Congenital Transmission of Visceral Leishmaniasis (Kala Azar) from an Asymptomatic Mother to Her Child
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Congenital Transmission of Visceral Leishmaniasis (Kala Azar) From an Asymptomatic Mother to Her Child Christoph K. Meinecke, MD*; Justus Schottelius, PhD‡; Linda Oskam, PhD§; and Bernhard Fleischer, MD‡ ABSTRACT. In this article, we report the case of a results and polymerase chain reaction of this material 16-month-old German boy who was admitted to the Chil- were negative. A Montenegro skin test result was posi- dren’s Hospital of Stuttgart with a 4-week history of tive, indicating a previous infection with Leishmania. intermittent fever, decreased appetite, weakness, fatigue, Western blot analysis showed specific recognition by and difficulty sleeping. He was healthy at birth and maternal antibodies of antigens of Leishmania cultured remained so for the first 15 months of his life. On admis- from the boy’s tissue. sion, physical examination showed enlarged cervical, ax- Visceral leishmaniasis is endemic to several tropical illary, and inguinal lymph nodes, as well as hepato- and subtropical countries, but also to the Mediterranean splenomegaly. Laboratory data revealed pancytopenia, region. It is transmitted by the sand fly (Phlebotomus, elevated liver function tests, and hypergammaglobuline- Lutzomyia). Occasional nonvector transmissions also mia. Blood, stool, and urine culture results were negative. have been reported through blood transfusions, sexual Viral infections and rheumatologic and autoimmune dis- intercourse, organ transplants, excrements of dogs, and orders were ruled out, but a positive titer for Leishmania sporadically outside endemic areas. Only 8 cases of con- antibodies was noted. In a liver and bone marrow biopsy, genital acquired disease have been described before the amastigote form of the parasite could not be seen in 1995, when our case occurred. cells. The promastigote form of Leishmania was found In our patient, additional evaluation showed that the and the diagnosis of visceral leishmaniasis was made by asymptomatic mother must have had a subclinical infec- combining the cultures of both the liver and the bone tion with Leishmania that was reactivated by pregnancy, marrow biopsy material in 5 mL 0.9% saline on brain and then congenitally transmitted to the child. Visceral heart infusion agar, supplemented with defibrinated rab- leishmaniasis has to be considered in children with fe- bit blood and incubated at 25 to 26°C for 5 days. The ver, pancytopenia, and splenomegaly, even if the child parasite was identified by Southern blot analysis as has not been to an endemic area and even if there is no Leishmania infantum. evidence of the disease in his environment, because Specific therapy with the antimonial compound so- leishmaniasis can be transmitted congenitally from an dium stibogluconate with a dose of 20 mg/kg body asymptomatic mother to her child. Pediatrics 1999;104(5). weight was begun immediately. Within 4 days, the pa- URL: http://www.pediatrics.org/cgi/content/full/104/5/ tient became afebrile. The side effects of treatment, in- e65; visceral leishmaniasis in infants, kala azar, congeni- cluding erosive gastritis, cholelithiasis, worsening hepa- tal transmission, nonvector transmission. tosplenomegaly, elevation of liver enzymes, pancreatitis, and electrocardiogram abnormalities, necessitated the discontinuation of treatment after 17 days. On discharge ABBREVIATIONS. EIA, enzyme-linked immunosorbent assay; 4 weeks later, the patient was stabilized and afebrile with IFA, immunofluorescence assay; CF, complement fixation test; ECG, electrocardiogram; PCR, polymerase chain reaction. a normal spleen, normal complete blood count, normal gammaglobulins, and decreasing antibody titers to Leish- mania. During the next 24 months, the patient experi- isceral leishmaniasis is endemic to several enced intermittent episodes of abdominal pain, de- tropical and subtropical countries but also to creased appetite, recurrent arthralgia, and myalgia. But at the Mediterranean region. It is transmitted by his last examination in January 1998, he was well; all V the sand fly (Phlebotomus, Lutzomyia). Occasional symptoms mentioned above had disappeared. Because the child had never left Germany, nonvector nonvector transmissions also have been reported transmission was suspected and household contacts were through blood transfusions, sexual intercourse, or- examined. His mother was the only one who had a pos- gan transplants, excrements of dogs, and sporadi- itive antibody titer against Leishmania donovani com- cally outside endemic areas. Only 8 cases of congen- plex. She had traveled several times to endemic Mediter- ital acquired disease have been described before ranean areas (Portugal, Malta, and Corse) before