Prevalence of symptomatic tinea capitis and associated causative organisms in the Greater Accra Region, Ghana.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Yazdanbakhsh.
Explore the source record for details and available documents.
In addition to proteins, glycolipids can be targets of antibody responses and contribute to host-pathogen interaction. Following the structural analysis of Ascaris lumbricoides-derived glycolipids, the antibody responses of a group of children with no, light and heavy infections were analysed. The role of the phosphorylcholine moiety, present on Ascaris glycoproteins and glycolipids, in antibody reactivity of these infected individuals was determined. Children carrying heavy infections showed highest IgG reactivity to glycolipids compared to lightly or non-infected children. Substantial IgG antibody reactivity to both (glyco)proteins and glycolipids was found to be directed to the phosphorylcholine moiety as determined by either removal of this group or a competition assay. This was most pronounced for glycolipids, where removal of the phosphorylcholine moieties by hydrofluoric acid treatment abrogated IgG antibody reactivity. Measurement of IgG4 and IgE isotypes showed no IgG4 reactivity to Ascaris glycolipids, but raised IgE responses were detected in subjects with light or no Ascaris infections, suggesting that IgE responses to glycolipids may play a role in controlling parasite burden. Differences found in antibody profiles to glycolipids and (glyco)proteins, indicate that these different classes of compounds may have distinct roles in shaping of and interacting with humoral immune responses.
Chronic helminth infections induce strong type 2 and regulatory immune responses and are known to influence immune activity to other antigens such as allergens and vaccines. Since malaria and helminth infections often coincide geographically in the same tropical regions, the question arises whether helminth infections modulate the immune responses towards the malaria parasite and affect its course of disease. Here, we will review studies on co-infections in both animal models and in human populations, and discuss the changes in the immune system seen. Furthermore, the implications of helminth infection for the efficacy of malaria vaccines will be discussed.
A statistical method that analyses correlation structures in families to delineate the contribution of genetic, household and environmental factors on clustering of infection, has been applied to data collected in an area endemic for brugian filariasis in South Sulawesi, Indonesia. Infection was assessed both by microfilaraemia and by anti-filarial IgG4. The results confirmed earlier findings that genetic factors play an important role in clustering of infection. When clustering of infection was analysed in children (< 10 years of age) and adults (> 20 years of age) separately, it was found that the genetic factors influence clustering of infection in children more profoundly than environmental or household effects. In contrast, genetic factors could not fully explain the clustering of infection seen in adults, which seemed to be mainly determined by household and environmental effects. The data have implications for genotyping studies in brugian filariasis; they indicate that it may be important to concentrate on the younger age groups where individual environmental effects have not yet overruled the genetic influences on gain/loss of infection.
Explore the source record for details and available documents.
A multicentre evaluation of the Brugia Rapid dipstick test was performed using 1263 serum samples in four international laboratories, i.e. T.D. Medical College (TDMC, India), National Institutes of Health (NIH, USA), Swiss Tropical Institute (STI, Switzerland) and Leiden University Medical Centre (LUMC, Netherlands). In comparison with microscopy, the dipstick demonstrated sensitivities of 97.2% (70 of 72) at TDMC, 91.6% (175 of 191) at LUMC and 100% (six of six) at STI. Sera of chronic patients showed a positivity rate of 11.3% (19 of 168) and 61.2% (71of 116) at TDMC and LUMC, respectively. All 266 sera of non-endemic normals from STI, NIH and LUMC tested negative with the dipstick. At LUMC, sera of 'endemic normals' (amicrofilaraemics with no clinical disease) from an area with approximately 35% microfilaria positivity showed 60.8% positive results (31 of 51), thus demonstrating the likelihood of many cryptic infections occurring in this population. Specificities of the test with Onchocerca volvulus sera were 98.8% (80 of 81) and 100% (10 of 10) at the NIH and STI, respectively; while specificity with Loa loa sera at the NIH was 84.6% (44 of 52). At the STI, the dipstick test also demonstrated 100% specificity when tested with 75 sera from various protozoan and helminthic infections.
