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Immunodiagnosis of Bancroftian filariasis by enzyme linked immunosorbent assay using Litomosoides carinii and Setaria cervi antigens.

An ELISA was developed using cross-reacting antigens of Litomosoides carinii and Setaria cervi to detect antibodies in filarial patients. The diagnostic potential of the test was investigated in 80 symptomatic cases of filariasis, 40 asymptomatic carriers and 50 normal subjects of an area around Lucknow endemic for Bancroftian filariasis. By the criteria laid down for ELISA positivity for filariasis, 86.2% of the symptomatic cases could be detected by this test. Only four of 40 asymptomatic carriers and one of 50 normal subjects gave a positive ELISA response. Purified antigenic fractions of S. cervi are also promising for detecting asymptomatic carriers.

Antibodies↗

A common anti-DNA antibody idiotype and anti-phospholipid antibodies in sera from patients with schistosomiasis and filariasis with and without nephritis.

The serum concentration of a public idiotype (16/6 ID), originally identified on a human hybridoma-derived monoclonal anti-DNA antibody, was raised in patients with S. mansoni and filariasis with or without nephritis, compared to patients with S. haematobium (in which nephritis does not occur) or idiopathic nephritis not associated with infection. There was no significant difference in 16/6 ID levels between patients with or without renal disease, whether associated with S. mansoni or filarial infection. The 16/6 ID-positive antibodies did not bind to native or denatured DNA, using competitive fluid-phase inhibition studies. Anti-cardiolipin antibody (ACA) concentration was increased in patients with either S. mansoni or filarial infection. In filariasis, both IgG and IgM ACA isotypes were elevated, irrespective of the presence of nephritis. In S. mansoni infection, IgA ACA were limited to patients with renal disease, and IgG ACA isotype to patients without overt nephritis. Both isotypes of anti-cardiolipin antibody correlated with levels of the 16/6 ID in patients with S. mansoni or filariasis. The 16/6 idiotype was therefore a feature of chronic helminthic infection, but was not related to anti-DNA antibody levels or specificity. The occurrence of nephritis as a complication of these infections was not related to the prevalence of the 16/6 idiotype.

Antibodies, Antinuclear↗

Impact of single-dose ivermectin on community microfilaria load in bancroftian filariasis infection: two years post treatment.

The concept of annual single-dose treatment for the control and possible interruption of transmission of lymphatic filariasis has brought much hope to the previously hopeless disease. The logistics for implementing this enormous public health intervention have wide ramifications and will depend on the efficiency of drug delivery and distribution at various levels of the health system. In sub-Saharan Africa, where the public health services are inadequate, this becomes even more important. Six communities in southern Ghana known to be endemic for filariasis were treated with single-dose ivermectin in January/February 1997 as part of pilot programme activities. The 1998 treatment could not take place because of unavailability of the drug. The 1999 community microfilaraemia prevalence and intensity were reduced by only 25.5% and 39.5% of pre-treatment levels, respectively. The implications of any shortfalls on the drug delivery system on the goal of elimination of lymphatic filariasis are discussed.

Adolescent↗

Lymphatic filariasis on the coast of Ghana.

Parasitological, clinical and entomological surveys for lymphatic filariasis were carried out in 6 villages and 3 towns on the coast of Ghana. Few or no filarial infections were observed in the towns or in the villages east of Accra. However, Wuchereria bancrofti microfilaraemia was common in the 4 western villages, with overall prevalences of 9.2%-25.4% and overall microfilariae (mf) geometric mean intensities of 321-1172 mf/mL of blood. In the same villages, hydrocele affected 8.5%-27.9% of adult males (aged > or = 20 years), and 5.6%-6.6% of adult individuals had elephantiasis (mainly of the legs). In general, the patterns of filarial infection and disease in the endemic villages resembled those observed in endemic villages in the coastal part of East Africa, with the exception that in the Ghanaian focus more females than males were affected by elephantiasis. Entomological surveys revealed that Anopheles gambiae s.l. and A. funestus were vectors of filariasis in the endemic villages. Only negligible prevalences of microfilaraemia were observed in town communities located close to highly endemic villages. Control of filariasis in this area is difficult with presently available measures, and new control tools, especially development of new drug regimens for mass treatment, are greatly needed.

