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The American Journal of Tropical... Mar 2018The treatment of mansonelliasis is still a challenge because there are few clinical trials for the treatment of the disease. This double-blind, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
The treatment of mansonelliasis is still a challenge because there are few clinical trials for the treatment of the disease. This double-blind, randomized, placebo-controlled study (phase III clinical trial) was conducted to evaluate the effectiveness of a single oral dose of ivermectin (0.15 mg/kg) in the reduction of the microfilaraemia and the occurrence of adverse effects in infected people compared with the control group treated with placebo. A total of 49 microfilaraemic patients were randomly selected from the municipality of Lábrea, State of Amazonas, in the Brazilian Amazon. Among them, 40 patients have concluded the study, 19 treated with ivermectin and 21 treated with placebo. In the first and third days after the treatment, all the patients were clinically evaluated, and the diagnostic and quantification of blood microfilariae through blood filtration in polycarbonate membranes was performed. A significant reduction of the microfilaraemia (99.9%) was observed in the patients who received ivermectin. Slight changes in laboratory test results, without clinical importance, were seen in treated and control groups. Our results suggest that ivermectin is effective and safe for the treatment of infections caused by .
Topics: Administration, Oral; Adolescent; Adult; Animals; Anthelmintics; Brazil; Double-Blind Method; Drug Administration Schedule; Female; Humans; Ivermectin; Male; Mansonella; Mansonelliasis; Microfilariae; Middle Aged; Treatment Outcome
PubMed: 29313486
DOI: 10.4269/ajtmh.17-0698 -
Parasites & Vectors Jan 2018Filariasis and leishmaniasis are two neglected tropical diseases in Mali. Due to distribution and associated clinical features, both diseases are of concern to public...
BACKGROUND
Filariasis and leishmaniasis are two neglected tropical diseases in Mali. Due to distribution and associated clinical features, both diseases are of concern to public health. The goal of this study was to determine the prevalence of co-infection with filarial (Wuchereria bancrofti and Mansonella perstans) and Leishmania major parasites in two ecologically distinct areas of Mali, the Kolokani district (villages of Tieneguebougou and Bougoudiana) in North Sudan Savanna area, and the district of Kolondieba (village of Boundioba) in the South Sudan Savanna area.
METHODS
The prevalence of co-infection (filarial and Leishmania) was measured based on (i) Mansonella perstans microfilaremia count and/or filariasis immunochromatographic test (ICT) for Wuchereria bancrofti-specific circulating antigen, and (ii) the prevalence of delayed type hypersensitivity (DTH) responses to Leishmania measured by leishmanin skin test (LST).
RESULTS
In this study, a total of 930 volunteers between the age of 18 and 65 were included from the two endemic areas of Kolokani and Kolondieba. In general, in both areas, filarial infection was more prevalent than Leishmania infection with an overall prevalence of 15.27% (142/930) including 8.7% (81/930) for Mansonella perstans and 8% (74/930) for Wuchereria bancrofti-specific circulating antigen. The prevalence of Leishmania major infection was 7.7% (72/930) and was significantly higher in Tieneguebougou and Bougoudiana (15.05%; 64/425) than in Boundioba (2.04%; 8/505) (χ = 58.66, P < 0.0001). Among the filarial infected population, nearly 10% (14/142) were also positive for Leishmania with an overall prevalence of co-infection of 1.50% (14/930) varying from 2.82% (12/425) in Tieneguebougou and Bougoudiana to 0.39% (2/505) in Boundioba (P = 0.0048).
CONCLUSION
This study established the existence of co-endemicity of filarial and Leishmania infections in specific regions of Mali. Since both filarial and Leishmania infections are vector-borne with mosquitoes and sand flies as respective vectors, an integrated vector control approach should be considered in co-endemic areas. The effect of potential interaction between filarial and Leishmania parasites on the disease outcomes may be further studied.
