Emergence of multidrug-resistant tuberculosis in a community-based directly observed treatment programme in rural South Africa.

OBJECTIVE: Although little studied in developing countries, multidrug-resistant tuberculosis (MDR-TB) is considered a major threat. We report the molecular epidemiology, clinical features and outcome of an emerging MDR-TB epidemic. METHODS: In 1996 all tuberculosis suspects in the rural Hlabisa district, South Africa, had sputum cultured, and drug susceptibility patterns of mycobacterial isolates were determined. Isolates with MDR-TB (resistant to both isoniazid and rifampicin) were DNA fingerprinted by restriction fragment length polymorphism (RFLP) using IS6110 and polymorphic guanine-cytosine-rich sequence-based (PGRS) probes. Patients with MDR-TB were traced to determine outcome. Data were compared with results from a survey of drug susceptibility done in 1994. RESULTS: The rate of MDR-TB among smear-positive patients increased six-fold from 0.36% (1/275) in 1994 to 2.3% (13/561) in 1996 (P = 0.04). A further eight smear-negative cases were identified in 1996 from culture, six of whom had not been diagnosed with tuberculosis. MDR disease was clinically suspected in only five of the 21 cases (24%). Prevalence of primary and acquired MDR-TB was 1.8% and 4.1%, respectively. Twelve MDR-TB cases (67%) were in five RFLP-defined clusters. Among 20 traced patients, 10 (50%) had died, five had active disease (25%) and five (25%) were apparently cured. CONCLUSIONS: The rate of MDR-TB has risen rapidly in Hlabisa, apparently due to both reactivation disease and recent transmission. Many patients were not diagnosed with tuberculosis and many were not suspected of drug-resistant disease, and outcome was poor.     

Twice-weekly, directly observed treatment for HIV-infected and uninfected tuberculosis patients: cohort study in rural South Africa.

OBJECTIVE: To determine the effectiveness of twice-weekly directly observed therapy (DOT) for tuberculosis (TB) in HIV-infected and uninfected patients, irrespective of their previous treatment history. Also to determine the predictive value of 2-3 month smears on treatment outcome. METHODS: Four hundred and sixteen new and 113 previously treated adults with culture positive pulmonary TB (58% HIV infected, 9% combined drug resistance) in Hlabisa, South Africa. Daily isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice a week to 2 months and HR twice a week to 6 months in the community. RESULTS: Outcomes at 6 months among the 416 new patients were: transferred out 2%; interrupted treatment 17%; completed treatment 3%; failure 2%; and cured 71%. Outcomes were similar among HIV-infected and uninfected patients except for death (6 versus 2%; P = 0.03). Cure was frequent among adherent HIV-infected (97%; 95% CI 94-99%) and uninfected (96%; 95% CI 92-99%) new patients. Outcomes were similar among previously treated and new patients, except for death (11 versus 4%; P = 0.01), and cure among adherent previously treated patients 97% (95% CI 92-99%) was high. Smear results at 2 months did not predict the final outcome. CONCLUSION: A twice-weekly rifampicin-containing drug regimen given under DOT cures most adherent patients irrespective of HIV status and previous treatment history. The 2 month smear may be safely omitted. Relapse rates need to be determined, and an improved system of keeping treatment interrupters on therapy is needed. Simplified TB treatment may aid implementation of the DOTS strategy in settings with high TB caseloads secondary to the HIV epidemic.     

Tuberculosis treatment outcomes: directly observed therapy compared with self-administered therapy

Effective treatment of tuberculosis requires adherence to a minimum of 6 months treatment with multiple drugs. To improve adherence and cure rates, directly observed therapy is recommended for the treatment of pulmonary tuberculosis. We compared treatment outcomes among all culture-positive patients treated for active pulmonary tuberculosis (n = 372) in San Francisco County, California from 1998 through 2000. Patients treated by directly observed therapy at the start of therapy (n = 149) had a significantly higher cure rate compared with patients treated by self-administered therapy (n = 223) (the sum of bacteriologic cure and completion of treatment, 97.8% versus 88.6%, p < 0.002), and decreased tuberculosis-related mortality (0% vs. 5.5%, p = 0.002). Rates of treatment failure, relapse, and acquired drug resistance were similar between the two groups. Forty-four percent of patients who received self-administered therapy had risk factors for nonadherence and should have been assigned to directly observed therapy. We conclude that treatment plans that emphasize directly observed therapy from the start of therapy have the greatest success in improving tuberculosis treatment outcomes.     

Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa.

OBJECTIVE: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). SETTING: Hlabisa, South Africa. PATIENTS: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. METHODS: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. RESULTS: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P<0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. CONCLUSION: Relapse rates are acceptably low following successful DOT with a twice weekly rifampicin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention.     

Tuberculosis at Chris Hani Baragwanath Hospital: an intervention to improve patient referrals to district clinics.

SETTING: A study in 2001 described the process of managing tuberculosis (TB) at Chris Hani Baragwanath hospital, the numbers of patients diagnosed and poor outcomes of referring patients to clinics in the adjacent sub-districts. The present study describes and evaluates an intervention to address the problems. OBJECTIVES: To describe the intervention process (education and referral of TB patients) and the subsequent results over a 2-year period from 2003 to 2005. METHODS: The process of establishing the system and how it was evaluated at district clinics in Johannesburg are described. RESULTS: In the first 2 years of operation, August 2003 to July 2005, 13,138 patients were registered. Extra-pulmonary tuberculosis (EPTB) was diagnosed in 34%. Of the 46% tested for human immunodeficiency virus (HIV), 93% were positive. Successful referral to clinics was achieved for 94% of patients. CONCLUSIONS: Very large numbers of patients are diagnosed with TB at Chris Hani Baragwanath Hospital. A TB care centre has successfully addressed important referral, education and registration requirements for the comprehensive management of TB with links to clinics. It is suggested that this model be applied at other hospitals.     

Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.

SETTING: An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload. OBJECTIVE: To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania. DESIGN: Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat. FINDINGS: A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83). CONCLUSION: Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes.     

Combating tuberculosis: barriers to widespread non-governmental organisation involvement in community-based tuberculosis treatment in South Africa.

OBJECTIVES: To explore barriers to indigenous non-governmental organisation (NGO) involvement in community-based tuberculosis treatment delivery in high incidence areas. DESIGN: Qualitative study comprising in-depth interviews with key informants in non-government organisations and the formal health sector. Participant observation and documentary review methods were also employed. SETTING: Six non-governmental organisations involved in community-based tuberculosis care delivery in South Africa. SUBJECTS: Directors and Programme Managers of organisations and formal health sector personnel involved in tuberculosis control. RESULTS: Four major barriers were identified. Lack of adequate funding was the central issue linked to most of the other barriers identified, which included lack of adequate collaboration, competition, and a paucity of human resources. CONCLUSIONS: While indigenous non-governmental organisations face significant barriers to involvement in TB care delivery, on their part there is a need for closer collaboration of efforts as well as a more rigorous approach towards monitoring and evaluation of their contribution in order to fully realise their potential. Government and other external funders also need to increase their commitment to ensuring greater participation of these organisations in high TB incidence areas.     

Challenges to pediatric HIV care and treatment in South Africa

It is estimated that almost 300,000 children in South Africa have human immunodeficiency virus (HIV) infection. The disease is responsible for reversing decreases in child mortality. Few data exist evaluating the outcomes of the prevention of mother-to-child transmission of HIV (PMTCT) program, although PMTCT coverage appears to be low. Hospitals are still witnessing large numbers of admissions of HIV-infected children. Postnatal transmission of HIV is high, reflecting poor education of and support for women in their infant feeding choices. Too few infants and children are entering care through early diagnosis, which should be widely available. Cotrimoxazole prophylaxis coverage is inadequate, contributing to high morbidity and mortality in infants. The number of children receiving antiretroviral therapy (ART) is increasing steadily. However, significant inequalities in access to ART exist between and within provinces. Challenges for pediatric ART include a lack of sufficiently trained health care personnel and inadequate facilities, as well as the complexity of drug regimens and formulations. The compartmentalization of the ART rollout program hinders PMTCT and makes it difficult for children to be identified and referred into appropriate services. This article delineates the challenges to pediatric HIV care in South Africa and provides some practical recommendations to improve it.     

