Modeling potential responses to smallpox as a bioterrorist weapon.

We constructed a mathematical model to describe the spread of smallpox after a deliberate release of the virus. Assuming 100 persons initially infected and 3 persons infected per infectious person, quarantine alone could stop disease transmission but would require a minimum daily removal rate of 50% of those with overt symptoms. Vaccination would stop the outbreak within 365 days after release only if disease transmission were reduced to <0.85 persons infected per infectious person. A combined vaccination and quarantine campaign could stop an outbreak if a daily quarantine rate of 25% were achieved and vaccination reduced smallpox transmission by > or = 33%. In such a scenario, approximately 4,200 cases would occur and 365 days would be needed to stop the outbreak. Historical data indicate that a median of 2,155 smallpox vaccine doses per case were given to stop outbreaks, implying that a stockpile of 40 million doses should be adequate.

Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections.

A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial effect. Pretreatment of monkeys delayed onset of viremia and delayed death several additional days. Interferon-alpha2b (2 x 10(7) IU/kg/day) had a similar effect in monkeys, delaying viremia and death by only several days. Effective treatment of Ebola infections may require a combination of drugs that inhibit viral replication in monocyte/macrophage-like cells while reversing the pathologic effects (e.g., coagulopathy) consequent to this replication.

Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel.

BACKGROUND: The arbovirus infections West Nile fever (WNF) and sandfly fever (SFF) are both endemic in the Middle East. Despite the fact that the mosquito and sandfly vectors of these viruses are still found in Israel, SFF has not been reported since 1948, whereas outbreaks of WNF occur periodically. It is suspected that some of the cases of nonspecific febrile illnesses in Israel may in fact be either WNF or SFF. AIM: To determine the extent of past arbovirus infections in subgroups of Israeli soldiers. METHODS: Sera from random samples of three groups of healthy soldiers aged 18-20 (n=273), 21-30 (n=497), and 40-55 years (n=285) were examined for IgG and IgM antibodies to West Nile virus (WNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Naples virus (SFNV), using an ELISA method. RESULTS: The prevalence of antibodies increased with age for all three viruses examined, and ranged from 7.0%, 0, and 2.8%, for WNV, SFSV, AND SFNV, respectively, in soldiers aged 18-20 years, to 41.9%, 23.7%, and 30.8%, in those aged 40-55 years. The percentage of seropositives for IgG who were also IgM positive were 1.0%, 5.9%, and 3.4%, for WNV, SFSV, AND SFNV, respectively. 17.5% of the seropositives for WNV were also positive for SFSV, as compared with 5.7% among the WNV-seronegatives. Among the seropositives for WNV, 23.99% were positive for SFNV, compared with 9.1% of WNV seronegatives. 48.2% of seropositives for SFSV were positive for SFNV, as compared with 8.4% for SFSV-seronegatives. In the age agroup 40-55 years, there were significantly higher prevalence rates in those born in Israel compared with those born abroad. CONCLUSIONS: There is still significant exposure to WNV, SFSV, and SFNV in Israel. Arborviruses are probably responsible for many cases of non-specific febrile illness in this region.

[Anti-Hantavirus antibodies in school children in Salvador, Bahia]. / Anticorpos anti-hantavírus em escolares de Salvador, Bahia.

Hantavirosis are emerging diseases in the Americas. Although considered rare in children, among the five cases diagnosed in Brazil, one was in this age group. To know the serum-prevalence of hantavirosis in the pediatric group (schoolchildren) of low social economic level in Salvador, Bahia State, and to associate demographic, socio-economic and environmental factors to the serologic results, a standard questionnaire was applied and blood samples were collected from 379 students of two public schools. Sera were tested by indirect Immunofluorescent Antibody (IFA) IgG for Hantaan Virus (HTN) and Immunoenzymatic test (ELISA) for Sin Nombre viruses. Ages varied from five to seventeen years with a mean age of 10.2 years. The proportion of sera positive to HTN virus was 13.2%, and there were no positive antibodies to SN virus. The frequency of positivity was higher in the older group, similar among sexes and racial groups, and there was no association with the exposure to urban rodents. The antibodies anti-HTN serum-prevalence in low social economic level school children is high and confirm the circulation of hantaviruses in Salvador-Bahia, Brazil; the nonobservation of antibodies anti-SN indicates that the species are other than Sin Nombre Virus.

