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To evaluate the success of mass drug administration for lymphatic filariasis, WHO has recommended two rapid tests, Brugia Rapid (BR) to detect the presence of IgG4 antibodies against Brugia sp and Filariasis Test Strip (FTS) to detect antigens of Wuchereria bancrofti. As a country co-endemic for Brugia sp. and W. bancrofti, Indonesia needs a single diagnostic tool that can detect the exposure to both species. This study aimed to evaluate the efficacy of mass drug administration by measuring Bm14-specific IgG4 levels in blood samples of the population living in a co-endemic area of B. timori and W. bancrofti in Southwest Sumba Regency. A total of 132 plasma samples obtained before and one year after DEC-albendazole administration, which have been previously tested with BR and FTS, were examined for IgG4 against Bm14 using enzyme-linked immunosorbent assay. The results showed that before treatment all 32 individuals (100%) with BR+/ FTS+ were also positive for Bm14-specific IgG4, while in BR+ or FTS+ group there were90% samples detected positive. At one year after treatment, positive results for Bm14-specific IgG4 were still detected in 96.9% samples with BR+/ FTS+, 78.8% samples with BR+/ FTS- and 82.9% samples with BR-/ FTS+. On the other hand, the BR-/ FTS- group also had high rate of Bm14-specific IgG4 positivity either before treatment (62,5%) and at one year after treatment (43.8%). The lowest decrease of Bm14-specific IgG4 positivity at one year after treatment was shown in the double positive group (3.1%), while the highest was in the double negative group (18.7%). The measurement of IgG4 against Bm14 has the potential as a sensitive diagnostic tool to evaluate the success of MDA in the areas co-endemic for B. timori and W. bancrofti.

We assessed the impact of three annual vs five semiannual rounds of mass drug administration (MDA) with ivermectin plus albendazole followed by praziquantel for the control or elimination of lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminth (STH) infections and schistosomiasis in Lofa County, Liberia. The study started in 2012 and was interrupted in 2014 during the Ebola virus outbreak. Repeated cross-sectional surveys were conducted in individuals 5 years and older to measure infection markers. Wuchereria bancrofti antigenemia prevalences decreased from 12.5 to 1.2% (90% reduction) and from 13.6 to 4.2% (69% reduction) one year after three rounds of annual or five rounds of semiannual MDA, respectively. Mixed effects logistic regression models showed decreases in odds of antigenemia positivity were 91 and 74% at that time in the annual and semiannual treatment zones, respectively (p 0.001). Semiannual MDA was slightly more effective for reducing Onchocerca volvulus microfiladermia prevalence and at follow-up 3 were 74% (from 14.4 to 3.7%) and 83% (from 23.6 to 4.5%) in the annual and semiannual treatment zones, respectively. Both treatment schedules had similar beneficial effects on hookworm prevalence. Thus, annual and semiannual MDA with ivermectin and albendazole had similar beneficial impacts on LF, onchocerciasis, and STH in this setting. In contrast, MDA with praziquantel had little impact on hyperendemic Schistosoma mansoni in the study area. Results from a long-term follow-up survey showed that improvements in infection parameters were sustained by routine annual MDA provided by the Liberian Ministry of Health after our study endpoint.

In Southeast Asia, Anopheles lesteri (recently synonymized with An. paraliae) is a competent vector for Plasmodium parasites, but its ability to transmit parasites that cause lymphatic filariasis has yet to be determined. In this study, the susceptibility of An. lesteri and An. paraliae to Brugia malayi parasites was determined by comparing with the control mosquito, Aedes togoi. We found that the infection prevalence per infected mosquito in An. paraliae was significantly lower than that in Ae. togoi in all experiments (p 0.05). Reciprocal crosses (female An. paraliae x male An. lesteri) produced highly susceptible F

Human filariae are vector-borne parasites and the causative agents of various diseases, including human onchocerciasis and lymphatic filariasis. Onchocerciasis causes a spectrum of cutaneous and ophthalmologic manifestations (including blindness) and has long been a major public health problem in Bioko Island (Equatorial Guinea). Bioko Island has been included in the WHO's Onchocerciasis Control Program since 1987. In Bioko Island, the specificity and sensitivity of clinical Onchocerca volvulus diagnosis is key. The objective of this work was to update onchocerciasis elimination progress in Bioko Island, after 18 years of mass ivermectin intervention, and the general filariasis situation through a rapid and accurate molecular method. A cross-sectional study was conducted in Bioko Island from mid-January to mid-February 2014. A total of 543 subjects were included in the study. Whole blood and one skin snip (from lumbar regions) were analysed with a real time PCR assay. Two other skin biopsies were analysed by an expert microscopist. All positive samples were confirmed by sequencing. Traditional microscopic examination of the skin biopsies failed to detect any microfilariae. However, 11 (2.03%) infections were detected using PCR assay, including one O. volvulus, two Mansonella streptocerca, seven Mansonella perstans and one Loa loa infections. PCR assays in blood detected 52 filariae-positive individuals (9.6%) which harboured M. perstans or L. loa. The low prevalence of O. volvulus confirms the success of the Onchocerciasis Control Programme and suggests that Mass Drug Administration in Bioko Island can be interrupted in the near future. The very high prevalence of M. perstans found in skin snips assays raises doubts about the reliability of microscope-based diagnosis of O. volvulus infections.

Coinfection is less commonly observed in individuals around the world, yet it is more common than the single infection. Around 800 million people worldwide are infected with helminths as a result of various diseases. Lymphatic filariasis (LF) and visceral leishmaniasis (VL) are chronic, deadly, crippling, and debilitating neglected tropical diseases (NTDs) that are endemic in tropical and subtropical regions of the world. Due to poor hygienic conditions, poverty, and genetic predisposition, those living in endemic areas are more likely to develop both leishmaniasis and filariasis. One of the key challenges in the management of LF/VL coinfection is the development of an effective therapeutic strategy that not only treats the first episode of VL but also prevents LF. However, there is a scarcity of knowledge and data on the relationship between LF and VL coinfection. While reviewing it was apparent that only a few studies relevant to LF/VL coinfections have been reported from southeastern Spain, Sudan, and the Indian subcontinents, highlighting the need for greater research in the most affected areas. We also looked at LF and VL as a single disease and also as a coinfection. Some features of the immune response evolved in mammalian hosts against LF and VL alone or against coinfection are also discussed, including epidemiology, therapeutic regimens, and vaccines. In addition to being potentially useful in clinical research, our findings imply the need for improved diagnostic methodology and therapeutics, which could accelerate the deployment of more specific and effective diagnosis for treatments to lessen the impact of VL/LF coinfections in the population.

Lymphatic filariasis (LF) has been targeted by the World Health Organization for elimination by the year 2020. However, migration of infected individuals from areas where LF is endemic to areas considered non-endemic or foci for the control and elimination may jeopardize the achievement of this goal. The aim of the present study was to evaluate the occurrence of filarial infection by way of circulating filarial antigen (CFA) circulation using the point of care AD12-immunochromatography card (POC-ICT) among immigrants from Haiti residing in Chapecó, Santa Catarina, between May and October 2015. Of the 420 subjects examined, 77.4% were male, aged 19-54 years. Ten (2.38%) were POC-ICT positive. Of this total, one was not found. Two individuals were negative for Og4C3-ELISA and DNA/Wb-PCR in all biological samples, but positive for the anti-filarial antibody Bm14 and only one showed microfilaremia (1mf/mL). These findings point to the importance of the Brazilian surveillance action to reduce the possibility of reintroduction of LF in Chapecó, Santa Catarina, by infected immigrants, and to guarantee the success of the National LF Elimination Plan.

