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PLoS Neglected Tropical Diseases Aug 2021Loa 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...
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.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Child; Coinfection; Female; Gabon; Humans; Loa; Loiasis; Male; Mansonella; Mansonelliasis; Microscopy; Middle Aged; Parasite Load; Parasitemia; Prevalence; Serologic Tests; Young Adult
PubMed: 34398886
DOI: 10.1371/journal.pntd.0009623 -
Parasites & Vectors Aug 2021The tropical disease onchocerciasis (river blindness), caused by Onchocerca volvulus filarial nematodes, is targeted for elimination by mass treatment with nematocidal...
BACKGROUND
The tropical disease onchocerciasis (river blindness), caused by Onchocerca volvulus filarial nematodes, is targeted for elimination by mass treatment with nematocidal and antimicrobial drugs. Diagnosis of O. volvulus infections is based on counts of skin-borne microfilariae, but additional diagnostic tools, e.g. worm- or host-derived small RNAs, proteins or metabolites, are required for high-throughput screening. N-acetyltyramine-O,β-glucuronide (NATOG) was suggested as a biomarker for onchocerciasis but its viability as diagnostic tool has been challenged.
METHODS
We performed a screening program of urine samples from individuals from Cameroon infected with O. volvulus, Loa loa, Mansonella perstans or a combination thereof. Urine metabolites were measured by liquid chromatography-mass spectrometry (LC-MS). Principle component analysis (PCA) revealed that onchocerciasis causes complex changes of the urine metabolome.
RESULTS
The mean NATOG content was elevated in urine of O. volvulus-infected compared with non-infected individuals, but NATOG levels showed considerable variation. However, 13.8% of all O. volvulus-infected individuals had high NATOG levels never reached by individuals without filarial infections or only infected with L. loa or M. perstans. Therefore, the identification of individuals with high NATOG levels might be used to screen for the elimination of onchocerciasis after mass drug application. Additional metabolites, including a compound identified as cinnamoylglycine, had high PC1/PC2 loadings in the data set. Mean levels of cinnamoylglycine were increased in O. volvulus-infected individuals, and 17.2% of all O. volvulus individuals had elevated cinnamoylglycine levels not reached by the controls.
CONCLUSIONS
On an individual level, NATOG alone had poor discriminative power distinguishing infected from non-infected individuals. However, 13.8% of all O. volvulus-infected individuals had NATOG levels never reached by individuals without filarial infections or infected with only L. loa or M. perstans. Discrimination of O. volvulus infections from controls or individuals suffering from multiple infections was improved by the measurement of additional metabolites, e.g. cinnamoylglycine. Thus, measuring a combination of urine metabolites may provide a way to assess onchocerciasis on the population level. This provides the possibility to design a strategy for large-scale onchocerciasis epidemiological screening programs based on urine rather than invasive techniques.
Topics: Animals; Biomarkers; Cameroon; Chromatography, Liquid; Glucuronides; Glycine; Humans; Mass Spectrometry; Metabolome; Onchocerca volvulus; Onchocerciasis; Onchocerciasis, Ocular
PubMed: 34380554
DOI: 10.1186/s13071-021-04893-1 -
Travel Medicine and Infectious Disease 2021The aetiologies of fever are poorly understood in sub-Saharan Africa. We aimed to assess the burden of malaria and bacteria in Côte d'Ivoire.
BACKGROUND
The aetiologies of fever are poorly understood in sub-Saharan Africa. We aimed to assess the burden of malaria and bacteria in Côte d'Ivoire.
METHODS
Blood samples from 438 febrile and 346 afebrile people were screened using molecular tools.
RESULTS
Plasmodium falciparum was the most common microorganism associated with fever (46.8% in febrile, 23.4% in afebrile people; p < 0.001). Bacteraemia was detected in 21.7% of febrile people and 12.7% of afebrile people (p = 0.001). Streptococcus pneumoniae was the main cause of bacteraemia (7.1% of febrile and 0.6% of afebrile individuals; p < 0.001). Non-typhoidal Salmonella spp. was detected in 4.5% of febrile people and 1.2% of afebrile individuals (p < 0.001). Salmonella enterica Typhi and S. enterica Paratyphi were only detected in febrile subjects (1.4% and 2.1%), as well as Tropheryma whipplei (0.9%), Streptococcus pyogenes (0.7%), and Plasmodium ovale (4.6%). The prevalence in febrile and afebrile people was similar for Staphylococcus aureus (3.6-4.9%), Rickettsia felis (5.5-6.4%), Mansonella perstans (3.0-3.2%), and Plasmodium malariae (1.6-2.3%). Comorbidities were higher in febrile than in afebrile subjects (10.3% versus 5.5%; p = 0.01); 82% involving P. falciparum. All patients co-infected with P. falciparum and S. pneumoniae were febrile whereas 30% of those infected by P. falciparum alone were not (p = 0.02). Among febrile participants, 30.4% with malaria and 54.7% with bacteraemia had received neither antimalarial nor antibiotic therapy.
CONCLUSION
Identification of etiologies of acute febrile diseases in sub-Saharan Africa proposes keys to successful treatment and prevention of infectious diseases. Vaccination campaigns may decrease the morbidity of mono- and co-infections by preventable microorganisms.
Topics: Bacteremia; Cote d'Ivoire; Humans; Malaria; Malaria, Falciparum; Retrospective Studies
PubMed: 34146685
DOI: 10.1016/j.tmaid.2021.102105 -
Research and Reports in Tropical... 2021Mansonellosis is caused by three filarial parasite species from the genus that commonly produce chronic human microfilaraemias: and . The disease is widespread in... (Review)
Review
Mansonellosis is caused by three filarial parasite species from the genus that commonly produce chronic human microfilaraemias: and . The disease is widespread in Africa, the Caribbean and South and Central America, and although it is typically asymptomatic it has been associated with mild pathologies including leg-chills, joint-pains, headaches, fevers, and corneal lesions. No robust mansonellosis disease burden estimates have yet been made and the impact the disease has on blood bank stocks and the monitoring of other filarial diseases is not thought to be of sufficient public health importance to justify dedicated disease management interventions. Mansonellosis´s Ceratopogonidae and Simuliidae vectors are not targeted by other control programmes and because of their small size and out-door biting habits are unlikely to be affected by interventions targeting other disease vectors like mosquitoes. The ivermectin and mebendazole-based mass drug administration (iMDA and mMDA) treatment regimens deployed by the WHO´s Elimination of Neglected Tropical Diseases (ESPEN) programme and its forerunners have, however, likely impacted significantly on the mansonellosis disease burden, principally by reducing the transmission of in Africa. The increasingly popular plan of using iMDA to control malaria could also affect parasite prevalence and transmission in Latin America in the future. However, a potentially far greater mansonellosis disease burden impact is likely to come from short-course curative anti- therapeutics, which are presently being developed for onchocerciasis and lymphatic filariasis treatment. Even if the WHO´s ESPEN programme does not choose to deploy these drugs in MDA interventions, they have the potential to dramatically increase the financial and logistical feasibility of effective mansonellosis management. There is, thus, now a fresh and urgent need to better characterise the disease burden and eco-epidemiology of mansonellosis so that effective management programmes can be designed, advocated for and implemented.
PubMed: 34079424
DOI: 10.2147/RRTM.S274684 -
Parasite (Paris, France) 2021The standard techniques for diagnosis of human filariasis are the microscopic examination of blood smears or skin biopsies, which are relatively invasive and poorly...
The standard techniques for diagnosis of human filariasis are the microscopic examination of blood smears or skin biopsies, which are relatively invasive and poorly sensitive at low levels of infection. Recently, filarial DNA has been detected in fecal samples from non-human primates in Central Africa. The aim of this study was to demonstrate proof-of-concept of a non-invasive molecular diagnosis technique for human filariasis by targeting fragments of 12S rDNA, Cox1, ITS1 and LL20-15kDa ladder antigen-gene by conventional PCR in DNA extracted from stool samples of 52 people infected with Mansonella perstans and/or Loa loa. Of these, 10 patients were infected with soil-transmitted helminths (Trichuris trichiura and/or Ascaris lumbricoides), and none were positive for Necator americanus. Interestingly, no filarial gene fragments were detected in the stools of any of the 52 patients. Future studies should evaluate whether a co-infection with soil-transmitted helminths causing gastrointestinal bleeding and likely allowing (micro)filaria exit into the digestive tract, may facilitate the molecular detection of filarial DNA fragments in stool samples.
Topics: Animals; Ascaris lumbricoides; Helminths; Humans; Polymerase Chain Reaction; Soil; Trichuris
PubMed: 34047694
DOI: 10.1051/parasite/2021046 -
Biomedicine & Pharmacotherapy =... May 2021Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high... (Review)
Review
Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high prevalence in developing countries, filarial infections are responsible for some of the most debilitating morbidities and a vicious cycle of poverty and disease. Global initiatives set to eradicate these infections include community mass treatments, vector control, provision of care for morbidity, and search for vaccines. However, there are growing challenges associated with mass treatments, vector control, and antifilarial vaccine development. With the emergence of genome editing tools and successful applications in other infectious diseases, the integration of genetic editing techniques in future control strategies for filarial infections would offer the best option for eliminating filarial infections. In this review, we briefly discuss the mechanisms of the three main genetic editing techniques and explore the potential applications of these powerful tools to control filarial infections.
Topics: Animals; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Filariasis; Filaricides; Filarioidea; Gene Editing; Genetic Therapy; Humans; Protozoan Vaccines
PubMed: 33581654
DOI: 10.1016/j.biopha.2021.111292 -
Parasitology Research Dec 2021Filariae are vector-borne parasitic nematodes that are endemic worldwide, in tropical and subtropical regions. Important human filariae spp. include Onchocerca volvulus,... (Review)
Review
Filariae are vector-borne parasitic nematodes that are endemic worldwide, in tropical and subtropical regions. Important human filariae spp. include Onchocerca volvulus, Wuchereria bancrofti and Brugia spp., and Loa loa and Mansonella spp. causing onchocerciasis (river blindness), lymphatic filariasis (lymphedema and hydrocele), loiasis (eye worm), and mansonelliasis, respectively. It is estimated that over 1 billion individuals live in endemic regions where filarial diseases are a public health concern contributing to significant disability adjusted life years (DALYs). Thus, efforts to control and eliminate filarial diseases were already launched by the WHO in the 1970s, especially against lymphatic filariasis and onchocerciasis, and are mainly based on mass drug administration (MDA) of microfilaricidal drugs (ivermectin, diethylcarbamazine, albendazole) to filarial endemic areas accompanied with vector control strategies with the goal to reduce the transmission. With the United Nations Sustainable Development Goals (SDGs), it was decided to eliminate transmission of onchocerciasis and stop lymphatic filariasis as a public health problem by 2030. It was also requested that novel drugs and treatment strategies be developed. Mouse models provide an important platform for anti-filarial drug research in a preclinical setting. This review presents an overview about the Litomosoides sigmodontis and Acanthocheilonema viteae filarial mouse models and their role in immunological research as well as preclinical studies about novel anti-filarial drugs and treatment strategies.
