Journal Article > Meta-AnalysisFull Text
PLoS Negl Trop Dis. 2009 July 7; Volume 3 (Issue 7); DOI:10.1371/journal.pntd.0000488
Yun O, Lima MA, Ellman T, Chambi W, Castillo S, et al.
PLoS Negl Trop Dis. 2009 July 7; Volume 3 (Issue 7); DOI:10.1371/journal.pntd.0000488
BACKGROUND:
Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness.
METHODOLOGY:
From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs.
RESULTS:
Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population.
CONCLUSIONS:
These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed.
Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness.
METHODOLOGY:
From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs.
RESULTS:
Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population.
CONCLUSIONS:
These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 2008 October 4; Volume 103 (Issue 2); DOI:10.1016/j.trstmh.2008.09.001
Roddy P, Marchiol A, Jeffs B, Palma PP, Bernal O, et al.
Trans R Soc Trop Med Hyg. 2008 October 4; Volume 103 (Issue 2); DOI:10.1016/j.trstmh.2008.09.001
In 2005, a Marburg haemorrhagic fever (MHF) outbreak occurred in Uíge province, Angola, which had its epicentre in Uíge municipality. Concurrently, a health facility located a considerable distance from the outbreak's epicentre reported a drastic reduction in attendance, possibly due to a remote effect of the ongoing MHF outbreak. Health officials should devise strategies to ensure that communities far from a filovirus haemorrhagic fever epicentre are not adversely affected by interventions at the epicentre and, to the greatest extent possible, ensure that these peripheral communities receive essential medical care during an epidemic.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2011 May 24; Volume 5 (Issue 5); DOI:10.1371/journal.pntd.0001183
Grolla A, Jones SM, Fernando L, Strong JE, Stroher U, et al.
PLoS Negl Trop Dis. 2011 May 24; Volume 5 (Issue 5); DOI:10.1371/journal.pntd.0001183
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.
Journal Article > ResearchFull Text
J Infect Dis. 2007 November 15; Volume 196 (Issue s2); DOI:10.1086/520544
Roddy P, Weatherill D, Jeffs B, Abaakouk Z, Dorion C, et al.
J Infect Dis. 2007 November 15; Volume 196 (Issue s2); DOI:10.1086/520544
From 27 March 2005 onwards, the independent humanitarian medical aid agency Medecins Sans Frontieres, together with the World Health Organization, the Angolan Ministry of Health, and others, responded to the Marburg hemorrhagic fever (MHF) outbreak in Uige, Angola, to contain the epidemic and care for those infected. This response included community epidemiological surveillance, clinical assessment and isolation of patients with MHF, safe burials and disinfection, home-based risk reduction, peripheral health facility support, psychosocial support, and information and education campaigns. Lessons were learned during the implementation of each outbreak control component, and the subsequent modifications of protocols and strategies are discussed. Similar to what was seen in previous filovirus hemorrhagic fever outbreaks, the containment of the MHF epidemic depended on the collaboration of the affected community. Actively involving all stakeholders from the start of the outbreak response is crucial.
Journal Article > ResearchFull Text
PLOS One. 2012 December 28; Volume 7 (Issue 12); DOI:10.1371/journal.pone.0052986
Roddy P, Howard N, Van Kerkhove MD, Lutwama J, Wamala JF, et al.
PLOS One. 2012 December 28; Volume 7 (Issue 12); DOI:10.1371/journal.pone.0052986
A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect.
Journal Article > ResearchFull Text
Popul Health Metr. 2012 September 4 (Issue 1); DOI:10.1186/1478-7954-10-18.
Caleo GNC, Sy AP, Balandine S, Polonsky JA, Palma PP, et al.
Popul Health Metr. 2012 September 4 (Issue 1); DOI:10.1186/1478-7954-10-18.
During 2010, a community-based, sentinel site prospective surveillance system measured mortality, acute malnutrition prevalence, and the coverage of a Médecins Sans Frontières (MSF) intervention in four sous-préfectures of Lobaye prefecture in southwestern Central African Republic. We describe this surveillance system and its evaluation.
Protocol > Research Study
BMC Infect Dis. 2015 June 12; Volume 15 (Issue 1); DOI:10.1186/s12879-015-0963-3
Denoeud-Ndam L, Dicko A, Baudin E, Guindo O, Grandesso F, et al.
BMC Infect Dis. 2015 June 12; Volume 15 (Issue 1); DOI:10.1186/s12879-015-0963-3
Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded. Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking. The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.
