Luis Mora

Disseminated histoplasmosis in infants

BACKGROUND Disseminated histoplasmosis usually occurs in immunocompromised patients who reside in Histoplasma capsulatum-endemic regions. It has also been described in immunocompetent infants after exposure to a large inoculum of the pathogen resulting in case fatality rates of 40 to 50%. METHODS From 1983 through 1996 all infants with documented disseminated histoplasmosis were treated with amphotericin B followed by daily ketoconazole for 3 months. Immunologic workups were performed at the time of diagnosis and at 4 to 6 weeks of therapy. Surviving patients were followed for at least 1 year. Time to resolution of signs and symptoms was recorded, as were complications. RESULTS We managed 40 patients with disseminated histoplasmosis. The age in months at diagnosis was 15.3+/-10.2 (mean +/- SD), and 24 were male. All patients were from endemic regions and they presented with fever, spleen and/or liver enlargement and hematologic abnormalities. Diagnosis was made by histology and culture of bone marrow, spleen, lymph node, bronchoalveolar or liver samples. Twenty patients presented with T cell deficiency that resolved at 4 to 6 weeks of therapy in all of the retested patients, and 10 of 12 tested patients had hyperglobulinemia that resolved. Thirty-five (88%) patients were cured by treatment; 4 died and 1 relapsed. CONCLUSIONS Disseminated histoplasmosis should be considered in infants from endemic areas who present with fever, hepatosplenomegaly and hematologic abnormalities. These patients develop transient hyperglobulinemia and T cell deficiency that resolve with treatment. Treatment with amphotericin B followed by an oral azole for 3 months is effective in most patients.

Vitamin K-dependent clotting factors in normal breast-fed infants

BREAST-FEEDING has been implicated as a necessary factor in the pathogenesis of hemorrhagic disease of the newborn infant, ~ but little is known of its role in coagulation abnormalities beyond the neonatal period. Vitamin K is approximately four times more concentrated in cow milk than in breast milkfl and clotting factors depending on this vitamin are decreased in normal term infants, and even more reduced in premature infants. 3.4 Deficiency of vitamin K-dependent clotting factors with clinical bleeding has occasionally been reported in breast-fed infants older than one month, but these infants usually had also had diarrhea or had received antibiotic therapy? ,6 Since the levels ot ~ vitamin K-dependent clotting factors in healthy older breast-fed infants have not been systematically assessed, vitamin deficiency cannot be attributed to breast-feeding per se. To determine if breast-feeding during the first month of infancy is associated with an increased risk of bleeding caused by vitamin K deficiency, the present investigation compared coagulation studies and the levels of vitamin K-dependent clotting factors in normal breast-fed and bottle-fed infants.

Visceral Leishmaniasis in Costa Rica: First Case Report

We describe a 15-month-old eutrophic immunocompetent male who presented with fever, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Leishmania amastigotes were identified in spleen and bone marrow specimens. In addition, tissue culture, animal inoculation, and isoenzyme analysis identified the parasite as Leishmania donovani infantum or Leishmania donovani chagasi. The infant was successfully treated with an antimonial drug. These findings represent the first case of visceral leishmaniasis reported in Costa Rica.

Hemoglobin Perth in Costa Rica

To the Editor: Unstable hemoglobins are characterized by intracellular precipitation of hemoglobin that leads to inclusion body formation. Those patients usually present with congenital syndrome that includes hemolytic anemia during infancy. Clinical features show a high variability in almost all affected individuals at any age [1,2]. A 3 years and 9-month-old male presented with acute hemolytic anemia and jaundice from age 2 years. The initial cell blood count showed normal leucocytes and platelet counts, a hemoglobin of 4.9 g/dl, MCVof 88.3 fl, MCH of 22.9 pg and reticulocyte count of 58% uncorrected. Red cell morphology showed marked anisopoikilocytosis. Inclusion body formation was found in peripheral blood smears after incubation at 378C with supravital staining. Hemoglobin electrophoresis on cellulose acetate showed an HbA2 of 5.6% and fetal hemoglobin of 2.9%. As the parents and siblings never presented with anemia, jaundice, splenomegaly, or an abnormal hemoglobin electrophoretic pattern, b-thalassemia diagnosis was not considered and the patient was classified as having a non-immune hemolytic anemia (NIHA). However, because the patient’s condition did not fit a classic NIHA, a new hemoglobin electrophoresis was performed using fresh hemolysate; a previously unnoticed slow band near the origin was observed. We considered other diagnostic possibilities, such as the most frequent slow hemoglobins: A2 or Constant Spring. As the former has normal erythrocyte morphology without clinical features, Constant Spring was considered more likely, mainly because such patients have normal or slightly high values of MCV like in our patient. The slow band found in the hemoglobin electrophoresis prompted us to do an HPLC analysis. That analysis discarded Constant Spring. The a1, a2, and b-chain globins genes were amplified by PCR and the amplicons purified in order to find mutations in the direct nucleotide sequence. A multiplex gap-PCR test for a-chain globin genes deletions of the rightward ( a 3.7) and the leftward ( a 4.2) were negative. All those tests confirmed that the patient was heterozygous for hemoglobin Perth (codon 32 CTG>CCG or Leu32Pro). We believe this is a de novo mutation because parents and siblings of the propositus are clinically normal. De novo mutation has been reported as being common [3]. At present, our patient requires monthly transfusions of packed red cells and he is receiving hydroxyurea. Carriers of Perth hemoglobin usually show improvement in their clinical features with transfusion therapy [4] although other treatment approaches, including partial splenectomy, may be considered [5].