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To investigate the hypothesis that T cells recognizing specific Ags localize to the site of disease activity in human bancroftian filariasis, we have compared the repertoire of TCR Vbeta gene segments in lesions vs blood in individual patients by RT-PCR ELISA. Vbeta14 and Vbeta24 were overrepresented (5% greater in tissue compared with PBMCs and/or tissue/PBMC ratios in the highest 5% of all tissue/PBMC ratios for all Vbetas for all subjects) in 50% and 40% of study subjects, respectively. Overrepresentation of these two Vbetas did not occur in any control subject. In comparing three patient groups, the proportion of individuals meeting at least one criterion for Vbeta14 overrepresentation was shown to increase in tandem with our current concepts of disease progression (asymptomatic filariasis = 25%; clinical filariasis with active infection = 60%; clinical filariasis without active infection = 71%). In 6 of the 10 individuals with Vbeta14 overrepresentation, Vbeta14 represented >20% of the entire lesional Vbeta repertoire. All but one of the 20 study subjects had at least one Vbeta gene segment that was overrepresented in tissue compared with PBMCs. Only a small number of Vbetas, usually three or less, were overrepresented in any single filariasis patient. However, in the same tissue, no differences between patient groups were found when IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-12 mRNA expression were examined. Taken together, these findings suggest that, in principle, in essentially all patients, whether with subclinical or with clinical filariasis, distinct and limited T cell populations are concentrated in affected tissue.

Individuals with clinical manifestations of lymphatic filariasis may be currently infected or not. Twenty-five individuals from a Wuchereria bancrofti-endemic area of Brazil were classified as being asymptomatic microfilaremic individuals, antigenemic individuals with clinical filariasis, or nonantigenemic individuals with clinical filariasis. Intracellular cytokine staining of mitogen-stimulated peripheral blood mononuclear cells (PBMC) showed that the frequency of either gamma interferon (IFN-gamma)- or interleukin-4 (IL-4)-producing cells was higher in the nonantigenemic individuals with clinical filariasis than in the asymptomatic microfilaremic individuals (geometric means, 22.1 versus 10.7% [P = 0.02] and 2.9 versus 1.4% [P = 0.01], respectively). When the asymptomatic microfilaremic individuals and antigenemic individuals with clinical filariasis were grouped together to constitute all actively infected individuals, the frequency of IFN-gamma-producing cells was also lower than in the nonantigenemic individuals with clinical filariasis (P = 0.04). Likewise, the frequency of IL-4-producing cells in the actively infected individuals was also lower than in the nonantigenemic individuals with clinical filariasis (P = 0.02). No differences in the frequency of IFN-gamma-, IL-4-, or IL-5-producing cells in purified CD4 T lymphocytes were found among the groups. These findings suggest that the presence of antigenemia, which is an indicator of current active infection, is closely associated with the frequency of IFN-gamma- and IL-4-producing cells in lymphatic filariasis. The differences found in the frequency of cytokine-producing cells among the three groups appear to be due to a subset of cells other than CD4 T cells.

The in vitro transendothelial migration of circulating filarial antigen-specific T-cells was examined in Wuchereria banerofti infection. Circulating T-cells from individuals with filaria-induced lymphatic pathology (LP) had significantly greater migration through unstimulated HUVEC monolayers than did T-cells from asymptomatic infected (MF) individuals (P = 0.04). In contrast to the MF individuals where no effect was seen, transendothelial migration of 48-hr filarial antigen stimulated T-cells from LP individuals was significantly (P = 0.01) greater than migration of 48-hr media-stimulated T-cells. In six of seven patients examined, inhibition of the VLA-4/VCAM-1 pathway resulted in greater than 50% inhibition of transendothelial migration of T-cells.

Twenty-eight Brazilians from an area in which Wuchereria bancrofti is endemic were classified as asymptomatic microfilaremic or having clinical filariasis with active infection or without current active infection. Total accumulation of antigen-specific interleukin (IL)-4 and IL-5 in 48 h peripheral blood mononuclear cell supernatants was not significantly different between groups. However, when cytokine kinetics were examined, responses segregated according to infection status. Sustained production of IL-4 and IL-5 beyond the first 24 h of stimulation and production of interferon-gamma were seen only in the group with clinical filariasis without active infection. CD8 T cells were the major source of IL-5 production in this group, while CD8 production of IL-5 was undetectable in any subject with active infection (asymptomatic microfilaremic or with clinical filariasis and active infection). These findings indicate that active infection, rather than clinical status, is most closely associated with cytokine patterns in lymphatic filariasis.

