Encephalitis lethargica

Definition

Encephalitis lethargica is an inflammation of the brain caused by two trypanosomes (microscopic protozoan parasites). The illness, which can be fatal, is transmitted from one infected person to another by the tsetse fly. While it can occur globally, encephalitis lethargica is especially prevalent in Africa.

Description

Encephalitis lethargica is a vector-borne disease, meaning it is transmitted to a susceptible person by a living creature. The tsetse fly lives in moist vegetation near lakes and rivers and in grassy areas. People living near these regions are most susceptible the bite of a tsetse fly infected with the trypasosomes that cause encephalitis lethargica. The disease is also known as African trypanosomiasis, sleeping sickness, sleepy sickness, and von Economo's disease. Another form of the trypanosome-borne disease that occurs in North, Central, and South America is called Chagas disease.

Other subspecies of the trypanosome parasite can infect animals such as cattle, who can also harbor the trypanosomes that are infectious to humans.

Demographics

The form of encephalitis lethargica known as African trypanosomiasis occurs only in the sub-Saharan area of Africa. Tsetse flies are endemic in this region. However, for as yet unknown reasons, there are regions where tsetse flies are found, but the disease is absent. There have been several epidemics in Africa in the nineteenth and twentieth centuries. From 1896–1906, Uganda and the Congo basin were affected. A more wide-ranging epidemic occurred in 1920. Finally, an epidemic that began in 1970 is still occurring.

The latest epidemic is a result of the relaxed surveillance for the disease that happened with the near-eradication of the disease in the 1960s. As of 2004, the disease is a threat to more than 60 million people in 36 sub-Saharan African countries. In 1999, nearly 45,000 cases were reported, according to the World Health Organization (WHO). These cases represent individuals who were able to seek treatment and receive a definitive diagnosis at local health care centers. The actual number of cases was likely much higher, with estimates ranging from 300,000–500,000 cases actually occurring. In Africa, the disease occurs primarily in rural areas, where health care is least available. Poverty and encephalitis lethargica are associated with one another.

Causes and symptoms

The disease is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The first species is found in central and West Africa. The infection is chronic; it persists for months or years with no display of symptoms. When they do emerge, the disease is at an advanced stage and the symptoms are more severe. T. brucei rhodesiense is found primarily in southern and eastern Africa. It causes an infection whose symptoms appear quickly (acute infection). This disease is more severe. Fortunately, the rapid appearance of symptoms offers more of a chance for quick detection.

Both trypanosomes are transferred to the tsetse fly when the fly obtains a blood meal from an infected person. The trypanosomes then multiply in the blood of the fly, and can be transferred to a susceptible person on whom the fly subsequently feeds.

The early symptoms of the disease include fever, severe headache , joint pain , and swelling of the lymph nodes. These symptoms can disappear and reoccur. Later, symptoms of what is called the neurological phase emerge and often include the characteristic symptoms of the disease: extreme weakness, paralysis of eye muscles, sleepiness, disruption of the sleep cycle, and a lapse into a deep and fatal coma. Transmission of the trypanosomes across the placenta from a pregnant woman to the fetus can occur. Typically this causes spontaneous abortion or death of the fetus.

Diagnosis

The most useful diagnostic sign is swollen cervical glands. This indicates the presence of the parasite. Populations can be screened for clinical signs of the disease (the early phase symptoms) and the use of tests that detect antibodies to the parasite in the blood. An early diagnostic sign of the bite of the tsetse fly is the appearance of a painful red sore (chancre) at the site of the bite.

A type of diagnosis called phase diagnosis can be used to help determine the level of advancement of the disease. Cerebro-spinal fluid is obtained by the technique of lumbar puncture and analyzed. Phase diagnosis requires medical and laboratory staff, and is typically done in a clinic. The long period, symptom-free period of a Trypanosoma brucei gambiense infection can complicate and delay diagnosis.

Treatment team

Physicians and nurses are the primary team involved in treating encephalitis lethargica. Additionally, public health workers in Africa and other areas affected with the tsetse fly receive help from health agencies throughout the world, who provide aid and strategies to reduce populations of the fly, educate local peoples to bite prevention methods, and treat affected individuals. Warring factions, with resulting political instability and hunger in the Sub-Saharan region of Africa have led to difficulty in controlling the spread of the tsetse fly and the disease.

Treatment

The choice of treatment depends on whether the disease is detected earlier or later in the infection. Early-stage infections can be treated using two drugs; suramine and pentamidine. An agreement between the World Health Organization and the drug's manufacturer (Aventis) has guaranteed continued production of the compounds.

Treatment of the later, neurological symptoms requires a drug that can cross the blood-brain barrier to reach the parasite. Currently only one drug (melarsoprol) is commercially available. The drug causes harsh side effects and itself has a fatal complication rate approaching 10%. As well, resistance of the trypanosomes to the drug is increasing. A second drug (eflornithine) exists, but is not commercially available. It is active only against Trypanosoma brucei gambiense. There is no vaccine for the disease.

Recovery and rehabilitation

Recovery from the early stage of the disease can be complete. Recovery from the neurological stage is typically incomplete, with varying degrees of impaired brain function often resulting. Once the person reaches the stage of coma, the disease is invariably fatal.

Clinical trials

As of early 2004, there were no clinical trials in progress for the study of encephalitis lethargica. Rather, efforts to increase screening of susceptible populations and to increase the supply of drugs is the identified priority for scientists working with the disease.

Prognosis

If treated early, a person with encephalitis lethargica can be cured. If not treated early, the prognosis is much less favorable due to resulting brain damage. Encephalitis lethargica is fatal if untreated.

Resources

BOOKS

Dumas, Michel, et. al. Progress in Human African Trypanosomiasis, Sleeping Sickness. New York: Springer Verlag, 1999.

Ramen, Fred. Sleeping Sickness and Other Parasitic Tropical Diseases (Epidemics). New York: Rosen Publishing Group, 2002.

OTHER

African Trypanosomiasis or Sleeping Sickness. World Health Organization. (January 27 2004). <http://www.who.int/int-fs/en/fact259.html>

East African Trypanosomiasis. Centers for Disease Control and Prevention. (January 27 2004). http://www.cdc.gov/ncidod/dpd/parasites/…osomisasis/factsht_ea_trypanosomiasis.htm

ORGANIZATIONS

Centers for Disease Control and Prevention (CDC). 1600 Clifton Road, Atlanta, GA 30333. (404) 639-3311 or (800) 311-3435. <http://www.cdc.gov>.

World Health Organization (WHO). Avenue Appia 20, 1211 Geneva, Geneva, Switzerland. +41 22 791 21 11; Fax: +41 22 791-3111. [email protected]. <http://www.who.int>.

Brian Douglas Hoyle, PhD