In recent years, a wide range of diagnostic tests has become available for use in resource-constrained settings. Accordingly, a huge number of guidelines, performance evaluations and implementation ...reports have been produced. However, this wealth of information is unstructured and of uneven quality, which has made it difficult for end-users, such as clinics, laboratories and health ministries, to determine which test would be best for improving clinical care and patient outcomes in a specific context. This paper outlines a six-step guide to the selection and implementation of in vitro diagnostic tests based on Médecins Sans Frontières' practical experience: (i) define the test's purpose; (ii) review the market; (iii) ascertain regulatory approval; (iv) determine the test's diagnostic accuracy under ideal conditions; (v) determine the test's diagnostic accuracy in clinical practice; and (vi) monitor the test's performance in routine use. Gaps in the information needed to complete these six steps and gaps in regulatory systems are highlighted. Finally, ways of improving the quality of diagnostic tests are suggested, such as establishing a model list of essential diagnostics, establishing a repository of information on the design of diagnostic studies and improving quality control and postmarketing surveillance.
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.
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.
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.
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.
Objective
To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.
Methods
Five seropanels from patients, ...intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany.
Results
Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5–100) and a specificity of 100% (95% CI: 86.3–100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5–100) and a specificity of 96% (95% CI: 79.6–99.9). Panel 2 consisted of 193 pre‐characterised anti‐HCV‐positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3–99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1–100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti‐HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co‐infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8–82.8) after 20 min and 73.9% (95% CI: 51.3–88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4–99.9).
Conclusion
This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false‐negative results in almost 25% of the HIV‐positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.
Objectif
Evaluer la précision diagnostique de deux tests rapides d'anticorps: OraQuick HCV de OraSure et MultiSure HCV de MP Biomedicals.
Méthodes
Cinq séries d’échantillons sanguins de patients, d'usagers de drogues injectables et de donneurs de sang avec et sans infection par le VHC ont été utilisées dans les deux tests rapides immunochromatographiques. La sensibilité, la spécificité et les valeurs prédictives ont été calculées. En outre, des séries d’échantillons sanguins de 10 séroconversions ont été utilisées pour évaluer l'identification précoce de l'infection par le VHC. L’étude a été réalisée dans un laboratoire de l'Institut Paul Ehrlich en Allemagne.
Résultats
La série 1 contenait 55 échantillons positifs et 25 négatifs. Le test OraQuick HCV avait une sensibilité de 100% (IC95%: 93,5 à 100) et une spécificité de 100% (IC95%: 86,3 à 100). Le test MultiSure HCV avait une sensibilité de 100% (IC95%: 93,5 à 100) et une spécificité de 96% (IC95%: 79,6 à 99,9). La série 2 était composée de 193 échantillons de patients pré‐caractérisés anti‐VHC positifs. Le test OraQuick HCV a identifié 191 échantillons correctement et MultiSure HCV, 192. La sensibilité était de 99,0% (IC95%: 96,3 à 99,9) pour le test OraQuick HCV et de 99,5% (IC95%: 97,1 à 100) pour le test MultiSure HCV. La série 3 était composée d’échantillons de séroconversion de 10 patients. Le test OraQuick HCV a détecté toutes ces 10 infections alors que le test MultiSure HCV en a détecté 6 et était indéterminé pour 2. La série 4 était composée de 53 échantillons de donneurs de sang de sang anti‐VHC négatifs. Les deux tests ont correctement identifié tous les 53 échantillons. La série 5 était composée de 26 échantillons de patients coinfectés VHC/VIH. La sensibilité du test OraQuick HCV était de 65,2% (IC95%: 42,8 à 82,8) après 20 minutes et 73,9% (IC95%: 51.3‐88.9) après 40 minutes d'incubation; le test MultiSure HCV y avait une sensibilité de 96,2% (IC95%: 80,4 à 99,9).
Conclusion
Cette évaluation a révélé une bonne sensibilité pour les deux tests de dépistage rapide, quoique le test MultiSure HCV a détecté moins de séroconversions. Le test OraQuick a donné des résultats VHC faux négatifs dans presque 25% des échantillons VIH positifs. Par conséquent, le test MultiSure devrait être utilisé avec prudence dans les zones à forte incidence, tandis que le test OraQuick pourrait être moins adapté dans les zones prévalentes pour le VIH.
