Chagas disease in immunocompromised patients.

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

Deep Sequencing to Detect Diversity of Trypanosoma cruzi Infection in Patients Coinfected With Human Immunodeficiency Virus and Chagas Disease.

Chagas disease, caused by Trypanosoma cruzi, can reactivate and cause severe acute disease in immunocompromised patients such as those infected with human immunodeficiency virus (HIV). We conducted amplicon deep sequencing of a 327-bp fragment of the tcscd5 gene using an Ion Torrent PGM directly from clinical samples from HIV patients with high parasitemia. We describe the within-host diversity, both characterizing the discrete typing unit of the infections and confirming the presence of multistrain infections, directly from clinical samples. This method can rapidly provide information on the genetic diversity of T. cruzi infection, which can have direct impacts on clinical disease.

Insights sobre a evolução e dispersão da resistência aos piretróides entre Triatoma infestans andinos silvestres da Bolívia

Abstract: Sylvatic populations of Triatoma infestans represent a challenge to Chagas disease control as they are not targeted by vector control activities and may play a key role in post-spraying house reinfestation. Understanding sylvatic foci distribution and gene flow between sylvatic and domestic populations is crucial to optimize vector control interventions and elucidate the development and spread of insecticide resistance. Herein, the genetic profiles of five Andean T. infestans populations from Bolivia with distinct insecticide susceptibility profiles were compared. Multilocus genotypes based on eight microsatellites and the DNA sequence of a fragment of the cytochrome B (cytB) gene were obtained for 92 individuals. CytB haplotypes were analyzed with previously reported Bolivian T. infestans haplotypes to evaluate putative historical gene flow among populations. Each specimen was also screened for two nucleotide mutations in the sodium channel gene (kdr), related to pyrethroid resistance (L1014 and L9251). Significant genetic differentiation was observed among all populations, although individuals of admixed origin were detected in four of them. Notably, the genetic profiles of adjacent domestic and sylvatic populations of Mataral, characterized by higher levels of insecticide resistance, support their common ancestry. Only one sylvatic individual from Mataral carried the kdr mutation L1014, suggesting that this mechanism is unlikely to cause the altered insecticide susceptibility observed in these populations. However, as the resistance mutation is present in the area, it has the potential to be selected under insecticidal pressure. Genetic comparisons of these populations suggest that insecticide resistance is likely conferred by ancient trait(s) in T. infestans sylvatic populations, which are capable of invading domiciles. These results emphasize the need for stronger entomological surveillance in the region, including early detection of house invasion, particularly post-spraying, monitoring for resistance to pyrethroids and the design of integrative control actions that consider sylvatic foci around domestic settings and their dispersion dynamics.

Congenital Chagas disease: current diagnostics, limitations and future perspectives.

PURPOSE OF REVIEW: Congenital transmission is an important route of Trypanosoma cruzi infection, both in Latin America and internationally, with considerable populations of infected women of child-bearing age residing in the United States and Europe. This review examines recent literature on congenital Chagas disease, with a focus on the changing clinical spectrum and potential new diagnostic tools. RECENT FINDINGS: Vertical transmission occurs in approximately 5-10% of births from T. cruzi-infected mothers. Historically, congenital Chagas disease was associated with high levels of neonatal morbidity and mortality. Bolivian birth cohort data from the early 1990s to the present indicate that the incidence of symptomatic neonatal disease has declined. Treatment with trypanocides is greater than 90% effective and well tolerated in infants. Current programs face challenges from the multistep screening algorithm, low sensitivity of microscopy and high loss to follow-up. SUMMARY: Congenital Chagas disease remains an important contributor to the global disease burden because of T. cruzi. PCR and related molecular techniques represent the most sensitive diagnostic modalities for early detection but require further optimization for resource-limited settings. Several novel diagnostic tests show promise for the future but further validation and adaptation to field settings are needed.

Experimental hut evaluation of a novel long-lasting non-pyrethroid durable wall lining for control of pyrethroid-resistant Anopheles gambiae and Anopheles funestus in Tanzania.

BACKGROUND: A novel, insecticide-treated, durable wall lining (ITWL), which mimics indoor residual spraying (IRS), has been developed to provide prolonged vector control when fixed to the inner walls of houses. PermaNet® ITWL is a polypropylene material containing non-pyrethroids (abamectin and fenpyroximate) which migrate gradually to the surface. METHODS: An experimental hut trial was conducted in an area of pyrethroid-resistant Anopheles gambiae s.l. and Anopheles funestus s.s. to compare the efficacy of non-pyrethroid ITWL, long-lasting insecticidal nets (LLIN) (Interceptor®), pyrethroid ITWL (ZeroVector®), and non-pyrethroid ITWL + LLIN. RESULTS: The non-pyrethroid ITWL produced relatively low levels of mortality, between 40-50% for An. funestus and An. gambiae, across all treatments. Against An. funestus, the non-pyrethroid ITWL when used without LLIN produced 47% mortality but this level of mortality was not significantly different to that of the LLIN alone (29%, P = 0.306) or ITWL + LLIN (35%, P = 0.385). Mortality levels for An. gambiae were similar to An. funestus with non-pyrethroid ITWL, producing 43% mortality compared with 26% for the LLIN. Exiting rates from ITWL huts were similar to the control and highest when the LLIN was present. An attempt to restrict mosquito access by covering the eave gap with ITWL (one eave open vs four open) had no effect on numbers entering. The LLIN provided personal protection when added to the ITWL with only 30% blood-fed compared with 69 and 56% (P = 0.001) for ITWL alone. Cone bioassays on ITWL with 30 min exposure after the trial produced mortality of >90% using field An. gambiae. CONCLUSIONS: Despite high mortality in bioassays, the hut trial produced only limited mortality which was attributed to pyrethroid resistance against the pyrethroid ITWL and low efficacy in the non-pyrethroid ITWL. Hut ceilings were left uncovered and may have served as a potential untreated refuge. By analogy to IRS campaigns, which also do not routinely treat ceilings, high community coverage with ITWL may still reduce malaria transmission. Restriction of eave gaps by 75% proved an inadequate barrier to mosquito entry. The findings represent the first 2 months after installation and do not necessarily predict long-term efficacy.

