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  • Diagnostic Value of Histological Analysis of Punch Biopsies in Suspected Cutaneous Buruli Ulcer: A Study on 32 Cases of Confirmed Buruli Ulcer in Cameroon

    Ibrahim, YL; Masouye, I; Tschanz, E; Atangana, P; Etard, JF; Serafini, M; Mueller, YK; Trellu, LT (Karger, 2019-05-07)
    Background: Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. In this prospective study, we aim to clarify the main histopathological features of cutaneous BU based on 4-mm skin punch biopsies and to evaluate the diagnostic value of this method. Methods: Between 2011 and 2013, a prospective study was conducted in Cameroon. Dry swabs from ulcerative lesions and fine-needle aspirates of nonulcerative lesions were examined for Ziehl-Neelsen (ZN) staining, followed by PCR targeting IS2404 and culture. Two 4-mm punch biopsies were performed in the center and in the periphery of each lesion. Results: The 364 patients included in the study had 422 lesions (381 were ulcerative and 357 lesions were biopsied). Among the 99 ulcerated lesions with a final diagnosis of BU, histological features for BU were fulfilled in 32 lesions. 32/32 showed subcutaneous necrosis with a neutrophilic inflammatory infiltrate. 26/32 presented alcohol-resistant bacilli confirmed by ZN stain on histology. Conclusion: Punch biopsies help in establishing the correct diagnosis of BU and also in the differential diagnosis of chronic ulcers. The main histological feature for BU is diffuse coagulative necrosis of subcutaneous tissue, with acid-fast bacilli detected by ZN stain.
  • Health Care Workers' Perceptions of Point-of-Care Testing in a Low-Income Country-A Qualitative Study in Southwestern Uganda

    Rasti, R; Nanjebe, D; Karlström, J; Muchunguzi, C; Mwanga-Amumpaire, J; Gantelius, J; Mårtensson, A; Rivas, L; Galban, F; Reuterswärd, P; Andersson Svahn, H; Alvesson, H; Boum, Y; Alfvén, T (Public Library of Science, 2017-07-27)
    Point-of-care (POC) tests have become increasingly available and more widely used in recent years. They have been of particular importance to low-income settings, enabling them with clinical capacities that had previously been limited. POC testing programs hold a great potential for significant improvement in low-income health systems. However, as most POC tests are developed in high-income countries, disengagement between developers and end-users inhibit their full potential. This study explores perceptions of POC test end-users in a low-income setting, aiming to support the development of novel POC tests for low-income countries.
  • A Guide to Aid the Selection of Diagnostic Tests

    Kosack, C; Page, A-L; Klatserc, P (World Health Organization, 2017-06-26)
    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 endusers, 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 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.
  • Clinical Research in Neglected Tropical Diseases: The Challenge of Implementing Good Clinical (Laboratory) Practices

    Ravinetto, R; Alirol, E; Mahendradhata, Y; Rijal, S; Lutumba, P; Sacko, M; El-Safi, S; Lim, K; van Loen, H; Jacobs, J; Peeling, RW; Chappuis, F; Boelaert, M (Public Library of Science, 2016-11-03)
  • Analysis of Diagnostic Findings From the European Mobile Laboratory in Guéckédou, Guinea, March 2014 Through March 2015

    Kerber, R; Krumkamp, R; Diallo, B; Jaeger, A; Rudolf, M; Lanini, S; Bore, JA; Koundouno, FR; Becker-Ziaja, B; Fleischmann, E; Stoecker, K; Meschi, S; Mély, S; Newman, ENC; Carletti, F; Portmann, J; Korva, M; Wolff, S; Molkenthin, P; Kis, Z; Kelterbaum, A; Bocquin, A; Strecker, T; Fizet, A; Castilletti, C; Schudt, G; Ottowell, L; Kurth, A; Atkinson, B; Badusche, M; Cannas, A; Pallasch, E; Bosworth, A; Yue, C; Pályi, B; Ellerbrok, H; Kohl, C; Oestereich, L; Logue, CH; Lüdtke, A; Richter, M; Ngabo, D; Borremans, B; Becker, D; Gryseels, S; Abdellati, S; Vermoesen, T; Kuisma, E; Kraus, A; Liedigk, B; Maes, P; Thom, R; Duraffour, S; Diederich, S; Hinzmann, J; Afrough, B; Repits, J; Mertens, M; Vitoriano, I; Bah, A; Sachse, A; Boettcher, JP; Wurr, S; Bockholt, S; Nitsche, A; Županc, TA; Strasser, M; Ippolito, G; Becker, S; Raoul, H; Carroll, MW; De Clerck, H; Van Herp, M; Sprecher, A; Koivogui, L; Magassouba, N; Keïta, S; Drury, P; Gurry, C; Formenty, P; May, J; Gabriel, M; Wölfel, R; Günther, S; Di Caro, A (Oxford University Press, 2016-09-16)
     A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015.
  • Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus

