, 25 (68%) were retained at 1 month, and 19 (51%) were retained at 4 months. Independent predictors of PrEP uptake among all bar patrons, and only men (108 screened and 34 initiators), included younger age (OR 0.92 [0.88-0.97]) and lifetime number of sexual partners (OR 1.07 [1.02-1.13]). CONCLUSIONS: Community-based PrEP delivery after engagement at shebeens in rural South Africa is a feasible and novel approach to reach a traditionally difficult-to-engage population, particularly young men. In this small sample, sexual risk behaviours predicted PrEP uptake. Hazardous drinking was not a barrier to PrEP initiation.

Factors associated with low tuberculosis preventive therapy prescription rates among health care workers in rural South Africa.

BACKGROUND: Despite extensive rollout of tuberculosis preventive therapy (TPT) in South Africa to reduce the incidence of tuberculosis among people living with HIV (PWH), rates of initiation and completion have remained suboptimal. OBJECTIVE: This study aimed to identify factors associated with low TPT prescription rates among health care workers (HCWs) in rural South Africa. METHODS: A cross-sectional study was conducted using an anonymous 39-item questionnaire guided by the Consolidated Framework for Implementation Research (CFIR). HCWs from a government district hospital and 14 primary healthcare clinics (PHCs) in the rural Msinga sub-district of KwaZulu-Natal were surveyed from November 2019 to January 2020. Self-reported data on prescription rates as well as knowledge, attitudes, beliefs, and practices regarding isoniazid preventative therapy, the current TPT regimen, were obtained. Factor analysis and logistic regression were used to determine associations with low prescription rates (< 50% of PWH) for TPT prescribers, and results were placed within CFIR-driven context. RESULTS: Among 160 HCWs, the median (IQR) age was 39 (33-46) years, 76% were women, 78% worked at a PHC, and 44% had experience prescribing TPT. On multivariable analysis, prescribers (n = 71) who believed their patients would not disclose TPT use to others were significantly less likely to prescribe TPT (aOR 4.19 95% CI 1.35-13.00; p = 0.01). Inadequate isoniazid supplies trended towards significance (aOR 10.10 95% CI 0.95-106.92; p = 0.06) in association with low prescription rates. CONCLUSIONS: Strengthening HCW training to emphasize TPT prescription to all eligible PWH regardless of beliefs about patient disclosure and ensuring a consistent isoniazid supply at the health systems-level are both critical steps to enhancing TPT implementation in rural South Africa.

Mobility and structural barriers in rural South Africa contribute to loss to follow up from HIV care.

Retention in HIV care is crucial to sustaining viral load suppression, and reducing HIV transmission, yet loss to follow-up (LTFU) in South Africa remains substantial. We conducted a mixed methods evaluation in rural South Africa to characterize ART disengagement in neglected rural settings. Using convenience sampling, surveys were completed by 102 PLWH who disengaged from ART (minimum 90 days) and subsequently resumed care. A subset (n = 60) completed individual in-depth interviews. Median duration of ART discontinuation was 9 months (IQR 4-22). Participants had HIV knowledge gaps regarding HIV transmission and increased risk of tuberculosis. The major contributors to LTFU were mobility and structural barriers. PLWH traveled for an urgent family need or employment, and were not able to collect ART while away. Structural barriers included inability to access care, due to lack of financial resources to reach distant clinics. Other factors included dissatisfaction with care, pill fatigue, lack of social support, and stigma. Illness was the major precipitant of returning to care. Mobility and structural barriers impede longitudinal HIV care in rural South Africa, threatening the gains made from expanded ART access. To achieve 90-90-90, future interventions, including emphasis on patient centered care, must address barriers relevant to rural settings.

'PrEP should be for men only': Young heterosexual men's views on PrEP in rural South Africa.

BACKGROUND: Gaps persist in HIV testing, treatment, and prevention services for men, leading to higher attributable mortality compared to women. We sought to characterise HIV prevention knowledge, risk behaviours, and interest in pre-exposure prophylaxis (PrEP) among young men in rural South Africa. METHODS: We conducted interviews with HIV-negative heterosexual men which were thematically analysed to identify key themes. RESULTS: Among 31 participants, median age was 26 (IQR23-31), 77% were unemployed, 52% reported previous STI, 84% reported casual sexual partners. Men acknowledged inconsistent condom use with multiple partners, reporting high-risk sexual behaviour despite recognised risk. Mistrust between partners was common. Respondents reported willingness to take PrEP to protect themselves and their partner, though anticipated stigma and structural barriers. Men worried that if their female partner had PrEP, she would become sexually active with others. CONCLUSIONS: In rural South Africa, young heterosexual men acknowledged high HIV-risk behaviour, expressed concern about acquiring HIV, and recognised the value of PrEP. Men were often not supportive of their female partners taking PrEP. Implementing HIV prevention services needs to incorporate young men's perspectives and may require gender-specific interventions, including addressing stigma, differentiated service delivery models such as community-based services or adapting facility services to target men.

