Inflammatory and regulatory CCL and CXCL chemokine and cytokine cellular responses in patients with patent Mansonella perstans filariasis.

Mansonella perstans (Mp) filariasis is present in large populations in sub-Saharan Africa, and to what extent patent Mp infection modulates the expression of immunity in patients, notably their cellular cytokine and chemokine response profile, remains not well known. We studied the spontaneous and inducible cellular production of chemokines (C-X-C motif) ligand 9 (CXCL9) [monokine induced by interferon (IFN)-γ (MIG)], CXCL-10 [inducible protein (IP)-10], chemokine (C-C motif) ligand 24 (CCL24) (eotaxin-2), CCL22 [macrophage-derived chemokine (MDC)], CCL13 [monocyte chemotactic protein-4 (MCP-4)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], CCL17 [thymus- and activation-regulated chemokine (TARC)] and interleukin (IL)-27 in mansonelliasis patients (Mp-PAT) and mansonelliasis-free controls (CTRL). Freshly isolated peripheral mononuclear blood cells (PBMC) were stimulated with helminth, protozoan and bacterial antigens and mitogen [phytohaemagglutinin (PHA)]. PBMC from Mp-PAT produced spontaneously (without antigen stimulation) significantly higher levels of eotaxin-2, IL-27, IL-8, MCP-4 and MDC than cells from CTRL, while IFN-γ-IP-10 was lower in Mp-PAT. Helminth antigens activated IL-27 and MCP-4 only in CTRL, while Ascaris antigen, Onchocerca antigen, Schistosoma antigen, Entamoeba antigen, Streptococcus antigen, Mycobacteria antigen and PHA stimulated MIG release in CTRL and Mp-PAT. Notably, Entamoeba antigen and PHA strongly depressed (P < 0·0001) eotaxin-2 (CCL24) production in both study groups. Multiple regression analyses disclosed in Mp-PAT and CTRL dissimilar cellular chemokine and cytokine production levels being higher in Mp-PAT for CCL24, IL-27, IL-8, MCP-4, MDC and PARC (for all P < 0·0001), at baseline (P < 0·0001), in response to Entamoeba histolytica strain HM1 antigen (EhAg) (P < 0·0001), Onchocerca volvulus adult worm-derived antigen (OvAg) (P = 0·005), PHA (P < 0·0001) and purified protein derivative (PPD) (P < 0·0001) stimulation. In Mp-PAT with hookworm co-infection, the cellular chemokine production of CXCL10 (IP-10) was diminished. In summary, the chemokine and cytokine responses in Mp-PAT were in general not depressed, PBMC from Mp-PAT produced spontaneously and selectively inducible inflammatory and regulatory chemokines and cytokines at higher levels than CTRL and such diverse and distinctive reactivity supports that patent M. perstans infection will not polarize innate and adaptive cellular immune responsiveness in patients.

CD39 and immune regulation in a chronic helminth infection: The puzzling case of Mansonella ozzardi.

BACKGROUND: Chronic helminth infections typically induce an immunoregulatory environment, with markedly reduced immune responses to both parasite-specific and unrelated bystander antigens. Here we tested whether these changes are also observed in human infections with Mansonella ozzardi, a neglected filarial nematode widely distributed across Latin America. METHODS: CD4+ T cell populations from microfilaremic (Fil+) and uninfected (Fil-) inhabitants in M. ozzardi-endemic riverine communities in Brazil were characterized by flow cytometry analysis. Plasma concentrations of a wide range of cytokines and chemokines were measured. We examined whether M. ozzardi infection is associated with suppressed in vitro lymphoproliferative and inflammatory cytokine responses upon stimulation with filarial antigen, unrelated antigens or mitogens. PRINCIPAL FINDINGS/CONCLUSIONS: Fil+ subjects had lower plasma levels of selected inflammatory cytokines, such as TNF-α, IL-8, and IL-6, than their Fil- counterparts. However, we found no evidence for attenuated T-cell responses to filarial antigens or co-endemic pathogens, such as malaria parasites and Toxoplasma gondii. CD4+ T cells expressing CD39, an ectonucleosidase involved in the generation of the anti-inflammatory molecule adenosine, were increased in frequency in Fil+ subjects, compared to uninfected controls. Significantly, such an expansion was directly proportional to microfilarial loads. Surprisingly, CD39 blocking with a neutralizing antibody suppressed antigen-driven lymphoproliferation in vitro, while decreasing inflammatory cytokine responses, in Fil+ and Fil- individuals. These findings suggest that circulating CD4+ CD39+ T cells comprise subsets with both regulatory and stimulatory roles that contribute to the immune homeostasis in chronic M. ozzardi infection.

