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Background: Mosquito-borne diseases such as malaria and encephalitis are still the cause of several hundred thousand deaths annually. The excessive use of chemical insecticides for transmission control has led to environmental pollution and widespread resistance in mosquitoes. Botanical insecticides' efficacies improvement has thus received considerable attention recently. Methods: The larvicidal effects of three essential oils from the Citrus family and limonene (their major ingredient) were first investigated against malaria and filariasis mosquito vectors. An attempt was then made to improve their efficacies by preparing nanoliposomes containing each of them. Results: The larvicidal effect of nanoformulated forms was more effective than non-formulated states. Nanoliposomes containing Citrus aurantium essential oil with a particle size of 52 ± 4 nm showed the best larvicidal activity (LC50 and LC90 values) against Anopheles stephensi (6.63 and 12.29 µg/mL) and Culex quinquefasciatus (4.9 and 16.4 µg/mL). Conclusion: Due to the green constituents and high efficacy of nanoliposomes containing C. aurantium essential oil, it could be considered for further investigation against other mosquitoes' populations and field trials. [ABSTRACT FROM AUTHOR]

Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good. [ABSTRACT FROM AUTHOR]

Abstract Lymphatic filariasis causes global morbidity. Wolbachia, an endo-symbiotic intracellular bacterium of the filarial nematode helps in their growth and development, regulates fecundity in female worms and contributes to the immunopathogenesis of the disease. However, genes and proteins of Wolbachia that may act as putative vaccine candidates are not known. In this study, we cloned recombinase-A protein of Wolbachia from Brugia malayi (wBmRecA) and carried out its detailed biochemical and immunological characterization. Bioinformatics analysis, circular dichroism and fluorescence spectral studies showed significant sequence and structural similarities between wBmRecA and RecA of other alpha-proteo- bacterial species. wBmRecA was ubiquitously expressed in all the three major life stages of B. malayi , including excretory-secretory products of the adult worm. In silico studies suggested immunogenic potential of wBmRecA, and mice immunized with wBmRecA exhibited elevated levels of immunoglobulins IgG1, IgG2a, IgG2b and IgG3 in their serum along with increased percentages of CD4+, CD8+ T cells and CD19+ B cells in their spleens. Notably, splenocytes from immunized mice showed increased m-RNA expression of T-bet, elevated proinflammatory cytokines IFN-γ and IL-12, while peritoneal MФs exhibited increased levels of iNOS, downregulated Arg-1 and secreted copious amounts of nitric oxide which contributed to severely impaired development of the infective larvae (Bm-L3). Interestingly, sera from immunized mice promoted significant cellular adherence and cytotoxicity against microfilariae and Bm-L3. Importantly, wBmRecA demonstrated strong immuno-reactivity with bancroftian sera from endemic normal individuals. These results suggest that wBmRecA is highly immunogenic, and should be explored further as a putative vaccine candidate against lymphatic filariasis. [ABSTRACT FROM AUTHOR]

In recent years, numerous studies screening mosquitoes for filarioid helminths (xenomonitoring) have been performed in Europe. The entomological monitoring of filarial nematode infections in mosquitoes by molecular xenomonitoring might serve as the measure of the rate at which humans and animals expose mosquitoes to microfilariae and the rate at which animals and humans are exposed to the bites of the infected mosquitoes. We hypothesized that combining the data obtained from molecular xenomonitoring and phenological studies of mosquitoes in the urban environment would provide insights into the transmission risk of filarial diseases. In our search for Dirofilaria spp.-infected mosquitoes, we have found Setaria tundra-infected ones instead, as in many other European studies. We have observed that cross-reactivity in PCR assays for Dirofilaria repens, Dirofilaria immitis, and S. tundra COI gene detection was the rule rather than the exception. S. tundra infections were mainly found in Aedes mosquitoes. The differences in the diurnal rhythm of Aedes and Culex mosquitoes did not seem a likely explanation for the lack of S. tundra infections in Culex mosquitoes. The similarity of S. tundra COI gene sequences found in Aedes vexans and Aedes caspius mosquitoes and in roe deer in many European studies, supported by data on Ae. vexans biology, suggested host preference as the most likely cause of the mosquito genus-biased infections. High diversity of the COI gene sequences isolated in the city of Wroclaw in south western Poland and the presence of identical or almost identical sequences in mosquitoes and roe deer across Europe suggests that S. tundra has been established in most of Europe for a very long time. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs) account for a large disease burden in sub-Saharan Africa. While the general cost-effectiveness of NTD interventions to improve health outcomes has been assessed, few studies have also accounted for the financial and education gains of investing in NTD control. Methods: We built on extended cost-effectiveness analysis (ECEA) methods to assess the health gains (e.g. infections, disability-adjusted life years or DALYs averted), household financial gains (out-of-pocket expenditures averted), and education gains (cases of school absenteeism averted) for five NTD interventions that the government of Madagascar aims to roll out nationally. The five NTDs considered were schistosomiasis, lymphatic filariasis, and three soil-transmitted helminthiases (Ascaris lumbricoides, Trichuris trichiura, and hookworm infections). Results: The estimated incremental cost-effectiveness for the roll-out of preventive chemotherapy for all NTDs jointly was USD125 per DALY averted (95% uncertainty range: 65–231), and its benefit-cost ratio could vary between 5 and 31. Our analysis estimated that, per dollar spent, schistosomiasis preventive chemotherapy, in particular, could avert a large number of infections (176,000 infections averted per $100,000 spent), DALYs (2,000 averted per $100,000 spent), and cases of school absenteeism (27,000 school years gained per $100,000 spent). Conclusion: This analysis incorporates financial and education gains into the economic evaluation of health interventions, and therefore provides information about the efficiency of attainment of three Sustainable Development Goals (SDGs). Our findings reveal how the national scale-up of NTD control in Madagascar can help address health (SDG3), economic (SDG1), and education (SDG4) goals. This study further highlights the potentially large societal benefits of investing in NTD control in low-resource settings. [ABSTRACT FROM AUTHOR]

Culex quinquefasciatus Say, a widely distributed mosquito in tropical and subtropical areas, is the most important vector of the filarial parasite Wuchereria bancrofti , the causative agent of lymphatic filariasis. In India, filariasis is endemic in 17 States and six Union Territories, putting about 553 million people at risk of infection. Vector control, which aims to prevent pathogen transmission through interventions targeting adult mosquito vectors, is a significant component of control of the disease. Chemical-based control represents a chief strategy in the management of mosquito vectors; however, continuous application of insecticides has led to the development of resistance in many mosquito vectors around the world. The current study aims to observe the variability of expression of carboxylesterase isozymes that play a role in detoxifying insecticides into non-toxic compounds, in different life stages of Culex mosquitoes, to understand levels of insecticide susceptibility that may be used in integrated mosquito management for efficient vector control. C. quinquefasciatus were collected from different localities of sub-Himalayan West Bengal, India, and adult and larval bioassays were performed against one organophosphate insecticide (chlorpyrifos) and two synthetic pyrethroid insecticides (deltamethrin and lambda-cyhalothrin). The activity of α- and β-carboxylesterases (quantitative assay) were measured in larvae and adults of C. quinquefasciatus using a microplate assay, and measured qualitative expression by native polyacrylamide gel electrophoresis. The study shows a differential activity of α- and β-carboxylesterases both in quantitative and qualitative assays. The quantitative assay reveals that larvae exhibit a 12.2-fold higher level activity of α-carboxylesterase and about 5.0-fold higher level of activity of β-carboxylesterase than adults. Some carboxylesterase isozymes, i.e., α-Est I-IV, α-Est VII and α-Est XI-XV were exclusively expressed in larvae, whereas α-Est V-VI and α-Est IX were expressed only in adults. In larvae, all β-Est I-IX were expressed, while in adults only β-Est IV-V was expressed. The results of adult and larval insecticide bioassay are also as per the above findings showing an LC90 value of 0.017 ppm, 0.097 ppm and 0.072 ppm in the larva, and LC90 value of 0.0015 ppm, 0.721 ppm, 0.364 ppm in adults against chlorpyrifos, deltamethrin and lambda-cyhalothrin, respectively. [ABSTRACT FROM AUTHOR]