    Dittrich, S; Tadesse, BT; Moussy, F; Chua, A; Zorzet, A; Tängdén, T; Dolinger, DL; Page, AL; Crump, JA; D'Acremont, V; Bassat, Q; Lubell, Y; Newton, PN; Heinrich, N; Rodwell, TJ; González, IJ (Public Library of Science, 2016-08-25)
    Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40°C, ≤90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40°C, ≤90% non-condensing humidity; and iv) minimal sample collection needs (50-100μL, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.
  • Evaluation of Two Rapid Screening Assays for Detecting Hepatitis C Antibodies in Resource-Constrained Settings

    Kosack, CS; Nick, S (Wiley-Blackwell, 2016-03-06)
    To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.
  • Evaluation of the Nova StatSensor® XpressTM Creatinine Point-Of-Care Handheld Analyzer

    Kosack, Cara Simone; de Kieviet, Wim; Bayrak, Kubra; Milovic, Anastacija; Page, Anne Laure (Public Library of Science, 2015-04-17)
    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.
  • Decontamination methods for samples preserved in cetylpyridinium chloride and cultured on thin-layer agar.

    Ardizzoni, E; Mulders, W; Sanchez-Padilla, E; Varaine, F; de Jong, B C; Rigouts, L (2014-08-01)
    Long transportation times of samples to culture laboratories can lead to higher contamination rates and significant loss of viability, resulting in lower culture positivity rates. Thin-layer agar (TLA) is a sensitive culture method for the isolation of Mycobacterium tuberculosis that has been optimised with N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) decontaminated samples. The combination of the TLA culture method and other decontamination procedures has not been extensively validated.
  • Teleradiology quality assurance - lessons learnt

    Spijker, Saskia (SpringerLink, 2014-06)
  • Médecins Sans Frontières teleradiology history

    Spijker, Saskia (SpringerLink, 2014-06)
  • Analysis of a novel field dilution method for testing samples that exceed the analytic range of point-of-care blood lead analyzers.

    Neri, Antonio James; Roy, Joannie; Jarrett, Jeffery; Pan, Yi; Dooyema, Carrie; Caldwell, Kathleen; Umar-Tsafe, Nasir Tsafe; Olubiyo, Ruth; Brown, Mary Jean (Taylor and Francis Group, 2013-10)
    Investigators developed and evaluated a dilution method for the LeadCare II analyzer (LCII) for blood lead levels >65 μg/dL, the analyzer's maximum reporting value. Venous blood samples from lead-poisoned children were initially analyzed in the field using the dilution method. Split samples were analyzed at the US Centers for Disease Control and Prevention (CDC) laboratory using both the dilution method and inductively coupled plasma-mass spectrometry (ICP-MS). The concordance correlation coefficient of CDC LCII vs. ICP-MS values (N = 211) was 0.976 (95 % confidence interval (CI) 0.970-0.981); of Field LCII vs. ICP-MS (N = 68) was 0.910 (95% CI 0.861-0.942), and CDC LCII vs. Field LCII (N = 53) was 0.721 (95% CI 0.565-0.827). Sixty percent of CDC and 54% of Field LCII values were within ±10% of the ICP-MS value. Results from the dilution method approximated ICP-MS values and were useful for field-based decision-making. Specific recommendations for additional evaluation are provided.
  • Rapid Diagnostic Tests for Non-Malarial Febrile Illness in the Tropics

    Chappuis, F; Alirol, E; d'Acremont, V; Bottieau, E; Yansouni, C P; Division of International and Humanitarian Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland; Médecins Sans Frontières, Operational Centre Geneva, Geneva, Switzerland. (2013-02-15)
    The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.
  • Challenges and Opportunities for the Implementation of Virological Testing in resource-limited settings

