Visceral Leishmaniasis (Kala-Azar)

Essentials of Diagnosis

General Considerations

Kala-azar is widespread geographically wherever sandfly vectors are found. In each locale the disease has its own peculiar clinical and epidemiologic features. It occurs in the Mediterranean littoral, equatorial Africa, Ethiopia, eastern India, central Asia and China, and South America. Although man is the major reservoir, animal reservoirs such as the dog are important. The incubation period varies from weeks to months. The parasites exist in one form in the body, as oval Leishman-Donovan bodies which parasitize reticulo-endothelial cells and lead to their proliferation. They are easily detected in the spleen, liver, and bone mar-row, and may be found in blood.

Clinical Findings

A. Symptoms and Signs: The fever is generally mild and is not usually associated with prostration. The characteristic double daily remission may escape detection. The spleen usually enlarges much more than the liver and may be palpable by the second month. Enlargement is painless, steady, and rapid, usually in waves with bouts of fever. At first doughy, the spleen finally becomes large and hard. Wasting occurs without anorexia.

Post kala-azar dermal leishmaniasis may appear 1-2 years after apparent cure, especially in India but also in the Sudan and China. This may simulate leprosy as multiple hypopigmented macules or nodules which develop on pre-existing lesions. There may even be a degree of leontiasis. They take the form of erythematous patches, often on the face.

B. Laboratory Findings: There is usually progressive gross leukopenia (seldom over 3000/cmm after the first 1-2 months), with relative or (usually) abso lute monocytosis. Nevertheless, an occasional leuko-cytosis, due to concurrent sepsis, may be confusing. Diagnosis must always be confirmed by demonstrating Leishman-Donovan bodies in blood, sternal marrow, liver. or spleen. Blood culture is highly successful, and a nonspecific complement fixation test has been devised which is often positive in the first month but is meaningless in the presence of chronic pulmonary tuberculosis. Diagnosis may be supported by a positive formol-gel test, in which a drop of commercial formalin in 1 ml of serum produces opacity in 2 hours.

Differential Diagnosis

Kala-azar which is of subacute or acute onset resembles enteric fever (but there is no toxemia and Widal's test is negative) or malaria (in which case re sponse to antimalarial therapy may aid the diagnosis, since concomitant malaria parasites may be present in the blood in kala-azar). Many patients present with abdominal enlargement, weakness, and wasting; these patients have irregular fevers and the spleen and liver are palpable, which differentiates this disease from brucellosis. Characteristic double (rarely triple) daily remissions (evening and morning) occur early.

Chronic cases may also be confused with infectious mononucleosis, leukemia, anemias due to other causes, and tuberculosis. Post kala-azar dermatitis may resemble leprosy.

Treatment

General treatment must include a diet rich in protein and vitamins. Specific treatment is primarily with pentavalent antimonials, to which cases from India respond best whereas those from the Sudan are most resistant. Children tolerate antimonials well. In all cases resistance to antimonials can develop with inadequate dosage. In addition to antimonials, aromatic diamidines are powerful agents. They should be preceded by injection of epinephrine or an antihistaminic to minimize reactions. They are less effective for post-kala-azar dermal lesions. Fresh solutions only should be given and ampules stored away from heat. Intravenous injection must be given slowly.

1. Antimony sodium gluconate (Pentostam®, Solustibosan®, Stibinol®), 0.2 gm followed by 0.6 gm daily as 5% solution IM or IV for patients weighing over 30 kg. Continue treatment for 6-10 days.

2. Pentamidine isethionate (Lomidine®), 2-4 mg/kg IV or (preferably) IM, daily or on alternate days, up to 15 injections.

3. Stilbamidine isethionate is used only in anti-mony-resistant cases and must be given with great care because it is unstable and may produce immediate reactions or delayed trigeminal hyperesthesia.

The initial adult dose is 25 mg IV daily, increasing by 10-20 mg daily to 2 mg/kg daily. The most that should be given is about 10 injections or a total of about 15 mg/kg.

4. Ethylstibamine (Neostibosan®), 0.2 gm initially IV, then 0.3 gm IV daily or every 2 days for 16 doses.

5. Urea stibamine (carbostibamid e), IV in 10 ml water daily, in doses of 0.05, 0.1, 0.15, and sub-sequently 0.2 gm for about 15 days.

Prognosis

Therapy is effective but there may be relapses. Keep the patient under observation for at least 6 months. The spleen, blood picture, and body weight should return to normal.

Splenectomy before repetition of a course of treatment may be advisable in refractory cases.

Cutaneous Leishmaniasis

(Oriental Sore)

Cutaneous swellings follow the bites of sandflies infected with Leishmania tropica after an interval of weeks or even years. Oriental sore is widespread in distribution, including Latin America. The swellings may ulcerate and discharge pus, or they may remain dry. Dry and moist forms are caused by locally distinct leishmanias.

Lesions tend to heal spontaneously, but secondary infection may lead to gross extension. Moist ulcerated lesions are covered with a scab and exude purulent material as a result of secondary infection.

Leishmanias cannot be detected in purulent discharge but may be seen in scrapings from the cleaned edge. Needle biopsy material from the edge can be cultured in NNN medium.

Single lesions may be cleaned, covered, and left to heal. Topical or local treatment with carbon dioxide snow, infrared therapy, or radiotherapy is often effec tive.

Antibiotics may be required for secondary infections. Antimony sodium gluconate or ethylstibamine (Neostibosan®) as for visceral leishmaniasis may be effective.

Mucocutaneous (Nasooral) Leishmaniasis

(Espundia)

Espundia is a chronic infection, caused by L bra-ziliensis, which occurs in many countries of Latin America. It is characterized by cutaneous and naso-oral involvement, either by direct extension or, more often, metastatically.

The initial lesions on exposed skin, often the ears, take more varied forms than is usual with oriental sore. Naso-oral involvement may follow healing of lesions, even after a considerable interval, or may develop simultaneously.

The anterior part of the cartilaginous septum is commonly involved, and there may be gross and hideous erosion, including bone. Regional lymphadenitis is common.

Leishman-Donovan bodies may be found in aspirated tissue juice, and leishmanias may be cultured. If an injection of a suspension of killed leptomonads produces a fully developed papule in 2 days which disappears after a week (positive Montenegro's test), the diagnosis is fairly certain. A negative Montenegro's test is meaningless.

Specific treatment may be combined, if necessary, with local or systemic antibiotics or sulfon-amides. Give antimony sodium gluconate (Pento stam®, Solustibosan®, Stibinol®), 600 mg IM or IV daily for 6-10 days; or amphotericin B, 0.25-1 mg/kg, by slow infusion daily or every 2 days for up to 8 weeks.

Single doses containing 350 mg base of cyclo-guanil pamoate IM are not producing uniformly good results. Ethylstibamine (Neostibosan®) may be given as for visceral leishmaniasis.

Pyrimethamine (Dara-prim®) appears to be a promising alternative drug in the treatment of espundia in a dosage of 50 mg/day orally for 15 days. This treatment cycle should be repeated up to 4 times at 15-day intervals.

Submitted By:
DR. ALAM SHAH
The author is resident of New Zealand.

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