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International Journal of Infectious Diseases (2009) 13, e504—e507
http://intl.elsevierhealth.com/journals/ijid
CASE REPORT
Atypical disseminated leishmaniasis similar to
post-kala-azar dermal leishmaniasis in a Brazilian AIDS
patient infected with Leishmania (Leishmania)
infantum chagasi: a case report
Dimas Carnaúba Jr a, Cassiana Tami Konishi a, Valéria Petri b,c,
Isabel Cristina Pedro Martinez c, Laura Shimizu c,
Vera Lucia Pereira-Chioccola d,*
a
Centro de Referência em DST/AIDS de Santo Amaro, São Paulo, SP, Brazil
Universidade Federal de São Paulo, São Paulo, SP, Brazil
c
Hospital Ipiranga, São Paulo, SP, Brazil
d
Laboratorio de Parasitologia, Instituto Adolfo Lutz, Av. Dr Arnaldo, 351, 8 andar, CEP 01246-000, São Paulo, SP, Brazil
b
Received 5 August 2008; received in revised form 14 January 2009; accepted 19 January 2009
Corresponding Editor: William Cameron, Ottawa, Canada
KEYWORDS
Leishmania (Leishmania)
infantum chagasi;
AIDS;
Disseminated
leishmaniasis
Summary We report the case of an atypical disseminated leishmaniasis with similar clinical
characteristics to post-kala-azar dermal leishmaniasis, an uncommon disease in South America.
This occurred in a Brazilian patient with AIDS, 3 years after the first episode of American visceral
leishmaniasis.
# 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Introduction
Leishmaniases are endemic in 88 countries, 72 of which are
developing countries. The worldwide prevalence of the disease is estimated at 12 million cases, with 400 000—600 000
new cases per year for visceral forms.1,2 In Brazil, approximately 2500—5000 cases are reported each year.3
* Corresponding author. Tel.: +55 11 3068 2991;
fax: +55 11 3068 2890.
E-mail address: [email protected]
(V.L. Pereira-Chioccola).
The genus Leishmania causes a wide spectrum of human
diseases, ranging from self-limited cutaneous to the more
severe diffuse cutaneous and visceral forms, as a consequence of the complex host immunological response.4,5
The causative agent of the American viscerotropic leishmaniasis in Latin-America is Leishmania (Leishmania) infantum
chagasi included in the subgenus Leishmania.4,5
Despite some differences in cost of treatment, toxicity,
drug resistance, and endemic region, treatment is usually
based on the use of leishmanicidal drugs, principally injections of pentavalent antimony compounds.1,2,4,6 However,
a significant proportion of the apparently cured
1201-9712/$36.00 # 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijid.2009.01.022
Atypical disseminated leishmaniasis in an AIDS patient
patients infected with Leishmania (Leishmania) donovani
in India, Nepal, Bangladesh, and East African countries
develop post-kala-azar dermal leishmaniasis (PKDL).7 This
manifestation is a form of cutaneous leishmaniasis characterized by maculopapular or nodular lesions on the face,
limbs or trunk, which appear after a symptom-free period
following the end of visceral leishmaniasis treatment. The
interval between kala-azar and PKDL is estimated as being
months to years in India, but is considerably shorter in
Africa (0—6 months).7—10 The association of Leishmania
(Leishmania) infantum with PKDL is highly unusual
in patients living in Europe11 and rarely present in
patients infected with L. (L.) infantum chagasi in South
America.12,13
Since the onset of the AIDS era, co-infection with HIV and
leishmaniasis has become a high-priority emergent disease
appearing throughout the world.2 In Brazil, both infections
are highly prevalent. In the past, both target populations
were geographically separated. Currently, overlap appears
because of the expansion of leishmaniasis into urban areas
and of HIV infection into rural ones. Despite antiretroviral
therapy, approximately 100 cases of this co-infection are
reported per year in Brazil.14,15
Here, we report an AIDS patient with visceral leishmaniasis caused by L. (L.) infantum chagasi. After recurrence
and the development of an atypical disseminated leishmaniasis with PKDL-like appearance of skin lesions, the patient
died.
Table 1
e505
Case report
The case is that of a 42-year-old male who had migrated to
Sao Paulo City, Brazil from São José do Egito, Pernambuco, an
area of Brazil endemic for visceral leishmaniasis, 27 years
previously. He was found positive for HIV in1993 and had since
undergone several different schedules of antiretroviral therapy. The overall clinical events, including CD4+ T cell counts,
plasma viral load values, and treatments at each time period
are shown in Table 1. Each event of antiretroviral therapy was
made according to the guidelines of the previously established National Program of Sexual Diseases and AIDS of the
Health Ministry of Brazil.16
Even on antiretroviral therapy, his CD4+ levels were found
to have decreased and plasma viral load to have increased in
May 2000. As a result, he had cerebral toxoplasmosis (July
2001) and hepatitis C (December 2002). In January 2004, his
medication was again changed to stavudine, lamivudine and
efavirenz because his CD4+ T cell count was decreased (144
cells/mm3) and his plasma viral load was 812 copies/ml. In
November 2004 he was hospitalized after presenting with
fever, weight loss, diarrhea, epistaxis, and hepatosplenomegaly (Figure 1A). The diagnosis of visceral leishmaniasis was
confirmed due to the presence of amastigotes in the bone
marrow aspirate. The specific leishmaniasis was treated with
N-methylglucamine antimonate (glucantime, 20 mg/kg/day)
for 13 days, when he developed acute pancreatitis. At this
time, the glucantime was replaced with liposomal ampho-
Main clinical events
Period (month/year) Clinical event
CD4+ T cell Plasma
Treatment a
count
viral load
(cells/mm3) (copies/ml)
02/93
07/96
01/97
04/97
05/00
07/01
12/02
01/04
11/04
385
612
697
388
104
352
168
144
181
NA
NA
NA
45 000
290 000
200
6860
812
<400
NA
72
NA
<400
Positive for HIV/oral moniliasis
ddI intolerance
Cerebral toxoplasmosis
Hepatitis C
NA
NA
10/06
Visceral leishmaniasisb
(hepatosplenomegaly/cachexia/ diarrhea/fever)
Ambulatory follow-up
Visceral leishmaniasis (second episode)
(hepatosplenomegaly/cachexia/diarrhea/fever)
Visceral leishmaniasis (third episode)
(severe anemia/ epistaxis/hepatosplenomegaly)
Visceral leishmaniasis (fourth episode)
78
831
06/07
02/08
Multiple cutaneous lesions on face/thorax
Death (visceral leishmaniasis)
66
09
<50
<50
01/05
05/05
12/05
AZT
AZT/ddI
AZT/3TC
AZT/3TC
d4T/NVP/SQV
d4T/3TC/IDV/RTV
d4T/3TC/SQV/RTV
d4T/3TC/EFV
d4T/3TC/EFV—glucantime,c
amphotericin B d
d4T/3TC/EFV—glucantime
d4T/3TC/EFV—glucantime
d4T/3TC/EFV—liposomal
amphotericin
d4T/3TC/ATV/RTV—
liposomal amphotericin
d4T/3TC/ATV/RTV
d4T/3TC/ATV/RTV
NA, not available; ATV, atazanavir; ddI, didanosine; EFV, efavirenz; IDV, indinavir; 3TC, lamivudine; NVP, nevirapine, RTV, ritonavir; SQV,
saquinavir; d4T, stavudine; AZT, zidovudine.
a
Antiretroviral treatment was conducted as per the instructions established by the National Program of Sexual Diseases and AIDS of the
Health Ministry of Brazil.
b
Confirmed by bone marrow aspirate examination.
c
For 13 days; developed acute pancreatitis.
d
Treatment replaced.
e506
D.C. Jr et al.
Figure 1 Visceral leishmaniasis: clinical and histopathological diagnosis, and species genotyping by PCR. (A) Hepatosplenomegaly.
