Hantavirus Pulmonary Syndrome in Five Pediatric Patients --- Four States, 2009

Hantavirus pulmonary syndrome (HPS) is a reportable infectious disease with a high case-fatality rate, transmitted to humans by exposure to rodents. Each year, 20--40 cases of HPS occur in the United States; cases in persons aged <17 years make up fewer than 7% of those cases, and cases in children aged <10 years are exceptionally rare. CDC received reports of five pediatric cases of HPS occurring during May 16--November 25, 2009, among children aged 6--14 years from Arizona, California, Colorado, and Washington. Three of the children were aged <10 years, and all five had exposure to rodents. This report summarizes the five cases, including the clinical findings and likely means of transmission of a hantavirus. Thrombocytopenia, elevated white blood cell (WBC) count, and pulmonary infiltrates were observed in all five children; elevated hematocrit was observed in three. One child died, and three of the four children who recovered required mechanical ventilation during hospitalization. Clinicians should consider HPS in the differential diagnosis for children with unexplained acute respiratory distress, especially if recent rodent exposure is noted. Public health agencies should promote preventive measures, including rodent control in housing and play areas, and children should be advised to avoid contact with rodents and areas of infestation.

Case 1

On May 16, a boy aged 6 years who lived in Colorado went to a Texas hospital with a 2-day history of diarrhea and shortness of breath. On initial examination, the child had cyanotic lips and nail beds, with cold extremities. His pulse was 163, and his temperature was 101°F (38.3°C). Soon after arrival at the hospital, the child became apneic and had no palpable pulse. Chest compressions were initiated, and the child was intubated and ventilated. A chest radiograph revealed bilateral infiltrates, and blood analysis demonstrated elevated hematocrit, elevated WBC count, and thrombocytopenia (Table). Within 2 hours of admission to the hospital, the boy died from apparent cardiac failure secondary to shock. The child had been treated with intravenous fluids, ceftriaxone, epinephrine, atropine, and albuterol. The working diagnosis at the time of the child's death was shock and sepsis caused by pneumonia.

An enzyme-linked immunosorbant assay (ELISA) performed by the Colorado Department of Public Health and Environment revealed Sin Nombre hantavirus--specific serum immunoglobulin M (IgM). An environmental assessment conducted at the boy's home in Colorado found rodent droppings and nesting materials under his bed and in bushes in front of the home where the boy had played.

Case 2

On June 7, an adolescent boy aged 14 years went to a Washington emergency department with a 5-day history of shortness of breath, chest pain, cough, and fever. Upon admission, the child had a fever of 103°F (39.4°C), pulse of 100, and a respiratory rate varying between 40 and 60. He was thrombocytopenic and had elevated WBC with atypical lymphocytosis (Table). A chest radiograph revealed bilateral interstitial infiltrates. No details were provided regarding treatment or any suspicion of HPS.

Because of worsening respiratory distress and hypoxia, the patient was intubated and mechanically ventilated for approximately 24 hours. He improved and was discharged home on June 13. An ELISA of serum detected Sin Nombre hantavirus--specific IgM at the Washington State Public Health Laboratories. A follow-up environmental assessment found rodent fecal contamination in a container of corn that the youth reported hand-grinding 8 days before illness onset.

Case 3

On July 12, a boy aged 6 years went to a Colorado emergency department with a 5-day history of fever (maximum 103°F [39.4°C]), erythematous facial rash, and myalgia. Upon admission the boy's pulse was 120, respiratory rate 48, and oxygen saturation 72% on room air. Dyspnea was apparent with coarse breath sounds, wheezes, and crackles on auscultation. His WBC count was elevated, and thrombocytopenia was noted (Table). A chest radiograph revealed bilateral diffuse pulmonary infiltrates with pleural effusions. HPS was suspected, and the boy was treated with intravenous fluids, ceftriaxone, and azithromycin.

The boy was intubated and mechanically ventilated from July 12 to July 20; he was discharged on July 22. Serum ELISA performed by the Colorado Department of Public Health and Environment revealed positive Sin Nombre hantavirus IgM. Family members reported that approximately 10 days before hospitalization the child was bitten on the finger by a mouse. During environmental assessment, evidence of rodent infestation was observed in outbuildings and abandoned vehicles but not within the house.

