Are insecticide-treated bednets more protective against Plasmodium falciparum than Plasmodium vivax-infected mosquitoes?

BACKGROUND: The outcomes of insecticide-treated bednet (ITN) interventions for malaria control in Papua New Guinea tend to suggest a differential protective effect against Plasmodium falciparum and Plasmodium vivax. Little is known about the impact of ITNs on the relative abundance of mosquitoes infected with either P. falciparum or P. vivax. This paper describes the biting cycle of P. falciparum and P. vivax-infected mosquitoes and the impact of an ITN intervention on the proportion of mosquitoes infected with either parasite species. METHODS: Entomological investigations were performed in East Sepik (ESP) and New Ireland Provinces (NIP) of PNG. Mosquitoes were collected using the all-night (18:00 - 06:00) landing catch and CDC light-trap methods and species specific malaria sporozoite rates were determined by ELISA. RESULTS AND DISCUSSION: The distribution of sporozoite positive mosquitoes in three four-hour periods (18:00-22:00, 22:00-02:00 & 02:00-06:00) showed that a higher proportion of P. vivax-infected mosquitoes were biting before people retired to bed under the protection of bednets. In the intervention village, the 308 mosquitoes collected before ITNs were introduced included eight (2.0%) P. falciparum-positive and four (1.0%) P. vivax-positive specimens, giving a parasite ratio of 2:1. The sporozoite rate determined from 908 mosquitoes caught after ITNs were introduced showed a significant decrease for P. falciparum (0.7%) and a slight increase for P. vivax (1.3%), resulting in a post intervention parasite ratio of 1:2. In the East Sepik Province, where ITNs were not used, P. falciparum remained the dominant species in 12 monthly mosquito collections and monthly P. falciparum:P. vivax formula varied from 8:1 to 1.2:1. CONCLUSION: These findings suggest that people sleeping under treated bednets may be more exposed to P. vivax than P. falciparum-infected mosquitoes before going to sleep under the protection of bednets. This difference in the biting behaviour of mosquitoes infected with different malaria parasites may partly explain the change in the P. falciparum:P. vivax formula after the introduction of ITNs

Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana

Background The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. Methodology/Principal Findings The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes—across health system functions–stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system–national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00–1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were least integrated. Extent of integration was partial at all levels of the health system with a CII of 0.48–0.68; however it was higher at the district compared to the national and regional levels. Conclusions/Significance To ensure further integration of the NTDP, planning and finance management activities must be decentralized to involve regional and district levels of the health system. The study provides an empirical measure of extent of integration and indicators to guide further integration. Author Summary Two main strategies have been used to address diseases that affects large sections of populations. One strategy called targeted or vertical programme sets up separate system from the general health system with its own human resources, management, implementation, data reporting and evaluation systems. Integrated (also called horizontal) strategy on the other hand uses existing health system structures to implement activities to control target health problems. Integrated strategy is preferred because it strengthens country health systems. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a dedicated management structure at the national level but uses general health system structures at the regional and district levels to implement activities. This study assessed the extent of integration of the NTDP into the health system at the national, regional and district levels. It was found that the NTDP activities were better integrated at the district compared to the regional and national levels of the health system. Furthermore, it also found that service delivery activities were most integrated while financing and planning activities were least integrated at all levels of the health system. These findings provide points to guide efforts to make the NTDP more integrated and can be applied to other health programmes

A School-Based Cross-Sectional Survey of Adverse Events following Co-Administration of Albendazole and Praziquantel for Preventive Chemotherapy against Urogenital Schistosomiasis and Soil-Transmitted Helminthiasis in Kwale County, Kenya

Background Soil-transmitted helminths and schistosomiasis are mostly prevalent in developing countries due to poor sanitation and lack of adequate clean water. School-age children tend to be the target of chemotherapy-based control programmes because they carry the heaviest worm and egg burdens. The present study examines adverse events (AEs) experienced following co-administration of albendazole and praziquantel to school-age children in a rural area in Kwale County, Kenya. Methods Children were treated with single doses of albendazole and praziquantel tablets and then interviewed using a questionnaire for post treatment AEs. Results Overall, 752 children, 47.6% boys, participated in the study. Their median (interquartile range) age was 12.0 (10.0–14.0) years. A total of 190 (25.3%) children reportedly experienced at least one AE. In total, 239 cases of AEs were reported with the most frequent being abdominal pains (46.3%), dizziness (33.2%) and nausea (21.1%). Majority of the reported AEs (80.8%) resolved themselves while 12.1% and 6.3% were countered by, respectively, self-medication and visiting a nearby health facility. More girls (60.5%) than boys (39.5%) reported AEs (P = 0.027). Conclusions The AEs were mild and transient, and were no worse than those expected following monotherapy. The current study adds to the evidence base that dual administration of albendazole and praziquantel in school-based mass drug administration is safe with only mild adverse events noted

Shrinking the lymphatic filariasis map of Ethiopia: reassessing the population at risk through nationwide mapping

BACKGROUND Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. METHODOLOGY/PRINCIPAL FINDING A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. CONCLUSIONS We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale

Modelling strategies to break transmission of lymphatic filariasis : aggregation, adherence and vector competence greatly alter elimination

Background: With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. Methods: We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. Results: In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. Conclusion: Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be analysed to effectively tailor programmes in the drive for elimination

Application of a Polymerase Chain Reaction-ELISA to Detect Wuchereria bancrofti in Pools of Wild-Caught Anopheles punctualatus in a Filariasis Control Area in Papua New Guinea

