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

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

Chagas Cardiomyopathy Manifestations and Trypanosoma cruzi Genotypes Circulating in Chronic Chagasic Patients

Chagas disease caused by Trypanosoma cruzi is a complex disease that is endemic and an important problem in public health in Latin America. The T. cruzi parasite is classified into six discrete taxonomic units (DTUs) based on the recently proposed nomenclature (TcI, TcII, TcIII, TcIV, TcV and TcVI). The discovery of genetic variability within TcI showed the presence of five genotypes (Ia, Ib, Ic, Id and Ie) related to the transmission cycle of Chagas disease. In Colombia, TcI is more prevalent but TcII has also been reported, as has mixed infection by both TcI and TcII in the same Chagasic patient. The objectives of this study were to determine the T. cruzi DTUs that are circulating in Colombian chronic Chagasic patients and to obtain more information about the molecular epidemiology of Chagas disease in Colombia. We also assessed the presence of electrocardiographic, radiologic and echocardiographic abnormalities with the purpose of correlating T. cruzi genetic variability and cardiac disease. Molecular characterization was performed in Colombian adult chronic Chagasic patients based on the intergenic region of the mini-exon gene, the 24Sα and 18S regions of rDNA and the variable region of satellite DNA, whereby the presence of T.cruzi I, II, III and IV was detected. In our population, mixed infections also occurred, with TcI-TcII, TcI-TcIII and TcI-TcIV, as well as the existence of the TcI genotypes showing the presence of genotypes Ia and Id. Patients infected with TcI demonstrated a higher prevalence of cardiac alterations than those infected with TcII. These results corroborate the predominance of TcI in Colombia and show the first report of TcIII and TcIV in Colombian Chagasic patients. Findings also indicate that Chagas cardiomyopathy manifestations are more correlated with TcI than with TcII in Colombia

Anterior ankle arthroscopy, distraction or dorsiflexion?

Anterior ankle arthroscopy can basically be performed by two different methods; the dorsiflexion- or distraction method. The objective of this study was to determine the size of the anterior working area for both the dorsiflexion and distraction method. The anterior working area is anteriorly limited by the overlying anatomy which includes the neurovascular bundle. We hypothesize that in ankle dorsiflexion the anterior neurovascular bundle will move away anteriorly from the ankle joint, whereas in ankle distraction the anterior neurovascular bundle is pulled tight towards the joint, thereby decreasing the safe anterior working area. Six fresh frozen ankle specimens, amputated above the knee, were scanned with computed tomography. Prior to scanning the anterior tibial artery was injected with contrast fluid and subsequently each ankle was scanned both in ankle dorsiflexion and in distraction. A special device was developed to reproducibly obtain ankle dorsiflexion and distraction in the computed tomography scanner. The distance between the anterior border of the inferior tibial articular facet and the posterior border of the anterior tibial artery was measured. The median distance from the anterior border of the inferior tibial articular facet to the posterior border of the anterior tibial artery in ankle dorsiflexion and distraction was 0.9 cm (range 0.7–1.5) and 0.7 cm (range 0.5–0.8), respectively. The distance in ankle dorsiflexion significantly exceeded the distance in ankle distraction (P = 0.03). The current study shows a significantly increased distance between the anterior distal tibia and the overlying anterior neurovascular bundle with the ankle in a slightly dorsiflexed position as compared to the distracted ankle position. We thereby conclude that the distracted ankle position puts the neurovascular structures more at risk for iatrogenic damage when performing anterior ankle arthroscopy

Sex, Subdivision, and Domestic Dispersal of Trypanosoma cruzi Lineage I in Southern Ecuador

Trypanosoma cruzi is transmitted by blood sucking insects known as triatomines. This protozoan parasite commonly infects wild and domestic mammals in South and Central America. However, triatomines also transmit the parasite to people, and human infection with T. cruzi is known as Chagas disease, a major public health concern in Latin America. Understanding the complex dynamics of parasite spread between wild and domestic environments is essential to design effective control measures to prevent the spread of Chagas disease. Here we describe T. cruzi genetic diversity and population dynamics in southern Ecuador. Our findings indicate that the parasite circulates in two largely independent cycles: one corresponding to the sylvatic environment and one related to the domestic/peridomestic environment. Furthermore, our data indicate that human activity might promote parasite dispersal among communties. This information is the key for the design of control programmes in Southern Ecuador. Finally, we have encountered evidence of a sexual reproductive mode in the domestic T. cruzi population, which constitutes a new and intriguing finding with regards to the biology of this parasite

A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

In the wake of emerging T. cruzi infection in children of periurban Arequipa, Peru, we conducted a prospective field trial to evaluate alternative targeted screening strategies for Chagas disease across the city. Using insect vector data that is routinely collected during Ministry of Health insecticide application campaigns in 3 periurban districts of Arequipa, we separated into 4 categories those households with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Residents of all infected-vector households and a random sample of those in the other 3 categories were invited for serological screening for T. cruzi infection. Subsequently, all residents of households within a 15-meter radius of detected seropositive individuals were invited to be screened in a ring case-detection scheme. Of 923 participants, 21 (2.28%) were seropositive. There were no significant differences in prevalence across the 4 screening strategies, indicating that household entomologic factors alone could not predict the risk of infection. Indeed, the most predictive variable of infection was the number of years a person lived in a location with triatomine insects. Therefore, a simple residence history questionnaire may be a useful screening tool in large, diverse urban environments with emerging Chagas disease

The Evolution of Social Orienting: Evidence from Chicks (Gallus gallus) and Human Newborns

Converging evidence from different species indicates that some newborn vertebrates, including humans, have visual predispositions to attend to the head region of animate creatures. It has been claimed that newborn preferences for faces are domain-relevant and similar in different species. One of the most common criticisms of the work supporting domain-relevant face biases in human newborns is that in most studies they already have several hours of visual experience when tested. This issue can be addressed by testing newly hatched face-na\uefve chicks (Gallus gallus) whose preferences can be assessed prior to any other visual experience with faces

Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases

Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells