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PloS One 2023Life-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem....
The design and development of a study protocol to investigate Onchocerca volvulus, Loa loa and Mansonella perstans-mediated modulation of the metabolic and immunological profile in lean and obese individuals in Cameroon.
BACKGROUND
Life-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem. Metabolic disorders like type 2 diabetes and cardiovascular diseases are among the ten leading causes of death defined by the WHO in 2019. Results from animal and observational human studies suggest a connection between the decline in human helminth infections and rise of life-style-associated metabolic diseases in developing regions. This trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. We hypothesize that the induction of regulatory immune responses during filarial infection reduces obesity-induced low-grade inflammatory immune responses and thereby improves metabolic parameters, whereas anthelmintic treatment abolishes this protective effect.
METHODS/DESIGN
Participants infected with Mansonella perstans, Onchocerca volvulus and/or Loa loa being lean (BMI <25), overweight (BMI >25 and <30) or clinically obese (BMI ≥30) from Littoral regions of Cameroon will be evaluated for their parasitological, immunological, metabolic and biochemical profile before and after treatment of their parasitic infections. Anthropomorphic measurements and a detailed questionnaire will complement our analysis. The investigation will assess blood immune cell populations, serum adipokines and cytokines that could be influenced by the parasite infection and/or metabolic diseases. Further, parameters like blood glucose, homeostatic model assessment of insulin resistance (HOMA-IR), circulating lipids and circulating makers of liver function will be monitored. Parameters will be assessed before treatment, 12 and 18 months after treatment.
CONCLUSION
The focus of this study is to obtain a comprehensive metabolic profile of the participants in rural areas of Cameroon and to investigate the relationship between filarial immunomodulation and metabolic diseases. This study will elucidate the effect of anti-filarial treatment on the metabolic and immunological parameters that partake in the development of insulin resistance, narrowing in on a potential protective effect of filarial infections on metabolic diseases.
TRIAL REGISTRATION
doi.org/10.1186/ISRCTN43845142, ISRCTN43845142 February 2020 Trial title Effects of filarial parasite infection on type 2 diabetes Issue date: 27.10.22, V.1.
Topics: Animals; Humans; Mansonella; Onchocerca volvulus; Loa; Mansonelliasis; Cameroon; Diabetes Mellitus, Type 2; Insulin Resistance; Loiasis; Obesity
PubMed: 37267236
DOI: 10.1371/journal.pone.0285689 -
Memorias Do Instituto Oswaldo Cruz Mar 2018The 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... (Comparative Study)
Comparative Study
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).
Topics: Adolescent; Adult; Aged; Animals; Bayes Theorem; Brazil; Child; Female; Filtration; Humans; Male; Mansonella; Mansonelliasis; Middle Aged; Polycarboxylate Cement; Polymerase Chain Reaction; Predictive Value of Tests; Rural Population; Sensitivity and Specificity; Specimen Handling; Young Adult
PubMed: 29412356
DOI: 10.1590/0074-02760170321 -
Tropical Medicine & International... Dec 2000The protein Ov20/OvS1 was used as antigen in ELISA and Western blot in order to differentiate onchocerciasis from African mansonelliasis and to characterize the...
Use of the recombinant Onchocerca volvulus protein Ov20/OvS1 for the immunodiagnostic differentiation between onchocerciasis and mansonelliasis and for the characterization of hyperreactive onchocerciasis (sowda).
The protein Ov20/OvS1 was used as antigen in ELISA and Western blot in order to differentiate onchocerciasis from African mansonelliasis and to characterize the hyperreactive form of Onchocerca volvulus infection (sowda). The specificity of the IgG4 Western blot was 98% for the differentiation between persons with onchocerciasis and Mansonella microfilariae (mf) carriers (125 persons with M. perstans and 92 with M. streptocerca), whereas the IgG4 ELISA showed a specificity of 81% in 137 M. perstans mf carriers and 85% in 94 M. streptocerca mf carriers. The sensitivity of Ov20/OvS1 in identifying onchocerciasis using the IgG4 ELISA was 75% for 103 O. volvulus mf carriers with the generalized and 89% for 44 patients with the sowda form of onchocerciasis. IgE antibodies against OvS1 were found in 95% of 39 patients with hyperreactive onchocerciasis but only in 15% of 47 persons with the generalized form. Thus, Ov20/-OvS1 appears a promising candidate antigen for the diagnosis of onchocerciasis and in particular for the detection of the sowda type of disease.
