Cellular immune response of Mastomys and gerbils in experimental filariasis

Summary
objective  To determine mitogenic and antigen-specific cellular immune responses of two species of rodents, viz . Meriones unguiculatus and Mastomys coucha to assess the usefulness of the A. viteae/Mastomys model for cellular immune studies in experimental filariasis.
methods  Lymphocyte blast transformation test (LTT) using spleen cells of normal and A. viteae infected animals.
results  The proliferative response of gerbils was much higher than that of Mastomys to both ConA and filarial antigens. Cells of both species of rodents did not respond to microfilarial (mf) antigen, however, their mitogenic response differed during infection. Some degree of nonspecific suppression was observed in gerbils during prepatent and patent stages of infection, while Mastomys revealed highest proliferation during patent microfilaraemia. Mastomys cells did not respond to adult or mf antigen,while adult-specific proliferation was detected in the case of gerbils.
conclusion  The A. viteae /gerbil model shows more similarity to human filarial infection regarding cellular immune response. Markedly low responsiveness of a high percentage of Mastomys and wide variations in the cellular response to nonspecific mitogen limit the usefulness of Mastomys coucha in immunological studies, especially cellular immunity.     

Serum immunoglobulin levels in Indonesians with bancroftian filariasis.

Serum immunoglobulin (Ig) levels (IgA, IgM, IgG, IgE) were determined on 185 Indonesians mostly males with and without microfilaremia and with and without clinical disease (hydrocele and elphantiasis). No significant differences were found in IgA and IgE levels in any of the groups but significantly higher IgG levels were found in microfilariae positive persons than those without microfilaremia. Persons with microfilariae alone and symptoms alone, but not both, had higher levels of IgM. There were no correlations between disease category and Ig levels.     

Serological diagnosis of bancroftian and malayan filariasis.

A study was undertaken to define the sensitivity and specificity of serological tests in bancroftian and malayan filariasis and correlate the findings with clinical disease. Sera were collected from subjects on three different islands in the Philippines: one endemic for bancroftian filariasis, another endemic for malayan filariasis and the third without endemic filariasis. Antibodies were measured, using rugia malayi as the source of antigen. Antibodies against adult worms measured by indirect immunofluorescence were found at a titer of 1:8 or greater in all patients with bancroftian or malayan filariasis but not in the control subjects. There was no relationship of antibody titer to clinical status. Antibodies against microfilariae were measured by indirect immunofluorescence and microfilarial agglutination. A high correlation was observed between the two methods. These antibodies were found in only one quarter, approximately, of patients with filariasis. Microfilarial antibodies were found more commonly in those patients with chronic lymphatic obstruction. It is concluded that measurement of antibodies to adult worms is a useful indicator of infection while microfilarial antibodies are correlated with disease.     

Detection of circulating parasite antigen in bancroftian filariasis by counterimmunoelectrophoresis

We used counterimmunoelectrophoresis (CIEP) with rabbit antibodies to Dirofilaria immitis and Brugia malayi to detect soluble filarial antigen in sera collected in a Wuchereria bancrofti-endemic area in South India. Filarial antigen was detected in 38 of 38 sera from microfilaremic patients, 3 of 48 sera from amicrofilaremic patients with lymphatic pathology, and 3 of 5 sera from former microfilaria carriers with negative blood examinations 6 months or more after diethylcarbamazine therapy. One of 32 endemic control sera, 0 of 35 nonendemic sera, and 0 of 20 B. malayi sera were positive. Antigenemia was equally detectable in sera collected at night or during the day (when microfilariae are absent from the blood). Parasite antigen was also detected in the urine of patients with positive serum tests. Antibodies to circulating filarial antigen (also detected by CIEP) were absent in all but 2 antigen-positive sera but present in 22 of 45 antigen-negative sera from clinical filariasis patients and in 9 of 31 antigen-negative sera from endemic controls. Parasite antigen detection by CIEP appears to be a sensitive, specific, and practical diagnostic test for active W. bancrofti infection.     

Tanzania filariasis project. Survey methodology and clinical manifestations of bancroftian filariasis.

In a Bancroftian filariasis survey on the coast of Tanzania microfilaria rates rose with age reaching 53% in the 60-69 year group followed by a slight fall above this age. The most important clinical manifestations were hydrocoele, funiculitis and elephantiasis, with hydrocoele presenting the most serious public health problem. Hydrocoele rates increased with age reaching 90% above the age of 70. The highest proportion of large hydrocoeles were also in the older age groups. A satisfactory methodology was established for the planning of future surveys leading to control.     

Transmission of bancroftian filariasis in tea agro-ecosystem of Assam, India

Tea industry is a labor intensive agro-industry and filariasis is mostly localized among the tea garden workers in Assam. The workers live inside the gardens in colonies. Studies conducted in two cosecutive years revealed that among the host seeking Culex quinquefasciatus average infection rate was 4.6% and with 2.1 larvae per mosquito. The overall prevalence of infective mosquitos was 0.8% with average L3 load of 2.0 per mosquito. The probability of infected mosquitos surviving to have complete development of filarial larvae (13 days) was 0.17. The expectation of infective life was 1.416 days for man biting Cx. quinquefasciatus and the estimated adult survival rate of was 87.6%. It has been estimated that a total of 22,569 mosquito bites were received/man/year in tea garden environment out of which 182 bites/man/year were infective (0.806%). The monthly biting rate varied from 310-4,758.5 bites per man (mean 1,846 +/- 1,389.7 SD). Monthly transmission index of W. bancrofti filaria showed two periods of transmission. In both the year no infection was detected during February and March and infection rate remained low up to May (average infection in April 0.72% and in May 0.48%).     

