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Fatal sickle cell disease and Zika virus infection in girl from Colombia.

To the Editor: Zika virus, a mosquito-borne flavivirus, causes a usually self-limiting febrile and exanthematic arthralgia syndrome that resembles dengue and chikungunya (1). This arboviral disease has emerged in tropical areas of Latin America, particularly in Brazil and Colombia (2), as a public health threat in 2015 and has spread into areas to which dengue virus (DENV) and chikungunya virus (CHIKV) are endemic (1-4).

Cases of severe and fatal Zika virus infection have not been described (5), and the spectrum of clinical disease remains uncertain in the setting of rapidly evolving epidemics of this arbovirus in Latin America (1). We report a person with sickle cell disease who acquired a Zika virus infection and died.

The patient was a 15-year-old girl who in October 2015 came to the outpatient clinic of the Hospital of Malambo (a primary-level public hospital) in Malambo (Atlantico Department) in northern Colombia. In this region, during September 22, 2015-January 2, 2016, a total of 468 suspected cases of Zika virus infection and 4 reverse transcription PCR (RT-PCR)-confirmed cases have been reported. This patient had a high fever (temperature >40[degrees]C), arthralgias, retro-ocular pain, abdominal pain, myalgias, and jaundice for the previous 4 days. She had sickle cell disease for 5 years (hemoglobin genotype SC identified by DNA analysis), but no previous hospitalizations or episodes of vaso-occlusive crises. She had never had dengue, chikungunya, or acute chest syndrome.

At admission to the hospital, the patient had a pulse rate of 112 beats/min, a respiratory rate of 24 breaths/min, a blood pressure of 110/70 mm Hg, and a temperature of 39.0[degrees]C. She had abdominal pain, no petechiae, and no lymphadenopathy. The patient was given acetaminophen. Results of a neurologic assessment were unremarkable. Clinical laboratory findings are shown in the Table.

Given these manifestations, she was given a diagnosis of a DENV infection and referred to Barranquilla Hospital Metropolitano (Barranquilla, Colombia) where she was admitted 1 day later. Physical examination showed a pulse rate of 122 beats/min, a respiratory rate of 34/min (peripheral capillary oxygen saturation 93%), a blood pressure of 112/58 mm, and a temperature of 37.5[degrees]C. She had generalized jaundice, respiratory distress, severe abdominal pain, hepatomegaly, and splenomegaly, but no lymphadenopathy. The patient was conscious (stuporous) and had a Glasgow Coma Scale score of 13. Cardiovascular assessment showed tachycardia and a holosystolic murmur (grade II) but no other findings.

The patient was then transferred to the pediatric intensive care unit, where she was intubated and mechanical ventilation was initiated. Her condition was considered life threatening; the patient had severe acute respiratory distress syndrome and progressive hypoxemia despite ventilator treatment, and laboratory findings worsened (Table).

The patient was given transfusions of blood products for treatment of anemia and thrombocytopenia. Chest radiograph and ultrasound showed an extensive right-side hemothorax. The result of a Zika virus-specific real-time RT-PCR was positive (Table). Her clinical condition deteriorated. Despite intensive treatment, the patient did not recover and died 37 hours later. An autopsy showed hepatic panacinar necrosis, erythrophagocytosis of Kupffer cells, and severe decrease of splenic lymphoid tissue (functional asplenia) with multiple drepanocytes and splenic sequestration, but no signs of yellow fever or malaria (online Technical Appendix Figure, http://wwwnc.cdc.gov/EID/article/22/5/15-1934-Techapp1.pdf).

Although sickle cell disorders are not common in Colombia, their frequency is higher along the Caribbean coast (including Atlantico Department) and 2 times that of the rest of Colombia) (6). Although chronic diseases, such as sickle cell disorders, are considered to be a risk factor for development of severe dengue and chikungunya (7,8), no cases have been reported in association with Zika. Reports of patients co-infected with DENV and CHIKV are rare, few details are available, and mostly restricted to few fatal cases of dengue (9). In patients with dengue, deaths might be higher among those who have a hemoglobin SC genotype, as recently reported (10). Onset of vaso-occlusion in persons with sickle cell disorders is often triggered by inflammation, as has been reported in DENV infections and which probably occurred in our patient (8). This complication and severe splenic sequestration, detected by autopsy, probably caused her death.

