Cara S. Kosack

Antimalarial efficacy of sulfadoxine–pyrimethamine, amodiaquine and a combination of chloroquine plus sulfadoxine–pyrimethamine in Bundi Bugyo, western Uganda

We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine–pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed‐up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re‐infections. PCR‐adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1–47.7) in the SP group, 20.6% (14/68, 95% CI 11.7–32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1–33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Ugandas first‐line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long‐term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14‐day follow‐ups. Antimalarial policy decisions should therefore be based on 28‐day studies, with PCR adjustment to distinguish re‐infections.

Feasibility of using teleradiology to improve tuberculosis screening and case management in a district hospital in Malawi

PROBLEM Malawi has one of the worlds highest rates of human immunodeficiency virus (HIV) infection (10.6%), and southern Malawi, where Thyolo district is located, bears the highest burden in the country (14.5%). Tuberculosis, common among HIV-infected people, requires radiologic diagnosis, yet Malawi has no radiologists in public service. This hinders rapid and accurate diagnosis and increases morbidity and mortality. APPROACH Médecins Sans Frontières, in collaboration with Malawis Ministry of Health, implemented teleradiology in Thyolo district to assist clinical staff in radiologic image interpretation and diagnosis. LOCAL SETTING Thyolo districts 600 000 inhabitants are mostly subsistence-level or migrant farmers living in extreme poverty. Health facilities include one public hospital and 38 primary health centres. Understaffing and the absence of a radiologist make the diagnosis of tuberculosis difficult in a population where this disease affects 66% of patients with HIV infection. RELEVANT CHANGES From September 2010-2011, 159 images (from 158 patients) were reviewed by teleradiology. Teleradiology changed patient management in 36 cases (23.5%). Two (1.3%) of them were cases of pulmonary tuberculosis not previously suspected by clinical staff. In addition, the radiologists review corrected the misdiagnosis of tuberculosis and averted inappropriate treatment in 16 patients (10.5%). LESSONS LEARNT Teleradiology can improve tuberculosis diagnosis and case management, especially if criteria to identify the patients most suitable for referral are developed and the radiologist is conversant with local resources and health problems. Designating a clinical focal point for teleradiology ensures sustainability. Staff need time to adapt to a new teleradiology programme.

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.

Implementing the Xpert® MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries.

Background The Xpert® MTB/RIF (Xpert) is an automated molecular test for simultaneous detection of tuberculosis (TB) and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB) or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings. Methods Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire. Findings In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4) and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support. Conclusion The implementation of Xpert was feasible and significantly increased TB detection compared to microscopy, despite the high rate of inconclusive results. Xpert implementation was accompanied by considerable operational and logistical challenges. To further decentralize diagnosis, simpler, low-cost TB technologies well-suited to low-resource settings are still urgently needed.

Diagnostic accuracy evaluation of the ImmunoFlow HCV rapid immunochromatographic test for the detection of hepatitis C antibodies

2% of the worlds population lives with a hepatitis C virus (HCV) infection with highest rates in developing countries. The most common mode of transmission takes place via unsafe blood transfusions and unsafe therapeutic injections. Thus, screening potential blood donors for hepatitis C infection is a must to ensure safe blood transfusions. Rapid immunochromatographic tests are the best suitable test format to be used for screening for blood donors in resource-limited settings. The ImmunoFlow HCV from Core Diagnostics was evaluated at the Paul-Ehrlich-Institute, Germany for its test accuracy on three seropanels. Panel 1 consisted of 26 HCV positive and 55 negative samples, panel 2 of 193 HCV positive samples. Panel 3 contained 116 samples of 10 patients during seroconversion period. 39 of these 116 samples were characterized as HCV positive. The HCV ImmunoFlow had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.8-100) when samples of panel 1 were tested. 191 samples of the 193 samples in panel 2 were correctly by the HCV Immunoflow, resulting in a sensitivity of 99.0%. 9 of 10 HCV infections were detected by the HCV ImmunoFlow when panel 3 was used. This evaluation revealed good sensitivity of the HCV ImmunoFlow test from and compares favorably with the results from the WHO evaluation and a systematic review conducted of field evaluations of Hepatitis C rapid diagnostic and other point of care tests.

Evaluation of two rapid screening assays for detecting hepatitis C antibodies in resource‐constrained settings

To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.

