Tuesday, April 10, 2012

Trichinellosis


This week at Infection Landscapes I will cover trichinellosis, which is another roundworm infection. This roundworm does not cause a substantial burden throughout the world, but it is worth describing here because it does occupy some unique landsdcapes at the interface between human and animal ecology in both domestic and sylvan habitats.

The Worm. Trichinellosis is cause by nematode helminths of the genus Trichinella. While there are eight known species of the genus, only three are of major importance in causing human infection: Trichinella spiralis, T. nativa, and T. britovi. The majority of human infections are caused by T. spiralis.

Trichinella spiralis larva

Let's consider the life cycle. The defining feature of the T. spiralis life cycle is that larvae encyst in the skeletal muscle tissue of the host, wherein they await the consumption of their current host by another predatory or scavenging host to infect that new host and complete the life cycle. First, infection occurs when a new host ingests raw meat (i.e. the raw muscle tissue) containing the infectious encysted larvae. Upon reaching the stomach of the new host, the larvae excyst triggered by the acid and pepsin in the gastric environment. The free larvae subsequently make their way to the small intestine where they penetrate the mucous membrane of the epithelium and develop into adults after four molts. As adults, males and females mate and the females produce motile larvae after approximately one week. These larvae then penetrate the epithelium and ultimately gain the circulation (lymph and blood) to seek out skeletal muscle tissue. When the larvae reach the muscle tissue each larva will invade a single skeletal muscle cell wherein they encyst and become the infectious larvae capable of infecting new hosts. The process of encystation is unique in that the worm hijacks the host muscle cell and creates a new intracellular environment, call a nurse cell, which encapsulates and maintains the viability of the infectious larvae for many years until, one day, it finds itself in the stomach of a new host after being eaten raw along with its previous host:

Trichinella spiralis larvae encapsulated in nurse cells within the skeletal muscle tissue of the host

Below is nice graphic from the Centers for Disease Control and Prevention (CDC) depicting the life cycle of this helminth:


Note that Trichinella does not require intermediate hosts. It is capable of completing its life cycle in a single species of either its primary hosts, such as rodents, pigs, or wild game, or incidental hosts, such as humans.

The Disease. The vast majority of Trichinella infections are asymptomatic. When clinical disease does occur, it follows one or both of two courses: enteral or parenteral disease.

Enteral disease will typically present in association with high volume infections and symptoms include diarrhea and gastric discomfort such as dyspepsia and nausea fairly soon (within ~ 1 week) after infection.

Parenteral disease is also associated with high volume infections and results from the migration of large numbers of larvae out of the small intestine and into the circulation with potential dissemination to many different organ systems. Fever, muscle pain, edema and vasculitis are typical presentations of parenteral disease, which follow from the systemic inflammation induced by the circulating larvae. Periorbital edema is considered a classic sign of parenteral trichinellosis, however it is not pathognomonic:


If the worms invade the central nervous system encephalitis can develop, as can other severe neurologic pathology involving pulmonary function and/or motor coordination. Although quite rare, when it does occur death is most often due to encephalitis, myocarditis or pneumonia following the extensive inflammatory responses associated with high volume infection.

The Epidemiology and the Landscape. As mentioned above, trichinellosis does not constitute a large global burden of disease. There are approximately 10,000 new infections each year and the vast majority of these are asymptomatic or of mild presentation. Currently, there are likely over 11 million people infected globally, with most infections occurring in China and Southeast Asia. The maps below published in Clinical Microbiology Reviews show the global distribution of Trichinella species:


World map showing the distribution areas of Trichinella spiralis (Tsp), Trichinella pseudospiralis from north America (TpsN), T. pseudospiralis from Europe and Asia (TpsP), T. pseudospiralis from Tasmania (TpsA), Trichinella papuae (Tpa), and Trichinella zimbabwensis (Tzi) (Clin. Microbiol. Rev. January 2009 vol. 22 no. 1 127-145)