In summary, this case indicates that patients with sickle cell disorders and suspected arboviral infections should be closely monitored. Given current epidemics of Zika virus infection in Colombia (746 RT-PCR-confirmed cases and 11,712 suspected cases during September 22, 2015-January 2, 2016), atypical and severe manifestations and concurrent conditions in patients should be assessed to prevent additional deaths (2).

References

(1.) Rodriguez-Morales AJ. Zika: the new arbovirus threat for Latin America. J Infect Dev Ctries. 2015;9:684-5. http://dx.doi.org/10.3855/jidc.7230

(2.) Pan American Health Organization. Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas--epidemiological alert 2015 [cited 2016 Jan 1]. http://www.paho.org/hq/index.php?option=com_docman&task=doc_download&Itemid=&gid=32405&lang=en

(3.) Alfaro-Toloza P, Clouet-Huerta DE, Rodriguez-Morales AJ. Chikungunya, the emerging migratory rheumatism. Lancet Infect Dis. 2015;15:510-2. http://dx.doi.org/10.1016/S1473-3099(15)70160-X

(4.) Campos GS, Bandeira AC, Sardi SI. Zika Virus Outbreak, Bahia, Brazil. Emerg Infect Dis. 2015;21:1885-6. http://dx.doi.org/ 10.3201/eid2110.150847

(5.) Kwong JC, Druce JD, Leder K. Zika virus infection acquired during brief travel to Indonesia. Am J Trop Med Hyg. 2013; 89:516-7. http://dx.doi.org/10.4269/ajtmh.13-0029

(6.) Fong C, Lizarralde-Iragorri MA, Rojas-Gallardo D, Barreto G. Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia. Genet Mol Biol. 2013;36:494-7. http://dx.doi.org/10.1590/S1415-47572013000400005

(7.) Economopoulou A, Dominguez M, Helynck B, Sissoko D, Wichmann O, Quenel P, et al. Atypical chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Reunion. Epidemiol Infect. 2009;137:534-41. http://dx.doi.org/10.1017/S0950268808001167

(8.) Moesker FM, Muskiet FD, Koeijers JJ, Fraaij PL, Gerstenbluth I, van Gorp EC, et al. Fatal dengue in patients with sickle cell disease or sickle cell anemia in Curacao: two case reports. PLoS Negl Trop Dis. 2013;7:e2203. http://dx.doi.org/10.1371/journal.pntd.0002203

(9.) Bravo JR, Guzman MG, Kouri GP. Why dengue haemorrhagic fever in Cuba? 1. Individual risk factors for dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Trans R Soc Trop Med Hyg. 1987;81:816-20. http://dx.doi.org/10.1016/0035-9203(87)90041-1

(10.) Rankine-Mullings A, Reid ME, Moo Sang M, Richards-Dawson MA, Knight-Madden JM. A retrospective analysis of the significance of haemoglobin SS and SC in disease outcome in patients with sickle cell disease and dengue fever. EBioMedicine. 2015;2:935-9. http://dx.doi.org/10.1016/j.ebiom.2015.07.002

Address for correspondence: Alfonso J. Rodriguez-Morales, Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnologica de Pereira, Pereira, Risaralda, Colombia; email: arodriguezm@utp.edu.co

Author affiliations: Entidades Promotoras de Salud Barrios Unido Mutual, Quibdo, Colombia (L. Arzuza-Ortega); Empresa Social del Estado Hospital de Malambo, Malambo, Colombia (A. Polo); Hospital Metropolitano, Barranquilla, Colombia (G. Perez-Tatis, H. Lopez-Garcia); Instituto Nacional de Salud, Bogota, Colombia (E. Parra, L.C. Pardo-Herrera, A.M. Rico-Turca); Hospital Universitario de Sincelejo, Sincelejo, Colombia, (W. Villamil-Gomez); Universidad del Atlantico, Barranquilla (W. Villamil-Gomez); Universidad de Cartagena, Cartagena, Colombia (W. Villamil-Gomez); Universidad Tecnologica de Pereira, Pereira, Colombia (A.J. Rodriguez-Morales)

