Adaptation of a malaria surveillance system for use in a visceral leishmaniasis elimination programme

Background Successful public practice relies on generation and use of high-quality data. A data surveillance system (the Disease Data Management System [DDMS]) in use for malaria was adapted for use in the Indian visceral leishmaniasis elimination programme. Methods A situational analysis identified the data flows in current use. Taxonomic trees for the vector of visceral leishmaniasis in India, Phlebotomus argentipes, were incorporated into the DDMS to allow entry of quality assurance and insecticide susceptibility data. A new quality assurance module was created to collate the concentration of DDT that was applied to walls during the indoor residual spraying (IRS) vector control programme. Results The DDMS was implemented in Bihar State and used to collate and manage data from sentinel sites in eight districts. Quality assurance data showed that DDT was under-applied to walls during IRS; this, combined with insecticide susceptibility data showing widespread vector resistance to DDT prompted a national policy change to using compression pumps and alpha-cypermethrin insecticide for IRS. Conclusions The adapted DDMS centralises programmatic data and enhances evidence-based decision making and active policy change. Moving forward, further modules of the system will be implemented, allowing extended data capture and streamlined transmission of key information to decision makers

Enhancing Decision Support for Vector-Borne Disease Control Programs—The Disease Data Management System

Data is at the core of any successful vector-borne disease control or elimination activity. At the early stages of control, monitoring data can help prioritize limited funding and resources to maximize impact. During the pre-elimination and elimination phases, surveillance data itself becomes the primary intervention by quickly identifying persistent transmission [1]. In addition, it has been identified that spatial decision-support tools will be crucial to integrate with health information systems (HIS) as countries strive for elimination [2]. The Disease Data Management System (DDMS) is a tool designed to meet the data management and decision-support needs of vector-borne disease control programs as they transition through control to elimination. The development and functionality of the DDMS has been described elsewhere [3], and particular advantages and disadvantages are highlighted in Box 1. Here, we describe the implementation and impact of the system in disease-endemic countries, user feedback, and future challenges

Spatial and Temporal Trends in Insecticide Resistance among Malaria Vectors in Chad Highlight the Importance of Continual Monitoring.

BACKGROUND A longitudinal Anopheles gambiae s.l. insecticide resistance monitoring programme was established in four sentinel sites in Chad 2008-2010. When this programme ended, only sporadic bioassays were performed in a small number of sites. METHODS WHO diagnostic dose assays were used to measure the prevalence of insecticide resistance to 0.1% bendiocarb, 4% DDT, 0.05% deltamethrin, 1% fenitrothion, and 0.75% permethrin in the main malaria vectors at the beginning and end of the malaria transmission season for three years 2008-2010, with subsequent collections in 2011 and 2014. Species and molecular identification of An. gambiae M and S forms and kdr genotyping was performed using PCR-RLFP; circumsporozoite status was assessed using ELISA. RESULTS Between 2008 and 2010, significant changes in insecticide resistance profiles to deltamethrin and permethrin were seen in 2 of the sites. No significant changes were seen in resistance to DDT in any site during the study period. Testing performed after the period of routine monitoring had ended showed dramatic increases to DDT and pyrethroid resistance in 3 sites. No resistance to organophosphate or carbamate insecticides was detected. An. arabiensis was the predominate member of the An. gambiae complex in all 4 sites; adult collections showed temporal variation in species composition in only 1 site. Kdr analysis identified both 1014F and 1014S alleles in An. gambiae S only. Circumsporozoite analysis showed the highest vector infection rates were present in Donia, a site with extensive use of agricultural insecticides. CONCLUSIONS During the monitoring gap of four years, significant changes occurred in resistance prevalence in 3 of the 4 sites (p = <0.001), endangering the efficacy of currently implemented malaria control interventions. Significant changes in insecticide resistance profiles and a lack of kdr resistance alleles in adult populations highlight the urgent need for comprehensive entomological monitoring to be implemented and sustained in country

Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in the visceral leishmaniasis vector Phlebotomus argentipes

