India Trip: A Tropical Medicine Break

FROM 1/22/08:

Finally! The long awaited, highly acclaimed "demonstration of an in-depth understanding of one tropical disease." And the topic? Japanese Encephalitis. Spectacular.

I chose to write about Japanese Encephalitis primarily for three reasons. One, I just found it to be interesting. Two, it is a tropical disease with just enough incidence to have both an adequately accessible volume of written material on it and also to be potentially clinically significant if I were to ever pursue Infectious Disease -- which I currently certainly plan to do. And three, its pathology is not so diverse and broad that the amount of information out there would result in my demonstration of knowledge being long, tiring, and tedious or so superficial as to be readily found on any "health" website on the Internet. Alright, Japanese Encephalitis time.

Culex tritaeniorhynchus. I have no idea how to pronounce it and will likely never in my life be able to spell it, but this mosquito is the source of the thousands of cases of Japanese Encephalitis virus (JEV) which occur every year throughout South and East Asia. Numbers on the actual rate of infection vary and are believed to be underestimated, but the average guess is that 35 - 50,000 people experience symptomatic JEV infections a year with another 250x as many suspected asymptomatic infections. Mortality rates vary as well based on accessibility and quality of medical care, but they range from 5-10% in areas with access to intensive care units all the way up to 35% in poorer, undeveloped areas.

The virus itself is an arbovirus (meaning arthropod (i.e. insect) born virus) of the family flaviviridae (a collection of single stranded RNA viruses) thus relating it to the Dengue Fever and West Nile viruses. It exists where ever the Culex mosquito exists, its only carrier, which allows it to spread west to Pakistan, east to Japan, and down south, rarely, to Australia in a triangle of territory that covers almost half the world's population. It is not endemic in all these regions (meaning it is native and naturally prevalent to the area), but rather in some areas occurs in sporadic epidemics that come and go (meaning it occurs in bouts where it otherwise does not normally exist.) It has a seasonal occurrence typically arising from June to September in most states with the bugs most active at dusk and evening hours.

Assuming you are unfortunate enough to have both been infected with the virus and then become symptomatic, here is kind of what you can expect. The flu at first. Initially, like many viruses, you will just feel like crap. Most people experience fevers, headaches, nausea, vomiting, diarrhea, and muscle pains (myalgias) though most commonly not all these symptoms are experienced by each and every patient. These symptoms can last a few days or more and will eventually lead into altered mental status and altered neurology as the virus moves from the blood to the brain (thus making it an encephalitis [en- meaning "within", kephalos- meaning "head", and -itis meaning "inflammation.") The mental status changes can range from mild confusion and agitation all the way to delirium and coma. Beyond this 85% of children and 10% of adults will experience seizures which are associated with a particularly poor outcome. A few other things to look for include nuchal rigidity (stiff neck) in 33 - 66% of cases, cranial nerve palsies in 33% of cases, and Parkinson like symptoms (tremor, masked facies, rigidity, etc.) in a good majority. A few unusual and rare presentations include mutism and acute flaccid paralysis.

If you look towards the labs, upon spinal tap you will often find the typical viral meningitis picture in the cerebral spinal fluid (CSF). Opening pressure will be normal to mildly elevated, CSF protein will frequently be mildly elevated as well, and white blood cells (WBCs) will vary from 10 to several thousand with a lymphocyte predominance. With regards to blood related studies, a complete blood count (CBC) could possibly show a mild leukocytosis (increased WBCs; mostly neutrophils) or thrombocytopenia (decreased platelets) while an examination of electrolytes could show hyponatremia (decreased blood sodium.) Curiously, a recent study of a 2005 Indian outbreak also showed an increase in liver function tests (LFTs) in children with AST elevated in 100% of cases and ALT in 47.2% of cases. All these nonsensitive and nonspecific tests aside, the key to a diagnosis of JEV is an ELISA of both the blood and CSF. Assuming both are done, almost 100% of cases can be picked up. Unfortunately ELISAs are not typically easily or cheaply done especially in the field. Fortunately a newer test, IgM enzyme dot immunoassay, of the CSF is much easier and portable with almost the same accuracy its sensitivity and specificity being 98.3% and 99.2% respectively.

EEGs, CT scans, and MRIs can also show fairly characteristic patterns as well, but, like the other tests mentioned earlier, they are generally not sensitive or specific and so are only supportive.

It is worth noting, half way through this, that there are three aspects of JEV infection that make it a particularly treacherous disease. One, already touched upon, is the fact that most of those who become symptomatic become severely so. The second is that there is no cure. This is not uncommon for viral infections as most do not, but even recent trials with interferon-alpha and steroids, which have shown positive results with other viral related illnesses, have shown no significant benefit for JEV. Essentially all one can do is attempt to control the symptoms administering antiepileptics for seizures, mannitol for increased intracranial pressure, and ventilation for respiratory failure. The third aspect of JEV infection which makes it not a disease to be taken lightly is its long term sequelae. Personality and cognitive changes are frequent and it is estimated that up to 50% of symptomatic patients will have lasting neurological damage including seizures, paralysis, movement disorders, and blindness.

Thankfully, for all its dreariness, there is some hope. If you happen to have been previously infected with Dengue Fever or West Nile virus cross-reactivity will significantly decrease your morbidity and mortality. Since I would gather most of you have been infected with neither of the two, there's always technology to assist. Through a variety of vaccines, currently a killed version and shortly a live version in the US, we can, through a few shots, provide nearly 100% protection against the disease. Moreover, the side effects of the vaccine are relatively minor and uncommon making mass vaccination possible even with the relatively low incidence of the disease. While country to country vaccination policies differ significantly, in the US the CDC currently only recommends getting the JEV vaccine if (1) you are planning to travel to an afflicted nation for greater than one month OR (2) you are planning on spending a major part of your time outside in endemic areas OR (3) you are entering a specific area with an active epidemic. Needless to say you probably don't know anyone that has ever gotten one, and if they claim they did they are probably mistaken. Someday with better public health measures and vector control maybe most of Asia can say that too.

And that's all I got to say about that.

Sources not cited include:

Mandell, Bennett, & Dolin. Principles and Practice of Infectious Disease. 6th ed. Philadelphia Churchill Livingstone, 2005.

Kallen, Alexander. "Japanese Encephalitis." http://www.emedicine.com/med/topic3158.htm WebMD, 2008.

Online Etymology Dictionary. "Encephalitis." http://dictionary.reference.com/browse/encephalitis Douglas Harper, 2001.