Tuesday, December 4, 2012

But it was just a dip in the lake: a look into the parasitic disease Schistosomiasis

by KS#1

You know the feeling you get after a Thanksgiving meal when your stomach is so full it makes your abdomen appear to protrude with a “food baby?”  Now imagine that same feeling, without being full.  In fact, imagine it while feeling starved, malnourished, and dehydrated.  These are a few of the symptoms of schistosomiasis; a disease caused by eukaryotic microbes from the Schistosoma genus. Why should we care?  Let’s imagine for a minute that we are 8 years old again. The summer temperature is scorching and we are craving nothing more than a dip in the lake out back.  Now, here in the US and in other highly developed countries, that would be fine.  However, in some regions of Africa, our 8 year old selves have just subjected our bodies to possible infection and subsequent schistosomiasis. Schistosomiasis is one of the most infectious parasitic diseases in the world, second only to malaria (1). Approximately 240 million people are infected each year (2), most commonly through unsanitary conditions and contaminated fresh water sources.  Unfortunately, that includes most lakes and rivers in southern and sub-Saharan Africa. Even the Nile River has been known to play host to the infectious larvae of schistosomes (1).  It should come as no surprise then, that children are the most commonly infected age group, as they are the most likely to play in contaminated waters. 
Figure 1: The life cycle of Schistosomes.  The human is the location of

 the adult blood fluke.  The fluke then lays eggs which are excreted into the
 environment to hatch into miracidium.  These miracidium can then  infect
 snails, where transformation from miracidium into sporocytes can occur.
  The sporocytes give rise to cercariae (the larval stage) which can swim
 freely in fresh water to infect humans through skin penetration.
Of clinical isolates, the two most commonly isolated schistosomes are Schistosoma haematobium and Schistosoma mansoni, both found in warmer climates with most infectious cases deriving from African populations (1).  The life cycle of these blood flukes is fairly simple, rotating between the human – where the adult fluke is found – and the snail, the intermediate host (3). The blood fluke miracida (the pre-larval hatched form of Schistosomas) infect snails where the fluke transforms into sporocysts.  These give rise to cercaria (infectious larvae) which can then survive in fresh water to infect humans through skin penetration.  Now, our bodies are well equipped to battle most pathogens, and if the initial burrow site causes any inflammation, the cercaria are destroyed by various immunological pathways.  Unfortunately, should our bodies not react to the initial infection, the cercaria make their way to the lungs or liver, where they develop into the adult form.  It is from there that they migrate into the intestinal (S. masoni) or urinary (S. haematobium ) tracts to lay their eggs.  The eggs are then excreted back into the environment to hatch into miracida and the cycle begins again (1, Figure 1).   
Going back to our example, simple childhood tendencies have given rise to a blood fluke navigating its way through our bodies. What does this mean as a patient? We can expect to develop a rash at the site of infection which is typically mild and often goes untreated.  In 1-2 months the symptoms have progressed and we begin to experience fever, chills, cough and muscle aches - common influenza symptoms.   Since viral infections pass, no drastic action is taken and only the symptoms are treated. A year or so later, we now experience abdominal pain, difficulty passing urine, and blood in the stool or urine.  These symptoms clearly indicate something is wrong and a trip to the doctor is arranged. The doctor sends urine and stool samples to the lab to check for the presence of eggs and sends a blood sample for serological analysis.  The urine and blood tests come back positive for infection with S. haematobium.  In some rare cases, eggs can be deposited in the brain or nervous tissue which can lead to severe migraine-like headaches, sporadic paraphasia, and brain lesions.  In such a case, diagnosis may need to occur through surgical excision of the lesions and biopsy (4).  Luckily, this time the fluke appears to have settled solely in the urinary tract. The doctor prescribes Praziquantel, the only anti-helmintic medicine available to treat helminthes infections.  Symptoms subside and diagnostic tests reveal we are no longer infected with the parasite. 
Great! Right…? Well, yes, but there are drawbacks to this route of treatment.  Unfortunately, Praziquantel is only a treatment, not prevention.  Subsequent infections may still occur upon exposure to more contaminated water.  Currently, there is ongoing research to find a suitable candidate for vaccine production against these parasites in hopes of combating this truly unfortunate disease.  Most recently, Lochmatter et al. discovered that immunization of mice with the first extracellular domain of SmTOR (S. mansoni tetraspanning orphan receptor) led to a decrease in adult worm burden.  Immunization also led to the production of anti-rSMTORRed1 (the first domain name) antibodies which may act as a memory response to any further inoculation with the parasite (5).  Lochmatter et al.’s paper is set to be put to print in December 2012 so currently no data on re-inoculation is available. 
So what can be done in the meantime?  Prevention is most successful through avoiding any interaction with contaminated waters; just a splash can cause infection if the skin is weak or already injured.  If contaminated waters are the only water source in the area, small amounts should be boiled for at least 1 minute and cooled before consumption or bathing. Control of the snail populations can also be an effective measure of prevention. However, any chemical treatments of contaminated waters may harm other species in the area, and if not continued, could allow re-inhabitation of the snails (1).  While we wait for a better solution, the best that community education can do is inform the public about these parasites and the subsequent disease, and hope that parents don’t let their children go for that dip in the lake.

References

1.     Global Health – Division of Parasitic Diseases and Malaria. Parasites – Shistosomiasis. Centers for Disease Control and Prevention.  Last updated 7 November 2012.  Accessed 14 November 2012.
2.     World Health Organization. Schistosomiasis. 2012. Accessed 14 November 2012.
3.     Mitreva, Maedonka.  The genome of a blood flue associated with human cancer. Nature Genetis. 27 January 2012. 44:116-118.
4.     Imai, Kentaro; T. Koibuchi, T. Kumagai, T Maeda, Y. Osada, N. ohta, M. Koga, H. Nakamura, T. Miura, A. Iwamoto, and T. Fujii.  Cerebral schistosomiasis due to Schistosoma haematobium confirmed by PCR analysis of the brain specimen.  Clinical Journal of Microbiology. October, 2011. 49(10):3703-3706. 
5.     Lochmatter, C.; C.L. Schneider, K. Ingram, J. Keiser, and J.A. Schifferli. Schistosoma masoni tetraspanning orphan receptor (SmTOR): a new vaccine candidate against schistosomiasis. Clinical & Experimental Immunology. 1 November 2012 (online publication, set for release in print December 2012).  170(3):342-357.

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