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Mansonella ozzardi, a filarioid parasite, causes human mansonellosis in the Americas. We identified raccoons (Procyon lotor) as wildlife reservoirs of M. ozzardi in Costa Rica. Noting the sympatry of free-ranging raccoons and humans, we conclude that mansonellosis is a considerable public health risk in the region.

Mansonella spp. have been reported to have a wide global distribution. Despite the distribution and co-occurrence with other filarial parasites like Wuchereria bancrofti, Onchocerca volvulus and Loa loa, it is given little attention. There are few surveillance programmes for assessing the distribution of mansonellosis, due to the associated mild to no symptoms experienced by infected people. However, addressing this infection is critical to the onchocerciasis control program as current rapid diagnostic tools targeting O. volvulus have the tendency to cross react with Mansonella species. In this study we identified and characterised M. perstans from five sites in two districts in the Volta Region of Ghana and compared them to samples from other regions. Night blood smears and filter blood blots were obtained from individuals as part of a study on lymphatic filariasis. The Giemsa-stained smears were screened by microscopy for the presence of filarial parasites. Genomic DNA was extracted from blood blots from 39 individuals that were positive for M. perstans and Nested PCR targeting the internal spacer 1 (ITS-1) was conducted. Of these, 30 were sequenced and 24 sequences were kept for further analysis. Phylogenetic analysis of 194 nucleotide positions showed no differences in the samples collected. The similarities suggests that there could be one species in this area. However, more robust studies with larger sample sizes are required to draw such conclusions. We also observed a clustering of the samples from Ghana with reference sequences from Africa and Brazil, suggesting they could be related. This study draws further attention to a neglected infection, presents the first characterisation of M. perstans in Ghana and calls for more population-based studies across different geographical zones to ascertain species variations and disease distribution., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Opoku, de Souza. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Loiasis is endemic in the northern and western part of the Republic of Congo. Between 2004 and 2010, surveys were conducted, using the RAPLOA method, in all departments of the Republic of Congo to assess the distribution of loiasis. Prior to 2004, only two parasitological surveys on loiasis had been conducted in Congo and mainly in the Department of Lékoumou, in the southwestern of the country. In 2019, we conducted a parasitological survey in this same department, more than 30 years after the first surveys., Methods: The study was conducted in 21 villages. Loa loa and Mansonella perstans microfilaremia levels were quantified using 50 µl calibrated blood smears., Results: A total of 2444 individuals were examined. The median age of the screened individuals was 43 (interquartile range: 30-57, range: 18-91) years old. The overall prevalences of L. loa and M. perstans microfilaremia were 20.0% [95% confidence intervals (CI) 18.0-21.6%] and 1.0% (95% CI 0.6-1.4%) respectively. The proportion of individuals with a microfilarial density of L. loa > 8000 mf/ml and > 30,000 mf/ml were 5.1% (95% CI 4.3-6.1%) and 1.1% (95% CI 0.8-1.7%), respectively. The overall community microfilarial load was 3.4 mf/ml., Conclusions: Prevalences and intensities of L. loa infection remained generally stable between the late 1980s and 2019 in the Lékoumou Department. In contrast, parasitological indicators for M. perstans have declined sharply in the intervening years for an unknown reason., (© 2023. The Author(s).)

Background: Mansonellosis is an undermapped insect-transmitted disease caused by filarial nematodes that are estimated to infect hundreds of millions of people. Despite their prevalence, there are many outstanding questions regarding the general biology and health impacts of the responsible parasites. Historical reports suggest that the Colombian Amazon is endemic for mansonellosis and may serve as an ideal location to pursue these questions., Methods: We deployed molecular and classical approaches to survey Mansonella prevalence among adults belonging to indigenous communities along the Amazon River and its tributaries near Leticia, Colombia., Results: Loop-mediated isothermal amplification (LAMP) assays on whole-blood samples detected a much higher prevalence of Mansonella ozzardi infection (approximately 40%) compared to blood smear microscopy or LAMP performed using plasma, likely reflecting greater sensitivity and the ability to detect low microfilaremias and occult infections. Mansonella infection rates increased with age and were higher among men. Genomic analysis confirmed the presence of M. ozzardi that clusters closely with strains sequenced in neighboring countries. We successfully cryopreserved M. ozzardi microfilariae, advancing the prospects of rearing infective larvae in controlled settings., Conclusion: These data suggest an underestimation of true mansonellosis prevalence, and we expect that these methods will help facilitate the study of mansonellosis in endemic and laboratory settings., Competing Interests: Potential conflicts of interest. C. K. S. C., Z. L., A. S., and S. R. are employed by New England Biolabs, a manufacturer and vendor of molecular biology reagents. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Doxycycline is used for treatment of Mansonella perstans infection. Immune modulatory effects of both M. perstans and doxycycline have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans-infected individuals before and after doxycycline treatment to characterize doxycycline effects on host T-cell immunity., Methods: Immune characterization of doxycycline-treated M. perstans-infected individuals was performed as part of an open-label randomized clinical trial. Immune cell population phenotyping by flow cytometry and functional in vitro T-cell assays were performed at baseline, 6 months, and "long term" (18-24 months) after treatment start. Treatment efficacy, based on peripheral blood microfilaria (mf) burden, was correlated with immune parameters and effects on immune response against concomitant Mycobacterium tuberculosis infection were determined., Results: Immune population phenotyping indicated changes in functional T-cell responses after doxycycline treatment. Constitutive and superantigen-induced T-cell activation and polarization towards T-helper type (TH) 1 phenotype at baseline declined after doxycycline treatment, whereas low proportions of TH17 and TH1* cells at baseline increased significantly at follow-up. In accordance, long-term decline in antigen-specific TH1 responses against concomitant M. tuberculosis infection was seen. Notably, only TH17 and TH1* changes after 6 months and TH17 at baseline were negatively correlated with M. perstans microfilaria burden or reduction, whereas long-term changes were not associated with treatment efficacy., Conclusions: We found long-term immune modulatory effects of doxycycline treatment leading to decreased constitutive T-cell activation, polarization towards TH17/TH1*, and impaired immune response against concomitant M. tuberculosis infection., Competing Interests: Potential conflicts of interests. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Mansonella perstans is among the most neglected of the neglected tropical diseases and is believed to cause more human infections than any other filarial pathogen in Africa. Based largely upon assumptions of limited infection-associated morbidity, this pathogen remains understudied, and many basic questions pertaining to its pathogenicity, distribution, prevalence, and vector-host relationships remain unanswered. However, in recent years, mounting evidence of the potential for increased Mansonella infection-associated disease has sparked a renewal in research interest. This, in turn, has produced a need for improved diagnostics, capable of providing more accurate pictures of infection prevalence, pathogen distribution, and vector-host interactions., Methodology/principal Findings: Utilizing a previously described pipeline for the discovery of optimal molecular diagnostic targets, we identified a repetitive DNA sequence, and developed a corresponding assay, which allows for the sensitive and species-specific identification of M. perstans in human blood samples. Testing also demonstrated the ability to utilize this assay for the detection of M. perstans in field-collected mosquito samples. When testing both sample types, our repeat-targeting index assay outperformed a ribosomal sequence-targeting reference assay, facilitating the identification of additional M. perstans-positive samples falsely characterized as "negative" using the less sensitive detection method., Conclusions/significance: Through the development of an assay based upon the systematic identification of an optimal DNA target sequence, our novel diagnostic assay will provide programmatic efforts with a sensitive and specific testing platform that is capable of accurately mapping M. perstans infection and determining prevalence. Furthermore, with the added ability to identify the presence of M. perstans in mosquito samples, this assay will help to define our knowledge of the relationships that exist between this pathogen and the various geographically relevant mosquito species, which have been surmised to represent potential secondary vectors under certain conditions. Detection of M. perstans in mosquitoes will also demonstrate proof-of-concept for the mosquito-based monitoring of filarial pathogens not vectored primarily by mosquitoes, an approach expanding opportunities for integrated surveillance., Competing Interests: The authors have no competing interests to disclose., (Copyright: © 2022 Pilotte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Infection with Mansonella perstans is a neglected filariasis, widely distributed in sub-Saharan Africa, characterized by an elusive clinical picture; treatment for mansonellosis is not standardized. This retrospective study aimed to describe the clinical features, treatment schemes and evolution, of a large cohort of imported cases of M. perstans infection seen in four European centres for tropical diseases., Methods: Mansonella perstans infections, diagnosed by identification of blood microfilariae in migrants, expatriates and travellers, collected between 1994 and 2018, were retrospectively analysed. Data concerning demographics, clinical history and laboratory examinations at diagnosis and at follow-up time points were retrieved., Results: A total of 392 patients were included in the study. Of the 281 patients for whom information on symptoms could be retrieved, 150 (53.4%) reported symptoms, abdominal pain and itching being the most frequent. Positive serology and eosinophilia were present in 84.4% and 66.1%, respectively, of those patients for whom these data were available. Concomitant parasitic infections were reported in 23.5% of patients. Treatment, administered to 325 patients (82.9%), was extremely heterogeneous between and within centres; the most commonly used regimen was mebendazole 100 mg twice a day for 1 month. A total of 256 (65.3%) patients attended a first follow-up, median 3 months (interquartile range 2-12) after the first visit; 83.1% of patients having received treatment based on mebendazole and/or doxycycline, targeting Wolbachia, became amicrofilaremic, 41.1-78.4% of whom within 12 months from single treatment., Conclusions: Lack of specific symptoms, together with the inconstant positivity of parasitological and antibody-based assays in the infected population, makes the clinical suspicion and screening for mansonellosis particularly difficult. Prospective studies evaluating prevalence of infection in migrants from endemic areas, infection-specific morbidity, presence of Wolbachia endosymbionts in M. perstans populations from different geographical areas and efficacy of treatment regimens are absolutely needed to optimize the clinical management of infection., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine.)