Topics: Acanthocheilonema; Animals; Elephantiasis, Filarial; Filarioidea; Humans; Loiasis; Male; Mice; Models, Animal
PubMed: 33547508
DOI: 10.1007/s00436-020-07026-2 -
Acta Tropica Apr 2021Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and... (Comparative Study)
Comparative Study
Infections with the filarial nematodes Loa loa and Mansonella perstans are among the most neglected filarial infections. L. loa is endemic in 11 countries of Central and West Africa and loiasis is estimated to affect about 20 million people. M. perstans infection is widespread in more than 30 countries of sub-Saharan Africa. Due to the difficulty in diagnosing loiasis and M. perstans mansonellosis on a clinical basis, the diagnosis of infection with L. loa and M. perstans relies on laboratory techniques. Definitive diagnosis is based on the detection, identification, and quantification of circulating microfilariae (mf) by microscopy of concentrated blood. However, this is impractical for screening purposes as it requires expert laboratory personnel, considerable blood manipulation, and is time consuming, especially for the final issue of negative result reports, which are very common in the population visited outside endemic areas. The aim of the current work is the preliminary evaluation of the performance of the in-house real-time PCR described by Ta and colleagues compared to the routine microscopic approach for the screening of filarial infections in the clinical setting outside endemic areas, using samples from patients accessing the dedicated outpatient clinics for migrants and travelers of a reference centre for tropical diseases in Northern Italy.
Topics: Adult; Animals; Female; Humans; Loiasis; Male; Mansonelliasis; Microfilariae; Microscopy; Real-Time Polymerase Chain Reaction; Retrospective Studies
PubMed: 33484727
DOI: 10.1016/j.actatropica.2021.105838 -
The Journal of Veterinary Medical... Feb 2021This study aimed to detect filarial parasites in blood samples of Japanese black bears (Ursus thibetanus japonicus) collected from Iwate Prefecture, Japan. Positive...
This study aimed to detect filarial parasites in blood samples of Japanese black bears (Ursus thibetanus japonicus) collected from Iwate Prefecture, Japan. Positive amplicons were obtained from 26 out of 30 samples by nested PCR targeting 18S ribosomal RNA gene and first internal transcribed spacer regions. DNA sequences of Mansonella sp. close to M. ozzardi and Dirofilaria sp. were detected for eight and 11 positive amplicons, respectively. Co-infection was detected for the remaining seven amplicons. Dirofilaria sp. was identified as D. ursi by further genetic analysis of 5S ribosomal RNA gene sequence. The results of this study will contribute to further investigations of Japanese black bears for monitoring their risk as a reservoir of possible zoonotic filarial parasites.
Topics: Animals; Female; Filariasis; Filarioidea; Japan; Male; RNA, Ribosomal, 18S; Ursidae
PubMed: 33311003
DOI: 10.1292/jvms.20-0466 -
EClinicalMedicine Nov 2020Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in...
BACKGROUND
Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in individuals with high microfilarial densities (MFD). We developed the first statistical models enabling prediction of SAE risk in individuals with a given MFD.
METHODS
We used individual participant data from two trials conducted in loiasis-onchocerciasis co-endemic areas in Cameroon. among the 10 506 ivermectin-treated subjects included in the analysis, 38 (0·36%) developed an ivermectin-related SAE. To predict individual-level risk of SAE, we developed mixed multivariate logistic models including subjects' sex, age, pre-treatment and MFDs, and study region.
FINDINGS
The models predicted that regardless of sex, about 1% of people with 20 000 microfilariae per millilitre of blood (mf/mL), 10% of people with 50 000 mf/mL and about one third of those with 100 000 mf/mL will develop an SAE. For a given MFD, males have a three-fold higher risk of developing an SAE than females.
INTERPRETATION
By enabling the prediction of post-ivermectin SAE risk in communities with known distribution of MFDs, our results can guide decisions on the choice of ivermectin-based treatment strategies. They also predict that 37 SAEs were prevented in 2015 by using a Test-and-Treat strategy in the Okola District of Cameroon.
FUNDING
UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases; Institut de Recherche pour le Développement; Mectizan Donation Program; Bill & Melinda Gates Foundation
PubMed: 33294807
DOI: 10.1016/j.eclinm.2020.100582