Background: The occurrence of the major vectors of Chagas disease has historically been linked to poor rural housing, but urban or peri-urban infestations are increasingly being reported. We evaluated a simple risk index to detect houses infested with Triatoma infestans and tested whether house infestation and vector abundance increased across the urban-to-rural gradient in Avia Terai, an endemic municipality of the Argentine Chaco; whether the association between infestation and selected ecological determinants varied across the gradient; and whether urban and periurban infestations were associated with population settlement history. Methods: We conducted a screening survey of house infestation in 2296 urban, peri-urban and rural dwellings to identify high-risk houses based on a simple index, and then searched for triatomines in all high-risk houses and in a systematic sample of low-risk houses. Results: The risk index had maximum sensitivity and negative predictive value, and low specificity. The combined number of infested houses in peri-urban and urban areas equalled that in rural areas. House infestation prevalence was 4.5%, 22.7% and 42.4% across the gradient, and paralleled the increasing trend in the frequency of domestic animals and peridomestic structures. Multiple logistic regression analysis showed that house infestation was positively and significantly associated with the availability of poultry and bug refuges in walls, and was negatively associated with domestic insecticide use. Several pieces of evidence, including absence of spatial aggregation of house infestation, support that T. infestans has been a long-established occupant of urban, peri-urban and rural settings in Avia Terai. Conclusions: An integrated vector management strategy targeting chicken coops and good husbandry practices may provide more cost-effective returns to insecticide-based vector elimination efforts.

Background The elimination of Triatoma infestans, the main domestic vector of Trypanosoma cruzi, is lagging behind expectations in the Gran Chaco region. We implemented an insecticide-based intervention program and assessed its long-term effects on house infestation and bug abundance in a resource-constrained municipality (Pampa del Indio, northeastern Argentina) inhabited by creole and the Qom indigenous people (2007–2016). Key questions were whether district-wide data integration revealed patterns concealed at lower spatial levels; to what extent preintervention infestation and pyrethroid resistance challenged the effectiveness of insecticide-based control efforts, and how much control effort was needed to meet defined targets. Methods Supervised vector control teams i) georeferenced every housing unit at baseline (1,546); ii) evaluated house infestation using timed-manual searches with a dislodging aerosol across four rural areas designated for district-wide scaling up; iii) sprayed with pyrethroid insecticide 92.7% of all houses; iv) periodically monitored infestation and promoted householder-based surveillance, and v) selectively sprayed the infested houses, totaling 1,823 insecticide treatments throughout the program. Results Baseline house infestation (mean, 26.8%; range, 14.4–41.4%) and bug abundance plummeted over the first year postintervention (YPI). Timed searches at baseline detected 61.4–88.0% of apparent infestations revealed by any of the methods used. Housing dynamics varied widely among areas and between Qom and creole households. Preintervention triatomine abundance and the cumulative frequency of insecticide treatments were spatially aggregated in three large clusters overlapping with pyrethroid resistance, which ranged from susceptible to high. Persistent foci were suppressed with malathion. Aggregation occurred mainly at house compound or village levels. Preintervention domestic infestation and abundance were much greater in Qom than in creole households, whereas the reverse was recorded in peridomestic habitats. House infestation, rare (1.9–3.7%) over 2–6 YPI, averaged 0.66% (95% confidence interval, 0.28–1.29%) at endpoint. Conclusions Upscale integration revealed multiple coupled heterogeneities (spatial, sociodemographic and biological) that reflect large inequalities, hamper control efforts, and provide opportunities for targeted, sustainable disease control. High-coverage, professional insecticide spraying combined with systematic surveillance-and-response were essential ingredients to achieve the quasi-elimination of T. infestans within 5 YPI and concomitant transmission blockage despite various structural threats and constraints.

