Infection & Autoimmunity

 Biology, Medicine, Zoology  No Responses »
Nov 052011
 

There seems to be mounting evidence that infection and autoimmune disorders have an interesting–if frustrating–relationship: people exposed to more microbes are less likely to develop an autoimmune disorder. This American Life did a story (transcript / audio; skip to “Act Three”) on a fellow named Jasper Lawrence who had asthma super bad. One day he hears tell of the theory that most folks in developing countries don’t have asthma and that this is because they have hookworm.

So Jasper goes to Africa and spends a considerable amount of time literally going to remote villages and walking barefoot through the communal latrine while very confused villagers looked on. Not too long after, Jasper’s asthma pretty much disappears. (He then started selling hookworms on the Internet to other asthmatics but the Man shut him down.)

The whole idea behind this is something called the Hygiene Hypothesis (PBS video): the idea that excessive cleanliness prevents certain opportunities to acquire immunity and that this lack of immunity is related to the increasing incidence of autoimmune disease in industrialized countries and urban environments.


One of the players in the research is Dr. David Pritchard (NYT article):

While carrying out field work in Papua New Guinea in the late 1980s, he noticed that Papuans infected with the Necator americanus hookworm, a parasite that lives in the human gut, did not suffer much from an assortment of autoimmune-related illnesses, including hay fever and asthma. Over the years, Dr. Pritchard has developed a theory to explain the phenomenon.

“The allergic response evolved to help expel parasites, and we think the worms have found a way of switching off the immune system in order to survive,” he said. “That’s why infected people have fewer allergic symptoms.”

…

In the tropics, where it is common, hookworm kills 65,000 people a year and afflicts hundreds of thousands with anemia. In low numbers in adults in a controlled experiment, Dr. Pritchard said, the worms have not caused problems.

…

After Dr. Pritchard’s self-infection experiment, the National Health Services ethics committee let him conduct a study in 2006 with 30 participants, 15 of whom received 10 hookworms each. Tests showed that after six weeks, the T-cells of the 15 worm recipients began to produce lower levels of chemicals associated with inflammatory response, indicating that their immune systems were more suppressed than those of the 15 placebo recipients. Despite playing host to small numbers of parasites, worm recipients reported little discomfort.

Trial participants raved about their allergy symptoms disappearing.

So now it seems that H. pylori may also be protective against asthma.

Infection with the gastric bacterium Helicobacter pylori provides reliable protection against allergy-induced asthma, immunologists from the University of Zurich have demonstrated in an animal model together with allergy specialists from the University Medical Center of the Johannes Gutenberg University Mainz. Their results published in the Journal of Clinical Investigation confirm the hypothesis recently put forward that the dramatic increase in allergic diseases in industrial societies is linked to the rapid disappearance of specific micro-organisms that populate the human body.

The hygiene hypothesis reminds me of a computer science problem: memory and computation time are inversely related. It seems that in medicine–and most everything else, I guess–we run into a similar problem; we want to avoid harmful infection but we also want to avoid autoimmune disease.

Loa Loa Filariasis

 Medicine  No Responses »
Nov 042011
 

Today’s parasite is Loa Loa:

Identification of microfilariae by microscopic examination is a practical diagnostic procedure. Examination of blood samples will allow identification of microfilariae of Loa loa. It is important to time the blood collection with the known periodicity of the microfilariae. The blood sample can be a thick smear, stained with Giemsa or hematoxylin and eosin (see staining (biology)). For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lyzed in 2% formalin (Knott’s technique), or filtration through a Nucleopore membrane.

Antigen detection using an immunoassay for circulating filarial antigens constitutes a useful diagnostic approach, because microfilaremia can be low and variable. Interestingly, the Institute for Tropical Medicine reports that no serologic diagnostics are available. While this was once true, and many of recently developed methods of Antibody detection are of limited value—because substantial antigenic cross reactivity exists between filaria and other helminths, and a positive serologic test does not necessarily distinguish between infections—up and coming serologic tests that are highly specific to Loa loa were furthered in 2008. They have not gone point-of-care yet, but show promise for highlighting high-risk areas and individuals with co-endemic loiasis and onchocerciasis. Specifically, Dr. Thomas Nutman and colleagues at the National Institutes of Health have described the a luciferase immunoprecipitation assay (LIPS) and the related QLIPS (quick version). Whereas a previously described LISXP-1 ELISA test had a poor sensitivity (55%), the QLIPS test is both practical, as it requires only a 15 minutes incubation, and has high sensitivity and specificity (97% and 100%, respectively). No report on the distribution status of LIPS or QLIPS testing is available, but these tests would help to limit complications derived from mass ivermectin treatment for onchocerciasis or dangerous strong doses of diethylcarbamazine for loiasis alone (as pertains to individual with high Loa loa microfilarial loads).