Background: Current Global Program to Eliminate Lymphatic Filariasis (GPELF) that prohibits pregnant mothers and children below two years of age from coverage targeted interruption of transmission after 5–6 rounds of annual mass drug administration (MDA). However, after more than 10 rounds of MDA in India the target has not been achieved, which poses challenge to the researchers and policy makers. Several studies have shown that in utero exposure to maternal filarial infections plays certain role in determining the susceptibility and disease outcome in children. But the mechanism of which has not been studied extensively. Therefore the present study was undertaken to understand the mechanism of immune modulation in children born to filarial infected mother in a MDA ongoing area. Methodology and principal finding: To our knowledge this is the first study to conduct both cellular and humoral immunological assays and follow up the children until older age in a W bancrofti endemic area,where the microfilariae (Mf) rate has come down to <1% after 10 rounds of MDA. A total 57 (32: born to infected, 25: born to uninfected mother) children were followed up. The infection status of children was measured by presence of Mf and circulating filarial antigen (CFA) assay. Filaria specific IgG1, IgG2, IgG3 and IgG4 responses were measured by ELISA. Plasma level of IL-10 and IFN-γ were evaluated by using commercially available ELISA kit. The study reveals a high rate of acquisition of filarial infection among the children born to infected mother compared to uninfected mothers. A significantly high level of IgG1 and IgG4 was observed in children born to infected mother, whereas high level of IgG3 was marked in children born to uninfected mother. Significantly high level of IL-10 positively correlated with IgG4 have been observed in infected children born to infected mother, while high level of IFN-γ positively correlated with IgG3 was found in infection free children born to mother free from infection at the time of pregnancy. Moreover a negative correlation between IL-10and IFN-γ has been observed only among the infected children born to infected mother. Significance conclusion: The study shows a causal association between maternal filarial infection and impaired or altered immune response in children more susceptible to filarial infection during early childhood. As lymphatic damage that commences in childhood during asymptomatic stage has major implications from public health point of view, understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health by implementing MDA campaigns towards all women of childbearing age and young children in achieving the target of global elimination of LF. [ABSTRACT FROM AUTHOR]

Brugia malayi is a causative agent of lymphatic filariasis, a major tropical disease. The infective L3 parasite stage releases immunomodulatory proteins including the venom allergen-like proteins (VALs), which are members of the SCP/TAPS (Sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. BmVAL-1 is a major target of host immunity with >90% of infected B. malayi microfilaraemic cases being seropositive for antibodies to BmVAL-1. This study is part of ongoing efforts to characterize the structures and functions of important B. malayi proteins. Recombinant BmVAL-1 was produced using a plant expression system, crystallized and the structure was solved by molecular replacement and refined to 2.1 Å, revealing the characteristic alpha/beta/alpha sandwich topology of eukaryotic SCP/TAPS proteins. The protein has more than 45% loop regions and these flexible loops connect the helices and strands, which are longer than predicted based on other parasite SCP/TAPS protein structures. The large central cavity of BmVAL-1 is a prototypical CRISP cavity with two histidines required to bind divalent cations. The caveolin-binding motif (CBM) that mediates sterol binding in SCP/TAPS proteins is large and open in BmVAL-1 and is N-glycosylated. N-glycosylation of the CBM does not affect the ability of BmVAL-1 to bind sterol in vitro. BmVAL-1 complements the in vivo sterol export phenotype of yeast mutants lacking their endogenous SCP/TAPS proteins. The in vitro sterol-binding affinity of BmVAL-1 is comparable with Pry1, a yeast sterol transporting SCP/TAPS protein. Sterol binding of BmVAL-1 is dependent on divalent cations. BmVAL-1 also has a large open palmitate-binding cavity, which binds palmitate comparably to tablysin-15, a lipid-binding SCP/TAPS protein. The central cavity, CBM and palmitate-binding cavity of BmVAL-1 are interconnected within the monomer with channels that can serve as pathways for water molecules, cations and small molecules. [ABSTRACT FROM AUTHOR]

Abstract: Proposed at the beginning of the twentieth century to explain the origin of eukaryotic organelles from prokaryotes, endosymbiosis is now medically defined by various interaction patterns between microorganisms and their residing hosts, best exemplified by the bacterial endosymbiont Wolbachia identified in arthropods and filarial nematodes, which can influence normal development, reproduction, survival and transmission of the hosts. Based on the transmission modes, vertical or horizontal, and the function of the endosymbionts, the host–symbiont dependence can be divided into primary or secondary. In dermatology, the role of endosymbionts in skin ectoparasitosis has aroused great interests in the past years. Riesia pediculicola is a primary bacterial endosymbiont in body lice Pediculus humanus, and supplement their hosts with vitamin B, especially pantothenic acid. In cimicosis, the Gram‐negative Wolbachia can synthesize biotin and riboflavin, which are crucial for the growth and reproduction of the bedbug Cimex lectularius. In human demodicosis and rosacea, further study is required to prove the pathogenic role of the Gram‐negative bacteria Bacillus oleronius or the Gram‐positive bacteria Bacillus cereus demonstrated in the Demodex mites. The high infection rate of adult female ticks Ixodes ricinus with the Gram‐negative bacteria Midichloria mitochondrii present in the mitochondria in diverse ovarian cells, with the high seroprevalence rate in tick‐exposed subjects, raises the possibility that this non‐pathogenic endosymbiont may play a role in immune response and successful transmission of the tick‐borne pathogen. The anaerobic protozoan Trichomonas vaginalis and bacteria Mycoplasma hominis are two obligate parasites in the urogenital epithelium, with partially overlapping symptoms. Intracellular localization of Mycoplasma hominis can avoid host immune response and penetration of antibiotics, while Trichomonas vaginalis infected with Mycoplasma hominis seems to have a higher cytopathic activity and amoeboid transformation rate. Further study on the biology and pathogenesis of different endosymbionts in dermatological parasitosis will help for the development of new treatment modalities. [ABSTRACT FROM AUTHOR]

Filarial infections of humans cause some of the most important neglected tropical diseases. The global efforts for eliminating filarial infections by mass drug administration programs may require additional tools (safe macrofilaricidal drugs, vaccines, and diagnostic biomarkers). The accurate and sensitive detection of viable parasites is essential for diagnosis and for surveillance programs. Current community-wide treatment modalities do not kill the adult filarial worms effectively; hence, there is a need to identify and develop safe macrofilaricidal drugs. High-throughput sequencing, mass spectroscopy methods and advances in computational biology have greatly accelerated the discovery process. Here, we describe post-genomic developments toward the identification of diagnostic biomarkers and drug targets for the filarial infection of humans. [ABSTRACT FROM AUTHOR]

