Experimental Lassa fever virus infection successfully treated with ribavirin.
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To determine the distribution of Lassa virus in West Africa, a serological survey was undertaken. A number of mission hospital supplied sera from patients admitted with a history of fever and specimens were also collected in New York from missionaries who had experienced an unusual febrile illness while working in Africa. More cases of Lassa fever were detected among missionaries than among Africans, possibly because many African patients had left hospital before the complement fixation tests had become positive. Although most adults had fairly high fever and some were prostrated, fever was less severe in the children examined. In general the findings confirm that not all Lassa fever patients have the severe syndrome described in the original reports.
A survey to detect individuals with antibodies to Lassa virus was undertaken among hospital personnel in the eastern and southern provinces of Sierra Leone late in 1974. Sera were evaluated by the complement fixation test. The data obtained showed that some contacts of Lassa fever patients in the 1972 epidemic had developed antibodies to the virus; individuals who had never reported being sick also showed evidence of infection, with significant CF antibody titres in their sera. Surviving Lassa fever patients from the 1972 epidemic still had easily measurable levels of persisting CF antibodies. The significance of these data is discussed; in addition it is recommended that the CF test should continue to be the method of choice in mass surveys for this virus disease until other tests can be developed.
This article reviews the current state of knowledge on the viral haemorrhagic fevers that infect man, namely smallpox, chikungunya fever, dengue fever, Rift Valley fever, yellow fever, Crimean haemorrhagic fever, Kyasanur Forest disease, Omsk haemorrhagic fever, Argentinian haemorrhagic fever (Junin virus), Bolivian haemorrhagic fever (Machupo virus), Lassa fever, haemorrhagic fever with renal syndrome, and Marburg and Ebola virus diseases.
At least thirty-seven different viruses have been isolated from wild mammals in West Africa since 1962. Some of these, including Lassa virus, are already known to cause serious human morbidity and mortality. Crimean haemorrhagic fever-Congo virus, Dugbe virus, Mokola virus, and a smallpox-like agent from a gerbil in Dahomey are briefly discussed. An account of social and ecologic factors affecting man, domestic animals, and their interaction with wild mammals is given.
The only non-human host of Lassa virus so far identified is the multimammate mouse, Praomys (Mastomys) natalensis, but its precise role in the natural Lassa fever cycle remains to be determined. This species is also an important link in the plague cycle in southern Africa and is one of the commonest rodents of Africa. It is a prolific breeder and can be kept and bred easily in captivity. It is thus an excellent laboratory animal, although it needs to be handled with care because it is aggressive towards man and bites readily. The current status of knowledge of its taxonomy, ecology, distribution, and role as a disease vector is reviewed, but attention is drawn to the possibly disastrous consequences of attempting to eradicate a vector species before the natural cycle of the disease and the ecology of the vector are fully understood.
In the light of recent knowledge on a complex of diseases caused by a new group of viruses, arenaviruses, virological studies largely directed toward small field mammals were undertaken during 1973-1974 aiming at etiological clarification of Korean hemorrhagic nephrosonephritis (KHNN). Specimens were collected in an endemic area of KHNN located north to northeast of Seoul. Virus isolation tests with 299 urine specimens and 131 mite pools recovered from small mammals and 14 acute stage sera from typical cases yielded negative results. Complement-fixation (CF) tests failed to detect antibodies against the antigens of Congo, lymphocytic choriomeningitis (LCM), Tacaribe, and Pichinde viruses among 366 small mammal sera. In addition, CF tests of 59 of the above sera against Apoi and Lassa virus antigens were negative. The results do not support the likelihood of an arenavirus being transmitted among Korean small field mammals, the overwhelming majority of which were Apodemus agrarius. A hypothesis that KHNN is caused by a virus of small field mammal origin was not proved within the technical limit of relatively unsophisticated methods employed herein.
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Immunoglobulin M antibodies can be measured by indirect immunofluorescence in sera of patients suffering from Lassa fever or Marburg virus disease 4-7 days after onset of illness. Titres reach a peak 1-2 weeks later. These antibodies disappear, or titres decrease considerably, 1-2 months after onset of illness. Antiviral IgG antibodies can be detected at the same time as, or a little later than, IgM antibodies, but they persist much longer. None of the three patients discussed in this paper who died of Lassa fever developed IgG antibodies and only one developed IgM antibodies.
Lassa, Marbourg and Ebola viruses are characterised by their endemo-epidemicity in tropical Africa, by their potential of inter-human transmission, by their gravity (30 to 50% mortality in cases admitted to hospital) and by the difficulty of their aetiological diagnosis. This results in a public health problem for countries in non-endemic regions receiving travellers coming from Africa. This problem is related to the risk of importation of cases, a risk which should not be exaggerated but nor should it be underestimated. Appropriate measures may be suggested in the light of assessment of the risk: organisation of specialised hospital facilities, laboratory and coordination service.