Background Interruption of domestic vector-borne transmission of Trypanosoma cruzi is still an unmet goal in several American countries. In 2007 we launched a long-term intervention program aimed to suppress house infestation with the main domestic vector in southern South America (Triatoma infestans) and domestic transmission in Pampa del Indio, a resource-constrained, hyperendemic municipality with 1446 rural houses inhabited by Creole and indigenous people, in the Argentine Chaco ecoregion. Here, we assessed whether the 10-year insecticide-based program combined with community mobilization blocked vector-borne domestic transmission of T. cruzi to humans and dogs. Methods We carried out two municipality-wide, cross-sectional serosurveys of humans and dogs (considered sentinel animals) during 2016–2017 to compare with baseline data. We used a risk-stratified random sampling design to select 273 study houses; 410 people from 180 households and 492 dogs from 151 houses were examined for antibodies to T. cruzi using at least two serological methods. Results The seroprevalence of T. cruzi in children aged <16 years was 2.5% in 2017 (i.e., 4- to 11-fold lower than before interventions). The mean annual force of child infection (λ) sharply decreased from 2.18 to 0.34 per 100 person-years in 2017. One of 102 children born after interventions was seropositive for T. cruzi; he had lifetime residence in an apparently uninfested house, no outside travel history, and his mother was T. cruzi-seropositive. No incident case was detected among 114 seronegative people of all ages re-examined serologically. Dog seroprevalence was 3.05%. Among native dogs, λ in 2016 (1.21 per 100 dog-years) was 5 times lower than at program onset. Six native adult dogs born after interventions and with stable lifetime residence were T. cruzi-seropositive: three had exposure to T. infestans at their houses and one was an incident case. Conclusions These results support the interruption of vector-borne transmission of T. cruzi to humans in rural Pampa del Indio. Congenital transmission was the most likely source of the only seropositive child born after interventions. Residual transmission to dogs was likely related to transient infestations and other transmission routes. Sustained vector control supplemented with human chemotherapy can lead to a substantial reduction of Chagas disease transmission in the Argentine Chaco.

Background Trypanosoma cruzi, the protozoan agent of Chagas disease, is comprised of at least 6 genetic lineages (TcI-TcVI). Their geographical distribution, clinical associations and reservoir hosts are not fully elucidated, as genotyping is hampered due to the difficulty in isolating representative populations of organisms. Lineage-specific serological techniques may address these issues. Methods Trypanosoma cruzi lineage-specific serological assays were performed on human, canine, feline and armadillo sera from the Gran Chaco in northern Argentina, a region of ongoing transmission. Synthetic peptides representing lineage-specific epitopes of the trypomastigote small surface antigen (TSSA) were used in ELISA, and the TcII/V/VI shared epitope peptide (TSSApep-II/V/VI) was used in the Chagas Sero K-SeT rapid diagnostic test (RDT). Results Chagas Sero K-SeT RDT, using Protein G to detect human and canine IgG, was at least as sensitive as TSSApep-II/V/VI ELISA using specific secondary antibodies. For sera from humans TSSApep-II/V/VI seroprevalence by Chagas Sero K-SeT was 273/393 (69.5%), for dogs 48/73 (65.8%) and for armadillos 1/7 (14.3%); by ELISA for cats 5/19 (26.3%). The seroprevalence for humans was similar to that for Bolivian patients, amongst whom we previously observed an association of TSSApep-II/V/VI seropositivity with severity of cardiomyopathy. In humans, prevalence of TSSApep-II/V/VI recognition was associated with locality, and with increasing and decreasing age within the Qom and Creole populations, respectively. For dogs TSSApep-II/V/VI recognition was associated with being born before community-wide insecticide spraying (P = 0.05) and with Qom household (P < 0.001). Conclusions We show here that Chagas Sero K-SeT RDT can replace ELISA for TSSApep-II/V/VI serology of humans and dogs; for humans there were statistically significant associations between a positive Chagas Sero K-SeT RDT and being resident in Area IV, and for dogs association with Qom household or with being born before the mass spraying campaign; we also show that with cats the TcII/V/VI epitope can be detected by ELISA. We assessed the lineage distribution in an unprecedented 83% of the human T. cruzi-seropositive population. These results form the basis for more detailed studies, enabling rapid in-the-field surveillance of the distribution and clustering of these lineages among humans and mammalian reservoirs of T. cruzi infection.