(B) Histopathological examination of the liver biopsy revealing amastigotes and chronic inflammation (hematoxylin—eosin staining).
Non-pruritic, erythematous maculopapular lesions on (C) face and (D) thorax. (E) Species genotyping by PCR; the RV1—RV2 marker
amplified a 145-bp product from the LT1 fragment of Leishmania donovani complex kDNA minicircles. The amplified PCR product was
analyzed by electrophoresis on 2% agarose gel; lane 1, 100-bp ladder (the lowest band shown is 100 bp); lane 2, patient sample; lane 3,
negative control.
tericin B (50 mg/day for 3.2 weeks). After hospital discharge,
in ambulatory follow-up, he took glucantime (81 mg) weekly.
Over the course of two years he had three other recurrent
episodes of visceral leishmaniasis (May 2005, December 2005,
and October 2006) and was again treated with glucantime
and liposomal amphotericin B. In October 2006, his antiretroviral therapy consisted of stavudine, lamivudine, atazanavir and ritonavir. His plasma viral load was becoming
undetectable, but his CD4+ T cell count was still gradually
decreasing (78 cells/mm3). In June 2007, his CD4+ T cell
count was 66 cells/mm3 when he developed multiple cutaneous lesions on the face and thorax (Figure 1, C and D).
Leishmania infection was also determined by the presence of
amastigotes in histopathological examinations prepared from
liver biopsies (Figure 1B) and skin lesions. The confirmation of
American visceral leishmaniasis and species identification as
L. (L.) infantum chagasi were made by PCR as previously
described.17 The RV1—RV2 marker amplified a 145-bp
sequence from the LT1 fragment of L. (L.) donovani complex
kDNA minicircles18,19 (Figure 1E). He died of disseminated
leishmaniasis in February 2008.
Discussion
Cutaneous manifestations of Leishmania and HIV co-infection
have been described in some patients having visceral leishmaniasis or as the only clinical manifestation of the disease.
Cutaneous dissemination is generally observed among
severely immunocompromised patients, and lesions tend to
localize symmetrically.11,20 In the present case, the patient
developed visceral recurrent leishmaniasis, despite antiretroviral, liposomal amphotericin B, and glucantime thera-
pies. As a result, he developed an atypical disseminated
leishmaniasis with PKDL-like appearance of skin lesions
(non-itchy maculopapular erythematous lesions on the face
and thorax).
The fact that the patient had a controlled viral load during
the last five years, as determined in plasma, lead us to
suppose that the antiretroviral therapy was efficient in
accordance with the established guidelines.16 However,
the low CD4+ T cell production was constant, suggesting a
lack of immune function, and finally the patient died of
disseminated visceral leishmaniasis.
As the incidence of HIV increases in areas in which Leishmania species are endemic, visceral leishmaniasis is being
recognized more frequently as an opportunistic infection in
patients with AIDS. This case also emphasizes the potential
use of PCR to confirm the diagnosis, for Leishmania species
genotyping, and for clinical evaluation and follow-up of HIV
patients undergoing antiretroviral therapy who have previously had leishmaniasis or patients living in leishmaniasis
endemic areas. In addition, atypical disseminated leishmaniasis with cutaneous lesions, similar to PKDL, should be
considered in AIDS patients undergoing both antimony compound and antiretroviral treatment.
Conflict of interest: No conflict of interest to declare.
References
1. Desjeux P. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 2004;27:305—18.
2. World Health Organization. Leishmaniasis; 2008. Available at:
http://www.who.int/tdr/diseases/leish/diseaseinfo.htm
(accessed March 2008).
Atypical disseminated leishmaniasis in an AIDS patient
3. Ministério da Saúde do Brasil (Health Ministry of Brazil). Manual
de controle da leishmaniose visceral americana [American visceral leishmaniasis: surveillance and control. Technical manual].
Available at: http://portal.saude.gov.br/portal/arquivos/pdf/
manual_leish_visceral2006.pdf (accessed March 2008).