Three new viruses have been identified in Africa during the present decade. They may cause sporadic cases or limited outbreaks, and they are probably endemic in areas which are still ill-defined. Severe forms of infection lead to the haemorrhagic syndrome or to hypovolemic shock, the physiopathology of which is being studied. The case-fatality ratio of severe cases is between 30 and 85 per cent. Nosocomial outbreaks have been observed, but they can be avoided if appropriate barrier nursing measures are carried out for the treatment of patients or adequate protection measures for sampling and examination of laboratory specimens. As such cases may be transferred outside the endemic zone, this implies that countries receiving travellers from Africa should have hospitals with specialized units for strict isolation and treatment of these patients.
There are seven exotic diseases of concern; three of these, the most unpredictable and least understood, are Lassa fever, Marburg virus disease and Ebola virus disease. In this article the epidemiologic aspects of these diseases are discussed, with particular emphasis on exportation from their indigenous areas in Africa and on the occurrence of secondary cases. Any of these conditions could be brought into Canada either by aeromedical evacuation or inadvertently. Between 1972 and 1978 there were seven occasions when Canada could have been involved with handling cases of Lassa fever. The Government of Canada has purchased several containment bed and transit isolators. These units, with filtered air under negative pressure, accommodate infectious patients being transported and cared for without contaminating medical attendants or the environment.
Three cases of Lassa fever occurred in Onitsha, East Central State, Nigeria, in January and February 1974. The first case was a 19-year-old Nigerian; the other 2 cases were German missionary physicians at St Charles Borromeo Hospital, Onitsha, one of whom cared for the patient who was the first case. Thus, 2 of the 3 cases were hospital acquired. Investigations failed to discover a village outbreak or the source of virus for the first case. A serosurvey of 258 hospital staff members and contacts of the 3 cases showed no other persons with antibody to Lassa virus. The absence of Lassa virus antibody in a high-risk group indicates a low or nonexistent level of past Lassa virus activity in southeastern Nigeria.
The conditions necessary for fusion from inside (FFWI) of the BHK-21 cell culture affected by the Lassa and Mopeya arenaviruses were studied. The fusion was shown to occur only in the slightly acid medium and at lower pH meanings for the Mopeya virus, than for the Lassa virus.
Despite a late beginning, the construction of the arenavirus taxon and its placement in the scheme of the International Committee on Taxonomy of Viruses has now been completed. The bringing together of the member viruses has already provided valuable indications of promising laboratory and field study approaches; in the future this classification will contribute further to our understanding of the natural history and disease processes of the human pathogens of the group.
Viral contamination is at least as important in hospital laboratories and wards as contamination by bacteria or microscopic fungi, but it is much more insidious and sometimes unrecognized. There are two main types: The first has a purely technical effect and only interest the virologist. This is contamination of reagents, reference strains, cell cultures, etc.., by foreign viral agents. It may be the cause of errors on diagnosis or regrettable errors of interpretation of certain experimental data. It is most difficult to detect, if not to avoid. The second is much more worrying as it is liable to cause disease in man, which may induce severe, and even fatal infections in patients or in the medical, para-medical and technical personnel. This is the case with type B hepatitis virus which tends to invade surgical units using extra-corporeal circulation, hemodialysis units and transplantation units, blood transfusion centres, dental units and even causes victims in routine laboratories. However, type B hepatitis is not the only virus which may lead to severe infections; other viruses include: poxvirus, cytomegalovirus, arbovirus, etc. Finally, other often severe accidents may occur in research laboratories and in the pharmaceutical industry, owing to manipulation of dangerous viruses or by contact with experimental animals, e.g. rodents, or monkeys, which contain the virus in a latent state, e.g. lymphocytic choriomeningitis, Sabin virus, Marburg virus, type A hepatitis virus, etc. With regard to such accidents, we are almost completely powerless from the therapeutic point of view and, even poorly equipped, from the point of view of prophylaxis.
Arenaviruses have unique structural characteristics; they are pleomorphic, have a mean diameter of 110-130 nm, and consist of a membranous envelope with surface projections surrounding an interior containing ribosomes and filaments. Virus particles bud from plasma membranes of infected cells and in many cases large intracytoplasmic inclusion bodies are formed. These characteristics allow generic identification, but not differentiation of individual viruses. Ultrastructural identification of virus particles and pathological processes in infected tissues of man and experimental animals is important in understanding the nature of arenaviral pathogenesis Such identification also contributes to our understanding of the mechanisms of viral shedding and transmission in reservoir host species.