Adolescent↗

Circulating connective tissue metabolites in patients with bancroftian filariasis.

Sera from adults from an area of Tanzania with high endemicity for Wuchereria bancrofti infection were examined for 4 serological markers of extracellular matrix activity, namely the amino-terminal propeptide of type III procollagen (PIIINP), the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and hyaluronan. Sera from individuals with non-filarial elephantiasis and from healthy Danes were included as controls. No association was observed between the mean serum concentration of PIIINP or PICP and the clinical, microfilarial or circulating filarial antigen status of the individuals. The mean concentration of ICTP was significantly higher (P < 0.01) in sera from individuals with filarial and non-filarial elephantiasis than in sera from individuals living in filariasis endemic areas but without elephantiasis or in the Danish control sera. Among individuals from the filariasis endemic area, the mean serum concentration of hyaluronan was significantly higher (P < 0.01) in microfilaraemic than in amicrofilaraemic individuals, and significantly higher (P < 0.01) in individuals who had circulating filarial antigens than in those who did not, but there was no relation to the clinical status. The significance of the findings are discussed in relation to the pathological processes taking place in bancroftian filariasis.

Adolescent↗

Detection of circulating antigen in bancroftian filariasis by sandwich ELISA using filarial serum IgG.

The utility of the IgG fraction of human filarial serum immunoglobulin in detecting circulating antigen by sandwich enzyme linked immunosorbent assay (ELISA) was studied. 27 of 33 sera from persons with microfilaraemia, 19 of 30 sera from clinical cases of filariasis, 4 of 30 sera from normal persons from a region endemic for filariasis showed the presence of circulating filarial antigen. All the 20 normal sera from the area where filariasis was not endemic gave negative reaction for filarial antigen. Those sera from persons with microfilaraemia that showed the presence of circulating antigen also showed an apparent positive correlation between the microfilarial density and the antigen titre.

Antigens, Helminth↗

Filariasis: nutritional interactions in human and animal hosts.

Vector-borne nematodes of the Order Filarioidea produce chronic, debilitating human infections which are usually nonfatal but are associated with a high degree of severe morbidity. Weight loss often accompanies infection and is probably a consequence of the increased energy cost associated with filarial fever, lymphangitis and lymphadenitis. In onchocerciasis, weight loss is associated with heavy worm loads as assessed by abundant nodules and large numbers of skin microfilariae. Experimental infections using rodent filariae have confirmed these observations and have also shown that low protein diets render hosts more susceptible to infection; nevertheless, parasite growth and embryogenesis is retarded in stunted female worms from protein deficient animals. In the absence of appropriate evidence, studies of experimental filariasis suggest that human protein-energy malnutrition may delay the development of stage-specific acquired immunity with a corresponding prolongation of patency. Epidemiological and experimental evidence shows that filarial nematodes acquire certain nutrients directly from their hosts. Of major importance in this respect is vitamin A which is taken up preferentially by human and rodent filariae; in humans, symptoms of hypovitaminosis A often accompany infection and could be an aggravating factor in onchocerciasis. Filariae also appear to require other specific nutrients such as iodine, thiamine and pyridoxine; dietary levels of these nutrients affect the host-parasite relationships in filariasis and pyridoxine seems to be of particular importance in this respect. Filarial parasites obviously compete with their hosts for available nutrients and, in the real world, human filariasis is often associated with a deterioration in the plane of nutrition of infected individuals.

Adult↗

Bancroftian filariasis: a 13-year follow-up study of asymptomatic microfilariae carriers and endemic normals in Orissa, India.

