Immunity in Filarial Infections: Lessons from Animal Models and Human Studies

Kwarteng, Alexander; Ahuno, Samuel Terkper

doi:10.1111/sji.12533

Cited by 18 publications

(18 citation statements)

References 75 publications

(84 reference statements)

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“…In humans, the manifestations of filarial infection exist on a spectrum with two evident extremes; most cases are asymptomatic yet characterized by the presence of circulating microfilariae, whereas those with chronic pathology more often present as amicrofilaremic (King and Nutman 1991, Michael et al 1994, Pfarr et al 2009, Kwarteng and Ahuno 2017. It has been proposed that this is a result of the parasite exerting an immunomodulatory influence on the host, and a failure of that modulation, respectively (Ottesen 1984, Mai-zels and Lawrence 1991), though alternatives have been proposed that emphasize infection status over disease status as a reflection of the immune response (Freedman 1998, Nicolas et al 1999, Jaoko et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that this is a result of the parasite exerting an immunomodulatory influence on the host, and a failure of that modulation, respectively (Ottesen 1984, Mai-zels and Lawrence 1991), though alternatives have been proposed that emphasize infection status over disease status as a reflection of the immune response (Freedman 1998, Nicolas et al 1999, Jaoko et al 2006). In addition, asymptomatic ''latent'' infections are characterized by the presence of adult parasites but not microfilariae (Turner et al 1993, Kwarteng andAhuno 2017). Considering this variety of manifestations and the intimate involvement of the immune response in each, it is reasonable to suspect certain host factors as early indicators of ultimate microfilaremia status.…”

Section: Introductionmentioning

confidence: 99%

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The Course ofBrugia malayiMicrofilaremia in Experimentally Infected Cats

Evans

Burkman

Dzimianski

et al. 2021

Vector-Borne and Zoonotic Diseases

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As one of the causative agents of lymphatic filariasis in humans, Brugia malayi has been established as the laboratory model of choice for studying this infection owing to its viability in small animal hosts, with the domestic cat being significant among these. The usefulness of individual feline infections is highly dependent on the levels of circulating microfilariae in the blood; thus, characterizing the course of microfilaremia benefits our understanding of this model. In B. malayi-endemic regions, cats are also known reservoirs of infection, and describing microfilaremia in a controlled setting may improve transmission modeling. We followed the course of B. malayi infection in 10 experimentally infected cats from inoculation to ultimate resolution. Seven cats developed patency, with a peak microfilaria concentration of 6525/mL. In addition, to identify cellular responses with potential value as predictors of patency, we measured the peripheral blood leukocyte counts during the first 8 months of infection and tested for correlations with lifelong microfilaria production. No strong relationships were observed, though cell values did appear to shift with the maturation phases of the parasite. The data we present reflect the course of microfilaremia in an important laboratory model under controlled conditions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Course ofBrugia malayiMicrofilaremia in Experimentally Infected Cats

Evans

Burkman

Dzimianski

et al. 2021

Vector-Borne and Zoonotic Diseases

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“…Shorter-lived worms will have higher resurgence because resurgence rates are approximately proportional to 1/L, where L is the lifespan of the worm in the human host [ 2 ]. Hence, missing an annual MDA for soil-transmitted helminthiases (STH) and schistosomiasis programs (lifespans from 1 to 10 years [ 3–7 ]) will be more severe than for onchocerciasis and lymphatic filariasis (LF) (lifespans from 5 to 15 years [ 8 , 9 ]) ( Figure 1 ) (but unlike LF, onchocerciasis MDA treatments are not strongly adulticidal [ 10 ]). Similar analysis for trachoma estimated that the doubling time (time over which the number of cases double) for resurgence may vary from 1–2 months in highly endemic settings to 4–8 months in lower endemic settings [ 11 ], suggesting that trachoma programs face a greater resurgence risk relative to the helminths.…”

mentioning

confidence: 99%

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation

Toor

Adams

Aliee

et al. 2020

Clinical Infectious Diseases

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Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.

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“…In the present study, we elucidated the effect of diabetes on antifilarial response, in LF+ subjects. Anti-filarial response is complex and multifaceted and involves both the innate and adaptive arms of the immune system (30). For innate immunity, we studied TLR signaling, and for adaptive immunity, we studied filarial antigeninduced responses.…”

Section: Discussionmentioning

confidence: 99%

Augmented Innate and Adaptive Immune Responses Under Conditions of Diabetes–Filariasis Comorbidity

et al. 2021

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Metainflammation, as seen in chronic diabetes subjects, impairs immunity and increases the susceptibility to infections. In the present study, the effect of diabetes on immune response against filariasis was studied. Both toll-like receptor (TLR)-mediated and crude antigen-induced immune responses were quantified, in whole blood cultures from filariasis-infected subjects (LF+), with and without diabetes. Blood cultures were stimulated with TLR ligands (TLR2 and TLR4) or filarial antigen or were left unstimulated (control) for 18 h. Cytokine, chemokine, and defensin secretion was quantified by ELISA. Expression of HLA-DR, B7-1, B7-2, activation marker (CD69), and Th (Th1, Th2, Th17, and Th9) phenotypes was quantified by flow cytometry. Expression of immunomodulatory effectors (Cox-2, HO-1, IDO-1, and p47Phox) and Th-polarizing transcription factors (T-bet, GATA3, and ROR-γt) was quantified by quantitative PCR. Secretion of IL-27, IL-1Ra, IL-12, IL-33, IL-9, and SDF-1 was increased under diabetes conditions with increased Th9 polarization and increased expression of Cox-2 and IDO. Overall, diabetes was found to augment both TLR-mediated and antigen-induced inflammation, which can promote chronic pathology in LF+ subjects.

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Immunity in Filarial Infections: Lessons from Animal Models and Human Studies

Abstract: Our understanding of immunity to filarial infection is enigmatic and continues to be passionately debated. The mechanisms whereby filarial nematodes are killed in vivo and how these parasites avoid these mechanisms are poorly understood.

Cited by 18 publications

References 75 publications

The Course ofBrugia malayiMicrofilaremia in Experimentally Infected Cats

The Course ofBrugia malayiMicrofilaremia in Experimentally Infected Cats

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation

Augmented Innate and Adaptive Immune Responses Under Conditions of Diabetes–Filariasis Comorbidity

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