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Background Trypanosoma cruzi , the agent of Chagas disease, is a protozoan parasite transmitted to humans by blood-sucking triatomine vectors. However, and despite its utmost biological and epidemiological relevance, T . cruzi development inside the digestive tract of the insect remains a poorly understood process. Methods/Principle findings Here we showed that Gp35/50 kDa mucins, the major surface glycoproteins from T . cruzi insect-dwelling forms, are involved in parasite attachment to the internal cuticle of the triatomine rectal ampoule, a critical step leading to its differentiation into mammal-infective forms. Experimental evidence supporting this conclusion could be summarized as follows: i) native and recombinant Gp35/50 kDa mucins directly interacted with hindgut tissues from Triatoma infestans , as assessed by indirect immunofluorescence assays; ii) transgenic epimastigotes over-expressing Gp35/50 kDa mucins on their surface coat exhibited improved attachment rates (~2–3 fold) to such tissues as compared to appropriate transgenic controls and/or wild-type counterparts; and iii) certain chemically synthesized compounds derived from Gp35/50 kDa mucins were able to specifically interfere with epimastigote attachment to the inner lining of T . infestans rectal ampoules in ex vivo binding assays, most likely by competing with or directly blocking insect receptor(s). A solvent-exposed peptide (smugS peptide) from the Gp35/50 kDa mucins protein scaffolds and a branched, Gal f -containing trisaccharide (Gal f β1–4[Gal p β1–6]GlcNAcα) from their O -linked glycans were identified as main adhesion determinants for these molecules. Interestingly, exogenous addition of a synthetic Gal f β1–4[Gal p β1–6]GlcNAcα derivative or of oligosaccharides containing this structure impaired the attachment of Dm28c but not of CL Brener epimastigotes to triatomine hindgut tissues; which correlates with the presence of Gal f residues on the Gp35/50 kDa mucins’ O -glycans on the former but not the latter parasite clone. Conclusion/Significance These results provide novel insights into the mechanisms underlying T . cruzi- triatomine interplay, and indicate that inter-strain variations in the O -glycosylation of Gp35/50 kDa mucins may lead to differences in parasite differentiation and hence, in parasite transmissibility to the mammalian host. Most importantly, our findings point to Gp35/50 kDa mucins and/or the Gal f ...

Trypanosoma cruzi, the etiological agent of Chagas disease, was initially classified into 6 Discrete Typing Units (DTUs). The hybrid DTUs TcV and TcVI are the most frequent in domestic transmission cycles throughout the Southern Cone countries of South America. Here, we genotyped parasite isolates from human residents in Pampa del Indio municipality, Chaco, to further characterize the structure of T. cruzi populations, and to assess the degree of overlapping between the domestic and sylvatic transmission cycles. Artificial xenodiagnostic tests were performed to blood samples from 125 T. cruzi-seropositive people (age range, 3-70 years) who represented 14.3% of all seropositive residents identified. Parasites were obtained from feces of T. cruzi-infected Triatoma infestans examined 30 or 60 days after blood-feeding, and grown in vitro. The cultured parasites were genotyped by means of two PCR-based protocols. DTUs were determined from 39 (31%) patients residing in 28 dwellings. The only DTUs identified were TcV (92%) and TcVI (8-36%). Households with more than one parasite isolate consistently displayed the same DTU. Further sequencing of a fragment of the TcMK gene from selected samples argue against the occurrence of mixed TcV-TcVI infections in the study population. Sequencing data revealed an unexpected degree of genetic variability within TcV including two apparently robust subgroups of isolates. Our results for human residents confirm the predominance of hybrid lineages (TcV and to a much lesser extent TcVI) and the absence of sylvatic genotypes (TcI and TcIII) in (peri)domestic transmission cycles in the Argentinean Chaco area.

We assessed whether fluralaner administered to outbred healthy dogs reduced or supressed site infestation and abundance of pyrethroid‐resistant populations of Triatoma infestans Klug (Heteroptera: Reduviidae). We conducted a placebo‐controlled before‐and‐after efficacy trial in 28 infested sites in Castelli (Argentine Chaco) over 10 months. All 72 dogs initially present received either an oral dose of fluralaner (treated group) or placebo (control group) at month 0 posttreatment (MPT). Preliminary results justified treating all 38 control‐house dogs with fluralaner 1 month later, and 71 of 78 existing dogs at 7 MPT. Site‐level infestation and triatomine abundance were evaluated using timed manual searches with a dislodging aerosol. In the fluralaner‐treated group, infestation dropped significantly from 100% at baseline to 19% over 6–10 MPT whereas mean abundance fell highly significantly from 5.5 to 0.8–0.9 triatomines per unit effort. In the placebo group, site infestation and mean abundance remained stable between 0 and 1 MPT, and strongly declined after fluralaner administration from 13.0−14.7 ‐ triatomines at 0–1 MPT to 4.0–4.2 over 6–10 MPT. Only one of 81 noninfested sites before fluralaner treatment became infested subsequently. Fluralaner significantly reduced the site‐level infestation and abundance of pyrethroid‐resistant T. infestans and should be tested more widely in Phase III efficacy trials.