The Global Programme to Eliminate Lymphatic Filariasis has two main components: interrupting transmission of lymphatic filariasis (LF) and managing morbidity and preventing disability. However, interventions to prevent and manage LF-related disabilities in endemic communities have been of limited extent. The aim of this study was to describe the prevalence of morbidity and its correlation with filarial infection, thereby filling a gap that existed regarding the data on morbidity in Brazil. Presence of Wuchereria bancrofti microfilaria was investigated using the thick smear technique. Information on parasitosis-related clinical manifestations was obtained using a questionnaire applied by community health agents with previous training and capacitation to know about and identify the disease. To analyze correlations, Pearson's correlation coefficient was used with the corresponding statistical significance test. 23,673 individuals were investigated: 323 presented microfilaremia (1.36%) and 741 (3.13%) had clinical complaints that were attributable to LF. Acute dermatolymphangioadenitis (ADLA) was the most prevalent condition (2.2%). Lymphedema, ADLA and chyluria were more commonly reported among female patients. There were positive associations between all the clinical complaints reported and filarial infection. Hydrocele presented the most strongly positive association (r=0.699; p

Lymphatic filariasis (LF) has been known in Egypt since ancient times. By 1930s it was recognized to be a major public health problem in the Nile Delta, and to be caused by Wuchereria bancrofti and transmitted by Culex pipiens. Remarkably, as a result of widespread DEC treatment and intensive vector control by the Ministry of Health and Population (MoHP), the infection rate of LF declined in the 1960s. However, relaxation of these efforts resulted in resurgence of filariasis in the 1980s and 1990s. In 2000, Egypt was among the first countries to join the WHO global efforts to eliminate LF as a public health problem by initiating a national LF elimination programme (NLFEP). This article reviews the history of LF control activities and summarizes the NLFEP extensive interventions to eliminate LF in Egypt. Based on MoHP data, mass drug administration (MDA) with DEC and ALB was started in 2000 in 161 implementation units (IUs). Additional IUs were included in subsequent MDA rounds, with the last IU included in 2007. MDA stopping surveys were conducted based on WHO guidelines (2005; 2011). Information about the presence of those suffering from lymphoedema/elephantiasis and hydrocele patients was collected, and care provided to those needing care in five rural health units (RHU) by primary health care system providers who were given training on LF morbidity management and disability prevention (MMDP). The NLFEP made excellent progress due to strong collaboration between different ministries, through intensive training and supervision, and the use of advocacy for mobilization of endemic communities. The epidemiological coverage for all MDA rounds was effectively ≥80%. Antigenemia levels found in schoolchildren during transmission assessment surveys (TAS) in 166 IUs approximately 10 years after stopping MDA was 0%. In 2017, TAS conducted in additional 29 IUs indicated 0.1% antigenemia and 0% microfilaremia. In 2015, the registration of chronic LF patients was updated to 1472 lymphoedema and 18 hydrocele patients. Lymphoedema patients were trained on self-management, and hydrocele patients were referred to local General Hospitals for surgery. Thus, after over a decade of sustained effort, Egypt met the WHO criteria for successful elimination of LF as a public health problem. In December 2017, WHO validated Egypt as the first country in the Eastern Mediterranean Region to successfully achieve elimination.

In 2000, Yemen joined the WHO global efforts to eliminate lymphatic filariasis (LF) as a public health problem by initiating a National LF Elimination Programme (NLFEP), that was fully integrated with the National Leprosy Elimination Programme (NLEP), the Ministry of Public Health and Population. This article reviews the NLFEP extensive efforts and interventions to eliminate LF in Yemen. LF mapping was started in 2000, followed by five annual rounds of mass drug administration (MDA) with ivermectin and albendazole in 8 implementation units (IUs) during 2002-2006. The epidemiological coverage for all MDA rounds was ≥80%. Based on WHO guidelines of 2005, MDA was stopped in 7 IUs, additional MDA rounds were continued in one IU until 2011. Microfilaremia monitoring and evaluation, and MDA stopping surveys were conducted based on WHO guidelines of 2005 and 2011. Information about the presence of patients suffering from lymphoedema/elephantiasis and hydrocele was collected, and basic care provided to all chronic cases by NLEP coordinators, trained on LF morbidity management and disability prevention (MMDP). As of 2017, a total of 610 lymphoedema patients were trained on self-management, and 31 hydrocele patients were referred to local General Hospitals for surgery. The NLFEP made excellent progress due to integration with NLEP, strong collaboration with national and international bodies, intensive training and supervision, and the use of robust advocacy for mobilization of endemic communities. Transmission assessment surveys (TAS), conducted in 2013 and 2016, indicated 0% antigenemia levels in schoolchildren in the 8 IUs. Thus, after almost two decades of sustained effort, Yemen met the WHO criteria for successful elimination of LF as a public health problem. In 2019, WHO validated Yemen as the second country in the WHO' Eastern Mediterranean Region to successfully eliminate LF as a public health problem.

In the Philippines, ten NTDs are prevalent, but only six namely LF, schistosomiasis, STH, food-borne trematodiases, rabies and leprosy are considered to be of public health importance. The 81 provinces in the country are endemic for at least one of these NTDs. Others may be endemic for two or even more of these diseases. Since 2000, after the Philippines accepted and implemented the WHO guidelines for NTDs prevention, control and elimination, significant progress has been achieved in reducing the magnitude of NTDs endemic in the country. Since 2009, out of 46 filariasis-endemic provinces, the number of provinces that has eliminated LF has progressively increased so that by 2015, 76% are already LF-free. By 2019, only four provinces remain endemic for LF. For schistosomiasis, as of 2012, report from the Department of Health (DOH) put the number of high endemic provinces at 10, moderately endemic at 6 and low to elimination levels at 12. For STH, results of the National Parasite Survey in the Philippines among school-aged children conducted in 2015 by the Research Institute for Tropical Medicine, the research arm of the Philippine DOH, however, showed that the overall cumulative prevalence was 28.4% with a prevalence range between 7.1% and 67.4%. The figures are way above the

The control and eventual elimination of neglected tropical disease (NTD) requires the expansion of interventions such as mass drug administration (MDA), vector control, diagnostic testing, and effective treatment. The purpose of this paper is to present the evidence base for decision-makers on the cost and cost-effectiveness of lymphatic filariasis (LF) and onchocerciasis prevention, treatment, and control. A systematic review of the published literature was conducted. All studies that contained primary or secondary data on costs or cost-effectiveness of prevention and control were considered. A total of 52 papers were included for LF and 24 papers were included for onchocerciasis. Large research gaps exist on the synergies and cost of integrating NTD prevention and control programs, as well as research on the role of health information systems, human resource systems, service delivery, and essential medicines and technology for elimination. The literature available on costs and cost-effectiveness of interventions is also generally older, extremely focal geographically and of limited usefulness for developing estimates of the global economic burden of these diseases and prioritizing among various intervention options. Up to date information on the costs and cost-effectiveness of interventions for LF and onchocerciasis prevention are needed given the vastly expanded funding base for the control and elimination of these diseases.

We present a case of congenital lymphedema in a 7-year-old boy in Sierra Leone with active filarial infection and penile edema. The genital edema with onset at 6 months of age may have been due to a congenital abnormality in lymphatic drainage. Other possible causes of childhood lymphedema, including Milroy's disease, are discussed.

