Impact of Long-Term Treatment with Ivermectin on the Prevalence and Intensity of Soil-Transmitted Helminth Infections

Soil-transmitted helminth (intestinal worm) infections are very common in developing countries and are an important cause of illness. Mass de-worming treatments of school children are an important strategy to reduce illness caused by these infections in communities without access to clean water and sanitation. Few studies have examined the effect of repeated mass treatments in the long-term in controlling these infections. The objective of the present study was to assess the impact of the drug ivermectin used for the control of onchocerciasis (river blindness), that has important effects against intestinal worms, on the epidemiology of intestinal worms in children when administered repeatedly for 15–17 years. We compared the epidemiology of infections between children living in communities that received ivermectin with communities that never received the drug. The data suggest that ivermectin has important differential effects on intestinal worms with a greater impact on infections with Trichuris trichiura and little impact on Ascaris lumbricoides and hookworms infections. Our data suggest that long-term ivermectin treatments may provide health benefits through effects on T. trichiura infections but that the addition of second de-worming drug such as albendazole may be required for the control of other intestinal worm infections

MR

Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF+ or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes

Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability

The symbiosis of filarial nematodes and rickettsial Wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis. Depletion of Wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability. The aim of this study was to investigate if antibiotic intervention of BALB/c mice infected with the rodent filaria Litomosoides sigmodontis with rifampicin or the combination of rifampicin and doxycycline can be used to shorten the treatment period. Both regimens, when given over a period of 14 days initiated with infection, were sufficient to deplete Wolbachia as evidenced by immunohistology and semiquantitative PCR. Worm development and filarial load were significantly reduced in experiments followed up until 63 days p.i. The therapy inhibited embryogenesis and led to filarial sterility. In contrast, treatment with doxycycline alone for 21 days led only to a modest reduction of Wolbachia , filarial growth retardation, worm viability and fertility. In conclusion, the combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections