James W. LeDuc

Association of intraspecific wounding with hantaviral infection in wild rats (Rattus norvegicus).

The potential for hantaviral transmission among wild Norway rats by wounding associated with aggressive interactions was evaluated using a prospective sero-epidemiological study coupled with a mark-release-recapture survey. There was a significant association between an animals serological status and the presence of wounds. Longitudinal studies of marked and released animals showed seroconversion between captures was associated with wounding between captures more often (33%) than expected by chance, while unwounded animals seroconverted less often (8%) than expected. Typically, less than a 5% difference was found when comparing the incidence of seroconversion with the predicted rate based on wounding and seroprevalence. Infection was highly associated with the onset of sexual maturity and aggression but decoupled from rat age and the length of environmental exposure. Seroconversions occurred at times most associated with aggressive encounters and least associated with amicable behaviours that could lead to aerosol transmission.

Domestic Cases of Hemorrhagic Fever with Renal Syndrome in the United States

Although serologic studies have identified hantaviral infection in the United States, acute disease has not been recognized. This study describes 3 cases of domestically acquired hemorrhagic fever with renal syndrome (HFRS) in the United States. Infection was due to a local strain of Seoul virus (Baltimore rat virus). A review of the clinical features indicated a mild illness characterized by nausea, vomiting, renal and liver failure similar to HFRS described elsewhere for rat-borne viruses. Follow-up of 2 patients identified persistent hypertension and renal disease providing further evidence of an association between past hantaviral infection and hypertensive renal disease.

Effects of hantaviral infection on survival, growth and fertility in wild rat (Rattus norvegicus) populations of Baltimore, Maryland.

Survival, growth rates, body size and fertility of wild caught Norway rats (Rattus norvegicus), infected and uninfected with a Hantavirus (antigenically related to Seoul virus), were compared. No differences were found in the survival of seronegative versus seropositive rats, as measured by mark–recapture experiments. Growth rates, as measured by weight gain but not by increased body length, were slower in seropositive, sexually mature (>200 g) rats, although no differences in the ultimate body size of infected versus uninfected rats were found. No differences in external measures of sexual maturity, or in embryo counts or testes sizes, were found for infected versus uninfected rats. We conclude that hantaviral infections have little or no impact on demographic processes in Norway rat populations.

Risk factors associated with antibodies to leptospires in inner-city residents of Baltimore: a protective role for cats.

Leptospiral antibody prevalence was 16% in residents of Baltimore. Seropositivity was associated with age, gender, race, and bird ownership, reduced the antibody risk associated with age and race from odds ratios (95% confidence interval) of 3.3 (2.0, 5.5) and 3.3 (1.1, 9.3), respectively, to the baseline level. These data establish the high prevalence of leptospiral antibody in Baltimore and suggest a protective role for cats in reducing the risk of human infection.

Haemorrhagic fever with renal syndrome: evaluation of ELISA for detection of Puumala-virus-specific IgG and IgM

IgM and IgG ELISA to Puumala virus were evaluated using sera from patients with haemorrhagic fever with renal syndrome (HFRS) from different geographical regions: Sweden, Denmark, Norway, Belgium and the European USSR. IgM ELISA proved useful in the diagnosis of HFRS in patients from all the regions mentioned above. Specific IgM could be detected as early as day 1 post onset of disease, and patients remained IgM-positive for several months. Specific IgG ELISA antibodies were also frequently detected in acute sera, and acute-convalescent serum pairs often failed to show a significant titre rise or increase in optical density (OD) values. This limits the use of IgG ELISA in patient diagnosis. Sera collected 2 years after infection revealed higher IgG ELISA OD readings than convalescent sera, and very high values were still detectable 10 to 20 years postinfection. IgG ELISA is therefore useful for the testing of immunity and in seroepidemiological studies. Acute and convalescent sera from HFRS patients in Korea and the Asian USSR showed no or only very weak reactivity in the Puumala virus IgG and IgM ELISA. These results are consistent with the one-way crossing described earlier.

Association of chronic renal disease, hypertension, and infection with a rat-borne hantavirus

We report an association between past infection with an indigenous rat-borne hantavirus and chronic renal disease, hypertension, and cerebrovascular accidents among individuals using the Johns Hopkins Medical Institution from January 1986 through October 1988. A sample population of 1148 patients receiving quantitative total urine protein tests was screened for IgM and IgG antibodies to three different hantaviruses. Fifteen seropositives (1.3%) were found, of which 12 resided in inner city Baltimore in areas where Norway rats infected with a hantavirus had been captured.

Evidence of the presence of two hantaviruses in Slovenia, Yugoslavia

Thirty-three cases of hemorrhagic fever with renal syndrome (HFRS) have been serologically confirmed in Slovenia during the last five years. The clinical picture varied from mild to severe, with a mortality rate of 3%. Serum samples from 240 patients suspected of having HFRS were tested by immunofluorescence using four different hantaviral antigens. Three reactivity patterns were observed. Using capture enzyme immunoassay, IgM was detected in 100% acute-phase serum samples of patients. The distribution of hantaviral infections in small mammals was examined in two natural foci of HFRS. Two hantaviruses were found in these mammals. In one area, Clethrionomys glareolus was the predominant species, and most of their sera reacted to highest titer with Puumala virus; mild illness was diagnosed in this area. In the second location, Apodemus flavicollis predominated, and most of their sera reacted to highest titer with Hantaan virus; severe illness was diagnosed in this area.

WHO program on emerging virus diseases.

Infectious diseases, and especially viral diseases, are important, evolving complex public health problems. Their ultimate prevention and control will increasingly require sophisticated interaction between epidemiologic resources, molecular expertise, and application of modern statistical tools. The integration of epidemiologic and laboratory sciences is central to the success of a coordinated approach to new, emerging and re-emerging infectious diseases, and the WHO is attempting to facilitate and strengthen these resources internationally by focusing on improved surveillance, infrastructure building, applied research, and improved prevention and control strategies. Reference virus laboratories, especially those that deal with exotic virus diseases, will play a key role in implementation of the program, since these laboratories are likely to be called upon to assist in the identification of new, emerging, or re-emerging diseases. Thus, ensuring that these laboratories are well prepared to perform their critical tasks is essential to the ultimate success of the program.