Topics: Adult; Animals; Chromatography, Affinity; Coinfection; Cross-Sectional Studies; Endemic Diseases; Female; Filariasis; Healthy Volunteers; Humans; Leishmaniasis; Male; Mali; Microscopy; Middle Aged; Prevalence; Skin Tests; Sudan; Young Adult
PubMed: 29310700
DOI: 10.1186/s13071-017-2531-8 -
Journal of Clinical Microbiology Dec 2017
Topics: Animals; Blood; Eosinophilia; Humans; Immunoglobulin E; Male; Mansonella; Mansonelliasis; Microfilariae; Young Adult
PubMed: 29180506
DOI: 10.1128/JCM.03268-15 -
Parasites & Vectors Nov 2017Approximately 114 million people are infected with Mansonella perstans in large proportions of Africa. In contrast to other filariae that infect humans, M....
BACKGROUND
Approximately 114 million people are infected with Mansonella perstans in large proportions of Africa. In contrast to other filariae that infect humans, M. perstans-infected individuals show no distinct pathology or specific clinical picture, indicating a well-tuned adaptation to the host. In addition, since M. perstans adult worms reside in serous cavities which are difficult to access, research has been hindered and there is a paucity of knowledge about the biology of M. perstans, especially the development of the different life stages as well as M. perstans-driven immune responses. Thus in this study, an in vitro culture system was developed which allows an in-depth analysis of M. perstans.
RESULTS
Culicoides species were caught in Ediki (Kumba), Southwest Region within Cameroon following a blood meal on a microfilaremic donor that had 1500 microfilariae/ml of peripheral blood and kept in captivity for 12 days at 23 °C. In a pilot experiment, 15 infective larvae were obtained from the midges and co-cultured with a confluent monolayer of monkey kidney epithelial cells (LLC-MK2) in DMEM medium supplemented with 10% FBS for up to 77 days. The resulting survival rates of 33% revealed that the cell-conditioned medium was suitable for long-term maintenance of M. perstans worms. To confirm these preliminary observations, 249 infective larvae were cultured for 50 days and their development was monitored daily and microscopically graded for motility. In total, 170 (68.3%) filariae survived and 124 (49.8%) larvae moulted between days 21-30 to become L5 stage larvae which were motile and showed continuous vigorous movement.
CONCLUSION
We have established an in vitro culture system for the generation and long-term maintenance of viable M. perstans worms. This technique will be an important tool to study parasite biology and development, the role in host immunity, and might be helpful to discover novel treatment strategies against this filariae.
Topics: Animals; Cameroon; Cell Line; Ceratopogonidae; Coculture Techniques; Culture Media; Epithelial Cells; Haplorhini; Humans; Kidney; Larva; Mansonella; Mansonelliasis; Microfilariae; Time Factors
PubMed: 29126431
DOI: 10.1186/s13071-017-2515-8 -
International Journal of Ophthalmology 2017
PubMed: 29062789
DOI: 10.18240/ijo.2017.10.26 -
Cytokine Apr 2018Mansonellosis is an endemic disease in the South and Central America. In Brazil, one of the etiological agents is Mansonella ozzardi. This filarial infection is yet...
Mansonellosis is an endemic disease in the South and Central America. In Brazil, one of the etiological agents is Mansonella ozzardi. This filarial infection is yet poorly understood, with a controversial morbity, presenting since a oligosymptoms, malaria-like signs or without complaint in humans. The knowledge of the human immune response to microfilariae infection is limited mainly by different evolutionary cycles of the parasite in the host. In addition, the prevalence of this filarial parasite infection is high in several regions of Amazonas State. A cross-sectional study was conducted in an endemic area for microfilariae of M. ozzardi (MF) infection in the Amazonas State, Brazil. Proinflammatory and regulatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-gamma, and IL-17A) were measured in cryopreserved serum using the Cytometric Bead Array techniques (CBA) in 54 patients diagnosed with M. ozzardi infection and 55 individuals without the infection were included in the study (Controls). The IL-4, IL-6 and IL-10 level increased in infected patients with MF infection, while IL-17A increased in control only. When we compared controls to patients with high or low parasite load, the increased level of IL-6 and IL-10 were maintained. IL-6 contributes to the proinflammatory activity and IL-10 modulates Th1, Th2 and Th17 immune response. Furthermore, IL-4 was detected as a marker in the MF infection and MF patients with low parasite load, indicating the action of the Th2 cell response. The complex network of cytokines acting during M. ozzardi infection depends on a fine balance to determine a host protective effect or filarial persistence. Therefore, these results suggest that the immune response in MF infection is modulated by IL-6/IL-10 axis.