Background: Malaria and filariasis are significant vector-borne diseases that are co-endemic in the same human populations. This study aims to collate the evidence, probability, and characteristics of malaria and filariasis co-infections in participants among studies reporting the co-occurrence of both diseases., Methods: We searched for potentially relevant articles reporting the co-occurrence of malaria and filariasis in five electronic databases (Embase, PubMed, Scopus, Medline, and CENTRAL) from inception to May 22, 2022. We estimated the pooled prevalence and probability of malaria and filariasis co-infections among study participants using random-effects meta-analyses and synthesized the characteristics of patients with co-infections narratively., Results: We identified 951 articles, 24 of which (96,838 participants) met eligibility criteria and were included in the systematic review. Results of the meta-analysis showed a pooled prevalence of malaria and filariasis co-infections among participants of 11%. The prevalence of co-infections was 2.3% in Africa, 0.2% in Asia, and 1.6% in South America. The pooled prevalences of malaria and Wuchereria bancrofti, malaria and Loa loa, malaria and Mansonella perstans co-infections were 0.7%, 1.2%, and 1.0%, respectively. The meta-analysis results showed that the co-infections between two parasites occurred by probability (P = 0.001). Patients with co-infections were at increased risk of having an enlarged spleen, a lower rate of severe anemia, lower parasite density, and more asymptomatic clinical status. Patients with co-infections had decreased levels of C-X-C motif chemokine 5, tumor necrosis factor-α, interleukin-4, c4 complement, and interleukin-10. In addition, patients with co-infections had a lower interleukin-10/tumor necrosis factor-α ratio and higher interleukin-10/interleukin-6 ratio., Conclusion: The present study showed that the prevalence of malaria and filariasis co-infections was low and varied between geographical areas in the selected articles. Co-infections tended to occur with a low probability. Further studies investigating the outcomes and characteristics of co-infections are needed., Competing Interests: The authors have declared that no competing interests exist.

Background: Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation, and outcome of these infections in a reference travel clinic over the past decades., Methods: We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within 3-12 months., Results: A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6, Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130, unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year on average in the 1990s to 6.3/year in the past decade, when loiasis became predominant. Cases reported symptoms in >80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively)., Conclusions: The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Regular and comprehensive epidemiological surveys of the filarial nematodes Mansonella perstans and Loa loa in children, adolescents and adults living across Bioko Island, Equatorial Guinea are lacking. We aimed to demonstrate that blood retained on malaria rapid diagnostic tests, commonly deployed for malaria surveys, could be used as a source of nucleic acids for molecular based detection of M. perstans and L. loa. We wanted to determine the positivity rate and distribution of filarial nematodes across different age groups and geographical areas as well as to understand level of co-infections with malaria in an asymptomatic population., Methodology: M. perstans, L. loa and Plasmodium spp. parasites were monitored by qPCR in a cross-sectional study using DNA extracted from a subset malaria rapid diagnostic tests (mRDTs) collected during the annual malaria indicator survey conducted on Bioko Island in 2018., Principal Findings: We identified DNA specific for the two filarial nematodes investigated among 8.2% (263) of the 3214 RDTs screened. Positivity rates of M. perstans and L. loa were 6.6% and 1.5%, respectively. M. perstans infection were more prominent in male (10.5%) compared to female (3.9%) survey participants. M. perstans parasite density and positivity rate was higher among older people and the population living in rural areas. The socio-economic status of participants strongly influenced the infection rate with people belonging to the lowest socio-economic quintile more than 3 and 5 times more likely to be L. loa and M. perstans infected, respectively. No increased risk of being co-infected with Plasmodium spp. parasites was observed among the different age groups., Conclusions/significance: We found otherwise asymptomatic individuals were infected with M. perstans and L. loa. Our study demonstrates that employing mRDTs probed with blood for malaria testing represents a promising, future tool to preserve and ship NAs at room temperature to laboratories for molecular, high-throughput diagnosis and genotyping of blood-dwelling nematode filarial infections. Using this approach, asymptomatic populations can be reached and surveyed for infectious diseases beyond malaria., Competing Interests: The authors have declared that no competing interests exist.