Mass Drug Administration is being carried out in Andaman and Nicobar Islands, India since 2004. Cross sectional microfilaria ( Mf ) survey was conducted in Nancowry group of islands, the lone foci of diurnally sub periodic form of bancroftian filariasis in Nicobar district, to examine its eligibility for Transmission Assessment Survey (TAS). A total of 2561 individuals (coverage: 23.9%) were screened from five islands. The overall Mf prevalence was 3.28%. Except one island, all other islands recorded Mf prevalence >1%, ranging from 2.5% to 5.3%, indicating persistence of infection despite six annual rounds of MDA. Mf prevalence was age dependent and was higher among males, but not significantly different between genders. Age and gender specific analysis showed a significant reduction in all the age classes among females vis a vis pre-MDA prevalence while the reduction was significant only in 21–30 and 41–50 age classes in males. Exposure to day biting and forest dwelling Downsiomyia nivea can be attributed for the persistent infection besides non-compliance for MDA. Based on fits of modified negative binomial distribution, true prevalence of Mf carriers in the community was estimated to be 4.74%, which is markedly higher (about 24%) than the observed prevalence of 3.28%. Follow up of cohorts showed evidence of continued persistence of infection and acquisition of new infections post six rounds of MDA. As the Mf prevalence was above >1% in four of the five islands, this area is not eligible for TAS, warranting continuation of MDA. Mass DEC fortified salt is suggested as an adjunct to hasten elimination of infection.

Urban lymphatic filariasis (LF) has been listed among the challenges to the ongoing global efforts to eliminate LF. This is partly because the control strategies developed for rural areas - where most LF occurs - do not easily comply with human organization and behaviour in urban areas, and partly because the urban vectors thrive and proliferate in poorly planned urban settlements. This study investigated LF infection, disease and transmission in the medium-sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds of mass drug administration (MDA). Three representative sites with varying distance from the city centre were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigens (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Although there was evidence of considerable reduction in infection and transmission, there was still LF in the city, with mf and CFA prevalences well above the cut-off levels for stopping MDA. In this respect, the LF situation resembled that seen in nearby rural areas outside the city. The study emphasizes the importance of motivating the urban individuals to engage and comply with the full range of LF intervention measures (MDAs, use of mosquito proofing measures including bed nets, environmental sanitation to prevent vector breeding) in order to reach successful LF control in the city. The high LF disease burden noted, despite the reduction in infection and transmission, moreover emphasizes the importance of allocating resources for morbidity management, to ensure true elimination of LF as a public health problem.

This study assessed impact of community based self care integrative treatment provided through mass camps in villages of three districts of Kerala, India endemic for lymphatic filariasis (LF). Two most endemic Primary Health centres (PHCs) were selected from each of the three districts, where maximum concentration of LF patients is recorded. Fourteen one day LF camps, each attended by 30-40 patients were conducted. Trained Accredited Social Health Activists encouraged LF patients to attend camps. Skin wash and drying, care of bacterial entry points using dermatology drugs, and simple yoga and breathing exercises were demonstrated in these camps. Patients were advised to continue these self care activities daily at home for six months. The quality of life (QoL) of LF patients was determined for Indian life style domains using validated and pretested specific questionnaire (LF-specific QoL questionnaire-LFSQQ). It addressed conditions and state of individuals with reference to LF. The questionnaire had 7 domains and each domain consisted of a series of questions with likert scale (no problem, mild, moderate, severe, most severe). 446 patients attended one day camps to get training on integrative self care treatment. 425 patients (95.3%) were followed up after six months and QoL was reassessed. Each patient's QoL in mobility, self care, usual activity, pain and discomfort and social relationship significantly improved (P value

In a placebo controlled field trial, the effects of doxycycline (200mg/day) for 23 days followed by doxycycline (200mg/day) in combination with albendazole (ABZ) (400mg/day) for 7 days on depletion of Wolbachia endobacteria from Wuchereria bancrofti and microfilaricidal activity were studied in 68 patients (34 males and 34 females) from West Bengal, India. The drugs in combination (i.e., doxycycline+ABZ) provided the best efficacy by totally eliminating the circulating microfilaria (mf) (in 42% cases) on day 365 with (99.8%, P

Onchocerciasis control by vector control was instigated in southwest Burkina Faso in January 1969 by ORSTOM/OCCGE, and continued until operations were taken over by the WHO Onchocerciasis Control Programme (OCP) in February 1975, which itself ceased operations in the area in 1989 when onchocerciasis was judged to have been reduced to insignificant levels. Initially (1969-1975) vector immigration maintained unacceptably high levels of transmission, but OCP was much larger than the preceding campaign and in 1975 the Annual Transmission Potential (ATP) dropped below 100 at all sites in the Comoe river valley except Folonzo, which continued to be subject to reinvasion, along with the whole of the Leraba river valley. However, after the southern extension of the OCP in 1979, ATPs dropped below 100 everywhere in the Comoe basin (including the Leraba valley), and further dropped to insignificant levels after the western extension of the OCP in 1985. Thus transmission dropped more quickly in the Comoe river valley than the Leraba river valley (which had been subject to vector reinvasion), and this was also reflected in prevalence of microfilaraemia in the human population. After 1986 prevalence was less than 5% in all villages in the Comoe river valley (except for two, which subsequently dropped to 0% and 3.7% by 1999). However, in 2001 (12 years after the cessation of vector control) the prevalence in one village in the Comoe river valley had increased to 39.6%, and two more had increased above 5% by 2007. New epidemiological surveys in 2011 and 2012 showed that in 13 out of 30 villages in the Comoe river valley prevalence of microfilaraemia was above 5%, although this was not observed in the Leraba river valley where prevalence remained low. This is the first documented case of recrudescence of onchocerciasis in the old OCP area, and the reasons are not clear. It is possible that there has been immigration of parasites with humans or vectors from areas where there has been a shorter period of control, or that control has been less effective. It is possible that in spite of very low levels of transmission the local parasite population was never reduced to a level below the transmission breakpoint, or that there has been a local recrudescence due to stochastic population effects. In any case it is clear that the distribution of ivermectin against lymphatic filariasis in the area since 2004 has failed to prevent the recrudescence of onchocerciasis, and the Burkina Faso Programme National de Lutte contre l'Onchocercose (PNLO - Ministere de la Sante) has instigated a programme of Community Directed Treatment with Ivermectin specifically aimed at onchocerciasis in accordance with the strategy developed by APOC and recommended to governments by OCP when it was dissolved in 2002.

Seventy-one individuals who had been examined for Wuchereria bancrofti microfilaraemia in 1975, some of whom had been offered mass treatment with diethylcarbamazine (DEC) in subsequent years, were re-identified in 1996 and examined for microfilaraemia, circulating filarial antigenemia and cellular and humoral immunoresponsiveness to crude antigen homogenates prepared from Brugia pahangi parasite material. 85.9% of the study individuals had the same infection status in 1975 and 1996, suggesting strong predisposition to infection over extended periods of time. IL-4, IL-5 and IFNγ responses were associated with being infection negative in 1996 whereas IL-10 responses were associated with being infection positive. Similarly, specific IgG3 and IgE were strongly associated with being infection negative in 1996 whereas specific IgG4, and thus high IgG4/IgE ratios, were strongly associated with being infection positive. Intermediary levels of mainly IL-5, IFNγ and PBMC stimulation indices were observed for study individuals who changed from being infection positive in 1975 to infection negative in 1996, or vice versa, suggesting a transition in cellular immunoresponsiveness associated with changing infection status. The findings suggest that some people are more disposed to infection with bancroftian filariasis than others and that this is largely unaffected by treatment with DEC. The findings also suggest that specific cellular and antibody responses are more related to current than past infection status, and that IL-4, IL-5, IFNγ, specific IgG3 and IgE are associated with parasite clearance, whereas IL-10 and specific IgG4 are associated with parasite protection.

A parasitological survey was conducted among children and adolescents in the municipality of Jaboatão dos Guararapes, Brazil to describe the occurrence and spatial distribution of lymphatic filariasis. Microfilaraemia was investigated through the thick smear technique, using 50 μl of capillary blood that was collected at night. The spatial analysis used a digital base map of the municipality, divided into districts, which were classified as hypoendemic, mesoendemic or hyperendemic. 8670 children were examined and 96 cases of microfilaraemia were identified (1.1%). The prevalence rate did not differ significantly between the sexes. Occurrences of filarial infection increased with increasing age: the greatest prevalence was recorded between 15 and 18 years of age (P0.05). There were 49 reports of clinical manifestations. The spatial distribution of microfilaraemia according to residential district showed that 13 (54.2%) of the 24 districts investigated were positive. Approximately 33% of the districts were hyperendemic. The results demonstrated that the pediatric population had intense early exposure to the parasite, thus characterizing filariasis as endemic in the municipality. The spatial analysis allowed identification of areas with greater occurrence of infection among children, and showed localities where the populations most exposed to transmission were concentrated. Epidemiological surveillance of microfilaraemia among children and spatial analysis are important local transmission indicators and form instruments for planning actions within the Global Program to Eliminate Lymphatic Filariasis, since they make it possible to identify priority areas.

To evaluate the effect of multiple rounds of annual single dose of DEC (6 mg/kg) or albendazole (400mg) given alone or in combination on Wuchereria bancrofti microfilaraemia, anti-filarial IgG1 and IgG4 and antigenaemia.A total of 170 participants were randomly assigned to albendazole (n = 62), DEC (n = 54), and DEC plus albendazole (DEC/ALB) combination (n = 54). Blood samples were collected at pre-treatment in 1998, at 1 week and 6 months after the first treatment and thereafter before subsequent treatments in 1999 and 2000. Effects of treatment on W. bancrofti infection were determined by changes in levels of microfilaraemia, antifilarial antibodies and circulating filarial antigen.Comparison of geometric mean microfilariae intensities between DEC/ALB combination and DEC or albendazole single therapy groups after two rounds of annual treatment and 24 months follow-up showed that combination therapy resulted in a greater reduction of microfilaraemia than single therapy with either albendazole (p0.001) or DEC alone (p = 0.146). The overall levels of anti-filarial antibodies decreased significantly (p = 0.028 for IgG1 and p0.043 for IgG4) in all treatment groups at 24 months follow-up. Additionally, overall reduction in geometric mean circulating filarial antigen levels at 24 months was 44%, 60% and 85% for albendazole, DEC and DEC/ALB groups, respectively.These study findings suggest that albendazole improved efficacy of DEC and mass administration of a combination of the two drugs would therefore enhance the interruption of transmission of W. bancrofti in endemic areas. This information has important implications for the ongoing Global Program for Elimination of Lymphatic Filariasis.

In 2000, the American Samoa Department of Health initiated a campaign of annual mass drug administration (MDA) with albendazole and diethylcarbamazine (DEC) to eliminate transmission of filariasis. Drug coverage was well below prescribed targets in the first three campaigns, ranging from 24 to 52% of the total population. Evaluation findings from a variety of formative research methods identified opportunities to improve MDA coverage and ensuing program modifications resulted in increased drug coverage of 65-71% in the following four annual distributions. Partnering with churches for drug distribution and using multiple media channels for health promotion led to sustained program improvements. With the increased emphasis on the use of mass distribution for delivery of drugs for a number of neglected tropical diseases, other programs may benefit from a similar approach.

Successful elimination of lymphatic filariasis (LF) requires accurate identification of residual foci of transmission and stringent surveillance strategies to combat potential resurgence. This is challenging in areas where the day-biting Aedes polynesiensis is endemic, such as Samoa, since in previous studies no geographical clustering of infection has been demonstrated. Another challenge for this low prevalence phase is the choice of diagnostic assay as testing for circulating filarial antigen (CFA) or microfilariae (Mf) alone may not have adequate sensitivity. This could be solved by using the commercially available filariasis Cellabs enzyme linked immunosorbent assay (CELISA) to measure antibody. In the current study five Samoan villages were chosen based on previous epidemiological assessments to represent a range of infection prevalences. CFA, Mf, and antibody levels in children ≤ 10 years had been recorded and results linked to household of residence and/or primary school of attendance. To ascertain the location of exposure, two scenarios based on potential foci of transmission around communities and schools were explored. Both scenarios revealed significant spatial clusters of households with infected individuals and a relationship to antibody positive children when they were included in the spatial analysis. Fasitoo-Tai had the highest LF prevalence and largest geographical spatial clusters for both scenarios. In Falefa, spatial clusters were detected only for the primary school scenario. In Tafua, which spanned an area of 19.5 km(2), no spatial clusters were detected. Lastly, in Siufaga, the village with the lowest LF prevalence, significant clustering of infected individuals was observed and, for the primary school scenario, this was geographically related to exposure. These promising findings are the first published evidence of spatial clustering of LF in a day-biting Ae. polynesiensis endemic area.

One of the two main goals of the Global Programme to Eliminate Lymphatic Filariasis (LF) is to provide care for those suffering from the devastating clinical manifestations of this filarial infection. Among the 120 million infected people worldwide, up to 16 million have lymphoedema. The WHO strategy for managing lymphoedema is based on rigorous skin hygiene, exercise, antibiotics and antifungals when indicated. The aim is to reduce acute attacks of adenolymphangitis and cellulitis responsible for lymphoedema progression and disability. The objective of our study was to assess the effectiveness of home-based lymphoedema management implemented by the national health system of Burkina Faso. Any patient was eligible to participate in the study if suffering from LF-related lymphoedema of a lower limb at any stage, and receiving care as part of the health education and washing project between April 2005 and December 2007. The primary readout was the occurrence of an acute attack in the month preceding the consultation reported by the patient or observed by the care-giver. In all, 1089 patients were enrolled in the study. Before lymphoedema management intervention, 78.1% (95%CI: 75.5–80.5) of the patients had an acute attack in the month preceding the consultation; after four and half months of lymphoedema management, this was reduced to 39.1% (95%CI: 36.2–42.1). A reduction of acute attacks related to the number of consultations or related to the patients’ age and gender was not observed. Our results suggest that the home-based lymphoedema management programme in the primary health care system of Burkina Faso is effective in reducing morbidity due to LF in the short-term (4.5 months). The lymphoedema management requires no additional human resources, but whether its effect can be sustained remains to be seen.

Antibody tests are useful for mapping the distribution of lymphatic filariasis (LF) in countries and regions and for monitoring progress in elimination programs based on mass drug administration (MDA). Prior antibody tests have suffered from poor sensitivity and/or specificity or from a lack of standardization. We conducted a multicenter evaluation of a new commercial ELISA that detects IgG4 antibodies to the recombinant filarial antigen Bm14. Four laboratories tested a shared panel of coded serum or plasma samples that included 55 samples from people with microfilaremic Wuchereria bancrofti or Brugia infections and 26 control samples. Qualitative results were identical in all four test sites. In addition, each laboratory tested samples from their own serum banks. The test detected antibodies in 32 of 36 samples (91%) from people with Brugian filariasis and in 96 of 98 samples (98%) from people with Bancroftian filariasis. Specificity testing showed that many serum or plasma samples from patients with other filarial infections such as onchocerciasis had positive antibody tests. Specificity was otherwise excellent, although 3 of 30 samples from patients with ascariasis and 4 of 51 with strongyloidiasis had positive antibody tests; it is likely that some or all of these people had previously lived in filariasis-endemic areas. Antibody test results obtained with eluates from blood dried on filter paper were similar to those obtained with plasma tested at the same dilution. This test may be helpful for diagnosing LF in patients with clinical signs of filariasis. It may also be a useful tool for use in LF endemic countries to monitor the progress of filariasis elimination programs and for post-MDA surveillance.