Background Indoor residual spraying (IRS) with DDT has been the primary strategy for control of the visceral leishmaniasis (VL) vector Phlebotomus argentipes in India but efficacy may be compromised by resistance. Synthetic pyrethroids are now being introduced for IRS, but with a shared target site, the para voltage-gated sodium channel (VGSC), mutations affecting both insecticide classes could provide cross-resistance and represent a threat to sustainable IRS-based disease control. Methodology/Principal findings A region of the Vgsc gene was sequenced in P. argentipes from the VL hotspot of Bihar, India. Two knockdown resistance (kdr) mutations were detected at codon 1014 (L1014F and L1014S), each common in mosquitoes, but previously unknown in phlebotomines. Both kdr mutations appear largely recessive, but as homozygotes (especially 1014F/F) or as 1014F/S heterozygotes exert a strong effect on DDT resistance, and significantly predict survivorship to class II pyrethroids in short-duration bioassays. The mutations are present at high frequency in wild P. argentipes populations from Bihar, with 1014F significantly more common in higher VL areas. Conclusions/Significance The Vgsc mutations detected appear to be a primary mechanism underlying DDT resistance in P. argentipes and a contributory factor in reduced pyrethroid susceptibility, suggesting a potential impact if P. argentipes are subjected to suboptimal levels of pyrethroid exposure, or additional resistance mechanisms evolve. The assays to detect kdr frequency changes provide a sensitive, high-throughput monitoring tool to detecting spatial and temporal variation in resistance in P. argentipes

Development of a Simple Dipstick Assay for Operational Monitoring of DDT

Background Indoor residual spraying (IRS) of DDT is used to control visceral leishmaniasis (VL) in India. However, the quality of spraying is severely compromised by a lack of affordable field assays to monitor target doses of insecticide. Our aim was to develop a simple DDT insecticide quantification kit (IQK) for monitoring DDT levels in an operational setting. Methodology/ principle findings DDT quantification was based on the stoichiometric release of chloride from DDT by alkaline hydrolysis and detection of the released ion using Quantab chloride detection strips. The assay was specific for insecticidal p,p`-DDT (LoQ = 0.082 g/m2). Bostik discs were effective in post spray wall sampling, extracting 25–70% of active ingredient depending on surface. Residual DDT was sampled from walls in Bihar state in India using Bostik adhesive discs and DDT concentrations (g p,p`-DDT/m2) were determined using IQK and HPLC (n = 1964 field samples). Analysis of 161 Bostik samples (pooled sample pairs) by IQK and HPLC produced excellent correlation (R2 = 0.96; Bland-Altman bias = −0.0038). IQK analysis of the remaining field samples matched HPLC data in identifying households that had been under sprayed, in range or over sprayed. Interpretation A simple dipstick assay has been developed for monitoring DDT spraying that gives comparable results to HPLC. By making laboratory-based analysis of DDT dosing accessible to field operatives, routine monitoring of DDT levels can be promoted in low- and middle- income countries to maximise the effectiveness of IRS

Development and evaluation of a quick perception method in beginning reading

Thesis (M.A.)--Boston University, 1941. This item was digitized by the Internet Archive

Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India

Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). However, to achieve sustained elimination of VL, an appropriate post elimination surveillance programme should be designed, and crucial knowledge gaps in vector bionomics, human infection and transmission need to be addressed. This review examines the outstanding knowledge gaps, specifically in the context of Bihar State, India. The knowledge gaps in vector bionomics that will be of immediate benefit to current control operations include better estimates of human biting rates and natural infection rates of P. argentipes, with L. donovani, and how these vary spatially, temporally and in response to IRS. The relative importance of indoor and outdoor transmission, and how P. argentipes disperse, are also unknown. With respect to human transmission it is important to use a range of diagnostic tools to distinguish individuals in endemic communities into those who: 1) are to going to progress to clinical VL, 2) are immune/ refractory to infection and 3) have had past exposure to sand flies. It is crucial to keep in mind that close to elimination, and post-elimination, VL cases will become infrequent, so it is vital to define what the surveillance programme should target and how it should be designed to prevent resurgence. Therefore, a better understanding of the transmission dynamics of VL, in particular of how rates of infection in humans and sand flies vary as functions of each other, is required to guide VL elimination efforts and ensure sustained elimination in the Indian subcontinent. By collecting contemporary entomological and human data in the same geographical locations, more precise epidemiological models can be produced. The suite of data collected can also be used to inform the national programme if supplementary vector control tools, in addition to IRS, are required to address the issues of people sleeping outsid