Background: Loa loa and Mansonella perstans-the causative agents of loiasis and mansonellosis-are vector-borne filarial parasites co-endemic in sub-Saharan Africa. Diagnosis of both infections is usually established by microscopic analysis of blood samples. It was recently established that the odds for detecting Plasmodium spp. is higher in capillary (CAP) blood than in venous (VEN) blood. In analogy to this finding this analysis evaluates potential differences in microfilaraemia of L. loa and M. perstans in samples of CAP and VEN blood., Methods: Recruitment took place between 2015 and 2019 at the CERMEL in Lambaréné, Gabon and its surrounding villages. Persons of all ages presenting to diagnostic services of the research center around noon were invited to participate in the study. A thick smear of each 10 microliters of CAP and VEN blood was prepared and analysed by a minimum of two independent microscopists. Differences of log2-transformed CAP and VEN microfilaraemia were computed and expressed as percentages. Furthermore, odds ratios for paired data were computed to quantify the odds to detect microfilariae in CAP blood versus in VEN blood., Results: A total of 713 participants were recruited among whom 52% were below 30 years of age, 27% between 30-59 years of age and 21% above 60 years of age. Male-female ratio was 0.84. Among 152 participants with microscopically-confirmed L. loa infection median (IQR) microfilaraemia was 3,650 (275-11,100) per milliliter blood in CAP blood and 2,775 (200-8,875) in VEN blood (p<0.0001), while among 102 participants with M. perstans this was 100 (0-200) and 100 (0-200), respectively (p = 0.44). Differences in linear models amount up to an average of +34.5% (95% CI: +11.0 to +63.0) higher L. loa microfilaria quantity in CAP blood versus VEN blood and for M. perstans it was on average higher by +24.8% (95% CI: +0.0 to +60.5). Concordantly, the odds for detection of microfilaraemia in CAP samples versus VEN samples was 1.24 (95% CI: 0.65-2.34) and 1.65 (95% CI: 1.0-2.68) for infections with L. loa and M. perstans, respectively., Conclusion: This analysis indicates that average levels of microfilaraemia of L. loa are higher in CAP blood samples than in VEN blood samples. This might have implications for treatment algorithms of onchocerciasis and loiasis, in which exact quantification of L. loa microfilaraemia is of importance. Furthermore, the odds for detection of M. perstans microfilariae was higher in CAP than in VEN blood which may pre-dispose CAP blood for detection of M. perstans infection in large epidemiological studies when sampling of large blood quantities is not feasible. No solid evidence for a higher odds of L. loa microfilariae detection in CAP blood was revealed, which might be explained by generally high levels of L. loa microfilaraemia in CAP and VEN blood above the limit of detection of 100 microfilariae/ml. Yet, it cannot be excluded that the study was underpowered to detect a moderate difference., Competing Interests: The authors have declared that no competing interests exist.

Mansonella perstans, a filarial nematode, infects large populations in Africa and Latin America. Recently, a potential new species, Mansonella sp "DEUX," was reported. Carriage of endosymbiotic Wolbachia opens treatment options for Mansonella infections. Within a cross-sectional study, we assessed the prevalence of filarial infections in 834 Gabonese individuals and the presence of the endosymbiont Wolbachia. Almost half of the participants (400/834 [48%]) were infected with filarial nematodes, with Mansonella sp "DEUX" being the most frequent (295/400 [74%]), followed by Loa loa (273/400 [68%]) and Mansonella perstans (82/400 [21%]). Being adult/elderly, male, and living in rural areas was associated with a higher risk of infection. Wolbachia carriage was confirmed in M. perstans and Mansonella sp "DEUX." In silico analysis revealed that Mansonella sp "DEUX" is not detected with currently published M. perstans-specific assays. Mansonella infections are highly prevalent in Gabon and might have been underreported, likely also beyond Gabon., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Mansonella perstans infection can be considered one of the most neglected tropical infectious diseases. Very few studies have reported on the clinical picture caused by infection with this nematode. Therefore, our study was aimed to describe the clinical patterns and treatment of imported M. perstans infection by migrants from Africa., Methods: The present study evaluated a large cohort of migrants who have been diagnosed, examined and treated for imported M. perstans infection at a Spanish reference center (Hospital Carlos III Tropical Medicine Unit, Madrid, Spain) over a 19-year period. Most patients voluntarily attend the emergency unit or are referred from primary care or general hospitals in Madrid. Chi-square test was used to compare the association between categorical variables. The continuous variables were compared by Student's t-test or the Mann-Whitney test. The corresponding regression models were used for multivariate analysis., Results: Five hundred three cases of migrants from tropical and subtropical areas with M. perstans infection were identified. Two hundred sixty-four patients were female (52.5%). The mean age (± SD) was 44.6 ± 18.2 years (range: 16-93 years). The mean time (± SD) between the arrival in Spain and the first consultation was 8.6 ± 18.0 months. The major origin of the patients was Equatorial Guinea (97.6%). Regarding the clinical picture, 257 patients were asymptomatic (54.7%) and 228 were symptomatic (45.3%); 190 patients had pruritus (37.8%), 50 (9.9%) had arthralgia, 18 patients had Calabar-like swelling (3.6%), and 15 (3%) had abdominal pain. Four hundred forty-two (87.9%) migrants had hyper-IgE, and 340 (67.6%) had eosinophilia. One hundred ninety-five patients had coinfections with other filarial nematodes (38.8%), and 308 migrants had only M. perstans infection (61.2%). Four hundred thirty-seven cases (86.9%) had been treated with anti-filarial drugs; 292 cases were treated with one anti-filarial drug, and 145 cases were treated with combined anti-filarial therapy. Additionally, 20 (4%) cases received steroids and 38 (7.6%) cases received antihistamines., Conclusions: A long series of M. perstans infections is presented in sub-Saharan immigrants whose data indicate that it should be included in the differential diagnosis in patients with pruritus or analytical alterations such as eosinophilia or hyper-IgE presentation, and they also have a high number of coinfections with other microorganisms whose treatment needs to be protocolized.

We reviewed Giemsa-stained thick blood smears, obtained through the national malaria surveillance program in the Amazon region of Ecuador, by light microscopy for Mansonella spp. microfilariae. Of 2,756 slides examined, 566 (20.5%) were positive. Nested PCR confirmed that the microfilariae were those of M. ozzardi nematodes, indicating that this parasite is endemic to this region.

Treating Mansonella perstans is challenged by the low efficacy of registered antihelminthics. Wolbachia endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with Wuchereria bancrofti and Onchocerca volvulus infections. This open-label, randomized study sought to confirm that i) Wolbachia are present in M. perstans in Ghana and ii) doxycycline treatment will deplete Wolbachia and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with M. perstans infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg/day for 6 weeks, and monitored for MF and Wolbachia levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, Wolbachia were depleted from MF by ≥ 1-log drop compared with baseline levels. We conclude that M. perstans in Ghana harbor Wolbachia that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.