The natural history of human filarial infections leading to development of disease has been a subject of intense debate. The models proposed so far have largely been based on cross-sectional data on microfilariae (Mf) and disease prevalence in filariasis endemic areas. In an attempt to study the parasitological and clinical consequences of filarial infection in Beldal (Orissa, India), an area endemic for Bancroftian filariasis, cohorts of 59 asymptomatic Mf carriers (AS) and 187 asymptomatic and amicrofilaraemic subjects or 'endemic normals' ('EN'), were followed-up and a fraction (73% and 46% respectively) re-examined after 13 years to monitor (a) Mf prevalence, (b) Mf density, (c) circulating filarial antigen (CFA) and (d) chronic disease manifestations. The Mf prevalence and density were also monitored in Mf carriers after 1 and 4 years. Both Mf prevalence and density decreased progressively in the cohort of Mf carriers over a period of 13 years in Beldal. Only 37% of them continued to be microfilaraemic and the Mf density in these subjects was only 10% of the original level. However, loss of circulating Mf in this cohort did not result in loss of CFA and 95% remained CFA positive regardless of Mf status. About 23% of males in the 'EN' cohort developed hydrocoele while only 5.7% of male Mf carriers, who were not treated with DEC, had developed hydrocoele after 13 years. A cohort of Mf carriers in another area, Jatni, was also examined after 10 years to study the parasitological and clinical outcome. In this area, about 59% of the Mf carriers continued to be microfilaraemic after 10 years. These results reveal that in Mf carriers adult filarial worms persist for several years and that loss of circulating Mf with or without chemotherapy with DEC (single 12-day course) does not influence adult worm survival. The findings have been discussed in the context of 'static' and 'dynamic' models describing the relationship between infection and disease in human filariasis.

Adolescent↗

Transmission of the nocturnal periodic strain of Wuchereria bancrofti by Culex quinquefasciatus: establishing the potential for urban filariasis in Thailand.

Control programmes have reduced the prevalence of Bancroftian filariasis in Thailand to low levels. Recently, there has been an influx of more than one million Myanmar immigrants into urban centres of Thailand. The prevalence of patent Wuchereria bancrofti infection in these immigrants (2-5%) has prompted concern in the public health community that the potential now exists for a re-emergence of Bancroftian filariasis in Thailand. It is possible that an urban cycle of transmission could become established. The Myanmar immigrants are infected with the nocturnal periodic (urban) type W. bancrofti for which Culex quinquefasciatus serves as the main vector. The Thai strains of Cx. quinquefasciatus have never been reported to transmit Bancroftian filariasis. Our results of feeding experiments demonstrated that the Thai Cx. quinquefasciatus are permissive for the development of Myanmar W. bancrofti to infective third-stage larvae thus establishing the potential for establishing an urban cycle of transmission in Thailand. We also adapted the SspI repeat PCR assay for the identification of infective mosquitoes that was capable of detecting a single infective stage larvae in a pool of 100 mosquitoes.

Adolescent↗

Protective immunity in human Bancroftian filariasis: inverse relationship between antibodies to microfilarial sheath and circulating filarial antigens.

The existence and the nature of protective immunity in human filariasis continues to be a subject of intense debate. While there is no broad consensus on functional immunity against larval and adult stage parasites, anti-microfilarial immunity has been demonstrated to be mediated by antibodies to the microfilarial sheath. In the present study, circulating filarial antigens (CFA), a marker of active filarial infection in human Bancroftian filariasis, was found to be inversely associated with antibodies to microfilarial sheath in a cohort of 411 subjects representing all categories of filariasis across the clinical spectrum of the disease. Approximately 80% of humans of all age groups (5-65 years) were found to have either CFA or anti-sheath antibodies. The inverse relationship observed between these two parameters was found to be independent of the clinical manifestation; both symptomatic and asymptomatic cases were found to display similar inverse association between CFA and anti-sheath antibodies. The prevalence of anti-sheath antibodies in the paediatric group was found to be very high as compared to adults; 78% of children below the age of 10 years tested positive for anti-sheath antibodies although the mf rate and CFA rate were only 4.5% and 22.7%, respectively, in this age group, indicating that developing larvae or juvenile adult stage parasites could have been the source of antigenic stimulus for induction of antibodies to the microfilarial sheath.

