Trypanosoma cruzi - the vector-parasite paradox

Trypanosoma cruzi and the majority of its insect vectors (Hemiptera, Reduviidae, Triatominae) are confined to the Americas. But while recent molecular studies indicate a relatively ancient origin for the parasite (~65 million years ago) there is increasing evidence that the blood-sucking triatomine vectors have evolved comparatively recently (<5 mya). This review examines the evidence for these ideas, and attempts to reconcile the apparent paradox by suggesting that marsupial opossums (Didelphidae) may have played a role, not just as original reservoir hosts, but also as original vectors of the parasite

Comparative evaluation of pyrethroid insecticide formulations against Triatoma infestans (Klug): residual efficacy on four substrates

We investigated the residual efficacy of four insecticide formulations used in Chagas disease vector control campaigns: cyfluthrin 12.5% suspension concentrace (SC), lambda- cyhalothrin 10% wettable powder (WP), deltamethrin 2.5% SC, and 2.5% WP on four types of circular blocks of wood, straw with mud, straw with mud painted with lime, and mud containing 5% of cement. Three concentrations of these insecticides were tested: the LC90 (previously determined on filter paper), the double of the LC90, and the recommended operational dose. For each bioassay test, 15 third-stage nymphs of Triatoma infestans (Klug) (Hemiptera: Reduviidae) were exposed for 120 h to each treatment at 24 h, 30, 60, 90, and 180 days post-spraying. Mortality rates, moulting history and behaviour were recorded at 24, 48, 72, and 120 h of exposure. Mortality rates were highest during the first 30 days post-spraying. Highest mortality rates (above 50%) were observed for deltamethrin 2.5% SC and lambda-cyhalothrin 10% WP on wood blocks up to three months post-spraying. Mud was the substrate on which treatments showed lowest persistence, with the other two substrates showing intermediate residual efficacy of all treatments. During the first 30 days WP formulations were not as effective as SC flowable formulations but, overall in the longer term, WP gave grater mortality rates of T. infestans nymphs exposed at up to six months post-spraying. Porous surfaces, especially mud, showed most variability presumably due to absorption of the insecticide. In contrast the less porous surfaces (i.e. wood and lime-coated mud) kept mortality rates high for longer post-treatment, irrespective of the insecticide concentration used

Analysis of antenal sensilla patterns of Rhodnius prolixus from Colombia and Venezuela

Antennal sensilla patterns were used to analyze population variation of domestic Rhodnius prolixus from six departments and states representing three biogeographical regions of Colombia and Venezuela. Discriminant analysis of the patterns of mechanoreceptors and of three types of chemoreceptors on the pedicel and flagellar segments showed clear differentiation between R. prolixus populations east and west of the Andean Cordillera. The distribution of thick and thin-walled trichoids on the second flagellar segment also showed correlation with latitude, but this was not seen in the patterns of other sensilla. The results of the sensilla patterns appear to be reflecting biogeographic features or population isolation rather than characters associated with different habitats and lend support to the idea that domestic R. prolixus originated in the eastern region of the Andes.Fil: Esteban, Lyda. Universidad Industrial de Santander; ColombiaFil: Angulo, Víctor Manuel. Universidad Industrial de Santander; ColombiaFil: Dora Feliciangeli, M.. Universidad de Carabobo; VenezuelaFil: Catala, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentin

Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance

Class A serine &#x3B2;-lactamases (SBLs) are key antibiotic resistance determinants in Gram-negative bacteria. SBLs neutralize &#x3B2;-lactams via a hydrolytically labile covalent acyl-enzyme intermediate. Klebsiella pneumoniae carbapenemase (KPC) is a widespread SBL that hydrolyzes carbapenems, the most potent &#x3B2;-lactams; known KPC variants differ in turnover of expanded-spectrum oxyimino-cephalosporins (ESOCs), for example, cefotaxime and ceftazidime. Here, we compare ESOC hydrolysis by the parent enzyme KPC-2 and its clinically observed double variant (P104R/V240G) KPC-4. Kinetic analyses show that KPC-2 hydrolyzes cefotaxime more efficiently than the bulkier ceftazidime, with improved ESOC turnover by KPC-4 resulting from enhanced turnover (k&lt;sub&gt;cat&lt;/sub&gt;), rather than altered K&lt;sub&gt;M&lt;/sub&gt; values. High-resolution crystal structures of ESOC acyl-enzyme complexes with deacylation-deficient (E166Q) KPC-2 and KPC-4 mutants show that ceftazidime acylation causes rearrangement of three loops; the &#x3A9;, 240, and 270 loops, which border the active site. However, these rearrangements are less pronounced in the KPC-4 than the KPC-2 ceftazidime acyl-enzyme and are not observed in the KPC-2:cefotaxime acyl-enzyme. Molecular dynamics simulations of KPC:ceftazidime acyl-enyzmes reveal that the deacylation general base E166, located on the &#x3A9; loop, adopts two distinct conformations in KPC-2, either pointing "in" or "out" of the active site; with only the "in" form compatible with deacylation. The "out" conformation was not sampled in the KPC-4 acyl-enzyme, indicating that efficient ESOC breakdown is dependent upon the ordering and conformation of the KPC &#x3A9; loop. The results explain how point mutations expand the activity spectrum of the clinically important KPC SBLs to include ESOCs through their effects on the conformational dynamics of the acyl-enzyme intermediate

Study protocol for a prospective, longitudinal cohort study investigating the medical and psychosocial outcomes of UK combat casualties from the Afghanistan war: the ADVANCE Study.

INTRODUCTION: The Afghanistan war (2003-2014) was a unique period in military medicine. Many service personnel survived injuries of a severity that would have been fatal at any other time in history; the long-term health outcomes of such injuries are unknown. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) study aims to determine the long-term effects on both medical and psychosocial health of servicemen surviving this severe combat related trauma. METHODS AND ANALYSIS: ADVANCE is a prospective cohort study. 1200 Afghanistan-deployed male UK military personnel and veterans will be recruited and will be studied at 0, 3, 6, 10, 15 and 20 years. Half are personnel who sustained combat trauma; a comparison group of the same size has been frequency matched based on deployment to Afghanistan, age, sex, service, rank and role. Participants undergo a series of physical health tests and questionnaires through which information is collected on cardiovascular disease (CVD), CVD risk factors, musculoskeletal disease, mental health, functional and social outcomes, quality of life, employment and mortality. ETHICS AND DISSEMINATION: The ADVANCE Study has approval from the Ministry of Defence Research Ethics Committee (protocol no:357/PPE/12) agreed 15 January 2013. Its results will be disseminated through manuscripts in clinical/academic journals and presentations at professional conferences, and through participant and stakeholder communications. TRIAL REGISTRATION NUMBER: The ADVANCE Study is registered at ISRCTN ID: ISRCTN57285353

Elimination of Rhodnius prolixus in Central America

Rhodnius prolixus is one of the main vectors of Trypanosoma cruzi, causative agent of Chagas disease. In Central America, it was first discovered in 1915 in El Salvador, from where it spread northwest to Guatemala and Mexico, and southeast to Nicaragua and Costa Rica, arriving also in Honduras in the late 1950s. Indoor residual spraying (IRS) by the antimalaria services of Costa Rica prevented its spread southwards, and similar IRS programmes appear to have eliminated it from El Salvador by the late 1970s. In 1997, by resolution of the Ministers of Health of the seven Central American countries, a multinational initiative against Chagas disease (IPCA) was launched with one of the specific objectives being the elimination of R. prolixus from the region. As a result, more and more infested areas were encountered, and progressively sprayed using an IRS strategy already deployed against Triatoma infestans in the southern cone countries of South America. In 2008, Guatemala became the first of these countries to be formally certified as free of Chagas disease transmission due to R. prolixus. The other infested countries have since been similarly certified, and none of these has reported the presence of R. prolixus since June 2010. Further surveillance is required, but current evidence suggests that R. prolixus may now been eliminated from throughout the mesoamerican region, with a corresponding decline in the incidence of T. cruzi infections