Background: In the Brazilian Amazon, the filarial nematode Mansonella ozzardi co-exists with malaria parasites and thick blood smear microscopy is considered the diagnostic gold standard. Transfusion of M. ozzardi microfilariae does not establish new infections, however microfilariae can survive approximately 2 years in blood-recipients with unknown risk of pathology. Data on transfusion-transmitted filariasis are lacking. This study investigated M. ozzardi parasitemias in blood donors from decentralized centers of "Fundação Hematologia e Hemoterapia do Estado do Amazonas/HEMOAM," Northern Brazil., Study Design and Methods: Cross-sectional investigation employing blood smear microscopy (n = 356) and qualitative nested-M. ozzardi-PCR (227 out of 356) in donor candidates from 19 hemocenters in interior/rural municipalities of Amazonas state., Findings: Participants were mostly young males. Positivity by microscopy was 7.9% (28 out of 356) and 23.8% by M. ozzardi-PCR (54 out of 227). Parasitaemias were found in 16 out of 19 municipalities. In 54 M. ozzardi-positives, 24 were ineligible; among 30 that donated, 27 were interdicted by seropositivity (22 anti-HBc, 3 anti-HBc + HBsAg, 1 Chagas+malaria, 1 VDRL). Seropositivty was higher in M. ozzardi-PCR-positives vs M. ozzardi-PCR-negatives (OR = 15.8, 95% CI 4.5-56.1, p < 0.0001). Three M. ozzardi contaminated blood units were transfused, but no follow-up information on the recipients is available., Main Conclusions: Our study provides important baseline data on M. ozzardi among blood donors from the Brazilian Amazon. Further investigations in endemic areas are necessary to clarify possible association between M. ozzardi and other infections and also to elucidate whether there is any significant clinical effect upon transfusion of contaminated blood., (© 2018 AABB.)

Mansonella ozzardi (Nematoda: Onchocercidae) is a little studied filarial nematode. This human parasite, transmitted by two families of dipteran vectors, biting midges (most of them members of the genus Culicoides) and blackflies (genus Simulium), is endemic to the Neotropical regions of the New World. With a patchy geographical distribution from southern Mexico to north-western 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. Studies conducted in Haiti between 1974 and 1984 allowed the first complete description of the adult worm and permitted clarification of the taxonomic position of this filarial species. This paper reports the known geographical distribution of M. ozzardi in Neotropical regions of the Americas, and focuses on the current situation in Haiti where this filariasis remains a completely neglected public health problem.

Human filariae are vector-borne parasites and the causative agents of various diseases, including human onchocerciasis and lymphatic filariasis. Onchocerciasis causes a spectrum of cutaneous and ophthalmologic manifestations (including blindness) and has long been a major public health problem in Bioko Island (Equatorial Guinea). Bioko Island has been included in the WHO's Onchocerciasis Control Program since 1987. In Bioko Island, the specificity and sensitivity of clinical Onchocerca volvulus diagnosis is key. The objective of this work was to update onchocerciasis elimination progress in Bioko Island, after 18 years of mass ivermectin intervention, and the general filariasis situation through a rapid and accurate molecular method. A cross-sectional study was conducted in Bioko Island from mid-January to mid-February 2014. A total of 543 subjects were included in the study. Whole blood and one skin snip (from lumbar regions) were analysed with a real time PCR assay. Two other skin biopsies were analysed by an expert microscopist. All positive samples were confirmed by sequencing. Traditional microscopic examination of the skin biopsies failed to detect any microfilariae. However, 11 (2.03%) infections were detected using PCR assay, including one O. volvulus, two Mansonella streptocerca, seven Mansonella perstans and one Loa loa infections. PCR assays in blood detected 52 filariae-positive individuals (9.6%) which harboured M. perstans or L. loa. The low prevalence of O. volvulus confirms the success of the Onchocerciasis Control Programme and suggests that Mass Drug Administration in Bioko Island can be interrupted in the near future. The very high prevalence of M. perstans found in skin snips assays raises doubts about the reliability of microscope-based diagnosis of O. volvulus infections., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The human filarial worm Mansonella ozzardi is highly endemic in the large tributaries of the Amazon River. This infection is still highly neglected and can be falsely negative when microfilariae levels are low., Objectives: This study investigated the frequency of individuals with M. ozzardi in riverine communities in Coari municipality, Brazilian Amazon., Methods: Different diagnostic methods including polymerase chain reaction (PCR), blood polycarbonate membrane filtration (PCMF), Knott's method (Knott), digital thick blood smears (DTBS) and venous thick blood smears (VTBS) were used to compare sensitivity and specificity among the methods. Data were analysed using PCMF and Bayesian latent class models (BLCM) as the gold standard. We used BLCM to calculate the prevalence of mansonelliasis based on the results of five diagnostic methods., Findings: The prevalence of mansonelliasis was 35.4% by PCMF and 30.1% by BLCM. PCR and Knott methods both possessed high sensitivity. Sensitivity relative to PCMF was 98.5% [95% confidence interval (CI): 92.0 - 99.7] for PCR and 83.5% (95% CI: 72.9 - 90.5) for Knott. Sensitivity derived by BLCM was 100% (95% CI 93.7 - 100) for PCMF, 100% (95% CI: 93.7 - 100) for PCR and 98.3% (95% CI: 90.6 - 99.9) for Knott. The odds ratio of being diagnosed as microfilaremic increased with age but did not differ between genders. Microfilariae loads were higher in subjects aged 30 - 45 and 45 - 60 years., Main Conclusions: PCMF and PCR were the best methods to assess the prevalence of mansonelliasis in our samples. As such, using these methods could lead to higher prevalence of mansonelliasis in this region than the most commonly used method (i.e., thick blood smears).