Adolescent↗

[Role of Culex quinquefasciatus in the transmission of bancroftian filariasis in the Federal Islamic Republic of Comoros (Indian Ocean)].

In October 1988-January 1989, as a part of a malaria and filariasis control programme in Federal Islamic Republic of Comoros an entomological survey was carried out in 19 rural and urban localities of Grande Comore. Anjouan and Moheli Islands. The potential breeding places were examined and pyrethrum spray catches were made to evaluate the indoor resting densities of mosquitos. A total of 14.578 adult mosquitos potential vectors of filariasis was collected: 94.5% Culex quinquefasciatus, 3.5% Anopheles gambiae s. str. 1.9% A. funestus and 0.1% other anopheline species. A. funestus, uniformly spread in Moheli, was present only in the south-west coast of Anjouan and absent in Grande Comore. A. gambiae and Cx quinquefasciatus were present in Grande Comore. A. gambiae and Cx quinquefasciatus were present in the three islands with different densities in the villages. Only Cx quinquefasciatus specimens la maximum of 150 for each locality) were dissected to search filaria larvae being the Anopheles specimens used to evaluate the malaria transmission. The global infection rate (9.4%) and the infectivity rate (0.9%) observed in Cx quinquefasciatus are higher than indices reported in previous surveys. All the larvae in the third development instar (L3) were identified as Wuchereria bancrofti. The results suggest that in FIR of Comoros W. bancrofti is well adopted to local Cx quinquefasciatus population. Because of the presence of high mosquito density this species plays a prominent role in the transmission of lymphatic filariasis in that area. The high transmission levels calls for the implementation of a specific control program.

Animals↗

A controlled trial of ivermectin and diethylcarbamazine in lymphatic filariasis.

Ivermectin is a new antifilarial drug that can be given in a single oral dose. To compare the efficacy and side effects of ivermectin with those of diethylcarbamazine, the standard antifilarial treatment, we conducted a randomized, double-blind trial in 40 South Indian men with lymphatic filariasis caused by Wuchereria bancrofti. Patients were randomly assigned to one of three treatments: a single low dose of ivermectin (mean [+/- SE], 21.3 +/- 0.7 micrograms per kilogram of body weight; n = 13) followed by placebo for 12 days; a single high dose of ivermectin (mean, 126.2 +/- 3.7 micrograms per kilogram; n = 13) followed by placebo for 12 days; or diethylcarbamazine for 13 days (6 mg per kilogram per day for 12 days preceded by 3 mg per kilogram for 1 day; n = 14). Eleven patients were initially assigned to receive placebo and after five days were reassigned to one of the three treatment groups. At day 12 there was complete clearance of microfilariae from the blood in all 26 men who took ivermectin and in 11 of the 14 men who took diethylcarbamazine. At six months the numbers of detectable microfilariae (as a percentage of the pretreatment values) were 18.3 percent after low-dose ivermectin and 19.5 percent after high-dose ivermectin, as compared with 6.0 percent after diethylcarbamazine (P less than 0.05). The side effects were confined to the first five days and were similar in the three treatment groups. We conclude that in lymphatic filariasis, the clinical response to a single dose of ivermectin compares favorably with that after the standard 12-day course of diethylcarbamazine. Given the practical advantages of single-dose administration, ivermectin should become a useful medication for the control of bancroftian filariasis.

Adult↗

Studies on filariasis transmission in Kwale, a Tanzanian coastal village, and the results of mosquito control measures.