Objetivo
Evaluar la precisión diagnóstica de la prueba rápida para la detección de anticuerpos anti‐VHC OraQuick de OraSure y el análisis de anticuerpos Multisure HCV de MP Biomedicals.
Métodos
Se analizaron cinco paneles de suero de pacientes, usuarios de drogas intravenosas y donantes de sangre con y sin infección por VHC, utilizando dos pruebas rápidas inmunocromáticas. Se calcularon la sensibilidad, especificidad y valores predictivos. Adicionalmente, se utilizaron paneles de suero de 10 seroconversores para evaluar la identificación temprana de la infección por VHC. Este estudio se realizó en un laboratorio del Instituto Paul Ehrlich en Alemania.
Resultados
El panel 1 contenía 55 muestras positivas y 25 muestras negativas. La prueba OraQuick HCV tenía una sensibilidad del 100% (IC 95%: 93.5–100) y una especificidad del 100% (IC 95%: 86.3–100). La prueba Multisure HCV tenía una sensibilidad del 100% (IC 95%: 93.5–100) y una especificidad del 96% (IC 95%: 79.6–99.9). El Panel 2 consistía de 193 muestras pre‐caracterizadas de pacientes anti‐VHC‐positivas. La prueba OraQuick HCV identificó 191 muestras correctamente y la Multisure HCV, 192. La sensibilidad era del 99.0% (IC 95%: 96.3–99.9) para la prueba OraQuick HCV y 99.5% (IC 95%: 97.1–100) para la prueba Multisure HCV. El Panel 3 estaba compuesto de muestras de 10 pacientes con seroconversión. La prueba OraQuick HCV detectó todas las 10 infecciones, mientras que la prueba Multisure HCV detectó 6, y era indeterminada en 2. El Panel 4 incluía 53 muestras de sangre anti‐VHC negativas de donantes de sangre. Ambas pruebas identificaron correctamente a las 53. El Panel 5 consistía de 26 muestras de pacientes coinfectadas con VHC/VIH. La sensibilidad de la prueba OraQuick HCV era del 65.2% (IC 95%: 42.8–82.8) después de 20 minutos y del 73.9% (IC 95%: 51.3–88.9) después de 40 minutos de incubación. La prueba Multisure HCV tenía una sensibilidad del 96.2% (IC 95%: 80.4–99.9).
Conclusión
Esta evaluación reveló una buena sensibilidad para ambas pruebas de cribado rápido, aunque la prueba MultiSure HCV detectó menos seroconversiones. El OraQuick dio resultados de falsos negativos de VHC en casi un 25% de los sueros VIH positivos. Por lo tanto la prueba MultiSure debería utilizarse con precaución en lugares con una alta incidencia, mientras que la de OraQuick podría ser menos adecuada en áreas con prevalencia de VIH.
Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case ...management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.
•Evaluation of rapid immunochromatographic ImmunoFlow HCV from Core Diagnostics at the Paul-Ehrlich-Institute, Germany on three seropanels.•Overall the sensitivity and the specificity were >99.0% and ...100%.•Nine of ten patients during the seroconversion period were correctly identified.
2% of the world's 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.
High quality diagnostic imaging can provide increased diagnostic accuracy and help guide medical decision-making and management, however challenges for radiology in resource-limited settings are ...numerous. Diagnostic imaging and teleradiology have financial and logistical implications, so evidence of impact is crucial. We sought to test the hypothesis that the implementation of computed radiography with teleradiology consultation support will significantly change diagnoses and treatment plans in a resource limited setting.
Paired before-after study to determine the therapeutic impact of an add-on diagnostic test. 'Preliminary Plan' and 'Final Plan' forms allowed direct comparison of diagnosis and treatment plans at initial consultation and following radiography and teleradiology. Consecutive consenting patients were included until the sample size (600) was reached. Changes in both diagnosis and treatment plan were analysed in the whole cohort, with sub-analyses of children aged <5 years, and cases of chest radiography.
