1. TWO CLUSTERS OF HANTAVIRUS INFECTION IN TEXAS Diseases in Nature Transmissible to Man June 12, 2007 JL Alexander, TDSHS, Zoonosis Control Division MN Rivers, Texas Tech University Health Sciences Center, Amarillo RE Rohde, Clinical Laboratory Science, Texas State University JR Pierce Jr, Amarillo Bi-City-County Health District & Texas Tech University Health Sciences Center, Amarillo

2. Outline General review of hantavirus Report of two clusters in Texas Review of Texas data Implications of this report

3. Chronically infected rodent Virus is present in aerosolized excreta, particularly urine Horizontal transmission of infection by intraspecific aggressive behavior Virus also present in throat swab and feces Secondary aerosols, mucous membrane contact, and skin breaches are also sources of infection Transmission of Hantaviruses

4. Peromyscus maniculatus Deer mouse Sigmodon hispidus Cotton rat

5. Subfamily Sigmodontinae associated viruses Virus HostLocation Sin nombrePeromyscus maniculatus West & Central U.S. & Canada U.S. & Canada Monongahela Peromyscus maniculatus Eastern U.S. & Monongahela Peromyscus maniculatus Eastern U.S. &Canada New YorkPeromyscus leucopus Eastern U.S. New YorkPeromyscus leucopus Eastern U.S. BayouOryzomys palustris Southeastern U.S. Black Creek Canal Sigmodon hispidusFlorida Numerous other hantaviruses have been identified but not linked to human disease Numerous other hantaviruses have been identified but not linked to human disease Hantaviruses in the New World

6. Subfamily Sigmodontinae associated viruses Virus Host Location AndesOligoryzomys longicaudatusArgentina & Chile OranOligorozomys longicaudatus Northwest Argentina LechiguanasOligoryzomys flavescensCentral Argentina Hu39694UnknownCentral Argentina Laguna NegraCalomys lauchaParaguay & Bolivia BermejoOligoryzomys chacoensisNorthwest Argentina JuquitibaUnknownBrazil ChocloOligoryzomys fulvescensPanama Numerous other hantaviruses have been identified but not linked to human disease Numerous other hantaviruses have been identified but not linked to human disease Hantaviruses in the New World

7. Most Frequent OtherRare FeverDizzinessRhinorrhea MyalgiaArthralgia Sore Throat Nausea/VomitingCough Shortness of Breath (late in the course of disease) HPS - Clinical Presentation

8. Number of Cases of Hantavirus Pulmonary Syndrome (HPS) (Region of the Americas, 1993–2004*) 321 331 592 362 48 99 88 35 Panama Brazil Paraguay Uruguay Argentina Chile 36 Bolivia USA Canada = No. of cases * 2004 using preliminary data. Total cases = 1910

9. Hantavirus Pulmonary Syndrome Cases by Reporting State United States – March 26, 2007 Total Cases (N=465 in 31 States) 0 Cases >=10 Cases 5-9 Cases 1-4 Cases

10. Hantavirus Pulmonary Syndrome, United States Descriptive Demographic Statistics March 26, 2007 Mean=38 [1-83] N Male Female 465 (100%) 292 (64%) 173 (37%) White 355 (78%) American Indian 87 (19%) Black Asian 3 ( 1%) Hispanic65 (14%) Dead165 (35%) Age (years) 7 ( 2%)

11. Hantavirus in North America Usually sporadic, few clusters reported CDC review (Emerg Inf Dis 1997;3:361) in 1997 of 160 cases determined that few (7%) occurred in clusters As opposed to South American hantaviruses, no human-to-human transmission has been described in North America Sin nombre most common type Typically HPS but may have infection without pneumonia

12. Cluster #1 – Randall county 07/03 50 year old plumber’s assistant previously healthy. Smokes. Daily alcohol consumption. Seen in ED with four days of chills, myalgias, vomiting, cough, and shortness of breath. Thought to have cold and sent home on symptomatic treatment

13. Cluster #1 – contd Returns to ED two days later with worsening shortness of breath WBC=9100 (73% segs, 12% bands); H/H=17.5/52.3; plts=92,000. CXR=RML/RLL interstitial infiltrates Rapidly deteriorates and dies 48 hours later Autopsy = diffuse bilateral pulmonary edema with sparse interstitial inflammation Serum IgM & IgG positive for Sin Nombre virus Epidemiologic investigation significant peridomestic exposure to mice

16. Cluster #1 – contd 42 year old common law wife also ill with cold, vomiting and fever. Goes to ED, signs out AMA IgG and IgM positive for SNV Manager of trailer park had been ill one year previously, admitted to hospital with undiagnosed bilateral pneumonia and eventually recovered. IgG positive for SNV one year later.

17. Cluster #2 – Crosby county 04/02 Elderly mother expired on 4 th day post-admission due to “pneumonia” Middle-aged daughter expired with ARD within 24 hours of admittance 4 days later

18. Cluster #2 – contd During mother’s illness, case’s younger brother and family from out of state had visited residence, opened a cabinet and received a “face full of dust” Approximately two weeks later brother began exhibiting malaise, fever, myalgia; seen in ED and released 1 week later, brother readmitted with respiratory symptoms, tested positive for SNV IgG and IgM Recovered uneventfully

19. April/May 2002 Younger brother had visited home during the mother’s illness and became ill within 4 weeks after returning to AZ Middle-aged daughter expired with ARD within 24 hours of admittance 4 days later Elderly mother expired on 4 th day post-admission due to “pneumonia”

22. Texas HPS cases 1993 - 2006 32 cases SNV =26, Bayou virus = 4, Unknown = 2 All cases were hospitalized. BV cases were restricted to coastal counties. 19/26 (73%) of SNV cases occurred in Panhandle Plains counties. Mortality was 40% (46% for SNV vs. 0% for BV) Those aged 20-64 years were overrepresented (63% of cases vs. 49% of pop)

24. High Plains Ecoregion 62.5% (20/32) of Texas HPS cases 4.7% Texas Pop

25. Texas HPS – age and gender

26. Texas HPS cases 1993 – 2006 (cont) Common clinical characteristics included:  fever ≥101°F (83%)  nausea and/or vomiting (94%), diarrhea (67%), headache (86%),  hematocrit ≥55% (30%), platelets ≤100,000 (93%), creatinine ≥1.5 (60%), leukocyte count ≥20,000 (48%), bands ≥10% (85%). 85% of HPS cases reported seeing peridomestic rodents or rodent excreta. 85% of HPS cases were initially seen by a physician and dismissed to home, later to be admitted to the hospital

27. Texas HPS – clinical characteristics

28. Hantavirus Texas clusters - conclusions We described two Texas clusters of Hantavirus infection Both clusters involved Sin nombre virus and occurred in the Texas Panhandle. 6 people were infected. Five developed an illness consistent with HPS; one person developed evidence of Hantavirus infection without HPS. Overall mortality was 50% The diagnosis was initially overlooked in 4/6 patients and was only suspected when HPS was diagnosed in an epidemiologically related case

29. Acknowledgements James Schuermann, BS, TDSHS Zoonosis Branch Thomas Gerald, TTUHSC Research Associate Fellow Investigators  Megan Rivers, TTUHSC Medical Student  Dr. James Alexander, TDSHS  Rodney Rohde, Texas State University