The disappearance of bancroftian filariasis from Charleston, South Carolina

I suggest the hypothesis that bancroftian filariasis, endemic since the early days of slavery in Charleston, South Carolina, disappeared around 1930 by virtue of the long-term effects of a municipal sewerage-water system begun in the 1890s or thereabouts. These public works, originally intended to abate typhoid and related diseases, helped to eliminate filariasis by reducing the availability of polluted domestic waters which are the preferred breeding sites for the urban vector, Culex quinquefasciatus (= fatigans). Cause and effect having been separated by some three decades, the epidemiologic connections between these events in Charleston seem not to have been appreciated hitherto.     

Persistence of parasite antigenemia following diethylcarbamazine therapy of bancroftian filariasis

This study was designed to reexamine the efficacy of diethylcarbamazine for bancroftian filariasis with special reference to changes in serum parasite antigen levels and antifilarial antibody titers after treatment. Patients with asymptomatic microfilaremia were treated with 6 mg/kg diethylcarbamazine daily for 12 days. Microfilaria counts fell dramatically after treatment, as expected. IgG antibody titers to adult and microfilarial antigens of B. malayi were increased 1 month after treatment in most patients. Titers fell slowly to or below pretreatment levels, but remained positive during subsequent months. Parasite antigen levels, measured by monoclonal antibody-based enzyme immunoassay, decreased to 72%, 58%, 53%, and 48% of pretreatment values 1, 3, 6, and 12 months after diethylcarbamazine treatment, respectively. Parasite antigen levels decreased similarly in subjects with and without residual microfilaremia after treatment. These results suggest that diethylcarbamazine has only partial macrofilaricidal activity against W. bancrofti with this dosage schedule. The sustained, impressive reductions in microfilaria counts after treatment despite significant persistence of parasite antigenemia may be explained by sublethal effects of the drug on adult worms. We believe that parasite antigen detection represents a valuable new approach for monitoring the efficacy of antifilarial drug therapy which we hope will lead to improved use of existing drugs and aid in the evaluation of new drugs for filariasis.     

Transmission intensity and the immunoepidemiology of bancroftian filariasis in East Africa

Previous attempts to determine the interactions between filariasis transmission intensity, infection and chronic disease have been limited by a lack of a theoretical framework that allows the explicit examination of mechanisms that may link these variables at the community level. Here, we show how deterministic mathematical models, in conjunction with analyses of standardized field data from communities with varying parasite transmission intensities, can provide a particularly powerful framework for investigating this topic. These models were based on adult worm population dynamics, worm initiated chronic disease and two major forms of acquired immunity (larval- versus adult-worm generated) explicitly linked to community transmission intensity as measured by the Annual Transmission Potential (ATP). They were then fitted to data from low, moderate and moderately high transmission communities from East Africa to determine the mechanistic relationships between transmission, infection and observed filarial morbidity. The results indicate a profound effect of transmission intensity on patent infection and chronic disease, and on the generation and impact of immunity on these variables. For infection, the analysis indicates that in areas of higher parasite transmission, community-specific microfilarial rates may increase proportionately with transmission intensity until moderated by the generation of herd immunity. This supports recent suggestions that acquired immunity in filariasis is transmission driven and may be significant only in areas of high transmission. In East Africa, this transmission threshold is likely to be higher than an ATP of at least 100. A new finding from the analysis of the disease data is that per capita worm pathogenicity could increase with transmission intensity such that the prevalences of both hydrocele and lymphoedema, even without immunopathological involvement, may increase disproportionately with transmission intensity. For lymphoedema, this rise may be further accelerated with the onset of immunopathology. An intriguing finding is that there may be at least two types of immunity operating in filariasis: one implicated in anti-infection immunity and generated by past experience of adult worms, the other involved in immune-mediated pathology and based on cumulative experience of infective larvae. If confirmed, these findings have important implications for the new global initiative to achieve control of this disease.     

应用快速免疫色谱测试卡监测班氏丝虫病防治远期效果

我省永嘉县、温岭县和玉环县为单一班氏丝虫病流行县。经过 40多年的防治 ,已于 1988年先后达到卫生部颁布的基本消灭丝虫病标准。刘思成等[1] 报道 ,采用传统的厚血膜法诊断丝虫病 ,低密度微丝蚴极易遗漏。我省在达到基本消灭丝虫病标准后 ,残存的传染源绝大多数为低密度微丝蚴血症者。快速免疫色谱测试卡 (ＩＣＴ卡 ) ,是ＷＨＯ/ＴＤＲ推荐的免疫色谱诊断技术。郑惠君等[2 ] 报道 ,ＩＣＴ卡用于班氏丝虫病的诊断、疗效考核及丝虫病防治后期监测具有快速、简便、敏感性高和特异性强的优点。为评价我省 3个单一班氏丝虫病流行县的丝虫病防治…     

Non-involvement of nulliparous females in the transmission of bancroftian filariasis.

