Pharmacotherapy of Trypanosomiasis

PST 06106

Basic Pharmacotherapy

Session 12: Pharmacotherapy of Trypanosomiasis

Learning objectives

By the end of this session students are expected to be able to:

Define trypanosomiasis

Explain the clinical presentation of trypanosomiasis

Outline diagnosis of trypanosomiasis

Describe pharmacological treatment of trypanosomiasis

Describe monitoring of trypanosomiasis therapy

Activity: Buzzing

What is Trypanosomiasis?

Definition of Trypanosomiasis

Two distinct forms of the genus

Trypanosoma

occur in humans.

One is associated with African trypanosomiasis (sleeping sickness) and the other with American trypanosomiasis (Chagas disease)

Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease.

The parasites concerned are protozoa belonging to the Trypanosoma genus.

They are transmitted to humans by tsetse fly (

Glossina

genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic

parasites

Definition of Trypanosomiasis

Cont

…

Two forms of the disease exist.

The slow-progressing form, caused by

Trypanosoma

brucei

gambiense

, is found in Western and Central Africa.

The faster progressing form, caused by T. b.

rhodesiense

, is found in Eastern and Southern Africa

Mother-to-child infection: the trypanosome can cross the placenta and infect the

fetus

.

Mechanical transmission through other blood sucking insects is possible.

Accidental infections have occurred in laboratories due to pricks from contaminated needles.

Clinical presentation of Trypanosomiasis

In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph.

This is known as a

haemolymphatic

phase, which entails bouts of fever, headaches, joint pains and itching.

After their inoculation, parasites proliferate at the site of infection, leading to an inflammatory nodule or ulcer.

This trypanosomal chancre arises in about 50% of all rhodesiense—but rarely in gambiense—infections.

After 3–4 weeks, the chancre usually heals with overlying desquamation, sometimes with altered pigmentation.

Parasites spread to the draining lymph node and reach the bloodstream, initiating the

haemolymphatic

stage of the disease.

This stage is characterised by general malaise, headache, and fever of an undulating type.

In rhodesiense infection, with its more acute course,

pancarditis

with congestive heart failure, pericardial effusion, and pulmonary oedema can cause fatalities at this early stage, whereas gambiense infection shows a more insidious development that is frequently unrecognised or misdiagnosed.

A typical sign of

gambiense

human African

trypanosomiasis

is generalised lymphadenopathy that develops after several weeks, frequently in the posterior triangle of the neck

Clinical

presentation of Trypanosomiasis

cont.

…

In the second stage the parasites cross the blood-brain barrier to infect the central nervous system.

This is known as the neurological phase.

In general this is when more obvious signs and symptoms of the disease appear: changes of behaviour, confusion, sensory disturbances and poor coordination.

Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease.

Diagnosis of Trypanosomiasis

The diagnosis of African Trypanosomiasis is made through laboratory methods, because the clinical features of infection are not sufficiently specific.

The diagnosis rests on finding the parasite in body fluid or tissue by microscopy.

The parasite load in

T. b. rhodesiense

infection is substantially higher than the level in

T. b. gambiense

infection.

T. b. rhodesiense

parasites can easily be found in blood.

Diagnosis of Trypanosomiasis

Cont

…

They can also be found in lymph node fluid or in fluid or biopsy of a chancre.

The classic method for diagnosing

T. b. gambiense

infection is by microscopic examination of lymph node aspirate, usually from a posterior cervical node.

It is often difficult to detect

T. b. gambiense

in blood. Concentration techniques and serial examinations are frequently needed.

Serologic testing is available outside the U.S. for

T. b. gambiense

; however, it normally is used for screening purposes only and the definitive diagnosis rests on microscopic

Diagnosis of Trypanosomiasis

Cont

…

All patients diagnosed with African trypanosomiasis must have their cerebrospinal fluid examined to determine whether there is involvement of the central nervous system, since the choice of treatment drug(s) will depend on the disease stage.

The World Health Organization criteria for central nervous system involvement include increased protein in cerebrospinal fluid and a white cell count of more than 5.

Trypanosomes can often be observed in cerebrospinal fluid in persons with second stage infection

.

Activity

: Small Group Discussion

What

is the

treatment

of Trypanosomiasis?

Pharmacological treatment of Trypanosomiasis

The type of treatment depends on the stage of the disease.

The drugs used in the first stage of the disease are of lower toxicity and easier to administer.

The earlier the disease is identified, the better the prospect of a cure.

Treatment success in the second stage depends on a drug that can cross the blood-brain barrier to reach the parasite.

Such drugs are toxic and complicated to administer.

Monitoring of Trypanosomiasis Therapy

Monitor clinically and by using laboratory test

In both early- and late-stage trypanosomiasis, symptoms usually resolve after treatment, and the

parasitemia

clears on repeat blood smears.

Patients who have recovered from late-stage East African trypanosomiasis should undergo

lumbar punctures

every 3 months for the first year.

Patients who have recovered from West African trypanosomiasis should undergo lumbar punctures every 6 months for 2 years

.

Monitoring of Trypanosomiasis

Therapy

Cont

….

If symptoms return, the CSF WBC count is higher than 20/µL, CSF

pleocytosis

occurs((presence of an abnormally large number lymphocytes in cerebrospinal fluid), or trypanosomes are still present in blood or CSF, a relapse is suggested.

However, a persistently elevated CSF WBC count may also be observed in recovering patients; thus, the change (increase or decrease) in the WBC count is more diagnostically helpful than the count by itself.

If a relapse is noted, repeat treatment with

melarsoprol

or

eflornithine

may be considered

Key Points

Human

African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease.

It is caused by infection with protozoan parasites belonging to the genus

Trypanosoma

.

They are transmitted to humans by tsetse fly (

Glossina

genus) bites which have acquired their infection from human beings or from animals harbouring human pathogenic parasites.

The type of treatment depends on the disease stage whereby drugs used in the first stage are safer and easier to administer than those for second stage.

Also, the earlier the disease is identified, the better the prospect of a cure

.

Evaluation

What

is trypanosomiasis?

What is the pathophysiology of trypanosomiasis?

What are the signs and symptoms of trypanosomiasis?

How is the treatment of trypanosomiasis?

References

Wells

BG,

DiPiro

J,

Schwinghammer

T (2013),

Pharmacotherapy Handbook

(6

th

Ed). New York, NY: McGraw-Hill.

DiPiro

JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):

Pharmacotherapy: A Pathophysiologic Approach

(7

th

ed

): New York, NY: McGraw-Hill.

Katz M D.,

Matthias KR.,

Chisholm-Burns M A.,

Pharmacotherapy(2011)

Principles & Practice Study Guide: A Case-Based Care Plan Approach

:

New York, NY: McGraw-Hill.

Schwinghammer

TL, Koehler JM (2009)

Pharmacotherapy Casebook: A Patient-Focused Approach

(7

th

ed

): New York, NY: McGraw-Hill.

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