World map showing the distribution areas of Trichinella nativa (Tna), Trichinella britovi (Tb), Trichinella murrelli (Tm), Trichinella nelsoni (Tne), Trichinella genotype T6 (T6), Trichinella genotype T8 (T8), and Trichinella genotype T9 (T9). In some regions, the distribution areas of these encapsulated species and genotypes overlap between them (Clin. Microbiol. Rev. January 2009 vol. 22 no. 1 127-145)


Transmission to humans occurs within two fairly distinct landscapes, one domestic and one sylvan. The vast majority of infections in the world are transmitted by consuming inadequately prepared pork. Domestic pigs, and particularly the ways in which pigs feed under specific farming practices, are the common vehicle responsible for most human infection. You will recall from the description above that a critical and defining feature of trichinellosis is that an infected host must be consumed by a new host for transmission of the helminth to occur in the new host. As such, two additional features immediately emerge in shaping the ecology of transmission. First, the eating habits of key reservoir hosts (and the farming practices that maintain these habits for domestic animals); and, second, the eating habits of humans, particularly with respect to food preparation.

Domestic pig farming practices vary dramatically across the world. In many low and middle income countires, where most trichinellosis infections occur, as well as in some high income countries, garbage feeding is a common practice in raising domestic animals. As such, pigs will very often encounter dead rodents, which they eat, in these food sources. Rodents are a common reservoir host for T. spiralis and serve as important hosts in maintaining infection in pigs. Moreover, while sources of garbage are prime locations for rodents, and thus encounters with the pigs who might feed on the garbage, this rodent-pig cycle is by no means limited to such loci. Indeed, better resourced farms that can afford better quality feed can also be quite attractive sources of food to rodent species. Finally, the rodents are not essential to maintain infection in pigs. Pig cannibalism, either as it occurs naturally or due to specific farming practices of adding pig remains to feed, can be an important source of transmission for pigs, which can maintain infection within a pig community without any external hosts. Of course, if pig products used for human consumption are properly cooked then transmission is blocked and the pig infection cycle is irrelevant. However, in addition to varied farming practices throughout the world, there are also varied food preparation practices when it comes to pork, which brings us back to the second important feature in transmission.

So, the domestic landscape epidemiology of trichinellosis is defined by the intersection of farming and food preparation in the geographic spaces where T. spiralis is endemic. Below is a nice graphic developed by G.J. Jackson at the Division of Microbiology, US Food and Drug Administration and published by the Food and Agriculture Organization of the United Nations, which depicts this domestic cycle and the sylvan cycle to be described below:

 
In the developed world, many human infections result from contact with the sylvan cycle. Game animals, particularly bears, are frequently infected, albeit with different species of Trichinella. If these game meats are not properly prepared by cooking, then humans can ingest the intramuscular larvae and become infected. While this sylvan transmission cycle accounts for many infections in some developed countries, for example in the United States, this transmission cycle is by no means limited to developed countries. Indeed, the sylvan cycle can be an active transmission route in many developing regions as well. For example, the consumption of wild cat meats or feral pigs in sub-Saharan Africa can lead to human infection.

While the largest absolute number of incident and prevalent cases occur in Southeast Asia and are mostly transmitted via the domestic cycle, the largest density of human infection may be among arctic indigenous communities, where transmission occurs following consumption of polar and brown bears, foxes, and pinniped marine mammals:


Prevention and Control. Prevention of trichinellosis in humans is comprised of 2 primary strategies: management of farming practices and preparation of meat products. Where domestic pigs are raised for human consumption care should be taken to employ some basic control measures. The adoption of the following control regulations should apply universally, and are especially important when garbage feeding is used: 1) prevent pigs from eating any dead animal carcasses, 2) strictly control rodent populations, 3) prevent contact between pigs and sylvan animal species, and 4) prevent pigs from eating other pigs, either dead or alive. 

The second prevention strategy consists of proper food preparation. Thoroughly cooking all pork and game meats at 165 degrees F (74 degrees C) is the most effective way of killing the larvae in the meat and, thus, blocking transmission. Freezing pork (but not game meats) can also kill T. spiralis, however freezing must occur at 5 degrees F (-15 degrees C) for at least 20 days, or -4 degrees F (-20 degrees C) for at least 3 days, in cuts of meat that are less than 6 inches in thickness. Other species of Trichinella are much more resistant to freezing and, thus, this method is not useful for game meats. 
  

