Congenital visceral leishmaniasis in Ukraine: case report

Annals of Tropical Paediatrics (2010) 30, 161–164

Congenital visceral leishmaniasis in Ukraine: case report A. ZINCHUK & A. NADRAGA Department of Infectious Diseases, Lviv National Medical University, Lviv, Ukraine (Accepted February 2010)

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Abstract An 8-month-old boy was diagnosed with visceral leishmaniasis in the Ukraine, a non-endemic area. His mother had been treated for visceral leishmaniasis at 28–32 weeks gestation whilst working in Alicante, Spain and delivered her infant at 38 weeks gestation by elective caesarean section in Ukraine. It is presumed that the infant’s infection was as a result of vertical transmission.

Introduction

Case Report

Because of increased international travel, migration and tourism, the incidence of infections endemic to tropical and subtropical regions is increasing in Eastern Europe where previously such infections were rare. Ukraine is considered to be a non-endemic area for visceral leishmaniasis with the exception of Crimea where sporadic cases of VL were diagnosed in the past. From 1990 to 2006, 31 cases of leishmaniasis were reported in immigrants living in Ukraine, and 15 cases were reported during 2007 to 2008, eight of which were visceral leishmaniasis (VL).1,2 In August 2007, the first death of a patient with VL was reported in Ukraine, an 8-year-old child who lived in Kiev and who, prior to becoming ill, had been on a family vacation on the shores of the Black Sea near the city of Feodosia in Crimea, Ukraine.2 In such cases, diagnostic and treatment failure can be a considerable problem. An infant with congenital VL is reported together with a review of the literature.

A critically ill, 8-month-old boy presented to the Department of Haematology, Lviv Regional Children’s Hospital with fever, hepatosplenomegaly and anaemia. Born in Lviv to a primigravida mother, he was delivered by elective caesarean section at 38 weeks gestation. Birthweight was 2800 g and length 49 cm. For 2 years before and during the pregnancy, the mother had been working in Alicante, Spain as a maid and she returned to Ukraine just before the delivery. During the 28th to 30th weeks of pregnancy, she had become ill and developed a fever, hepatosplenomegaly, anaemia and thrombocytopenia. She was diagnosed as having a septic illness. Although none of the treatment she received was effective, her illness appeared to have resolved. However, serological testing (IgG and IgM antibody levels by ELISA) demonstrated infection by Leishmania infantum. During the next 2 weeks (weeks 31–32 of pregnancy) she was treated with a full course of liposomal amphotericin B (3 mg/kg days 1–5 followed by a single dose 3 mg/kg on day 10). After delivery, the child’s general health was satisfactory, although during the neo-

Reprint requests to: Professor A. Nadraga, Lviv National Medical University, 79005, 69Pekarska Street, Lviv, Ukraine. Fax: z380322755947; email: [email protected]/[email protected] # W. S. Maney & Son Ltd 2010 DOI: 10.1179/146532810X12703902516400

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natal period his mother noted a periodic rise in temperature without apparent cause. Nevertheless, the child’s general health remained good during the neonatal period and medical attention was not sought at that time. At 8 months of age, he became severely ill for the first time; he developed weakness, pallor, loss of appetite and a fever (39–40uC), and he slept poorly. Given the child’s extreme pallor, presence of ecchymosis and hepatosplenomegaly, acute leukaemia was suspected. After 3 days, the child was admitted in a critical condition to the Department of Haematology, Lviv Regional Children’s Hospital. On admission, temperature was 39.5uC, there was tachypnoea (35–40 resp/min), petechiae and ecchymosis on the lower limbs, lymphadenopathy (cervical, axcillary and brachial) and the liver was 3 cm and the spleen 10 cm below the costal margin. Heart rate was 135–150 beats/min which reflected body temperature elevation. Heart auscultation revealed a soft apical, systolic murmur. There was no meningism. Investigations. Haemoglobin was 44 g/dl, red blood cell count 2.0361012/L, reticulocytes 6%, leucocytes 5.86109/L (differential: myelocytes 1%, neutrophils 28%, segmented 1%, lymphocytes 67%, monocytes 3%), platelets 256109/L and ESR was 60 mm/h. Total serum protein was 68 g/L, albumin 35.3%, globulin 64.7% (a1 -8.7%, a2 -12.8%, b 11.6%, c -31.6%). Total serum bilirubin was 12.6 mmol/L, direct bilirubin 3.4 mmol/L, alanine aminotransferase 98 U/L (15–45 U/L), aspartate aminotransferase 280 U/L (10– 40), BUN 5.4 mmol/L (1.8–5.9), creatinine 76.1 mmol/L (20–50), sodium 139 mmol/L (135–150), calcium 2.2 mmol/L (2.2–2.7) and potassium 1.9 mmol/L (1.3–1.9). Chest radiograph was normal and ultrasound examination confirmed hepatosplenomegaly and lymphadenopathy. On Doppler echocardiography, the heart and great vessels were normal. Bacterial culture and gram stain of the blood, urine and stool were negative, as were serological tests for HIV, syphilis, hepatitis B and hepatitis C.

