Are HCT Patients in Brazil at Increased Risk of Zika and Other Mosquito-Transmitted Infections?

Since 2015, Brazil has experienced a triple epidemic of dengue, chikungunya, and Zika infections, putting the more than 2,000 hematopoietic cell transplantation (HCT) recipients in the country at risk of contracting these mosquito-transmitted infections.

In a prospective study published in Blood Advances, Clarisse Martins Machado, MD, PhD, from the virology laboratory at the Institute of Tropical Medicine at the University of São Paulo in Brazil, and co-authors assessed the prevalence, morbidity, and mortality of dengue, chikungunya, and Zika infections in symptomatic recipients of HCT and patients with malignant blood disorders.

Based on their findings, “diagnostic tests for dengue, Zika, and chikungunya infections should be added to the laboratory portfolio for the differential diagnosis of febrile transplant recipients living in endemic countries,” the authors wrote, as well as in those returning from regions with known circulation of such mosquito-transmitted viruses, also known as arboviruses.

Using a case-definition approach, researchers identified HCT recipients with suspected arboviruses. A suspected case was defined as (a) presence of fever and exanthema or (b) fever or exanthema plus one of the following: thrombocytopenia, myalgia, arthralgia, conjunctivitis, retro-orbital pain, headache, nausea, or vomiting. The investigators then confirmed a diagnosis of dengue, chikungunya, or Zika virus through real-time polymerase chain reaction in plasma and urine samples.

Between February and May 2016, researchers identified 26 patients with suspected arboviral infection based on these requirements for a “suspected case”: 19 were HCT recipients (median age = 37 years; range not provided) and seven had hematologic disorders (median age = 15 years; range not provided). Nine of those patients (3 with hematologic malignancy) had a confirmed diagnosis of arboviral infection (34.6%):

  • dengue (n=3; 11.5%)
  • chikungunya (n=2; 7.7%)
  • Zika (n=4; 15.4%)

“Fever and exanthema are good markers of arbovirus infection, as laboratory-confirmed cases were found in [approximately] 35 percent of included patients,” the authors noted. However, the similarity of symptoms between patients with and without arboviral infection should yield “a high index of suspicion” in patients with those symptoms.

“It is important to highlight that symptoms are similar in dengue, Zika, and Chikungunya infections, and diagnostic tests are mandatory to determine the agent,” Dr. Machado told ASH Clinical News. “We still do not know what the long-term consequences of Zika and chikungunya may be, and prompt diagnostic investigation in suspect cases is important.”

For example, thrombocytopenia was the most frequent symptom in infected patients, occurring in 55.5 percent, but it also occurred in 37.5 percent of non-infected patients (p=0.67). See TABLE for all reported symptoms.

Morbidity in HCT and hematologic malignancy patients with chikungunya or Zika virus was “likely similar to the immunocompetent population,” the authors reported, with more severe cases having thrombocytopenia (<20,000/mm3), all of which occurred with dengue virus infection. One patient had intestinal bleeding and another had extreme weight loss and persistent viremia (>1 month). Though “thrombocytopenia was a well-characterized dengue virus event,” it was not as evident in patients with chikungunya or Zika infection.

Only patients with dengue or Zika virus had prolonged viremia or viruria (lasting ≥7 days after symptom onset). Zika viremia was persistent for at least 7 days in one patient with a hematologic malignancy. The authors noted that the patient also had delayed neutrophil engraftment (27 days). Overall, they added, “viruria lasted longer and should be the preferred sample for diagnosing Zika virus in suspected cases.”

The study is limited by its small patient population and the non-systematic way in which patients were identified. “To evaluate the real incidence of arboviral infections, regular sampling should be done irrespective of the presence of symptoms during epidemics,” Dr. Machado said. “Some arboviral complications may have been unrecognized, and consequently underestimated in the study.”

The authors report no relevant conflicts of interest.


Reference

Machado CM, de Souza Pereira BB, Felix AC, et al. Zika and chikungunya virus infections in hematopoietic stem cell transplant recipients and oncohematological patients. Blood Adv. 2017;1:624-7.

TABLE. Frequency of Symptoms in Patients With and Without Arboviral Infection
Frequency
Symptom

Arboviral Infection

(n=9)

No Arboviral Infection

(n=16)*

p Value

Fever

8 (88.8%)

11 (68.7%)

0.36

Exanthema

6 (66.6%)

12 (75%)

0.67

Headache

5 (55.5%)

6 (37.5%)

0.43

Myalgia

5 (55.5%)

8 (50%)

1.0

Thrombocytopenia

5 (55.5%)

6 (37.5%) 0.67

Nausea

4 (44.4%) 6 (37.5%)

1.0

Arthralgia

4 (44.4%)

5 (31.2%)

0.67

Somnolence

3 (33.3%)

1 (6.25%)

0.11

Diarrhea

2 (22.2%)

2 (12.5%)

0.60

Vomiting

2 (22.2%)

2 (12.5%)

0.60

Abdominal pain

1 (11.1%)

3 (18.7%)

1.0

Conjunctivitis

1 (11.1%)

1 (6.25%)

1.0

Bleeding

1 (11.1%)

3 (18.7%)

1.0

Agitation

0

2 (12.5%)

0.52

*Not all clinical data were available in one case.

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