Rationale : South Africa has a high prevalence of tuberculosis (TB) and HIV-coinfected adults in whom TB is often diagnosed late in the course of disease. Objectives: Improved case-finding approaches for TB and HIV are needed to reduce mortality and prevent transmission. Methods: We identified newly diagnosed index TB cases in a rural district and enrolled their households in a TB-HIV contact-tracing study. A group of randomly selected control households were enrolled to determine community prevalence of undetected TB and HIV. Field teams screened participants for TB symptoms, collected sputum specimens for smear microscopy and culture, provided HIV counseling and testing, and collected blood for CD4 testing. Participants were referred to public clinics for TB treatment and antiretroviral therapy. Measurements and Main Results: We evaluated 2,843 household contacts of 727 index patients with TB and 983 randomly selected control household members. The prevalence of TB in household contacts was 6,075 per 100,000 (95% confidence interval, 5,789-6,360 per 100,000), whereas the prevalence detected in randomly selected households was 407 per 100,000 (95% confidence interval, 0-912 per 100,000; prevalence difference, 5,668 per 100,000; P , 0.001). TB detected among contacts was less likely to be smear-positive than in the index patients (6% vs. 22%; P , 0.001). Most contacts with culture-confirmed TB were asymptomatic. At least one case of undiagnosed TB was found in 141 (19%) of 727 contact versus 4 (1%) of 312 control households. HIV testing was positive in 166 (11%) of 1,568 contacts tested versus 76 (14%) of 521 control participants tested (odds ratio, 1.48; P ¼ 0.02). Conclusions: Active case finding in TB contact households should be considered to improve TB and HIV case detection in high-prevalence settings, but sensitive diagnostic tools are necessary. Keywords: tuberculosis; HIV; AIDS; case detection; contact tracingThe World Health Organization (WHO) global tuberculosis (TB) control policy advocates the DOTS strategy, which relies on passive case detection in symptomatic individuals presenting to health services (1). Despite the success of DOTS in reducing TB mortality in settings of low HIV prevalence, evidence suggests that additional strategies are necessary for TB control in high-HIV-prevalence areas (2, 3). Intensified case finding in individuals infected with HIV has recently been incorporated into HIV-TB control strategies (4), but this approach still relies on patient presentation at a health facility. Obstacles to selfpresentation, such as distance to the nearest health facility, sex, and age, have all been associated with delayed time to diagnosis of TB from onset of symptoms (5-9). Additionally, HIVassociated TB is more likely to be smear-negative than TB in individuals who are HIV-negative (10).The case detection strategy in South Africa has been heavily dependent on sputum smear microscopy and passive case detection. Although mycobacterial culture is available, its use is incomplete, particularly...

Symptom screening is a recommended component of intensified case-finding (ICF) for pulmonary tuberculosis (TB) among HIV-infected individuals. Symptomatic individuals are further investigated to either exclude or diagnose pulmonary TB, thus reducing the number of individuals requiring costly laboratory investigation. Those with laboratory evaluations negative for pulmonary TB or who lack symptoms may be eligible for antiretroviral therapy (ART) and/or TB isoniazid preventive therapy (IPT). A four-part symptom screen has been recommended by the World Health Organization (WHO) for identifying TB suspects and those unlikely to have TB. A meta-analysis of studies among HIV-infected individuals calculated a sensitivity of 90.1% for the four-part symptoms screen - of any of cough, fever, night sweats, or weight loss - among patients in clinical care, making it an effective tool for identifying most patients with TB. An important population for intensified case-finding not included in that meta-analysis was HIV-infected pregnant women. We undertook a cross-sectional survey among HIV-infected pregnant women receiving prenatal care at community clinics in South Africa. We obtained a four-symptom review and sputum smear microscopy and mycobacterial culture on all participants. Among 1415 women, 226 (16%) had a positive symptom screen, and 35 (2.5%) were newly diagnosed with culture-positive TB. Twelve were on TB treatment at the time of screening, yielding 47 (3.3%) women with prevalent TB. Symptom screening among women without known TB had a sensitivity of 28% and specificity of 84%. The poor performance of symptom screening to identify women with TB suggests that other approaches may be needed for intensified case-finding to be effective for this population.

Background WHO treatment guidelines recommend efavirenz in first line antiretroviral therapy (ART). Efavirenz commonly causes early transient neuro-psychiatric adverse events. We present 20 cases with severe encephalopathy accompanied by ataxia due to efavirenz toxicity Methods Consecutive HIV-infected adults taking efavirenz-containing ART admitted to Tshepong hospital, Klerksdorp, South Africa with ataxia and encephalopathy were included in this case series. Results We identified 20 women admitted to hospital with severe ataxia. All received efavirenz-based ART for a median of 2 years. All had severe ataxia and none had nystagmus. Eleven had features of encephalopathy. Median weight was 34kg (IQR:29.7–35.3); median CD4 count 299 cells/mm3 (IQR:258-300) and most (18 of 19) were virally suppressed. Eight patients had a record of prior weights and 7 of 8 showed signicant weight loss with a median weight loss of 10.8 kg (IQR:8–11.6). All cases had plasma efavirenz assays, 19 were supra-therapeutic (more than twice upper level of therapeutic range) and 15 had concentrations above the upper limit of assay detection. Ataxia resolved after withdrawal of efavirenz at a median time of 2 months (IQR:1.25–4), and recurred in two of three patients when rechallenged. Admissions prior to diagnosis were frequent with 10 cases admitted previously. Three women died. Conclusion Efavirenz toxicity may present with severe reversible ataxia often with encephalopathy years after its initiation; likely in genetic slow metabolizers. We recommend that patients whose weight is <40kg receive lower doses of efavirenz and that therapeutic drug monitoring (TDM) be considered, and efavienz stopped in patients presenting with ataxia.