Filarial Parasite Research Articles

Quinolone-fused cyclic sulfonamide as a novel benign antifilarial agent

Search of potent antifilarial drugs has been a major thrust area in tropical medicine research over the decades. Herein, we report 4,7-dimethyl-3,4,7,8-tetrahydro-3λ6-[1,2]thiazino[4,3-f]quinoline-3,3,8-trione (8l) as a new class of antifilarial agent which is extremely potent, with lethality against all the developmental stages (oocyte, microfilaria and adult) of the filarial parasite Setaria cervi. Molecular investigation on its mode of action revealed that 8l is a typical inducer of reactive oxygen species that triggers oxidative stress inside the filarid and further signals induction of apoptosis by activating both intrinsic and extrinsic pathways. Moreover, 8l is also active against Wolbachia, the essential endosymbiont of several human infectious filarids. Selective toxicity against filarial parasites and non-toxic nature in rat model were found as unique traits of 8l to be a future medicine. Taken en masse, this maiden report on a novel quinolone fused cyclic sulfonamide presents a promising therapeutic lead for lymphatic filariasis in future.

Occurrence of Dipetalonema gracile in a wild population of woolly monkey Lagothrix poeppiigii in the northeastern Peruvian Amazon.

Dipetalonema gracile (Rudolphi, 1809) (Filarioidea: Onchocercidae) is one of six species of cavities filarial parasites of Neotropical non-human primates. The present study recorded the occurrence of D. gracile, provides morphological and morphometric data and extends the geographical distribution. Adult filariae were obtained from the thoracic and abdominal cavities of 38 specimens of woolly monkey, which were used for local human consumption, in the northeastern Peruvian Amazon. Male and female filarids were processed and analysed using light and scanning electron microscopy. Details of the cephalic papillae, post-cloacal bands and papillae, vulva, phasmid position and lateral appendages are showed by scanning electron microscopy and is recorded the occurrencce of Lagothrix poeppigii monkey as a new host of this filaria in the Yavari-Mirin river basin, Peruvian Amazon.

A superhydrophobic cone to facilitate the xenomonitoring of filarial parasites, malaria, and trypanosomes using mosquito excreta/feces.

Background: Molecular xenomonitoring (MX), the testing of insect vectors for the presence of human pathogens, has the potential to provide a non-invasive and cost-effective method for monitoring the prevalence of disease within a community. Current MX methods require the capture and processing of large numbers of mosquitoes, particularly in areas of low endemicity, increasing the time, cost and labour required. Screening the excreta/feces (E/F) released from mosquitoes, rather than whole carcasses, improves the throughput by removing the need to discriminate vector species since non-vectors release ingested pathogens in E/F. It also enables larger numbers of mosquitoes to be processed per pool. However, this new screening approach requires a method of efficiently collecting E/F. Methods: We developed a cone with a superhydrophobic surface to allow for the efficient collection of E/F. Using mosquitoes exposed to either Plasmodium falciparum, Brugia malayi or Trypanosoma brucei brucei, we tested the performance of the superhydrophobic cone alongside two other collection methods. Results: All collection methods enabled the detection of DNA from the three parasites. Using the superhydrophobic cone to deposit E/F into a small tube provided the highest number of positive samples (16 out of 18) and facilitated detection of parasite DNA in E/F from individual mosquitoes. Further tests showed that following a simple washing step, the cone can be reused multiple times, further improving its cost-effectiveness. Conclusions: Incorporating the superhydrophobic cone into mosquito traps or holding containers could provide a simple and efficient method for collecting E/F. Where this is not possible, swabbing the container or using the washing method facilitates the detection of the three parasites used in this study.

Insulin receptor knockdown blocks filarial parasite development and alters egg production in the southern house mosquito, Culex quinquefasciatus.

