Please comment on the possible diagnosis related to the history of insect bites, the patient's clinical symptoms and the relative travel history. Routine examination of thin blood films revealed the following:

 

 

 

1. Thin blood film	2. Thin blood film	3. Thin blood film

 

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ANSWER AND DISCUSSION OF DIAGNOSTIC QUIZ #42 (June, 2004)

The images presented in Diagnostic Quiz #42 are the following:

COMMENT: This was a case of African trypanosomiasis, probably caused by T.b. rhodesiense (East African Trypanosomiasis) based on travel history (Kenya, Uganda), the severity of symptoms, and overall description of the case. Although the woman lived in Brazil where Trypanosoma cruzi is found (cause of Chagas' disease, American Trypanosomiasis), the African trypomastigotes and the American trypomasitgotes look quite different.

 

COMMENTS: There are over 55 million people in 36 countries at risk and approximately 50,000 new cases per year of African trypanosomiasis The African trypomastigotes (both East and West African trypomastigotes) (see right photograph above) have a very small kinetoplast (the dot at one end of the organism), while T. cruzi tends to have a very large kinetoplast that appears to go beyond the body of the organism (see left photograph above). Note that both organisms can actually be in a "C" shape; this alone does not indicate infection with T. cruzi.

LIFE CYCLE: Trypanosomal forms are ingested by the tsetse fly (Glossina sp.) when a blood meal is taken. Once the short, stumpy trypomastigote reaches the midgut of the tsetse fly, it transforms into a long slender procyclic stage. The organisms multiply in the lumen of the midgut and hindgut of the fly. After approximately 2 weeks, the organisms migrate back to salivary glands through the hypopharynx and salivary ducts, where the organisms attach to the epithelial cells of the salivary ducts and then transform to their epimastigote forms. In the epimastigote forms, the nucleus is posterior to the kinetoplast, in contrast to the trypomastigote, in which the nucleus is anterior to the kinetoplast. There is continued multiplication within the salivary gland, and metacyclic (infective) forms develop from the epimastigotes in 2 to 5 days. With development of the metacyclic forms, the tsetse fly is now infective. During the act of feeding, the fly introduces the metacyclic trypanosomal forms into the next victim in saliva injected into the puncture wound. The entire developmental cycle in the fly takes about 3 weeks and once infected, the tsetse fly remains infected for life. The course of infection in African trypanosomiasis occurs in three stages. Soon after inoculation of the metacyclic trypanosomes by an infected tsetse fly, an inflammatory lesion develops at the site of inoculation; this lesion is called the trypanosomal chancre. Trypomastigotes then invade the local lymphatics and later the bloodstream. After a time, the organisms invade the choroid plexus and enter the brain and cerebrospinal fluid (CSF). There is quite a bit of variation between the two diseases caused by East African and West African trypanosomiasis. In the East African disease (T. b. rhodesiense), chancres are common, the hemolymphatic stage is severe, and rapidly progresses to a fatal meningoencephalitis, often within months of infection. With the West African form of the disease (T. b. gambiense), chancres are uncommon, the hemolymphatic stage may even be inapparent, and meningoencephalitis progresses very slowly, often over several years, thus the "sleeping sickness" syndrome.

During the course of the infection, the number of trypomastigotes in the blood fluctuates. This relapsing parasitemia is due to the host's immune response to the parasites. Each decline in parasite number results from the antibody-mediated destruction of trypomastigotes bearing a particular variant surface glycoprotein (VSG). Each new wave of parasitemia represents the growth of a trypomastigote population expressing an antigenically different VSG. This process of ANTIGENIC VARIATION is a feature of all African trypomastigotes. Since each trypomastigote expresses only one VSG at a time and has as many as 1,000 different VSG genes, the number of different variable antigen types (VATs) that can be expressed during an infection is quite large. The continued response of the host to the new/different variable antigen types leads to elevated gamma globulins, particularly the IgM levels, including the CSF. Generally, if an individual does not have an elevated IgM, they almost certainly do not have African trypanosomiasis.

KEY POINTS - LABORATORY DIAGNOSIS

1. Trypomastigotes are highly infectious, and health care workers must use bloodborne pathogen precautions.

2. Trypomastigotes may be detected in aspirates of the chancre and enlarged lymph nodes in addition to blood and CSF.

3. Concentration techniques, such as centrifugation of CSF and blood, should be used in addition to thin and thick smears (Giemsa or Wright's stain).

4. Trypomastigotes are in highest numbers in the blood during febrile periods.

5. Multiple daily blood examinations may be necessary to detect the parasite.

6. Blood and CSF specimens should be examined during therapy and 1 to 2 months posttherapy