Case 4

On July 12, a girl aged 9 years living in Arizona went to a New Mexico hospital with chest pain and shortness of breath. Symptoms began with abdominal discomfort on July 6, which was followed by headache, vomiting, and myalgia. Upon examination, the girl's temperature was 99.9°F (37.7°C), and her pulse was 162. Laboratory findings included thrombocytopenia, elevated hematocrit, and elevated WBC count (Table). A chest radiograph revealed diffuse interstitial infiltrates. During transport to a tertiary care facility for further treatment, the child's temperature reached 103.8°F (39.9°C). HPS was suspected, and the girl was treated with intravenous fluids, ceftriaxone, and vancomycin.

Because of worsening signs of pulmonary distress, the girl was intubated and received extracorporeal membrane oxygenation therapy for 4 days. She remained on a ventilator until July 22 and was hospitalized until August 5. Serum tested with a commercial immunoblot assay revealed Sin Nombre hantavirus immunoglobulin G (IgG). Evidence of rodents was found at three residences frequented by the girl in Arizona: the family home, grandparents' home, and a summer home where she played in an underground dugout that had rodent burrows.

Case 5

On November 25, an adolescent boy aged 13 years went to a California emergency department with a 5-day history of fever (maximum 102.6°F [39.2°C]), cough, posttussive vomiting, diarrhea, and abdominal pain. Physical examination revealed a tender chest, with crackles and diminished breath sounds in the lower lobes of the lungs, and a respiratory rate of 30. Laboratory findings included elevated WBC, elevated hematocrit, and thrombocytopenia (Table). Chest radiographs revealed diffuse interstitial opacities with pleural effusion. Treatment included intravenous fluids, ceftriaxone, clindamycin, and azithromycin. The patient received supplemental oxygen by nasal cannula and was discharged home on December 3.

Testing for hantavirus was requested on day 4 of hospitalization. Serum was submitted to a commercial diagnostic laboratory, and Sin Nombre hantavirus IgM and IgG antibodies were detected by immunoblot assay. Extensive remodeling was under way in the youth's home at the time of illness, including removal and replacement of floors and walls. Three mice were trapped in the youth's kitchen and garage approximately 3 months before disease onset, but the patient had no known direct or indirect contact with the rodents.

Reported by: C Levy, MS, Arizona Dept of Health Svcs. K Gains, MS, Southeast Land and Environment, Prowers County; V Crocco, Chaffee County Environmental Health Dept; J Brown, MSN, Prowers County Nursing Svc; E Lawaczeck, DVM, W Ray, M Miller, MS, M Klaber, MS, A Doussette, MS, Colorado Dept of Public Health and Environment. C Ralston, Benton-Franklin Health District; N Marsden-Haug, MPH, Washington State Dept of Health. C Fritz, DVM, California Dept of Public Health. C Watson, MSN, Nevada County Public Health Dept. A MacNeil, PhD, J Mills, PhD, PE Rollin, MD, S Nichol, PhD, Special Pathogens Bur, Div of Viral and Rickettsial Diseases, National Center for Zoonotic Vector-Borne, and Enteric Diseases; B Knust, DVM, EIS Officer, CDC.

Editorial Note:

HPS was first described in 1993 and has been a nationally notifiable disease* since 1995. As of December 18, 2009, a total of 537 cases of HPS had been reported to CDC, with a case-fatality rate of 36%. Of all confirmed cases, <7% have occurred in children aged <17 years, and only four cases have occurred in children aged <10 years, including the two children aged 6 years and one child aged 9 years described in this report (the fourth case was in a child aged 8 years). Although reports of HPS in persons aged <17 years are uncommon, the clinical illnesses of the pediatric patients in this report were similar to those observed in adults. HPS typically has a 2--10 day prodrome with nonspecific viral symptoms, and the acute respiratory phase often commences abruptly (2). In all five cases summarized in this report, the children had illnesses for 2--6 days preceding onset of acute respiratory symptoms. Thrombocytopenia and elevated WBC count were observed in all five cases, and three children had elevated hematocrit; these hematologic signs are comparable to those typical of HPS in adult patients (3,4). A previous review of 12 pediatric HPS cases in New Mexico found thrombocytopenia in 100% and elevated WBC count and hemoconcentration in 27% of cases (5).

