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PLoS Neglected Tropical Diseases Jan 2018The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-infected individuals present...
Mansonella perstans microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses.
The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-infected individuals present no distinct clinical picture associated with certain pathology. Due to its relatively silent nature, research on this tropical disease has been neglected, especially M. perstans-driven immune responses. A hindrance in obtaining data on M. perstans-specific responses has been the inability to obtain adult worms since their habitats in serous cavities are difficult to access. Thus, in this study, for the first time, we used Mansonella perstans worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from M. perstans microfilaremic individuals (Mp MF+) from Cameroon. Moreover, systemic immune profiles in sera and immune cell composition in peripheral blood from Mp MF+ and amicrofilaremic individuals (Mp MF-) were obtained. Our data reveal that Mp MF+ individuals showed significantly reduced cytokine (IL-4, IL-6 and IL-12p70) and chemokine levels (IL-8 and RANTES), but significantly higher MIP-1β as well as increased M. perstans-specific IgG4 levels compared to Mp MF- individuals. In contrast, upon re-stimulation with worm antigen extract, IFN-γ, IL-13, IL-10 and IL-17A secretion was enhanced in cell cultures from Mp MF+ individuals when compared to those from cultures of healthy European individuals. Moreover, analysis of immune cell composition in peripheral blood from Mp MF+ individuals revealed increased type 2 helper T (Th2), natural killer (NK), regulatory B and T cell (Breg and Treg) subsets but decreased type 1 regulatory T (Tr1) cells. In summary, this study deciphers for the first time, M. perstans-specific immune responses using worm antigen extract and shows that patent M. perstans infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific IgG4 levels.
Topics: Adaptive Immunity; Adult; Aged; Animals; Antibodies, Helminth; B-Lymphocyte Subsets; Cytokines; Female; Humans; Immunity, Innate; Male; Mansonella; Mansonelliasis; Middle Aged; T-Lymphocyte Subsets
PubMed: 29324739
DOI: 10.1371/journal.pntd.0006184 -
Emerging Infectious Diseases Mar 2017We obtained ribosomal and mitochondrial DNA sequences from residents of Amazonas state, Brazil, with Mansonella parasitemias. Phylogenetic analysis of these sequences...
We obtained ribosomal and mitochondrial DNA sequences from residents of Amazonas state, Brazil, with Mansonella parasitemias. Phylogenetic analysis of these sequences confirm that M. ozzardi and M. perstans parasites occur in sympatry and reveal the close relationship between M. perstans in Africa and Brazil, providing insights into the parasite's New World origins.
Topics: Animals; DNA, Protozoan; DNA, Ribosomal Spacer; Humans; Mansonella; Mansonelliasis; Parasitemia; Phylogeny
PubMed: 28221120
DOI: 10.3201/eid2303.161159 -
Acta Tropica Apr 2021Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and... (Comparative Study)
Comparative Study
Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and West Africa and loiasis is estimated to affect about 20 million people. M. perstans infection is widespread in more than 30 countries of sub-Saharan Africa. Due to the difficulty in diagnosing loiasis and M. perstans mansonellosis on a clinical basis, the diagnosis of infection with L. loa and M. perstans relies on laboratory techniques. Definitive diagnosis is based on the detection, identification, and quantification of circulating microfilariae (mf) by microscopy of concentrated blood. However, this is impractical for screening purposes as it requires expert laboratory personnel, considerable blood manipulation, and is time consuming, especially for the final issue of negative result reports, which are very common in the population visited outside endemic areas. The aim of the current work is the preliminary evaluation of the performance of the in-house real-time PCR described by Ta and colleagues compared to the routine microscopic approach for the screening of filarial infections in the clinical setting outside endemic areas, using samples from patients accessing the dedicated outpatient clinics for migrants and travelers of a reference centre for tropical diseases in Northern Italy.
