-
Frontiers in Immunology 2023Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of...
Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing glycans with plasma from uninfected individuals and from individuals infected with , , and , four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from and infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of infected individuals. For these infection groups, , and , we further studied the different IgG subclasses to glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.
Topics: Humans; Animals; Filariasis; Antibodies, Helminth; Brugia malayi; Antigens; Immunoglobulin G
PubMed: 36949937
DOI: 10.3389/fimmu.2023.1102344 -
Frontiers in Tropical Diseases Mar 2023Filariae are vector borne parasitic nematodes, endemic in tropical and subtropical regions causing avoidable infections ranging from asymptomatic to stigmatizing and...
Filariasis research - from basic research to drug development and novel diagnostics, over a decade of research at the Institute for Medical Microbiology, Immunology and Parasitology, Bonn, Germany.
Filariae are vector borne parasitic nematodes, endemic in tropical and subtropical regions causing avoidable infections ranging from asymptomatic to stigmatizing and disfiguring disease. The filarial species that are the major focus of our institution's research are causing onchocerciasis (river blindness), and spp. causing lymphatic filariasis (elephantiasis), causing loiasis (African eye worm), and spp causing mansonellosis. This paper aims to showcase the contribution of our institution and our collaborating partners to filarial research and covers decades of long research spanning basic research using the animal model to development of drugs and novel diagnostics. Research with the model has been extensively useful in elucidating protective immune responses against filariae as well as in identifying the mechanisms of filarial immunomodulation during metabolic, autoimmune and infectious diseases. The institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn (UKB), Bonn, Germany has also been actively involved in translational research in contributing to the identification of new drug targets and pre-clinical drug research with successful and ongoing partnership with sub-Saharan Africa, mainly Ghana (the Kumasi Centre for Collaborative Research (KCCR)), Cameroon (University of Buea (UB)) and Togo (Laboratoire de Microbiologie et de Contrôle de Qualité des Denrées Alimentaires (LAMICODA)), Asia and industry partners. Further, in the direction of developing novel diagnostics that are sensitive, time, and labour saving, we have developed sensitive qPCRs as well as LAMP assays and are currently working on artificial intelligence based histology analysis for onchocerciasis. The article also highlights our ongoing research and the need for novel animal models and new drug targets.
PubMed: 38655130
DOI: 10.3389/fitd.2023.1126173 -
PLoS Neglected Tropical Diseases Jan 2023[This corrects the article DOI: 10.1371/journal.pntd.0010615.].
Correction: Targeting a highly repetitive genomic sequence for sensitive and specific molecular detection of the filarial parasite Mansonella perstans from human blood and mosquitoes.
[This corrects the article DOI: 10.1371/journal.pntd.0010615.].
PubMed: 36701268
DOI: 10.1371/journal.pntd.0011096 -
Frontiers in Tropical Diseases Jan 2023Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is...
Conventional diagnosis of filarial infections is based on morphological identification of microfilariae using light microscopy and requires considerable expertise, is time-consuming, and can be subjective. Loop-mediated isothermal amplification (LAMP) has advantages over microscopy or PCR because of its operational simplicity, rapidity and versatility of readout options. LAMP assays represent a major step forward in improved filarial diagnostic tools suitable for low resource settings and field applicability. The study goal was to retrospectively evaluate the performance and suitability of the O-150, RF4, and Mp419 LAMP assays for diagnosing , and infections, respectively, in humans and vectors under experimental and natural field conditions. Surveys were conducted in four health districts of Cameroon using skin snip and thick blood film methods to detect skin () and blood ( and ) dwelling microfilaria in humans. Engorged vectors (., ., and spp.) were evaluated by LAMP. Dissected, wild-caught vectors were also analyzed. LAMP showed a prevalence of 40.4% (), 17.8% () and 36.6% () versus 20.6% (), 17.4% () and 33.8% () with microscopy. spp. were dissected for microscopy and pooled for LAMP. The O-150 LAMP assay infection rate was 4.3% versus 4.1% by microscopy. spp. were dissected and analyzed individually in the LAMP assay. The RF4 LAMP assay infection rate was 23.5% versus 3.3% with microscopy. The RF4 LAMP assay also detected parasites in spp. fed on low microfilaremic volunteers. The Mp419 LAMP assay infection rate was 0.2% for and 0.04% for , while three other species were LAMP-negative. The sensitivity, species specificity, rapidity and ease of its use of these filarial LAMP assays, and validation of their performance in the field support use as alternatives to microscopy as diagnostic and surveillance tools in global health programs aimed to eliminate onchocerciasis.
PubMed: 36684508
DOI: 10.3389/fitd.2022.1016176 -
PLoS Neglected Tropical Diseases Dec 2022Mansonella 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...
Targeting a highly repetitive genomic sequence for sensitive and specific molecular detection of the filarial parasite Mansonella perstans from human blood and mosquitoes.
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.
Topics: Animals; Humans; Mansonella; Parasites; Culicidae; Mosquito Vectors; Genomics; Mansonelliasis
PubMed: 36580452
DOI: 10.1371/journal.pntd.0010615 -
PLoS Neglected Tropical Diseases Dec 2022
PubMed: 36512531
DOI: 10.1371/journal.pntd.0010921 -
PLoS Neglected Tropical Diseases Nov 2022Community presence of loiasis must be determined before mass drug administration programmes for lymphatic filariasis and onchocerciasis can be implemented. However,...
