Journal Article > ResearchSubscription Only
Pediatr Blood Cancer
Pediatric blood and cancer. 2023 December 5; Online ahead of print; e30792.; DOI:10.1002/pbc.30792
Luna‐Fineman S, Castellanos M, Metzger ML, Baez LF, Peña Hernandez A, et al.
Pediatr Blood Cancer
Pediatric blood and cancer. 2023 December 5; Online ahead of print; e30792.; DOI:10.1002/pbc.30792
BACKGROUND/OBJECTIVES
High‐risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology‐Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes.
METHODS
Newly diagnosed children less than 18 years of age with high‐risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation.
RESULTS
Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty‐one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five‐year abandonment‐sensitive event‐free survival and overall survival (AS‐EFS, AS‐OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5‐year AS‐OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006).
CONCLUSION
Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.
High‐risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology‐Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes.
METHODS
Newly diagnosed children less than 18 years of age with high‐risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation.
RESULTS
Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty‐one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five‐year abandonment‐sensitive event‐free survival and overall survival (AS‐EFS, AS‐OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5‐year AS‐OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006).
CONCLUSION
Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.
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
Rev Soc Bras Med Trop. 2016 December 1; Volume 49 (Issue 6); 721-727.; DOI:10.1590/0037-8682-0415-2016
Brum-Soares L, Cubides JC, Burgos I, Monroy C, Castillo L, et al.
Rev Soc Bras Med Trop. 2016 December 1; Volume 49 (Issue 6); 721-727.; DOI:10.1590/0037-8682-0415-2016
INTRODUCTION
Geographical, epidemiological, and environmental differences associated with therapeutic response to Chagas etiological treatment have been previously discussed. This study describes high seroconversion rates 72 months after benznidazole treatment in patients under 16 years from a project implemented by Doctors Without Borders in Guatemala.
METHODS
An enzyme-linked immunosorbent assay was used to detect Trypanosoma cruzi IgG antibodies in capillary blood samples from patients 72 months after treatment. Fisher's exact test was used to establish association between characteristics, such as sex, age, and origin of patients, and final seroconversion. Kappa index determined concordance between laboratory tests. The level of significance was set to 5%.
RESULTS
Ninety-eight patients, aged 6 months to 16 years, were available for follow-up. Sex and origin were not associated with seroconversion. Individuals older than 13 were more prone to maintain a positive result 72 months after treatment, although results were not highly significant. Laboratory tests presented elevated Kappa concordance (95% CI) = 0.8290 (0.4955-1), as well as high (97%) seroconversion rates.
CONCLUSIONS
The high seroconversion rate found in this study emphasizes the importance of access to diagnosis, treatment, and follow-up of individuals affected by Chagas disease. Moreover, it contradicts the idea that it is not possible to achieve a cure with the currently available drugs. This study strongly supports expanding programs for patients infected with T. cruzi in endemic and non-endemic countries.
Geographical, epidemiological, and environmental differences associated with therapeutic response to Chagas etiological treatment have been previously discussed. This study describes high seroconversion rates 72 months after benznidazole treatment in patients under 16 years from a project implemented by Doctors Without Borders in Guatemala.
METHODS
An enzyme-linked immunosorbent assay was used to detect Trypanosoma cruzi IgG antibodies in capillary blood samples from patients 72 months after treatment. Fisher's exact test was used to establish association between characteristics, such as sex, age, and origin of patients, and final seroconversion. Kappa index determined concordance between laboratory tests. The level of significance was set to 5%.
RESULTS
Ninety-eight patients, aged 6 months to 16 years, were available for follow-up. Sex and origin were not associated with seroconversion. Individuals older than 13 were more prone to maintain a positive result 72 months after treatment, although results were not highly significant. Laboratory tests presented elevated Kappa concordance (95% CI) = 0.8290 (0.4955-1), as well as high (97%) seroconversion rates.
CONCLUSIONS
The high seroconversion rate found in this study emphasizes the importance of access to diagnosis, treatment, and follow-up of individuals affected by Chagas disease. Moreover, it contradicts the idea that it is not possible to achieve a cure with the currently available drugs. This study strongly supports expanding programs for patients infected with T. cruzi in endemic and non-endemic countries.
Journal Article > ResearchFull Text
Water Practice and Technology. 2024 March 29; DOI:10.2166/wpt.2024.074
Caballero A, Garcia M, Pérez-Sabino F, Lickes S, Guzmán-Quilo C, et al.
Water Practice and Technology. 2024 March 29; DOI:10.2166/wpt.2024.074
There is a need for access to clean potable water worldwide. However, almost every source of surface water in Guatemala is contaminated. This study assesses the potential exposure to water contaminants in proximity to Medecins Sans Frontieres's (MSF) chronic kidney disease clinic population in La Gomera, Guatemala during wet and dry seasons. Five municipal wells and four artisanal wells (servicing approximately 18.9% of La Gomera) were selected for their proximity to MSF La Gomera clinic to determine the presence of coliforms, physicochemical parameters, heavy metals, and pesticide residues. Water samples were collected over 3 consecutive days during La Gomera's wet season and again during the dry season. Wet season 2022: Total coliforms and Escherichia coli exceeded the acceptable limits for several artisanal wells but were not detected in municipal wells. Mercury and arsenic were detected in all wells during at least one sampling period. Dry season 2023: Total coliforms exceeded the acceptable limits for all wells and E. coli was detected in all four artisanal wells. Lead and arsenic were detected in all wells. Our results suggest that water from artisanal wells does not meet COGUANOR or WHO microbiological criteria for human consumption.
Journal Article > ResearchFull Text
Miller AC, Rohloff P, Blake A, Dhaenens E, Shaw L, et al.
2020 December 5; Volume 19; DOI:10.1186/s12942-020-00250-0
Background
Population-representative household survey methods require up-to-date sampling frames and sample designs that minimize time and cost of fieldwork especially in low- and middle-income countries. Traditional methods such as multi-stage cluster sampling, random-walk, or spatial sampling can be cumbersome, costly or inaccurate, leading to well-known biases. However, a new tool, Epicentre’s Geo-Sampler program, allows simple random sampling of structures, which can eliminate some of these biases. We describe the study design process, experiences and lessons learned using Geo-Sampler for selection of a population representative sample for a kidney disease survey in two sites in Guatemala.
Results
We successfully used Epicentre’s Geo-sampler tool to sample 650 structures in two semi-urban Guatemalan communities. Overall, 82% of sampled structures were residential and could be approached for recruitment. Sample selection could be conducted by one person after 30 min of training. The process from sample selection to creating field maps took approximately 40 h.
Conclusion
In combination with our design protocols, the Epicentre Geo-Sampler tool provided a feasible, rapid and lower-cost alternative to select a representative population sample for a prevalence survey in our semi-urban Guatemalan setting. The tool may work less well in settings with heavy arboreal cover or densely populated urban settings with multiple living units per structure. Similarly, while the method is an efficient step forward for including non-traditional living arrangements (people residing permanently or temporarily in businesses, religious institutions or other structures), it does not account for some of the most marginalized and vulnerable people in a population–the unhoused, street dwellers or people living in vehicles.
Population-representative household survey methods require up-to-date sampling frames and sample designs that minimize time and cost of fieldwork especially in low- and middle-income countries. Traditional methods such as multi-stage cluster sampling, random-walk, or spatial sampling can be cumbersome, costly or inaccurate, leading to well-known biases. However, a new tool, Epicentre’s Geo-Sampler program, allows simple random sampling of structures, which can eliminate some of these biases. We describe the study design process, experiences and lessons learned using Geo-Sampler for selection of a population representative sample for a kidney disease survey in two sites in Guatemala.
Results
We successfully used Epicentre’s Geo-sampler tool to sample 650 structures in two semi-urban Guatemalan communities. Overall, 82% of sampled structures were residential and could be approached for recruitment. Sample selection could be conducted by one person after 30 min of training. The process from sample selection to creating field maps took approximately 40 h.
Conclusion
In combination with our design protocols, the Epicentre Geo-Sampler tool provided a feasible, rapid and lower-cost alternative to select a representative population sample for a prevalence survey in our semi-urban Guatemalan setting. The tool may work less well in settings with heavy arboreal cover or densely populated urban settings with multiple living units per structure. Similarly, while the method is an efficient step forward for including non-traditional living arrangements (people residing permanently or temporarily in businesses, religious institutions or other structures), it does not account for some of the most marginalized and vulnerable people in a population–the unhoused, street dwellers or people living in vehicles.
Journal Article > ResearchFull Text
BMC Infect Dis. 2024 March 4; Volume 24 (Issue S1); 277.; DOI:10.1186/s12879-024-09018-4
Shephard M, Matthews S, Kularatne R, Andrewartha K, Blondeel K, et al.
BMC Infect Dis. 2024 March 4; Volume 24 (Issue S1); 277.; DOI:10.1186/s12879-024-09018-4
BACKGROUND
In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening ‘women at risk’ for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries – Australia, Guatemala, Morocco and South Africa.
METHODS
Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs).
RESULTS
One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1,296 samples for CT/NG and 1,380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV.
CONCLUSION
This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV.
In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening ‘women at risk’ for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries – Australia, Guatemala, Morocco and South Africa.
METHODS
Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs).
RESULTS
One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1,296 samples for CT/NG and 1,380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV.
CONCLUSION
This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV.
Journal Article > CommentaryAbstract
Disasters. 2010 June 7; Volume 34 (Issue 4); 973-995.; DOI:10.1111/j.1467-7717.2010.01178.x
Lucchi E
Disasters. 2010 June 7; Volume 34 (Issue 4); 973-995.; DOI:10.1111/j.1467-7717.2010.01178.x
Cities are fast becoming new territories of violence. The humanitarian consequences of many criminally violent urban settings are comparable to those of more traditional wars, yet despite the intensity of the needs, humanitarian aid to such settings is limited. The way in which humanitarian needs are typically defined, fails to address the problems of these contexts, the suffering they produce and the populations affected. Distinctions between formal armed conflicts, regulated by international humanitarian law, and other violent settings, as well as those between emergency and developmental assistance, can lead to the neglect of populations in distress. It can take a lot of time and effort to access vulnerable communities and implement programmes in urban settings, but experience shows that it is possible to provide humanitarian assistance with a significant focus on the direct and indirect health consequences of violence outside a traditional conflict setting. This paper considers the situation of Port-au-Prince (Haiti), Rio de Janeiro (Brazil) and Guatemala City (Guatemala).