BackgroundMass drug administration (MDA) of ivermectin has become the main intervention to control onchocerciasis or “river blindness”. In Togo, after many years of MDA, Onchocerca volvulus infection has declined dramatically, and elimination appears achievable, but in certain river basins the current situation remains unknown. We have conducted parasitological, serological, ophthalmological, and entomological assessments in northern and central Togo within the river basins of Ôti, Kéran and Mô.Methodology/Principal findingsExaminations were completed in 1,455 participants from 11 onchocerciasis sentinel villages, and O. volvulus transmission by Simulium damnosum sensu lato (s.l.) was evaluated. In children (aged 1–10 years), the prevalence of microfilariae (Mf) was 2.3% and in adults it ranged from 5.1 to 13.3%. Positive IgG4 responses to O. volvulus adult (crude) worm antigen (OvAg) and the recombinant Ov16 antigen were in all-ages 48.7% and 34.4%, and 29.1% and 14.9% in children, respectively. In the river basin villages of Kéran, Mô and Ôti, the IgG4 seroprevalences to OvAg in children were 51.7%, 23.5% and 12.7%, respectively, and to the Ov16 antigen 33.3% (Kéran) and 5.2% (Ôti). Onchocerciasis ocular lesions (punctate keratitis, evolving iridocyclitis and chorioretinitis) were observed in children and young adults. O. volvulus-specific DNA (Ov150) was detected by poolscreen in vector samples collected from Tchitchira/Kéran(22.8%), Bouzalo/Mô(11.3%), Baghan/Mô(2.9%) and Pancerys/Ôti(4.9%); prevalences of O. volvulus infection in S. damnosum s.l. were, respectively, 1%, 0.5%, 0.1% and 0.2%.Conclusions/SignificanceIn the northern and central river basins in Togo, interruption of O. volvulus transmission has not yet been attained. Patent O. volvulus infections, positive antibody responses, progressive ocular onchocerciasis were diagnosed, and parasite transmission by S. damnosum s.l. occurred close to the survey locations. Future interventions may require approaches selectively targeted to non-complying endemic populations, to the seasonality of parasite transmission and national onchocerciasis control programs should harmonize cross-border MDA as a coordinated intervention.

Cytostatic drugs used in cancer therapy were evaluated for their capacity to inhibit Echinococcus multilocularis metacestode growth and proliferation. Metacestode tissues were exposed in vitro to docetaxel, doxorubicin, navelbine, paclitaxel, and vorinostat for 1 week, then incubated in drug-free culture, and thereafter metacestodes were injected into the peritoneum of Meriones unguiculatus. Magnetic resonance imaging (MRI) and simultaneous positron emission tomography (PET) were applied to monitor in vivo growth of drug-exposed E. multilocularis in Meriones. At 3 month p.i., docetaxel (at 10 μM, 5 μM and 2 μM) inhibited in vivo growth and proliferation of E. multilocularis, and at 5 months p.i., only in the 2 μM docetaxel exposure group 0.3 cm3 of parasite tissue was found. With paclitaxel and navelbine the in vivo growth of metacestodes was suppressed until 3 months p.i., thereafter, parasite tissues enlarged up to 3 cm3 in both groups. E. multilocularis tissues of more than 10 g developed in Meriones injected with metacestodes which were previously exposed in vitro to doxorubicin, navelbine, paclitaxel or vorinostat. In Meriones infected with metacestodes previously exposed to docetaxel, the in vivo grown parasite tissues weighted 0.2 g. In vitro cultured E. multilocularis metacestodes exposed to docetaxel did not produce vesicles until 7 weeks post drug exposure, while metacestodes exposed to doxorubicin, navelbine and vorinostat proliferated continuously. In summary, docetaxel, and less efficaciously paclitaxel, inhibited in vivo and in vitro parasite growth and proliferation, and these observations suggest further experimental studies with selected drug combinations which may translate into new treatment options against alveolar echinococcosis.