Anticorpos anti-hantavírus em escolares de Salvador, Bahia / Anti-Hantavirus antibodies in school children in Salvador, Bahia

Hantavirosis are emerging diseases in the Americas. Although considered rare in children, among the five cases diagnosed in Brazil, one was in this age group. To know the serum-prevalence of hantavirosis in the pediatric group (schoolchildren) of low social economic level in Salvador, Bahia State, and to associate demographic, socio-economic and environmental factors to the serologic results, a standard questionnaire was applied and blood samples were collected from 379 students of two public schools. Sera were tested by indirect Immunofluorescent Antibody (IFA) IgG for Hantaan Virus (HTN) and Immunoenzymatic test (ELISA) for Sin Nombre viruses. Ages varied from five to seventeen years with a mean age of 10.2 years. The proportion of sera positive to HTN virus was 13.2%, and there were no positive antibodies to SN virus. The frequency of positivity was higher in the older group, similar among sexes and racial groups, and there was no association with the exposure to urban rodents. The antibodies anti-HTN serum-prevalence in low social economic level school children is high and confirm the circulation of hantaviruses in Salvador-Bahia, Brazil; the nonobservation of antibodies anti-SN indicates that the species are other than Sin Nombre Virus.

As hantaviroses são doenças emergentes nas Américas e, em todo o mundo, os casos clínicos descritos foram infreqüentes entre crianças. O objetivo de investigar a freqüência de escolares portadores de anticorpos (IgG) anti-hantavírus justifica-se porque poucos estudos soroepidemiológicos pesquisaram a infecção por hantavírus no grupo pediátrico. Nos espécimes séricos de 379 escolares, de duas Escolas públicas da cidade do Salvador, Bahia, foram pesquisados os anticorpos anti-Hantaan (HTN) e anti-Sin Nombre (SN). A soropositividade de anticorpos anti-HTN foi de 13,2% (50/379) e todos os escolares foram soronegativos para o vírus SN. A soropositividade anti-HTN aumentou proporcionalmente com a idade. Não houve associação entre a soropositividade anti-HTN e as características relacionadas à exposição a roedores urbanos. A soroprevalência de anticorpos anti-HTN nos escolares estudados foi elevada e reforçou a hipótese de circulação de hantavírus em Salvador. A não observação de portadores de anticorpos anti-SN indica, provavelmente, a circulação de outros sorotipos nesta região, mais relacionados antigenicamente ao sorotipo Hantaan.

Plan of action. Information.

PIP: This article provides information on WHO¿s strategic plan of action to aid countries around the world in detecting and controlling emerging infectious diseases. Activities are conducted through an organizational structure that ensures cost-sharing among all the 190 member states of WHO. Four major goals incorporating specific tasks are suggested: 1) the strengthening of global surveillance of infectious diseases through WHO collaborating centers; 2) the rebuilding of the international infrastructure to recognize, report, and respond to emerging and resurgent infectious diseases through laboratory and communication improvement 3) the fostering of applied research through greater practical use of the biotechnological revolution, and 4) the enhancement of the international capacity for infectious disease prevention and control through defined and practical public health steps. To implement this program, a workshop has been conducted and the WHONET program for laboratories has been introduced. In addition, clear guidance will be needed on the question of when to make changes in the antimicrobials recommended for specific diseases. The WHO strategy aims to enhance the capacity of local and national public health laboratories, to foster applied research to address practical problems, and to improve infectious disease prevention and control.^ieng

Yellow fever: a decade of reemergence.

Since the 1980s, yellow fever has reemerged across Africa and in South America. The total of 18 735 yellow fever cases and 4522 deaths reported from 1987 to 1991 represents the greatest amount of yellow fever activity reported to the World Health Organization (WHO) for any 5-year period since 1948. There is an excellent vaccine against yellow fever. At present, a high proportion of travelers to at-risk areas are reported to be immunized, reflecting widespread knowledge about the International Health Regulations. In South America, yellow fever remains an occupational hazard for forest workers, who should be immunized. However, Aedes aegypti mosquitoes are now present in urban areas in the Americas (including southern parts of the United States), and there is concern that yellow fever could erupt in explosive outbreaks. In Africa, a large proportion of cases have occurred in children. The WHO, the United Nations Children's Fund (UNICEF), and the World Bank have recommended that 33 African countries at risk for yellow fever add the vaccine to the routine Expanded Programme on Immunization; studies show that this would be highly cost-effective. To date, financing yellow fever vaccine has been a major problem for these countries, which are among the poorest in the world. For this reason, WHO has launched an appeal to raise $70 million for yellow fever control in Africa.