    Roberts, Teri; Bygrave, Helen; Fajardo, Emmanuel; Ford, Nathan; Médecins Sans Frontières Access Campaign, Geneva, Switzerland. teri.roberts@geneva.msf.org (2012-10-09)
    Though the advantages of routine virological monitoring for patients on anti-retroviral therapy have been established, cost and complexity limit its full implementation. Monitoring is important for diagnosing virological failure early on, before the development of drug resistance mutations, and to trigger early adherence interventions. Simple and cost-effective viral load tests that facilitate simplification and decentralization of testing and strategies, such as the use of dried blood spots and pooled sample testing, which further aid simplification, are becoming available. In addition, replacing immunological monitoring with virological monitoring in non-viremic patients in a phased manner will reduce the costs associated with dual immuno-virological monitoring. Going forward, the simplification of testing paired with price reducing strategies that will allow for healthy competition between multiple manufacturers will enable the implementation of viral load testing in resource-poor settings. It is important that future HIV and AIDS treatment guidelines provide clear recommendations for routine virological monitoring and that governments and donors fund the implementation of accurate and operationally proven testing platforms in a comprehensive manner.
  • Use of filter paper as a transport medium for laboratory diagnosis of cholera under field conditions

    Page, Anne-Laure; Alberti, Kathryn P; Guénolé, Alain; Mondongue, Vital; Lonlas Mayele, Sylvaine; Guerin, Philippe J; Quilici, Marie-Laure; Epicentre, Paris, France; Institut Pasteur, Centre National de Reference des Vibrions et du Cholera, Unite des Bacteries Pathogenes Enteriques, Paris, France; Ministry of Health, Kinshasa, Democratic Republic of Congo; Medecins Sans Frontieres, Brussels, Belgium; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom (American Society for Microbiology, 2011-06-22)
    Confirmation of a cholera epidemic is based on bacteriological identification of the agent and requires the sending of samples to a culture laboratory, often in countries with limited resources. Comparison of the use of filter paper with the use of Cary-Blair reference medium for stool transport showed that this simple transport medium is appropriate for the recovery of Vibrio cholerae.
  • Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien; Médecins sans Frontiérès, Medical Department, Brussels Operational Center, Brussels, Belgium. (2010-09)
    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tests (INNO-LIA HIV-I/II Score) and NEW LAV BLOT II (Bio-Rad). Four hundred and forty three sequential stored HIV-positive serum samples, of known HIV-type, were evaluated. Genie II HIV1/HIV2, Immunoflow HIV1-HIV2 and SD Bioline HIV 1/2 3.0 had 100% sensitivity (95% CI, 98.9-100%) while for First Response HIV Card Test 1-2.0 this was 99.5% (95% CI, 98.2%-99.9%). In terms of discriminatory capacity, Genie II HIV1/HIV2 identified 382/ 384(99.5%) HIV-1 samples, 49/ 52(95%) HIV-2 and 7/7(100%) HIV-positive untypable samples. Immunoflow HIV1-HIV2 identified 99% HIV-1, 67% HIV-2 and all HIV-positive untypable samples. First Response HIV Card Test 1-2.0 identified 94% HIV-1, 64% HIV-2 and 57% HIV-positive untypable samples. SD-Bioline HIV 1/2 3.0 was the worst overall performer identifying 65% HIV-1, 69% HIV-2 and all HIV-positive untypable samples. The use of SD Bioline HIV 1/2 3.0 (the current standard in Guinea-Conakry) as a discriminatory HIV test is poor and may be best replaced by Immunoflow HIV1-HIV2.
  • Outbreak of hepatitis E virus infection in Darfur, Sudan: effectiveness of real-time reverse transcription-PCR analysis of dried blood spots

    Mérens, Audrey; Guérin, Philippe Jean; Guthmann, Jean-Paul; Nicand, Elisabeth; National Reference Laboratory for Hepatitis E, Hospital Val-de-Grâce, Paris, France; Epicentre, Paris, France (2009-04-01)
    Biological samples collected in refugee camps during an outbreak of hepatitis E were used to compare the accuracy of hepatitis E virus RNA amplification by real-time reverse transcription-PCR (RT-PCR) for sera and dried blood spots (concordance of 90.6%). Biological profiles (RT-PCR and serology) of asymptomatic individuals were also analyzed.
  • Field evaluation of a rapid immunochromatographic assay for detection of Trypanosoma cruzi infection by use of whole blood