Topics: Adult; Animals; Antigens, Helminth; Blotting, Western; Diagnosis, Differential; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Humans; Mansonelliasis; Onchocerca volvulus; Onchocerciasis; Recombinant Proteins; Retinol-Binding Proteins; Sensitivity and Specificity
PubMed: 11169279
DOI: 10.1046/j.1365-3156.2000.00655.x -
Sante (Montrouge, France) 1994There are currently two methods for the direct diagnosis of malaria: the thin blood smear and the thick blood smear. A third cytological method, called the QBC malaria... (Clinical Trial)
Clinical Trial Review
There are currently two methods for the direct diagnosis of malaria: the thin blood smear and the thick blood smear. A third cytological method, called the QBC malaria test (QBC), has been developed. The first studies comparing the three methods report conflicting results. Thus, there is a need for a study of the three methods in parallel and to evaluate the logistic factors which have not been previously assessed. In an analysis of imported malaria, one worker performed the three tests, blind, in parallel with each of 813 samples. The following values were determined: intrinsic validity; predictive values, species diagnostic power; and logistic factors. QBC had the following characteristics: sensitivity = 93.8%; specificity = 99.8%; positive predictive value = 99.3%; negative predictive value = 98.3%; correct species diagnosis = 91.3%; time required for test = 3.7 +/- 0.1 min; storage of tubes at +4 degrees C in the dark = 50 days; cost per test = 27.3 FF (as compared to 24 FF for thin smear and 17.3 FF for thick smear). Although unsuitable for use in countries where malaria is endemic, other than for some specialised situations, QBC is valuable for the diagnosis of imported malaria. In view of our findings, we suggest the following approach to diagnosis: use of the QBC and thin smear tests in parallel first reading the QBC result, as positivity contributes to reading the thin smear result for confirmation of species diagnosis and assessment of parasitaemia.
Topics: Acridine Orange; Hematologic Tests; Humans; Loiasis; Malaria; Malaria, Falciparum; Malaria, Vivax; Mansonelliasis; Microscopy, Fluorescence; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Time Factors
PubMed: 7921703
DOI: No ID Found -
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 -
PLoS Neglected Tropical Diseases Jan 2022Regular and comprehensive epidemiological surveys of the filarial nematodes Mansonella perstans and Loa loa in children, adolescents and adults living across Bioko...
Characterising co-infections with Plasmodium spp., Mansonella perstans or Loa loa in asymptomatic children, adults and elderly people living on Bioko Island using nucleic acids extracted from malaria rapid diagnostic tests.
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.
Topics: Adolescent; Adult; Animals; Child; Coinfection; Cross-Sectional Studies; DNA, Helminth; Equatorial Guinea; Female; Humans; Loa; Loiasis; Malaria; Male; Mansonella; Mansonelliasis; Middle Aged; Plasmodium; Prevalence; Socioeconomic Factors
PubMed: 35100277
DOI: 10.1371/journal.pntd.0009798 -
Parasite Epidemiology and Control May 2018, and are widespread helminth parasites in the tropics. Their distribution remains difficult to determine as it may change during national disease control programs and...
BACKGROUND
, and are widespread helminth parasites in the tropics. Their distribution remains difficult to determine as it may change during national disease control programs and with regional mass drug administration (MDA). Epidemiological surveys are of importance to evaluate the geographical distribution of these helminth parasites and the diseases they may cause, however, up to date epidemiological evaluations on and in Togo are rare, and surveys on are important especially under the aspect of MDA of ivermectin which is performed since decades.
METHODS
Dry blood samples ( = 924) were collected from rural populations in the Régions Central and Plateaux in Togo, and analyzed by parasite-specific real-time PCR and ELISA techniques.
RESULTS
Dry blood samples from 733 persons where investigated by real-time PCR tested for DNA of blood-circulating microfilaria, and a prevalence of 14.9% was detected. Distinct differences were observed between genders, positivity was higher in men increasing with age, and prevalence was highest in the Région Plateaux in Togo. IgG4 responses to antigen (OvAg) were studied in 924 persons and 59% were found positive. The distribution of parasite infestation between age and gender groups was higher in men increasing with age, and regional differences were detected being highest in the Région Plateaux. The diagnostic approach disclosed 64,5% positive IgG4 responses to infective third-stage larvae-specific antigen (SsL3Ag) in the surveyed regions. Antigen cross reactivity of SsL3Ag with parasite co-infections may limit the calculated prevalence. Singly IgG4 positive for SsL3Ag were 13.9%, doubly positive for OvAg and SsL3Ag were 35.5% and triply positive for , and were 9.9%.
CONCLUSIONS
Mansonelliasis, onchocerciasis and strongyloidiasis remain prevalent in the surveyed regions, yet with local differences. Our observations suggest that transmission of , may be ongoing. The degree of positive test results in the examined rural communities advocate for the continuation of MDA with ivermectin and albendazole, and further investigations should address the intensity of transmission of these parasites.
PubMed: 29774301
DOI: 10.1016/j.parepi.2018.03.001 -
Journal of Travel Medicine Nov 2022Infection with Mansonella perstans is a neglected filariasis, widely distributed in sub-Saharan Africa, characterized by an elusive clinical picture; treatment for...
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.
Topics: Animals; Humans; Mansonella; Mansonelliasis; Retrospective Studies; Travel; Mebendazole; Prospective Studies; Travel-Related Illness; Wolbachia
PubMed: 35417002
DOI: 10.1093/jtm/taac048 -
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 -
Parasites & Vectors Dec 2023Loiasis 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...
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.
Topics: Animals; Humans; Adult; Middle Aged; Mansonella; Loiasis; Mansonelliasis; Loa; Congo; Prevalence; Microfilariae
PubMed: 38071391
DOI: 10.1186/s13071-023-06056-w