Lymphatic filariasis, commonly known as elephantiasis, is a painful and profoundly disfiguring disease. Wuchreria bancrofti (Wb) is responsible for >90% of infections and the remainder are caused by Brugia spp. Mosquitoes of the genera Culex (in urban and semi-urban areas), Anopheles (in rural areas of Africa and elsewhere), and Aedes (in Pacific islands) are the major vectors of W. bancrofti. A preventive chemotherapy called mass drug administration (MDA), including albendazole with ivermectin or diethylcarbamazine citrate (DEC) is used in endemic areas. Vector control strategies such as residual insecticide spraying and long-lasting insecticidal nets are supplemental to the core strategy of MDA to enhance elimination efforts. However, increasing insecticide resistance in mosquitoes and drug resistance in parasite limit the effectiveness of existing interventions, and new measures are needed for mosquito population control and disruption of mosquito-parasite interactions to reduce transmission. Mosquito insulin signaling regulates nutrient metabolism and has been implicated in reduced prevalence and intensity of malaria parasite, Plasmodium falciparum, infection in mosquitoes. Currently no data are available to assess how insulin signaling in mosquitoes affects the development of multi-cellular parasites, such as filarial nematodes. Here, we show that insulin receptor knockdown in blood fed C. quinquefasciatus, the major vector of Wb in India, completely blocks the development of filarial nematode parasite to the infective L3 stage, and results in decreased ecdysteroid production and trypsin activity leading to fewer mosquito eggs. These data indicate that a functional mosquito insulin receptor (IR) is necessary for filarial parasite development and mosquito reproduction. Therefore, insulin signaling may represent a new target for the development of vector control or parasite blocking strategies.

Filaria specific antibody response profiling in plasma from anti-retroviral na\xefve Loa loa microfilaraemic HIV-1 infected people

BackgroundIn West and Central Africa areas of endemic Loa loa infections overlap with regions of high prevalence of human immunodeficiency virus type 1 (HIV-1) infections. Because individuals in this region are exposed to filarial parasites from birth, most HIV-1 infected individuals invariably also have a history of filarial parasite infection. Since HIV-1 infection both depletes immune system and maintains it in perpetual inflammation, this can hamper Loa loa filarial parasite mediated immune modulation, leading to enhanced loaisis.MethodsIn this study we have assessed in plasma from asymptomatic anti-retroviral (ARV) naïve Loa loa microfilaraemic HIV-1 infected people the filarial antibody responses specific to a filariasis composite antigen consisting of Wbgp29-BmR1-BmM14-WbSXP.The antibody responses specific to the filariasis composite antigen was determined by enzyme linked immunosorbent assay (ELISA) in plasma from ARV naïve Loa loa microfilaraemic HIV-1 infected participants. In addition the filarial antigen specific IgG antibody subclass profiles were also determined for both HIV-1 positive and negative people.ResultsBoth Loa loa microfilaraemic HIV-1 positive and negative individuals showed significantly higher plasma levels of IgG1 (P < 0.0001), IgG2 (P < 0.0001) and IgM (P < 0.0001) relative to amicrofilaraemic participants. A significant increase in IgE (P < 0.0001) was observed exclusively in Loa loa microfilaraemic HIV-1 infected people. In contrast there was a significant reduction in the level of IgG4 (p < 0.0001) and IgG3 (P < 0.0001) in Loa loa microfilaraemic HIV-1 infected individuals.ConclusionsLoa loa microfilaraemia in ARV naïve HIV-1 infected people through differential reduction of plasma levels of filarial antigen specific IgG3, IgG4 and a significant increase in plasma levels of filarial antigen specific IgE could diminish Loa loa mediated immune-regulation. This in effect can result to increase loaisis mediated immunopathology in antiretroviral naive HIV-1 infected people.

Inhibition efficiency of a newly isolated flavonoid compound from Vitex negundo L. leaves against cattle-endosymbiont Setaria cervi: Phytomedicine for lymphatic filariasis

Experimental studies has been carried out to isolate and identify an active antifilarial compound from Vitex negundo L. plant as it has been used for treatment against filariasis in Indian traditional system of medicine. In vitro antifilarial assay has been carried out against adult filarial parasite Setaria cervi worms by both worm motility and MTT reduction assays. Levels of oxidative stress parameters MDA, carbonyl content and nitric oxide levels have been detected. The isolated compound exhibited significant antifilarial activity in dose dependent manner. The active compound has been chemically characterized and identified as 4,5-diethyl-3′-ethoxy-pyro-flavone.

