• Treatment of Marburg and Ebola hemorrhagic fevers: A strategy for testing new drugs and vaccines under outbreak conditions.

      Bausch, D G; Sprecher, A G; Jeffs, B; Boumandouki, P; Tulane University Health Sciences Center, New Orleans, LA, United States. (2008-04)
      The filoviruses, Marburg and Ebola, have the dubious distinction of being associated with some of the highest case-fatality rates of any known infectious disease-approaching 90% in many outbreaks. In recent years, laboratory research on the filoviruses has produced treatments and vaccines that are effective in laboratory animals and that could potentially drastically reduce case-fatality rates and curtail outbreaks in humans. However, there are significant challenges in clinical testing of these products and eventual delivery to populations in need. Most cases of filovirus infection are recognized only in the setting of large outbreaks, often in the most remote and resource-poor areas of sub-Saharan Africa, with little infrastructure and few personnel experienced in clinical research. Significant political, legal, and socio-cultural barriers also exist. Here, we review the present research priorities and environment for field study of the filovirus hemorrhagic fevers and outline a strategy for future prospective clinical research on treatment and vaccine prevention.
    • Treatment of neuropathic pain in Sierra Leone.

      Lacoux, P; Ford, N; Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK. office@london.msf.uk (Elsevier, 2002-07)
      During Sierra Leone's violent decade-long war, the warring parties used amputation, especially of arms, as a means of terror. In a camp for amputees in the capital city Freetown, Médecins Sans Frontières established a clinic and a treatment programme for neuropathic pain. Insecurity and cultural and language barriers have complicated this work, but medical and humanitarian benefits have been demonstrated. Pain services are virtually non-existent in less-developed countries. There have recently been no major treatment advances for neuropathic or phantom pain; however, the general body of knowledge about amputation pain can be increased by observations from these difficult settings.
    • Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980-2004.

      Olliaro, P L; Guerin, P J; Gerstl, S; Haaskjold, A A; Rottingen, J A; Sundar, S; UNICEF/UNDP/World Bank/WHO Special Programme on Research and Training in Tropical Diseases, WHO, Geneva, Switzerland. olliarop@who.int (Elsevier, 2005-12)
      The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.
    • Treatment outcomes in a cohort of Palestine refugees with diabetes mellitus followed through use of E-Health over 3 years in Jordan

      Khader, Ali; Ballout, Ghada; Shahin, Yousef; Hababeh, Majed; Farajallah, Loai; Zeidan, Wafaa; Abu-Zayed, Ishtaiwi; Kochi, Arata; Harries, Anthony D; Zachariah, Rony; et al. (John Wiley & Sons Ltd, 2014-02)
      The aim of this study was to use E-Health to report on 12-month, 24-month and 36-month outcomes and late-stage complications of a cohort of Palestine refugees with diabetes mellitus (DM) registered in the second quarter of 2010 in a primary healthcare clinic in Amman, Jordan.
    • Treatment outcomes in a cohort of patients with chronic hepatitis B and human immunodeficiency virus co-infection in Mumbai, India

      Isaakidis, Petros; Mansoor, Homa; Zachariah, Rony; Da Silva, Esdras A.; Varghese, Bhanumati; Deshpande, Alaka; Dal Molin, Tiago A.; Ladomirska, Joanna; Arnould, Line; Reid, Tony (2012-10)
    • Tuberculosis treatment in a refugee and migrant population: 20 years of experience on the Thai-Burmese border.

      Minetti, A; Camelique, O; Hsa Thaw, K; Thi, S; Swaddiwudhipong, W; Hewison, C; Pinoges, L; Bonnet, M; Guerin, P J; Médecins Sans Frontières, Paris, France. andrea.minetti@epicentre.msf.org (International Union Against Tuberculosis and Lung Disease, 2010-12)
      Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants.
    • Tungiasis: a highly neglected disease among neglected diseases. Case series from Nduta refugee camp (Tanzania).