(i) To determine the frequencies of urogenital pathologies in men infected with bancroftian filariasis, and (ii) to evaluate the role of ultrasonography (USG) as a diagnostic tool to differentiate between diverse pathologies with different clinical implications. To date, all types of scrotal enlargement resulting from lymphatic filariasis (LF) have been summarized under one term: "filaricele".Data were compiled from recruitment phases for field trials in an endemic area for LF in Ghana. 1453 men aged 18 years and above underwent ultrasound examinations of the scrotum. Observation parameters were: Filaria Dance Sign (FDS), dilation of supratesticular lymphatic vessels, thickness of scrotal skin, occurrence and amount of fluid accumulation, echogenicity of the fluid between the layers of the tunica vaginalis, as well as position and homogenicity of testis, epididymis and spermatic cord. In 1132 men, blood samples were taken for parasitological analysis.In 56% of examined patients, fluid accumulation around the testis was detected (38% subclinical-, 18% clinical stages). Differentiation of the echogenicity of the fluid revealed echo-free hydrocele (EFH) in 47% and echo-dense hydrocele (EDH) in 9%. Patients without hydrocele and subclinical stages had a thinner scrotal skin than those in clinical stages or with lymphscrotum (P0.001). In the EDH group the scrotal skin was thicker than in the EFH group (P0.001). 1.4% had a lymphscrotum. FDS was detected in 24% of all 1453 volunteers who underwent USG. The number of worm nests correlated with microfilarial load and levels of circulating filarial antigen (P0.001; 20% microfilaremic, 48% antigen positive).In an unexpected high number of men (56%) fluid accumulation around the testis was detected by USG of which more than one third (38%) presented with subclinical stages. The study showed that echo-dense and echo-free fluid could be differentiated and that a considerable number of cases had EDH (9%) posing a risk to develop necrotic testis and infertility and therefore requiring immediate surgical intervention. USG thus turned out to be a useful diagnostic technique to differentiate between those cases requiring immediate surgical intervention from those that can be treated with (anti-wolbachial and hyperpermeability reducing) drugs that ameliorate or halt progression of the disease.

Procedures for health facility-based management of lymphoedema and adenolymphangitis (ADL) have proved very effective in some countries. Unfortunately, in resource-poor communities of Africa where health facilities are few, overburdened and inaccessible, an alternative approach is required. Community-based care (CC), patient care (PC) and health facility care (HC) approaches were compared. In the CC arm, communities were required to select one of their members for care-giving to its affected members, while in the PC, participants were allocated to groups under a leader with responsibility for care giving to group members. In HC, care was given by the nearest health facility. Caregivers from the three arms were trained and supplies were kept at the local government health office. At the sixth month of intervention, 325 lymphoedema and adenolymphangitis patients had been recruited into the study as participants. Within 12 months, compliance with hygiene practices increased from 29.4% to 62.6% and ADL episodes declined from 43.1% to 4.4% in the community designs arm and the cost on the health system was minimal. However, in the patient and health care arms, compliance and accessibility to supplies was severely affected by poor coordination, delay in resource collection leading to very minimal effect on lesions, odour, ADL frequency and duration. Participants abandoned the health facilities after the second visit. Community care approach was more culturally acceptable and effective for the management lymphoedema and ADL than other approaches.

Successful public–private partnerships for health control have usually included nongovernmental development organisations (NGDOs), and these have long been in the forefront of pinpointing particular social and health issues. The immensely successful control and elimination programmes for onchocerciasis are a case in point. NGDOs were the driving force in early advocacy for onchocerciasis control in West Africa, leading eventually to the remarkably effective and long lasting partnership of the Onchocerciasis Control Programme (OCP). With the donation of Mectizan ® , NGDOs were the driving force in developing onchocerciasis control in non-OCP countries, especially programmes for community based action. These were, further modified by the African Programme for Onchocerciasis Control (APOC) to become the successful Community Directed Interventions. NGDOs came together to coordinate activities in partnership with the World Health Organisation (WHO). Innovations by NGDOs led to integration of mass drug administration for Vitamin A deficiency and then for other parasitic diseases, leading to the current trend of preventive chemotherapy. The success of the NGDO Group for Onchocerciasis Control has led to the creation of similar groups for trachoma control and lymphatic filariasis elimination. These groups have now come together to form an NGDO Network for Neglected Tropical Disease control.

Identification of communities with people that could benefit from adenolymphangitis (ADL) and lymphoedema morbidity management within Lymphatic Filariasis Elimination Programmes (NLFEP) in many African countries is a major challenge to programme managers. Another challenge is advocating for proportionate allocation of funds to alleviating the suffering that afflicted people bear. In this study we developed a rapid qualitative technique of identifying communities where morbidity management programme could be situated and documenting the pain and distress that afflicted persons endure. Estimates given by health personnel and by community resource persons were compared with systematic household surveys for the number of persons with lymphoedema of the lower limb. Communities in Northeastern Nigeria, with the largest number of lymphoedema cases were selected and a study of local knowledge, physical, psychosocial burden and intervention-seeking activities associated with the disease documented using an array of techniques (including household surveys, key informant interviews, group discussions and informal conversations). Health personnel gave a more accurate estimate of the number of lymphoedema patients in their communities than either the community leader or the community directed ivermectin distributor (CDD). Community members with lymphoedema preferred to confide in health personnel from other communities. The people had a well developed local vocabulary for lymphoedema and are well aware of the indigenous transmission theories. Although the people associated the episodic ADL attacks with the rains which were more frequent at that period they did not associate the episodes with gross lymphoedema. There were diverse theories about lymphoedema causation with heredity, accidental stepping on charmed objects and organisms, breaking taboos. The most popular belief about causation, however, is witchcraft (60.9%). The episodic attacks are dreaded by the afflicted, since they are accompanied by severe pain (18%). The emotional trauma included rejection (27.5%) by family, friends and other community members to the extent that divorce and isolation are common. Holistic approach to lymphoedema morbidity management should necessarily be an integral component of the ongoing transmission elimination programme. Any transmission prevention effort that ignores the physical and psychological pain and distress that those already afflicted suffer is unethical and should not be promoted.

