Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (514 page)

   Who Should Be Suspected?

Children are at highest risk for disease. Symptoms depend on the organ primarily affected; the liver is involved most commonly (approximately 85%). Severe VLM may be characterized by fever, wheezing and bronchopneumonia, hepatosplenomegaly, anemia, or other symptoms. Arthritis and vasculitis have been described. CNS invasion may occur with severe consequences, including eosinophilic meningitis, encephalitis, and other abnormalities. Ocular larva migrans is based on clinical findings and examination.

   Laboratory Findings

Direct detection
: Eggs are not detected by O&P examination.

Histology
: Larvae may rarely be found in biopsy of granulomatous lesions.

Serology
: Not useful for diagnosis of CLM. For VLM,
Toxocara
-specific ELISA has a sensitivity approximately 75% with specificity >90%. Specificity may be improved by immunoblot testing and may be less sensitive in ocular than in visceral disease.

Core laboratory
: Significant eosinophilia (>30%) is seen in VLM but not CLM. Leukocytosis, increased IgE, and hypergammaglobulinemia are common.

LEISHMANIASIS

   Definition

Leishmaniasis is used to describe a wide variety of diseases caused by protozoan species (more than 20) of the genus
Leishmania
. The disease is transmitted by the bite of female sandflies (genus
Lutzomyia
in the Americas and
Phlebotomus
elsewhere). It has a wide geographic distribution. In humans, disease is caused by the intracellular proliferation of the amastigote stage of the pathogen.

   Who Should Be Suspected?

There are three common syndromes: cutaneous (oriental sore), mucosal, and visceral. The epidemiology and clinical characteristics depend on the species and vectors endemic to specific regions.

   In cutaneous leishmaniasis, the vectors are
Phlebotomus
flies. A nodule develops at the bite site, eventually ulcerating. Wet lesions have a raised border with a granulating, exudate-covered base. Dry lesions are typically smaller and crusted over. Resolution of cutaneous lesions occurs in weeks or months, leaving an atrophic scar. Some patients develop fever and systemic symptoms and may develop regional adenopathy. Diffuse cutaneous leishmaniasis, caused by
Leishmania aethiopica
in Africa and
Leishmania amazonensis
in South America, results from wide dissemination of amastigotes, forming plaques and nodules.

   Mucosal leishmaniasis (espundia) occurs only in the Americas. In a small subset of patients, mucosal leishmaniasis develops months or years after resolution of primary cutaneous leishmaniasis. Ulceration of the nasal mucosa develops and may be followed by involvement of the lips, soft palate, and pharynx or other adjacent tissues.

   Visceral leishmaniasis is caused by
Leishmania chagasi
in Latin America and
Leishmania donovani
and
Leishmania infantum
in Mediterranean regions, Africa, and Asia. Most infections are asymptomatic or show only mild symptoms. A minority of patients progress to fulminant disease (kala-azar), presenting with fever, malaise, weight loss, and hepatosplenomegaly. Patients have decreased granulocyte levels and increased globulins. The course may be complicated by malnutrition and failure to thrive, edema, and bleeding diatheses. Immunocompromised patients are at greatest risk for visceral leishmaniasis.

   Laboratory Findings

Histology
: Definitive diagnosis is made by the identification of
Leishmania
in tissues. The raised border of cutaneous lesions should be biopsied. For visceral leishmaniasis, aspirate of the liver, spleen, or bone marrow, buffy coat, or biopsy of affected organ is used for diagnosis.

Culture
: Leishmania may be isolated in culture, but the special techniques required are not widely available.

Serology
: Serology or the leishmanin skin tests (cutaneous, mucosal, or resolved visceral disease) are useful for diagnosis of leishmaniasis. IFA and EIA methods are most commonly used. Tests based on the rK39 antigen of
L. chagasi
are sensitive for active visceral leishmaniasis, but cross-reactions may limit their utility.

Core laboratory
: In visceral leishmaniasis, serum globulin (IgG) levels are markedly increased with decreased albumin and reversed A/G ratio. ESR is increased, caused by increased serum globulin. Anemia, leukopenia, and thrombocytopenia may be seen due to hypersplenism and decreased marrow production. Proteinuria and hematuria may be seen. Laboratory findings due to amyloidosis may be seen in chronic cases.

MALARIA

   Definition

Malaria is caused by infection by protozoan pathogens of the genus
Plasmodium
. Four species account for most human infections:
Plasmodium vivax
,
Plasmodium falciparum
,
Plasmodium malariae
, and
Plasmodium ovale. Plasmodium knowlesi
is emerging as an increasingly reported cause of malaria. Malaria is endemic in tropical regions of sub-Saharan Africa, Central and South America, and Asia.
Plasmodium falciparum
and
P. malariae
show a worldwide distribution.
Plasmodium vivax
is less common in equatorial Africa, whereas
P. ovale
is uncommon outside of Africa.
Plasmodium knowlesi
is the cause of a significant proportion of cases of malaria acquired in Southeast Asia. Regions with chloroquine-resistant
P. falciparum
are fairly well defined geographically, emphasizing the importance of determining where infection was acquired for therapeutic decisions. The Duffy blood group antigen serves as the erythrocyte binding ligand for
P. vivax
.