Trends in Parasitology
Volume 23, Issue 10, October 2007, Pages 459-462
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Neonatal tolerance and patent filarial infection

https://doi.org/10.1016/j.pt.2007.08.009Get rights and content

Lymphatic filariasis occurs in endemic pockets. Patent infections with long-term, high-grade microfilaremia do not develop in nonendemic individuals. It is tempting to speculate that individuals with intact immune responses to filarial antigens are capable of dealing with filarial exposure without developing persistent infection. There are published data that support the idea that only those individuals who are impaired in their immune defense against these parasites owing to neonatal tolerization become productively infected with the filarial parasites. If the model is correct, there are profound implications for global eradication.

Section snippets

Natural history of filarial infection

For most human diseases, our understanding of the natural history of infection is based on the outcome(s) of infection in people who have not experienced the disease previously, that is, naïve populations. Most current models of the course of lymphatic filarial infection, however, have been based on observations on endemic populations. It would, therefore, be instructive to review the literature on the course of filarial infection in previously unexposed individuals to see if such an

Experimental infections of humans

There have been four studies in which L3 larvae were injected experimentally into volunteers 4, 5, 6, 7 (for a review, see Ref. [8]). A total of 12 individuals appear to have been injected with substantial numbers of infective larvae. Seven out of 12 individuals in these studies did not become microfilaremic at any time. Only five indivisuals became microfilaremic, all of them transiently. All cleared their infections and remained amicrofilaremic thereafter.

The situation with endemic residents

In an endemic area, in contrast to the nonendemic individuals examined thus far [9], the response to filarial infection has been categorized as ‘spectral’. The spectrum of responses ranges from the so-called ‘endemic normal’ who shows no evidence of infection, through to individuals with chronic pathology who might or might not show evidence of microfilaremia. It is tempting to speculate that the endemic normal individuals resemble the US GIs, who experienced a very limited exposure to

Conclusion

One possible model of the natural course of infection is shown in Figure 1. This formulation of the nature of filarial infections in humans has important implications for the global effort to eradicate the disease. The very fact that humans are inherently resistant to filarial infection implies that once transmission has been lowered to the point that there are not many women in their reproductive phase who are currently infected, filarial infection might not return after one generation. This

Glossary

Acute disease
There are probably two different mechanisms by which acute symptoms can arise. A small fraction of individuals who live in an endemic area manifest symptoms of acute fever with chills and rigor, lymphadenitis, retrograde lymphangitis and funicitis (inflammation of the spermatic cord). This appears to be a reaction to incoming larvae. In other cases, patients with chronic disease can have acute exacerbations owing to secondary bacterial infection.
Asymptomatic microfilaremics

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