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 efficacious over multiple years and overcome some of the operational constraints of first-line control strategies, specifically 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 identified aesthetic value and observable entomological efficacy as key determinants of household acceptability. However, concerns have been raised regarding installation feasibility and anticipated cost-effectiveness. 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

Installation of insecticide-treated durable wall lining: evaluation of attachment materials and product durability under field conditions.

BACKGROUND: Insecticide-treated durable wall lining (DL) is a new method of vector control designed to supplement LLINs and overcome two inherent limitations of LLINs and IRS: nightly behavioural compliance and short residual activity, respectively. DL is a deltamethrin-treated polyethylene material, which when used to cover interior house walls, functions as long-lasting IRS. Because the DL concept anticipates minimal upkeep, a primary challenge is how to guarantee correct household installation and in situ longevity for several years. Field trials were undertaken on various wall surfaces in Ghana to identify a logistically feasible, durable and re-usable method for DL wall attachment and to pilot new methods for assessing DL durability. METHODS: Over fifty-five candidate attachment or fixing products, including mechanical fasteners, material anchors and adhesives, were evaluated for their ability to tolerate static loads (simulating long-term installation) and short-term heavy weights (imitating shock damage). Attachment products were also scored using qualitative logistical and feasibility criteria, including ease of preparation, grip of fixing to DL and possibility of re-use. RESULTS: The stress tests provided a standardised, reproducible and reliable system for assessing fixing effectiveness and DL durability, with 64% (14/22) of adhesives and 15% (2/13) of mechanical fasteners failing to meet the minimum requirements of attaching DL to mud walls for set time periods. For most fixings, less outward load (0.2-8.0 kg) was required to detach DL from the wall, compared to downward load (0.2-19.2 kg). Fixings were better able to grip DL onto concrete than clay surfaces. Using a plastic nail cap to increase DL attachment area greatly improved grip and outward load tolerance, more so than varying nail size, length or texture. CONCLUSIONS: Based on a series of systematic stress tests, optimized fixing products for polyethylene DL wall attachment were identified. In parallel, a detailed and adaptable method of DL household installation was developed for routine deployment in malaria endemic areas. These standardized stress tests will form the basis for comparative evaluations of new types of DL textile, which incorporate non-pyrethroid insecticides to control malaria transmitted by resistant mosquito populations

Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease.

Over the last 30 years, concomitant with successful transnational disease control programs across Latin America, Chagas disease has expanded from a neglected, endemic parasitic infection of the rural poor to an urbanized chronic disease, and now a potentially emergent global health problem. Trypanosoma cruzi infection has a highly variable clinical course, ranging from complete absence of symptoms to severe and often fatal cardiovascular and/or gastrointestinal manifestations. To date, few correlates of clinical disease progression have been identified. Elucidating a putative role for T. cruzi strain diversity in Chagas disease pathogenesis is complicated by the scarcity of parasites in clinical specimens and the limitations of our contemporary genotyping techniques. This article systematically reviews the historical literature, given our current understanding of parasite genetic diversity, to evaluate the evidence for any association between T. cruzi genotype and chronic clinical outcome, risk of congenital transmission or reactivation and orally transmitted outbreaks

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

Evidence and importance of genetic exchange among field populations of Trypanosoma cruzi.

Many eukaryotic pathogenic microorganisms that were previously assumed to propagate clonally have retained cryptic sexual cycles. The principal reproductive mode of Trypanosoma cruzi, the aetiological agent of Chagas disease, remains a controversial topic. Despite the existence of two recent natural hybrid lineages, a pervasive view is that recombination has been restrained at an evolutionary scale and is of little epidemiological relevance to contemporary parasite populations. This article reviews the growing number of field studies which indicate that natural hybridization in T. cruzi may be frequent, non-obligatory and idiosyncratic; potentially involving independent exchange of kinetoplast and nuclear genetic material as well as canonical meiotic mechanisms. Together these observations now challenge the traditional paradigm of preponderate clonal evolution in T. cruzi and highlight the need for additional, intensive and appropriately sampled field surveys, complemented by high resolution, combined nuclear and mitochondrial population genetics analyses

Chagas Disease in the United States: a Public Health Approach.