We have followed a population in an area endemic for Brugia malayi for three years after intensive treatment with diethylcarbamazine (DEC). Microfilariae were cleared from the circulation within four months in all eligible study participants (n = 60). There appeared to be a strong correlation between the maximum reduction in specific IgG4 and the number of days drug was taken under supervision (p = 0.41, P < 0.001), indicating that high total dosage of DEC is necessary for optimal reduction of active infection. In individuals with good compliance (at least 180 mg/kg of body weight, n = 34), we observed variable IgG4 patterns. All pre-treatment IgG4+ children (9-14 years old) and 40% of the IgG4+ adult population (> or = 15 years old) showed a gradual decrease in anti-filarial IgG4; 53% of these showed complete clearance of worm burden by the end of the study. In contrast, another group of male IgG4+ adults showed IgG4 patterns that started to increase between nine months and two years after treatment, indicating either a partial efficacy of DEC that allowed recovery of resident adult worms or reinfection.
In lymphatic filariasis, specific IgG4 responses to the parasite and their relationship with infection have been studied extensively, but only a few studies have concentrated on anti-filarial and total IgE. Here we have investigated the role of filarial infection pressure on production of IgE by considering length of exposure (age), filarial endemicity and parasitological status. Antibody levels were determined in 366 individuals, who were resident in 3 villages in South-Sulawesi, Indonesia, with varying degrees of filarial transmission intensity, as indicated by the prevalence of Brugia malayi microfilaraemia (0.7%, 9% and 32%, respectively). Anti-filarial IgE levels were significantly lower in the low transmission village than in the areas with intermediate and high filarial transmission; however, in the latter village a remarkable suppression of specific IgE was found. Microfilaria-positive individuals showed elevated levels of total IgE, but suppression of specific IgE, which has been reported before. Taken together, these observations suggest that 2 opposing mechanisms regulate anti-parasite IgE expression: increasing experience of filarial infection stimulates specific IgE, but antibody levels become specifically suppressed when microfilariae or adult worms develop. Using a simple mathematical model, we illustrate how anti-filarial IgE increases with parasite antigen up to a threshold level, but levels off and becomes down-regulated after the threshold is exceeded.
Explore the source record for details and available documents.
The last decades have seen a dramatic rise in the prevalence of allergic diseases throughout the industrialised world. The "hygiene hypothesis" postulates that this is due to a reduced exposure to infections during childhood. A cohort study in children from Gabon gave us the unique opportunity to examine the relationship between exposure to P. falciparum and atopy. 91 children, who had been closely followed for an average of 5 years and of whom the exact incidence of malaria attacks was known, underwent a skin-prick test with mite antigen. 16 children (18%) had a positive reaction. Gender or age had no effect on the outcome of the test. However, those tested positive had had less infections and a lower incidence of malaria than children tested negative (p = 0.017). Survival analysis shows that children with a high exposure to P. falciparum were at lower risk of an atopic skin reaction (p = 0.001). We postulate that the low exposure to the malaria parasite contributes to the development of an imbalanced immune system with a subsequent higher reactivity to the allergen tested. Immuno-suppression is commonly seen during a malaria attack and this correlates positively with the level of anti-inflammatory cytokines such as interleukin-10. High exposure to parasite antigens might counterbalance pro-inflammatory immune reactions and thus protect against allergic diseases. A better understanding of the relationship between parasitic infection and allergy will help us to develop strategies to prevent allergic disease without being exposed to infectious diseases.
Wolbachia bacteria seem to have evolved as essential endosymbionts of their filarial nematode hosts. Studies in mice have suggested that these bacteria are associated with systemic inflammatory reactions to filarial chemotherapy. We took blood samples from 15 Indonesian patients before and after treatment with diethylcarbamazine for Brugia malayi infection, and recorded the severity of any post-treatment inflammatory reactions. Blood from all three patients with severe adverse reactions and from one of six with moderate reactions was positive for Wolbachia DNA 4-48 h after diethylcarbamazine treatment. We suggest that these severe inflammatory reactions are associated with the release of endosymbionts into the blood after treatment for filariasis.