Seroepidemiology of helminths and the association with severe malaria among infants and young children in Tanzania.

The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is high, particularly in Africa, and co-infection is common. However, the effects of filarial infection on the risk of severe malaria are unknown. We used the remaining serum samples from a large cohort study in Muheza, Tanzania to describe vector-borne filarial sero-reactivity among young children and to identify associations between exposure to filarial parasites and subsequent severe malaria infections. We identified positive filarial antibody responses (as well as positive antibody responses to Strongyloides stercoralis) among infants as young as six months. In addition, we found a significant association between filarial seropositivity at six months of age and subsequent severe malaria. Specifically, infants who developed severe malaria by one year of age were 3.9 times more likely (OR = 3.9, 95% CI: 1.2, 13.0) to have been seropositive for filarial antigen at six months of age compared with infants who did not develop severe malaria.

Assessment of macrofilaricidal activity of leaf extracts of Terminalia sp. against bovine filarial parasite Setaria cervi.

Antifilarial potential of three medicinal plants namely, Terminalia bellerica, Terminalia chebula and Terminalia catappa was explored using Setaria cervi, a bovine filarial parasite at concentrations of 2.5, 5 and 10mg/ml. Amongst all the extracts, methanol extract of T. bellerica showed highest macrofilaricidal activity i.e. 84.63±1.11 at 10mg/ml in MTT reduction assay with IC50 value of 2.7mg/ml. which was better than the standard DEC i.e. 79.22±3.1% at 10mg/ml with IC50 value 2.84mg/ml. Other plant extracts showed mild in vitro macrofilaricidal activity. T. bellerica methanol extract exhibited significant GST activity of 18.86±0.21 and 12.83±0.03μM/ml/min at 5 and 10mg/ml with percentage inhibition value of 73.96% and 82.29% respectively. DEC showed GST activity value of 40.03±4.14 and 21.48±6.44μM/ml/min with percentage inhibition value of 21.76% and 58.01% at 5 and 10mg/ml respectively. Thus, methanol extract of leaves of T. bellerica exhibited highly significant antifilarial potential and needs detailed analysis.

Infective Larvae of Brugia malayi Induce Polarization of Host Macrophages that Helps in Immune Evasion.

Filarial parasites suppress, divert, or polarize the host immune response to aid their survival. However, mechanisms that govern the polarization of host MΦs during early filarial infection are not completely understood. In this study, we infected BALB/c mice with infective larvae stage-3 of Brugia malayi (Bm-L3) and studied their effect on the polarization of splenic MΦs. Results showed that MΦs displayed M2-phenotype by day 3 p.i. characterized by upregulated IL-4, but reduced IL-12 and Prostaglandin-D2 secretion. Increased arginase activity, higher arginase-1 but reduced NOS2 expression and poor phagocytic and antigen processing capacity was also observed. M2 MΦs supported T-cell proliferation and characteristically upregulated p-ERK but downregulated NF-κB-p65 and NF-κB-p50/105. Notably, Bm-L3 synergized with host regulatory T-cells (Tregs) and polarized M2 MΦs to regulatory MΦs (Mregs) by day 7 p.i., which secreted copious amounts of IL-10 and prostaglandin-E2. Mregs also showed upregulated expression levels of MHC-II, CD80, and CD86 and exhibited increased antigen-processing capacity but displayed impaired activation of NF-κB-p65 and NF-κB-p50/105. Neutralization of Tregs by anti-GITR + anti-CD25 antibodies checked the polarization of M2 MΦs to Mregs, decreased accumulation of regulatory B cells and inflammatory monocytes, and reduced secretion of IL-10, but enhanced IL-4 production and percentages of eosinophils, which led to Bm-L3 killing. In summary, we report hitherto undocumented effects of early Bm-L3 infection on the polarization of splenic MΦs and show how infective larvae deftly utilize the functional plasticity of host MΦs to establish themselves inside the host.