Parasitic nematodes have evolved powerful immunomodulatory molecules to enable their survival in immunocompetent hosts by subverting immune responses and minimizing pathological processes. One filarial molecule known to counteract host immune responses by inducing IL-10 and regulatory macrophages in mice is filarial cystatin. During a patent filarial infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive. The microfilarial larval stage was formerly shown to induce human regulatory monocytes and macrophages. Thus, here we aim was to determine how filarial cystatin of the human pathogenic filaria Brugia malayi (BmCPI-2) contributes to immune hyporesponsiveness in human monocytes and macrophages elicited by microfilaria. For this purpose, filarial cystatin was depleted from microfilarial lysate (Mf). Detecting the immunomodulatory potential of cystatin-depleted Mf revealed that IL-10, but not IL-8 and IL-6 induction in monocytes and macrophages is dependent on the presence of cystatin. In addition, the Mf-induced expression of the regulatory surface markers PD-L1 and PD-L2 in human monocytes, but not in macrophages, is dependent on cystatin. While Mf-treated monocytes result in decreased CD4+ T-cell proliferation in a co-culture assay, stimulation of T-cells with human monocytes treated with cystatin-depleted Mf lead to a restoration of CD4+ T-cell proliferation. Moreover, IL-10 induction by cystatin within Mf was dependent on p38 and ERK in macrophages, but independent of the ERK pathway in monocytes. These findings indicate that filarial nematodes differentially trigger and exploit various signaling pathways to induce immunomodulation in different myeloid cell subsets. [ABSTRACT FROM AUTHOR]

Prolonged existence of filarial parasites and their molecules within the host modulate the host immune system to instigate their survival and induce inflammatory responses that contribute to disease progression. Recombinant Brugia malayi pepsin inhibitor (rBm33) modulates the host immune responses by skewing towards Th1 responses characterized by secretion of inflammatory molecules such as TNF-α, IL-6, nitric oxide (NO). Here we also specified the molecular signaling events triggered by rBm33 in peripheral blood mononuclear cells (PBMCs) of filarial endemic normals (EN). rBm33 predominantly enhanced the levels of nitric oxide in cultured PBMCs but did not result in oxidative stress to the host cells. Further, rBm33 treatment of human PBMCs resulted in higher GSH/GSSG levels. MYD88 dependent activation was found to be associated with rBm33 specific inflammatory cytokine production. rBm33 triggered intracellular signaling events also involved JNK activation in host PBMCs. In addition, c-Fos and not NF-κB was identified as the transcription factor regulating the expression of inflammatory cytokines in rBm33 stimulated PBMCs. rBm33 marked its role in filarial pathology by altered levels of growth factors but did not have a significant impact on matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) activity of host PBMCs. Thus, the study outlines the signaling network of rBm33 induced inflammatory responses within the host immune cells. [ABSTRACT FROM AUTHOR]

Background: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. Methods: Children aged 5–18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. Findings: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. Interpretation: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. Trial registration: ClinicalTrials.gov No [ABSTRACT FROM AUTHOR]

Background: The Global Programme to Eliminate Lymphatic Filariasis (GPELF), launched in 2000, has the target of eliminating the disease as a public health problem by the year 2020. The strategy adopted is mass drug administration (MDA) to all eligible individuals in endemic communities and the implementation of measures to reduce the morbidity of those suffering from chronic disease. Success has been recorded in many rural endemic communities in which elimination efforts have centered. However, implementation has been challenging in several urban African cities. The large cities of West Africa, exemplified in Nigeria in Kano are challenging for LF elimination program because reaching 65% therapeutic coverage during MDA is difficult. There is therefore a need to define a strategy which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had reached 33 of the 44 Local Government Areas (LGAs) there remained eleven ‘urban’ LGAs which had not been covered by MDA. Given the challenges of achieving at least 65% coverage during MDA implementation over several years in order to achieve elimination, it may be challenging to eliminate LF in such settings. In order to plan the LF control activities, this study was undertaken to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs. Methods: The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in 981 people in three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum knock-down spray sheet collections (PSC) in different households. A proportion of mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR). Results: The results showed that none of the 981 subjects (constituted of <21% of children 5–10 years old) tested had detectable levels of CFA in their blood. Entomological results showed that An. gambiae s.l. had W. bancrofti DNA detectable in pools in Kano; W. bancrofti DNA was detected in between 0.96% and 6.78% and to a lesser extent in Culex mosquitoes where DNA was detected at rates of between 0.19% and 0.64%. DNA analysis showed that An. coluzzii constituted 9.9% of the collected mosquitoes and the remaining 90.1% of the mosquitoes were Culex mosquitoes. Conclusion: Despite detection of W. bancrofti DNA within mosquito specimens collected in three Kano urban LGAs, we were not able to find a subject with detectable level of CFA. Together with other evidence suggesting that LF transmission in urban areas in West Africa may not be of significant importance, the Federal Ministry of Health advised that two rounds of MDA be undertaken in the urban areas of Kano. It is recommended that the prevalence of W. bancrofti infection in the human and mosquito populations be re-assessed after a couple of years. [ABSTRACT FROM AUTHOR]

Background: The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission.Methods: A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system.Discussion: It is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes.Trial Registration: ClinicalTrials.gov, ID: NCT03036059 . Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425 . Registered on 23 February 2017. [ABSTRACT FROM AUTHOR]

Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red-FLBZ). The rate of microsomal red-FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red-FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red-FLBZ to FLBZ in a NADP+-dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red-FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species. [ABSTRACT FROM AUTHOR]

Background: There are growing demands for predicting the prospects of achieving the global elimination of neglected tropical diseases as a result of the institution of large-scale nation-wide intervention programs by the WHO-set target year of 2020. Such predictions will be uncertain due to the impacts that spatial heterogeneity and scaling effects will have on parasite transmission processes, which will introduce significant aggregation errors into any attempt aiming to predict the outcomes of interventions at the broader spatial levels relevant to policy making. We describe a modeling platform that addresses this problem of upscaling from local settings to facilitate predictions at regional levels by the discovery and use of locality-specific transmission models, and we illustrate the utility of using this approach to evaluate the prospects for eliminating the vector-borne disease, lymphatic filariasis (LF), in sub-Saharan Africa by the WHO target year of 2020 using currently applied or newly proposed intervention strategies. METHODS AND RESULTS: We show how a computational platform that couples site-specific data discovery with model fitting and calibration can allow both learning of local LF transmission models and simulations of the impact of interventions that take a fuller account of the fine-scale heterogeneous transmission of this parasitic disease within endemic countries. We highlight how such a spatially hierarchical modeling tool that incorporates actual data regarding the roll-out of national drug treatment programs and spatial variability in infection patterns into the modeling process can produce more realistic predictions of timelines to LF elimination at coarse spatial scales, ranging from district to country to continental levels. Our results show that when locally applicable extinction thresholds are used, only three countries are likely to meet the goal of LF elimination by 2020 using currently applied mass drug treatments, and that switching to more intensive drug regimens, increasing the frequency of treatments, or switching to new triple drug regimens will be required if LF elimination is to be accelerated in Africa. The proportion of countries that would meet the goal of eliminating LF by 2020 may, however, reach up to 24/36 if the WHO 1% microfilaremia prevalence threshold is used and sequential mass drug deliveries are applied in countries.Conclusions: We have developed and applied a data-driven spatially hierarchical computational platform that uses the discovery of locally applicable transmission models in order to predict the prospects for eliminating the macroparasitic disease, LF, at the coarser country level in sub-Saharan Africa. We show that fine-scale spatial heterogeneity in local parasite transmission and extinction dynamics, as well as the exact nature of intervention roll-outs in countries, will impact the timelines to achieving national LF elimination on this continent. [ABSTRACT FROM AUTHOR]