Topics: Adult; Animals; Female; Humans; Loiasis; Male; Mansonelliasis; Microfilariae; Microscopy; Real-Time Polymerase Chain Reaction; Retrospective Studies
PubMed: 33484727
DOI: 10.1016/j.actatropica.2021.105838 -
Parasites & Vectors Apr 2019Culicoides (Diptera; Ceratoponidae) are tiny, stout, blood-sucking flies with a near worldwide distribution. When present, they are often considered a biting nuisance...
BACKGROUND
Culicoides (Diptera; Ceratoponidae) are tiny, stout, blood-sucking flies with a near worldwide distribution. When present, they are often considered a biting nuisance but in addition, they are involved in the transmission of pathogens to humans, domestic and wild animals. Data on Culicoides species in the South-West region of Cameroon dates back to the 1950s. Over the decades, ecological transformation due to agriculture and deforestation may have affected the population dynamics of Culicoides and therefore our study provides an update of their bio-ecology in the region. Furthermore, the role of various Culicoides species in the transmission of parasitic filariae of the genus Mansonella remains inconclusive in this region. This study was designed to address these unknown issues and expand on current scientific knowledge.
RESULTS
Eight species of Culicoides (C. bedfordi, C. inornatipennis, C. fulvithorax, C. grahamii, C. imicola, C. milnei, C. neavei and C. kumbaensis) were collected using light traps and human baits. Culicoides grahamii was the most abundant species, followed closely by C. milnei. Three species (C. milnei, C. grahamii and C. inornatipennis) were common in all observed larval development sites. Only four species (C. inornatipennis, C. fulvithorax, C. grahamii and C. milnei) were collected on humans. Anthropophilic species were more abundant (P < 0.001) in the evening (4-7 pm) when compared to the morning collections (6-9 am). After overnight fly collections using a drop trap with a human microfilaremic donor, C. milnei emerged as the potential host for transmitting Mansonella perstans. Substantial heterogeneity was observed between the trap visiting cycles of the various species (P < 0.001). The biting cycle of the main vector, C. milnei, showed two peaks (10-11 pm and 4-5 am), the highest being 10-11 pm.
CONCLUSIONS
The Culicoides fauna of the South-West region of Cameroon has not changed significantly since the 1950s. Culicoides milnei was demonstrated to be the major vector of M. perstans in this part of Cameroon. It is essentially a nocturnal species which peaks in abundance between 10 and 11 pm.
Topics: Animals; Biodiversity; Cameroon; Ceratopogonidae; Female; Humans; Insect Vectors; Male; Mansonella; Mansonelliasis
PubMed: 30975194
DOI: 10.1186/s13071-019-3432-9 -
Frontiers in Immunology 2023Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of...
Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing glycans with plasma from uninfected individuals and from individuals infected with , , and , four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from and infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of infected individuals. For these infection groups, , and , we further studied the different IgG subclasses to glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.
Topics: Humans; Animals; Filariasis; Antibodies, Helminth; Brugia malayi; Antigens; Immunoglobulin G
PubMed: 36949937
DOI: 10.3389/fimmu.2023.1102344 -
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 -
Pathogens and Global Health May 2016Mansonella ozzardi (Nematoda: Onchocercidae) is an understudied filarial nematode, originally described by Patrick Manson in 1897, that can be transmitted by two... (Review)
Review
Mansonella ozzardi (Nematoda: Onchocercidae) is an understudied filarial nematode, originally described by Patrick Manson in 1897, that can be transmitted by two families of dipteran vectors, biting midges (most of them members of the genus Culicoides) and black flies (genus Simulium). With a patchy geographic distribution from southern Mexico to northwestern Argentina, human infection with M. ozzardi is highly prevalent in some of the Caribbean islands, along riverine communities in the Amazon Basin, and on both sides of the border between Bolivia and Argentina. There is no clinical entity unequivocally associated with M. ozzardi infection, although fever, arthralgia, headache, cold lower extremities, and itchy cutaneous rashes are occasionally mentioned in case report series. More recently, ocular manifestations (especially keratitis) have been associated with mansonelliasis, opening an important area of investigation. Here, we briefly review the biology, epidemiology, pathogenesis, and clinical aspects of M. ozzardi infection and point to some existing knowledge gaps, aiming to stimulate a research agenda to help filling them.