Immunomodulatory potential of recombinant filarial protein, rWbL2, and its therapeutic implication in experimental ulcerative colitis in mouse

Objective: Immunomodulation by helminth proteins has potential therapeutic implications in inflammatory bowel disease. In the present study, we have explored the therapeutic effect of a RAL family protein of filarial parasite Wuchereria bancrofti i.e., rWbL2 protein against DSS induced colitis in a mouse model.Materials and methods: Anti-inflammatory activity of rWbL2 on mice peritoneal exudate cells was analyzed under in vitro condition. The colitis mice were treated intraperitoneally (i.p.) with rWbL2 in increasing doses (10 µg, 25 µg, and 50 µg) on days 4, 5, and 6. Disease severity was assessed by disease activity index (DAI), macroscopic and histopathological scores, and enzyme myeloperoxidase activity (MPO) in the colon. The response of the cultured splenocytes from treated mice to Con-A stimulation, in terms of ELISA-based assessment of the protein followed by the assessment of mRNA expression of cytokines, was measured by real-time PCR analysis.Result: rWbL2 protein showed anti-inflammatory activity in vitro. Treatment with rWbL2 (at 25 µg/dose) effectively attenuated disease severity by reducing weight loss, DAI, mucosal edema, colon damage, and MPO activity. This therapeutic effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of pro-inflammatory cytokine IFN-γ and TNF-α by the splenocytes of treated mice followed by stimulation with Con-A.Conclusions: These results provide evidence of the strong immunomodulatory potential of rWbL2 protein implicating its therapeutic application against ulcerative colitis.

Full mitochondrial and nuclear genome comparison confirms that Onchocerca sp. \u201cSiisa\u201d is Onchocerca ochengi

Onchocerca ochengi is a nodule-forming filarial nematode parasite of cattle. It is the closest known relative of the human parasite Onchocerca volvulus, with which it shares the black fly vector Simulium damnosum. Onchocerca sp. “Siisa” was described in black flies and in cattle and, based on limited mitochondrial sequence information, appeared to be about equally phylogenetically distant from O. ochengi and O. volvulus. Based on molecular genetic markers and apparent interbreeding, we later proposed that O. sp. “Siisa” belongs to the species O. ochengi. However, we did not demonstrate directly that the hybrids were fertile, and we were still unable to resolve the phylogenetic relationship of O. ochengi, O. sp. “Siisa,” and O. volvulus, leaving some concerns with the conclusion mentioned above. Here, we present fully assembled, manually curated mitochondrial genomes of O. ochengi and O. sp. “Siisa,” and we compare multiple individuals of these two taxa with respect to their whole mitochondrial and nuclear genomes. Based on the mitochondrial genomes, O. ochengi and O. sp. “Siisa” are phylogenetically much closer to each other than to O. volvulus. The differences between them are well within the range of what is expected for within-species variation. The nuclear genome comparison provided no indication of genetic separation of O. ochengi and O. sp. “Siisa.” From this, in combination with the earlier literature, we conclude that O. ochengi and O. sp. “Siisa” should be considered one species.

The presence of filarial parasites of dogs in Serrae Province

Blood samples of 252 male and female dogs, aged between 7 months and 12 years, different races, and usefulness (utilities), which came from lowland and demi-highland and highland districts of Serrae province, of Macedonia-Greece. The purpose of this survey was to find out the infected dogs with filarial parasites. Ninety six (38,1%) out of the examined dogs were found to be infected with one or more parasitic species. The 86 (34,13%) dogs were infected with Dirofilaria immitis, the 84 (33,33%) dogs were infected with Dirofilaria repens and the 10 (3,97%) dogs were infected with Dipetalonema reconditum. Single infection, with Dirofilaria immitis was observed in 9, with Dirofilaria repens in 7, whereas, no single infection with Dipetalonema reconditum were observed. Mixed infection with Dirofilaria immitis + Dirafilaria repens were observed in 66, with Dirofilaria immitis + Dipetalonema reconditum were observed in 2, with Dirofilaria repens + Dipetalonema reconditum in 2 and finely, in 10 the combination with Dirofilaria immitis + Dirofilaria repens + Dipetalonema reconditum. The microfilarial burden per ml of the infected dogs fluctuated between 85 and 7.375. There were no any significant difference between the different group of dogs according sex, age, usefulness, longhair or shorthair as well as lowland and semi-highland districts, on the percentage of infected or microfilarial population of each.