Chemotherapy-based eradication programs are aimed at stopping transmission of Wuchereria bancroftiby its obligatory mosquito vector. This study compares one year post-treatment W. bancrofti infection rates of Anopheles punctulatus, the main vector of lymphatic filariasis in Papua New Guinea, using traditional dissection techniques and a polymerase chain reaction (PCR)-based ELISA of a parasite-specific Ssp I repeat. A total of 633 mosquitoes in 35 batches were dissected. Six batches contained W. bancrofti-infected mosquitoes, giving a minimum infection rate of 0.9%. This value was not different than the actual infection rate, which was 9 (1.4%) of 633 mosquitoes (P� 0.48). The DNA was extracted from 47 pools containing a mean of 13.2 mosquitoes per pool. A total of 621 mosquitoes were processed for the PCR-ELISA, including 486 caught by human bait and 135 by light trap, which included both dead and live mosquitoes. Of 23 pools of alcohol-preserved human-bait mosquitoes, seven were positive by the PCR-ELISA, giving an infection rate identical to that obtained by dissection of individual mosquitoes (1.4%). The minimum infection rates for pools of light-trap mosquitoes found dead and alive were 2.7% (2 of 74) and 4.9% (3 of 61), respectively. These values did not differ from each other (P � 0.84), but the overall infection rate of light- trap mosquitoes was greater than that of mosquitoes captured by human bait (3.7% versus 1.4%; P � 0.09). These data indicate that the PCR-ELISA of a W. bancrofti Ssp I repeat using pools of mosquitoes is comparable to traditional dissection techniques for monitoring transmission intensity following introduction of mass chemotherapy. This approach may also be useful for rapid and cost-effective assessment of transmission in endemic areas where the frequency of overt lymphatic pathology is low

Assessing the presence of Wuchereria bancrofti in vector and human populations from urban communities in Conakry, Guinea

The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 with the goal of interrupting transmission of lymphatic filariasis (LF) through multiple rounds of mass drug administration (MDA). In Guinea, there is evidence of ongoing LF transmission, but little is known about the most densely populated parts of the country, including the capital Conakry. In order to guide the LF control and elimination efforts, serological and entomological surveys were carried out to determine whether or not LF transmission occurs in Conakry.; The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in people recruited from all five districts of Conakry. Mosquitoes were collected over a 1-year period, in 195 households in 15 communities. A proportion of mosquitoes were analysed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR).; CFA test revealed no infection in the 611 individuals examined. A total of 14,334 mosquitoes were collected; 14,135 Culex (98.6 %), 161 Anopheles (1.1 %) and a few other species. Out of 1,312 Culex spp. (9.3 %) and 51 An. gambiae (31.7 %) dissected, none was infected with any stage of the W. bancrofti parasite. However, the LAMP assay revealed that 1.8 % of An. gambiae and 0.31 % of Culex spp. were positive, while PCR determined respective prevalences of 0 % and 0.19 %.; This study revealed the presence of W. bancrofti DNA in mosquitoes, despite the apparent absence of infection in the human population. Although MDA interventions are not recommended where the prevalence of ICT is below 1 %, the entomological results are suggestive of the circulation of the parasite in the population of Conakry. Therefore, rigorous surveillance is still warranted so that LF transmission in Conakry would be identified rapidly and adequate responses being implemented

The impact of residual infections on Anopheles-transmitted Wuchereria bancrofti after multiple rounds of mass drug administration

Background Many countries have made significant progress in the implementation of World Health Organization recommended preventive chemotherapy strategy, to eliminate lymphatic filariasis (LF). However, pertinent challenges such as the existence of areas of residual infections in disease endemic districts pose potential threats to the achievements made. Thus, this study was undertaken to assess the importance of these areas in implementation units (districts) where microfilaria (MF) positive individuals could not be found during the mid-term assessment after three rounds of mass drug administration. Methods This study was undertaken in Bo and Pujehun, two LF endemic districts of Sierra Leone, with baseline MF prevalence of 2 % and 0 % respectively in sentinel sites for monitoring impact of the national programme. Study communities in the districts were purposefully selected and an assessment of LF infection prevalence was conducted together with entomological investigations undertaken to determine the existence of areas with residual MF that could enable transmission by local vectors. The transmission Assessment Survey (TAS) protocol described by WHO was applied in the two districts to determine infection of LF in 6–7 year old children who were born before MDA against LF started. Results The results indicated the presence of MF infected children in Pujehun district. An. gambiae collected in the district were also positive for W. bancrofti, even though the prevalence of infection was below the threshold associated with active transmission. Conclusions Residual infection was detected after three rounds of MDA in Pujehun – a district of 0 % Mf prevalence at the sentinel site. Nevertheless, our results showed that the transmission was contained in a small area. With the scale up of vector control in Anopheles transmission zones, some areas of residual infection may not pose a serious threat for the resurgence of LF if the prevalence of infections observed during TAS are below the threshold required for active transmission of the parasite. However, robust surveillance strategies capable of detecting residual infections must be implemented, together with entomological assessments to determine if ongoing vector control activities, biting rates and infection rates of the vectors can support the transmission of the disease. Furthermore, in areas where mid-term assessments reveal MF prevalence below 1 % or 2 % antigen level, in Anopheles transmission areas with active and effective malaria vector control efforts, the minimum 5 rounds of MDA may not be required before implementing TAS. Thus, we propose a modification of the WHO recommendation for the timing of sentinel and spot-check site assessments in national programs

Antibodies against Merozoite Surface Protein (Msp)-119 Are a Major Component of the Invasion-Inhibitory Response in Individuals Immune to Malaria

Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-119 from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-119, we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum–immune humans and P. chabaudi–immune mice. In some individual human sera, MSP-119 antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-119–based vaccines