HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites.

INTRODUCTION: We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. METHODS: In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. RESULTS: Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. CONCLUSIONS: The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy.

Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives.

INTRODUCTION: Although individual HIV rapid diagnostic tests (RDTs) show good performance in evaluations conducted by WHO, reports from several African countries highlight potentially significant performance issues. Despite widespread use of RDTs for HIV diagnosis in resource-constrained settings, there has been no systematic, head-to-head evaluation of their accuracy with specimens from diverse settings across sub-Saharan Africa. We conducted a standardized, centralized evaluation of eight HIV RDTs and two simple confirmatory assays at a WHO collaborating centre for evaluation of HIV diagnostics using specimens from six sites in five sub-Saharan African countries. METHODS: Specimens were transported to the Institute of Tropical Medicine (ITM), Antwerp, Belgium for testing. The tests were evaluated by comparing their results to a state-of-the-art reference algorithm to estimate sensitivity, specificity and predictive values. RESULTS: 2785 samples collected from August 2011 to January 2015 were tested at ITM. All RDTs showed very high sensitivity, from 98.8% for First Response HIV Card Test 1-2.0 to 100% for Determine HIV 1/2, Genie Fast, SD Bioline HIV 1/2 3.0 and INSTI HIV-1/HIV-2 Antibody Test kit. Specificity ranged from 90.4% for First Response to 99.7% for HIV 1/2 STAT-PAK with wide variation based on the geographical origin of specimens. Multivariate analysis showed several factors were associated with false-positive results, including gender, provider-initiated testing and the geographical origin of specimens. For simple confirmatory assays, the total sensitivity and specificity was 100% and 98.8% for ImmunoComb II HIV 12 CombFirm (ImmunoComb) and 99.7% and 98.4% for Geenius HIV 1/2 with indeterminate rates of 8.9% and 9.4%. CONCLUSION: In this first systematic head-to-head evaluation of the most widely used RDTs, individual RDTs performed more poorly than in the WHO evaluations: only one test met the recommended thresholds for RDTs of ≥99% sensitivity and ≥98% specificity. By performing all tests in a centralized setting, we show that these differences in performance cannot be attributed to study procedure, end-user variation, storage conditions, or other methodological factors. These results highlight the existence of geographical and population differences in individual HIV RDT performance and underscore the challenges of designing locally validated algorithms that meet the latest WHO-recommended thresholds.

Current practice of epidemiology in Africa: highlights of the 3rd conference of the African epidemiological association and 1st conference of the Cameroon society of epidemiology, Yaoundé, Cameroon, 2014.

As the study of disease occurrence and health indicators in human populations, Epidemiology is a dynamic field that evolves with time and geographical context. In order to update African health workers on current epidemiological practices and to draw awareness of early career epidemiologists on concepts and opportunities in the field, the 3(rd) African Epidemiology Association and the 1st Cameroon Society of Epidemiology Conference was organized in June 2-6, 2014 at the Yaoundé Mont Febe Hotel, in Cameroon. Under the theme«Practice of Epidemiology in Africa: Stakes, Challenges and Perspectives¼, the conference attracted close to five hundred guest and participants from all continents. The two main programs were the pre-conference course for capacity building of African Early Career epidemiologists, and the conference itself, providing a forum for scientific exchanges on recent epidemiological concepts, encouraging the use of epidemiological methods in studying large disease burden and neglected tropical diseases; and highlighting existing opportunities.

[Service quality assurance by death analysis during the 2004 cholera outbreak in Douala]. / L'amélioration de la qualité par l'analyse des décès au cours de l'épidémie de choléra de 2004 à Douala.

Morbidity and mortality conferences (MMC) are used today in most medical departments as a tool for quality assurance as well as an educational tool. We introduced MMC with regard to cholera lethality during the 2004 cholera outbreak in Douala. The Delegation of Public Health (DPH) in Douala, coordinating body for the combat against the epidemic, decided to open cholera treatment units (CTU) in fourteen hospitals, equally distributed over the town. The CTUs' personnel was retrained on diagnostic and treatment protocols, procedures to follow and on management tools. To assure the quality of services, a provincial supervision team was constituted for the close follow-up of the CTUs. The supervision team had two main tasks, i.e. on-the-job training of the personnel involved in the care of cholera patients and systematic meetings whenever a cholera death occurred during hospital stay in order to analyse the reasons behind the death. We communicate our experience with these systematic meetings inspired by the MMC and aiming at the analysis of cholera deaths in the CTUs. Immediately after a cholera death in one of the CTUs, a meeting was organised by a member of the supervision team, assisted by the entire CTU team. During the meeting, the patient's file was re-examined as were the decisions token, the actions undertaken by the personnel, and the difficulties met. Alternative decisions and actions were discussed and conclusions based on the lessons learned formulated. Of all meetings minutes were kept. A monthly provincial meeting, joining all CTU teams, was organized for discussion of the minutes, exchange of experiences, and, eventually, adapting of protocols, procedures, and management tools. Five thousand and twenty cholera patients were notified during an 8-months-period (January-August 2004), 69 (1.4%) of the patients died, amongst them 8 before the declaration of the epidemic and 4 before hospital admission. Eleven CTUs out of a total of 14 organised 15 meetings concerning 39 (68%) of the 57 hospital based cholera deaths. Eight to eighteen CTU team members participated (with 2-5 physicians according to the CTU) and the meetings lasted between 1 and 2 hours. The meetings proceeded in a systematic way: after controlling for the presence of all CTU team members concerned, the patient's file was read together, team members were asked to elucidate what did not figure in the file, everybody was asked for commentaries and suggestions, the supervisor made a synthesis of the discussion, and, finally, conclusions and recommendations were formulated. The minutes of the meeting were sent to the DPH. The conclusions and recommendations aimed at the reception of the patients and his admission circuit, the diagnostic procedures, therapy, the case definition, the evaluation of the severity of the patient's status at the moment of admission, the surveillance during evolution of the patient, the respect of the therapeutical protocols, and the management of the CTU. In spite of the organisational, psychological, and socio-cultural difficulties, the meetings went off apparently without major reservations in the minds of the participants. These meetings analysing the reasons behind a case of cholera dying in a CTU gave the opportunity to discuss performance, to identify problems, and to search together for solutions. They were thought of as a tool for improving the quality of the service. Looking at the low over-all lethality rate during this major epidemic they seemed to have, at least partially succeeded.