Bancroftian filariasis is a major public health problem in the city of Recife in north-eastern Brazil. In some of its urban areas microfilaraemia prevalence reaches 14%. This study describes epidemiological characteristics, infection and disease, in 2 urban areas, Coque and Mustardinha, before control measures were applied. The parasitological survey was performed by a 'door-to-door' census covering 5563 subjects, aged between 5 and 65 years. Microfilaraemia was detected by the thick drop technique, using 45 microL of peripheral blood collected between 20:00 and 24:00. In both areas the prevalence of microfilaraemia was 10%, and males had higher prevalences of infection and disease than females. The prevalence of microfilaraemia was higher in the 15-24 and 25-34 years age groups in both sexes. Most microfilaria (mf) carriers (72.1% in Coque and 79.7% in Mustadrinha) had mf densities < 100/60 microL of blood. Females of reproductive age had significantly lower mf densities than males. The overall disease prevalence in both areas was 6.3%. Amongst the subjects who presented with chronic disease 15.7% were microfilaraemic. Chronic disease prevalence increased from 1.4% in the 5-14 years age group to 11.3% in the oldest age group. The most frequent clinical manifestation was hydrocele (5.4%), followed by lymphoedema (1.8%). The epidemiological pattern of filariasis in the populations studied was marked by high prevalence of microfilaraemia, low mf density, and relatively low prevalence of filarial disease considering the level of endemicity.

Bancroftian filariasis is spreading in towns of endemic areas in Recife, northeastern Brazil, where it is a major public health problem. This paper deals with the prevalence of microfilaraemia and filarial disease in two urban areas of Recife, studying their association with individual characteristics and variables related to the exposure to the vectors. The parasitologic survey was performed through a "door-to-door" census and microfilaraemia was examined by the thick-drop technique using 45 microliters of peripheral blood collected between 20:00 and 24:00 o'clock. 2,863 individuals aged between 5 and 65 years were interviewed and submitted to clinical examination. Males aged between 15 and 44 years old presented the greatest risk of being microfilaraemic. Microfilaraemia was also significantly associated with no use of bednet to sleep. The risk of being microfilaraemic was greater among those who had lived in the studied areas for more than 5 years. The overall disease prevalence was 6.3%. Males presented the greatest risk of developing acute disease. The risk of developing chronic manifestations was also greater among males and increased with age. We found no association between time of residence, bednet use, microfilaraemia and acute and chronic disease. We may conclude that in endemic areas there are subgroups of individuals who has a higher risk of being microfilariae carriers due to different behaviours in relation to vector contact.

Despite the common association of filarial infection with elephantiasis, the great majority of those infected are in fact clinically asymptomatic microfilariae carriers. The assumption has been that infection but not disease exists in these presymptomatic persons. In an area Brazil where Wuchereria bancrofti is endemic, flow studies done with dynamic radionuclide lymphoscintigraphy were used to compare 30 limbs from asymptomatic microfilaremic subjects with 16 control limbs. Geometric mean values for T1/2 (19.8 vs. 37.7 min; P < .001), appearance time (7.9 vs. 27.9 min; P < .001), percent uptake at the region of interest (0.67% vs. 0.14%; P < .001), and peak activity (62.6 vs. 2.6 cps; P < .001) each indicated an enhanced pattern of rapid, increased lymph flow in asymptomatic microfilaremic subjects. The abnormal lymphatic function in these subjects indicates that current passive intervention strategies may need to change if the debilitating sequelae of this parasitic infection are to be avoided.

Despite many millions of doses administered over the past 40 years, basic and crucial issues regarding the use, mode of action, and effectiveness of diethylcarbamazine (DEC) in many clinical situations remain unresolved. To directly investigate whether the well-known microfilaricidal and macrofilaricidal actions of DEC actually result in subsequent improvement in existing damage to lymphatic vessels or lymph nodes, 29 study subjects in Recife, Brazil were stratified into three groups according to the severity of clinical manifestations of lymphatic insufficiency. After baseline radionuclide lymphoscintigraphy was performed, subjects were treated with two courses of DEC separated by at least a six-month interval and then rescanned one year after the baseline scan. A side-by-side comparison of images obtained at baseline with those obtained at follow-up in 13 asymptomatic microfilaremic individuals, six individuals with filarial fever, and in 10 individuals with chronic pathology demonstrated essentially unchanged lymphatic morphology in all but one individual whose disease actually progressed in the face of therapy. We conclude that two 12-day treatment courses of DEC did not have a demonstrable direct or indirect effect on existing structural damage to the lymphatic system even in those individuals with preclinical disease.

To obtain high-resolution radionuclide lymphoscintigraphic images of affected limbs in persons with both symptomatic and asymptomatic filarial infection, 36 volunteers were recruited from a Wuchereria bancrofti-endemic area of Recife, Brazil, for a prospective, controlled analysis. Subjects were stratified after determination of serologic and clinical determinants of filarial infection status. Widespread lymphatic abnormalities were found in clinically asymptomatic microfilaremic persons, who had been assumed to have infection but not disease. All patients with clinical manifestations of lymphatic pathology and marked abnormalities. No correlation was found between clinical findings and actual lymphatic function as demonstrated by lymphoscintigraphy. The initial diagnosis of lymphatic filariasis, whether asymptomatic or symptomatic, is based on nonimaging laboratory criteria. After diagnosis, lymphoscintigraphy is a valuable tool for initial assessment of any lymphatic damage. Changes in strategies for therapeutic interventions in asymptomatic microfilaremic persons, who are not usually aggressively treated, may be warranted.