Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity.

Objective: Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infected subjects are more insulin sensitive than STH-uninfected subjects.

Design: We performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.

Methods: From 646 adults, stool samples were screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR.

Relationship between carotid intima media thickness and helminth infections on Flores Island, Indonesia.

Objective: To examine the association between helminth infections and atherosclerosis.

Background: Chronic helminth infection, which can lead to poor nutritional status and anti-inflammatory response, might protect against the development of atherosclerosis.

Methods: A cross-sectional study was performed in Flores, Indonesia, an area highly endemic for soil-transmitted helminths (STH).

Blood pressure class and carotid artery intima-media thickness in a population at the secondary epidemiological transition.

Objectives: Data relating blood pressure (BP) class to subclinical organ damage are infrequently reported in populations with a traditional 'nonwestern' lifestyle. As the relevance of BP stratification to cardiovascular prognosis has not been elucidated in these low-income countries at the second epidemiological transition, we aimed to study the effect of BP class on carotid artery intima-media thickness (IMT) in Flores Island, Indonesia.

Methods: A cross-sectional study was performed in 476 inhabitants (men/women) of Flores.

Specificity of predominant IgG4 antibodies to adult and microfilarial stages of Brugia malayi.

Human infections with filarial nematodes such as Brugia malayi are accompanied by unusually high titres of parasite-specific IgG4 antibodies. We have compared the profile of antigens recognised by filarial-specific IgG1 and IgG4 isotypes by Western blotting. Serum samples were collected from 120 subjects exposed to Brugia malayi, divided into three groups of asymptomatic amicrofilaraemic (endemic normal), microfilaraemic, and elephantiasis patients.

Antibody responses to filarial infective larvae are not dominated by the IgG4 isotype.

The humoral immune response in humans to filarial parasites is generally dominated by the IgG4 isotype, when measured by ELISA against somatic adult worm extract. In contrast, as we report here, antibodies reactive to somatic extracts of infective larvae are more equally represented by IgG1 and IgG4. Moreover, binding to surface exposed epitopes in immunofluorescence on larval stages is mediated foremost by IgG1 and IgM, secondarily by IgG2 and IgG3, and very little by IgG4.

Differential decline in filaria-specific IgG1, IgG4, and IgE antibodies in Brugia malayi-infected patients after diethylcarbamazine chemotherapy.

In human filariasis, the predominant serum antibody is IgG4, accompanied by significant IgE production. The ratio of IgG4 to IgE is highest in asymptomatic microfilaremic carriers, while chronic disease is associated with elevated IgG1-3. The changes in isotypes following chemotherapy with diethylcarbamazine (DEC) were studied in 2 groups of Brugia malayi-infected patients from Sumatra and South Kalimantan, Indonesia.

Specific T cell unresponsiveness in human filariasis: diversity in underlying mechanisms.

In an attempt to overcome T cell unresponsiveness to filarial antigens, 65 individuals belonging to the three clinical groups of elephantiasis patients, microfilaraemics, and asymptomatic amicrofilaraemics who exhibited unresponsiveness to Brugia malayi adult worm antigen (BmA) were studied. Peripheral blood mononuclear cells were cocultured with antigen and one of the following reagents that have been reported to be effective in reconstituting T cell proliferation: interleukin-2 (IL-2), interleukin-7 (IL-7), anti-interleukin-4, anti-interleukin-10, anti-CD2, anti-CD27, anti-CD28, indomethacin, phorbol myristate acetate (PMA), or calcium ionophore (A23187). We were able to overcome antigen-specific unresponsiveness in only a minority of the individuals studied.

Differential antibody isotype reactivity to specific antigens in human lymphatic filariasis: gp15/400 preferentially induces immunoglobulin E (IgE), IgG4, and IgG2.