Immune response in Mansonella ozzardi infection modulated by IL-6/IL-10 axis in Amazon region of Brazil.

Mansonellosis is an endemic disease in the South and Central America. In Brazil, one of the etiological agents is Mansonella ozzardi. This filarial infection is yet poorly understood, with a controversial morbity, presenting since a oligosymptoms, malaria-like signs or without complaint in humans. The knowledge of the human immune response to microfilariae infection is limited mainly by different evolutionary cycles of the parasite in the host. In addition, the prevalence of this filarial parasite infection is high in several regions of Amazonas State. A cross-sectional study was conducted in an endemic area for microfilariae of M. ozzardi (MF) infection in the Amazonas State, Brazil. Proinflammatory and regulatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-gamma, and IL-17A) were measured in cryopreserved serum using the Cytometric Bead Array techniques (CBA) in 54 patients diagnosed with M. ozzardi infection and 55 individuals without the infection were included in the study (Controls). The IL-4, IL-6 and IL-10 level increased in infected patients with MF infection, while IL-17A increased in control only. When we compared controls to patients with high or low parasite load, the increased level of IL-6 and IL-10 were maintained. IL-6 contributes to the proinflammatory activity and IL-10 modulates Th1, Th2 and Th17 immune response. Furthermore, IL-4 was detected as a marker in the MF infection and MF patients with low parasite load, indicating the action of the Th2 cell response. The complex network of cytokines acting during M. ozzardi infection depends on a fine balance to determine a host protective effect or filarial persistence. Therefore, these results suggest that the immune response in MF infection is modulated by IL-6/IL-10 axis.

Imported Infections with Mansonella perstans Nematodes, Italy.

We report 74 patients in Italy infected with Mansonella perstans nematodes, a poorly described filarial parasite. M. perstans nematodes should be included in the differential diagnosis for patients with eosinophilia from disease-endemic countries. Serologic analysis is useful for screening, and testing for microfilaremia in peripheral blood should be performed for parasite-positive patients.

Influence of Mansonella perstans microfilaraemia on total IgE levels in Gabonese patients co-infected with Loa loa.

Mansonella (M.) perstans filariasis is widely found in Africa, including Gabon where Loa loa is also endemic. This study reports the total IgE titres according to different bioclinical forms of single or co-infection with L. loa and M. perstans in 138 patients and 20 healthy controls. The median parasite density was significantly higher in cases of loiasis. IgE titres were higher in patients with microscopic dual-infection and in the group of patients with occult loiasis plus M. perstans microfilaraemia (8425 [5292-20,679]KUI/L and 6304 [1045-10,326]KUI/L, respectively), compared to individuals with either microfilaraemic Loa loa (3368 [1414-7074]KUI/L) or Mansonella (4370 [1478-7334]KUI/L) single infections (p<0.01). IgE levels were positively correlated with M. perstans microfilaraemia (rho=0.27; p<0.01). Compared to single infections, dual M. perstans-L. loa infection induces very high total IgE titres. Studies correlating IgE titres and clinical symptoms are needed to confirm the involvement of this immunoglobulin in the pathological processes during filariasis.

Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation.

Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively. Maternal Mansonella perstans infection was associated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gamma interferon (IFN-γ), IL-5 and IL-13 responses; other maternal helminth infections showed little effect. Tetanus immunisation during pregnancy was associated with higher infant responses to TT; maternal BCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-γ, IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN-γ, IL-5 and IL-13 responses to both immunogens. We conclude that maternal helminth infections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunisation on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunisation programmes.

Expanded numbers of circulating myeloid dendritic cells in patent human filarial infection reflect lower CCR1 expression.

