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Mosquitoes
Published in Jerome Goddard, Public Health Entomology, 2022
Lymphatic filariasis. Several species of nematode worms may cause lymphatic filariasis, an important human mosquito-borne disease occurring in much of the world (Figure 9.8). Malayan filariasis, caused by Brugia malayi, is mostly confined to Southeast Asia, and the Bancroftian form, Wucheria bancrofti, is prevalent over much of the tropical world. In 2000, the WHO estimated that 120 million people were infected with Bancroftian or Brugian filariasis, with an additional 1.34 billion persons at risk.11 That number is now significantly lower due to mass drug administration using ivermectin, diethylcarbamazine, and other compounds.12 In the Western Hemisphere, 80% of lymphatic filariasis occurs in Haiti, likely imported from Africa with the slave trade.13 Human filariasis is transmitted solely by mosquitoes, and there is no multiplication of the parasite, only development, in the mosquito vector. In addition, the adult worms may live up to 10 years in humans.14
The Host Immune Response Against Parasitic Helminth Infection
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
T-cell-mediated immune responses are found commonly in helminth infections, the pathological consequences of which are most often reflected in granuloma formation. Such granulomata have been best studied in Schistosoma mansoni infections, where T-cell control of their size and development has been documented (45, 46). Indeed, work with T cells from patients with recent S. mansoni infections has indicated that CD3+CD4+ T cells mediate granulomatous hypersensitivity (47). Furthermore, work done with murine schistosome antigen-reactive T-cell clones has indicated not only that these "helper/inducer" cells regulate the formation of granulomas but also that they produce lymphokines such as eosinophil stimulation promoter and macrophage-activating factor. These products may contribute to the recruitment of cells to the area of granulomatous inflammation (48). While granulomas presumably act to isolate and thereby eradicate the parasite, often these local areas of immunological activity actually damage normal tissue. For example, in schistosomiasis, scarring of the portal tracts resulting from the fibrosis following granuloma formation (46) can lead to cirrhosis and portal hypertension. In lymphatic filariasis, similar fibrotic reactions have been found surrounding adult parasites in the lymphatic channels and lymph nodes (1); this "scarring" is felt to be in part responsible for the lymphedema, elephantiasis, hydrocele, and chyluria found in this condition.
An Overview of Helminthiasis
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Leyla Yurttaș, Betül Kaya Çavușoğlu, Derya Osmaniye, Ulviye Acar Çevik
Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type common in tropical regions, coastal areas and island in the Pacific, Africa, America, and Asia. The disease has been seen in people aged 10 years and older. Filarial worms cause a variety of clinical pathologies depending on the degree of host immune reaction. The subcutaneous filariasis causes skin itching, scratch marks and papules until the entire skin is dry and tempered. Filariases that affect the skin are caused by Wuchereria bancrofti, Brugia malayi, Loa loa, and Onchocerca volvulus (Kalungi et al. 2017).
The relevance of studying insect–nematode interactions for human disease
Published in Pathogens and Global Health, 2022
Zorada Swart, Tuan A. Duong, Brenda D. Wingfield, Alisa Postma, Bernard Slippers
From a public health perspective, the main treatment strategy for filariasis is preventative chemotherapy in the form of Mass Drug Administration (MDA) [6–8]. Mass Drug Administration programs administer antiparasitic medication to all members of a community at risk without first testing individuals for an infection. Mathematical models predicted that these regimens are not sufficient to keep the disease controlled in areas with high prevalence [9]. Adherence to the dosing schedule is one of the challenges associated with MDA as successful elimination requires at least five doses of anti-filarial drugs and one or more doses are often missed [10,11]. Only two combinations of three different drugs are available to treat filariasis and all three target the larval stage of the nematodes only, leaving adult worms unaffected [12,13].
Lymphatic filariasis vaccine development: neglected for how long?
Published in Expert Review of Vaccines, 2021
Vivek P Chavda, Anjali Pandya, Sreeranjini Pulakkat, Moinuddin Soniwala, Vandana Patravale
As per the World Health Organization (WHO), ‘Lymphatic filariasis (LF) is a vector-borne neglected tropical disease that causes the damage of the lymphatic system and can lead to lymphoedema (elephantiasis) and hydrocele (excess fluid inside the human scrotal sac) in infected individuals’ [1]. The filarial parasites that cause this infection are carried by mosquitoes. Invasion from parasitic nematodes (roundworms or helminths) of the family Filariodidea, such as Wuchereria bancrofti (W.bancrofti), Brugia malayi (B.malayi), or Brugia timori, causes the disease [2,3]. LF affects the lymphatic system and can cause abnormal growth of bodily parts, resulting in discomfort, physical disability, and social stigma. More than 198 million people were infected globally in 2000, approximately 130 million people in 2014, while the 2018 projection of approximately 51 million infected people indicates the progress made thus far toward the eradication of LF as a public health burden due to implementation of chemotherapy in 2000 [4]. LF continues to endanger 859 million people in 50 countries all over the world, necessitating preventative treatment to halt the spread of such a parasitic disease. The annual benchmark estimation of LF patients suggests 25 million males having hydrocele and over 15 million persons with lymphedema. At least 40 million individuals continue to suffer from these chronic illness symptoms [5]. Preventing LF could help to reduce possible suffering and stigma among the vulnerable underprivileged population.
Moxidectin: an oral treatment for human onchocerciasis
Published in Expert Review of Anti-infective Therapy, 2020
Philip Milton, Jonathan I. D. Hamley, Martin Walker, María-Gloria Basáñez
Other than moxidectin, the drugs furthest along in clinical and pre-clinical development are anti-Wolbachia therapies, targeting the endosymbiotic Wolbachia pipientis bacterium within the parasite [90–92]. Depletion of Wolbachia (by >90%), following treatment with tetracycline antibiotics such as doxycycline, exerts a potent but protracted macrofilaricidal activity, reducing the adult worms’ life-expectancy by 70–80%, from approximately 10 years to 2–3 years [93]. This slow-killing action contributes to its safety and tolerability profile [91,93]. Although not directly microfilaricidal, microfilaridermia loads decrease progressively as a result of female worm sterilization by inhibition of the parasite’s embryogenesis [90]. Furthermore, microfilariae from doxycycline-treated individuals exhibit retarded development to the infective, L3 stage, if ingested by blackfly vectors for at least 5 months after treatment compared to microfilariae from placebo-treated patients [94]. Data from animal models of filariasis also show that, during the course of treatment, larvae entering the vertebrate host do not establish as adult worms, thereby indicating a prophylactic effect [95]. To achieve the critical efficacy threshold of >90% Wolbachia depletion [90], a 4–6-week course of 100–200 mg of doxycycline is required [93]. As L. loa does not harbor W. pipientis, the parasite is unaffected by anti-Wolbachia therapies [96], which can, therefore, be safely used to treat onchocerciasis in loiasis co-endemic areas [97].