HIV-1 in the United Kingdom: population dynamics and genetic evolution

Background: Phylogenetic characterisation of local HIV-1 epidemics can be used to understand emerging transmission networks. We analysed subtype-unassigned sequences in the UK HIV Drug Resistance Database (UK HIV DRD) to map the emergence and origin of genetically diverse recombinant strains using phylogenetic analyses, near full-length sequencing of plasma HIV-1 and CD4 cell count decline. Methods: 55,556 genotyped pol sequences (protease amino acids 1-99, RT amino acids 1-234) were analysed for evidence of recombination. Near full-length single genome sequencing of plasma HIV-1 was performed on stored specimens from six patients with a putative A1/D novel recombinant strain. Recombination and phylogenetic analyses were performed using RIP, PhyML, jpHMM, Simplot, SCUEAL and FastTree v2.3.1. Evolutionary analysis of putative novel recombinants was performed using Bayesian Evolutionary Analysis by Sampling Trees (BEAST). Geographic screening for additional instances of recombinant structures was performed using HIV BLAST and the Los Alamos National HIV database. Demographic data were available for 50/72 patients. CD4 cell count decline was assessed using linear regression. Results: The proportion of subtype-unassigned HIV-1 strains in the UK HIV DRD increased significantly during 1999-2008 (p

Quantifying late-stage host-seeking behaviour of Anopheles gambiae at the insecticidal net interface using a baited-box bioassay

Background Insecticide-treated nets (ITNs) are losing efficacy against pyrethroid-resistant malaria vector populations throughout Africa. Safeguarding bed net efficacy, vital for effective malaria control, requires greater knowledge of mosquito–ITN interactions and how this impacts on the mosquito. Methods A purpose-built benchtop apparatus with a closed 10 cm cubic chamber (the ‘Baited-box’) was used to video record behaviour of individual free-flying female Anopheles gambiae during approach and blood-feeding on a human hand through untreated nets and ITNs at close range. Time and duration of defined behavioural events, and knockdown and mortality at 1- and 24-h post-exposure respectively, were recorded for pyrethroid susceptible and resistant mosquitoes. Results Using three human volunteers differing in relative attractiveness to mosquitoes, 328 mosquitoes were individually tested. There were no significant differences between response rates to ITNs and untreated nets (P > 0.1) or between resistant (Tiassalé) and susceptible (Kisumu) mosquito strains, at untreated nets (P = 0.39) or PermaNet 2.0 (P = 1). The sequence of behavioural events from host-seeking to completion of blood-feeding was consistent in all tests but duration and start time of events involving net contact were reduced or delayed respectively with ITNs. Blood-feeding durations at untreated nets (means from 4.25 to 8.47 min (95% confidence interval (CI) = 3.39–9.89) at 3 human volunteers) were reduced by 37–50% at PermaNet 2.0, in susceptible (mean 2.59–4.72 min, 95% CI = 1.54–5.5, P =  0.2), and neither ITN type showed detectable spatial repellency. After initial contact, blood-feeding commenced later at Olyset (mean 2.76 min, 95% CI = 1.74–3.76, P = 0.0009) and PermaNet (mean 2.4 min, 95% CI = 1.52–3.33, P = 0.0058) than untreated netting (mean 0.68 min, 95% CI = 0.42–0.94). Conclusions The baited box offers a simple method for detailed characterization of mosquito behavioural responses to insecticidal nets, for comparing entomological modes of action between nets and for defining the behavioural responses of particular mosquito strains or populations. The device has potential as a screening assay in the search for novel net treatments and for investigations into behavioural resistance mechanisms

Pyrethroid-treated bed nets impair blood feeding performance in insecticide resistant mosquitoes

The blood feeding performance of female mosquitoes directly impacts their ability to transmit malaria. Yet their host seeking and blood feeding behaviours in the presence of insecticide-treated nets (ITNs) are still poorly understood. This work explores how both insecticide resistant and susceptible Anopheles gambiae s.l. mosquitoes interact with pyrethroid nets (PermaNet 2.0 or Olyset net) or an untreated net (UTN) while attempting to blood feed on a human arm. Regardless of mosquito resistance status, the ITNs did not efficiently prevent host searching but reduced blood feeding success by 34.1 (29.31–38.95) %. The Permanet and Olyset net reduced to 227.5 (208.19–246.77) sec and 235.9 (214.03–257.74) sec the average blood feeding duration from 369.9 (342.78–397.04) sec with the UTN. The ingested blood volume was on average 22% lower for all mosquitoes exposed to insecticide. When feeding through ITNs, the blood volume flow rate of the susceptible strain increased by 35%, but no significant difference was found in the resistant strain. Thus, whilst the presence of the insecticide in ITNs reduced mosquito blood feeding success and blood volume, the mosquito’s ability to respond by accelerating her rate of blood ingestion may further reduce the impact of ITNs on resistant mosquitoes