6 comments:

  1. It is really interesting to find a disease that is not overwhelmingly found in developing areas, but which is also found in developed areas (due to gaming practices) and arctic indigenous communities. One aspect, however, that should also be taken into account is that because the symptoms of trichinellosis infections are relatively diffuse and benign, there may be a significant underestimation of the prevalence of trichinellosis infections. Then again, because its effects are not as serious as some other infections, that may not be as big of an issue. It would still be interesting to see if an education program promoting safe cooking practices in the indigenous arctic community would have any significant health benefits.

    ReplyDelete
  2. This worm seems suspiciously easy to control compared to many other worms that have more than one means of transmission. Although the ability of the larvae to form nurse cells and be viable for long periods of time in the host can pose a problem in identifying cases.

    ReplyDelete
  3. An interesting thought regarding the education program for proper cooking technique, Caleb. Even if the education campaign were not identified as particularly important for Trichinellosis, a lot of the principles in designing that kind of an education program could be carried over into other diseases as well.

    I also really like how the science of this disease contributes to the design of its public health policy. For example, the difference in freezing tolerance of different species would necessitate an understanding of which species were most prevalent in a community before really undertaking a public health effort like the education campaign. If, for example, 99% of cases occurred with a freezing-sensitive species, it may be financially more effective to educate populations on how to freeze meat properly as opposed to cooking it properly. This saves money and may make the intervention better accepted among the population. But, it requires laboratory work to identify the species in question and design policy accordingly.

    ReplyDelete
  4. In response to Caleb and Zach,

    You both mentioned educational campaigns and wondered about cost-effectiveness of different prevention techniques. I wonder, frankly, if there is no intervention for this disease which is cost effective. If there are only 10,000 cases annually, and many are asymptomatic, I wonder if even the cheapest intervention would simply not be worth it. A cheap intervention that I could think of would be warning labels on raw pork products. However, I could see there being a lot of push back from industry on such a move.
    I am also skeptical that freezing would be an effective technique. There seem to be too many caveats with this approach, such as the exact pathogen, the temperature and timing, the thickness of the meat etc. I think that for any intervention to work, it needs to be as simple as possible. I also think that the lengthy freezing time required makes freezing difficult to implement effectively.

    ReplyDelete
    Replies
    1. In response to Diana Julie,

      I think any form of increase awareness would be beneficial especially since one of the main ways of prevention for Trichinellosis is by food preparation (1). Understanding to avoid undercooked pork, walrus, horse and bear and other wild game meat by cooking at least to 145F (63C) can help. Moreover, not only would freezing help but also irradiation will kill these parasites. However neither irradiation or freezing is needed if the meat is thoroughly cooked as indicated in the article. Moreover, just smoking and pickling don’t kill the trichinella and clean sanitary conditions for where the meat is processed would be another prevention method. Also in response to your comment about the real life impacts of this method and the feasibility can be seen in Europe. Pork, horse and wild boar meat from East Europea accounted for many of the Trichinelosis cases and it was proposed for Switzerland to implement a meat control program for Trichniella for entire slaughter pig population of the country (2). They did say it would lead to an a huge increase in costs in order to implement and create the infrastructure necessary along with the veterinary services needed.

      1. Mayo Clinic, Tricinosis Prevention http://www.mayoclinic.org/diseases-conditions/trichinosis/basics/prevention/con-20027095
      2. Müller N1, Sager H, Schuppers M, Gottstein B. [Methods for investigating Trichinella infections in domestic and wild animals]. Schweiz Arch Tierheilkd. 2006 Sep;148(9):463-71 http://www.ncbi.nlm.nih.gov/pubmed/17024975

      Delete
  5. This is an extremely interesting infection since it affects varying communities across the world who feed on animal meat. Since the largest density of human infections occur among arctic indigenous communities who live in extreme weather condition, i was wondering if freezing the meat is enough to kill the larvae, T. spiralis or if the meat needs to be cooked at 165 degrees Fahrenheit as well?

    ReplyDelete