Perceptions of HIV Preexposure Prophylaxis Among Young Pregnant Women from Rural KwaZulu-Natal, South Africa.

Young sub-Saharan women are at particularly high risk of HIV acquisition during pregnancy and the postpartum period and would potentially benefit from preexposure prophylaxis (PrEP). From June to August 2016, we interviewed 187 HIV negative pregnant women 18-24 years old in Tugela Ferry, Kwazulu-Natal province, a rural and among the poorest subdistricts in South Africa. Demographic data, HIV and PrEP knowledge, HIV risk, and readiness for oral tenofovir-based PrEP were collected using an information-motivation-behavior model-formatted instrument. Mean age was 20.3 years, 179 (95.7%) were unemployed, and 137 (73.3%) reported sex with one partner in the last month. Most were concerned that their sexual partner (95.2%) potentially had HIV or had other sexual partners in the last month (36.4%). Despite this, only 7 (3.7%) women reported that condoms had been used consistently during sex; most (97.3%) felt powerless to negotiate condom use with their partner. There was widespread interest in taking PrEP (97.3%), and most women (>97%) reported possessing the skills to take pills regularly, would commit to monthly visits, and were motivated to remain HIV negative to take care of their families. Young pregnant rural South African women are cognizant of their HIV risk and interested in prevention. Impending motherhood may portend increased interest in HIV prevention. We identified three potential obstacles to successful PrEP rollout among young pregnant women: hesitation about PrEP effectiveness (46%), perceived HIV stigma (53.5%), and risk compensation through decreased condom use (9.6%). Comparative studies of motivations, skills, and rates of initiation and adherence among pregnant and nonpregnant women are needed to inform optimal implementation efforts.

Low expression Macrophage Migration Inhibitory Factor (MIF) alleles and tuberculosis in HIV infected South Africans.

Host immunity is crucial for controlling M. tuberculosis infection. Functional polymorphisms in the cytokine macrophage migration inhibitory factor (MIF) show global population stratification, with the highest prevalence of low expression MIF alleles found in sub-Saharan Africans, which is a population with the greatest confluence of both TB and HIV infection and disease. We investigated the association between MIF alleles and tuberculosis (TB) and HIV in South Africa. We acquired clinical information and determined the frequency of two MIF promoter variants: a functional -794 CATT5-8 microsatellite and an associated -173 G/C SNP in two HIV-positive cohorts of patients with active laboratory-confirmed TB and in controls without active TB who were all HIV positive. We found a greater frequency of low expression MIF promoter variants (-794 CATT5,6) among TB disease cases compared to controls (OR = 2.03, p = 0.023), supporting a contribution of genetic low MIF expression to the high prevalence of TB in South Africa. Among those with HIV, circulating MIF levels also were associated with lower CD4 cell counts irrespective of TB status (p = 0.016), suggesting an influence of HIV immunosuppression on MIF expression.

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.

Predictors of loss to follow-up among patients on ART at a rural hospital in KwaZulu-Natal, South Africa.

INTRODUCTION: Improved HIV outcomes as a result of expanded antiretroviral therapy (ART) access is threatened by increasing rates of loss to follow up (LTFU) among those on ART, largely reported in urban populations. Some reports suggest that LTFU rates are overestimated due to patient movement to other facilities and inadequate medical records. STUDY OBJECTIVE: To define the proportion disengaging from HIV care as well as the characteristics of those LTFU in order to design and implement appropriate interventions to increase retention. METHODS: We performed a retrospective review of patients who discontinued ART at a central hospital ART clinic in rural South Africa and compared with patients receiving care at the 15 primary health clinics (PHCs) to determine the true proportion of those who were LTFU. We also compared those who discontinued ART with those who did not at the central hospital ART clinic to determine predictors of loss to follow up. RESULTS: Among 3242 patients on ART, 820 were originally marked as LTFU. Among all patients, 272 (8.4%) were found at a clinic on treatment, 56 (1.7%) were found at a clinic from which they had since discontinued treatment, and 10 (0.3%) returned to care between June and July 2016, leaving 475 (14.7%) unaccounted for and thus categorized as 'true' LTFU. Factors found to be associated with discontinuation include being male, age 18-35, having a CD4 count under 200 cells/µL, and being on ART for under six months. CONCLUSIONS: Young men with low CD4 counts early after ART initiation are at highest risk of ART disengagement in this rural South African HIV clinic. Novel interventions targeting this group are needed to improve retention in care.

"It's about my life": facilitators of and barriers to isoniazid preventive therapy completion among people living with HIV in rural South Africa.

Despite the recent rollout of Isoniazid Preventive Therapy (IPT) to prevent TB in people living with HIV in South Africa, adherence and completion rates are low. To explore barriers to IPT completion in rural KwaZulu-Natal, South Africa, we conducted individual semi-structured interviews among 30 HIV patients who had completed or defaulted IPT. Interview transcripts were analyzed according to the framework method of qualitative analysis. Facilitators of IPT completion included knowledge of TB and IPT, accepting one's HIV diagnosis, viewing IPT as similar to antiretroviral therapy, having social support in the community and the clinic, trust in the healthcare system, and desire for health preservation. Barriers included misunderstanding of IPT's preventive role in the absence of symptoms, inefficient health service delivery, ineffective communication with healthcare workers, financial burden of transport to clinic and lost wages, and competing priorities. HIV-related stigma was not identified as a significant barrier to IPT completion, and participants felt confident in their ability to manage stigma, for example by pretending their medications were for unrelated conditions. Completers were more comfortable communicating with health care workers than were defaulters. Efforts to facilitate successful IPT completion must include appropriate counseling and education for individual patients and addressing inefficiencies within the health care system in order to minimize patients' financial and logistical burden. These patient-level and structural changes are necessary for IPT to successfully reduce TB incidence in this resource-limited setting.

Cost-Effectiveness of Community-Based TB/HIV Screening and Linkage to Care in Rural South Africa.

South Africa has one of the highest burdens of TB worldwide, driven by the country's widespread prevalence of HIV, and further complicated by drug resistance. Active case finding within the community, particularly in rural areas where healthcare access is limited, can significantly improve diagnosis and treatment coverage in high-incidence settings. We evaluated the potential health and economic consequences of implementing community-based TB/HIV screening and linkage to care. Using a dynamic model of TB and HIV transmission over a time horizon of 10 years, we compared status quo TB/HIV control to community-based TB/HIV screening at frequencies of once every two years, one year, and six months. We also considered the impact of extending IPT from 36 months for TST positive and 12 months for TST negative or unknown patients (36/12) to lifetime use for all HIV-infected patients. We conducted a probabilistic sensitivity analysis to assess the effect of parameter uncertainty on the cost-effectiveness results. We identified four strategies that saved the most life years for a given outlay: status quo TB/HIV control with 36/12 months of IPT and TB/HIV screening strategies at frequencies of once every two years, one year, and six months with lifetime IPT. All of these strategies were very cost-effective at a threshold of $6,618 per life year saved (the per capita GDP of South Africa). Community-based TB/HIV screening with linkage to care is therefore very cost-effective in rural South Africa.

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.

Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down-Referred from a District Hospital to Primary Health Clinics in Rural South Africa.

BACKGROUND: HIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa. METHODS: We retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients' demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes. RESULTS: Of 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC. CONCLUSION: Decentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased patient education, active communication between hospitals and PHCs, and tracing of patients lost to follow up. Decentralized and integrated care is successful for carefully selected TB/HIV coinfected patients and should be expanded.

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.

Stressors and resources of caregivers of patients with incurable progressive illness in sub-Saharan Africa.

Family caregivers are central to palliative care in sub-Saharan Africa. Yet although supporting caregivers requires a comprehensive understanding of caregiver burden, there has been little research into this topic in Africa. Using the Stress Process Model to investigate the burden experienced by caregivers in South Africa and Uganda, we interviewed 37 caregivers and analyzed the data thematically. Caregivers' primary stressors related to day-to-day patient care and emotional support; secondary stressors included financial hardship, family responsibilities, and social isolation. Caregivers' social, relational, spiritual, and psychological resources mediated the effects of these stressors. Strengthening one resource strengthened others, but the failure of one resource hindered other resources, exacerbating burden. In providing caregiver support, policymakers and service providers should focus on enhancing caregivers' resources as well as alleviating their stressors.

Minimal diversity of drug-resistant Mycobacterium tuberculosis strains, South Africa.