To date, few studies have addressed the sequelae of lymphatic filariasis, a mosquito-transmitted disease, on the quality of life of affected women in the Americas. In this qualitative study, we conducted 28 semi-structured interviews and 3 focus groups of women with lymphedema or elephantiasis of the leg living in filariasis-endemic areas of the Dominican Republic. Women in our study described a spectrum of consequences associated with their lymphedema but physical, functional, and psychological limitations were not always associated with severity of lymphedema. Data suggests that management frameworks need to be expanded to address women's explanatory models of illness, the cultural practices of seeking traditional healers for initial care, psychological distress, coping strategies unique to women, and the practice of self treating with antibiotics without medical supervision. Further research to better understand the depth and breadth of psychological states and coping strategies of women; the health seeking and self-management practices; and the strain on social support networks of women is needed in order to assist health program planners in establishing culturally tailored and gender-specific interventions for Dominican women.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF), which includes alleviation of disability and suffering of patients, is implemented primarily in India by primary health care system. The present study assesses the current practices related to lymphoedema care among clinicians of primary healthcare system in three filarial endemic districts of Orissa, India. The results are based on the data obtained through in-depth interviews with 50 clinicians from primary health centres (PHCs) and private clinics located in 22 PHCs sampled from three districts. All clinicians are aware of common as well as atypical manifestations of LF and offered treatment to them. The most commonly dealt complaints are lymphoedema of chronic LF and acute lymphangitis. All the clinicians reported that they prescribed diethylcarbamazine (DEC) for the treatment of patients with acute episodes, and only 50% of them prescribed antibiotics along with DEC. However, there is no uniform pattern either in the dosage of DEC or in the use of antibiotics. In this study, all the clinicians are aware that repeated acute episodes leads to lymphoedema. Majority of clinicians (94%) prescribed DEC to prevent this progression. For reduction of oedema, they offered a variety of treatments and more than half of the clinicians prescribed DEC. The study districts have been covered by the mass drug administration (MDA) of DEC under the GPELF. In order for the GPELF as a whole to prove successful and sustainable, those persons who are already suffering from LF need to be cared for and their suffering is to be relieved. Current practices of clinicians, both at government and private health institutions should be improved. With the revised knowledge that bacterial infections play a key role in the progression of disease, the attitude of clinicians towards the treatment of LF has to be changed.

The possible role of Mansonia uniformis mosquitoes in the transmission of lymphatic filariasis was assessed in an endemic area of Uganda, by examining their diurnal biting cycle, host preference and ability to support the development of experimental and natural Wuchereria bancrofti infections. Anopheles gambiae s.l. served as controls. Human landing catches revealed that outdoor biting peaked early in the evening (19:00-20:00h), while indoor biting peaked around midnight (23:00-24:00h). By far the majority of indoor collected M. uniformis had derived their blood meals from humans. Both biting and feeding behaviour were therefore compatible with a potential for transmission. In experimentally fed M. uniformis (total of 1915), the microfilariae were seen to ex-sheath and to start migration, but the L1s accumulated in the thorax and only few developed further. In dissections from Day 11 onwards, 4.6% (43/932) of M. uniformis had L2 larvae and 0.7% (7/932) had L3 larvae of W. bancrofti. The corresponding figures for An. gambiae s.l. were 13.4% and 4.6%, respectively. Dissection of wild caught M. uniformis (total of 6823) did not reveal any natural infections with W. bancrofti infective larvae, whereas wild caught An. gambiae s.l. had an infective rate of 1.3%. Other filarial species, and mermithids, were common in M. uniformis. It is concluded that M. uniformis has a limited potential to support development of W. bancrofti to the infective stage, and it does not appear to play a role as a vector under natural conditions.

A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4 antibodies to Bm14, and associations between antibody reactivity and the different variables were statistically analyzed. IgG4 reactivity to Bm14 was highly positively associated with CFA, and to a lesser extent with age. However, an expected association with household exposure to infective filarial larvae was not found. Bm14 antibody reactivity thus appeared mainly to reflect actual infection of individuals with adult filarial worms rather than ongoing exposure to transmission. The analyses moreover suggested that many of the CFA negative but Bm14 positive individuals had early or low level infections where antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including break of transmission and post-elimination surveillance, in LF control.

Health status is the standardized description of health condition of individuals either normal or ill due to diseases and is presented as multidimentional profiles. In an effort to develop an indicator to assess the impact of morbidity intervention against lymphatic filariasis (LF), we assessed the health status of seven different clinical manifestations (health states) of LF from the patient's perspective. One hundred and seventy-four filarial patients either with hydrocele or lymphoedema were involved in the study. Acute episode of adenolymphangitis (ADL) among chronic patients was considered as co-morbidity. Severity levels, focusing on physical, mental and social dimensions of health were defined and quantified, using seven domains and five levels (7D5L) instrument, an extended form of EuroQol (5D3L). All the seven domains of health are affected by filarial disease, with the levels of severity varying with health states. The mean severity score of ADL (25.8) was significantly higher compared to lymphoedema (10.7) and hydrocele (6.9) (P

The filarial parasite Brugia timori is of great public health importance in some islands of Eastern Indonesia. To establish a simple serological test for the identification and post-treatment monitoring of areas endemic for B. timori, a rapid immunochromatographic dipstick test (Brugia Rapid, BR) was evaluated on microfilaraemic and amicrofilaraemic individuals. This test is based on the detection of anti-filarial IgG4 antibodies that react with a recombinant Brugia malayi antigen (BmR1). In our study area on Alor island the prevalence of microfilaraemia was 26%. With the BR test, 100% of 196 sera from microfilaraemic persons and 76% of 563 sera from amicrofilaraemic persons, either symptomatic or asymptomatic, reacted positive. All 50 control sera from areas non-endemic for lymphatic filariasis gave negative BR test results. This study showed that the BR test can be also used to detect antibodies against B. timori. Due to the high prevalence of IgG4 antibodies as detected by the BR test (81%), no significant correlation with the prevalence of microfilaraemia could be detected within the endemic village. The BR test also shows great promise to be employed as a monitoring tool for B. timori in the framework of the Global Program to Eliminate Lymphatic Filariasis (GPELF).

The prevalence of entry lesions in limbs was significantly higher in limbs with filarial lymphoedema (80.88%) than in normal limbs (42.86%, P = 0.000012). Among the various entry lesions in the lymphoedematous limbs, the prevalence of web space intertrigo was significantly higher in those who had acute dermatolymphangioadenitis (ADLA) than those who did not have ADLA (P = 0.04). Entry lesions were present only in 25% of those not using footwear, while 84.3% of those using footwear regularly or irregularly had these lesions (P = 0.01). None of the patients with good limb hygiene had ADLA, while 64% of those with fair to poor limb hygiene had ADLA (P = 0.02). Since the majority of the entry lesions were asymptomatic, training of patients and health care givers to specifically look for and treat these along with advice for good limb hygiene practices should form an important component of foot care programme for optimum filarial morbidity management.

Serum and urine samples were randomly collected from residents in two rural areas at different altitudes in Nepal, and were examined for Wuchereria bancrofti antigens and antibodies (IgG4) to filarial antigens, respectively. In Judigaun, located at 900 m in altitude, 25.2% of 238 serum samples were positive for antigen, and 50.8% of 244 urine samples were positive for antibody. The level of IgG4 antibodies was higher among antigen positive individuals than among the antigen negatives. In Kotyang, located at 1100–1300 m, the prevalence of antigenemia was 15.4% of 117 serum samples.

Homologues of human macrophage migration inhibitory factor (hMIF) have been reported from vertebrates, invertebrates and prokaryotes, as well as plants. Filarial parasites produce two homologues of hMIF viz., MIF-1 and MIF-2, which play important role in the host immune modulation. Earlier, we have characterized MIF-1 ( Wba-mif-1 ) from Wuchereria bancrofti , the major causal organism of human lymphatic filariasis. Here, we are reporting the molecular and biochemical characterization of MIF-2 from this parasite ( Wba-mif-2 ). The complete Wba-mif-2 gene and its cDNA were amplified, cloned and sequenced. The size of Wba-mif-2 gene and cDNA were found to be 4.275 kb and 363 bp, respectively. The gene annotation revealed the presence of a large intron of 3.912 kb interspersed with two exons of 183 bp and 180 bp. The alignment of derived amino acid sequences of Wba-MIF-2 with Wba-MIF-1 showed 44% homology. The conserved CXXC oxido-reductase catalytic site present in Wba-mif-1 was found absent in Wba-mif-2 coding sequence. The amplified Wba-mif-2 cDNA was cloned into an expression vector pRSET-B and transformed into salt inducible Escherichia coli strain GJ1158. The expressed recombinant Wba-MIF-2 protein showed tautomerase activity against l -dopachrome methyl ester and the specific activity was determined to be 18.57 ± 0.77 μmol/mg/min. Three known inhibitors of hMIF tautomerase activity significantly inhibited the tautomerase activity of recombinant Wba-MIF-2. Although the conserved CXXC oxido-reductase motif is absent in Wba-mif-2 , the recombinant protein showed significant oxido-reductase activity in the insulin reduction assay, possibly because of the presence of vicinal cysteine residues.