Background: For a given prevalence of Loa loa microfilaremia, the proportion of people with high densities varies significantly between communities. We hypothesized that this variation is related to the existence of familial clusters of hypermicrofilaremic individuals that would be the consequence of a genetic predisposition to present high L. loa microfilarial densities., Methods: A familial study was performed in 10 villages in the Okola Health District of Cameroon. Intrafamilial correlation coefficients and heritability estimates were assessed for both the presence of L. loa microfilaremia and individual microfilarial densities by controlling for age, sex, Mansonella perstans coinfection, and household effects., Results: Pedigrees were constructed for 1126 individuals. A significant familial susceptibility to be microfilaremic for L. loa was found for first-degree relatives (ρ = 0.08, P < .05; heritability = 0.23). Regarding individual microfilarial densities, a significant familial aggregation was demonstrated (ρ = 0.36 for first-degree and 0.27 for second-degree relatives). For first-degree relatives, the highest coefficient was found between mothers and daughters (ρ = 0.57). The overall heritability estimate for L. loa microfilarial density was 0.24 (P = .003)., Conclusions: A significant genetic component governs L. loa microfilarial density. This supports the hypothesis that a genetic predisposition to be hypermicrofilaremic exists, leading to the presence of familial clusters of individuals at risk for postivermectin severe adverse events. This finding should be taken into account while developing sampling strategies (including a household-level sampling) to identify villages where community-directed treatment with ivermectin cannot be applied., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Haiti, like most limited-resources countries in the world, faces numerous neglected infectious diseases. They represent a real public health issue with lethal consequences especially in children. We are reviewing here the available literature on four neglected infectious diseases, mansonelliasis, tungiasis, leprosy and anthrax. Filariasis, due to Mansonella ozzardi , has been totally neglected since its discovery in 1920 in Haiti; it persists in coastal homes with a high prevalence in adults when an effective treatment is available. The skin lesions caused by Tunga penetrans have existed since the pre-Columbian period in Haiti. They persist in the most retreated and hard-to-reach areas where the population lives in precarious conditions and in extreme poverty. New available research data show the importance of the problem with very high prevalence rates in some rural communities far away from any healthcare center. Cases of leprosy are recently reemerging as no monitoring program has been in place since 2004. Finally, anthrax is still endemic; small epidemics resurfacing periodically in families in rural areas. Screening of people for these diseases and managing the cases are necessary to improve health and reduce morbidity and mortality in Haiti., Competing Interests: The authors have no conflicts of interest to declare

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.

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.

Background: Mansonellosis was first reported in Ghana by Awadzi in the 1990s. Co-infections of Mansonella perstans have also been reported in a small cohort of patients with Buruli ulcer and their contacts. However, no study has assessed the exact prevalence of the disease in a larger study population. This study therefore aimed to find out the prevalence of M. perstans infection in some districts in Ghana and to determine the diversity of Culicoides that could be potential vectors for transmission., Methods: From each participant screened in the Asante Akim North (Ashanti Region), Sene West and Atebubu Amantin (Brong Ahafo Region) districts, a total of 70 μl of finger prick blood was collected for assessment of M. perstans microfilariae. Centre for Disease Control (CDC) light traps as well as the Human Landing Catch (HLC) method were used to assess the species diversity of Culicoides present in the study communities., Results: From 2,247 participants, an overall prevalence of 32% was recorded although up to 75% prevalence was demonstrated in some of the communities. Culicoides inornatipennis was the only species of Culicoides caught with the HLC method. By contrast, C. imicola (47%), C. neavei (25%) and C. schultzei (15%) were caught by the CDC light trap method. A wide diversity of other Culicoides spp. was also identified but correlation was only found between the prevalence of C. inornatipennis and M. perstans during the dry season., Conclusions: Here we demonstrate for the first time that M. perstans is highly prevalent in three districts in Ghana. We found a wide spectrum of Culicoides spp. Culicoides inornatipennis was the most anthropophilic and is therefore likely to be the species responsible for transmission of infection but formal proof has yet to be obtained., Trial Registration: NCT02281643 . Registered October 26, 2014. 'Retrospectively registered'., Trial Registry: ClinicalTrials.gov.

Mansonellosis is endemic in several regions of Africa, the Caribbean, and Latin America. Mansonella ozzardi and Mansonella perstans have been reported in Latin America, including the Amazon region. A morphological and molecular microfilariae study was performed in Pauini (Brazil). Blood samples were collected from 40 individuals, and were analyzed by Giemsa-stained blood film and by two different nested polymerase chain reactions which detect internal transcribed spacer-1 and the major sperm protein gene. By microscopy, 14 of 40 were positive: 11 as M. ozzardi and three as M. perstans-like infections. Both molecular methods detected 19 positive cases as M. ozzardi, including those 14 individuals detected by microscopy, without detectable genetic differences among any of the 19 positive samples. Molecular techniques showed an improvement of mansonellosis diagnosis and may become an effective tool to evaluate the present status of M. ozzardi and M. perstans in Latin America., (© The American Society of Tropical Medicine and Hygiene.)

The relationship between the frequency of loiasis objective symptoms and microfilaraemic or amicrofilaraemic infection was assessed in 1148 exposed patients also infected, or not, with Mansonella perstans. Filarial infections were detected by direct microscopy, leucoconcentration and serology, with prevalence values of 39.5% Loa loa, 5.6% M. perstans and 3.4% co-infection with both filarial species. Amicrofilaraemic or occult loiasis (OL) predominated among L. loa-infected individuals, with a prevalence of 58.2%. Hypermicrofilaraemia (>8000 microfilariae (mf)/ml) was found in 18.4% of L. loa microfilaraemic patients, with 25.7% of them harbouring more than 30,000 mf/ml. Up to 34% of patients with OL showed evidence of Calabar swelling, compared with 26.3% of microfilaraemic patients (P= 0.03). Overall 5.3% of patients presented with adult worm migration across the eye, representing 16.3% of microfilaraemic individuals and 11.4% of amicrofilaraemic patients (P= 0.13). This symptom was similarly found in patients with more than 30,000 mf/ml (22%), those with microfilaraemia between 8 and 30,000 mf/ml (15.4%) and also in individuals with low or without microfilaraemia (16.1%) (P= 0.7). Five (14.3%) hypermicrofilaraemic patients did not present any L. loa-specific objective symptoms, as well as all the patients with single M. perstans infection. The presence of adult eye worm migration as a strong predictor of high microfilaraemia density would obscure the real burden of L. loa hypermicrofilaraemia in exposed individuals. For epidemiological purposes and control strategies, the mapping of L. loa in endemic areas should also take into account the group of patients with occult loiasis.

The study of the interactions among parasites within their hosts is crucial to the understanding of epidemiology of disease and for the design of effective control strategies. We have conducted an assessment of infections with Loa loa, Mansonella perstans, Wuchereria bancrofti, and Plasmodium falciparum in eastern Cameroon using a highly sensitive and specific quantitative polymerase chain reaction assay using archived dried whole blood spots. The resident population (N = 1,085) was parasitized with M. perstans (76%), L. loa (39%), and P. falciparum (33%), but not with W. bancrofti Compared with single infections (40.1%), coinfection was more common (48.8%): 21.0% had L. loa-M. perstans (Ll(+)/Mp(+)/Pf(-)), 2.7% had L. loa-P. falciparum (Ll(+)/Pf(+)/Mp(-)), 15.1% had M. perstans-P. falciparum (Mp(+)/Pf(+)/Ll(-)), and 10.0% had L. loa-M. perstans-P. falciparum (Ll(+)/Mp(+)/Pf(+)). Interestingly, those with all three infections (Ll(+)/Mp(+)/Pf(+)) had significantly higher L. loa microfilaria (mf) counts than either single Ll(+) (P = 0.004) or double Ll(+)/Mp(+) (P = 0.024) infected individuals. Of those infected with L. loa, the mean estimated counts of L. loa mf varied based on location and were positively correlated with estimated intensities of M. perstans mf. Finally, at a community level, heavy L. loa infections were concentrated in a few individuals whereby they were likely the major reservoir for infection., (© The American Society of Tropical Medicine and Hygiene.)

