Comparison of serological and parasitological assessments of Onchocerca volvulus transmission after 7 years of mass ivermectin treatment in Mexico.
OBJECTIVE AND METHOD: To compare the utility of an ELISA using 3 recombinant antigens with that of the skin biopsy to estimate incidence of infections in a sentinel cohort of individuals living in an endemic community in southern Mexico during a set of 11 subsequent ivermectin treatments. RESULTS: The apparent community prevalence of infection and microfilarial skin infection before and after 11 treatments with ivermectin plus nodulectomy were 78% and 13%, and 0.68 mf/mg and 0.04 mf/mg, respectively, as measured by skin biopsy. Of a group of 286 individuals participating in all surveys, a sentinel cohort of 42 mf and serologically negative individuals had been followed since 1994. The annual percentage of individuals becoming positive in this cohort was 24% (10/42), 28% (9/33), 0%, and 4.3% (1/23) in 1995, 1996, 1997 and 1998, respectively. Likewise, the incidence in children 5 years and under (n = 13) within this sentinel cohort was 15% (2/13), 18% (2/11), 0% and 11% (1/9), respectively. All individuals became positive to both tests simultaneously, indicating that seroconversion assessed infection incidence as accurately as skin biopsy in the sentinel group. CONCLUSION: Incidence monitoring of a sentinel cohort provides an estimation of the parasite transmission in the community; it is less costly than massive sampling, and a finger prick blood test might be more acceptable in some communities. (+info)
Distribution of the blinding and nonblinding strains of Onchocerca volvulus in Nigeria.
Onchocerciasis remains an important public health problem throughout much of sub-Saharan Africa. Nigeria is the country whose population is most afflicted by onchocerciasis; however, little is known concerning the epidemiology of onchocerciasis in this country. Previous studies demonstrated that onchocerciasis in West Africa exists in two forms, which differ in their clinical and epidemiologic characteristics. This is believed to be due to the existence of 2 strains of Onchocerca volvulus, the causative agent of onchocerciasis. The O-150 polymerase chain reaction has been developed to differentiate these 2 strains, and this method has been used to map the distribution of the blinding and nonblinding strains of O. volvulus in Nigeria. The strain distribution is consistent with what is known concerning the ecology and epidemiology of onchocerciasis in this country. The results also suggest that migration may be affecting the historic distribution of the 2 strains of the parasite in Nigeria. (+info)
Population biology of human onchocerciasis.
Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology. (+info)
Induction of histamine release in parasitized individuals by somatic and cuticular antigens from Onchocerca volvulus.
The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P < 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P < 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed. (+info)
Analysis of renal function in onchocerciasis patients before and after therapy.
The occurrence of renal abnormalities was investigated in patients with onchocerciasis in comparison to individuals without onchocerciasis in Guinea. Serum creatinine levels, excretion of urinary marker proteins, and kidney size by ultrasound were determined. A high prevalence of glomerular as well as tubular dysfunctions was observed; however, no association with onchocerciasis could be detected. We also hypothesized that patients with hyperreactive onchocerciasis might be prone to develop immune-mediated glomerular disorders; however, this could not be verified. Following treatment with ivermectin, a slight but significant increase in the excretion of urinary albumin and alpha1-microglobulin was seen five days after treatment in all treated patients, whereas levels of proteinuria were significantly higher five days after treatment only in patients with high microfilarial densities. Our results indicate that ivermectin can cause glomerular and tubular disturbances in patients with onchocerciasis; however, these are minor and do not seem to be clinically relevant. (+info)
Prenatal immune priming in onchocerciasis-onchocerca volvulus-specific cellular responsiveness and cytokine production in newborns from infected mothers.
This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly elevated in infected mothers and their infants. One year post partum, O. volvulus-specific IgG4 was strongly reduced in children of infected mothers, while IgG1 responses weakened only slightly. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the bacterial antigens streptolysin-O (SL-O) or purified protein derivative (PPD). UCBC from neonates born to O. volvulus-infected mothers responded lower (P < 0.01) to Con A (at 5 micrograms/ml), PPD (at 10 and 50 micrograms/ml) and O. volvulus-derived antigens (OvAg) (at 35 micrograms/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers positive for O. volvulus. Several Th1-type (IL-2, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2-type (IL-4, IL-5, IL-10, IL-13) cytokines were secreted by UCBC and PBMC in response to OvAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mitogens or antigens induced production of IL-4 in neonates. In response to OvAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced by UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low levels of IL-5 and IL-13, while higher amounts of IL-10 were found (P < 0. 01) in newborns from onchocerciasis-free mothers. In conclusion, maternal O. volvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines. (+info)
Structural studies of N-glycans of filarial parasites. Conservation of phosphorylcholine-substituted glycans among species and discovery of novel chito-oligomers.
N-Type glycans containing phosphorylcholine (PC-glycans), unusual structures found in the important human pathogens filarial nematodes, represent a novel target for chemotherapy. Previous work in our laboratories produced compositional information on the PC-glycan of ES-62, a secreted protein of the rodent parasite Acanthocheilonema viteae. In particular, we established using fast atom bombardment mass spectrometry (MS) analysis that PC was attached to a glycan with a trimannosyl core, with and without core fucosylation, carrying between one and four additional N-acetylglucosamine residues. In the present study, we demonstrate that this structure is conserved among filarial nematodes, including the parasite of humans, Onchocerca volvulus, for which new drugs are most urgently sought. Furthermore, by employing a variety of procedures, including collision-activated dissociation MS-MS analysis and matrix-assisted laser desorption MS analysis, we reveal that surprisingly, filarial nematodes also contain N-linked glycans, the antennae of which are composed of chito-oligomers. To our knowledge, this is the first report of such structures in a eukaryotic glycoprotein. (+info)
Temporal recruitment of neutrophils and eosinophils to the skin in a murine model for onchocercal dermatitis.
The parasitic helminth Onchocerca volvulus causes ocular onchocerciasis (river blindness) and onchocercal skin disease. To understand the immunologic basis for early stage skin disease, we developed a model in which C57B1/6 mice were immunized subcutaneously and injected intradermally (in the ear) with soluble O. volvulus antigens (OvAg). We found that ear thickness increased significantly after intradermal injection of OvAg and remained elevated for at least 7 days. Dermatitis was dependent on prior immunization, and was associated with an intense cellular infiltrate in the dermis. Neutrophils were the predominant inflammatory cells in the dermis 12 hr after intradermal injection, with only occasional eosinophils present. Conversely, increased ear thickness at later time points was associated with eosinophils, and neutrophils were only rarely detected. Both cell types were present at intermediate time points. These data indicate that recruitment of neutrophils and eosinophils to the skin is temporally regulated. (+info)