The main vectors of bancroftian filariasis in Kwale, Tanzania, were Anopheles gambiae complex and Culex p. quinquefasciatus. After vector control by the insecticides Dursban (chlorpyrifos) or Abate (temephos), the number of all man-biting mosquitoes was reduced by 94.8%, and that of house-resting mosquitoes by 95.3%. Anopheles gambiae complex were highly exophilic, possibly due to a high proportion of Anopheles merus in this village. The infection rate of A. gambiae complex rose significantly in the post-control samples (P less than 0.05), but nevertheless the overall reduction in filariasis transmission was 87.2%. The infection rate of A. gambiae complex caught off human bait was significantly higher than that of the spray-caught sample (P less than 0.05). It was suggested that the former sample contained a higher proportion of A. merus. This species may be a better vector of filariasis than freshwater forms.

Animals↗

Bancroftian filariasis in Kwale District of Kenya. III. Quantification of the IgE response in selected individuals from an endemic community.

One hundred and sixty-two individuals from a community in Kwale District, Kenya, endemic for bancroftian filariasis, were selected for a study on the IgE response to filarial antigen (prepared from adult Brugia pahangi). Following clinical and parasitological examination, the individuals were grouped into different categories, based on the presence/absence of microfilaraemia, the presence/absence of acute or chronic (hydrocele or elephantiasis) clinical manifestations, and age. The total and filarial-specific IgE responses were evaluated in all individuals, and the responses in the various categories were compared with each other and with the responses of control groups of individuals from filariasis-free areas. The majority of individuals from the endemic area had highly elevated serum concentrations of total IgE. Overall and within each clinical category, the concentration of total IgE was higher in those individuals from the endemic area who had microfilaraemias than in those that did not. The majority of individuals from the filariasis endemic area also had significantly elevated levels of filarial-specific IgE. In contrast, the concentration of specific IgE was lower in subjects with microfilariae than in those without, irrespective of their clinical status. Only a small proportion of total IgE was filarial-specific, the mean value varying from 0.4% to 9.8%, depending on category. Among the endemic individuals, the mean proportion of total IgE which was filarial-specific was 3.6 times higher in the microfilaria-negative than in the microfilaria-positive, indicating that much of the filarial-induced IgE in microfilaraemic individuals could be non-specific. No clear relationship was observed between the IgE response and the clinical manifestations or age of the endemic individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Lymphatic filariasis in man: demonstration of circulating antigens in Wuchereria bancrofti infection.

Five hundred and twenty-nine sera obtained from people dwelling in an area endemic for bancroftian filariasis were analysed for the presence of soluble circulating antigens (SCA) of filarial origin by counter immunoelectrophoresis and 303 were found positive. It, therefore, appears that 57.3% subjects could be diagnosed by the detection of SCA irrespective of their clinical status. Of the three groups investigated, microfilaraemic, amicrofilaraemic and clinical, SCA could be demonstrated in maximum number of sera obtained from clinical cases. The parasite specificity of the SCA was determined by enzyme linked immunosorbent assay (ELISA), immunofluorescent antibody test (IFAT), counter immunoelectrophoresis (CIEP) and gel diffusion (GD) using antisera raised against Litomosoides carinii in rabbits and antigens derived from Wuchereria bancrofti microfilariae or antigens present in sera of patients with bancroftian filariasis. This anti-carinii hyperimmune serum under study did not show positive reactions with parasites other than filaria, or with the sera obtained from pre-immunized rabbits and non-endemic controls. A demonstration of a distinct precipitin band in CIEP and GD indicates that either monospecific hyperimmune sera or monoclonal antibodies could be raised for the development of a simple method for immunodiagnosis of bancroftian filariasis.

Antigens↗

Differential recognition of microfilarial antigens by sera from immigrants into an area endemic for brugian filariasis.