In the search for potential vaccine candidates for the control of human lymphatic filariasis, we recently identified calponin-like protein, that regulates actin/myosin interactions, in a proinflammatory fraction F8 (45.24–48.64 kDa) of Brugia malayi adult worms. In the present study, the gene was cloned, expressed, and the recombinant Calponin of B. malayi (r-ClpBm) was prepared and characterized. r-ClpBm bears homology with OV9M of Onchocerca volvulus, a non-lymphatic filariid that causes loss of vision and cutaneous pathology . r-ClpBm was found to be a ∼45 kDa protein that folds into a predominantly α-helix conformation. The protective efficacy of r-ClpBm against B. malayi infection in Mastomys coucha was investigated by assessing the course of microfilaraemia and adult worm burden in the host immunized with r-ClpBm and subsequently infected with infective third stage larvae (L 3 ). Expression of the Calponin was detected in all life stages (microfilariae, L 3 , L 4 , L 5 and adults) of the parasite and immunization with r-ClpBm partially protected M. coucha against establishment of infection as inferred by ∼42% inhibition in parasite burden. Upregulated cellular proliferation, TNF-α, IFN-γ, IL-1β, IL-4, nitric oxide (NO) release, expression of iNOS, and specific IgG, IgG1 and IgG2b in immunized animals correlated with parasitological findings. r-ClpBm immunization caused degranulation in majority of mast cells indicating possible involvement of mast cell products in reducing the parasite survival. It appears that complex mechanisms including Th1, Th2, NO and mast cells are involved in the clearance of infection. To the best of our knowledge this is the first report on cloning, expression of the gene and purification of r-ClpBm, determination of its secondary structure and its ability to partially prevent establishment of B. malayi infection. Thus, r-ClpBm may further be studied and developed in combination with other protective molecules of B. malayi as a component of potential filarial cocktail vaccine candidate. [ABSTRACT FROM AUTHOR]

Summary Background Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito vectors, and in Sub-Saharan Africa it is caused by the nematode Wuchereria bancrofti . The disease has been targeted for global elimination with the annual mass drug administration (MDA) strategy. Vector control is known to play an important complementary role to MDA in reducing the transmission of LF. The effects of an MDA and insecticide-treated net intervention implemented in an endemic area of southeastern Tanzania are reported here. Methods A cross-sectional study assessing W. bancrofti circulating filarial antigen (CFA) was conducted in five primary schools in five different villages. Standard one pupils aged 6–9 years were screened for CFA using immunochromatographic test cards (ICT), with a total of 413 screened in 2012 and 659 in 2015. Just after CFA testing, the children were interviewed on their participation in the MDA campaign. Moreover, 246 heads of households in 2012 and 868 in 2015 were interviewed on their participation in MDA and utilization of long-lasting insecticide-treated nets (LLINs). Results The prevalence of CFA for the 413 children tested in 2012 was 14.3%, while it was 0.0% for the 659 children tested in 2015. The Tanzanian National Lymphatic Filariasis Elimination Programme reported annual treatment coverage for Rufiji District ranging from 54.3% to 94.0% during the years 2002–2014. The surveyed treatment was 51.6% in 2011 and 57.4% in 2014. With regard to LLINs, possession and utilization increased from 63.4% and 59.2%, respectively, in 2012, to 92.5% and 75.4%, respectively, in 2015. Conclusions The findings suggest that 12 rounds of MDA complemented with vector control through the use of insecticide-treated nets resulted in a marked reduction in W. bancrofti CFA in young school children. [ABSTRACT FROM AUTHOR]

Background: Following the World Health Assembly resolution on Elimination of lymphatic filariasis (ELF) as a public health problem by the year 2020, a Global Program (GPELF) was launched in 1997 to help endemic countries to initiate national programs. The current strategy to interrupt transmission of LF, is administration of once-yearly, single-dose, two-drug regimen (Albendazole with Diethylcarbamazine (DEC) to be used in endemic areas with the goal of reaching 65% epidemiological coverage for 4–6 years. We report findings of independent assessment from year 2010 to 2015 for last six rounds, after initial five rounds of Mass Drug Administration (MDA) since 2005 for ELF in endemic area of Gujarat. Methods: Independent assessment of MDA was performed to find coverage and compliance indicators, reasons for non-coverage and non-compliance in five Implementation Units (IUs). Pre, during and post MDA evaluations were done in three phases. The impact of MDA was measured by microfilaraemia survey. A total of eight sites, four random and four fixed sentinel sites were selected to calculate microfilaria rate (MF) per IUs per year. In years 2010 to 2015, we report results from 125,936 nocturnal blood smears and 17,405 population in 120 selected clusters. Four clusters were selected per year in each of the five IUs for assessment of MDA round. Result: Post MDA survey showed drug coverage between 81%-88% and epidemiological coverage 77%-89% across years. Main reasons for non-coverage were drug administrator related (the team did not visit or missed people) while non-compliance was population related (fear of side effects, sickness, people forgot or absent). During MDA findings show that the directly observed consumption is considerably improved from 58% in 2010 to 82% in 2015. The knowledge about benefits of drug provided also increased from 59% to 90% over the years. The current MF rate is less than one in all IUs with an overall 68% percent decrease from baseline year 2005 to year 2015. The average MF rate of Gujarat is 0.44 for year 2015. Conclusions: The findings show that achieving adequate epidemiological and drug coverage is possible by actual field level operation of the program in large endemic areas. The results and feedback from independent assessment, performed regularly, could guide the policymakers and program managers for mid-term corrections and to frame strategies to enhance program. Monitoring of coverage and impact indicator together informs decisions for reaching end-point of MDA. The impact indicator- microfilaria rate in all IUs of South Gujarat Region has reached and remained less than one percent signaling end-points of MDA. Post MDA stringent monitoring in form of TAS is recommended to keep vigil on maintenance of elimination achieved. [ABSTRACT FROM AUTHOR]