Background: Mansonellosis remains one of the most neglected of tropical diseases and its current distribution in the entire forest block of southern Cameroon is unknown. In order to address this issue, we have surveyed the distribution of Mansonella perstans in different bioecological zones and in addition, elucidated the influence of multiple rounds of ivermectin (IVM) based mass drug administration (MDA)., Methods: A mixed design was used. Between 2000 and 2014, both cross-sectional and longitudinal surveys were carried out in 137 communities selected from 12 health districts belonging to five main bioecological zones of the southern part of Cameroon. The zones comprised of grassland savanna (GS), mosaic forest savanna (MFS), forested savanna (FS), deciduous equatorial rainforest (DERF) and the dense humid equatorial rainforest (DHERF). The survey was carried out in some areas with no treatment history as well as those currently under IVM MDA. Individuals within the participatory communities were screened for the presence of M. perstans microfilariae (mf) in peripheral blood by the calibrated thick film method to determine both prevalence and geometric mean intensities at the community level., Results: Apart from sporadic cases in savanna areas, distribution of M. perstans was strongly linked to the equatorial rainforest zones. Before CDTI, the highest mean prevalence (70.0 %) and intensity (17,382.2 mf/ml) were obtained in communities in Mamfes' DHERF areas followed by communities in the DHERF zone of Lolodorf (53.8 % and 7,814.8 mf/ml, respectively). A longitudinal survey in Mamfe further showed that M. perstans infections had reduced by 34.5 % in DERF (P < 0.001) but not DHERF zones after ten years of IVM MDA. Further data from the cross-sectional study revealed that there was a decrease in prevalence in DHERF zones only after ten years of MDA. In DERF zones however, the infection was relatively lower after four years of MDA., Conclusions: The distribution of M. perstans in the southern part of Cameroon varies with bioecological zones and IVM MDA history. The zones with high prevalence and intensities lie in forested areas while those with low endemicity are in the savanna areas. MDA with ivermectin induced significant reduction in the endemicity of mansonellosis in the decidious equatorial rainforest. In contrast, the prevalence and intensity remained relatively high and stable in the dense humid equatorial rainforest zones even after a decade of mass drug administration with ivermectin. Since it is known that M. perstans down-regulates host's immune system, the findings from this work would be useful in designing studies to understand the impact of M. perstans on host immune response to vaccination and co-infection with other pathogens such as Mycobacterium spp. and Plasmodium spp. in areas of contrasting endemicities.

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.

INTRODUCTION Mansonella ozzardi is a widely distributed filaria worm in the Amazon region. This study aimed to determine the prevalence of M. ozzardi infection in riverine communities of Lábrea municipality, Amazonas State, Brazil. METHODS A diagnostic blood filtration method in a polycarbonate membrane was used. RESULTS M. ozzardi was found in 50.3% of the sample, with the highest prevalence in farmers/fishermen (69.4%; χ 2 = -19.14, p<0.001). The prevalence was higher in longer-term residents (≥11 years; 60.2%). CONCLUSIONS M. ozzardi infection rates are high near the Purus River, much greater than those previously reported based on diagnosis using thick blood smears.

Background: Mansonella perstans is a widespread, but relatively unknown human filarial parasite transmitted by Culicoides biting midges. Although it is found in many parts of sub-Saharan Africa, only few studies have been carried out to deepen the understanding of its ecology, epidemiology, and health consequences. Hence, knowledge about ecological drivers of the vector and parasite distribution, integral to develop spatially explicit models for disease prevention, control, and elimination strategies, is limited., Methodology: We analyzed data from a comprehensive nationwide survey of M. perstans infection conducted in 76 schools across Uganda in 2000-2003, to identify environmental drivers. A suite of Bayesian geostatistical regression models was fitted, and the best fitting model based on the deviance information criterion was utilized to predict M. perstans infection risk for all of Uganda. Additionally, we investigated co-infection rates and co-distribution with Wuchereria bancrofti and Plasmodium spp. infections observed at the same survey by mapping geographically overlapping areas., Principal Findings: Several bioclimatic factors were significantly associated with M. perstans infection levels. A spatial Bayesian regression model showed the best fit, with diurnal temperature range, normalized difference vegetation index, and cattle densities identified as significant covariates. This model was employed to predict M. perstans infection risk at non-sampled locations. The level of co-infection with W. bancrofti was low (0.3%), due to limited geographic overlap. However, where the two infections did overlap geographically, a positive association was found., Conclusions/significance: This study presents the first geostatistical risk map for M. perstans in Uganda. We confirmed a widespread distribution of M. perstans, and identified important potential drivers of risk. The results provide new insight about the ecologic preferences of this otherwise poorly known filarial parasite and its Culicoides vector species in Uganda, which might be relevant for other settings in sub-Saharan Africa.