The social and economic impact of lymphatic filariasis was studied in Northern Ghana. Qualitative methods of gathering information revealed that even though the disease was a problem to both men and women, men with hydrocele suffered a greater psychosocial burden. Particular attention was paid to them, distinguishing men with small hydroceles and men with large ones. Out of frustration men with small hydroceles sought health care from a wider range of places than men with larger ones. The pain associated with adenolymphangitis (ADL) renders them inactive for up to 5 days. Complications of lymph scrotum and ridicule from community members were a problem. Unmarried men in particular found it difficult to find a spouse with their condition, and various degrees of sexual dysfunction were reported amongst married men. The clinical significance and the value of time and attention for counseling to mitigate the effects of the disease on damaged male identity and the need for gender studies to address male issues and the need for including psychosocial issues in the calculating of disability adjusted life years (DALY's) is also discussed.

A longitudinal prospective surveillance for acute adenolymphagitis (ADL) was carried out in three villages in Rufiji district. A sample population of 3000 individuals aged 10 years and above was monitored fortnightly for a period of 12 months. The annual incidence of ADL was found to be 33 per 1000 population and was significantly higher in males than females (52.7/1000 and 18.7/1000 respectively). ADL episodes were more frequent in the age group of 40 years and above. Individuals with chronic manifestations seemed to be more vulnerable to ADL attacks with 62.2% of the total episodes occurring in this group. Furthermore, individuals with lymphoedema experienced more frequent acute episodes compared to those with hydrocele and 'normal exposed'. ADL episodes ranged from one to five per annum and the majority of the affected (60.4%) experienced a single episode. The average duration of an ADL episode was 8.6 days and in 72.5% of the episodes the affected individuals were incapacitated and unable to do their normal activities for an average duration of 3.7 days. The physical incapacitation associated with ADL episodes emphasizes the significance of lymphatic filariasis as a major public health problem of substantial socio-economic consequences.

Filarial lymphedema is complicated by frequent episodes of dermatolymphangioadenitis (DLA). Severe systemic symptoms during attacks of DLA resemble those of septicemia. The question we asked was whether bacterial isolates can be found in the peripheral blood of patients during the episodes of DLA. Out of 100 patients referred to us with 'filarial' lymphedema 14 displayed acute and five subacute symptoms of DLA. All were on admission blood microfilariae negative but had a positive test in the past. Blood bacterial isolates were found in nine cases, four acute (21%) and five subacute (26%). In 10 acute cases blood cultures were found negative. Six blood isolates belonged to Bacilli, four to Cocci and one was Sarcina. To identify the sites of origin of bacterial dissemination, swabs taken from the calf skin biopsy wounds and tissue fluid, lymph and lymph node specimens were cultured. Swabs from the calf skin biopsy wound contained isolates in nine (47%) cases. They were Bacilli in nine, Cocci in three, Acinetobacter and Erwinia in two cases. Tissue fluid was collected from 10 patients and contained Bacilli in four (40%) and Staphylococci in three (30%). Lymph was drained in four patients and contained isolates in all samples (100%). They were Staphylococcus epidermis, xylosus and aureus, Acinetobacter, Bacillus subtilis and Sarcina. Three lymph nodes were biopsied and contained Staphylococcus chromogenes, xylosus, Enterococcus and Bacillus cereus. In six cases the same phenotypically defined species of bacteria were found in blood and limb tissues or fluids. In the 'control' group of patients with lymphedema without acute or subacute changes all blood cultures were negative. Interestingly, swabs from biopsy wound of these patients contained isolates in 80%, tissue fluid in 68%, lymph in 70% and lymph nodes in 58% of cases. In healthy controls, tissue fluid did not contain bacteria, and lymph isolates were found only in 12% of cases. This study demonstrates that patients with acute episodes of DLA reveal bacteremia in a high percentage of cases. Diversity of blood and tissue bacterial isolates in these patients points to a breakdown of the skin immune barrier in lymphedema and subsequently indiscriminate bacterial colonization of deep tissues and spread to an blood circulation.

An antigen fraction (DssdI) was isolated from the aqueous-insoluble components of adult Setaria digitata. Rabbit antiserum to DssdI labeled the sheaths of Wuchereria and Setaria microfilariae suggesting DssdI to be surface associated. Antibody responses to DssdI were determined in Wuchereria bancrofti exposed individuals. IgM titre was highest in endemic normals (EN; asymptomatic amicrofilaraemic) followed by chronic filarial patients (CP) and asymptomatic microfilaraemics (AS). IgG titer was high in both chronic filariasis and endemic normals. The microfilaraemic group had the lowest titer. The seropositivity rate in AS was 28% for IgG and 10% for IgM, in CP 100% for IgG and 33% for IgM, and in EN 86% for both antibodies. An age-dependency of IgM but not of IgG antibodies was observed in endemic normals, with IgM prevalence reaching a plateau by 12 years of age. The subclass composition of the antibody response to DssdI appeared to be primarily IgG3 in endemic normals, IgG1 in chronic filariasis and IgG4 in asymptomatic microfilaraemics. Diethylcarbamazine (DEC) treatment led to a significant increase in IgG and IgM levels in microfilaraemic individuals. Of interest, the expression of IgG subclasses altered. There was an increased IgG3 and IgG1 response associated with a reciprocal decrease in IgG4 following DEC therapy.

The serum levels of three major granulocyte proteins were measured in patients with onchocerciasis, bancroftian filariasis and intestinal schistosomiasis and compared to controls from patients with malaria, Africans living in areas not endemic for these infections and healthy Germans. The investigation comprised the determination of the eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN/EPX), and the neutrophil/monocyte granule protein myeloperoxidase (MPO). ECP and EDN/EPX levels were found elevated only in the three helminth infections that are associated with eosinophilia, while MPO was found elevated in all tested disease groups. The levels of eosinophil granule proteins observed in the helminth diseases by far exceeded those described for bronchial asthma and atopic dermatitis. ECP, EDN/EPX and MPO serum levels reflect the ongoing disease and are related to functional activity of the respective leukopoetic system. ECP and EDN/EPX appear to be markers of the eosinophil effector system and MPO a marker of the neutrophil and/or monocyte/macrophage effector system. Significantly higher ECP levels in chronic hyperreactive onchodermatitis (sowda) versus generalized onchocerciasis seem to reflect an augmented degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates, indicating a more active mechanism of parasite clearance in sowda patients.

The study examines the changes in the disease parameters of lymphatic filariasis over a period of time based on three surveys during 1957, 1986 and 1992 in Pondicherry, South India. The overall prevalence of filarial disease in the three surveys was 4.7, 6.7 and 9.9% respectively. It was significantly higher in males (1957:5.3%; 1986:13.7%; 1992:18.8%) when compared to females (1957:3.8%; 1986:2.3%; 1992:2.7%) in all the three surveys (P0.05). The overall prevalence of acute adenolymphangitis declined from 1.0 in 1957 to 0.2 in 1986 and 0.04% in 1992. While the prevalence of hydrocele showed an increasing trend from 2.7 in 1957 to 11.9 in 1986 and 17.3% in 1992, the prevalence of lymphoedema (1.9 in 1957; 1.9 in 1986 and 1.8% in 1992) was stable over the same period. The prevalence of disease was relatively higher in all age groups of both male and female population in 1992 when compared either to 1957 or 1986. Similarly a monotonic increase in the prevalence of hydrocele was observed in all age groups in 1992 when compared to previous surveys. The implications of the changes in prevalence of the chronic manifestations when compared to the changes in the acute manifestations over a period of 35 years are discussed.