APC dysfunction has been postulated to mediate some of the parasite-specific T cell unresponsiveness seen in patent filarial infection. We have shown that live microfilariae of Brugia malayi induce caspase-dependent apoptosis in human monocyte-derived dendritic cells (DCs) in vitro. This study addresses whether apoptosis observed in vitro extends to patent filarial infections in humans and is reflected in the number of circulating myeloid DCs (mDCs; CD11c(-)CD123(lo)) in peripheral blood of infected microfilaremic individuals. Utilizing flow cytometry to identify DC subpopulations (mDCs and plasmacytoid DCs [pDCs]) based on expression of CD11c and CD123, we found a significant increase in numbers of circulating mDCs (CD11c(+)CD123(lo)) in filaria-infected individuals compared with uninfected controls from the same filaria-endemic region of Mali. Total numbers of pDCs, monocytes, and lymphocytes did not differ between the two groups. To investigate potential causes of differences in mDC numbers between the two groups, we assessed chemokine receptor expression on mDCs. Our data indicate that filaria-infected individuals had a lower percentage of circulating CCR1(+) mDCs and a higher percentage of circulating CCR5(+) mDCs and pDCs. Finally, live microfilariae of B. malayi were able to downregulate cell-surface expression of CCR1 on monocyte-derived DCs and diminish their calcium flux in response to stimulation by a CCR1 ligand. These findings suggest that microfilaria are capable of altering mDC migration through downregulation of expression of some chemokine receptors and their signaling functions. These observations have major implications for regulation of immune responses to these long-lived parasites.

At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells.

Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4(+) and CD8(+) T cells in filaria-infected (Fil(+)) and -uninfected (Fil(-)) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4(+) lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil(+), as were those of IL-10(+)/IL-4(+) double-producing CD4(+) cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil(+) compared to Fil(-) individuals. Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly produced by CD4(+)CD25(-) cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10-producing aTreg/Tr1s in Fil(+). Together, these data show that at steady state, IL-10-producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level.

Onchocerca volvulus-specific antibody and cytokine responses in onchocerciasis patients after 16 years of repeated ivermectin therapy.

The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 microg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-gamma at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity.

Comparison of different anthelminthic drug regimens against Mansonella perstans filariasis.

Mansonella perstans filariasis is widely present in Africa and equatorial America and its pathogenicity has recently been reconsidered. Effective treatment is lacking and there is no consensus on the optimal therapeutic approach. The aim of this study was to compare the effects of different drug regimens on M. perstans infection. Six different anthelminthic therapeutic protocols were undertaken on 165 subjects with M. perstans infection and their effects on microfilariae burden were evaluated. Diethylcarbamazine (DEC) was able to reduce microfilariae density in the majority of cases, but it seldom eliminated infection after a single treatment. Mebendazole appeared to be more active than DEC in eliminating the infection, with a comparable rate of overall responses. Ivermectin and praziquantel showed no modification of microfilariae concentration. Thiabendazole showed a small but significant activity against the infection. Combination treatments (DEC plus mebendazole) resulted in a significantly higher activity than the single drugs.

The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren.

BACKGROUND: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. METHODS: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. RESULTS: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. CONCLUSIONS: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.

The diverse expression of immunity in humans at distinct states of Onchocerca volvulus infection.