Mansonella perstans (Mp) filariasis is present in large populations in sub-Saharan Africa, and to what extent patent Mp infection modulates the expression of immunity in patients, notably their cellular cytokine and chemokine response profile, remains not well known. We studied the spontaneous and inducible cellular production of chemokines (C-X-C motif) ligand 9 (CXCL9) [monokine induced by interferon (IFN)-γ (MIG)], CXCL-10 [inducible protein (IP)-10], chemokine (C-C motif) ligand 24 (CCL24) (eotaxin-2), CCL22 [macrophage-derived chemokine (MDC)], CCL13 [monocyte chemotactic protein-4 (MCP-4 )], CCL18 [pulmonary and activation-regulated chemokine (PARC)], CCL17 [thymus-and activation-regulated chemokine (TARC)] and interleukin (IL)-27 in mansonelliasis patients (Mp-PAT) and mansonelliasis-free controls (CTRL). Freshly isolated peripheral mononuclear blood cells (PBMC) were stimulated with helminth, protozoan and bacterial antigens and mitogen [phytohaemagglutinin (PHA)]. PBMC from Mp-PAT produced spontaneously (without antigen stimulation) significantly higher levels of eotaxin-2, IL-27, IL-8, MCP-4 and MDC than cells from CTRL, while IFN-γ-IP-10 was lower in Mp-PAT. Helminth antigens activated IL-27 and MCP-4 only in CTRL, while Ascaris antigen, Onchocerca antigen, Schistosoma antigen, Entamoeba antigen, Streptococcus antigen, Mycobacteria antigen and PHA stimulated MIG release in CTRL and Mp-PAT. Notably, Entamoeba antigen and PHA strongly depressed (P < 0·0001) eotaxin-2 (CCL24) production in both study groups. Multiple regression analyses disclosed in Mp-PAT and CTRL dissimilar cellular chemokine and cytokine production levels being higher in Mp-PAT for CCL24, IL-27, IL-8, MCP-4, MDC and PARC(for all P < 0·0001), at baseline (P < 0·0001), in response to Entamoeba histolytica strain HM1 antigen (EhAg) (P < 0·0001), Onchocerca volvulus adult worm-derived antigen (OvAg) (P = 0·005), PHA (P < 0·0001) and purified protein derivative (PPD) (P < 0·0001) stimulation. In Mp-PAT with hookworm co-infection, the cellular chemokine production of CXCL10 (IP-10) was diminished. In summary, the chemokine and cytokine responses in Mp-PAT were in general not depressed, PBMC from Mp-PAT produced spontaneously and selectively inducible inflammatory and regulatory chemokines and cytokines at higher levels than CTRL and such diverse and distinctive reactivity supports that patent M. perstans infection will not polarize innate and adaptive cellular immune responsiveness in patients.

Background The infestation with Echinococcus multilocularis larvae may persist in humans for up to decades without evident clinical symptoms. Longitudinal investigations are needed to understand the dynamic immunological processes in alveolar echinococcosis (AE) patients associated with an active and progressive, a stable or a regressive course of disease. Methodology/Principal findings This study evaluated the E. multilocularis specific antibody responses, systemic cytokine, and chemokine serum levels over a 10-year follow-up period, as well as cellular responsiveness in AE patients. Our results demonstrate a rapid decrease in antibodies against E. multilocularis specific antigen Em2+. Especially in cured patients, these antibodies remained negative, making them a significant predictor for cured AE. E. multilocularis specific IgG4, and indirect hemagglutination IHA decreased later in time, after around 5 years. While total IgE did not show significant dynamics over the course of disease, E. multilocularis specific IgE decreased after one to two years, and increasing levels were a significant predictor of progressive disease. There was no significant change in systemic IL-8, IL-9, CCL18 or CCL20 serum levels over time. Univariate analysis across groups indicated lower IL-8 levels in cured patients; however, this result could not be confirmed by multivariate analysis. Levels of CCL17 decreased during treatment, especially in cured patients, and thus might serve as a predictive or risk factor for progressive disease. Levels of IL-10 and CCL13 decreased during disease, especially after five and ten years of intervention. The E. multilocularis antigen (EmAg) inducible cellular productions of MCP1(CCL13), TARC(CCL17) and PARC(CCL18) were lowest in patients with cured AE and infection-free controls, while the EmAg inducible cellular production of IFN-γ increased after cure. Significant positive cytokine and chemokine correlations were observed in AE patients for IL-9, IL-10, CCL13(MCP-4), CCL17(TARC) and CCL20(LARC)(for all p<0.001). E. multilocularis specific IgG4 response correlated positively with TARC (p<0.001). Both markers enhanced over time in progressive disease and decreased after cure. The levels of IL-8, IL-10, MCP4 and LARC enhanced with AE regression. Conclusions/Significance Repeated biomarker surveys are advisable to evaluate progression or regression of disease during longitudinal follow-up and such analyses can support imaging techniques and improve staging of AE patients.