The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

Diagnóstico de malaria por el método de la PCR anidada

In 1998, 256.697 malaria cases were confirmed in Colombia, 132,712 of which were caused by Plasmodium falciparum, 121. 161 by, and 2,824 mixed infections. Consequently, the Malaria Program of the National Reference Laboratory initiated an evaluation of the nested polymerase chain reaction (PCR) technique for malaria diagnosis. This technique amplifies variable sequences present in the 18s small subunit ribosomal RNA (ssrRNA) genes of P falciparum and P vivax. The infected blood samples were collected in Quibdó (Chocó) from 102 febrile patients who requested malaria diagnosis; the presence of parasites was established by both PCR and microscopical examination of thick blood smears. In order to evaluate the nested PCR, the following criteria were adopted: precision, accuracy, detection treshhold, sensitivity, specificity, positive and negative predictive values and Kappa index. General sensitivity was 100%, with a sensitivity for P vivax of 96.7% and for P falciparum of 100%. General specificity and specificity for both species wore 100%. The general positive predictive value was 90.0%, for P vivax 77.0% and for P falciparum 66.1%. The general negative predictive value was 90.3%. 90.6% for P vivax and 94.3% for P falciparum. The general concordance (or Kappa index) was 1 and the species concordance was 0.96. The detection treshhold of parasite DNA was 10 fg/ul. One sample diagnosed as P. vivax by microscopy was determined as a mixed infection of P falciparum and P vivax by nested PCR. Nested PCR can be employed as a diagnostic tool in the following roles: (1) a screening method for large scale epidemiological trials, (2) in evaluations of the malaria control program in Colombia, (3) in detection of early or low levels of persistent parasiternia, possibly indicative of drug-resistant malaria, and (4) as a reference test for planned diagnostic trials.En 1998, se presentaron en Colombia 256.697 casos de malaria: 132.712 por Plasmodium falciparum, 121.161 por Plasmodium vivax y 2.824 infecciones mixtas. Dada esta situación, el Programa de Malaria del Laboratorio Nacional de Referencia se propuso evaluar la PCR anidada frente a la gota gruesa, como método alternativo para el diagnóstico de malaria. Se utilizó la reacción en cadena de la polimerasa (PCR) anidada para amplificar secuencias variables de genes de la subunidad ribosomal pequeña 18s (ssrARN) de P falciparum y P vivax. Para evaluar la PCR, se recolectaron 102 muestras de pacientes febriles en Quibdó (Chocó) y se determinó la presencia de parásitos tanto por PCR como por observación microscópica (gota gruesa). Los resultados de las dos pruebas se compararon entre sí. Los criterios de evaluación fueron: precisión, exactitud, limite de detección, sensibilidad, especificidad, valores predictivos positivo (VPP) y negativo (VPN) e índice kappa. La PCR anidada presentó una sensibilidad general del 100%: 96,7% para Pvivax y 100% para P falciparum. La especificidad general para P vivax y para P falciparum fue del 100%. El VPP general de la prueba fue del 90% y el VPN fue de 90.3%; para P vivax, el VPP fue de 77,0% y el VPN de 90.6%: para P falciparum, el VPP fue de 66,1% y el VPN de 94,3%. El índice kappa generaI fue de 1 y el de especie fue de 0,96. El límite de detección del ADN parasitario fue de 10 fg/ml. La PCR anidada detectó una muestra con infección mixta de P. vivax y P. falciparun que, por gota gruesa, dio resultado positivo para P. vivax. Se recomienda el uso de la PCR anidada como método de tamizaje en estudios epidemiológicos para la evaluación del Programa de Control Nacional de Malaria, en estudios orientados a detectar de manera temprana parasitemias en pacientes tratados cuya posible causa pueda ser la resistencia a los antimaláricos y como prueba de referencia para evaluar nuevos métodos diagnósticos

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

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

Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape

The Measurement of Solar Diameter and Limb Darkening Function with the Eclipse Observations

The Total Solar Irradiance varies over a solar cycle of 11 years and maybe over cycles with longer period. Is the solar diameter variable over time too? We introduce a new method to perform high resolution astrometry of the solar diameter from the ground, through the observations of eclipses by reconsidering the definition of the solar edge. A discussion of the solar diameter and its variations must be linked to the Limb Darkening Function (LDF) using the luminosity evolution of a Baily's Bead and the profile of the lunar limb available from satellite data. This approach unifies the definition of solar edge with LDF inflection point for eclipses and drift-scan or heliometric methods. The method proposed is applied for the videos of the eclipse in 15 January 2010 recorded in Uganda and in India. The result shows light at least 0.85 arcsec beyond the inflection point, and this suggests to reconsider the evaluations of the historical eclipses made with naked eye.Comment: 16 pages, 11 figures, accepted in Solar Physics. arXiv admin note: text overlap with arXiv:astro-ph/0601109 by other author