Human filariasis caused by Mansonella ozzardi is a parasitic infection of a controversial pathology and poorly studied in Argentina. The aim of this study was not only to obtain data of the prevalence of M. ozzardi in Northwestern Argentina through comparison of infection rates in relation to sex and age group determining the range of distribution of mansonelliasis in the region but also to investigate the prevalence of the cases over time. Through field work carried between 1986 and 2010 by technicians of the National Ministry of Health, aiming to detect active cases of malaria in the Northwestern Argentina, blood samples were taken for smear and thick blood. 417 blood samples were examined, 381 of them (91.4%) were positive for M. ozzardi. The highest prevalence was found in Salta province (92.3%) mainly affecting the male sex (92.6%) and the age groups comprised between 48-57 years (97.0%) and ≥ 68 (90.7%). The paired t-test and Spearman coefficients showed significant differences in prevalence according to sex (t=2.677; p=0.015), and according infection rates in males and females/age (r=0.994; p=0.001; r=0.994, p=0.001, respectively). The prevalence over time showed a general pattern with the highest cases in 1986, decreasing later during the following years. Aguas Blancas, El Oculto and San Ramón de la Nueva Orán, exhibited a pattern of prevalence according to the general trend but Salvador Mazza and Tartagal, which are also localities close to the border with Bolivia, showed peaks of cases up to 2010. These results provide relevant information about M. ozzardi in Argentina, demonstrating not only its presence and endemicity after almost 100 years from its discovery in the country, but also its wide range of distribution in the region., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Immunochromatographic card test (ICT) is a tool to map the distribution of Wuchereria bancrofti. In areas highly endemic for loaisis in DRC and Cameroon, a relationship has been envisaged between high L. loa microfilaria (Mf) loads and ICT positivity. However, similar associations have not been demonstrated from other areas with contrasting levels of L. loa endemicity. This study investigated the cross-reactivity of ICT when mapping lymphatic filariasis (LF) in areas with contrasting endemicity levels of loiasis and mansonellosis in Cameroon., Methodology/principal Findings: A cross-sectional study to assess the prevalence and intensity of W. bancrofti, L. loa and M. perstans was carried out in 42 villages across three regions (East, North-west and South-west) of the Cameroon rainforest domain. Diurnal blood was collected from participants for the detection of circulating filarial antigen (CFA) by ICT and assessment of Mf using a thick blood smear. Clinical manifestations of LF were also assessed. ICT positives and patients clinically diagnosed with lymphoedema were further subjected to night blood collection for the detection of W. bancrofti Mf. Overall, 2190 individuals took part in the study. Overall, 24 individuals residing in 14 communities were tested positive by ICT, with prevalence rates ranging from 0% in the South-west to 2.1% in the North-west. Lymphoedema were diagnosed in 20 individuals with the majority of cases found in the North-west (11/20), and none of them were tested positive by ICT. No Mf of W. bancrofti were found in the night blood of any individual with a positive ICT result or clinical lymphoedema. Positive ICT results were strongly associated with high L. loa Mf intensity with 21 subjects having more than 8,000 L. loa Mf ml/blood (Odds ratio = 15.4; 95%CI: 6.1-39.0; p < 0.001). Similarly, a strong positive association (Spearman's rho = 0.900; p = 0.037) was observed between the prevalence of L. loa and ICT positivity by area: a rate of 1% or more of positive ICT results was found only in areas with an L. loa Mf prevalence above 15%. In contrast, there was no association between ICT positivity and M. perstans prevalence (Spearman's rho = - 0.200; p = 0.747) and Mf density (Odds ratio = 1.8; 95%CI: 0.8-4.2; p = 0.192)., Conclusions/significance: This study has confirmed the strong association between the ICT positivity and L. loa intensity (Mf/ml of blood) at the individual level. Furthermore, the study has demonstrated that ICT positivity is strongly associated with high L. loa prevalence. These results suggest that the main confounding factor for positive ICT test card results are high levels of L. loa. The findings may indicate that W. bancrofti is much less prevalent in the Central African region where L. loa is highly endemic than previously assumed and accurate re-mapping of the region would be very useful for shrinking of the map of LF distribution.

Background: Like other tropical African countries, Gabon is afflicted by many parasitic diseases, including filariases such as loiasis and mansonellosis. This study aimed to assess the prevalence of these two filarial diseases in febrile and afebrile children using quantitative real-time PCR and standard PCR assays coupled with sequencing., Methodology/principal Findings: DNA from blood specimens of 1,418 Gabonese children (1,258 febrile and 160 afebrile) were analyzed. Overall, filarial DNA was detected in 95 (6.7%) children, including 67 positive for M. perstans (4.7%), which was the most common. M. perstans was detected in 61/1,258 febrile children (4.8%) and 6/160 afebrile children (3.8%, P = 0.6). Its prevalence increased statistically with age: 3.5%, 7.7% and 10.6% in children aged ≤ 5, 6-10 and 11-15 years, respectively. M. perstans prevalence was significantly higher in Koulamoutou and Lastourville (12% and 10.5%, respectively) than in Franceville and Fougamou (2.6% and 2.4%, respectively). Loa loa was detected in seven febrile children including one co-infection with M. perstans. Finally, 21 filarial DNA positive were negative for M. perstans and Loa loa, but ITS sequencing could be performed for 12 and allowed the identification of a potential new species of Mansonella provisionally called "DEUX". Mansonella sp. "DEUX" was detected only in febrile children., Conclusions/significance: Further study should be performed to characterize Mansonella sp. "DEUX" and evaluate the clinical significance of mansonellosis in humans.

Large parts of African and American countries are colonized by Mansonella, a very common but poorly described filarial nematode. Bloodsucking flies of the genus Culicoides are suspected to be the vector of Mansonella perstans, but no study in Senegal has confirmed that Culicoides can transmit the parasite. Designed specific real-time quantitative polymerase chain reaction (qPCR) can be used to identify microfilaria in stained blood smears. This study was performed in July and December 2010 in the southeastern Senegal, which is known to be endemic for M. perstans. We analyzed 297 blood smears from febrile and afebrile resident people by qPCR. The global prevalence of M. perstans was approximately 14.5% in both febrile and afebrile individuals. The age group of > 30 years had the highest prevalence (22.0%). No Culicoides among 1,159 studied specimens was positive for M. perstans and its vector in Senegal still requires identification., (© The American Society of Tropical Medicine and Hygiene.)

Objectives: To determine the frequency, clinical features, and factors associated with M. ozzardi infection in volunteers of a malaria screening campaign in the district of Alto Nanay in the Amazon jungle of Peru., Materials and Methods: A descriptive, analytical and cross-sectional study was performed. The participants were interviewed and examined by a physician and the data were recorded in a medical record. The diagnosis of M. ozzardi infection was performed using the method of thick blood smear and film., Results: The frequency of mansonelosis in this population was 47.8% (95% CI: 39.1 to 56.6). Through bivariate analysis we found that the report of decreased visual acuity or blurred vision and presence of subcutaneous tumors were the signs and symptoms statistically associated with the infection of microfilariae (p<0.05). Logistic regression found statistical association for residency in localities of the Pintuyacu or Alto Nanay rivers, employment in places far from the town center, the presence of subcutaneous tumors and skin thickening (p<0.05)., Conclusions: There was a high number of mansonelosis by M. ozzardi in the district of Alto Nanay which was significantly related to working outside the town center, residing in the area of the Pintuyacu River, and skin lesions.

The occurrence of Mansonella perstans was studied among people who had resided in Calabar metropolis for at least one year prior to the time of this study, which lasted from February to August, 2011. One thousand residents, comprising 530 males and 470 females, with an age range of 4 to 59 years, participated in the study, after an informed consent. Two millilitres of venous blood were collected at day time into EDTA bottles. The blood samples were processed by diluting 1ml of blood in 9 mls of 1% formalin and centrifuging the preparation at 3,000 revolutions per minute for 5 minutes. Deposits were left as blood smears on clean slides and after air-drying, were stained with 3% Giemsa solution for microscopy. Overall, the prevalence of Mansonella perstans was 2% (20 vs 1,000). The prevalence of the parasite among the females was 2.1% (10 vs 470) and males 1.9% (10 vs 530). Microfilaraemia only occurred among subjects aged between 25 and 45 years. The results of this study suggest that loiasis, which earned Calabar an unenviable mention in early medical literature, is no longer very prevalent in the area. Instead, a low prevalence of mansonelliasis occurs, in tandem with the existence of sparse farmlands of banana and plantain. Old stems of these crops provide suitable habitats for Culicoides species, which transmit Mansonella perstans.

Reported in Haiti as early as 1923, Mansonella ozzardi is still a neglected disease ignored by the health authorities of the country. This review is an update on the geographic distribution of the coastal foci of mansonelliasis in Haiti, the epidemiological profile and prevalence rates of microfilariae in people living in endemic areas, the clinical impact of the parasite on health and the efficiency of the transmission of the parasite among three Culicoides biting-midge species identified as vectors in Haiti. Additionally, interest in establishing a treatment programme to combat this parasite using a single dose of ivermectin is emphasised.

