The biology of Onchocerca ochengi, a filarial nematode from African cattle, and the implications on the epidemiology of the causative agent of river blindness, Onchocerca volvulus

Onchocerca ochengi is a common filarial parasite in African zebu cattle, which is non-pathogenic, in contrast to its closest known relative Onchocerca volvulus, which causes onchocerciasis (river blindness) in humans. In Cameroon it serves as an animal model to study the vector-borne disease, transmitted by the same black fly species of the Simulium damnosum complex. The present study focuses on the biology of O. ochengi, including its population dynamics in a longitudinal follow-up study of a cattle herd exposed to natural transmission since their birth. Another research focus lies on the decline in biting rates and transmission potentials of the local vector in formerly meso- and hyperendemic onchocerciasis foci in North Cameroon, in order to determine the actual risk for the population and prospects for elimination of river blindness. In the dry savannah focus at the Vina du Nord river basin the annual transmission potential dropped to 3.5 % of pre-control levels after 25 years of annual treatment of the human population with the microfilaricide ivermectin, whereas at the Vina du Sud focus on a highland plateau no transmission could be confirmed by molecular detection after 15 years of consecutive treatment intervention. The high cattle stock density on the Adamawa highlands has contributed to the regional interruption of transmission, and demonstrates that annual mass drug administration alone may not be sufficient to prevent onchocerciasis in hyperendemic foci. Moreover, a high genetic diversity of O. ochengi was shown in cattle and vector, including the discovery of a new mitochondrial haplotype with phylogenetic similarities to O. volvulus, and a putative hybrid of O. ochengi with O. dukei. Other results in studying the bovine onchocercosis model were insights into the reproductive biology of O. ochengi, time-scaled dynamics of immunological reactivity to recombinant O. volvulus antigens in zebu cattle naturally exposed to O. ochengi, the production and biochemical analysis of excretory-secretory products of O. ochengi adults, including their putative function, and the optimization of separating viable microfilariae of O. ochengi and O. gutturosa from adult uteri and cattle skin for subsequent culturing

Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases

The intraerythrocytic parasite Plasmodium—the causative agent of malaria—produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into the circulation during erythrocyte lysis. Hz is rapidly ingested by phagocytes and induces the production of several pro-inflammatory mediators such as interleukin-1β (IL-1β). However, the mechanism regulating Hz recognition and IL-1β maturation has not been identified. Here, we show that Hz induces IL-1β production. Using knockout mice, we showed that Hz-induced IL-1β and inflammation are dependent on NOD-like receptor containing pyrin domain 3 (NLRP3), ASC and caspase-1, but not NLRC4 (NLR containing CARD domain). Furthermore, the absence of NLRP3 or IL-1β augmented survival to malaria caused by P. chabaudi adami DS. Although much has been discovered regarding the NLRP3 inflammasome induction, the mechanism whereby this intracellular multimolecular complex is activated remains unclear. We further demonstrate, using pharmacological and genetic intervention, that the tyrosine kinases Syk and Lyn play a critical role in activation of this inflammasome. These findings not only identify one way by which the immune system is alerted to malarial infection but also are one of the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLRP3 inflammasome

Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon.

BACKGROUND:Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed. METHODS AND FINDINGS:Entomologic data from two former endemic river basins in North Cameroon were generated over a period of 43 and 48 months to follow-up transmission levels in areas under prolonged ivermectin control. Moreover, epidemiologic parameters of animal-borne Onchocerca spp. transmitted by the same local black fly vectors of the Simulium damnosum complex were recorded and their impact on O. volvulus transmission success evaluated. With mitochondrial DNA markers we unambiguously confirmed the presence of infective O. volvulus larvae in vectors from the Sudan savannah region (mean Annual Transmission Potential 2009-2012: 98, range 47-221), but not from the Adamawa highland region. Transmission rates of O. ochengi, a parasite of Zebu cattle, were high in both foci. CONCLUSIONS/SIGNIFICANCE:The high cattle livestock density in conjunction with the high transmission rates of the bovine filaria O. ochengi prevents the transmission of O. volvulus on the Adamawa plateau, whereas transmission in a former hyperendemic focus was markedly reduced, but not completely interrupted after 25 years of ivermectin control. This study may be helpful to gauge the impact of the presence of animal-filariae for O. volvulus transmission in terms of the growing human and livestock populations in sub-Saharan countries