New approaches to spatially analyse primary health care usage patterns in rural South Africa

OBJECTIVE: To develop indices to quantitatively assess and understand the spatial usage patterns of health facilities in the Hlabisa district of South Africa. METHODOLOGY: We mapped and interviewed more than 23 000 homesteads (approximately 200 000 people) in Hlabisa district, South Africa and spatially analysed their modal primary health usage patterns using a geographical information system. We generated contour maps of health service use and quantified the relationship between clinic catchments and distance-defined catchments using inclusion and exclusion error. We propose the distance usage index (DUI) as an overall spatial measure of clinic usage. This index is the sum of the distances from clinic to all client homesteads divided by the sum of the distances from clinic to all homesteads within its distance-defined catchment. The index encompasses inclusion, exclusion, and strength of patient attraction for each clinic. RESULTS: Eighty-seven per cent of homesteads use the nearest clinic. Residents of homesteads travel an average Euclidean distance of 4.72 km to attend clinics. There is a significant logarithmic relationship between distance from clinic and their use by homesteads (r(2)=0.774, P < 0.0001). The DUI values range between 31 and 198% (mean=110%, SD=43.7) for 12 clinics and highlight clinic usage patterns across the district. CONCLUSIONS: The DUI is a powerful and informative composite measure of clinic usage. The results of the study have important implications for health care provision in developing countries.     

Need for improvements in clinical practice to retain patients in pre-antiretroviral therapy care: Data from rural clinics in North West Province,South Africa

We examined current challenges with patient engagement in HIV prevention and care in South Africa by assessing the procedures of eight public health clinics in the North West Province. Procedures consisted of (1) an inventory/audit of the HIV Counseling and Testing, pre-antiretroviral therapy (pre-ART), and antiretroviral therapy (ART) patient registers; (2) extraction of data from a convenience sample of 39 HIV-positive patient files; and (3) 13 key informant interviews with clinic staff to characterize retention and re-engagement practices for patients. Incomplete registers revealed little evidence of follow-up services, particularly for pre-ART patients. The more detailed examination of patient files indicated substantial disparities in the proportion of pre-ART versus ART patients retained in care. Key informant interviews contextualized the data, with providers describing multiple procedures for tracking and ensuring service delivery for ART patients and fewer procedures to retain pre-ART patients. These findings suggest that enhanced strategies are needed for ensuring continued engagement in HIV care, with a particular emphasis on improving the retention of pre-ART patients. The preventive benefits of ART scale-up may not be achieved if improvements are not made in the proportion of earlier-stage HIV-positive patients who are successfully engaged in care.     

The church and paediatric HIV care in rural South Africa: a qualitative study

Religion has substantial – positive and negative – influence on South Africa's HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences of various stakeholders including religious leaders, healthcare workers and people infected/affected with/by HIV were investigated through participant observation, semi-structured interviews and focus group discussions. During the research the original focus on paediatric HIV care shifted to HIV care in general in reaction to participant responses. Participants identified three main barriers to positive church engagement in HIV care: (a) stigma and disclosure; (b) sexual associations with HIV and (c) religious beliefs and practices. All participant groups appreciated the opportunity and relevance of strengthening church involvement in HIV care. Opportunities for positive church engagement in HIV care that participants identified included: (a) comprehensive and holistic HIV care when churches and clinics collaborate; (b) the wide social reach of churches and (c) the safety and acceptance in churches. Findings indicate that despite barriers great potential exists for increased positive church engagement in HIV care in rural South Africa. Recommendations include increased medical knowledge and dialogue on HIV/AIDS within church settings, and increased collaboration between churches and the medical sector.