4. Grimaldi G, Tesh RB. Leishmaniasis of the New Word: current
concepts and implications for the future research. Clin Microbiol
Rev 1993;6:230—50.
5. Lainson R, Shaw JJ. New world leishmaniasis. The neotropical
Leishmania species. In: Collier L, Balows A, Sussman M, editors.
Topley and Wilson’s microbiology and microbial infectious diseases. 9th ed. Vol. 5. London: Arnold; 1998, p. 241—66.
6. Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P,
et al. Visceral leishmaniasis: current status of control, diagnosis,
and treatment, and a proposed research and development
agenda. Lancet Infect Dis 2002;2:494—501.
7. El Hassan AM, Ghalib HW, Zijlstra EE, Eltoum IA, Satti M, Ali MS,
et al. Post kala-azar dermal leishmaniasis in the Sudan: clinical
features, pathology and treatment. Trans R Soc Trop Med Hyg
1992;86:245—8.
8. El Hassan AM, Khalil EA, El Sheikh EA, Zijlstra EE, Osman A,
Ibrahim ME. Post kala-azar ocular leishmaniasis. Trans R Soc Trop
Med Hyg 1998;92:77—9.
9. Sundar S. Drug resistance in Indian visceral leishmaniasis. Trop
Med Int Health 2001;6:849—54.
10. Zijlstra EE, Musa AM, Khalil EA, EI-Hassan IM, EI-Hassan AM. Post
kala-azar dermal leishmaniasis. Lancet Infect Dis 2003;3:
87—98.
11. Antinori S, Longhi E, Bestetti G, Piolini R, Acquaviva V, Foschi A,
et al. Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired
immune deficiency syndrome. Br J Dermatol 2007;157:1032—6.
e507
12. Bittencourt A, Silva N, Straatmann A, Nunes VL, Follador I,
Badaró R. Post-kala-azar dermal leishmaniasis associated with
AIDS. Braz J Infect Dis 2003;7:229—33.
13. Moral L. Post-kala-azar dermal leishmaniasis and Leishmania
infantum. Br J Dermatol 1999;140:760.
14. Posada-Vergara MP, Lindoso JA, Tolezano JE, Pereira-Chioccola
VL, Silva MV, Goto H. Tegumentary leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome in 2
patients with AIDS. J Infect Dis 2005;192:1819—22.
15. Rabello A, Orsini M, Disch J. Leishmania/HIV co-infection in Brazil:
an appraisal. Ann Trop Med Parasitol 2003;97(Suppl 1):17—28.
16. Programa Nacional de DST/AIDS do Ministério da Saúde do Brasil.
Recomendações para terapia anti-retroviral em adultos infectados pelo HIV, 2008 [National Program of Sexual Diseases and AIDS
of the Health Ministry of Brazil; instructions for anti-retroviral
therapy in infected adults, 2008. Technical manual]. Available
at: http://www.aids.gov.br (accessed April 2009).
17. Gomes AH, Ferreira IM, Lima ML, Cunha EA, Garcia AS, Araujo MF,
et al. PCR identification of Leishmania in diagnosis and control of
canine leishmaniasis. Vet Parasitol 2007;144:234—41.
18. Lachaud L, Marchergui-Hammami S, Chabbert E, Dereure J,
Dedet JP, Bastien P. Comparison of six PCR methods using peripheral blood for detection of canine visceral leishmaniasis. J
Clin Microbiol 2002;40:210—5.
19. Ravel S, Cuny G, Reynes J, Veas F. A highly sensitive and rapid
procedure for direct PCR detection of Leishmania infantum within
human peripheral blood mononuclear cells. Acta Trop 1995;59:
187—96.
20. Ridolfo AL, Gervasoni C, Antinori S, Pizzuto M, Santambrogio S,
Trabattoni D, et al. Post-kala-azar dermal leishmaniasis during
highly active antiretroviral therapy in an AIDS patient infected
with Leishmania infantum. J Infect 2000;40:199—202.