Studies in animal models indicate that antibodies to surface antigens of microfilariae participate in the control of parasitaemia resulting from infections with lymphatic filarial nematodes. In an attempt to identify parasite antigens that elicit such 'protective' host responses, we compared the antigen recognition patterns of persons who remained amicrofilaraemic after 3-6 years of exposure to Brugia malayi with those of individuals who developed patent filariasis during the same period. IgG antibodies in sera from immigrants identified between 0 and 25 microfilarial antigens on Western blots. The highest degree of reactivity was observed with antigens in the 65-75 kD and 20-30 kD ranges, and with a group of high mol. wt antigens (greater than 180 kD). Sera from amicrofilaraemic donors preferentially reacted with 70/75 kD microfilarial antigens. A proportion of such sera inhibited the binding of monoclonal antibody MF1 to its target epitope; eight of nine inhibitory sera were from patients with active infections, evidenced by the presence of microfilariae or filarial antigens in the donors' blood, but who were amicrofilaraemic. These results indicate that some amicrofilaraemic residents of areas where brugian filariasis is endemic develop immune reactions to a microfilarial stage-specific antigen that was previously identified as a potentially 'protective' parasite antigen in animal models of lymphatic filariasis.

Adult↗

"Primary" pulmonary hypertension, eosinophilia, and filariasis in Ceylon.

;Primary' pulmonary hypertension, which is rare in western countries, was found to be relatively common in Ceylon. The clinical and haemodynamic features were studied. There were two distinct types of the disease, malignant and benign. Patients with the malignant form of the disease had a rapidly progressive illness of short duration and an invariably fatal outcome. Those with the benign form gave a long history and, in spite of severe pulmonary hypertension, were only slightly disabled. They seemed to tolerate the disease better. An important factor which determined the clinical course of the disease was the patency of the foramen ovale. This appeared to act as a safety valve permitting a right-to-left shunt in times of stress. The foramen ovale was closed in all patients with the malignant type. The therapeutic implications of this need further study. Many patients with ;primary' pulmonary hypertension had an unusually high eosinophil count (normal range for Ceylon, 0-500 per cu.mm.). Patients in hospitals often have higher counts ranging from 0-1000 per cu.mm. due to intestinal parasitic infestation. Patients with ;primary' pulmonary hypertension were found to have a significantly higher mean eosinophil count than age-matched, sex-matched controls admitted to the Cardiology Unit with chronic rheumatic heart disease and congenital heart disease. The higher count was not due to intestinal parasitic infestation, and none of the other known causes of a raised eosinophil count were present. Four patients had eosinophil counts over 3,000 per cu.mm., the range commonly associated with tropical pulmonary eosinophilia, a disease caused by filariasis. These patients did not manifest any of the symptoms of tropical pulmonary eosinophilia. Patients with ;primary' pulmonary hypertension were examined for evidence of filariasis (clinical, haematological, and serological). Volunteers from among patients with tropical pulmonary eosinophilia and symptom-free patients positive for Wuchereria bancrofti microfilaria were similarly tested and also catheterized for evidence of pulmonary hypertension. The results of these investigations and their significance are discussed. The geographical incidence of ;primary' pulmonary hypertension and filariasis was similar. Filarial worms are known to cause pulmonary hypertension in animals. There is sufficient evidence to suspect that the same may be true in humans. This may explain the high incidence of the disease in Ceylon and its unusually high prevalence among men.

Adolescent↗

Filariasis of the ankle: magnetic resonance imaging.

Filariasis is a world health problem that is frequently seen in tropical and subtropical countries. In endemic areas, the clinical spectrum of extremity swelling, lymphangitis, or elephantiasis is usually recognized as filariasis. In the United States, diagnosis of the disease may be more difficult because of lack of familiarity with this infection. We present a case of filaremic arthropathy of the ankle joint and the magnetic resonance imaging (MRI) findings of this disease. It is the first reported case of MRI findings in a human patient. MRI has been done on animal models with filariasis, and the findings are similar.

Adult↗