Background: The burden of loiasis has received limited attention and loiasis is still considered a benign condition. To assess whether loiasis bears any excess mortality, we did a retrospective cohort study in Cameroon.Methods: In 2001, 3627 individuals living in 28 villages were examined for Loa loa infection. In 2016, these villages were revisited and the vital status was determined for 3301 individuals (91%). The data were analysed at community level to assess the relation between the level of L loa infection in 2001 and standardised mortality rates (SMRs), and at individual level to assess the excess mortality relative to the 2001 microfilaraemia and to calculate the population-attributable fraction of mortality associated with L loa microfilaraemia.Findings: 915 deaths occurred during the follow-up time (mean time of 12·5 years [IQR 10·2-14·9]) between April, 2001, and March 22, 2016. Crude mortality rate was 20·3 deaths per 1000 person-years. SMRs increased by 4·1% when the proportion of participants infected with greater than 30 000 microfilariae per mL increased by 1% (p=0·030). People aged older than 25 years with greater than 30 000 microfilariae per mL in 2001 died significantly earlier than did amicrofilaraemic people (time ratio 0·67, 95% CI 0·48-0·95, p=0·024). The population-attributable fraction of mortality associated with presence of L loa microfilaraemia was 14·5% (95% CI 6·5-21·8, p=0·001).Interpretation: High-grade L loa microfilaraemia is associated with an increased mortality risk, suggesting that loiasis is not a benign condition and merits more attention because of its effect on onchocerciasis and lymphatic control strategies. Loiasis should be considered for inclusion in the WHO's list of neglected tropical diseases.Funding: Drugs for Neglected Diseases initiative. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases represent a major human and animal health problem in all tropical and subtropical countries worldwide. In this study, we investigated the one-pot synthesis of silver nanoparticles (AgNPs) using a cheap leaf extract of Carissa carandas (Apocynaceae). Bio-reduced AgNPs were characterized by UV-visible spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction analysis, atomic force microscopy, scanning electron microscopy and transmission electron microscopy. The acute toxicity of C. carandas extract and green-synthesized AgNPs was evaluated on eggs and larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus. AgNPs showed high toxicity against A. stephensi, A. aegypti, and C. quinquefasciatus larvae with LC values of 14.33, 15.69 and 16.95 μg/mL, respectively. A single treatment with AgNPs tested at 60 μg/mL led to no egg hatchability. The egg rafts of C. quinquefasciatus were more resistant to the toxic action of AgNPs if compared to A. aegypti and A. stephensi. C. carandas-fabricated AgNPs were found safer to non-target organisms Anisops bouvieri, Diplonychus indicus and Gambusia affinis, with LC ranging from 1097.87 to 17249.89 µg/ml. Overall, this research shed light on the mosquitocidal potential of C. carandas, a potential bio-resource for rapid, cheap and effective synthesis of poly-disperse and stable silver nanocrystals. [ABSTRACT FROM AUTHOR]

Human lymphatic filariasis is a neglected tropical disease, causing permanent and long-term disability with severe immunopathology. Abundant larval transcript (ALT) plays a crucial role in parasite establishment in the host, due to its multi-faceted ability in host immune regulation. Although ALT protein is a key filarial target, its exact function is yet to be explored. Here, we report epitope mapping and a structural model of Brugia malayi ALT-2, leading to development of a multi-epitope vaccine. Structural analysis revealed that ALT represents unique parasitic defence proteins belonging to a toxin family that carries a ‘knottin’ fold. ALT-2 has been a favourite vaccine antigen and was protective in filarial models. Due to the immunological significance of ALT-2, we mapped B-cell epitopes systematically and identified two epitope clusters, 1–30 and 89–128. To explore the prophylactic potential of epitope clusters, a recombinant multi-epitopic gene comprising the epitopic domains was engineered and the protective efficacy of recombinant ALT epitope protein (AEP) was tested in the permissive model, Mastomys coucha. AEP elicited potent antibody responses with predominant IgG1 isotype and conferred significantly high protection (74.59%) compared to ALT-2 (61.95%). This proved that these epitopic domains are responsible for the protective efficacy of ALT-2 and engineering protective epitopes as a multi-epitope protein may be a novel vaccine strategy for complex parasitic infections. [ABSTRACT FROM AUTHOR]

In Cameroon, many dietary spices are used by traditional healers to cure several diseases such as cancer and microbial infections. Aframomum daniellii, Dichrostachys cinerea and Echinops giganteus are Cameroonian spices widely used as flavourings and as food additives. Moreover, they are traditionally herbal remedies employed to treat several diseases, as well as to control populations of insect pests. In this research, we analysed the chemical composition of A. daniellii, D. cinerea and E. giganteus essential oils and we evaluated their larvicidal potential against larvae of the filariasis and West Nile virus vector Culex quinquefasciatus. The essential oils were obtained from different plant parts by hydrodistillation and their composition was analysed by GC-MS. The three spices exhibited different volatile chemical profiles, being characterized by 1,8-cineole, sabinene and β-pinene ( A. daniellii), geraniol and terpinen-4-ol ( D. cinerea), and silphiperfol-6-ene and presilphiperfolan-8-ol ( E. giganteus). Results showed that the highest larvicidal toxicity on Cx. quinquefasciatus was exerted by D. cinerea essential oil (LC = 39.1 μL L), followed by A. daniellii (pericarp essential oil: LC = 65.5 μL L; leaves: LC = 65.5μL L; seeds: LC = 106.5μL L) and E. giganteus (LC = 227.4 μL L). Overall, the chance to use the D. cinerea essential oil against Cx. quinquefasciatus young instars seems promising, since it is effective at moderate doses and could be an advantageous alternative to build newer mosquito control tools. [ABSTRACT FROM AUTHOR]

Although of limited veterinary significance, Onchocerca ochengi has become famous as a natural model or ‘analogue’ of human onchocerciasis (river blindness), which is caused by Onchocerca volvulus . On the basis of both morphological and molecular criteria, O. ochengi is the closest extant relative of O. volvulus and shares several key natural history traits with the human pathogen. These include exploitation of the same group of insect vectors (blackflies of the Simulium damnosum complex) and formation of collagenous nodules with a similar histological structure to human nodules. Here, we review the contribution of this natural system to drug and vaccine discovery efforts, as well as to our basic biological understanding of Onchocerca spp., over the past quarter-century. [ABSTRACT FROM AUTHOR]

The Global Programme to Eliminate Lymphatic Filariasis has made significant progress toward interrupting transmission of lymphatic filariasis (LF) through mass drug administration (MDA). Operational challenges in defining endpoints of elimination programs include the need to determine appropriate post-MDA surveillance strategies. As humans are the only reservoirs of LF parasites, one such strategy is molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), to provide an indirect indicator of infected persons nearby. MX could potentially be used to evaluate program success, provide support for decisions to stop MDA, and conduct post-MDA surveillance. American Samoa has successfully completed MDA and passed WHO recommended Transmission Assessment Surveys in 2011 and 2015, but recent studies using spatial analysis of antigen (Ag) and antibody (Ab) prevalence in adults (aged ≥18 years) and entomological surveys showed evidence of possible ongoing transmission. This study evaluated MX as a surveillance tool in American Samoa by linking village-level results of published human and mosquito studies. Of 32 villages, seropositive persons for Og4C3 Ag were identified in 11 (34.4%), for Wb123 Ab in 18 (56.3%) and for Bm14 Ab in 27 (84.4%) of villages. Village-level seroprevalence ranged from 0–33%, 0–67% and 0–100% for Og4C3 Ag, Wb123 Ab and Bm14 Ab respectively. PCR-positive Aedes polynesiensis mosquitoes were found in 15 (47%) villages, and their presence was significantly associated with seropositive persons for Og4C3 Ag (67% vs 6%, p<0.001) and Wb123 Ab (87% vs 29%, p = 0.001), but not Bm14 Ab. In villages with persons seropositive for Og4C3 Ag and Wb123 Ab, PCR-positive Ae. polynesiensis were found in 90.9% and 72.2% respectively. In villages without seropositive persons for Og4C3 Ag or Wb123 Ab, PCR-positive Ae. polynesiensis were also absent in 94.1% and 70.6% of villages respectively. Our study provides promising evidence to support the potential usefulness of MX in post-MDA surveillance in an Aedes transmission area in the Pacific Islands setting. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF), also known as elephantiasis, is a neglected tropical disease (NTD) targeted for elimination through a Global Programme to Eliminate LF (GPELF). Between 2000 and 2014, the GPELF has delivered 5.6 billion treatments to over 763 million people. Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF. Method: We combined previously established models to estimate the number of clinical manifestations and disability-adjusted life years (DALYs) averted from three benefit cohorts (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The economic savings associated with this disease prevention was then analysed in the context of prevented medical expenses incurred by LF clinical patients, potential income loss through lost-labour, and prevented costs to the health system to care for affected individuals. The indirect cost estimates were calculated using the human capital approach. A combination of four wage sources was used to estimate the fair market value of time for an agricultural worker with LF infection (to ensure a conservative estimate, the lowest wage value was used). Results: We projected that due to the first 15 years of the GPELF 36 million clinical cases and 175 (116-250) million DALYs will potentially be averted. It was estimated that due to this notable health impact, US$100.5 billion will potentially be saved over the lifetimes of the benefit cohorts. This total amount results from summing the medical expenses incurred by LF patients (US$3 billion), potential income loss (US$94 billion), and costs to the health system (US$3.5 billion) that were projected to be prevented. The results were subjected to sensitivity analysis and were most sensitive to the assumed percentage of work hours lost for those suffering from chronic disease (changing the total economic benefit between US$69.30-150.7 billion). Conclusions: Despite the limitations of any such analysis, this study identifies substantial health and economic benefits that have resulted from the first 15 years of the GPELF, and it highlights the value and importance of continued investment in the GPELF. [ABSTRACT FROM AUTHOR]