Insecticide-treated durable wall lining (ITWL): future prospects for control of malaria and other vector-borne diseases

While long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the cornerstones of malaria vector control throughout sub-Saharan Africa, there is an urgent need for the development of novel insecticide delivery mechanisms to sustain and consolidate gains in disease reduction and to transition towards malaria elimination and eradication. Insecticide-treated durable wall lining (ITWL) may represent a new paradigm for malaria control as a potential complementary or alternate longer-lasting intervention to IRS. ITWL can be attached to inner house walls, remain efcacious over multiple years and overcome some of the operational constraints of frst-line control strategies, specifcally nightly behavioural compliance required of LLINs and re-current costs and user fatigue associated with IRS campaigns. Initial experimental hut trials of insecticide-treated plastic sheeting reported promising results, achieving high levels of vector mortality, deterrence and blood-feeding inhibition, particularly when combined with LLINs. Two generations of commercial ITWL have been manufactured to date containing either pyrethroid or non-pyrethroid formulations. While some Phase III trials of these products have demonstrated reductions in malaria incidence, further large-scale evidence is still required before operational implementation of ITWL can be considered either in a programmatic or more targeted community context. Qualitative studies of ITWL have identifed aesthetic value and observable entomological efcacy as key determinants of household acceptability. However, concerns have been raised regarding installation feasibility and anticipated cost-efectiveness. This paper critically reviews ITWL as both a putative mechanism of house improvement or more conventional intervention and discusses its future prospects as a method for controlling malaria and other vector-borne diseases.

Phase III evaluation of the insecticidal efficacy and durability of a deltamethrin-treated polypropylene long-lasting net LifeNet®, in comparison with long-lasting nets made from polyester and polyethylene: study protocol.

BACKGROUND: Universal coverage of long-lasting insecticidal nets (LNs) made from polyester or polyethylene fibres has been adopted as the standard of care to control malaria among at-risk populations. To obtain a WHO recommendation, LNs must undergo prospective monitoring of insecticidal efficacy against mosquito vectors over 3 years of household use. The retention of bioefficacy and physical durability of a LN is influenced by net usage practices, textile polymer material and insecticide treatment technology. Fabric durability is the critical factor which determines the interval required between LN replacement campaigns. To investigate factors known to affect LN durability and bioefficacy, we describe a three-arm WHO Pesticide Evaluation Scheme (WHOPES) Phase III evaluation of a LN made uniquely from polypropylene (LifeNet®, Bayer CropScience) compared to standard LNs made from polyester and polyethylene, all treated with deltamethrin, over 3 years of use. METHODS: This is a prospective three-arm household randomized, equivalence trial of LNs in Tanzania, with nets as the unit of observation. Equal numbers of houses will be randomized to receive deltamethrin-treated polypropylene, polyester or polyethylene LNs; all sleeping spaces in a given household will be provided with one type of net. Bioefficacy (insecticidal activity against mosquitoes), insecticide content of net fibres, and fabric integrity (number, location and size of holes) will be measured every 6 months, using WHO cone or tunnel bioassays, chemical analysis and calculation of hole index, respectively. A cohort of LNs will be surveyed annually to assess survivorship (median LN survival time) and cumulative loss of fabric integrity. Field durability outcomes will be compared with laboratory strength tests. DISCUSSION: This is the first trial to compare the relative durability of three LNs each made from a different textile polymer, treated with the same insecticide, in the same community side-by-side over 3 years of use. Trial findings will 1) guide global health organizations on procurement policy and the type of textile polymer which maximizes the interval between LN replacement campaigns, and 2) stimulate manufacturers to improve product performance and development of longer lasting polymers. A full WHO recommendation may be granted to LifeNet® upon successful Phase III completion.

Development of peptide-based lineage-specific serology for chronic Chagas disease: geographical and clinical distribution of epitope recognition.

BACKGROUND: Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI-TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual's history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues. METHODOLOGY/PRINCIPAL FINDINGS: We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology. CONCLUSIONS/SIGNIFICANCE: These results demonstrate the considerable potential for synthetic peptide serology to investigate the infection history of individuals, geographical and clinical associations of T. cruzi lineages.