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Revista da Sociedade Brasileira de Medicina Tropical

Print version ISSN 0037-8682

Rev. Soc. Bras. Med. Trop. vol.47 no.4 Uberaba July/Aug. 2014

http://dx.doi.org/10.1590/0037-8682-0213-2013 

Short Communications

High visceral leishmaniasis mortality rate in Barra Mansa, a new area of visceral leishmaniasis transmission in the State of Rio de Janeiro, Brazil

Maria Inês Fernandes Pimentel[1]  [2] 

Elisabeth Larcher Maximiano Alves[3] 

Maria Hercília Fiuza Farias da Silva[4] 

Patrícia Gazenmüller Moza[2] 

Paula Maria Pereira de Almeida[2] 

Cristiane Silveira Cunha[3] 

Cíntia Xavier de Mello[1] 

Armando de Oliveira Schubach[1]  [5] 

[1]Laboratório de Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ

[2]Gerência de Doenças Transmitidas por Vetores e Zoonoses, Secretaria de Estado de Saúde do Rio de Janeiro, Rio de Janeiro, RJ

[3]Coordenação de Vigilância Epidemiológica, Secretaria Municipal de Saúde de Barra Mansa, Barra Mansa, RJ

[4]Santa Casa de Misericórdia de Barra Mansa, Barra Mansa, RJ

[5]Fundação Carlos Chagas Filho de Amparo à Pesquisa no Estado do Rio de Janeiro, Rio de Janeiro, RJ

ABSTRACT

Introduction

Nine cases of visceral leishmaniasis occurred recently in Barra Mansa, State of Rio de Janeiro, with a high mortality rate.

Methods

We reviewed the medical records of the patients.

Results

Eight were male; 7 were adults. Patients who died progressed to death quickly and presented with aggravating factors: systemic steroid therapy before diagnosis, bleeding, severe liver involvement, infection, and/or refusal to receive transfusion.

Conclusions

We warn clinicians to be aware of the emergence of visceral leishmaniasis in new areas and to keep in mind the possibility of atypical clinical pictures and aggravating factors, so timely diagnosis can be made and prompt and adequate treatment can be initiated.

Key words: Visceral leishmaniasis; Lethality; Epidemiology; Therapy

Visceral leishmaniasis (VL) is an anthropozoonosis caused by protozoa of the genus Leishmania and is transmitted by infected female sand flies during their blood meals. In the New World, the causative agent is Leishmania (Leishmania) chagasi, which is considered to be identical to Leishmania (Leishmania) infantum of the Old World1.

In Brazil, VL is endemic mainly in the states of the Northeast Region, but is also prevalent in the North Region, the Southeast Region, with the State of Minas Gerais having the highest prevalence, and the Midwest Region, with a high prevalence in the State of Mato Grosso do Sul2. While VL originally affected rural inhabitants of Brazil, urbanization has resulted in the progressive adaptation of the main VL vector, Lutzomyia longipalpis, to the peridomicile3,4, feeding predominantly on domestic dogs and chicken5,6 but also on synanthropic animals including opossums7,8. In the oldest VL endemic areas, most patients are male and/or children9. However, in the newer VL affected areas, larger numbers of adults have been diagnosed1, and patients present a more severe clinical picture.

In the State of Rio de Janeiro, several cases of VL occurred during the twentieth century; however, the number of autochthonous cases declined between 2000 and 2009. Since 2010, the incidence of human VL has resurged in Rio de Janeiro, mainly in the Paraíba do Sul River Valley. We examined the cases of human VL that occurred in Barra Mansa between 2010 and 2013 in order to better understand the behavior of VL in a geographic area where it was previously absent.

Through medical record analysis, we were unable to identify any cases of VL in Barra Mansa before 2010. No autochthonous cases of VL were present in the Brazilian diseases notification system (Sistema de Informação de Agravos de Notificação - SINAN) for Barra Mansa in the preceding decades. We reviewed the medical records of patients who had a diagnosis of VL in the City of Barra Mansa between November 2010 and September 2013. Nine patients were diagnosed with VL by their clinical picture, by parasitological confirmation through direct examination of bone marrow to visualize amastigotes by microscopy, by culture of bone marrow samples in appropriate media (Nicole-Novy-McNeal [NNN] medium with Schneider medium and 10% fetal bovine serum), and/or by positive specific serology (enzyme-linked immunosorbent assay [ELISA], immunochromatographic test with recombinant antigen rK39 [Kalazar Detect®], or immunofluorescence assay [IFA]).

Eight patients were male. Two were children under 5 years of age and 7 were adults. From the 9 cases, 3 patients presented with previous chronic diseases (heart disease and renal insufficiency) and 1 patient was addicted to alcohol and marijuana. A total of 4 patients died. The patients who died presented with bleeding, severe liver involvement, respiratory infection, or infection of unclear origin, or had systemic steroid therapy before diagnosis, and/or refused transfusion due to religious beliefs. The first 3 patients did not recover and died of VL. Patients 1 and 2 were diagnosed with VL post-mortem, although patient 2 had suspicion of VL a few weeks before death. Patients 4 to 7 recovered after successful treatment with amphotericin B or meglumine antimoniate; however, all were over the age of 40 years. Patient 8 died as a result of a severe liver dysfunction that was caused by VL. Patient 9, who was 26 years old, recovered after treatment with amphotericin B. Human immunodeficiency virus (HIV) serology was negative in all patients. The characteristics of the 9 patients are shown in Table 1.