In Sub-Saharan Africa, some individuals infected with malaria are also infected with helminths. However, the magnitude and distribution of such coinfections in relation to eco-systems remains poorly defined. This study was undertaken to determine the prevalence of Plasmodium falciparum and helminth coinfections among schoolchildren in relation to agro-ecosystems in Mvomero District, Tanzania.The agro-ecosystems were categorised as sugarcane, traditional flooding rice irrigation, improved non-flooding rice irrigation and savannah. Schoolchildren had their blood examined for P. falciparum and Wuchereria bancrofti; urine for Schistosoma haematobium and stool for intestinal helminths. Blood samples were also examined for haemoglobin concentration.A total of 578 schoolchildren (mean age = 7.96 years) were involved in the study. Overall, 60% of all schoolchildren had at least an infection of either P. falciparum, W. bancrofti, S. haematobium or hookworm. The highest prevalence of P. falciparum (75.3%), W. bancrofti (62.9%) and hookworm (24.7%) infections was observed among children in flooding rice irrigation ecosystem. P. falciparum+S. haematobium (10.9%) and P. falciparum+W. bancrofti (11.1%) were the most prevalent types of coinfection in the area. The highest prevalence of double parasitic infections was observed among children in the flooding rice irrigation ecosystems. The risk for acquiring coinfections of P. falciparum+W. bancrofti was significantly higher among children in the flooding rice irrigation ecosystem. Forty-five (7.8%) children were coinfected with three types of parasitic infections. The risk of acquiring triple infection among children from flooding rice irrigation was higher for P. falciparum+S. haematobium+W. bancrofti (p0.001). Seven schoolchildren (1.2%) were found infected with four parasites and all were from the flooding rice irrigation ecosystem. Significantly high P. falciparum geometric parasite density was observed among children coinfected with either hookworms or W. bancrofti (p0.001). On average, 17.8% (103/578) of the children had enlarged spleens. Over 3- and 4-folds increase in the risk of having an enlarged spleen were observed among children coinfected with P. falciparum+S. haematobium and P. falciparum+W. bancrofti, respectively. The overall prevalence of anaemia (11.5g/dl) was 61.9% (358/578).Malaria-helminth coinfections are prevalent among schoolchildren in rural Tanzania and the pattern varies between agro-ecosystems. Results of this study suggest that integrated control of malaria and helminthes should be designed based on the local agro-ecosystems.

The risk of infection (RI) with Wuchereria bancrofti by vector mosquitoes has been conventionally estimated from the biting population of all age classes. This estimate of RI had no correlation with microfilaria (mf) prevalence and intensity of infection in humans. A new method for estimating RI from a resting population of Culex quinquefasciatus is proposed based on a longitudinal study in seventeen sites in Pondicherry, India. Unlike previous estimates, RI calculated by the present method considering the density of parous mosquitoes collected per man-hour and the mean number of infective stage larvae per parous mosquito significantly correlated with mf prevalence in humans during both early (r = 0.559; P = 0.038) and late in the control operation (r = 0.572; P = 0.033). RI varied significantly between the early and late in the control operation and different sites. On average, RI was reduced significantly during the control operation. Further epidemiological implications are discussed.

Side reactions following ivermectin treatment were evaluated in sixty males with high density bancroftian microfilaremia (GM 1388/ml). Following a single oral dose of ivermectin of different strengths (20, 50, 100 or 200 micrograms/kg), microfilariae clearance and side reactions were monitored in a double blind fashion. Microfilaria levels fell rapidly after ivermectin administration in all dosage groups and 98% of pretreatment microfilariae was cleared after 12 h of treatment. The rate of microfilaria (mf) clearance was slower with 20 micrograms/kg than with the highest dose (200 micrograms/kg) administered. Forty-six patients (77%) became amicrofilaraemic within 2 weeks of treatment. Side reactions were noted in 97% of cases. The most common reactions were fever, headache, weakness, myalgia and cough which appeared by 12 h and subsided by 72 h following treatment. The frequency and intensity of side reactions were related to pretreatment mf densities and were independent of the dose administered. Unusual side reactions were noted in a few patients with high density microfilaraemia. These included intense cough, shortness of breath, blood tinged mucoid expectoration associated with patchy pneumonitis of the lung. Itchy rashes, lymphatic nodules and raised alkaline phosphatase level were also observed in some patients. These side reactions were transient, self limiting and were not serious enough to warrant any treatment. These exaggerated unusual reactions were possibly due to allergic response of the susceptible host to rapid killing of large number of microfilariae.

To harmonise the technique of filarial hydrocelectomy throughout the West African subregion, training workshops were organized in 10 endemic West African countries involving surgeries on Filarial hydrocele patients (Filariceles). Countries included Ghana, Nigeria, Niger, Burkina Faso, Senegal, Mali, Liberia, Gambia, Sierra Leone and Togo. Patients were recruited by the Filariasis programme managers in all these countries and workshops were done to train surgeons from teaching, government and district hospitals with funding mainly from the West African Filariasis Project. A total of 16 workshops were held in 10 West African Countries, and a total of 500 filarial hydrocele/chylocele cases were operated using the technique of total tunical resection without drainage with excellent postoperative results. The average operating time for a unilateral hydrocele was 45 min to 1h and for bilateral hydrocele was 1½ h to 2h depending on the size of the hydrocele .All patients were admitted for a minimum of 5 days postoperative. Training workshops were successfully organized in 10 out of the envisaged 12 west African Countries with 214 surgeons trained. Since 2004 till date the trained surgeons have also operated 2500 filaricele cases bringing it to a total of 3000 cases operated so far. Evaluation studies revealed that the infection rates in one country was initially 60% and then it later dropped to 20% and this was actually attributed to poor follow up by the selected National Coordinator. However complication rates in all the Countries where workshops were done ranged between 5% and 7% made up of infection, haematoma and or delayed wound healing. Recurrence rates have been very low about 3-5% per Country.

We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 μg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 μg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 μg/ml. Flavone immobilized female adult worms at 31.2 μg/ml (MTT>80%) and microfilariae at 62.5 μg/ml. Rutin killed microfilariae at 125 μg/ml and inhibited MTT-reduction in female worms for >65% at 500 μg/ml. Naringin had adulticidal effects at 125 μg/ml while chrysin killed microfilariae at 250 μg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.

Long term (greater than 200 day) Brugia malayi-infected nude mice with grossly dilated lymphatics were reconstituted with 10(8) primed spleen cells from heterozygous donors. Histological and ultrastructural examination at 7, 14, 21 and 28 days post-reconstitution revealed progressive fibrosis, obliterative lymph thrombus formation, interstitial infiltrates and extensive perilymphangitis. Formation of lymph thrombi/granulomas was associated with killing of adult worms and microfilariae, and the predominant cell types involved were large granular macrophages. Langhan's giant cells and eosinophils. Thus, the ability to initiate the formation of obstructive lesions in the dilated lymphatics of chronically parasitized nude mice by immunological reconstitution, suggests that several complex mechanisms might operate in stages to cause filarial elephantiasis.