      Najera Villagrana, SM; Garcia Naranjo Santisteban, A (Oxford University Press, 2019-06-24)
      Tungiasis is a highly prevalent yet neglected disease of populations affected by extreme poverty. It causes great discomfort and pain, leads to social stigmatization and, when left untreated, can cause serious complications. Although natural repellents have been shown to be effective, too little is being done in terms of systematic prevention and treatment. In addition, self-treatment (usually extraction of fleas with non-sterile sharp instruments) comports high risks of infection, notably with viral hepatitis and human immunodeficiency virus. In this article, we report seven severe cases of tungiasis in children living in a refugee camp in Tanzania, all of whom were treated with surgical extraction of the fleas because the topical treatment (dimethicone) was not available. Refugee camps-particularly in sub-Saharan Africa where tungiasis is endemic-should be considered high-risk areas for the condition. Aid organizations should engage in active case searching, and health promotion should be systematically carried out.
    • Typhoid fever outbreak in the Democratic Republic of Congo: Case control and ecological study

      Brainard, J; D’hondt, R; Ali, E; Van den Bergh, R; De Weggheleire, A; Baudot, Y; Patigny, F; Lambert, V; Zachariah, R; Maes, P; et al. (Public Library of Science, 2018-10-03)
      During 2011 a large outbreak of typhoid fever affected an estimated 1430 people in Kikwit, Democratic Republic of Congo. The outbreak started in military camps in the city but then spread to the general population. This paper reports the results of an ecological analysis and a case-control study undertaken to examine water and other possible transmission pathways. Attack rates were determined for health areas and risk ratios were estimated with respect to spatial exposures. Approximately 15 months after the outbreak, demographic, environmental and exposure data were collected for 320 cases and 640 controls residing in the worst affected areas, using a structured interview questionnaire. Unadjusted and adjusted odds ratios were estimated. Complete data were available for 956 respondents. Residents of areas with water supplied via gravity on the mains network were at much greater risk of disease acquisition (risk ratio = 6.20, 95%CI 3.39–11.35) than residents of areas not supplied by this mains network. In the case control study, typhoid was found to be associated with ever using tap water from the municipal supply (OR = 4.29, 95% CI 2.20–8.38). Visible urine or faeces in the latrine was also associated with increased risk of typhoid and having chosen a water source because it is protected was negatively associated. Knowledge that washing hands can prevent typhoid fever, and stated habit of handwashing habits before cooking or after toileting was associated with increased risk of disease. However, observed associations between handwashing or plate-sharing with disease risk could very likely be due to recall bias. This outbreak of typhoid fever was strongly associated with drinking water from the municipal drinking water supply, based on the descriptive and analytic epidemiology and the finding of high levels of faecal contamination of drinking water. Future outbreaks of potentially waterborne disease need an integrated response that includes epidemiology and environmental microbiology during early stages of the outbreak.
    • Ulcere de Buruli

      Comte E; MSF Suisse (2008-01)
    • L'Ulcère de Buruli, Un Exemple de Plaies Chroniques en Milieu Tropical

      Vuagnat, H; Comte, E; L'Hôpitaux Universaires de Genève, Suisse; Médecins Sans Frontières, Genève, Suisse (2009-06)
    • An unfolding tragedy of Chagas disease in North America.

      Hotez, Peter J; Dumonteil, Eric; Betancourt Cravioto, Miguel; Bottazzi, Maria Elena; Tapia-Conyer, Roberto; Meymandi, Sheba; Karunakara, Unni; Ribeiro, Isabela; Cohen, Rachel M; Pecoul, Bernard; et al. (PLoS, 2013-11)
    • Unique Human Immune Signature of Ebola Virus Disease in Guinea

      Ruibal, P; Oestereich, L; Lüdtke, A; Becker-Ziaja, B; Wozniak, DM; Kerber, R; Korva, M; Cabeza-Cabrerizo, M; Bore, JA; Koundouno, FR; et al. (Nature Publishing Group, 2016-05-05)
      Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
    • Unreported cases in the 2014-2016 Ebola epidemic: Spatiotemporal variation, and implications for estimating transmission