Lymphatic filarial infection in humans is associated with a strong skewing of the immune response towards the TH2 arm, with prominent interleukin 4-producing cells and elevated levels of immunoglobulin G4 (IgG4) and IgE antibodies in peripheral blood. To determine how such a generalized TH2 imbalance governs responses to individual parasite antigens, the profiles of isotypes of antibodies to two recombinant proteins of Brugia spp. were studied.

HLA and elephantiasis in lymphatic filariasis.

Lymphatic filariasis presents a spectrum of manifestations with infection-free asymptomatics at one end and elephantiasis at the other. In order to determine if any HLA antigens are associated with the development of elephantiasis, we compared the HLA frequencies in 55 elephantiasis patients with those in 40 controls consisting of individuals older than 45 years of age without any signs of elephantiasis. The only significant difference in class I antigen frequencies was observed for B27, which was present in 11% of the patients and absent in the controls.

Elevated cellular immune responses and interferon-gamma release after long-term diethylcarbamazine treatment of patients with human lymphatic filariasis.

Cellular immune responses to filarial antigens were examined in persons before and 1 year after beginning treatment with diethylcarbamazine (DEC). The subjects (17 microfilaremics, 13 asymptomatic amicrofilaremics, and 13 with elephantiasis) had not responded to Brgia malayi adult worm antigen (BmA) before chemotherapy. T cell proliferative responses to BmA improved significantly after therapy in the 3 clinical groups (P < .

T-cell activation and the balance of antibody isotypes in human lymphatic filariasis.

Human filarial infection presents a spectrum of clinical states with two major poles: asymptomatic microfilaraemia and amicrofilaraemic chronic disease. Microfilaremia is associated with a Th1-type tolerance, and maximal IgG4 antibodies, while elephantiasis patients react across a broad range of immune parameters. In this review, Rick Maizels and his colleagues discuss recent advances in the immunology of human filariasis and present a summary of their latest studies in an endemic area of Indonesia.

A polymerase chain reaction assay for the detection of Brugia malayi in blood.

There is need for sensitive, rapid, species-specific diagnosis of Brugia filarial parasites because traditional methods are tedious and time-consuming, with little guarantee of species specificity. A polymerase chain reaction (PCR)-based assay was developed using the Hha I family of highly repeated DNA sequences from Brugia. The assay was tested on 124 human blood samples collected in a field study in Indonesia.

Elevated levels of T cell activation antigen CD27 and increased interleukin-4 production in human lymphatic filariasis.

To assess the immunological changes occurring during filarial infection with or without elephantiasis, 145 patients in different clinical groups from an endemic area in Indonesia were compared with respect to plasma levels of both soluble CD25 (sCD25) and sCD27; interleukin-4 (IL-4) and interferon-gamma release by peripheral blood mononuclear cells was also measured in a smaller subset of individuals. Levels of sCD27 were significantly elevated in elephantiasis and microfilaremic patients compared with endemic normals (p < 0.002), whereas sCD25 levels remained low in microfilaremics and was only slightly elevated in elephantiasis patients compared with endemic normals (p < 0.

Primary structure of and immunoglobulin E response to the repeat subunit of gp15/400 from human lymphatic filarial parasites.

We have isolated and sequenced clones encoding the repeated subunit of the surface-associated glycoprotein gp15/400 from the two nematode species predominantly responsible for lymphatic filariasis in humans: Brugia malayi and Wuchereria bancrofti. The amino acid sequence of the 15-kDa subunit, derived from the nucleotide sequence of the gene fragment from B. malayi, is identical to that previously reported for B.

Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic human filariasis.

A population of 164 adult individuals resident in an area endemic for Brugia malayi lymphatic filariasis has been studied for humoral immune responses to filarial parasites. Antibody levels to Ag extracted from adult worms were determined for each of the IgG subclasses, for IgM and for IgE. The dominant isotype of antifilarial antibody was IgG4, which represented 88% of total IgG in asymptomatic microfilaremics, most of whom possessed 100 to 1000 micrograms/ml of specific antibody of this subclass (geometric mean 762 micrograms/ml).

T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis.