Physically, Calabar swellings (see image) are the primary tool for diagnosis. Identification of adult worms is possible from tissue samples collected during subcutaneous biopsies. Adult worms migrating across the eye are another potential diagnostic, but the short timeframe for the worm’s passage through the conjunctiva makes this observation less common.

In the past, health care providers use a provocative injection of Dirofilaria iminitis as a skin test antigen for filariasis diagnosis. If the patient was infected, the extract would cause an artificial allergic reaction and associated Calabar swelling similar to that caused, in theory, by metabolic products of the worm or dead worms.

Blood tests to reveal microfilaremia are useful in many, but not all cases, as one third of loiasis patients are amicrofilaremic. By contrast, eosinophilia is almost guaranteed in cases of loiasis, and blood testing for eosinophile fraction may be useful.

eMedicine sez:

Filariasis is a disease group affecting humans and animals caused by nematode parasites of the order Filariidae, commonly called filariae. Filarial parasites may be classified according to the habitat of the adult worms in the vertebral host. The cutaneous group includes Loa loa, Onchocerca volvulus, and Mansonella streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. The body-cavity group includes Mansonella perstans and Mansonella ozzardi.

Of the hundreds of described filarial parasites, only 8 species cause natural infections in humans. The parasites of the cutaneous and lymphatic groups are the most clinically significant. Other species of filariae may cause incomplete infections because they are unable to reach adult maturity in human hosts and therefore cannot produce microfilaria (eg, Dirofilaria immitis [dog heartworm], Dirofilaria [Nochtiella] repens, and Dirofilaria tenuis [raccoon heartworm]).

These infections have a significant economic and psychosocial impact in endemic areas, disfiguring and/or incapacitating more than 40 million individuals. Studies from the Indian subcontinent have shown that infected patients lose significant time from work because of the disease, costing the national treasury a minimum of $842 million per year.

Filariae have a specific geographic distribution. For example, W bancrofti is found in sub-Saharan Africa, Southeast Asia, India, and the Pacific Islands. B malayi is found in similar locations, but not in sub-Saharan Africa. B timori is concentrated to the Timor island of Indonesia.

It has been observed (especially in endemic areas), that the prevalence of microfilaremia increases with age, as adult worms are gradually acquired over years. Lymphatic filariasis is first contracted in childhood, and most individuals in endemic areas have been exposed by the third or fourth decade of life. The proportion of infected individuals remains constant. As with most helminths, adult filarial parasites replicate in a secondary host. The adult worm burden in an individual cannot increase unless the host is exposed to additional microfilaria. Infected individuals cannot sustain higher levels of parasitemia once they leave the endemic area.

Because the mosquito vector is inefficient, a relatively prolonged stay in an endemic area is usually required to acquire the infection. Disorganized urbanization is adding to the vector population and hence to the increased incidence and prevalence of such diseases in developing countries.

Eeeeew!

 Medicine  No Responses »
Sep 052011
 

Pinworms are really gross.

Pinworms are the most common worm infection in the United States. They are most common in school-age children.

Pinworm eggs are spread directly from person to person. They can also be spread by touching bedding, food, or other items contaminated with the eggs.

Typically, children are infected by unknowingly touching pinworm eggs and putting their fingers in their mouths. The eggs are swallowed, and eventually hatch in the small intestine. The worms mature in the colon.

Female worms then move to the child’s anal area, especially at night, and deposit more eggs. This may cause intense itching. The area may even become infected. When the child scratches the itching anal area, the eggs can get under the child’s fingernails. These eggs can be transferred to other children, family members, and items in the house.

E. Vermicularis lifecycle

E. vermicularis worm