Catastrophic presentation of Hantavirus infection… : Journal of Pediatric Critical Care

INTRODUCTION

Hanta hemorrhagic fever is a rodent-borne hemorrhagic fever which may present as hanta virus cardiopulmonary syndrome (HCPS) or hanta virus renal syndrome (HRS). It has a negative-sense single-stranded RNA genome. Infection occurs when humans encounter infected aerosolized saliva or excreta from infected rodents. While Europe and Asia have largely reported hantavirus renal syndrome,^[1] the Americas have reported cases of cardiopulmonary syndrome. Hanta virus infection in children has rarely been reported from our country. We present a child with severe cardiorespiratory with acute kidney injury due to hantavirus infection.

CASE REPORT

A 12-year-old previously healthy male child presented with fever, multiple episodes of vomiting for 2 days, progressive breathing difficulty, and 1 episode of hematemesis on the day of admission. The family lived in a single room in a slum area, and there was a history of recent flooding during the monsoon season with child playing in accumulated rainwater.

On admission, he was agitated with a respiratory rate of 44/min, with bilateral crepts and saturation of 88% on nonrebreathing mask at 15 L/min oxygen. He had a heart rate of 130/min with cold peripheries and weak peripheral pulses, and blood pressure 85/60 mmHg. He was in hypoxemic respiratory failure needing intubation on day 1. He received a fluid bolus (10 ml/kg) followed by an adrenaline infusion for his hypotensive shock.

The child had copious frothy fresh blood from the endotracheal tube suggestive of pulmonary hemorrhage, needing high positive end expiratory pressure (maximum 16), sedation, and paralysis. His chest X-ray showed bilateral fluffy opacities [Figure 1]. His initial oxygenation index (oxygenation Index) on day 1 was 10, which progressively worsened. Patients had anemia and thrombocytopenia (platelet count 90,000) with polymorphonuclear predominance, with a normal reticulocyte count, acanthocytes, and reduced platelets seen on peripheral smear. He had deranged renal functions (BUN 91 mg/dl, creatinine 2 mg/dl) with normal liver function tests (serum glutamic-oxaloacetic transaminase 37 U/L, serum glutamic pyruvic transaminase 10 U/L, INR 1.1, S. albumin 3 g/dl). He had high C-reactive protein (90 mg/dl) and procalcitonin (2 g/l) with negative blood culture. Two-dimensional echo was suggestive of marked systolic dysfunction with a left atrial left ventricular dilatation, moderate mitral regurgitation, trivial aortic regurgitation, and trivial tricuspid regurgitation. His Dengue, Leptospirosis and malaria workup was negative. Autoimmune workup was negative.

For worsening kidney injury [Table 1] and anuric status of the patient, peritoneal dialysis was started. Patient continued to have a dropped platelet count (lowest 10,000 cells/μl) [Figure 2] with INR 1.6. He again developed a massive pulmonary bleed on day 4 and was supported with multiple blood product transfusions of platelets, packed red blood cells, and fresh frozen plasma. He had worsening of oxygenation status with worst OI of 41 and PF of 59 [Figure 3], needing high-frequency oscillation ventilation.

On further investigation, hantavirus immunoglobulin M (IgM) and IgG were significantly positive (>15 U/ml) by enzyme immunoassay (EIA) (Focus technology, Cypress, CA, USA) from a private laboratory, clinching the diagnosis of HFRS coexisting with HCPS.

Despite all supportive care, he worsened and succumbed on pediatric intensive care unit day 5.

DISCUSSION

It was previously believed that hantavirus infection in Asia and Europe presents with predominantly kidney involvement or HRS. However, recent reports similar to ours have reported cases of HRS with lung involvement and pulmonary hemorrhage.^[2,3]

Cases of hanta virus infection in India have been sporadically described from Chennai, Cochin, Vellore, and Mumbai.^[2,4-7]

The differential diagnoses include dengue, malaria, scrub typhus and Leptospirosis. Leptospirosis presents in the monsoon season with pulmonary hemorrhage and/or renal failure and was a close differential in our case. It is possible that such cases are being missed in our country. Similarly, coinfection of Hantavirus infection with other tropical infections, such as tuberculosis, may be missed.^[6] There is currently no effective vaccine or definitive treatment. Treatment is supportive. Prevention of exposure to rodents reduces the risk of infection.

Pathogenesis is likely related to the direct effect of the virus as well as the immune response of the host. Virus multiplication in endothelial cells has been associated with increased secretion of vascular endothelial growth factor and decreased vascular endothelial cadherin leading to increased capillary permeability.^[8]

In addition, hantaviral infection has been shown to lead to the production of chemokines such as β1 integrin, intercellular Adhesion molecule in endothelial cells and platelets, which can lead to platelet activation and adhesion and leaky capillaries. In vitro studies also suggest a role of inflammatory cytokines and T lymphocytes.^[9]

The incubation period is 2–4 weeks. HFRS has 5 phases: febrile (3–7 days), hypotensive with hemorrhage and thrombocytopenia (few hours – 2 days). Oliguric phase (3–7 days), polyureic phase and convalescent phase (as long as 6 months). The hypotensive phase is characterized by pulmonary capillary leak, with cardiac dysfunction in severe cases.^[10]

Hantavirus infection in children is uncommon, with children comprising [11-13] A systemic review identifying poor prognostic factors from 25 studies on 7,284 patients found that hematocrit, bleeding and infiltrates on chest X-ray were associated with mortality.^[14]

Serological diagnosis is by detection of anti-Hantavirus IgM and IgG antibody; IgM is seen early in the course of the disease, whereas Ig G appears late. Methods include EIA, enzyme-linked immunosorbent assay (ELISA) or immunofluorescence assay (IFA), polymerase chain reaction (PCR), focus reduction neutralization test (FRNT), and immunoblot assay (IBA). EIA, ELISA and IBA have been shown to have higher sensitivity, whereas IFA assays have lower specificity.^[10] Diagnosis can also be made by RT PCR during the viraemic phase. Cost and availability of testing for Hantavirus is a major limiting factor. Treatment is supportive, and there is currently no definitive cure.

In conclusion, hantavirus infection, although uncommon in children, should be considered in cases of hemorrhagic fever with renal and pulmonary involvement. Early recognition is critical, as overlapping renal and pulmonary pathology can rapidly progress to fatal outcomes.

Keywords:

Hanta cardiopulmonary syndrome; hantavirus renal syndrome; hantavirus; pulmonary hemorrhage