Low incidence of rimantadine resistance in field isolates of influenza A viruses.

The spread of drug-resistant influenza viruses type A to close contacts in families, schools, and nursing homes has been well documented. To investigate whether drug-resistant influenza viruses circulate in the general population, 2017 isolates collected in 43 countries and territories during a 4-year period were tested for drug susceptibility in a bioassay. Drug resistance was confirmed by detection of specific mutations on the M2 gene that have been shown to confer resistance to amantadine or rimantadine. Sixteen viruses (0.8%) were found to be drug-resistant. Only 2 of these resistant viruses were isolated from individuals who received amantadine or rimantadine treatment at the time the specimens were collected. For 12 individuals use of amantadine or rimantadine could be excluded, and from the remaining 2 patients information about medication was unavailable. These results indicate that the circulation of drug-resistant influenza viruses is a rare event, but surveillance for drug resistance should be continued.

Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice.

OBJECTIVE: To investigate two hospital outbreaks of Lassa fever in southern central Nigeria. SETTING: Hospitals and clinics in urban and rural areas of Imo State, Nigeria. DESIGN: Medical records were reviewed in hospitals and clinics in both areas. Patients with presumed and laboratory confirmed Lassa fever were identified and contracts traced. Hospital staff, patients, and local residents were questioned, records were carefully reviewed, and serum samples were taken. Serum samples were assayed for antibody specific to Lassa virus, and isolates of Lassa virus were obtained. RESULTS: Among 34 patients with Lassa fever, including 20 patients, six nurses, two surgeons, one physician, and the son of a patient, there were 22 deaths (65% fatality rate). Eleven cases were laboratory confirmed, five by isolation of virus. Most patients had been exposed in hospitals (attack rate in patients in one hospital 55%). Both outbreak hospitals were inadequately equipped and staffed, with poor medical practice. Compelling, indirect evidence revealed that parenteral drug rounds with sharing of syringes, conducted by minimally educated and supervised staff, fuelled the epidemic among patients. Staff were subsequently infected during emergency surgery and while caring for nosocomially infected patients. CONCLUSION: This outbreak illustrates the high price exacted by the practice of modern medicine, particularly use of parenteral injections and surgery, without due attention to good medical practice. High priority must be given to education of medical staff in developing countries and to guidelines for safe operation of clinics and hospitals. Failure to do so will have far reaching, costly, and ultimately devastating consequences.

Improved specificity of testing methods for filovirus antibodies.

An epizootic among monkeys imported into the United States created an immediate need for detection of antibodies to filoviruses. Thousands of samples were submitted to the Centers for Disease Control and Prevention for testing. Problems of sensitivity and specificity existed in the methods available for these assays. The experiments described in this report resulted in improved methods for the detection of antibodies to filoviruses, both for indirect fluorescent antibody assays (IFA) by standardizing methods and the Western blot (WB) by minimizing antigen load and by incorporating skim milk in diluents.

Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain.

African filoviruses have caused outbreaks of fulminating hemorrhagic fever among humans. In 1989, related filoviruses were isolated from cynomolgus monkeys imported into the United States from the Philippines. The pathogenic potential of these new filoviruses was compared in 16 Asian monkeys (Macaca fascicularis-cynomolgus) and 16 African monkeys (Cercopithecus aethiops-African green) using African filoviruses from Zaire (Ebola virus) and Sudan or Asian filoviruses (Reston and Pennsylvania). African filovirus infections resulted in earlier death (P = .005), had a shorter duration of disease and median incubation period (3-4 vs. 7 days), and had earlier peak viremia (5-7 vs. 7-9 days). African green monkeys showed significantly higher survival than cynomolgus monkeys (P less than .01), and some were asymptomatic as have been humans accidentally infected with Asian filovirus. Rechallenge experiments showed that protection in survivors of filovirus infections against fatal challenge with Ebola (Zaire) virus is unpredictable. The minimal clinical disease observed in humans infected with the Reston strain is consistent with host- and virus-dependent pathogenicity.

Filovirus clearance in non-human primates.

There has been concern in the USA and Europe about filovirus outbreaks in recently imported monkeys, and possible transmission to human beings. Healthy monkeys have been found to have low-titre immunofluorescence antibody (IFA) to Asian filoviruses (Reston and Pennsylvania viruses) as well as to the African filoviruses that caused fulminating human outbreaks in the 1970s (Ebola [Zaire] and Sudan viruses). We have assessed whether such monkeys are a risk to man. We studied 42 non-human primates; 31 were experimentally infected with African and Asian filoviruses, 6 were infected during a documented Reston filovirus outbreak, and 5 had serological evidence suggestive of recent filovirus infection. During the first 15 days after infection, virus could be routinely recovered from serum or biopsy or necropsy tissue, and Asian filovirus RNA could be detected by polymerase chain reaction. 20 to 600 days after challenge, filovirus could no longer be recovered nor viral RNA detected in 141 serum, liver, spleen, or kidney specimens. Animals surviving filovirus infection develop high-titre, cross-reacting filovirus-specific antibody 14 to 21 days after infection, and this coincides with virus clearance. Healthy monkeys with low-titre filovirus antibody may be regarded as uninfected.

Lymphocytic choriomeningitis outbreak associated with nude mice in a research institute.

OBJECTIVE: After an employee at a cancer research institute was diagnosed with lymphocytic choriomeningitis, an investigation was performed to determine the extent of lymphocytic choriomeningitis virus (LCMV) infections among the institute's employees and to identify risk factors for infection. DESIGN: Retrospective cohort study. SETTING: A US cancer research institute. PARTICIPANTS: Eighty-two of 90 institute employees. MAIN OUTCOME MEASURES: Serum LCMV antibodies. RESULTS: Seven workers (9%) with definite LCMV infection (LCMV IgG antibody titer greater than or equal to 16) and one worker (1%) with probable infection (IgG titer = 8) were identified (10% overall seroprevalence). All infected employees handled animals or animal tissues and were more likely than other animal handlers to have worked with nude mice (Mus musculus) (P less than .02). Among the 31 employees who worked with nude mice at the institute, infected workers were more likely to clean the cages of nude mice (P much less than .001), change their bedding (P less than .01), and change their water (P less than .001). The institute had been injecting nude mice with LCMV-infected tumor cell lines and had recently increased the nude mouse population and the duration of experiments. These changes would have increased the LCMV burden at the facility and were temporally associated with the cluster of LCMV infections in employees. CONCLUSIONS: This LCMV outbreak, the first reported since 1974, is the first associated with nude mice. It illustrates the ongoing hazard LCMV poses in research laboratories. Since the symptoms of LCMV infection can be nonspecific, clinicians should consider this diagnosis in ill patients who report laboratory rodent exposure.