Thomas B. Nutman

Treatment of W. bancrofti (Wb) in HIV/Wb coinfections in South India.

Background The disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections. Methodology/Principal Findings To assess the influence of pre-existing Wuchereria bancrofti infection on HIV progression, we performed a case-controlled treatment study of HIV positive individuals with (FIL+) or without (FIL-) W. bancrofti infection. Twenty-eight HIV+/FIL+ and 51 matched HIV+/FIL- subjects were treated with a single dose of diethylcarbamazine and albendazole (DEC/Alb) and followed for a year at regular intervals. Sixteen of the HIV+/FIL+ subjects (54%) and 28 of the HIV+/FIL- controls (57%) were on antiretroviral therapy (ART) during the study. Following treatment, no differences were noted in clinical outcomes between the 2 groups. There also was no significant difference between the groups in the HIV viral load at 12 months as a percentage of baseline viral load (HIV+/FIL+ group had on average 0.97 times the response of the HIV+/FIL- group, 95% CI 0.88, 1.07) between the groups. Furthermore, there were no significant differences found in either the change in viral load at 1, 3, or 6 months or in the change in CD4 count at 3, 6, or 12 months between the 2 groups. Conclusions/Significance We were unable to find a significant effect of W. bancrofti infection or its treatment on HIV clinical course or surrogate markers of HIV disease progression though we recognized that our study was limited by the smaller than predicted sample size and by the use of ART in half of the patients. Treatment of W. bancrofti coinfection in HIV positive subjects (as is usual in mass drug administration campaigns) did not represent an increased risk to the subjects, and should therefore be considered for PLWHA living in W. bancrofti endemic areas. Trial Registration ClinicalTrials.gov NCT00344279

Immune Responses to Helminth Infection

Abstract Over 2 billion people worldwide are infected with helminths (worms). Helminth infections are a major public health problem worldwide due to their ability to cause significant morbidity and socioeconomic loss. Although not usually fatal, helminth infections induce a spectrum of pathological responses (with ensuing clinical manifestations) resulting in major morbidity in helminth - afflicted individuals. The immune response to helminths typically involves Type 2 responses (encompassing Th2, Type 2 innate lymphoid cell, eosinophil and antibody responses) and regulatory responses (encompassing regulatory cytokines and cellular subsets). In this chapter, we discuss recent advances in defining the immune cell types and molecules that are induced by helminth infections. We also report on the modulation of immune responses that enables the establishment of long-standing or persistent infection and its major mediators.

Etiology and Pathophysiology

Lymphatic filariasis caused by the lymph-dwelling filarial parasites infects over 120 million people. While the majority of the infections are subclinical, ~40 million have lymphedema and/or other pathological manifestations ranging from episodic adenolymphangitis, hydroceles, lymphedema, or elephantiasis. The adult worms residing in the lymphatics induce lymphatic dilatation rendering them dysfunctional. Progression to lymphedema and elephantiasis is mediated primarily from the host inflammatory responses to the parasite and perhaps to the Wolbachia endosymbiont or as a consequence of superimposed secondary bacterial and fungal infections.

Chapter 16 – Vascular Responses in Human Lymphatic Filariasis

Although two-thirds of the 120 million people infected with filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Filarial parasites reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology ensues and is considered to be the direct summation of multiple factors including the effect of tissue alterations induced by living and dead adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. This review will discuss the proposed mechanisms underlying pathogenesis, including a comprehensive discussion of the changes in the vascular system that underlies host pathology. The data suggest that a complex interaction involving a network of cytokines, vascular growth factors, factors affecting tissue remodeling, and innate immune factors underlies the development of vascular pathology in lymphatic filariasis.