Immunomodulatory Activity of Sulfonamide Chalcone Compounds in Mice Infected with Filarial Parasite, Brugia malayi.

Diethyl carbamazine (DEC) is being used as a sole drug to treat the lymphatic filariasis, although encountered with many limitations. Importantly, DEC works with putative host immunomodulating activities without any direct antifilarial effect. This study aimed to assess the possible modulatory effect on host immune system by sulfonamide chalcone compound, having direct antifilarial activity. The immunomodulatory activity of DEC and/or chalcone compound, 4t on mice peritoneal exudate cells (PECs) was analyzed initially in vitro. This was followed by the study of in vivo effect of these test agents in the parasitaemic BALB/c mice induced by Brugia malayi microfilariae. Cytokine profile and iNOS induction were measured from PECs of mice. 4t compound showed anti-inflammatory activity in vivo in contrast to DEC. Further 4t was found to increase anti-inflammatory and regulatory cytokines, IL-10 and TGF-β gene expression with down regulation of pro-inflammatory cytokines TNF-α and IFN-γ and iNOS in mice PECs in in vitro. In conclusion, chalcones having direct antifilarial effect also upsurges anti-inflammatory host immune response. Therefore, the results might be envisaged as 4t to be a better alternative to DEC in the chronic case of lymphatic filariasis.

Combinations of registered drugs reduce treatment times required to deplete Wolbachia in the Litomosoides sigmodontis mouse model.

Filarial parasites can be targeted by antibiotic treatment due to their unique endosymbiotic relationship with Wolbachia bacteria. This finding has led to successful treatment strategies in both, human onchocerciasis and lymphatic filariasis. A 4–6 week treatment course using doxycycline results in long-term sterility and safe macrofilaricidal activity in humans. However, current treatment times and doxycycline contraindications in children and pregnant women preclude widespread administration of doxycycline in public health control programs; therefore, the search for shorter anti-wolbachial regimens is a focus of ongoing research. We have established an in vivo model for compound screening, using mice infected with Litomosoides sigmodontis. We could show that gold standard doxycycline treatment did not only deplete Wolbachia, it also resulted in a larval arrest. In this model, combinations of registered antibiotics were tested for their anti-wolbachial activity. Administration of rifamycins in combination with doxycycline for 7 days successfully depleted Wolbachia by > 2 log (>99% reduction) and thus resulted in a significant reduction of the treatment duration. Using a triple combination of a tetracycline (doxycycline or minocycline), a rifamycin and a fluoroquinolone (moxifloxacin) led to an even greater shortening of the treatment time. Testing all double combinations that could be derived from the triple combinations revealed that the combination of rifapentine (15mg/kg) and moxifloxacin (2 x 200mg/kg) showed the strongest reduction of treatment time in intraperitoneal and also oral administration routes. The rifapentine plus moxifloxacin combination was equivalent to the triple combination with additional doxycycline (>99% Wolbachia reduction). These investigations suggest that it is possible to shorten anti-wolbachial treatment times with combination treatments in order to achieve the target product profile (TPP) requirements for macrofilaricidal drugs of no more than 7–10 days of treatment.

Mosquitoes and the Lymphatic Filarial Parasites: Research Trends and Budding Roadmaps to Future Disease Eradication.