      Dalziel, BD; Lau, MSY; Tiffany, A; McClelland, A; Zelner, J; Bliss, JR; Grenfell, BY (2018-01-22)
      In the recent 2014-2016 Ebola epidemic in West Africa, non-hospitalized cases were an important component of the chain of transmission. However, non-hospitalized cases are at increased risk of going unreported because of barriers to access to healthcare. Furthermore, underreporting rates may fluctuate over space and time, biasing estimates of disease transmission rates, which are important for understanding spread and planning control measures. We performed a retrospective analysis on community deaths during the recent Ebola epidemic in Sierra Leone to estimate the number of unreported non-hospitalized cases, and to quantify how Ebola reporting rates varied across locations and over time. We then tested if variation in reporting rates affected the estimates of disease transmission rates that were used in surveillance and response. We found significant variation in reporting rates among districts, and district-specific rates of increases in reporting over time. Correcting time series of numbers of cases for variable reporting rates led, in some instances, to different estimates of the time-varying reproduction number of the epidemic, particularly outside the capital. Future analyses that compare Ebola transmission rates over time and across locations may be improved by considering the impacts of differential reporting rates.
    • Unusual presentation of acute annular urticaria: A case report

      Guerrier, Gilles; Daronat, Jean-Marc; Deltour, Roger; Epicentre, Paris, France; Agence de Sant´e, Wallis, France (Hindawi Publishing Corporation, 2011-07)
      Acute urticarial lesions may display central clearing with ecchymotic or haemorrhagic hue, often misdiagnosed as erythema multiforme, serum-sickness-like reactions, or urticarial vasculitis. We report a case of acute annular urticaria with unusual presentation occurring in a 20-month-old child to emphasize the distinctive morphologic manifestations in a single disease. Clinicians who care for children should be able to differentiate acute urticaria from its clinical mimics. A directed history and physical examination can reliably orientate necessary diagnostic testing and allow for appropriate treatment.
    • Urban yellow fever outbreak—Democratic Republic of the Congo, 2016: Towards more rapid case detection

      Ingelbeen, B; Weregemere, NA; Noel, H; Tshapenda, GP; Mossoko, M; Nsio, J; Ronsse, A; Ahuka-Mundeke, S; Cohuet, S; Kebela, BI (Public Library of Sciences, 2018-12-07)
      Background Between December 2015 and July 2016, a yellow fever (YF) outbreak affected urban areas of Angola and the Democratic Republic of the Congo (DRC). We described the outbreak in DRC and assessed the accuracy of the YF case definition, to facilitate early diagnosis of cases in future urban outbreaks. Methodology/Principal findings In DRC, suspected YF infection was defined as jaundice within 2 weeks after acute fever onset and was confirmed by either IgM serology or PCR for YF viral RNA. We used case investigation and hospital admission forms. Comparing clinical signs between confirmed and discarded suspected YF cases, we calculated the predictive values of each sign for confirmed YF and the diagnostic accuracy of several suspected YF case definitions. Fifty seven of 78 (73%) confirmed cases had travelled from Angola: 88% (50/57) men; median age 31 years (IQR 25–37). 15 (19%) confirmed cases were infected locally in urban settings in DRC. Median time from symptom onset to healthcare consultation was 7 days (IQR 6–9), to appearance of jaundice 8 days (IQR 7–11), to sample collection 9 days (IQR 7–14), and to hospitalization 17 days (IQR 11–26). A case definition including fever or jaundice, combined with myalgia or a negative malaria test, yielded an improved sensitivity (100%) and specificity (57%). Conclusions/Significance As jaundice appeared late, the majority of cases were diagnosed too late for supportive care and prompt vector control. In areas with known local YF transmission, a suspected case definition without jaundice as essential criterion could facilitate earlier YF diagnosis, care and control.
    • The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa

      O'Brien, Daniel P; Comte, Eric; Serafini, Micaela; Ehounou, Geneviève; Antierens, Annick; Vuagnat, Hubert; Christinet, Vanessa; Hamani, Mitima D; du Cros, Philipp; Manson Unit, Médecins Sans Frontières, London, UK; Department of Infectious Diseases, Geelong Hospital, Geelong, VIC, Australia; Department of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. Electronic address: daniel.obrien@amsterdam.msf.org. (Elsevier, 2013-12-02)
      Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one of the least studied major neglected tropical diseases. In Africa, major constraints in the management of Buruli ulcer relate to diagnosis and treatment, and accessibility, feasibility, and delivery of services. In this Personal View, we outline key areas for clinical, diagnostic, and operational research on this disease in Africa and propose a research agenda that aims to advance the management of Buruli ulcer in Africa. A model of care is needed to increase early case detection, to diagnose the disease accurately, to simplify and improve treatment, to reduce side-effects of treatment, to deal with populations with HIV and tuberculosis appropriately, to decentralise care, and to scale up coverage in populations at risk. This approach will require commitment and support to strategically implement research by national Buruli ulcer programmes and international technical and donor organisations, combined with adaptations in programme design and advocacy. A critical next step is to build consensus for a research agenda with WHO and relevant groups experienced in Buruli ulcer care or related diseases, and we call on on them to help to turn this agenda into reality.
    • Use of a Cholera Rapid Diagnostic Test during a Mass Vaccination Campaign in Response to an Epidemic in Guinea, 2012

      Martinez-Pino, Isabel; Luquero, Francisco J; Sakoba, Kéïta; Sylla, Souleymane; Haile, Melatwork; Grais, RFebecca F; Ciglenecki, Iza; Quilici, Marie-Laure; Page, Anne-Laure; European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden ; Epicentre, Paris, France. (Public Library of Science, 2013-08-15)
      During the 2012 cholera outbreak in the Republic of Guinea, the Ministry of Health, supported by Médecins Sans Frontières - Operational Center Geneva, used the oral cholera vaccine Shanchol as a part of the emergency response. The rapid diagnostic test (RDT) Crystal VC, widely used during outbreaks, detects lipopolysaccharide antigens of Vibrio cholerae O1 and O139, both included in Shanchol. In the context of reactive use of a whole-cell cholera vaccine in a region where cholera cases have been reported, it is essential to know what proportion of vaccinated individuals would be reactive to the RDT and for how long after vaccination.
    • The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg outbreak in Angola

      Grolla, Allen; Jones, Steven M.; Fernando, Lisa; Strong, James E.; Ströher, Ute; Möller, Peggy; Paweska, Janusz T.; Burt, Felicity; Pablo Palma, Pedro; Sprecher, Armand; et al. (Public Library of Science, 2011-05-24)
      Background: Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. Methodology/Principal Findings: A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in ,4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. Conclusions/Significance: The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation.
    • The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource Constrained Settings: A Perspective from the Field

      van Griensven, Johan; De Weiggheleire, Anja; Delamou, Alexandre; Smith, Peter G; Edwards, Tansy; Vandekerckhove, Philippe; Ibrahima Bah, Elhadj; Colebunders, Robert; Herve, Isola; Lazaygues, Catherine; et al. (Oxford University Press, 2015-08-10)
      The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola Virus Disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, non-randomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea enrolled 102 patients by July 7, 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. While no efficacy data are available yet, current field experience supports the safety, acceptability and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from non-trial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.
    • Using European Travellers as an Early Alert to Detect Emerging Pathogens in Countries with Limited Laboratory Resources.

      Guerin, P J; Grais, RF; Rottingen, J A; Valleron, A J; Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway. philippe.guerin@epicentre.msf.org (2007)
      BACKGROUND: The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1) in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. METHODS: We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. RESULTS: Prior to a large epidemic in 1999-2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. CONCLUSION: This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control.