Chagas disease, leishmaniasis, onchocerciasis and lymphatic filariasis are all vectorborne neglected tropical diseases (NTDs) that are responsible for significant disease burden in impoverished children and adults worldwide. As vectorborne parasitic diseases, they can all be targeted for elimination through vector control strategies. Examples of successful vector control programmes for these diseases over the past two decades have included the Southern Cone Initiative against Chagas disease, the Kala-azar Control Scheme against leishmaniasis, the Onchocerciasis Control Programme and the lymphatic filariasis control programme in The Gambia. A common vector control component in all of these programmes is the use of adulticides including dichlorodiphenyltrichloroethane and newer synthetic pyrethroid insecticides against the insect vectors of disease. Household spraying has been used against Chagas disease and leishmaniasis, and insecticide-treated bed nets have helped prevent leishmaniasis and lymphatic filariasis. Recent trends in vector control focus on collaborations between programmes and sectors to achieve integrated vector management that addresses the holistic vector control needs of a community rather than approaching it on a disease-by-disease basis, with the goals of increased efficacy, sustainability and cost-effectiveness. As evidence of vector resistance to currently used insecticide regimens emerges, research to develop new and improved insecticides and novel control strategies will be critical in reducing disease burden. In the quest to eliminate these vectorborne NTDs, efforts need to be made to continue existing control programmes, further implement integrated vector control strategies and stimulate research into new insecticides and control methods. [ABSTRACT FROM AUTHOR]

Background: Given the continued successes of the world’s lymphatic filariasis (LF) elimination programs and the growing successes of many malaria elimination efforts, the necessity of low cost tools and methodologies applicable to long-term disease surveillance is greater than ever before. As many countries reach the end of their LF mass drug administration programs and a growing number of countries realize unprecedented successes in their malaria intervention efforts, the need for practical molecular xenomonitoring (MX), capable of providing surveillance for disease recrudescence in settings of decreased parasite prevalence is increasingly clear. Current protocols, however, require testing of mosquitoes in pools of 25 or fewer, making high-throughput examination a challenge. The new method we present here screens the excreta/feces from hundreds of mosquitoes per pool and provides proof-of-concept for a practical alternative to traditional methodologies resulting in significant cost and labor savings. Methodology/Principal Findings: Excreta/feces of laboratory reared Aedes aegypti or Anopheles stephensi mosquitoes provided with a Brugia malayi microfilaria-positive or Plasmodium vivax-positive blood meal respectively were tested for the presence of parasite DNA using real-time PCR. A titration of samples containing various volumes of B. malayi-negative mosquito feces mixed with positive excreta/feces was also tested to determine sensitivity of detection. Real-time PCR amplification of B. malayi and P. vivax DNA from the excreta/feces of infected mosquitoes was demonstrated, and B. malayi DNA in excreta/feces from one to two mf-positive blood meal-receiving mosquitoes was detected when pooled with volumes of feces from as many as 500 uninfected mosquitoes. Conclusions/Significance: While the operationalizing of excreta/feces testing may require the development of new strategies for sample collection, the high-throughput nature of this new methodology has the potential to greatly reduce MX costs. This will prove particularly useful in post-transmission-interruption settings, where this inexpensive approach to long-term surveillance will help to stretch the budgets of LF and malaria elimination programs. Furthermore, as this methodology is adaptable to the detection of both single celled (P. vivax) and multicellular eukaryotic pathogens (B. malayi), exploration of its use for the detection of various other mosquito-borne diseases including viruses should be considered. Additionally, integration strategies utilizing excreta/feces testing for the simultaneous surveillance of multiple diseases should be explored. [ABSTRACT FROM AUTHOR]

Background: Zambia is endemic for four of the global Preventive Chemotherapy Neglected Tropical Diseases (PC-NTD) targeted for elimination and control, namely schistosomiasis, trachoma, lymphatic filariasis (LF) and soil transmitted helminths (STH). These diseases are associated with disfigurement, reduced productivity, reduced cognitive potential and hence affect the economic development of the households, communities and the country. They largely affect communities with socioeconomic challenges, limited access to safe and clean water and lacking sanitary facilities. These diseases are preventable with chemotherapy being amenable to integrated community and school based mass drug administration coupled with PHASE strategies. This study explores lessons learnt from the implementation of mass drug administration for Schistosomiasis and Soiltransmitted helminths in Lusaka, Zambia. Methodology: Lusaka province was targeted by Ministry of Community development, Mother and Child Health as the area for implementation of mass drug administration for Schistosomiasis and Soil-transmitted helminths using identified 666 health service delivery posts as drug distribution points in selected districts. A total of 2,208,617 people were targeted to be dispensed with Praziquantel, while 773,016 were targeted to be dispensed with Mebendazole in Lusaka only. These medicines were given to all children and adults considered to be at high risk of Schistosomiasis and Soil Transmitted Helminths respectively. Specific targets to be met were set. Results: Luangwa, Chongwe and Shibuyunji districts surpassed their targets beyond 100%. Chirundu, Kafue and Rufunsa districts surpassed the 75% target. Lusaka district managed a coverage of 24% and this brought the overall provincial coverage to 41%. This was below the set target of 75%. Conclusion: The exercise revealed that implementation of MDA with high coverage is feasible. This needs to be improved in areas not meeting the set targets. [ABSTRACT FROM AUTHOR]

Background: Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT). Methodology/Principal Findings: Eleven bibliographic databases were searched using different names of all NTDs and various keywords relating to productivity. Additional references were identified through reference lists from relevant papers. Of the 5316 unique publications found in the database searches, thirteen papers were identified for lymphatic filariasis, ten for onchocerciasis, eleven for schistosomiasis, six for soil-transmitted helminths and three for trachoma. Besides the scarcity in publications reporting the degree of productivity loss, this review revealed large variation in the estimated productivity loss related to these NTDs. Conclusions: It is clear that productivity is affected by NTDs, although the actual impact depends on the type and severity of the NTD as well as on the context where the disease occurs. The largest impact on productivity loss of individuals affected by one of these diseases seems to be due to blindness from onchocerciasis and severe schistosomiasis manifestations; productivity loss due to trachoma-related blindness has never been studied directly. However, productivity loss at an individual level might differ from productivity loss at a population level because of differences in the prevalence of NTDs. Variation in estimated productivity loss between and within diseases is caused by differences in research methods and setting. Publications should provide enough information to enable readers to assess the quality and relevance of the study for their purposes. [ABSTRACT FROM AUTHOR]

Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as ‘neglected diseases of poverty’. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general public health care is often deeply troubled and fails to meet the basic health needs of impoverished populations. This presents particular challenges for the implementation of mass drug administration (MDA), which currently is the principal means of control and eventual elimination. Several MDA programmes face the dilemma that they are unable to attain and maintain the required drug coverage across target groups. In recognition of this, a qualitative study was conducted in the Morogoro and Lindi regions of Tanzania to gain an understanding of community experiences with, and perceptions of, the MDA campaign implemented in 2011 by the National Lymphatic Filariasis Elimination Programme. The study revealed a wide variation of perceptions and experiences regarding the aim, rationale and justification of MDA. There were positive sentiments about the usefulness of the drugs, but many study participants were sceptical about the manner in which MDA is implemented. People were particularly disappointed with the limited attempts by implementers to share information and mobilize residents. In addition, negative sentiments towards MDA for lymphatic filariasis reflected a general feeling of desertion and marginalization by the health care system and political authorities. However, the results suggest that if the communities are brought on board with genuine respect for their integrity and informed self-determination, there is scope for major improvements in community support for MDA-based control activities. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background: The Global Programme to Eliminate Lymphatic Filariasis recommends the transmission assessment survey (TAS) as the preferred methodology for determining whether mass drug administration can be stopped in an endemic area. Because of the limited experience available globally with the use of Brugia Rapid™ tests in conducting TAS in Brugia spp. areas, we explored the relationship between the antibody test results and Brugia spp. infection as detected by microfilaremia in different epidemiological settings. Methods: The study analyzes the Brugia Rapid™ antibody responses and microfilaremia in all ages at three study sites in: i) a district which was classified as non-endemic, ii) a district which passed TAS, and iii) a district which failed TAS. Convenience sampling was done in each site, in one to three purposefully selected villages with a goal of 500 samples in each district. Results: A total of 1543 samples were collected from residents in all three study sites. In the site which was classified as non-endemic and where MDA had not been conducted, 5 % of study participants were antibody positive, none was positive for microfilaremia, and age-specific antibody prevalence peaked at almost 8 % in the 25-34 year-old age range, with no antibody-positive results found in children under eight years of age. In the site that had passed TAS, 1 % of participants were antibody positive and none was positive for microfilaremia. In the site which failed TAS, 15 % of participants were antibody positive, 0.2 % were microfilaremic, and age-specific antibody prevalence was highest in 6-7 year olds (30 %), but above 8 % in all age levels above 8 years old. Conclusions: These results from districts which followed the current WHO guidance for mapping, MDA, and implementing TAS, while providing antibody profiles of treated and untreated populations under programmatic settings, support the choice of antibody prevalence in the 6- and 7-year-old age group in TAS for making stopping MDA decisions. Since only one study participant was microfilaremic, no conclusions could be drawn about the relationship between antibodies and microfilaremia and further longitudinal studies are required to understand this relationship. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors offer information on filariases, a systemic diseases caused by parasitic nematodes and mentions ways to control its spread. Topics discussed include different types of diseases such as onchocerciasis due to Onchocerca volvulus, and lymphatic filariasis caused primarily by Wuchereria bancrofti; need of mass drug administration (MDA) programs, and elimination of onchocerciasis from Africa.

Background: The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. Methodology/Principal Finding: We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6–7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. Conclusions: We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF. [ABSTRACT FROM AUTHOR]

Backround: Mass d-rug administration (MDA), for control of filariasis was launched by government of India in 1996. Under this programme, all the beneficiaries in the age group of 2 to 60 years (excluding pregnant mothers, people above 60 and having other illness), will be administered. Filariasis being endemic in the District Methodology: The MDA was carried out in the district in the month of May 2014. This study was conducted To assess the coverage and compliance of MDA in Bagalkot district in the year 2014. After visiting the selected cluster (3 rural and 1 urban) the information was collected from the 30 houses in each cluster randomly. Results: Out of 720 population surveyed 353 (49.02%) were males and 367 (50.98%) were female, 3.1% of geriatric population were given the drugs. 406 (56.4%) had taken full course, 58 (8.1%) had partially taken the drugs while 256 (35.5%) had either not received the drugs or had not taken the tablet. Though the coverage was high, the compliance was only 56.4%, which is much below the target of 85%. Main reason for noncompliance was lack of adequate information. Conclusion :Effective drug delivery strategies such as proper area demarcation, repeat house visits have to be done to improve coverage. Training of drug distributors to improve interpersonal communication & effective IEC activities are to be emphasized to improve compliance & achieve elimination of filariasis. [ABSTRACT FROM AUTHOR]

Mathematical modelling provides a useful tool for policy making and planning in lymphatic filariasis control programmes, by providing trend forecasts based on sound scientific knowledge and principles. This is now especially true, in view of the ambitious target to eliminate lymphatic filariasis as a public health problem globally by the year 2020 and the short remaining timeline to achieve this. To meet this target, elimination programmes need to be accelerated, requiring further optimization of strategies and tailoring to local circumstances. Insights from epidemiological transmission models provide a useful basis. Two general models of lymphatic filariasis transmission and control are nowadays in use to support decision-making, namely a population-based deterministic model (EPIFIL) and an individual-based stochastic model (LYMFASIM). Model predictions confirm that lymphatic filariasis transmission can be interrupted by annual mass drug administration (MDA), but this may need to be continued much longer than the initially suggested 4-6 years in areas with high transmission intensity or poor treatment coverage. However, the models have not been validated against longitudinal data describing the impact of MDA programmes. Some critical issues remain to be incorporated in one or both of the models to make predictions on elimination more realistic, including the possible occurrence of systematic noncompliance, the risk of emerging parasite resistance to anthelmintic drugs, and spatial heterogeneities. Rapid advances are needed to maximize the utility of models in decision-making for the ongoing ambitious lymphatic filariasis elimination programmes. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases with an economic impact create loss in commercial and labor outputs, particularly in countries with tropical and subtropical climates. Mosquito control is facing a threat because of the emergence of resistance to synthetic insecticides. Extracts from plants may be alternative sources of mosquito control agents because they constitute a rich source of bioactive compounds that are biodegradable into nontoxic products and potentially suitable for use to control mosquitoes. Insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. In view of the recently increased interest in developing plant origin insecticides as an alternative to chemical insecticide, in the present study, the adulticidal activity of silver nanoparticles (AgNPs) synthesized using Feronia elephantum plant leaf extract against adults of Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus was determined. The range of concentrations of synthesized AgNPs (8, 16, 24, 32, and 40 μg mL) and aqueous leaf extract (40, 80, 120, 160, and 200 μg mL) were tested against the adults of A. stephensi, A. aegypti, and C. quinquefasciatus. Adults were exposed to varying concentrations of aqueous crude extract and synthesized AgNPs for 24 h. Considerable mortality was evident after the treatment of F. elephantum for all three important vector mosquitoes. The synthesized AgNPs from F. elephantum were highly toxic than crude leaf aqueous extract to three important vector mosquito species. The results were recorded from UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy analysis (EDX), and transmission electron microscopy (TEM). Synthesized AgNPs against the vector mosquitoes A. stephensi, A. aegypti, and C. quinquefasciatus had the following lethal dose (LD) and LD values: A. stephensi had LD and LD values of 18.041 and 32.575 μg mL; A. aegypti had LD and LD values of 20.399 and 37.534 μg mL; and C. quinquefasciatus had LD and LD values of 21.798 and 39.596 μg mL. No mortality was observed in the control. These results suggest that the leaf aqueous extracts of F. elephantum and green synthesis of AgNPs have the potential to be used as an ideal eco-friendly approach for the control of the A. stephensi, A. aegypti, and C. quinquefasciatus. This is the first report on the adulticidal activity of the plant extracts and AgNPs. [ABSTRACT FROM AUTHOR]