Topics: Animals; Anthelmintics; Arthropod Vectors; Humans; Mansonella; Mansonelliasis; Neglected Diseases; Prevalence
PubMed: 27376501
DOI: 10.1080/20477724.2016.1190544 -
Blood Mar 2018
Topics: Adolescent; Animals; Humans; Lymphadenopathy; Male; Mansonella; Mansonelliasis
PubMed: 29599146
DOI: 10.1182/blood-2018-01-825364 -
Frontiers in Tropical Diseases Jan 2023Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is...
Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is time-consuming, and can be subjective. Loop-mediated isothermal amplification (LAMP) has advantages over microscopy or PCR because of its operational simplicity, rapidity and versatility of readout options. LAMP assays represent a major step forward in improved filarial diagnostic tools suitable for low resource settings and field applicability. The study goal was to retrospectively evaluate the performance and suitability of the O-150, RF4, and Mp419 LAMP assays for diagnosing , and infections, respectively, in humans and vectors under experimental and natural field conditions. Surveys were conducted in four health districts of Cameroon using skin snip and thick blood film methods to detect skin () and blood ( and ) dwelling microfilaria in humans. Engorged vectors (., ., and spp.) were evaluated by LAMP. Dissected, wild-caught vectors were also analyzed. LAMP showed a prevalence of 40.4% (), 17.8% () and 36.6% () versus 20.6% (), 17.4% () and 33.8% () with microscopy. spp. were dissected for microscopy and pooled for LAMP. The O-150 LAMP assay infection rate was 4.3% versus 4.1% by microscopy. spp. were dissected and analyzed individually in the LAMP assay. The RF4 LAMP assay infection rate was 23.5% versus 3.3% with microscopy. The RF4 LAMP assay also detected parasites in spp. fed on low microfilaremic volunteers. The Mp419 LAMP assay infection rate was 0.2% for and 0.04% for , while three other species were LAMP-negative. The sensitivity, species specificity, rapidity and ease of its use of these filarial LAMP assays, and validation of their performance in the field support use as alternatives to microscopy as diagnostic and surveillance tools in global health programs aimed to eliminate onchocerciasis.
PubMed: 36684508
DOI: 10.3389/fitd.2022.1016176 -
Asian Pacific Journal of Tropical... Mar 2016There are two species of filarial parasites with sheathless microfilariae known to commonly cause parasitaemias in humans: Mansonella perstans and Mansonella ozzardi. In... (Review)
Review
There are two species of filarial parasites with sheathless microfilariae known to commonly cause parasitaemias in humans: Mansonella perstans and Mansonella ozzardi. In most contemporary accounts of the distribution of these parasites, neither is usually considered to occur anywhere in the Eastern Hemisphere. However, Sir Patrick Manson, who first described both parasite species, recorded the existence of sheathless sharp-tailed Mansonella ozzardi-like parasites occurring in the blood of natives from New Guinea in each and every version of his manual for tropical disease that he wrote before his death in 1922. Manson's reports were based on his own identifications and were made from at least two independent blood sample collections that were taken from the island. Pacific region Mansonella perstans parasitaemias were also later (in 1923) reported to occur in New Guinea and once before this (in 1905) in Fiji. Although Mansonella-parasitaemias are generally regarded as benign, they are thought to be of public health importance because they can affect the epidemiological monitoring of other filarial diseases. In this article, we reviewed the historic literature concerning Pacific-origin Mansonella-parasitaemias in an attempt to explain how, despite repeated reports of Pacific-region Mansonella-parasitaemias, by as early as the 1970s, the WHO had arrived at the present-day view that Wuchereria bancrofti is the only cause of filarial parasitaemias in Papua New Guinea. We have also evaluated the evidence supporting the contemporary existence of Pacific-area parasitaemia-causing Mansonella parasites and assessed the relevance such parasites could have for present-day lymphatic filariasis elimination efforts in the region.
PubMed: 26972389
DOI: 10.1016/j.apjtm.2016.01.040