The possible involvement of nulliparous females of Culex quinquefasciatus in the transmission of bancroftian filariasis under field conditions was examined in Pondicherry, South India. Biting nulliparous females that had previously ingested partial blood meals were found infected with microfilariae/L1 stage larvae. None of them harboured infective-stage larvae. These findings suggest that nulliparous females are not involved in the transmission of filariasis. Therefore, their inclusion for estimating the transmission parameters is questionable. However, nulliparous females should also be dissected in order to determine the vector infection rates accurately. Infective larvae were encountered in females of all other age groups.     

Epidemiology of bancroftian filariasis in a semi-urban community of Kerala State

A community-based longitudinal study was initiated in 1983 in a semi-urban area, endemic for bancroftian filariasis to determine the incidence and prevalence, natural history and clinical pattern of filarial infection and also to study the impact of control measures on it. The base-line filariometric indices observed during the initial clinico-parasitological survey and entomological observations made during the first 12 months of this study are highlighted in this paper. 5.5 per cent of the examined population had microfilaraemia with average infestation of 8.1 per 20 cmm. The microfilaraemia found to have significant (P less than 0.001) relationship with age, but not with sex (P greater than 0.05). The filarial disease which had the prevalence of 3.6 per cent showed a significant (P less than 0.001) relationship to both age and sex. The youngest microfilaria (mf) carrier was of 2 years and with filarial swelling was of 6 years age. A significant (P less than 0.001) relationship of educational status and family size was observed with disease while it was non-significant (P greater than 0.05) with microfilaraemia. With the increase in per capita income of the individuals, a significant decrease in number of persons with microfilaraemia (P less than 0.01) as well as with disease (P less than 0.05) was noted. Culex quinquifasciatus, the vector for this infection was prevalent throughout the period of observation with highest density in September. Vector infection and infectivity rates ranged from 0 to 4.4 per cent and 0 to 2.2 per cent respectively.     

Surveillance of imported bancroftian filariasis after two-year multiple-dose diethylcarbamazine treatment

Myanmar migrants are at increased risk for nocturnally periodic Wuchereria bancrofti causing imported bancroftian filariasis. They have a significant influence on the effectiveness of diethylcarbamazine (DEC) mass treatment at the provincial level in the National Program to Eliminate Lymphatic Filariasis (PELF) during the fiscal years (FY) 2002-2006, in Thailand. Two oral doses of DEC 6 mg/kg are given twice a year to the eligible Myanmar migrants (> or = 2 years old). A 300 mg DEC provocation test is given once a year to all Myanmar migrants with work permits. Effectiveness evaluation parameters, such as cumulative index (CI) and the effectiveness ratio (ER), were obtained after 2 years of the multiple-dose DEC treatment program in Ranong Province, Southern Thailand. By cross-sectional night blood surveys at the end of FY 2003 in two districts of Ranong Province, the microfilarial positive rates (MPR) were 0.8% and 1.2% for Mueang Ranong and Kra Buri, respectively. The MPR in the agricultural (1.5%) and industrial (0.4%) occupations were not significantly different from each other. Our findings suggest that most untreated microfilaremics working in agriculture, with short-term residency in Thailand, may have delayed multiple-dose DEC treatment.     

Serological evaluation of the macrofilaricidal effects of diethylcarbamazine treatment in bancroftian filariasis

An Mr 200,000 phosphorylcholine-containing antigen (PC-Ag) of predominantly adult worm origin was found in the sera of humans infected with Wuchereria bancrofti. This paper describes results of a longitudinal study of changes in levels of PC-Ag in response to diethylcarbamazine (DEC) therapy as measured by two-site immunoradiometric assay (IRMA) and Western blotting. One hundred thirty-two residents of a bancroftian filariasis-endemic area of Papua New Guinea (PNG) were treated with a 72 mg/kg dose of DEC. A macrofilaricidal effect was seen with this dose of DEC as 34% of the treated subjects had localized side effects and long-term decreases in microfilariae (mf) counts were observed 12 months after treatment. The PC-Ag levels were reduced to 72%, 52%, and 51% of pretreatment values at 21 days and at six and 12 months after treatment. These decreases, observed by IRMA, were specifically associated with loss of the Mr 200,000 PC-Ag detected by immunoadsorption and Western blotting. From drug treatment data, the maximum half-life of PC-Ag in circulation was calculated to be 50 days, assuming a first-order decay process. This maximum half-life indicates that persistent antigenemia observed in the majority of treated subjects could only result from the survival of adult worms. In the absence of methods to directly demonstrate W. bancrofti adult worms, detection of serum PC-Ag levels provides a sensitive indirect measure of the dynamics of adult worm populations. This serological measurement may be useful in optimizing the macrofilaricidal and therapeutic effects of DEC and in assessing the macrofilaricidal action of new antifilarial drugs and immunological interventions.