Children infected with hantavirus can develop severe illness, similar to adults. Antivirals have not been shown to be effective in the treatment of HPS (6); therefore, medical interventions consist primarily of supportive care. Respiratory distress requiring mechanical ventilation was observed in four of the cases described in this report, similar to trends observed nationally (4). In case 1, the child died from apparent cardiac failure secondary to shock. Although cardiac functioning tests could not be obtained, abnormally low cardiac index and stroke volume with increased vascular resistance has been reported previously in HPS cases and is considered to be an important cause of death in persons with HPS (7). In case 4, the patient received extracorporeal membrane oxygenation therapy, which might be of benefit to HPS patients who require both oxygenation and circulatory support (8).

Hantaviruses are transmitted from rodent hosts to humans through inhalation of infectious aerosols of rodent excreta or direct inoculation into broken skin. In North America, Sin Nombre virus is the most common cause of HPS, and its reservoir is the deer mouse (Peromyscus maniculatus). The largest number of HPS illnesses has occurred in the southwestern United States, although cases have been reported in 31 states. Several rodent species distributed throughout the United States have been identified as reservoirs for hantaviruses, many of which have been associated with HPS. All the patients in this report had evidence of rodents in and around their homes, including places where the patients in cases 1 and 4 played. The patient in case 2 likely was exposed by hand-grinding contaminated corn; the patient in case 5 might have been exposed to rodent-contaminated areas or a virus-containing aerosol during remodeling of his home. The likely means of hantavirus transmission to the patient in case 3 was a mouse bite, reported previously in two pediatric cases (9). No evidence exists of person-to-person hantavirus transmission in the United States.

Current CDC recommendations to reduce the risk for hantavirus infection include trapping and excluding rodents and using personal protective equipment when handling potentially infected rodents or disturbing areas of rodent infestation. Recommended cleaning agents include household disinfectant or bleach solution (10). Rodent control activities should include outbuildings and places where children play. Educational efforts aimed at parents and children, including how to recognize the signs of rodent infestation and take proper precautions, are recommended. Although the reasons for the infrequent occurrence of HPS in children remain unknown, the cases in this report serve as a reminder that children are susceptible to hantavirus infection. More information is available from CDC at http://www.cdc.gov/ncidod/diseases/hanta/hps/index.htm.

References

1. Nationally notifiable conditions. Annual lists of infectious conditions. Available at: http://www.cdc.gov/ncphi/disss/nndss/phs/infdis.htm. Accessed December 21, 2009.
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3. Koster F, Foucar K, Hjelle B, et al. Rapid presumptive diagnosis of hantavirus cardiopulmonary syndrome by peripheral blood smear review. Am J Clin Pathol 2001;116:665--72.
4. Khan AS, Khabbaz RF, Armstrong LR, et al. Hantavirus pulmonary syndrome: the first 100 US cases. J Infect Dis 1996;173:1297--303.
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6. Mertz GJ, Miedzinski L, Goade D. Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America. Clin Infect Dis 2004;39:1307--13.
7. Hallin GW, Simpson SQ, Crowell RE, et al. Cardiopulmonary manifestations of hantavirus pulmonary syndrome. Crit Care Med 1996;24:252--8.
8. Dietl CA, Wernle JA, Pett SB, et al. Extracorporeal membrane oxygenation support improves survival of patients with severe hantavirus cardiopulmonary syndrome. J Thorac Cardiovasc Surg 2008;135:579--84.
9. St Jeor S. Three-week incubation period for hantavirus infection. Pediatr Infect Dis J 2004;23:974--5.
10. CDC. Hantavirus pulmonary syndrome---United States: updated recommendations for risk reduction. MMWR 2002;51(No. RR-9).

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Date last reviewed: 12/23/2009