Prevalence of sand fly fever, West Nile, Crimean-Congo hemorrhagic fever, and leptospirosis antibodies in Pakistani military personnel.

To determine the prevalence of antibodies to viral diseases known or suspected to be present in Pakistan, we studied 570 sera from three groups of adults; two of the groups were involved in outbreaks of hepatitis, and the third included men admitted to a hospital for evaluation of febrile illnesses. Immunoglobulin G antileptospiral antibody was found in 1 to 6% of the subjects, with the highest rate in enlisted military personnel hospitalized for febrile illness. One man in the group with febrile illness had significantly elevated immunoglobulin M antileptospiral antibody titers. However, in a group of recruits experiencing suspected non-A, non-B hepatitis, 19 (11%) of 173 had a 4-fold rise in immunoglobulin M antibody to leptospirosis. Antibody to sand fly fever viruses was found in 27 to 70%. Antibody to West Nile virus was present in 33 to 41% of subjects. Antibody reactive with Japanese encephalitis virus was present in 25%, but plaque reduction neutralization tests suggested this to be cross-reaction with West Nile virus. All 212 specimens tested for antibody to Crimean-Congo hemorrhagic fever and Hantaan viruses were negative. This study indicates that diseases known to be prevalent in other areas of southwest Asia and the Middle East are also prevalent in northern Pakistan and may impact on those traveling or working 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.

Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.

A commercially available immunoglobulin G (IgG) from horses, hyperimmunized to Ebola virus, was evaluated for its ability to protect cynomolgus monkeys against disease following i.m. inoculation with 1 000 PFU Ebola virus (Zaire '95 strain). Six monkeys were treated immediately after infection by i.m. infection of 6.0 ml IgG; these animals developed passive ELISA titers of 1:160 to 1:320 to Ebola, two days afer inoculation. However, the beneficial effects of IgG treatment were limited to a delay in onset of viremia and clinical signs, in comparison with untreated controls. The six IgG recipients had no detectable viremia day 5, in contrast with three virus infected controls whose viremias exceeded 7.0 log10 PFU/ml that day. The controls died on days 6, 6, and 7, while two IgG recipients died day 7 and the remaining 4 died day 8, all with high viremias. These results document that passively acquired antibody can have a beneficial effect in reducing the viral burden in Ebola-infected primates; however, effective treatment of human patients may require antibodies with higher specific activities and more favorable pharmacokinetic properties than the presently available equine IgG.

Laboratory acquired tick-borne meningoencephalitis: characterisation of virus strains.

BACKGROUND: The handling of tick-borne encephalitis (TBE) virus is potentially hazardous, as indicated by a number of laboratory-acquired infections in the prevaccination era. OBJECTIVES: (1) To reemphasize the hazard of handling TBE virus without being vaccinated by describing the case of a laboratory-acquired full-blown TBE in a microbiologist who isolated the virus from a blood sample. (2) To molecularly characterize the causative virus strain isolated in Slovenia in comparison with the European prototype strain Neudoerfl. STUDY DESIGN: The virological diagnosis of the laboratory infection was established by serology and virus isolation. The virus was characterized by restriction fragment analysis of PCR products of amplified genomic sequences and a panel of monoclonal antibodies reacting with the major envelope protein. RESULTS: The laboratory infection, most probably acquired by aerosol, resulted in a biphasic course of the disease with a severe meningoencephalitis in the second phase. Both by restriction fragment and monoclonal antibody analysis the Slovenian virus strains involved were indistinguishable from the European prototype strain. CONCLUSIONS: This report confirms the potential hazard of handling TBE virus in the laboratory without being vaccinated. The similarity of the virus isolates from Slovenia with the European prototype strain confirms the previously observed homogeneity of TBE virus strains from different European countries.