Highlights: [•] We conducted a systematic review on the costs of LF and onchocerciasis. [•] A total of 24 papers were identified for onchocerciasis and 52 papers for LF. [•] Research gaps exist on the cost of integrating NTD prevention and control programs. [•] The cost literature is generally older and extremely focal geographically. [•] Cost data is of limited usefulness for estimating global economic burden of these diseases. [ABSTRACT FROM AUTHOR]

Background: Vector monitoring in military stations would help in protecting the armed forces from vector borne diseases such as malaria, Japanese encephalitis and filariasis. Methods: Adult mosquitoes were collected from four villages around a military station in India using light traps and the species composition was estimated. Insecticide susceptibility of disease vectors against DDT, deltamethrin and permethrin was established using WHO kits. Results: The known malaria vectors constituted 4.9% of the total mosquito collections and Anopheles philippinensis/nivipes (2.05%) was the most abundant. Japanese encephalitis and dengue vectors constituted 25.3 and 0.05% whereas the known vectors of both Japanese encephalitis and filariasis formed 50.9%. The mean (±SEmean) of annual parasitic index, slide positivity and Plasmodium falciparum percentage among the civilian population during the study period were 1.46 ± 0.37, 1.65 ± 0.77 and 50.2 ± 10.7. The filariasis vector Culex quinquefasciatus was resistant to DDT with 65.4% mortality whereas the DDT resistance in the Japanese encephalitis vector Culex vishnui gr. with 91.9% mortality needs to be confirmed. All other species tested were susceptible to DDT, deltamethrin and permethrin. Conclusion: Targeted interventions are needed to reduce the disease burden and vector activity in the villages adjoining the military station. The use of insect repellents, bed nets and repellent impregnated uniforms by the troops should be ensured for protection from vector borne diseases. [ABSTRACT FROM AUTHOR]

The relationship between mosquito vectors and lymphatic filariasis (LF) parasites can result in a range of transmission outcomes. Anophelines are generally characterized as poor vectors due to an inability to support development at low densities. However, it is important to understand the potential for transmission in natural vectors to maximize the success of elimination efforts. Primary vectors in Papua New Guinea (n = 1209) were dissected following exposure to microfilaremic blood (range 8–233 mf/20 µl). We examined density dependent and species-specific parasite prevalence, intensity and yield, barriers to parasite development as well as impacts on mosquito survival. We observed strikingly different parasite prevalence and yield among closely related species. Prevalence of infective stage larvae (L3s) ranged from 4.2% to 23.7% in An. punctulatus, 24.5% to 68.6% in An. farauti s.s. and 61.9% to 100% in An. hinesorum at low and high density exposures, respectively. Injection experiments revealed the greatest barrier to parasite development involved passage from the midgut into the hemocoel. The ratio of L3 to ingested mf at low densities was higher in An. hinesorum (yield = 1.0) and An. farauti s.s. (yield = 0.5) than has been reported in other anopheline vectors. There was a negative relationship between mosquito survival and bloodmeal mf density. In An. farauti s.s., increased parasite yield and survival at low densities suggest greater competence at low microfilaremias. In Papua New Guinea the likelihood of transmission will be strongly influenced by vector composition and changes in the mf reservoir as a result of elimination efforts. Global elimination efforts will be strengthened by the knowledge of transmission potential in the context of current control measures. [ABSTRACT FROM AUTHOR]

Background: Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania. Methods: The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Results: Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Conclusions: Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination. [ABSTRACT FROM AUTHOR]

This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side – adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal. [ABSTRACT FROM AUTHOR]

Highlights: [•] Silver nanoparticles synthesized by plant extracts from aqueous silver nitrate solution. [•] Synthesized silver nanoparticles in the range of 8–80nm. [•] Silver nanoparticles exhibit significant larvicidal activity. [Copyright &y& Elsevier]

Abstract: Lymphatic filariasis affects approximately 3% of the whole world population. Mass drug administration is currently the major control strategy to eradicate this infection from endemic regions by year 2020. Combination drug treatments are highly efficient in controlling the infection. However, there are no effective vaccines available for human or animal lymphatic filariasis despite the identification of several subunit vaccines. Lymphatic filariasis parasites are multicellular organisms and potentially use multiple mechanisms to survive in the host. Therefore, there is a need to combine two or more vaccine candidate antigens to achieve the desired effect. In this study we combined three well characterized vaccine antigens of Brugia malayi, heat shock protein 12.6 (HSP12.6), Abundant Larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL) as a multivalent fusion vaccine. Putative immune individuals carry circulating antibodies against all three antigens. Depletion of these antigen specific antibodies from the sera samples removed the ability of the sera to participate in the killing of B. malayi L3 in an antibody dependent cellular cytotoxicity (ADCC) mechanism. Vaccination trials in mice with a bivalent [HSP12.6+ALT-2 (HA), HSP12.6+TSP-LEL (HT) or TSP-LEL+ALT-2 (TA)] or trivalent [HSP12.6+ALT-2+TSP-LEL (HAT)] vaccines using DNA, protein or heterologous prime boost regimen showed that trivalent HAT vaccine either as protein alone or as heterologous prime boost vaccine could confer significant protection (95%) against B. malayi L3 challenge. Immune correlates of protection suggest a Th1/Th2 bias. These finding suggests that the trivalent HAT fusion protein is a promising prophylactic vaccine against lymphatic filariasis infection in human. [Copyright &y& Elsevier]

Antifilarial antibody testing has been established as a sensitive and specific method of diagnosing lymphatic filariasis. However, the development of serological responses to specific filarial antigens and their relationship to acquisition of infection is poorly understood. In order to evaluate whether the development of antigen specific antifilarial antibodies precedes microfilaremia and antigenemia, we compared the antibody responses of serum samples collected between 1990 and 1999 from a cohort of 142 Haitian children followed longitudinally. Antigen status was determined using the Og4C3 ELISA and the presence of microfilaremia was detected using microscopy. Antibody responses to Wb123, a Wuchereria bancrofti L3 antigen, were measured using a Luciferase Immunoprecipitation System (LIPS) assay. Antibody responses to Bm14 and Bm33, Brugia malayi antigens and to a major surface protein (WSP) from Wolbachia were analyzed using a multiplex bead assay. Over follow-up, 80 (56%) of the children became antigen-positive and 30 (21%) developed microfilaremia. Detectable antibody responses to Bm14, Bm33, Wb123, and WSP developed in 95%, 100%, 92%, and 29% of children, respectively. With the exception of WSP, the development of antibody responses generally preceded detection of filarial antigen. Our results show that antifilarial antibody responses can serve as an important epidemiological indicator in a sentinel population of young children and thus, may be valuable as tool for surveillance in the context of lymphatic filariasis elimination programs. [ABSTRACT FROM AUTHOR]

Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process-the first initiated by the parasite and host innate immune system and the second propagated mainly by the host's adaptive immune system and by other factors (including secondary infections). [ABSTRACT FROM AUTHOR]