Urinary LAM grade, culture positivity, and mortality among HIV-infected South African out-patients.

SETTING: Four ambulatory clinics in Durban, South Africa. OBJECTIVE: To test the relationships of patient characteristics, time to mycobacterial culture positivity, and mortality with urinary lipoarabinomannan (LAM) grade category. DESIGN: Newly diagnosed human immunodeficiency virus (HIV) infected adults were screened for tuberculosis (TB) using sputum culture, tested for urinary LAM, and followed for up to 12 months. We performed multivariable ordinal logistic regression of risk factors for low (1 or 2) or high (3, 4, or 5) LAM grade. We used adjusted Cox regression models to determine the hazard ratios of time to culture positivity and death. RESULTS: Among 683 HIV-infected adults, median CD4 count was 215 cells/mm³ (interquartile range 86-361 cells/mm³), 17% had culture-confirmed TB, and 11% died during follow-up. Smoking, tachycardia (pulse > 100 beats/minute), CD4 count < 100 cells/mm³, and TB culture positivity were each associated with higher LAM grade. In multivariate models, a high urine LAM grade was associated with four-fold increased hazard of culture positivity (P = 0.001) and two-fold increased hazard of mortality (P = 0.02). Among patients treated for TB, these associations were no longer statistically significant. CONCLUSION: In this population, a higher urine LAM grade was associated with shorter time to culture positivity and mortality; however, these associations were not present for those starting anti-tuberculosis treatment.

Operational assessment of point-of-care diagnostics in rural primary healthcare clinics of KwaZulu-Natal, South Africa: a cross-sectional survey.

BACKGROUND: The World Health Organization (WHO) called for new clinical diagnostic for settings with limited access to laboratory services. Access to diagnostic testing may not be uniform in rural settings, which may result in poor access to essential healthcare services. The aim of this study is to determine the availability, current usage, and need for point-of-care (POC) diagnostic tests among rural primary healthcare (PHC) clinics in South Africa's KwaZulu-Natal (KZN) province. METHODS: We used the KZN's Department of Health (DoH) clinic classification to identify the 232 rural PHC clinics in KZN, South Africa. We then randomly sampled 100 of 232 rural PHC clinics. Selected health clinics were surveyed between April to August 2015 to obtain clinic-level data for health-worker volume and to determine the accessibility, availability, usage and need for POC tests. Professional healthcare workers responsible for POC testing at each clinic were interviewed to assess the awareness of POC testing. Data were survey weighted and analysed using Stata 13. RESULTS: Among 100 rural clinics, the average number of patients seen per week was 2865 ± 2231 (range 374-11,731). The average number of POC tests available and in use was 6.3 (CI: 6.2-6.5) out of a potential of 51 tests. The following POC tests were universally available in all rural clinics: urine total protein, urine leukocytes, urine nitrate, urine pregnancy, HIV antibody and blood glucose test. The average number of desired POC diagnostic tests reported by the clinical staff was estimated at 15 (CI: 13-17) per clinic. The most requested POC tests reported were serum creatinine (37%), CD4 count (37%), cholesterol (32%), tuberculosis (31%), and HIV viral load (23%). CONCLUSION: Several POC tests are widely available and in use at rural PHC clinics in South Africa's KZN province. However, healthcare workers have requested additional POC tests to improve detection and management of priority disease conditions. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02692274.

Diagnostic accuracy of C-reactive protein for active pulmonary tuberculosis: a meta-analysis.

SETTING: Systematic screening for active pulmonary tuberculosis (PTB) is recommended for high-risk populations, including people living with the human immunodeficiency virus (PLHIV); however, currently recommended TB screening tools are inadequate for most high-burden settings. OBJECTIVE: To determine whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active PTB. DESIGN: We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (10 mg/l cut-off point) for culture-positive PTB. Pooled diagnostic accuracy estimates were generated using random-effects meta-analysis for out-patients and in-patients, and for pre-specified subgroups based on HIV status and test indication. RESULTS: We identified nine unique studies enrolling 1793 adults from out-patient (five studies, 1121 patients) and in-patient settings (five studies, 672 patients), 72% of whom had confirmed HIV infection. Among out-patients, CRP had high sensitivity (93%, 95%CI 88-98) and moderate specificity (60%, 95%CI 40-75) for active PTB. Specificity was lowest among in-patients (21%, 95%CI 6-52) and highest among out-patients undergoing TB screening (range 58-81%). There was no difference in summary estimates by HIV status. CONCLUSION: CRP, which is available as a simple, inexpensive and point-of-care test, can be used to screen PLHIV presenting for routine HIV/AIDS (acquired immune-deficiency syndrome) care for active TB.

Evaluating the accessibility and utility of HIV-related point-of-care diagnostics for maternal health in rural South Africa: a study protocol.

INTRODUCTION: Poor healthcare access is a major barrier to receiving antenatal care and a cause of high maternal mortality in South Africa (SA). 'Point-of-care' (POC) diagnostics is a powerful emerging healthcare approach to improve healthcare access. This study focuses on evaluating the accessibility and utility of POC diagnostics for maternal health in rural SA primary healthcare (PHC) clinics in order to generate a model framework of implementation of POC diagnostics in rural South African clinics. METHOD AND ANALYSES: We will use several research methods, including a systematic review, quasi-experiments, survey, key informant interviews and audits. We will conduct a systematic review and experimental study to determine the impact of POC diagnostics on maternal health. We will perform a cross-sectional case study of 100 randomly selected rural primary healthcare clinics in KwaZulu-Natal to measure the context and patterns of POC diagnostics access and usage by maternal health providers and patients. We will conduct interviews with relevant key stakeholders to determine the reasons for POC deficiencies regarding accessibility and utility of HIV-related POC diagnostics for maternal health. We will also conduct a vertical audit to investigate all the quality aspects of POC diagnostic services including diagnostic accuracy in a select number of clinics. On the basis of information gathered, we will propose a model framework for improved implementation of POC diagnostics in rural South African public healthcare clinics. Statistical (Stata-13) and thematic (NVIVO) data analysis will be used in this study. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the University of KwaZulu-Natal (BE 484/14) and the KwaZulu-Natal Department of Health based on the Helsinki Declaration (HRKM 40/15). Findings of this study will be disseminated electronically and in print. They will be presented to conferences related to HIV/AIDS, diagnostics, maternal health and strengthening of health systems.

