Search

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: 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: 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.)

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: 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.)

Surveys for Mansonella perstans infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100microl of finger-prick blood. Among 575 and 991 examined individuals aged >or=1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1-4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15-19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4mf/100microl) than in the Luwero community (29.9mf/100microl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and M. perstans microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280].

Baseline epidemiological investigations on lymphatic filariasis were conducted for the first time in Uganda in 3 communities in the districts of Lira (Alebtong area), Soroti (Lwala area) and Katakwi (Obalanga area), located to the north of Lake Kyoga at an altitude of 1000-1100 m above sea level. Individuals from the communities were examined, in April-August 1998, for Wuchereria bancrofti specific circulating antigen (by ICT card test), microfilaraemia (by counting chamber and stained blood-smear techniques) and chronic clinical manifestations of lymphatic filariasis. Endophilic mosquitoes were sampled and dissected for filarial larvae. Prevalences of circulating filarial antigen positivity were 29%, 18% and 30% in the Alebtong, Lwala and Obalanga communities, respectively. Microfilaria (mf) prevalences were 18%, 9% and 21%, and geometric mean mf intensities among mf-positive individuals were 306, 171 and 402 mf/mL blood, in the same communities. Examination of stained blood smears revealed mf of both W. bancrofti and Mansonella perstans, but more than 80% of mf-positive individuals harboured the first of these parasites. Prevalences of hydrocoele in adult (> or = 20 years) males were 28%, 7% and 17%, and prevalences of limb elephantiasis in adults were 9%, 4% and 4%, in the Alebtong, Lwala and Obalanga communities, respectively. Anopheles gambiae s.l. (mainly An. gambiae s.s.) and An. funestus were common in all 3 communities, and showed W. bancrofti infectivity rates of 1.1-1.7% and 1.3-2.9%, respectively. It is concluded that lymphatic filariasis is highly endemic in these high-altitude areas of Uganda, with An. gambiae s.l. and An. funestus being the main vectors.

The prevalence of Loa loa and Mansonella perstans filariasis has been determined in 6 rural villages in eastern Gabon. Between 18.9 and 27.2% of people carry L. loa microfilariae with an overall microfilarial rate of 25.1%. The microfilarial rate for M. perstans was more variable, between 33.3 and 62.2% (average 49.1%). No significant difference was seen in the microfilarial rate with age over 15 years for either parasite, but men were infected more frequently than women. Anti-L. loa antibody titres were measured, using a homologous microfilarial antigen in ELISA. Taking the parasitological and immunological evaluations together, only 10% of the sample population appear to be free of these filarial infections. L. loa and M. perstans microfilaraemia and corresponding serology were also investigated twice in 150 people at a one-year interval. 99.1% of the cases who had no circulating L. loa microfilaria in March 1984 still did not show any 12 months later. Similarly, 97.1% of the untreated, microfilaraemic cases still harboured this parasite a year later. The same was not observed for M. perstans, since microfilariae appeared or disappeared in 26.7% of the cases. This suggests different dynamics for the two filarial infections. Variation in individual anti-L. loa antibody titres was low. The possibility of a genetic influence on the expression of loiasis is discussed.

A day blood smear survey for Mansonella ozzardi in the north coast communities of Trinidad recorded a prevalence of 4.8% in 4,488 persons examined. Prevalence rates were highest in the four western-most communities, where the vector, Culicoides phlebotomus, is a severe nuisance problem. Prevalence rates increased with age and were higher in males than in females. Mean microfilaria densities were low in both sexes up to 50 years of age but in older males the density increased with age. Wuchereria bancrofti infections were detected in five of the ten communities surveyed.

1934 Bantus and 379 Pygmies were investigated for Loa loa and Mansonella perstans filariasis in 7 villages in the Chaillu forest of the Congo. Bantus were more frequently infected with L. loa than Pygmies (18.9% of microfilariae carriers compared with 10.6%). In individuals over 30 years of age, males were more frequently infected than females. Microfilarial densities increased until the age of 20 years and then remained stable. Parasite load was not significantly different in the two ethnic groups. For mansonelliasis, the microfilarial rate was higher in the Pygmies (67.5% compared with 22.0%) and males of the 2 groups were more frequently infected than females. Microfilarial load was also higher in Pygmies than in Bantus (mean microfilarial densities (MfD 50) 13 and 2 respectively). In the Pygmy group, MfD 50 for M. perstans increased with age whereas it remained stable in the Bantus. 53.8% of the 249 questioned persons had experienced worm migration under the conjunctiva. Both ethnic groups were equally exposed to the vectors of L. loa and reasons for the difference in prevalence of microfilaria carriers are discussed. For mansonelliasis increased contact with vectors may explain the higher degree of infestation observed in Pygmies. Other filariases were infrequent in (Mansonella streptocerca), or absent from (Onchocerca volvulus and Wuchereria bancrofti), the study area.