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  • Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern uganda by high-resolution melt analysis.

    Kassaza, K; Long, AC; McDaniels, JM; Andre, M; Fredrickson, W; Nyehangane, D; Orikiriza, P; Operario, DJ; Bazira, J; Mwanga-Amumpaire, JA; et al. (BMC, 2021-02-25)
    The sample source (i.e. Giemsa-stained slides or blood spots) and type of LCGreen-based reagent mixes did not impact the success of PCR-HRM. The detection limit of 10- 5 ng and the ability to identify mixed haplotypes as low as 10 % was similar to other HRM platforms. The CVIET haplotype predominated in the clinical samples (66 %, 162/244); however, there was a large regional variation between the sample groups (94 % CVIET in Group 1 and 44 % CVIET in Group 2).
  • Evaluation of MicroScan Bacterial Identification Panels for Low-Resource Settings.

    Ombelet, S; Natale, A; Ronat, JB; Vandenberg, O; Hardy, L; Jacobs, J (MDPI, 2021-02-19)
    Bacterial identification is challenging in low-resource settings (LRS). We evaluated the MicroScan identification panels (Beckman Coulter, Brea, CA, USA) as part of Médecins Sans Frontières' Mini-lab Project. The MicroScan Dried Overnight Positive ID Type 3 (PID3) panels for Gram-positive organisms and Dried Overnight Negative ID Type 2 (NID2) panels for Gram-negative organisms were assessed with 367 clinical isolates from LRS. Robustness was studied by inoculating Gram-negative species on the Gram-positive panel and vice versa. The ease of use of the panels and readability of the instructions for use (IFU) were evaluated. Of species represented in the MicroScan database, 94.6% (185/195) of Gram-negative and 85.9% (110/128) of Gram-positive isolates were correctly identified up to species level. Of species not represented in the database (e.g., Streptococcus suis and Bacillus spp.), 53.1% out of 49 isolates were incorrectly identified as non-related bacterial species. Testing of Gram-positive isolates on Gram-negative panels and vice versa (n = 144) resulted in incorrect identifications for 38.2% of tested isolates. The readability level of the IFU was considered too high for LRS. Inoculation of the panels was favorably evaluated, whereas the visual reading of the panels was considered error-prone. In conclusion, the accuracy of the MicroScan identification panels was excellent for Gram-negative species and good for Gram-positive species. Improvements in stability, robustness, and ease of use have been identified to assure adaptation to LRS constraints.
  • Heat-stability study of various insulin types in tropical temperature conditions: New insights towards improving diabetes care.

    Kaufmann, B; Boulle, P; Berthou, F; Fournier, M; Beran, D; Ciglenecki, I; Townsend, M; Schmidt, G; Shah, M; Cristofani, S; et al. (Public Library of Science, 2021-02-03)
    Strict storage recommendations for insulin are difficult to follow in hot tropical regions and even more challenging in conflict and humanitarian emergency settings, adding an extra burden to the management of people with diabetes. According to pharmacopeia unopened insulin vials must be stored in a refrigerator (2-8°C), while storage at ambient temperature (25-30°C) is usually permitted for the 4-week usage period during treatment. In the present work we address a critical question towards improving diabetes care in resource poor settings, namely whether insulin is stable and retains biological activity in tropical temperatures during a 4-week treatment period. To answer this question, temperature fluctuations were measured in Dagahaley refugee camp (Northern Kenya) using log tag recorders. Oscillating temperatures between 25 and 37°C were observed. Insulin heat stability was assessed under these specific temperatures which were precisely reproduced in the laboratory. Different commercialized formulations of insulin were quantified weekly by high performance liquid chromatography and the results showed perfect conformity to pharmacopeia guidelines, thus confirming stability over the assessment period (four weeks). Monitoring the 3D-structure of the tested insulin by circular dichroism confirmed that insulin monomer conformation did not undergo significant modifications. The measure of insulin efficiency on insulin receptor (IR) and Akt phosphorylation in hepatic cells indicated that insulin bioactivity of the samples stored at oscillating temperature during the usage period is identical to that of the samples maintained at 2-8°C. Taken together, these results indicate that insulin can be stored at such oscillating ambient temperatures for the usual four-week period of use. This enables the barrier of cold storage during use to be removed, thereby opening up the perspective for easier management of diabetes in humanitarian contexts and resource poor settings.
  • The Mini-Lab: accessible clinical bacteriology for low-resource settings

    Natale, A; Ronat, JB; Mazoyer, A; Rochard, A; Boillot, B; Hubert, J; Baillet, B; Ducasse, M; Mantelet, F; Oueslati, S; et al. (Elsevier, 2020-06-01)
  • The impact of computed radiography and teleradiology on patients' diagnosis and treatment in Mweso, the Democratic Republic of Congo.

    Crumley, I; Halton, J; Greig, J; Kahunga, L; Mwanga, JP; Chua, A; Kosack, C (Public Library of Science, 2020-01-15)
    Introduction: 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. Method: 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. Results: 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. Conclusion: 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.
  • Best Practices of Blood Cultures in Low- and Middle-Income Countries

    Ombelet, S; Barbe, B; Affolabi, D; Ronat, JB; Lompo, P; Lunguya, O; Jacobs, J; Hardy, L (Frontiers Media, 2019-06-18)
    Bloodstream infections (BSI) have a substantial impact on morbidity and mortality worldwide. Despite scarcity of data from many low- and middle-income countries (LMICs), there is increasing awareness of the importance of BSI in these countries. For example, it is estimated that the global mortality of non-typhoidal Salmonella bloodstream infection in children under 5 already exceeds that of malaria. Reliable and accurate diagnosis of these infections is therefore of utmost importance. Blood cultures are the reference method for diagnosis of BSI. LMICs face many challenges when implementing blood cultures, due to financial, logistical, and infrastructure-related constraints. This review aims to provide an overview of the state-of-the-art of sampling and processing of blood cultures, with emphasis on its use in LMICs. Laboratory processing of blood cultures is relatively straightforward and can be done without the need for expensive and complicated equipment. Automates for incubation and growth monitoring have become the standard in high-income countries (HICs), but they are still too expensive and not sufficiently robust for imminent implementation in most LMICs. Therefore, this review focuses on “manual” methods of blood culture, not involving automated equipment. In manual blood cultures, a bottle consisting of a broth medium supporting bacterial growth is incubated in a normal incubator and inspected daily for signs of growth. The collection of blood for blood culture is a crucial step in the process, as the sensitivity of blood cultures depends on the volume sampled; furthermore, contamination of the blood culture (accidental inoculation of environmental and skin bacteria) can be avoided by appropriate antisepsis. In this review, we give recommendations regarding appropriate blood culture sampling and processing in LMICs. We present feasible methods to detect and speed up growth and discuss some challenges in implementing blood cultures in LMICs, such as the biosafety aspects, supply chain and waste management.
  • 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; et al. (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; et al. (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; et al. (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; et al. (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.
  • Médecins Sans Frontières teleradiology history

    Spijker, Saskia (SpringerLink, 2014-06)
  • Teleradiology quality assurance - lessons learnt

    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. (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.

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