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Letter
Congenital Visceral Leishmaniasis
Catharina C. Boehme,*
Ulrike Hain,* Astrid Novosel,* Susanna Eichenlaub,* Erna Fleischmann,*
and Thomas Löscher*
*University of Munich, Munich, Germany
Suggested
citation for this article
To the Editor: Visceral leishmaniasis (VL) is usually transmitted
by phlebotomine sandflies. Nonvector transmission occasionally occurs
through blood transfusions, contaminated needles of drug users, organ
transplants, or laboratory infection (1). Only
a few cases of congenital transmission have been reported. We describe
a case of VL in a German infant, who never had been to a VL-endemic area.
Most likely, the parasite was congenitally transmitted from the asymptomatic
mother to her child.
A 9-month-old girl had a 4-week history of intermittent fever, recurrent
upper respiratory tract infections, and failure to thrive. Physical examination
showed a distressed infant with bilaterally enlarged cervical lymph nodes,
hepatosplenomegaly, and a rectal temperature of 40°C. The following
laboratory results were remarkable: hemoglobin 6.4 mg/dL, erythrocyte
count 3.3 million/μL with 10.9% reticulocytes, platelet count 74,000/μL,
and leukocyte count 4,300/μL (29.8% neutrophils, 62.3% lymphocytes,
7.4% monocytes, 0.5% basophils, and 0% eosinophils). Serum electrophoresis
showed pronounced hypoalbuminemia and hypergammaglobulinemia. Abdominal
sonography verified hepatosplenomegaly. Cultures from blood and other
materials as well as additional investigations for a wide spectrum of
infectious diseases, including HIV infection, were negative. Leukemia
was suspected, and a bone marrow biopsy was performed. It showed enhanced
myelo-, erythro-, and thrombopoesis with slight lymphopenia but no leukemic
cells. However, Leishmania amastigotes were detected in bone marrow
macrophages at a density of ≈1 to 2 parasitized macrophages per
400× oil immersion field, corresponding to a Chulay score of 1+
(2). Serology was positive for Leishmania
spp. by indirect immunofluorescence antibody test, with cultured promastigotes
of L. donovani used as antigen (immunoglobulin G [IgG] antibody
titer 1:1,024). Specific antibodies against 14- and 16-kDa proteins of
L. infantum promastigotes (Figure) were confirmed
by immunoblot (3). Polymerase chain reaction (PCR)
on scrapings of stained bone marrow slides amplified a Leishmania
spp.–specific sequence of the internal transcribed spacer-1 gene (4),
and subsequent HaeIII-restriction fragment length polymorphism
helped identify the species as L. infantum (Figure).
Liposomal amphotericin B, at a daily dose of 4 mg per kg body weight,
was given by infusion on 6 consecutive days and repeated on days 14 and
21. The therapy was well tolerated. Within 3 days, the fever subsided.
The child recovered completely, and blood cell counts reached normal values
5 weeks after treatment was begun.
Since the child had never been outside Germany, vector transmission seemed
highly improbable. The girl was born to a 26-year-old prima gravida, prima
para, woman at 39 weeks' gestation by spontaneous labor; the infant's
birth weight was 3,350 g, and she was 51 cm long. She showed normal development
until the age of 8 months.
The mother had been healthy during pregnancy and had no history of serious
disease; she did not show any pathologic findings at clinical investigation
or in standard laboratory tests. However, Leishmania serologic
tests conducted on blood samples from the mother showed positive results
(IgG antibody titer 1:128 against promastigotes of L. donovani),
and immunoblot analysis confirmed specific antibodies (Figure).
During the last 15 years, she had spent holidays every year in Spain (Alicante)
but had never been to a tropical country. She stayed in Spain during weeks
29–32 of her pregnancy. However, she could not remember any episodes of
fever. She was not addicted to drugs nor had she ever received any blood
products. Microscopic and PCR examinations of the mother's blood (buffy
coat) and breast milk were performed with negative results. Cultures of
both specimens in NNN medium were also negative. Since she was asymptomatic,
a bone marrow biopsy was unwarranted. Four months later, she became pregnant
again. No abnormalities were noted during pregnancy, delivery, or development
of the second child.
Although sandflies (Phlebotomus mascittii Grassi, 1908) were recently
found for the first time at 3 different locations along the upper Rhine
Valley in southwestern Germany (5), no evidence
exists for autochthonous transmission of leishmaniasis in Germany. Congenital
transmission from the infected but asymptomatic mother is the most probable
scenario in our case. Since 1926, only 10 case reports of congenitally
acquired VL have been published (reviewed in 6).
Most cases have been observed after the mother had VL during pregnancy.
One previous report describes congenital transmission from an asymptomatic
mother to her child (6). However, this rarity
in reporting does not necessarily reflect the frequency of the event.
In VL-endemic areas, cases of congenital VL cannot be distinguished from
cases of infection by vector transmission during the first year of life.
Congenital transmission may occur either through blood exchange from the
mother to the child during labor or by transplacental infection during
pregnancy. Which of the 2 transmission routes led to infection in our
case is unclear. In the congenital cases reported to date, typical symptoms
of the disease developed from 4 weeks to 18 months (mean 8.5 months) after
birth. The incubation period after vector transmission is also highly
variable (typically 2–6 months but varying from 10 days to >10 years
[1]). All patients reported have been treated
with pentavalent antimonial agents; this treatment is still widely used
in VL-endemic areas, but it has considerable side effects, and resistance
is increasing (1). Liposomal amphotericin B is
the drug of choice for treating Mediterranean VL. An alternative, especially
for low-income countries, is oral treatment with miltefosine.
This report suggests that in infants with fever, splenomegaly, and pancytopenia,
VL should be considered even if the patient has not been to an disease-endemic
area. Congenital transmission is possible, not only as a consequence of
VL during pregnancy but also by transmission from an asymptomatic mother
to her child in utero or during labor.
References
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SL, Desjeux P, et al. Visceral
leishmaniasis: current status of control, diagnosis, and treatment,
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of amastigotes of Leishmania donovani in smears of splenic aspirates
from patients with visceral leishmaniasis. Am J Trop Med Hyg. 1983;32:475–9.
- Mary C, Lamouroux D, Dunan S, Quilici M. Western
blot analysis of antibodies to Leishmania infantum antigens:
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Suggested citation
for this article:
Boehme C, Hain U, Novosel
A, Eichenlaub S, Fleischmann E, Löscher T. Congenital visceral leishmaniasis
[letter]. Emerg Infect Dis [serial on the Internet]. 2006 Feb [date
cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no02/05-0449.htm
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