Errors generated by a point-of-care CD4+ T-lymphocyte analyser: a retrospective observational study in nine countries

Abstract Objective To estimate the proportion of invalid results generated by a CD4+ T-lymphocyte analyser used by Médecins Sans Frontières (MSF) in field projects and identify factors associated with invalid results. Methods We collated 25 616 CD4+ T-lymphocyte test results from 39 sites in nine countries for the years 2011 to 2013. Information about the setting, user, training, sampling technique and device repair history were obtained by questionnaire. The analyser performs a series of checks to ensure that all steps of the analysis are completed successfully; if not, an invalid result is reported. We calculated the proportion of invalid results by device and by operator. Regression analyses were used to investigate factors associated with invalid results. Findings There were 3354 invalid test results (13.1%) across 39 sites, for 58 Alere PimaTM devices and 180 operators. The median proportion of errors per device and operator was 12.7% (interquartile range, IQR: 10.3–19.9) and 12.1% (IQR: 7.1–19.2), respectively. The proportion of invalid results varied widely by country, setting, user and device. Errors were not associated with settings, user experience or the number of users per device. Tests performed on capillary blood samples were significantly less likely to generate errors compared to venous whole blood. Conclusion The Alere Pima CD4+ analyser generated a high proportion of invalid test results, across different countries, settings and users. Most error codes could be attributed to the operator, but the exact causes proved difficult to identify. Invalid results need to be factored into the implementation and operational costs of routine CD4+ T-lymphocyte testing.

Evaluation of the Nova StatSensor® XpressTM Creatinine Point-Of-Care Handheld Analyzer

Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification.

Teleradiology Usage and User Satisfaction with the Telemedicine System Operated by Médecins Sans Frontières

Médecins Sans Frontières (MSF) began a pilot trial of store-and-forward telemedicine in 2010, initially operating separate networks in English, French, and Spanish; these were merged into a single, multilingual platform in 2013. We reviewed the pattern of teleradiology usage on the MSF telemedicine platform in the 4-year period from April 2010. In total, 564 teleradiology cases were submitted from 22 different countries. A total of 1114 files were uploaded with the 564 cases, the majority being of type JPEG (n = 1081, 97%). The median file size was 938 kb (interquartile range, IQR 163–1659). A panel of 14 radiologists was available to report cases, but most (90%) were reported by only 4 radiologists. The median radiologist response time was 6.1 h (IQR 3.0–20). A user satisfaction survey was sent to 29 users in the last 6 months of the study. There was a 28% response rate. Most respondents found the radiologist’s advice helpful and all of them stated that the advice assisted in clarification of a diagnosis. Although some MSF sites made substantial use of the system for teleradiology, there is considerable potential for expansion. More promotion of telemedicine may be needed at different levels of the organization to increase engagement of staff.

Quality assessment of X-rays interpreted via teleradiology for Médecins Sans Frontières

Summary Médecins Sans Frontières (MSF) is a humanitarian organisation which provides emergency medical aid in challenging settings; field staff often diagnose and treat patients using limited resources and without the expertise of specialists. Teleradiology is available for MSF sites which use digital computed radiography (CR) imaging or conventional film and chemistry. We conducted a retrospective study of the quality of X-rays utilised by MSF for teleradiology diagnosis over a one-year period. All plain X-ray examinations referred for interpretation using two MSF teleradiology platforms in 2012 were assessed against 15 image criteria and further evaluated as being either diagnostic or non-diagnostic. The sites studied sent an average of 115 images (range 10-452). Images were a mixture of chest, skeletal and abdominal radiographs. The majority of the images were CR (n = 597, 74%). Three sites were MSF/Epicentre installed and operated (Epicentre is a research facility affiliated with MSF); five sites were operated by the ministry of health, imaging patients referred by MSF. The sites performing poorest for quality were all facilities which used film and chemistry (53% non-diagnostic images). The sites performing better for quality were facilities which used CR digital imaging (12% non-diagnostic images), two of which had also undergone radiographer training. Our study suggests that transitioning to CR digital imaging has the potential to improve image quality compared to film and chemistry. Radiography training should be made a priority for all sites with X-ray services. The continued utilisation of X-ray services by MSF where images have proven to be consistently poor should be re-considered.