TABLE 1 Socio-demographic characteristics, clinical features, diagnostic tests, and outcomes of 9 patients from Barra Mansa, State of Rio de Janeiro, Brazil with visceral leishmaniasis that occurred between November 2010 and September 2013. 

Patient Gender Age Clinical picture Duration of the disease until diagnosis VL serology Bone marrow Aggravating factors Treatment Outcome
1 Male 2 years 10 months Typical 2 months ND A (post mortem diagnosis) Steroid therapy, bleeding Amphotericin B as part of the protocol for febrile neutropenic patients U
2 Male 37 years Typical 6 months ELISA (+), Kalazar Detect®(+) A Patient did not accept transfusion; pulmonary infection; severe pancytopenia None (post mortem diagnosis) U
3 Male 3 years 10 months Typical 1 month IFA 1:160, Kalazar detect®(-) ND Infection of unclear origin Meglumine antimoniate; liposomal amphotericin B, late introduction U
4 Male 53 years Typical 3 months ND A No Meglumine antimoniate F
5 Female 51 years Typical 3 months IFA 1:640, Kalazar Detect®(+) A Renal insufficiency Liposomal amphotericin B F
6 Male 52 years Typical 6 months ND A Heart disease Liposomal amphotericin B F
7 Male 46 years Typical 2 months ND A Heart disease; chronic alcoholism and marijuana use Liposomal amphotericin B F
8 Male 20 years Atypical 15 days IFA 1:160, Kalazar Detect® (+) Direct exam (-) Culture (+) Severe liver involvement due to VL None (early death) U
9 Male 26 years Typical 4 months Kalazar Detect® (+) A No Liposomal amphotericin B F

VL: visceral leishmaniasis; ND: not performed; A: amastigotes in direct exam; ELISA: enzyme-linked immunosorbent assay; Kalazar Detect®: immunochromatographic test with recombinant antigen rK39; IFA: immunofluorescence assay; (+): positive test; (-): negative test; U: unfavorable outcome (death); F: favorable outcome (recovery).

The delayed diagnosis of the first patients, which occurred in a geographical area where VL was not previously observed, had a negative impact on the management of the cases. The patients with VL that were studied in Barra Mansa presented with unusual epidemiological and clinical characteristics, when compared to the reports of patients in areas where VL is endemic: 77.8% (7 out of 9 cases) of patients were adults, although the oldest patients recovered after therapy. In addition, the duration of the disease until clinical status worsened was short in 3 of the 4 patients who died. Furthermore, none of the patients were HIV-positive. In 1 case, the patient presented with an atypical clinical picture with severe liver involvement due to VL that resulted in premature death before treatment was initiated. The mortality rate of 44.4% (4 out of 9 cases) in Barra Mansa was much higher than the average VL mortality rate in the State of Rio de Janeiro in the preceding years (7.8% between 2000 and 2009)10.

It has been reported previously that in areas of Brazil where VL is endemic, several factors are associated with death in VL patients: HIV co-infection, other associated infections, bleeding, jaundice, severe anemia, older age, co-morbidities, cardiotoxicity due to treatment, and use of meglumine antimoniate in patients with co-morbidities1115. Some of these factors (bleeding, infection, and co-morbidities) were present in our patients; however, the small number of cases included in this study did not allow for statistical analysis regarding lethality. Importantly, co-morbidities were present in 3 out of the 5 patients who recovered after therapy.

To date, there has been no explanation as to why VL patients in Barra Mansa are older. It is possible that this is related to the fact that Barra Mansa was previously not a VL endemic area, resulting in the lack of previous contact of the older population with the parasite. The Epidemiologic Surveillance Services must remain vigilant in identifying VL infection in older patients in areas where VL was previously not present.

The diagnosis, treatment, and surveillance of cases of VL in Barra Mansa have resulted in the development of necessary control actions, including entomological research, active search for VL infected dogs, and euthanasia of seropositive dogs. In addition, VL is now considered in the differential diagnosis of fever, hepatomegaly, jaundice, and splenomegaly in the municipality of Barra Mansa. Between February 2013 and June 2014, some cases of suspected VL were reported; however, the VL diagnosis was subsequently discarded.

Attention must be given to the neglected disease of VL, as it is important to warn clinicians of the resurgence of VL in the State of Rio de Janeiro. It is necessary for clinicians in new areas where VL has spread to be aware that patients with VL may present with an atypical clinical picture, that the disease may rapidly evolve to a disease of much greater severity, and that co-morbidities and aggravating factors may affect the course of VL. The timely diagnosis of VL will allow for prompt and appropriate treatment to be initiated.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

FINANCIAL SUPPORT

Armando de Oliveira Schubach is the recipient of a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (Bolsista de Produtividade em Pesquisa).