Trypanosoma cruzi is the etiological agent of Chagas disease, usually transmitted by triatomine vectors. An estimated 20 to 30% of infected individuals develop potentially lethal cardiac or gastrointestinal disease. Sylvatic transmission cycles exist in the southern United States, involving 11 triatomine vector species and infected mammals such as rodents, opossums, and dogs. Nevertheless, imported chronic T. cruzi infections in migrants from Latin America vastly outnumber locally acquired human cases. Benznidazole is now FDA approved, and clinical and public health efforts are under way by researchers and health departments in a number of states. Making progress will require efforts to improve awareness among providers and patients, data on diagnostic test performance and expanded availability of confirmatory testing, and evidence-based strategies to improve access to appropriate management of Chagas disease in the United States

Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population structure, hybridization and a role for humans in Andean parasite dispersal.

An improved understanding of how a parasite species exploits its genetic repertoire to colonize novel hosts and environmental niches is crucial to establish the epidemiological risk associated with emergent pathogenic genotypes. Trypanosoma cruzi, a genetically heterogeneous, multi-host zoonosis, provides an ideal system to examine the sylvatic diversification of parasitic protozoa. In Bolivia, T. cruzi I, the oldest and most widespread genetic lineage, is pervasive across a range of ecological clines. High-resolution nuclear (26 loci) and mitochondrial (10 loci) genotyping of 199 contemporaneous sylvatic TcI clones was undertaken to provide insights into the biogeographical basis of T. cruzi evolution. Three distinct sylvatic parasite transmission cycles were identified: one highland population among terrestrial rodent and triatomine species, composed of genetically homogenous strains (Ar = 2.95; PA/L = 0.61; DAS = 0.151), and two highly diverse, parasite assemblages circulating among predominantly arboreal mammals and vectors in the lowlands (Ar = 3.40 and 3.93; PA/L = 1.12 and 0.60; DAS = 0.425 and 0.311, respectively). Very limited gene flow between neighbouring terrestrial highland and arboreal lowland areas (distance ~220 km; FST = 0.42 and 0.35) but strong connectivity between ecologically similar but geographically disparate terrestrial highland ecotopes (distance >465 km; FST = 0.016-0.084) strongly supports ecological host fitting as the predominant mechanism of parasite diversification. Dissimilar heterozygosity estimates (excess in highlands, deficit in lowlands) and mitochondrial introgression among lowland strains may indicate fundamental differences in mating strategies between populations. Finally, accelerated parasite dissemination between densely populated, highland areas, compared to uninhabited lowland foci, likely reflects passive, long-range anthroponotic dispersal. The impact of humans on the risk of epizootic Chagas disease transmission in Bolivia is discussed

Importation of Hybrid Human-Associated Trypanosoma cruzi Strains of Southern South American Origin, Colombia.

We report the characterization of Trypanosoma cruzi of southern South American origin among humans, domestic vectors, and peridomestic hosts in Colombia using high-resolution nuclear and mitochondrial genotyping. Expanding our understanding of the geographic range of lineage TcVI, which is associated with severe Chagas disease, will help clarify risk of human infection for improved disease control

Wild Trypanosoma cruzi I genetic diversity in Brazil suggests admixture and disturbance in parasite populations from the Atlantic Forest region.

BACKGROUND: Trypanosoma cruzi (Kinetoplastida, Trypanosomatidae) infection is an ancient and widespread zoonosis distributed throughout the Americas. Ecologically, Brazil comprises several distinct biomes: Amazonia, Cerrado, Caatinga, Pantanal and the Atlantic Forest. Sylvatic T. cruzi transmission is known to occur throughout these biomes, with multiple hosts and vectors involved. Parasite species-level genetic diversity can be a useful marker for ecosystem health. Our aims were to: investigate sylvatic T. cruzi genetic diversity across different biomes, detect instances of genetic exchange, and explore the possible impact of ecological disturbance on parasite diversity at an intra-species level. METHODS: We characterised 107 isolates of T. cruzi I (TcI; discrete typing unit, DTU I) from different major Brazilian biomes with twenty-seven nuclear microsatellite loci. A representative subset of biologically cloned isolates was further characterised using ten mitochondrial gene loci. We compared these data generated from Brazilian TcI isolates from around America. RESULTS: Genetic diversity was remarkably high, including one divergent cluster that branched outside the known genetic diversity of TcI in the Americas. We detected evidence for mitochondrial introgression and genetic exchange between the eastern Amazon and Caatinga. Finally, we found strong signatures of admixture among isolates from the Atlantic Forest region by comparison to parasites from other study sites. CONCLUSIONS: Atlantic Forest sylvatic TcI populations are highly fragmented and admixed by comparison to others around Brazil. We speculate on: the possible causes of Atlantic Forest admixture; the role of T. cruzi as a sentinel for ecosystem health, and the impact disrupted sylvatic transmission cycles might have on accurate source attribution in oral outbreaks

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