DOI: http://dx.doi.org/10.3201/eid2205.151934
Table. Clinical laboratory results for 15-year-old girl
with sickle cell disease who died of Zika virus infection,
Colombia *

                                                        Value at
                                          Baseline   hospitalization
Laboratory test                            value        (Malambo)

Leukocyte count, x [10.sup.9] cells/L      10.00          8.23
Hemoglobin level, g/dL                      7.00          8.10
Hematocrit, %                              28.00          25.00
MCV, fL/erythrocyte                        73.00          73.00
Reticulocytes, %                            1.00          1.00
Total bilirubin, mg/dL                       ND           2.97
Direct bilirubin, mg/dL                      ND           1.67
Platelet count/mL                            ND         54,000.00

PT, s                                        ND            ND
aPTT, s                                      ND            ND
ALT, mg/dL                                   ND            ND
AST, mg/dL                                   ND            ND
LDH, IU/L                                    ND            ND

Alkaline hemoglobin electrophoresis, %
  HbS                                        ND            ND
  HbC-E                                      ND            ND
  HbF                                        ND            ND

Malaria thick and thin                    Not done      Not done
blood smears ([dagger])
HIV-1 and HIV-2 ELISA ([dagger])          Not done      Not done
MAT for Leptospira spp. ([dagger])        Not done      Not done

RT-PCR for DENV ([dagger])                Not done      Not done
RT-PCR for CHIKV ([dagger])               Not done      Not done
RT-PCR for YFV ([dagger])                 Not done      Not done
RT-PCR for ZIKV ([dagger])                Not done      Not done

                                            Value 24 h later
Laboratory test                           (ICU, Barranquilla)

Leukocyte count, x [10.sup.9] cells/L              ND
Hemoglobin level, g/dL                            4.20
Hematocrit, %                                    13.00
MCV, fL/erythrocyte                                ND
Reticulocytes, %                                   ND
Total bilirubin, mg/dL                             ND
Direct bilirubin, mg/dL                            ND
Platelet count/mL                              76,000.00

PT, s                                     33.3 (control 13.10)
aPTT, s                                   45.0 (control 29.80)
ALT, mg/dL                                      2,245.00
AST, mg/dL                                      3,215.00
LDH, IU/L                                        441.00

Alkaline hemoglobin electrophoresis, %
  HbS                                            62.50
  HbC-E                                          37.50
  HbF                                             0.00

Malaria thick and thin                             -
blood smears ([dagger])
HIV-1 and HIV-2 ELISA ([dagger])                   -
MAT for Leptospira spp. ([dagger])                 -

RT-PCR for DENV ([dagger])                         -
RT-PCR for CHIKV ([dagger])                        -
RT-PCR for YFV ([dagger])                          -
RT-PCR for ZIKV ([dagger])                         +

* ICU, intensive care unit; ND, not determined;
MCV, mean corpuscular volume; PT, prothrombin time;
aPTT, activated partial thromboplastin time; ALT,
alanine aminotransferase; AST, aspartate
aminotransferase; LDH, lactate dehydrogenase;
Hb, hemoglobin; -, negative; MAT; microscopic
agglutination test; RT-PCR, reverse transcription PCR;
DENV, dengue virus; CHIKV, chikungunya virus;
YFV, yellow fever virus; ZIKV, Zika virus; +, positive.

([dagger]) Blood samples were obtained 5 days after
illness onset. These tests were performed at the
National Reference Laboratory of the National
Institute of Health, Bogota, Colombia.
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Article Details
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Title Annotation:LETTERS
Author:Arzuza-Ortega, Laura; Polo, Arnulfo; Perez-Tatis, Giamina; Lopez-Garcia, Humberto; Parra, Edgar; Par
Publication:Emerging Infectious Diseases
Article Type:Letter to the editor
Geographic Code:3COLO
Date:May 1, 2016
Words:1649
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