This study examined the development and persistence of immunity in humans presenting defined states of Onchocerca volvulus infection, i.e. in exposed endemic control individuals without microfilaridermia and clinical disease, in patients with patent or post-patent onchocerciasis, and in patients concurrently infected with Mansonella perstans. Onchocerca volvulus antigen (OvAg)-specific cellular reactivity was significantly diminished in microfilariae (mf)-positive patients, while the highest reactivity was measured in exposed but mf-negative endemic controls, those being free of any clinical signs of onchocercal disease. In patients who became post-patent, responses to OvAg were significantly augmented, but did not approach entirely the magnitude observed in endemic controls. In onchocerciasis patients with concurrent mansonelliasis, cellular unresponsiveness to OvAg persisted, even when mf of O. volvulus were eliminated permanently by repeated ivermectin therapy. Cells from mf-positive onchocerciasis patients produced significantly less interferon-gamma (IFN-gamma) (P < 0.01) and interleukin-5 (IL-5) (P < 0.05) in response to OvAg than those taken from endemic controls or post-patent individuals in whom IFN-gamma and IL-5 production was similarly high. In contrast, both OvAg-driven as well as spontaneous IL-10 secretion was higher in mf-positive patients than in endemic controls or post-patent cases. In all individuals examined, serological recognition of OvAg by immunoglobulins was dominated by IgG4; in mf-positive patients OvAg of 205,000-12,000 molecular weight (MW) were strongly bound. In post-patent individuals, and similarly in endemic controls. OvAg recognition by IgG4 varied from intense (with numerous antigens being recognized) to weak or absent antigen binding. Significantly elevated OvAg-specific IgG isotypes were measured in mf-positive onchocerciasis patients in comparison with endemic controls or post-patent individuals (with the exception of IgG3). IgG1, IgG2 and IgE were higher, but IgG4 was lower in endemic controls compared with post-patent onchocerciasis patients. The ratios of IgG4/IgG1 differed (P < 0.001) between endemic controls and mf-positive or post-patent onchocerciasis patients, with IgG4/IgG1 ratios of R < 3.0 being characteristic for endemic controls and post-patent O. volvulus infection. In conclusion, this cross-sectional immunoepidemiological investigation showed that distinct states of O. volvulus infection correlate with a particular cellular and humoral immune response. The mf-free condition appeared to be associated with a vigorous parasite-specific cellular reactivity and a particular cytokine production profile, while concurrent M. perstans infection depressed OvAg-specific cellular responsiveness. Antibody responses, in all likelihood, reflected the intensity and state of infection, and not the degree of acquired immunity protective against parasite aggregation.

Treatment of human Mansonella streptocerca infection with ivermectin.

We studied the short-term effects of a single dose of 150 micrograms/kg body weight ivermectin on Mansonella streptocerca in an area endemic for streptocerciasis, but not for onchocerciasis, in western Uganda. Six and 12 days after treatment no microfilaria (mf) were found in the skin of 53 out of 96 mf carriers living in 3 villages, and the geometric means of the mf densities of remaining mf carriers were only 33-40% of pretreatment levels. This reduction of mf density was highly significant (P < 0.0001). Immunohistological examination of skin biopsies showed degenerated and disintegrating mf surrounded by activated eosinophils (positive for activated cationic protein), macrophages, and neutrophils (positive for myeloperoxidase and defensin) on day 6 after treatment. Remarkable was the invasion of young, L1 protein-positive macrophages and the release of neutrophil defensin as signs of acute inflammation. We conclude that ivermectin has a strong microfilaricidal activity against M. streptocerca. Common adverse effects were increased pruritus and acute papular dermatitis in 45% of 86 mf carriers on day 6 after treatment. No serious adverse side-effects were noticed in about 700 treated persons.

Mansonella ozzardi: the course of patency in experimentally-infected patas monkeys.

Twenty-five of 30 patas monkeys (Erythrocebus patas) inoculated with varying numbers (35 to 135) of third-stage larvae of Mansonella ozzardi developed patent infections in an average of 163 days. There was no correlation between the size of the inoculum and the length of the prepatent period. Ten of the monkeys were monitored thereafter by regular blood examination for extended periods of time in order to characterize the onset, course and duration of patency. Typically, with the onset of patency, microfilaremias increased steadily, peaking at about 20 weeks and then decreased slowly stabilizing at low levels for up to 48 weeks. Thereafter microfilariae disappeared from the blood and occasionally reappeared in scanty numbers. Laparotomies and followup studies indicated that the spleen was involved in the suppression of peripheral microfilaremia as had been observed earlier in patas monkeys infected with Loa loa. In ten monkeys splenectomized after the initial "wave" of microfilaremia, it was observed that (a) 30% of the animals remained amicrofilaremic, (b) another 30% reestablished patent infections but microfilaremias were lower than presplenectomy levels, and (c) in the remaining 40%, levels of microfilaremia equaled or exceeded pre-splenectomy levels. Patent infections persisted for up to 212 weeks. One monkey splenectomized prior to inoculation with 87 larvae developed a patent infection with microfilaremia which persisted for 156 weeks. Three monkeys with low and high levels of microfilaremia bled at four hour intervals over a 28 hour period showed no evidence of periodicity in the microfilaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental infection of humans with filariae.