Topics: Adult; Animals; Biomarkers; Brazil; Cytokines; Female; Humans; Interleukin-10; Interleukin-4; Interleukin-6; Male; Mansonella; Mansonelliasis; Middle Aged
PubMed: 29032984
DOI: 10.1016/j.cyto.2017.09.033 -
Emerging Infectious Diseases Sep 2017We report 74 patients in Italy infected with Mansonella perstans nematodes, a poorly described filarial parasite. M. perstans nematodes should be included in the...
We report 74 patients in Italy infected with Mansonella perstans nematodes, a poorly described filarial parasite. M. perstans nematodes should be included in the differential diagnosis for patients with eosinophilia from disease-endemic countries. Serologic analysis is useful for screening, and testing for microfilaremia in peripheral blood should be performed for parasite-positive patients.
Topics: Adolescent; Adult; Africa South of the Sahara; Aged; Animals; Antibodies, Helminth; Child; Child, Preschool; Diagnosis, Differential; Emigrants and Immigrants; Eosinophilia; Female; Humans; Italy; Male; Mansonella; Mansonelliasis; Middle Aged; Retrospective Studies; Travel
PubMed: 28820369
DOI: 10.3201/eid2309.170263 -
Bioorganic & Medicinal Chemistry Letters Aug 2017The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West...
The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG's biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.
Topics: Animals; Biomarkers; Chromatography, Liquid; Glucuronides; Humans; Limit of Detection; Mass Spectrometry; Metabolomics; Neglected Diseases; Onchocerca volvulus; Onchocerciasis; Tyramine
PubMed: 28600214
DOI: 10.1016/j.bmcl.2017.05.082 -
PLoS Neglected Tropical Diseases May 2017
Topics: Adult; Albendazole; Animals; Anthelmintics; Doxycycline; Drug Therapy, Combination; Female; Humans; Ivermectin; Male; Mansonella; Mansonelliasis; Middle Aged; Prednisolone; Travel
PubMed: 28542192
DOI: 10.1371/journal.pntd.0005452 -
PLoS Neglected Tropical Diseases May 2017Filarial infections are tropical diseases caused by nematodes of the Onchocercidae family such as Mansonella perstans. The infective larvae (L3) are transmitted into the...
Filarial infections are tropical diseases caused by nematodes of the Onchocercidae family such as Mansonella perstans. The infective larvae (L3) are transmitted into the skin of vertebrate hosts by blood-feeding vectors. Many filarial species settle in the serous cavities including M. perstans in humans and L. sigmodontis, a well-established model of filariasis in mice. L. sigmodontis L3 migrate to the pleural cavity where they moult into L4 around day 9 and into male and female adult worms around day 30. Little is known of the early phase of the parasite life cycle, after the L3 is inoculated in the dermis by the vector and enters the afferent lymphatic vessels and before the moulting processes in the pleural cavity. Here we reveal a pulmonary phase associated with lung damage characterized by haemorrhages and granulomas suggesting L3 reach the lung via pulmonary capillaries and damage the endothelium and parenchyma by crossing them to enter the pleural cavity. This study also provides evidence for a transient inflammation in the lung characterized by a very early recruitment of neutrophils associated with high expression levels of S100A8 and S100A9 proteins.
Topics: Animals; Calgranulin B; Disease Models, Animal; Female; Filariasis; Filarioidea; Humans; Lung; Mice, Inbred BALB C; Neutrophils
PubMed: 28486498
DOI: 10.1371/journal.pntd.0005596