Final analysis included 536 cases. Diagnosis changed following radiography and teleradiology in 62% of cases, and treatment plans changed in 61%. In chest radiography cases, 70% of diagnoses and 62% of treatment plans changed, while in children <5 years 66% of diagnoses and 58% of treatment plans changed. Reduced final treatment plans were most common for exploratory surgery (72% decrease), surgical orthopaedic intervention (62% decrease), and TB treatment (52% decrease), allowing more conservative medical or surgical management in 61 cases. Increased final treatment plans were highest in the orthopaedic and interventional surgery and referral categories. Of 42 cases requiring interventional surgery in the final plan, 26 (62%) were identified only after radiography and teleradiology. 16 additional cases were indicated for orthopaedic surgery, 10 cases required patient transfer, and TB treatment was indicated in 45 cases. A change in the original prescription plan occurred in 41% of 536 cases, with one or more prescriptions stopped in 28% of all cases.
We found that computed radiography with teleradiology had significant clinical value in this resource-limited setting, with the potential to affect both patient outcomes and treatment costs through providing improved diagnostics and avoiding unnecessary treatments and medications.
Malaria rapid diagnostic tests (RDTs) are commonly used in Médecins Sans Frontières (MSF) programmes to detect acute malaria infection. Programmes in regions with both Plasmodium falciparum and ...non-falciparum malaria (i.e. Plasmodium ovale, Plasmodium malariae and Plasmodium vivax) use a three-band P. falciparum/Pan test such as the SD Bioline Malaria Ag P.f/Pan 05FK60 (Standard Diagnostics, Kyonggi, Republic of Korea), hereafter referred to as SD 05FK60, as used by the MSF-Holland clinics in Rakhine state, Myanmar. In spite of published reports of generally good test performance, medical and paramedical staff on the ground often doubt the diagnostic accuracy of these RDTs.
Parallel testing with malaria microscopy and RDT was conducted at two clinics in Rakhine state, Myanmar, for a period of 14 months as a programmatic response due to doubts and concerns of medical and paramedical staff into malaria RDTs.
A total of 2,585 blood samples from non-pregnant suspected malaria patients were examined by the SD 05FK60 RDT and microscopy at two clinics in Myanmar from October 2010 to December 2011. The reference standard microscopy diagnosed 531 P. falciparum and 587 P. vivax or P. malariae mono-infections. The overall sensitivity for P. falciparum detection by the SD 05FK60 was 90.2% (95% CI: 87.4-92.6) and for P. vivax/P. malariae 79.4% (95% CI: 75.9-82.6). The overall specificity for P. falciparum detection by the SD 05FK60 was 98.5% (95% CI: 97.7-99.1) and for P. vivax/P. malariae 98.7% (95% CI: 97.9-99.2). The sensitivity for P. falciparum was >91% for parasitaemia levels of >100-1,000 parasites/μl and increased for P. vivax/P. malariae with the parasitaemia level but was overall lower than for P. falciparum 25/408 and 13/420 cases, respectively, of P. falciparum and non-falciparum malaria were missed by the RDT.
In field conditions in Myanmar, the SD 05FK60 malaria RDT performed consistent with other reports. The test detected malaria caused by P. vivax/P. malariae to a lesser extent than P. falciparum infection. Sensitivity improved with increasing parasitaemia level, however even at higher levels some infections were missed. The SD 05FK60 is adequate for use in settings where high quality microscopy is not available.
Malawi has one of the world's 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.
Médecins Sans Frontières, in collaboration with Malawi's Ministry of Health, implemented teleradiology in Thyolo district to assist clinical staff in radiologic image interpretation and diagnosis.
Thyolo district's 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.
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 radiologist's review corrected the misdiagnosis of tuberculosis and averted inappropriate treatment in 16 patients (10.5%).
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.
In medical humanitarian assistance, the diagnosis of diseases plays a crucial role. Laboratory investigations are one of the main diagnostic tools utilized in Médecins Sans Frontières' (MSF) ...programs. Currently MSF supports and/or operates more than 130 laboratories in approximately 45 countries. The variety of analysis offered depends largely on the context of the program and the availability of context adapted tools and ranges from sophisticated laboratories specializing in tuberculosis culture to small laboratories within a primary health care program or operating as mobile clinics. The largest laboratories in MSF are found in programs with the main objective to diagnose, treat and monitor patients with tuberculosis and/or human immunodeficiency virus. Other MSF programs are either disease-specific (e.g., malaria, Chagas, kala azar or visceral leishmaniasis, sleeping sickness, malnutrition, sexually transmitted infections) or are integrated in primary or secondary health care structures.
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