This report summarizes the findings of the 17 published studies involving humans who have been experimentally infected with filarial parasites. Over the past 60 years, 45 individuals have been deliberately infected with Wuchereria bancrofti, Brugia malayi, Brugia pahangi, Loa loa, Mansonella perstans, Mansonella ozzardi, and/or Onchocerca volvulus. The findings from these experimental infections of humans have helped define microfilarial survival and periodicity within human hosts, the prepatent period for the causative agents of lymphatic filariasis, etiologic agents for particular clinical syndromes, immunologic and hematologic consequences of filarial infection, and the role of chemotherapeutic agents in the prevention and treatment of filarial infections.

Cell adherence to microfilariae of Onchocerca volvulus: a comparative study.

The conditions were examined for in vitro antibody-mediated adherence of granulocytes to microfilariae of Onchocera volvulus and Dirofilaria immitis. Reactivity in human sera from patients in endemic foci in Sudan was specific for O. volvulus and no reactions were observed with heterologous Onchocerca species or with Mansonella perstans. Microfilariae from skin, nodules or adult female worms were satisfactory targets for cell adherence, and the cells involved were almost exclusively eosinophils. The reaction was inhibited by indomethacin but not by nordihydroguaiaretic acid, an inhibitor of leukotriene production. Agents that slowed or stopped microfilarial motility (e.g. nifedipine, lidocaine, chloroquine) inhibited the reaction, probably by reducing target/cell contact. Ivermectin did not enhance the reaction, and in the absence of cells exerted only slight effects on the movement of microfilariae at higher concentrations (greater than 10 micrograms/ml). Antibody activity was labile, and did not persist well through freeze-thaw cycles. Some differences between homologous and heterologous mixtures (microfilariae/cells/serum) were seen but they could not be resolved satisfactorily. There were no apparent geographical differences between microfilariae from different foci in Sudan. In the D. immitis system neutrophils were the dominant cell type adhering to microfilariae, and the activity was stable to storage and freeze-thaw. No enhancement was detectable with diethylcarbamazine. Antibody activity was absorbable with microfilarial antigens and was reduced by agents that inhibited microfilarial motility. In dogs, adherence-mediating antibody was seen only in amicrofilaraemic animals with occult infection, and in only a minority of these sera. In humans the relationship to clinical findings was less clear, but patients with punctate keratitis were the most likely to have positive serum and were the most reactive in the assay. This system may therefore offer some insights into disease mechanisms in vivo, and its molecular mechanisms deserve further characterization.

Lack of evidence for transplacental transfer of microfilarial antigens in filariasis due to Loa loa and Mansonella perstans.

The transplacental transfer of microfilarial antigens could induce prenatal tolerance, or conversely resistance, which would influence the development of filariasis after birth. The passage across the placenta of immunogens constitutive of a crude microfilarial Loa loa extract has been investigated by dosing specific IgG, IgM and IgE antibodies in 92 maternal and corresponding cord blood samples, IgG levels were shown to be identical in about half of the mother-cord paired samples while in the other half the cord serum had a lower titre. Specific IgM or IgE could not be evidenced in any of the cord blood samples, even from those mothers who where harbouring L. loa microfilariae and/or specific antibodies. It is concluded that prenatal sensitization to the immunogenic preparation used is unlikely to have occurred.

Mansonella ozzardi in Haiti. IV. Evaluation of antibody reactivity to heterologous antigens.

Sera from individuals in an area of Haiti endemic for Mansonella ozzardi were analyzed for reactivity to antigens of Brugia pahangi, Dirofilaria immitis, Mansonella llewellyni or Ascaris lumbricoides using either an enzyme-linked immunosorbent assay or an indirect immunofluorescent antibody test. IgM and IgG reactivity to all antigens was observed with sera from both microfilaremic and amicrofilaremic individuals when compared to reactivity of sera from individuals from nonendemic areas. Antibody reactivity to B. pahangi was greater than that to other antigens. IgG reactivity of sera from endemic patients to filarial antigens was consistently greater than that of IgM. Antibody reactivity was not correlated with age or microfilarial density.