Antibiotic treatment (ceftriaxone and amoxicillin) was commenced and two packed red blood cell transfusions (80 ml) were given. Despite therapy, the patient remained febrile and in a critical condition. A sternal bone marrow examination showed no evidence of leukaemia. However, bone marrow examination demonstrated oval cells, 3–5 mm in size, with intracellular inclusions which were identified as amastigotes of Leishmania infantum. This was confirmed by the District Public Health Station, Lviv and the Central Public Health Station of the Ukrainian Ministry of Public Health, Kiev. The patient was transferred for further treatment to Lviv Regional Hospital for Infectious Diseases where specific treatment for VL with daily sodium stibogluconate (Pentostam), 20 mg/kg IV, was given for 20 days. The patient was also given intravenous infusions of glucose, albumin and one unit (80 ml) of packed red cells, and antipyretic therapy. He tolerated the treatment well with no adverse events. He showed clinical improvement on the 4th day after sodium stibogluconate was commenced and by the 7th day of therapy his temperature had normalised. Owing to the presence of severe leucopenia and neutropenia, he was given a 14-day course of antibiotic therapy (ceftazidime, ceftriaxone). He continued to improve and was discharged on the 30th day of hospitalisation. He continues to thrive, is developing normally and is being followed by infectious disease specialists.

Discussion VL results from infection by a protozoan parasite that is widely distributed in many sub-tropical and tropical countries. According to WHO statistics, each year there are 500,000 new VL cases,3 with approximately 60,000 people dying from the infection. India, Bangladesh, Brazil, Nepal and Sudan account for 90% of

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FIG. 1. Clinical course and laboratory investigations ( _ platelet count; – % – haemoglobin; –m– WBC count).

leishmaniasis cases. L. donovani and L. infantum/L. chagasi are responsible for most VL cases. The likelihood of infection depends on the presence of a natural reservoir and the person’s susceptibility to the parasite. In the Mediterranean basin (including Malta, France, Spain, Italy and Greece), sporadic cases of leishmaniasis occur and approximately 1000 new cases of leishmaniasis are reported annually, most often as a result of infection with L. infantum.4 In Mediterranean countries, VL is more often reported in children or immunocompromised hosts, such as those with HIV infection, whilst in Northern Europe VL may rarely occur as an opportunistic infection in AIDS patients who have contracted VL in endemic areas. Among the various illnesses caused by Leishmania, that caused by L. infantum characteristically has a rapidly progressive course, especially in young children, and, in the absence of specific therapy, is frequently lethal. In endemic regions, the disease is spread by sandfly species from canines, rodents and occasionally humans. Other infrequent

modes of transmission include medical procedures, blood transfusions, needle stick injuries, intravenous drug use, organ transplants and venereal transmission.5 Often, the source of VL cannot be identified. VL can also be transmitted vertically from mother to child, although cases of congenital VL are particularly rare. Our literature search on VL in infants and pregnant women used MEDLINE, Embase and the Cochrane database. The first case of mother-to-child transmission of VL was described in 19266 and since then only 11 confirmed clinical cases of mother-to-child transmission have been reported.7–10 However, transplacental transmission of infection to the infant has been questioned: there was no evidence of leishmaniasis in a fetus aborted at 20 weeks gestation by a woman with VL, despite massive placental dissemination of amastigotes.11 In several experimental studies, transplacental vertical transmission of leishmania and other parasites was demonstrated, but there are conflicting results regarding the possibility of vertical transmission in animals.12–14 The symptomatic form of VL has been reported in most of the cases in pregnant

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women;15,16 only two cases have been reported where infection in pregnant women remained asymptomatic.9 During pregnancy, both cellular and humoral immunity is suppressed, which can result in activation of infectious processes in the mother and increase the risk of transmission of VL to the infant. We consider that this case is an example of vertical transmission of VL in the prenatal or perinatal period. Arguing for vertical transmission are the clinical features in the mother’s 2nd/3rd trimesters combined with positive serology and the clear diagnosis in the child who had not visited an endemic area. Given that the infant was delivered by elective caesarean section, the fetus is likely to have been infected antenatally, either transplacentally or via the amniotic sac. It is possible that the infection was transmitted during the intranatal period due to fetal contact with the maternal circulation. However, this is unlikely because of the elective caesarean section and the presence of periodic fever in the neonatal period. Currently, the drug of choice for treatment of leishmaniasis in pregnant women and children is liposomal amphotericin B17 which is more efficient, less toxic and less teratogenic than common amphotericin. Physicians working in areas where leishmaniasis is not endemic should be aware of the possibility in migrants and visitors to endemic areas.

Acknowledgments The authors would like to thank Drs Anthony Shardt and Luba Wolchuk, visiting professors at Lviv National Medical University and Dr Dimitry Podorozhny at Birbeck Medical Group, Penrith, Scotland for editorial assistance and advice during preparation of the manuscript.

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