Impact of point-of-care diagnostics on maternal outcomes in HIV-infected women: systematic review and meta-analysis protocol.

INTRODUCTION: Studies indicate substandard diagnostic care, delayed and missed diagnosis as some of the contributing factors to maternal mortality. The clinical impact of point-of-care (POC) diagnostics has been shown in the monitoring and treatment of a variety of infectious diseases, including HIV/AIDS and tuberculosis. The objective of this systematic review is to investigate the impact of POC diagnostics on maternal outcomes for HIV-infected women. METHODS: We will conduct a systematic review to evaluate the impact of POC diagnostics for improving desired healthcare outcomes for HIV-infected women. The search strategy will involve electronic databases including: Cochrane Infectious Disease Group Specialised Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by 2 reviewers in parallel. Evidence will be synthesised using relevant systematic research tools: meta-analysis and subgroup analysis will be conducted using RevMan and Stata 13 will be used for meta-regressions. We will follow recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Intervention Reviews. ETHICS AND DISSEMINATION: We anticipate finding a large number of studies on POC diagnostic interventions on maternal outcomes in HIV-infected women, which, once summarised, will be useful to guide future diagnostic interventions. The protocol for the systematic review has been registered in PROSPERO. The study will be disseminated electronically and in print. It will also be presented to conferences related to HIV/AIDS, POC diagnostics and maternal health. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014015439.

Prevalence of cryptococcal antigenuria at initial HIV diagnosis in KwaZulu-Natal.

OBJECTIVES: The World Health Organization (WHO) recommends screening HIV-infected people for cryptococcal antigens to identify cryptococcosis, a major cause of AIDS-related deaths. As the burden of cryptococcosis is unknown in South Africa's KwaZulu-Natal province, we assessed the cryptococcal antigenuria prevalence among newly diagnosed HIV-infected adults there. METHODS: We conducted a cross-sectional study of newly diagnosed HIV-infected adults who received voluntary HIV testing in an out-patient clinic. Participants provided a urine specimen in a sterile container, and we performed testing with a WHO-endorsed rapid cryptococcal antigen lateral flow assay (Immy Inc., Norman, OK, USA) per the manufacturer's specifications. We assessed cryptococcal antigenuria prevalence among participants with CD4 counts < 200 cells/µL, and stratified results by CD4 count categories. RESULTS: Among 432 participants, the mean (± standard deviation) age was 36.1 ± 9.9 years and 172 (40%) were female. The overall estimated prevalence of cryptococcal antigenuria was 9.0% [95% confidence interval (CI) 6.5-12.1%]. CD4 counts were available for 319 participants (74%); the median CD4 count was 75 cells/µL [interquartile range (IQR) 34-129 cells/µL]. Participants with a negative cryptococcal antigenuria screening test had a median CD4 count of 79 cells/µL (IQR 36-129 cells/µL), while participants with a positive cryptococcal test had a median CD4 count of 41 cells/µL (IQR 10-112 cells/µL). The estimated prevalence of cryptococcal antigenuria among participants with CD4 counts < 50 cells/µL was 12.5% (95% CI 7.0-20.1%), which was significantly higher than that among participants with CD4 counts of 50-200 cells/µL (4.8%; 95% CI 2.3-8.7%). CONCLUSIONS: Nearly 1 in 10 newly diagnosed HIV-infected adults with CD4 counts < 200 cells/µL in KwaZulu-Natal had evidence of cryptococcal antigenuria. Point-of-care CD4 count testing and cryptococcal antigen screening may rapidly identify cryptococcosis at the time of HIV diagnosis.

Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa.

OBJECTIVE: To determine the accuracy and role of rapid C-reactive protein (CRP) testing in human immunodeficiency virus (HIV) infected individuals with presumed tuberculosis (TB). DESIGN: We enrolled HIV-infected adults (≥18 years)with a cough of ≥2 weeks and negative sputum smears for acid-fast bacilli in KwaZulu-Natal, South Africa. Participants were evaluated for pulmonary TB (PTB) by a nurse with rapid CRP, and independently by a physician by chest radiograph. Rapid CRP test results were compared with laboratory CRP and sputum sent for confirmation of TB. RESULTS: Among 93 participants, 55 (59%) were female, the mean age was 35 years, and the median CD4 count was 177/mm3. Forty-five (54%) participants were diagnosed with PTB. Diagnostic sensitivity and specificity were respectively 95% (95%CI 74­99) and 51%(95%CI 35­66) for rapid CRP >8 mg/l, 87% (95%CI 73­96) and 53% (95%CI 38­68) for nurse assessment, and 69% (95%CI 52­83) and 76% (95%CI 61­87) for physician examination. Combining a negative rapid CRP(≤8 mg/l) with nurse and physician assessments reduced the post-test probability of PTB from 22% to 6% and from 32% to 6%, respectively. CONCLUSION: Rapid CRP testing helped exclude PTB,and may be a valuable test in assisting nurses and physicians in TB-endemic regions.