REFERENCES

1. World Health Organization. Control of the leishmaniases: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22-26 March 2010. WHO Technical Report Series 949. Geneva: World Health Organization; 2010. [ Links ]

2. Ministério da Saúde. Brasil. Casos confirmados de Leishmaniose Visceral, Brasil, Grandes Regiões e Unidades Federadas. 1990 a 2011. 2012a. [Ctied 2013 May 21]. Available at: http://portal.saude.gov.br/portal/arquivos/pdf/2012_11_casos_de_lv_entre_1990_e_2011_final.pdf. [ Links ]

3. Marzochi MCA, Marzochi KBF. Tegumentary and visceral leishmaniases in Brazil: emerging anthropozoonosis and possibilities for their control. Cad Saude Publica 1994; 10 (supl 2):359-375. [ Links ]

4. Rangel O, Sampaio SMP, Ciaravolo RMC, Holcman MM. The distribution pattern of Lutzomyia longipalpis (Diptera: Psychodidae) in the peridomiciles of a sector with canine and human visceral leishmaniasis transmission in the municipality of Dracena, São Paulo, Brazil. Mem Inst Oswaldo Cruz 2012: 107:163-169. [ Links ]

5. Oliveira AG, Galati EA, Fernandes CE, Dorval ME, Brazil RP. Ecological aspects of phlebotomines (Diptera: Psychodidae) in endemic area of visceral leishmaniasis, Campo Grande, State of Mato Grosso do Sul, Brazil. J Med Entomol 2012; 49:43-50. [ Links ]

6. Nascimento BWL, Saraiva L, Teixeira Neto RG, Serra e Meira PCL, Sanguinette CC, Tonelli GB, et al. Study of sand flies (Diptera: Psychodidae) in visceral and cutaneous leishmaniasis areas in central western of Minas Gerais state - Brazil. Acta Trop 2013; 125:262-268. [ Links ]

7. Cabrera MA, Paula AA, Camacho LA, Marzochi MC, Xavier SC, Silva AV, et al. Canine visceral leishmaniasis in Barra de Guaratiba, Rio de Janeiro, Brazil: assessment of risk factors. Rev Inst Med Trop São Paulo 2003; 45:79-83. [ Links ]

8. Humberg RM, Oshiro ET, Cruz MS, Ribolla PE, Alonso DP, Ferreira AM, et al. Leishmania chagasi in opossums (Didelphis albiventris) in an urban area endemic for visceral leishmaniasis, Campo Grande, Mato Grosso do Sul, Brazil. Am J Trop Med Hyg 2012; 87:470-472. [ Links ]

9. Ministério da Saúde. Brasil. Manual de Vigilância e Controle da Leishmaniose Visceral. [Cited 2013 September 7]. Available at: http://10.1.1.213/portal/arquivos/pdf/manual_leish_visceral2006.pdf. [ Links ]

10. Ministério da Saúde. Brasil. Letalidade de Leishmaniose Visceral, Brasil, Grandes Regiões e Unidades Federadas. 2000 a 2011. 2012b. [Cited 2013 September 7]. Avaiable at: http://portal.saude.gov.br/portal/arquivos/pdf/2012_11_letalidade_por_lv_entre_1990_e_2011.pdf/ [ Links ]

11. Oliveira JM, Fernandes AC, Dorval MEC, Alves ML, Fernandes TD, Oshiro ET, et al. Mortalidade por leishmaniose visceral: aspectos clínicos e laboratoriais. Rev Soc Bras Med Trop 2010; 43:188-193. [ Links ]

12. Alvarenga DG, Escalda PMF, Costa ASV, Monreal MTFD. Leishmaniose visceral: estudo retrospectivo de fatores associados à letalidade. Rev Soc Bras Med Trop 2010; 43:194-197. [ Links ]

13. Brazuna JCM, Silva EA, Brazuna JM, Domingos IH, Chaves N, Honer MR, et al. Profile and geographic distribution of reported cases of visceral leishmaniasis in Campo Grande, State of Mato Grosso do Sul, Brazil, from 2002 to 2009. Rev Soc Bras Med Trop 2012; 45:601-606. [ Links ]

14. Araujo VEM, Morais MHF, Reis IA, Rabello A, Carneiro M. Early clinical manifestations associated with death from visceral leishmaniasis. PloS Negl Trop Dis 2012; 6:e1511. [ Links ]

15. Madalosso G, Fortaleza CM, Ribeiro AF, Cruz LL, Nogueira PA, Lindoso JAL. American visceral leishmaniasis: factors associated with lethality in the state of São Paulo, Brazil. J Trop Med 2012; article ID 821572. [ Links ]

Received: October 31, 2013; Accepted: January 22, 2014

Address to: Dra Maria Inês Fernandes Pimentel. INI/FIOCRUZ. Av. Brasil 4365, Manguinhos, 21040-360 Rio de Janeiro, RJ, Brasil. Phone/Fax: 55 21 3865-9541. e-mail: maria.pimentel@ini.fiocruz.br

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.