Integrated xenosurveillance of Loa loa, Wuchereria bancrofti, Mansonella perstans and Plasmodium falciparum using mosquito carcasses and faeces: A pilot study in Cameroon.
BACKGROUND
Community presence of loiasis must be determined before mass drug administration programmes for lymphatic filariasis and onchocerciasis can be implemented. However, taking human blood samples for loiasis surveillance is invasive and operationally challenging. A xenosurveillance approach based on the molecular screening of mosquitoes and their excreta/feces (E/F) for Loa loa DNA may provide a non-invasive method for detecting the community presence of loiasis.
METHODS
We collected 770 wild mosquitoes during a pilot study in a known loiasis transmission area in Mbalmayo, Cameroon. Of these, 376 were preserved immediately while 394 were kept in pools to collect 36-hour E/F samples before processing. Carcasses and E/F were screened for L. loa DNA. To demonstrate this method's potential for integrated disease surveillance, the samples were further tested for Wuchereria bancrofti, Mansonella perstans, and Plasmodium falciparum.
RESULTS
Despite limited sample numbers, L. loa DNA was detected in eight immediately-stored mosquitoes (2.13%; 95% CI 1.08 to 4.14), one carcass stored after providing E/F (0.25%; 95% CI 0.04 to 1.42), and three E/F samples (estimated prevalence 0.77%; 95% CI 0.15 to 2.23%). M. perstans and P. falciparum DNA were also detected in carcasses and E/F samples, while W. bancrofti DNA was detected in E/F. None of the carcasses positive for filarial worm DNA came from pools that provided a positive E/F sample, supporting the theory that, in incompetent vectors, ingested parasites undergo a rapid, complete expulsion in E/F.
CONCLUSIONS
Mosquito xenosurveillance may provide a useful tool for the surveillance of loiasis alongside other parasitic diseases.
Topics: Animals; Humans; Loa; Mansonella; Wuchereria bancrofti; Loiasis; Plasmodium falciparum; Pilot Projects; Culicidae; Cameroon; Mosquito Vectors; Malaria, Falciparum; Feces
PubMed: 36322515
DOI: 10.1371/journal.pntd.0010868 -
PLoS Neglected Tropical Diseases Oct 2022Malaria 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Animals; Humans; Prevalence; Interleukin-10; Interleukin-4; Coinfection; Tumor Necrosis Factor-alpha; Interleukin-6; Filariasis; Mansonelliasis; Malaria; Probability; Complement C4; Chemokines
PubMed: 36269701
DOI: 10.1371/journal.pntd.0010857 -
Therapeutic Advances in Infectious... 2022Studies conducted in 1984 demonstrated the presence of in the Darien and Colon provinces. Since then, there have not been further reports of this parasitic infection in...
INTRODUCTION
Studies conducted in 1984 demonstrated the presence of in the Darien and Colon provinces. Since then, there have not been further reports of this parasitic infection in Panama.
METHODOLOGY
We conducted a cross-sectional assessment of peripheral blood samples of individuals across Panama over a 4-year period (2013-2016) as part of malaria surveillance activities.
RESULTS
We identified microfilaria in 96 cases. Most of these cases were found in East Panama (78%) followed by the Darien region (22%). was the filarial parasite identified by morphological features in all cases.
CONCLUSION
After 36 years of epidemiological silence, we identified human cases of infection in Panama. This is, however, the first report of this filarial parasite's presence in the Eastern region of Panama. There is a need for further surveillance efforts to elucidate the epidemiology associated with infections in Panama.
PubMed: 36225853
DOI: 10.1177/20499361221122582 -
Pathogens (Basel, Switzerland) Aug 2022Equine filariosis (EF) is a neglected vector-borne disease caused by nematode species belonging to the Onchocercidae and Setariidae families. Aside from their zoonotic...
Equine filariosis (EF) is a neglected vector-borne disease caused by nematode species belonging to the Onchocercidae and Setariidae families. Aside from their zoonotic potential, some species are responsible for serious health problems in equids worldwide, leading to significant economic difficulties. Here, we molecularly investigated equine blood samples (320 horses and 109 donkeys from Egypt) and four adult worms isolated from the peritoneal cavity of 5 out of the 94 slaughtered donkeys. In addition, quantitative enzyme-linked immunoassays (ELISAs) targeting circulating cytokines were used to identify whether the immunological profile of the infected animals is a Th1 (i.e., INF-gamma as indicator) or Th2 (i.e., IL-5 and IL-10 as indicators) response type. Overall, 13.8% and 0.3% of the donkeys and horses, respectively, were scored as positive for filaroid DNA. The 18S phylogeny revealed the occurrence of three different filaroid species, identified here as () sp., and . Th1 (INF-gamma and IL-5) and Th2 (IL-10) immune response types were identified in equines infected with and () sp., respectively. These results provide new data on the species diversity of EF in Egypt and extend knowledge of the downregulation of the protective immune response by the potentially zoonotic sp. There is an urgent need to implement control measures to preserve equine health and limit the propagation of these vector-borne filaroids in Egypt.
PubMed: 36145411
DOI: 10.3390/pathogens11090979