giving 1995.1–8 In all these case reports, the mothers were birth to the boy. But she had never been symptomatic for symptomatic for the disease. In this article, we report visceral leishmaniasis. Her bone marrow, spleen, and the case of a boy who acquired the disease congeni- liver biopsy results were within normal limits. Culture tally by transmission from his asymptomatic mother. From the *Children’s Hospital of Stuttgart (Olgahospital), Stuttgart, Ger- METHODS many; ‡Bernhard Nocht Institute for Tropical Medicine, Hamburg, Ger- All diagnostic procedures and the treatment of the boy were many; and the §Department of Biomedical Research, Royal Tropical conducted at the Children’s Hospital of Stuttgart in Germany. The Institute, Amsterdam, the Netherlands. serologic tests on Leishmania donovani species included enzyme- Received for publication Oct 21, 1998; accepted May 17, 1999. linked immunosorbent assay (EIA; cutoff values: weak positive Reprint requests to (C.K.M.) Filderklinik, D-70794, Filderstadt, Germany. $10 antibody units and strong positive $30 antibody units), im- PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- munofluorescence assay (IFA; cutoff values: weak positive titers emy of Pediatrics. $1:20 and strong positive titers $1:80), and complement fixation http://www.pediatrics.org/cgi/content/full/104/5/Downloaded from www.aappublications.org/newse65 PEDIATRICS by guest on September Vol. 104 23, No.2021 5 November 1999 1of5 tests (CFs; cutoff values: weak positive titers $1:4 and strong mm per hour), pancytopenia (hemoglobin 7.8 g/dL, leukocytope- positive titers $1:16). The cultivation of liver and bone marrow nia with an absolute neutrophil count of 100–200/mL, platelets biopsy material was performed in 5 mL 0.9% saline on brain heart 40 000/mL), elevated liver function tests (serum glutamic oxaloa- infusion agar, supplemented with defibrinated rabbit blood cetic transaminase 153 U/L, serum glutamic pyruvate transami- (Difco, Detroit, MI) and incubated at 25 to 26°C for 5 days. Then nase 184 U/L, lactic acid dehydrogenase 467 U/L), with normal the promastigote form of Leishmania was detected by microscopy. bilirubin levels, and hypergammaglobulinemia (immunoglobulin The serologic tests, the cultivation, the microscopic examinations, G 2577 mg/dL). The results of a chest radiograph were within and the Western blot analysis of the mother’s serum against normal limits. Abdominal sonography verified the hepatospleno- Leishmania antigens from the child were performed at the Bern- megaly. Cardiac echography showed a mild pericardial effusion. hard Nocht Institute for Tropical Medicine in Hamburg, Germany. The results of three blood cultures were negative. Urine analysis The identification of the promastigotes was performed by South- and stool and urine culture results were also negative. Serologic ern blot analysis, using probe pDK209 at the Royal Tropical Insti- studies showed no evidence of brucellosis, leptospirosis, or Ep- tute, Department of Biomedical Research in Amsterdam, the Neth- stein-Barr virus infection. Human immunodeficiency virus infec- erlands. tion, rheumatologic, and autoimmune disorders were ruled out. A bone scan was negative, and a bone marrow aspirate showed no CASE REPORT evidence of malignancy, only a proliferation of lymphocytes and In February 1995, a 16-month-old boy from a small village in macrophages with increased hemophagocytosis. Because of the southwestern Germany was admitted to the Children’s Hospital severity of the illness, an antibiotic treatment was initiated empir- of Stuttgart with a 4-week history of intermittent fever up to 40°C, ically, without any clinical improvement. After 7 weeks of inter- decreased appetite, weakness, fatigue, and difficulty sleeping. He mittent fever, a positive titer for Leishmania antibodies (L donovani was born to a 31-year-old prima gravida, prima para at 40 weeks’ complex, IFA 1:640, EIA 68, CF 1:32) was noted. The results were gestation by vacuum extraction with a birth weight of 3720 g and confirmed on a second specimen. In a repeat liver and bone a length of 53 cm. The mother’s pregnancy was complicated by a marrow biopsy, the amastigote form of the parasite could not be febrile gastroenteritis, but the newborn was healthy, and the child seen in cells. Only by combined culture of both the liver and the remained healthy for the first year of his life. At 15 months of age, second bone marrow biopsy material was the promastigote form he developed fever, enlarged cervical lymph nodes, poor appetite, of Leishmania found and the diagnosis of visceral leishmaniasis and a transient icterus with elevated liver function tests. A pre- made. The parasite was identified as Leishmania infantum using sumptuous diagnosis of infectious mononucleosis was made. Be- Southern blot analysis. cause the symptoms