    Roddy, P; Goiri, J; Flevaud, L; Palma, P; Morote, S; Lima, N; Villa, L; Torrico, F; Albajar-Vinas, P; Médecins Sans Frontières – Spain, Barcelona, Spain; Centro Universitario de Medicina Tropical - Facultad de Medicina, Universidad Mayor de San Simon, Cochabamba, Bolivia; Laboratório de Doenças Parasitárias, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil. (American Society for Microbiology, 2008-06)
    Laboratory and clinical diagnostic classification of seropositive individuals, followed by treatment and supportive therapy, is an established component of Chagas disease control in endemic areas. However, most Chagas-infected patients live in remote areas where neither equipped laboratories nor skilled human resources are widely available. Employing a rapid diagnostic test (RDT), when using whole blood samples, is the best-option for Chagas disease control. A high sensitivity and specificity for the Chagas Stat-Pak(TM) RDT (Chembio Diagnostic Systems, Inc., Medford, NY) has been reported when assayed with serum and plasma but its validity for the detection of antibodies to Trypanosoma cruzi infection in whole blood is unknown. This cross-sectional study measured the sensitivity and specificity of the Chagas Stat-Pak(TM) when using whole blood and conventional serological assays as a comparison. The inter-observer reliability in the interpretation of the Chagas Stat-Pak(TM) results and 'ease of use' criterion needed to perform the Chagas Stat-Pak(TM) and conventional assays were also measured. The Chagas Stat-Pak(TM) yielded a high specificity [99.0%, (95%CI: 98.4%-99.4%)] but a relatively low sensitivity [93.4%, (95%CI: 87.4%-97.1%)]. The inter-observer reliability was excellent [kappa(n=1,913)= .999,(p<.0001)] and quantified 'ease of use' criterion suggested that the RDT is simple to perform. Despite the distinguished attributes of the Chagas Stat-Pak(TM), it is not an ideal diagnostic test for the population investigated in this study due to its relatively low sensitivity and high cost. The RDT manufacturer is called upon to improve the test if the international community hopes to make progress in controlling Chagasic infections in endemic areas.
  • Biological diagnosis of meningococcal meningitis in the African meningitis belt: current epidemic strategy and new perspectives.

    Chanteau, S; Rose, A; Djibo, S; Nato, F; Boisier, P; CERMES, Réseau International Institut Pasteur, PO Box 10887, Niamey, Niger. schanteau@cermes.org (Elsevier, 2007-09-03)
    Laboratory diagnosis is an essential component in surveillance of meningococcal epidemics, as it can inform decision-makers of the Neisseria meningitidis serogroup(s) involved and the most appropriate vaccine to be selected for mass vaccination. However, countries most affected face real limitations in laboratory diagnostics, due to lack of resources. We describe current diagnostic tools and examine their cost-effectiveness for use in an epidemic context. The conclusion is that current WHO recommendations to use only the latex agglutination assay (Pastorex) at epidemic onset is cost-effective, but recently developed rapid diagnostic tests for the major epidemic-causing meningococcal serogroups may prove a breakthrough for the future.
  • Reducing the Number of Sputum Samples Examined and Thresholds for Positivity: An Opportunity to Optimise Smear Microscopy.

    Bonnet, M; Ramsay, A; Gagnidze, L; Githui, W; Guerin, P J J; Varaine, F; Epicentre, Paris, France. maryline.bonnet@geneva.msf.org (International Union Against TB and Lung Disease, 2007-09)
    SETTING: Urban health clinic, Nairobi. OBJECTIVE: To evaluate the impact on tuberculosis (TB) case detection and laboratory workload of reducing the number of sputum smears examined and thresholds for diagnosing positive smears and positive cases. DESIGN: In this prospective study, three Ziehl-Neelsen stained sputum smears from consecutive pulmonary TB suspects were examined blind. The standard approach (A), > or = 2 positive smears out of 3, using a cut-off of 10 acid-fast bacilli (AFB)/100 high-power fields (HPF), was compared with approaches B, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3, one of which is > or = 10 AFB/100 HPF; C, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3; D, > or = 1 positive smear (> or = 10 AFB/100 HPF) out of 2; and E, > or = 1 positive smear (> or = 4 AFB/100 HPF) out of 2. The microscopy gold standard was detection of at least one positive smear (> or = 4 AFB/100 HPF) out of 3. RESULTS: Among 644 TB suspects, the alternative approaches detected from 114 (17.7%) (approach B) to 123 cases (19.1%) (approach E) compared to 105 cases (16.3%) for approach A (P < 0.005). Sensitivity ranged between 82.0% (105/128) for A and 96.1% (123/128) for E. The single positive smear approaches reduced the number of smears by 36% compared to approach A. CONCLUSION: Reducing the number of specimens and the positivity threshold to define a positive case increased the sensitivity of microscopy and reduced laboratory workload.

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