Take Two Hookworms and Call Me in the Morning

Life without hookworms

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Public health messages usually sound easier said than done: you know, eat right, exercise regularly, stop smoking. But back in 1931, a key public health message was, in our modern view, truly simple: “wear good shoes.” According to an article in Alabama’s Florence Times-News, wearing shoes was exceedingly important — and apparently not all that common — to help eradicate the intestinal parasite known as hookworm:

   

Two decades or more have passed since the attention of our people was turned prominently to the existence of hookworm disease in the States. At that time, every one knew that the presence of hookworm in the bowel would make a man lazy, and that backwardness among some children in the south was probably due to infestation with this organism.

The article, by the eminent editor of the Journal of the American Medical Association, Morris Fishbein, cited persistent heavy infestation in some Southern states, affecting “75 per cent or more of school children” in certain counties. This despite a five-year hookworm eradication campaign the Rockefeller Sanitary Commission had implemented across the South. The program featured testing, deworming treatment, and education about how to prevent reinfection and avoid soil pollution. When the effort ended in 1915, it had already reduced infection rates significantly, but articles such as Fishbein’s must have been important to maintaining prevention practices including the use of both sanitary toilets (instead of the open outdoors) and shoes: Walking barefoot through areas contaminated with fecal matter often resulted in infection.

Hookworm infection certainly provided an excellent argument for shoes. The invasion by tens of thousands of squirmy, blood-sucking worms was not only nauseating, it also had damaging effects such as delayed growth, anemia, and lethargy. Once known as the “the germ of laziness,” hookworm contributed significantly to school absenteeism and adult unemployment. The deworming campaign saw such positive effects as improvements in literacy, agricultural output, and income.

And yet. Today, growing evidence points to a significant downside to life without hookworm. Lately scientists have hypothesized that such parasites may play a critical health role by helping the immune system adjust to everyday environmental irritants without overreacting and producing excessive inflammation. The idea falls in line with the well-known “hygiene hypothesis.” First officially presented a dozen years ago, the hygiene hypothesis proposes that without prenatal or early life exposure to microorganisms and parasites — with which we coexisted throughout much of our evolutionary history — we have become prone to an imbalanced immune response later in life.

While modern medicine and improved cleanliness practices have eliminated many dreadful afflictions from the United States, others have escalated. Initial research on the hygiene hypothesis focused on asthma, allergies, and eczema, all of which have increased in prevalence dramatically in developed countries over the past 150 years. Research has expanded in surprising ways to consider other big-time chronic diseases linked to excess inflammation, including heart disease, depression, and obesity.

In an ironic twist, it appears that humans may actually benefit from limited, controlled exposure to some microorganisms and parasites. In particular, researchers have begun testing the effects of controlled exposure to hookworm and other intestinal parasites. Early research at University of Iowa showed that exposing mice to parasitic worms helped prevent inflammatory bowel disease. Additional studies demonstrated that the therapy could protect the mice from colitis, encephalitis, Type 1 diabetes, and asthma.

Human trials have been much more limited. Two small groups of adults — one whose members had colitis, and the other made up of those with Crohn’s disease — experienced reduced symptoms after being treated with whipworm for multiple weeks by University of Iowa researchers. But human research has stalled in the United States since the Food and Drug Administration classified parasitic worms as a drug in November 2009. Today, drug companies are working to create parasites that the FDA would approve for inflammatory bowel disease, according to Joel Weinstock, the Tufts University gastroenterologist who is a leading researcher in the field.

Meanwhile, ongoing international research in humans has not always found a positive effect. Recently, University of Nottingham researchers reported that a small group of adults infected with 10 hookworm for 16 weeks did not experience significant improvement in asthma. They did, however, experience a non-significant improvement in airway responsiveness, and the infection was, overall, well tolerated. The authors suggested that future studies should more closely mimic natural infection, including infection with more hookworm and for a longer period of time.

Moving forward, this field still includes many questions. It’s becoming clearer that we need to find a better balance when approaching public health and hygiene. To be clear, though, no one is suggesting that international deworming efforts should be stopped. Nor that we should eschew immunizations or indoor plumbing, water and sewage treatment, and organized garbage disposal. But perhaps one day we will also receive a healthy dose of microorganisms, and yes, even squirmy, wormy parasites, as part of modern medical care. • 6 May 2011

REFERENCES: Bleakley H, Disease and Development: Evidence from Hookworm Eradication in the American South. Quarterly Journal of Economics 122 (2007): 73–117. Strachan DP, Hay fever, hygiene, and household size. BMJ. 1989;299:1259-60. Okada H, Kuhn C, Feillet H, Bach JF, The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160:1-9. Elliott DE, Weinstock JV, Helminthic therapy: using worms to treat immune-mediated disease. Adv Exp Med Biol. 2009;666:157-66. Walk ST, Blum AM, Ewing SA, et al, Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflamm Bowel Dis. 2010;16:1841-9. Summers RW, Elliott DE, Urban JF Jr, et al, Trichuris suis therapy in Crohn’s disease. Gut. 2005;54:87-90. Summers RW, Elliott DE, Urban JF Jr, et al, Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 2005;128:825-32. Feary JR, Venn AJ, Mortimer K, et al, Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin Exp Allergy. 2010;40:299-306.

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