To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43 microfilaremics, 12 symptomatic amicrofilaremics, and 52 elephantiasis patients. Lymphocyte proliferation was higher in elephantiasis patients and asymptomatic amicrofilaremics than in microfilaremics (P < .004).

Recent advances in the application of molecular biology in filariasis.

Monitoring of filarial parasites in the host and vector has traditionally depended on morphological identification. Recently, species-specific DNA probes have been developed for Brugia malayi, Brugia pahangi and Wuchereria bancrofti. Repeated DNA sequences are useful in developing DNA probes because they evolve more rapidly then coding sequences and their high copy number increases the sensitivity of detection.

Ivermectin and diethylcarbamazine trials in leaf monkeys (Presbytis cristatus) infected with Wuchereria kalimantani.

Clinical trials of Ivermectin in single oral doses of 200, 400, and 1,000 mg/kg body weight or in multiple doses of 200 mg/kg body weight for 5 consecutive days were performed in leaf monkeys (Presbytis cristatus) infected with Wuchereria kalimantani. Optimal microfilaricidal effect occurred at 200 mg/kg body weight. The drug was less effective than diethylcarbamazine in this animal model for human filariasis but had no adverse effects.

Towards a filariasis-free community: evaluation of filariasis control over an eleven year period in Flores, Indonesia.

A population of 202 residents in an area endemic for Brugia timori lymphatic filariasis was treated in a diethylcarbamazine control programme commencing in 1977. All individuals were treated twice with diethylcarbamazine on a mass basis with additional selected treatment for cases with manifestations of infection. Clinical features of lymphatic filariasis were recorded annually until 1982, and the population re-assessed in 1988, six years after the completion of chemotherapy.

Secreted antigens of filarial nematodes: a survey and characterization of in vitro excreted/secreted products of adult Brugia malayi.

We report here a broad analysis of the excretory/secretory (E/S) products of adult Brugia malayi, collected by in-vitro cultivation of the parasite. Culture media and conditions were optimized, and non-essential amino acids were found to be crucial for efficient protein synthesis under cell- and serum-free culture conditions. A close correlation was found between total protein secretion, phosphorylcholine-bearing antigen release and lactate production on each day of culture, indicating that E/S molecules are actively secreted.

Heat shock cognate 70 is a prominent immunogen in Brugian filariasis.

A cDNA expression library constructed from RNA derived from adult stage Brugia pahangi (mixed sexes) was screened with pooled sera from chronic, amicrofilaremic cases of human lymphatic filariasis from the Indonesian island of Tanjungpinang, where Brugia malayi is endemic. Polyclonal antisera raised to purified beta-galactosidase fusion proteins from two of the most highly reactive clones identified a protein of Mr 70,000 in all stages examined (microfilariae, L3 and adults) of both B. malayi and Brugia pahangi.

Identification, synthesis and immunogenicity of cuticular collagens from the filarial nematodes Brugia malayi and Brugia pahangi.

The major structural proteins of the cuticle of the filarial nematode parasites Brugia malayi and Brugia pahangi were identified by extrinsic iodination and sensitivity to clostridial collagenase. At least 16 acidic components were identified in adult worms by 2-dimensional electrophoresis, with molecular weights ranging from 35,000 to 160,000. These proteins appear to be cross-linked by disulphide bonds, and localised in the basal and inner cortical layers of the cuticle.

Circulating antibodies and antigens in Presbytis monkeys infected with the filarial parasite Wuchereria bancrofti.

Levels of circulating filarial antigen, and humoral antibody to other defined antigenic targets, were measured over the course of experimental infection of three Presbytis cristatus monkeys with Wuchereria bancrofti. Circulating antigen levels, measured with an anti-phosphorylcholine monoclonal antibody, varied widely although all animals were positive for some period of the infection. Circulating antigen levels tended to be inversely related to the titre of anti-phosphorylcholine antibody, and this trend was maintained even following acid dissociation and inactivation of immune complexed host antibody.