The prevalence of mansonelliasis was studied in the municipality of Tefé, state of Amazonas, Brazil. The prevalence (thick blood smear method) was 13.6% (147/1,078), higher in the Solimões River region (16.3%) than in the Tefé River region (6.3%). In the sampled communities in the Solimões River region, a higher density of cases was observed, as indicated by a kernel analysis (odds ratio 0.34; 95% confidence interval: 0.20-0.57). Males had a higher prevalence (χ2 = 31.292, p < 0.001) than women. Mansonella ozzardi prevalence was higher in retirees and farmers (28.9% and 27%, respectively). Prevalence also significantly increased with age (χ2 = -128.17, p < 0.001), with the highest numbers occurring in persons older than 67 years.

During August 2010-December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer.

An epidemiologic (cross-sectional study) survey on 462 inhabitants in Corail, Haiti showed that 16.5% were infected with Mansonella ozzardi. This finding was determined from a single 20-μL sample of finger prick blood from each person. Among children, < 2% had a detectable microfilaremia. In persons > 15 years of age, the prevalence of infection for males and females was 23% and 21%, respectively. In general, the microfilaremias were low and 70% of positive persons had < 10 microfilariae per 20 μL of blood; only 5% had > 50 microfilariae. This study shows that persons living near mangrove marshes that are breeding sites for Culicoides furens and C. barbosai biting midges, which are recognized vectors of M. ozzardi in Haiti, are consequently more frequently infected than those living in downtown area of Corail or inland., (© The American Society of Tropical Medicine and Hygiene.)

Mansonella (M.) perstans filariasis is widely found in Africa, including Gabon where Loa loa is also endemic. This study reports the total IgE titres according to different bioclinical forms of single or co-infection with L. loa and M. perstans in 138 patients and 20 healthy controls. The median parasite density was significantly higher in cases of loiasis. IgE titres were higher in patients with microscopic dual-infection and in the group of patients with occult loiasis plus M. perstans microfilaraemia (8425 [5292-20,679]KUI/L and 6304 [1045-10,326]KUI/L, respectively), compared to individuals with either microfilaraemic Loa loa (3368 [1414-7074]KUI/L) or Mansonella (4370 [1478-7334]KUI/L) single infections (p<0.01). IgE levels were positively correlated with M. perstans microfilaraemia (rho=0.27; p<0.01). Compared to single infections, dual M. perstans-L. loa infection induces very high total IgE titres. Studies correlating IgE titres and clinical symptoms are needed to confirm the involvement of this immunoglobulin in the pathological processes during filariasis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Mansonella ozzardi infections are common in the riverside communities along the Solimões, Negro and Purus Rivers in the state of Amazonas (AM). However, little is known about the presence of this parasite in communities located in regions bordering AM and the state of Acre. The prevalence rate of M. ozzardi infections was determined in blood samples from volunteers according to the Knott method. A total of 355 volunteers from six riverine communities were enrolled in the study and 65 (18.3%) were found to be infected with M. ozzardi. As expected, most of the infections (25%) occurred in individuals involved in agriculture, cattle rearing and fishing and an age/sex group analysis revealed that the prevalence increased beginning in the 40-50-years-of-age group and reached 33% in both sexes in individuals over 50 years of age. Based on the described symptomatology, articular pain and headache were found to be significantly higher among infected individuals (56 and 65% prevalence, respectively, p < 0.05). Sera from volunteers were subjected to ELISA using a cocktail of recombinant proteins from Onchocerca volvulus to evaluate the specificity of the test in an endemic M. ozzardi region. No cross-reactions between M. ozzardi-infected individuals and recombinant O. volvulus proteins were detected, thus providing information on the secure use of this particular cocktail in areas where these parasites are sympatric.

Introduction: This study assessed the prevalence of Mansonella ozzardi in riverine communities of the Tefé River, Amazonas, Brazil., Methods: The prevalence of M. ozzardi was estimated by microscopic examination of thick blood smears., Results: The M. ozzardi prevalence rate was 6.3% (19/300). Filarial infection was found in 8 of the 11 communities surveyed, with prevalence rates varying from 2.5% to 22.2%., Conclusions: Tefé is a region of oil and natural gas exploration, in which there is a high turnover of workers. Migration patterns may facilitate the dissemination of mansonelliasis to other regions.

Mansonella ozzardi is a tissue-dwelling parasitic nematode, the causative agent of mansonelliasis in almost all Latin American countries. It has been described along the Argentine Yungas region. The microscopic diagnosis can yield false-negative test results at low microfilaremia levels. The aim of this study was to optimize the molecular diagnostic technique and compare it with the Knott's method and standard blood smear procedures (thin blood films and thick smears) in 92 blood samples of individuals from an endemic area. The PCR technique followed by the sequencing of the amplified product yielded 100 % sensitivity compared to the Knott's test, which is considered a reference method. Seven more cases of this parasitosis could only be identified with the molecular technique.

Introduction: Mansonella ozzardi, a human filarial nematode transmitted by Diptera Simuliidae flies (black flies), is widely spread in the Amazon, while the occurrence of mansonelliasis in the State of Rondônia (Western Amazonia) has not been reported thus far. The existence of this parasitic disease in this state is investigated in this study., Methods: A total of 4,452 people who lived alongside the Madeira, Mamore, Guapore, Machado and Preto Rivers, in the State of Rondônia, were examined using the thick blood smear method. Alongside the Machado and Guapore rivers, 2,112 adult simuliid specimens were captured., Results: Infected people were not reported, although simuliids with vector potential such as Cerqueirellum pydanielli, C. argentiscutum and C. amazonicum were found., Conclusions: This study registered no infected people. This finding may be explained by the individuals' low level of microfilaremia that is below the limit of detection of the diagnostic method used in the study or insufficient migration of people infected with M. ozzardi from endemic areas, making it impossible to introduce the disease into Rondônia. Further studies using more sensitive diagnostic techniques could shed light on this question.

Mansonella perstans is a vector-borne human filarial nematode, transmitted by tiny blood-sucking flies (biting midges). It is widespread in many parts of Sub-Saharan Africa and also occurs in parts of Central and South America. Despite the commonness of this parasite very few studies have been carried out on its epidemiology and on the morbidity resulting from it, and only few thorough drug trials have been conducted to look for effective and suitable drugs and drug regimens for treatment and control. Here, we review currently available knowledge on M. perstans infections in Africa, including documented aspects of biology, vectors, transmission, diagnosis, epidemiology, morbidity and treatment. It is concluded that there is an urgent need for more research on this widespread but greatly neglected infection in order to properly assess its public health significance and as a background for identifying and recommending optimal means and strategies for treatment and control., (Copyright © 2010 Elsevier B.V. All rights reserved.)