The mosquito-borne lymphatic filariasis (LF) is a parasitic, neglected tropical disease that imposes an unbearable human scourge. Despite the unprecedented efforts in mass drug administration (MDA) and morbidity management, achieving the global LF elimination slated for the year 2020 has been thwarted by limited MDA coverage and ineffectiveness in the chemotherapeutic intervention. Moreover, successful and sustainable elimination of mosquito-vectored diseases is often encumbered by reintroduction and resurgence emanating from human residual or new infections being widely disseminated by the vectors even when chemotherapy proves effective, but especially in the absence of effective vaccines. This created impetus for strengthening the current defective mosquito control approach, and profound research in vector–pathogen systems and vector biology has been pushing the boundaries of ideas towards developing refined vector-harnessed control strategies. Eventual implementation of these emerging concepts will offer a synergistic approach that will not only accelerate LF elimination, but also augurs well for its future eradication. This brief review focuses on advances in mosquito–filaria research and considers the emerging prospects for future eradication of LF.

Eulimdana clava (Nematoda: Filarioidea) infection in domestic pigeons (Columba livia domestica): Molecular characterization and pathological changes

Filarial nematodes of the Eulimdana genus inhabit subcutaneous tissue of various avian species, mostly Charadriiforme birds. In domestic pigeons, E. clava is the only species recorded in the subcutaneous tissue in a number of isolated cases. In the present study, we discuss the morphology and histopathology of filarial nematodes recovered from subcutaneous tissue of domestic pigeons in Bosnia and Herzegovina. In total 110 pigeons were submitted to necropsy at the Department of Pathology of the Faculty of Veterinary Medicine in Sarajevo. At necropsy, in four pigeons (3.6%) numerous thread-like 0.9–2.1 cm long nematode parasites were observed in the subcutaneous tissue, peritracheal and periesophageal connective tissue. In one pigeon, the parasites were also found free in the body cavity around the heart and lungs. In addition, several 80–90 μm long microfilariae were noted in the tissue cross-sections. No significant lesions were observed associated with adult parasites or microfilariae. Based on morphology, host species and localization detected parasites were identified as E. clava. Molecular analyses of the cox1 and 12S rRNA nucleotide sequences herein generated revealed the close genetic relationship to other filarioid nematodes. The importance of the nematodes in pigeons and the lack of sequences in genetic databases for comparison of avian filarial parasites are emphasized.

High resolution melting real-time PCR detect and identify filarial parasites in domestic cats

Objective: To detect and identify filarial parasites in dried blood spots (DBS) collected from domestic cats using high resolution melting real-time PCR (HRM RT-PCR). Methods: A total of 208 DBS were collected from domestic cats in a brugian filariasis endemic areas in Surat Thani Province, southern Thailand. Microfilariae were found in 9 blood slides using Giemsa-stained thick blood film. The extracted DNA from blood spot volumes of 10 and 20 μL DBS with positive filarial parasites in cats were performed using HRM RT-PCR method. The primers were designed based on the partial mitochondrial 12S rRNA gene for identifying Brugia malayi, Brugia pahangi, Dirofilaria immitis. All purified samples were then detected. Results: Using different volumes of 10 μL and 20 μL DBS could easily distinguish filarial parasites and showed similar results. PCR amplicons of Brugia malayi, Brugia pahangi and Dirofilaria immitis were determined at melting peak (temperature) of 75.70 77.46 and 73.56 respectively. All 9 positive DBS samples showed positive Brugia pahangi and similar nucleotide sequences. Conclusions: This HRM RT-PCR method is able to diagnose, identify and discriminate filarial parasites collected from DBS, which is simple and inexpensive compared with other probe-based genotyping methods. Furthermore, this method is useful to survey, prevent and control filariasis.

Mansonellosis: current perspectives.