Multidrug- (MDR) and extensively drug-resistant tuberculosis (XDR TB) are commonly associated with Beijing strains. However, in KwaZulu-Natal, South Africa, which has among the highest incidence and mortality for MDR and XDR TB, data suggest that non-Beijing strains are driving the epidemic. We conducted a retrospective study to characterize the strain prevalence among drug-susceptible, MDR, and XDR TB cases and determine associations between strain type and survival. Among 297 isolates from 2005-2006, 49 spoligotype patterns were found. Predominant strains were Beijing (ST1) among drug-susceptible isolates (27%), S/Quebec (ST34) in MDR TB (34%) and LAM4/KZN (ST60) in XDR TB (89%). More than 90% of patients were HIV co-infected. MDR TB and XDR TB were independently associated with mortality, but TB strain type was not. We conclude that, although Beijing strain was common among drug-susceptible TB, other strains predominated among MDR TB and XDR TB cases. Drug-resistance was a stronger predictor of survival than strain type.

Intensified specimen collection to improve tuberculosis diagnosis in children from Rural South Africa, an observational study.

BACKGROUND: In drug-resistant TB settings, specimen collection is critical for drug-susceptibility testing (DST). This observational study included multiple specimen types collected from pediatric TB suspects with the aim to determine diagnostic yield and inform clinical practice in children with drug-resistant and drug-susceptible TB. METHODS: From 03/2009-07/2010, TB suspects aged ≥6 months and ≤12 years were recruited among outpatient and inpatient settings. Subjects were new TB suspects or had persistent symptoms despite ≥2 months of TB treatment. The protocol included collection of a single blood and urine specimen, a single sputum induction and, if inpatients and <5 years of age, collection of 3 gastric aspirates (GA). Samples were cultured on solid and/or liquid media. DST was by 1% proportion method. RESULTS: Among 118 children with possible, probable or confirmed TB, the mean age was 4.9 years [SD 3.2] and 64 (62%) of those tested were HIV-positive. Eight (7%) subjects were culture-positive from at least one specimen; yield did not differ by HIV status or TB treatment history. Among those with positive cultures, 7/8 (88%) were from induced sputum, 5/6 (83%) from GA, 3/8 (38%) from blood, and 3/7 (43%) from urine. In subjects with both induced sputum and GA collection, sputum provided one additional case compared to GA. Multidrug resistant (MDR)-TB was detected by urine culture alone in one child >5 years old. Pan-resistant extensively drug resistant (XDR)-TB was identified by cultures from all sites in one subject. CONCLUSIONS: TB was cultured from HIV-positive and -negative children, and allowed for identification of MDR and XDR-TB cases. Urine and induced sputum each provided an additional TB diagnosis and, when compared to GA, may be considered a less invasive, same-day method of specimen collection for childhood TB suspects. This study illustrates the continued challenges and limitations of available strategies for pediatric TB diagnostics.

Chest radiograph findings and time to culture conversion in patients with multidrug-resistant tuberculosis and HIV in Tugela Ferry, South Africa.

BACKGROUND: The majority of patients with multidrug-resistant tuberculosis (MDR-TB) in South Africa are co-infected with HIV, but the radiographic features of MDR-TB and their relationship with time to sputum culture conversion in the antiretroviral therapy era have not been described. METHODS: We reviewed baseline chest radiographs for 56 patients with MDR-TB from a rural area of South Africa. We analyzed the association of cavities, consolidation, pleural effusion and hilar lymphadenopathy with time to sputum culture conversion, adjusting for HIV status, baseline sputum smear and CD4 count. RESULTS: Of the 56 subjects, 49 (88%) were HIV-positive, with a median CD4 count of 136 cells/mm(3) (IQR 65-249). Thirty-two (57%) patients were sputum smear positive. Twenty-two (39%) patients had a cavity and 37 (66%) patients had consolidations. Cavitary disease and consolidations were each associated with longer time to culture conversion on bivariate analysis but not after adjusting for sputum smear status (aORs 1.79 [0.94-3.42] and 1.09 [0.67-1.78], respectively). Positive baseline sputum smear remained independently associated with longer time to conversion (aOR 3.45 [1.39-8.59]). We found no association between pleural effusion or hilar lymphadenopathy and time to conversion. Seventy-nine percent of patients were cured at the end of treatment. CONCLUSIONS: Despite high rates of HIV co-infection and advanced immunodeficiency, the majority of patients had severe pathology on baseline chest radiograph. Nevertheless, culture conversion rates were high and treatment outcomes were favorable. Cavitation and consolidation do not appear to have an independent association with time to culture conversion beyond that of baseline sputum smear status.