Journal Article > ResearchFull Text
Mem Inst Oswaldo Cruz. 2009 November 1; Volume 104 (Issue 7); DOI:10.1590/S0074-02762009000700008
Escriba JM, Ponce E, Romero Ade D, Albajar Viñas P, Marchiol A, et al.
Mem Inst Oswaldo Cruz. 2009 November 1; Volume 104 (Issue 7); DOI:10.1590/S0074-02762009000700008
Between 1999-2002, Médécins Sans Frontières-Spain implemented a project seeking to determine the efficacy and safety of benznidazole in the treatment of recent chronic Chagas disease in a cohort of seropositive children in the Yoro Department, Honduras. A total of 24,471 children were screened for Trypanosoma cruzi IgG antibodies through conventional enzyme-linked immunosorbent assays (ELISA) on filter paper. Recombinant ELISA (0.93% seroprevalence) showed 256 initially reactive cases, including 232 confirmed positive cases. Of these, 231 individuals were treated with benznidazole (7.5 mg/kg/day) for 60 days and were followed with a strict weekly medical control and follow-up protocol. At the end of the project, 229 patients were examined by the Honduras Secretariat of Health for post-treatment serological assessments; 88.2% seroconverted after 18 months and 93.9% seroconverted after three years. No differences were found in the seroconversion rates according to age or sex. Most of the side effects of the treatment were minor. These results support the argument that in areas where T. cruzi I is predominant and in areas affected by T. cruzi II, when vector transmission has been interrupted, Chagas disease diagnosis and treatment are feasible, necessary and ethically indisputable.
Journal Article > ResearchAbstract
Trop Med Int Health. 2012 March 5; Volume 17 (Issue 5); DOI:10.1111/j.1365-3156.2012.02960.x
Pascual Martinez F, Picado A, Roddy P, Palma PP
Trop Med Int Health. 2012 March 5; Volume 17 (Issue 5); DOI:10.1111/j.1365-3156.2012.02960.x
Objectives Bihar, the poorest state in India, concentrates most of the visceral leishmaniasis (VL) cases in the country. A large proportion of the poor rural communities where VL is endemic are marginalized by their socio-economic status, intrinsically related to the caste system. In this study, we evaluated whether people from low socio-economic strata had difficulties accessing VL treatment in Bihar. As a secondary outcome, we evaluated whether people delaying their VL treatment had poorer clinical indicators at admission. Methods Data on 2187 patients with VL treated by Médecins Sans Frontières (MSF) in Vaishali district from July 2007 to December 2008 were analysed. Patients who reported having onset of symptoms ≥8 weeks before admission were defined as 'late presenters'. Logistic regression models were used to evaluate whether low castes had higher risk to be 'late presenters' compared to the rest of castes and whether 'late presenters' had poorer indicators at admission (i.e. haemoglobin level, spleen size). Results After adjusting for age, gender and distance to VL treatment facility, Mushars (the lowest caste in Bihar) had twice the odds to be 'late presenters' compared to the rest of castes (OR 2.05, 95% CI: 1.24-2.38). Subjects that had VL symptoms for ≥8 weeks had a larger spleen and lower haemoglobin level than those that were treated earlier. Conclusion Low castes have poor access to VL treatment in Bihar, and late presenters have poorer clinical indicators at admission. These findings have implications at individual and community levels and should stimulate targeted VL control programmes to ensure that marginalized communities in Bihar are properly treated.
Journal Article > ReviewFull Text
J Infect Dis. 2011 November 1; Volume 204 (Issue suppl_3); S791-S795.; DOI:10.1093/infdis/jir297
Roddy P, Colebunders R, Jeffs B, Palma PP, Van Herp M, et al.
J Infect Dis. 2011 November 1; Volume 204 (Issue suppl_3); S791-S795.; DOI:10.1093/infdis/jir297
Testing an innovative therapy for filovirus hemorrhagic fever (FHF) in an outbreak setting may be years away. Moreover, beyond anecdotal evidence, little is known about best practice for outbreak case management. Currently, Médecins Sans Frontières and others provide FHF patients with basic supportive treatment. We describe and discuss treatment possibilities, challenges, and potential next steps for FHF outbreak case management. More comprehensive supportive treatment, including vital sign monitoring, intensive care components, and goal-directed interventions may contribute to improved clinical outcome; the feasibility and effectiveness of this more comprehensive supportive treatment should be assessed. Our outlined summary may assist future FHF outbreak case management teams to create collaborative platforms and develop relevant treatment protocols aimed at improving clinical outcome.