The immune response to helminth infections has long been known to share key features with the allergic response. In particular, both are typified by enhanced T helper 2 (Th2) responses with high levels of interleukin-4 (IL-4), IL-5 and IL-13, accompanied by eosinophilia and abundant IgE production. Paradoxically, the geographical distribution of helminth parasitism and allergic disease is complementary rather than coincident. Thus, the question arises does the Th2 response to parasites protect or pre-empt the host from developing Th2-linked allergic manifestations? It is suggested that downregulatory immune mechanisms, which dampen the anti-parasite response, might benefit the host by blocking progression to atopic reactions. This is of relevance in explaining how the "hygiene hypothesis" might operate immunologically and in the design of therapeutics.
To dissociate the influence of host age from length of exposure on acquisition of filarial infection, we examined the development of microfilaraemia and anti-filarial IgG4 in all ages of a naive population that became suddenly exposed to Brugia malayi as a result of transmigration. Responses in 247 transmigrants, who had settled for periods of several months up to 6 years in their new homesteads, were compared with those of 133 life-long residents. As shown in earlier studies, anti-filarial IgG4 increased with age in the indigenous populations, whose age is equivalent to length of exposure. However, by examining transmigrants, it became clear that development of specific IgG4 was influenced by age, since levels of this antibody were consistently higher in transmigrant adults than in transmigrant children, despite an equal length of exposure to filarial infection. Examining microfilaraemia, it was confirmed that infection establishes more rapidly in adults than in children.
Explore the source record for details and available documents.
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.
BACKGROUND: Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. METHODS: 520 Gabonese schoolchildren were tested for skin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs in urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. FINDINGS: Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. INTERPRETATION: The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.
Understanding the basic immunology of an infectious disease requires insight into the pattern of T cell reactivity and specificity. Although lymphatic filariasis is a major tropical disease, the predominant T cell Ags of filarial species such as Brugia malayi are still undefined. We have now identified a prominent T cell Ag from B. malayi microfilariae (Mf) as Bm-SPN-2, a serpin secreted exclusively by this stage. Mf-infected mice mounted strong, but short-lived, Bm-SPN-2-specific Th1 responses, measured by in vitro production of IFN-gamma, but not IL-4 or IL-5, 14 days postinfection. By day 35, responsiveness to Bm-SPN-2 was lost despite enhanced reactivity to whole Mf extract. Single immunization with Mf extract also stimulated typical Th1 reactions to Bm-SPN-2, but IgG1 Ab responses dominated after repeated immunizations. Human patients displayed potent humoral responses to Bm-SPN-2 in both IgG1 and IgG4 subclasses. Thus, 100% (20 of 20) of the microfilaremic (MF(+)) patients bore IgG4 responses to Bm-SPN-2, while only 30% of endemic normal subjects were similarly positive. Following chemotherapy, Bm-SPN-2-specific Abs disappeared in 12 of 13 MF(+) patients, although the majority remained seropositive for whole parasite extract. PBMC from most, but not all, endemic subjects were induced to secrete IFN-gamma when stimulated with Bm-SPN-2. These findings demonstrate that Bm-SPN-2 is recognized by both murine and human T and B cells and indicate that their responses are under relatively stringent temporal control. This study also provides the first example of a stage-specific secreted molecule that acts as a major T cell Ag from filarial parasites and is a prime candidate for a serodiagnostic probe.
To assess the involvement of inflammatory mediators in the development of adverse reactions in filarial patients undergoing treatment, 29 microfilaremic subjects were treated with diethylcarbamazine (DEC). Before and at serial time points after initiation of treatment, plasma levels of inflammatory mediators and DEC were measured, and adverse reactions were recorded. Patients experienced no or mild, moderate, or severe adverse reactions. Increasing pretreatment microfilarial counts were associated with escalating severity of adverse reactions. Plasma concentrations of DEC were not different among patients suffering from varying degrees of illness. Interleukin (IL)-6, IL-10, lipopolysaccharide-binding protein (LBP), and soluble tumor necrosis factor receptors (sTNF-Rs) increased after treatment. IL-6 and LBP, however, showed the strongest association with adverse reactions. Increasing levels of these molecules were closely correlated with the mounting severity of adverse reactions, which raises the possibility that they play an important role in systemic inflammation that arises after DEC treatment of filarial patients.