Mansonellosis is a filarial disease caused by three species of filarial (nematode) parasites (Mansonella perstans, Mansonella streptocerca, and Mansonella ozzardi) that use humans as their main definitive hosts. These parasites are transmitted from person to person by bloodsucking females from two families of flies (Diptera). Biting midges (Ceratopogonidae) transmit all three species of Mansonella, but blackflies (Simuliidae) are also known to play a role in the transmission of M. ozzardi in parts of Latin America. M. perstans and M. streptocerca are endemic in western, eastern, and central Africa, and M. perstans is also present in the neotropical region from equatorial Brazil to the Caribbean coast. M. ozzardi has a patchy distribution in Latin America and the Caribbean. Mansonellosis infections are thought to have little pathogenicity and to be almost always asymptomatic, but occasionally causing itching, joint pains, enlarged lymph glands, and vague abdominal symptoms. In Brazil, M. ozzardi infections are also associated with corneal lesions. Diagnosis is usually performed by detecting microfilariae in peripheral blood or skin without any periodicity. There is no standard treatment at present for mansonellosis. The combination therapy of diethylcarbamazine plus mebendazole for M. perstans microfilaremia is presently one of the most widely used, but the use of ivermectin has also been proven to be very effective against microfilariae. Recently, doxycycline has shown excellent efficacy and safety when used as an antimicrobial against endosymbiotic Wolbachia bacteria harbored by some strains of M. perstans and M. ozzardi. Diethylcarbamazine and ivermectin have been used effectively to treat M. streptocerca infection. There are at present no estimates of the disease burden caused by mansonellosis, and thus its importance to many global health professionals and policy makers is presently limited to how it can interfere with diagnostic tools used in modern filarial disease control and elimination programs aimed at other species of filariae.

Integrated risk mapping and landscape characterisation of lymphatic filariasis and loiasis in South West Nigeria

Nigeria has the heaviest burden of lymphatic filariasis (LF) in sub-Saharan Africa, which is caused by the parasite Wuchereria bancrofti and transmitted by Anopheles mosquitoes. LF is targeted for elimination and the national programme is scaling up mass drug administration (MDA) across the country to interrupt transmission. However, in some regions the co-endemicity of the filarial parasite Loa loa (loiasis) is an impediment due to the risk of severe adverse events (SAEs) associated with the drug ivermectin. To better understand factors influencing LF elimination in loiasis areas, this study conducted a cross-sectional survey on the prevalence and co-distribution of the two infections, and the potential demographic, landscape, human movement, and intervention-related risk factors at a micro-level in the South West zone of Nigeria. In total, 870 participants from 10 communities on the fringe of a meso-endemic loiasis area of Osun State were selected. LF prevalence was measured by clinical assessment and using the rapid immunochromatographic test (ICT) to detect W. bancrofti antigen. Overall LF prevalence was low with ICT positivity ranging from 0 to 4.7%, with only 1 hydrocoele case identified. Males had significantly higher ICT positivity than females (3.2% vs 0.8%). Participants who did not sleep under a bed net had higher ICT positivity (4.0%) than those who did (1.3%). ICT positivity was also higher in communities with less tree coverage/canopy height (2.5–2.8%) than more forested areas with greater tree coverage/canopy height (0.9–1.0%). In comparison, loiasis was determined using the rapid assessment procedure for loiasis (RAPLOA), and found in all 10 communities with prevalence ranging from 1.4% to 11.2%. No significant difference was found by participants' age or sex. However, communities with predominately shrub land (10.4%) or forested land cover (6.2%) had higher prevalence than those with mosaic vegetation/croplands (2.5%). Satellite imagery showed denser forested areas in higher loiasis prevalence communities, and where low or no ICT positivity was found. Only one individual was found to be co-infected. GPS tracking of loiasis positive cases and controls also highlighted denser forested areas within higher loiasis risk communities and the sparser land cover in lower-risk communities. Mapping LF-loiasis distributions against landscape characteristics helped to highlight the micro-heterogeneity, identify potential SAE hotspots, and determine the safest and most appropriate treatment strategy.

Identification and characterization of a novel prolyl oligopeptidase in filarial parasite Setaria cervi

A 75 kDa serine protease having prolyl oligopeptidase activity has been purified from Setaria cervi, a bovine filarial parasite. The MALDI-MS/MS analysis of the purified protein revealed 6 peptides showing nearest match S9A (prolyl oligopeptidase) family protein from Plesiocystis pacifica. The ScPOP was found to be unique compared to mammalian POP with respect to its kinetic properties. To elucidate its role, filarial parasites were exposed to specific inhibitor of POP, Z-Pro-prolinal (ZPP) for 8 h. The inhibition of POP induced calcium signaling via phospholipase c stimulation which further triggered mitochondrial mediated apoptosis in filarial parasites.