TEXTE PARTIEL :
I. Introduction
Lassa fever is a generalized virus infection of man with multiple organ involvement. In severe cases it results in manifestations of pharyngitis, pneumonitis, myositis, myocarditis, encephalopathy, nephropathy and a degree of hemorrhagic diathesis.
The disease was first observed in early 1969 in a missionary nurse at Lassa, Nigeria, and two other missionary nurses who took care of her at a hospital in Jos, Nigeria; the index and one of the secondary cases died. About 1 year later, a short-lived but severe outbreak, seemingly hospital centered, occurred in Jos. The index case, hospitalized during the last days of 1969, had acquired the disease from unknown sources; there followed 27 other cases, mostly secondary but a few tertiary, with 13 deaths, including that of a resident physician. Two additional episodes have been observed since, one at Zorzor, Liberia, in March 1972 and a very recent one, at this writing still incompletely investigated, in the area of Panguma, Sierra Leone, where, over a 2-year period beginning in October 1970, 64 cases suspected of being Lassa fever were uncovered.
The virus is considered highly pathogenic and hazardous. Because severe, fatal laboratory-acquired infections have occurred, the properties of the virus and the experimental disease in laboratory animals have not been fully investigated.
II. The Virus
A. Morphology
Infected African green monkey kidney cells, Vero cell line, in cultures, observed under the electron microscope, reveal the presence of numerous pleomorphic particles of variable size. Among the smaller are round particles,
surrounded by an electron-dense limiting membrane, which contain a variable number (up to 8 or lO) of electron-dense granuIes. On the surfaces of these particles are seen projections or spikes.
Intracellular virion-like particles are also observed in vesicles or in invaginations. The presence of particles right under the limiting membrane, which appears thickened and as though pushed out, suggests that the virion reaches its extracellular stage by budding {SPEIR et al., 1970]. It has been estimated that the diameter of the virion-like particles (measured by electron microscopy) and of the infective particle (measured by filtration) is of the order of 70-80 nm.
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V. Epidemiology
The naturally acquired disease has been reported in Nigeria [FRAME et al., 1970; CAREY et al., 1972], Liberia [MONATH et al., 1972b and Sierra Leone [MONATH et al., 1972a]. It has been identified retrospectively and by antibody detection in Guinea [HENDERSON et aI., 1972]. The reservoir is unknown; if there is a reservoir in lower animals, the manner of transmission of the virus from it to man is also unknown. Once a human case appears, secondary and even tertiary cases arise, most likely by person-to-person transmission. It is not established how such transmission takes place; but the fact that the virus is present in throat washings in the acute stage of the illness gives grounds for suspecting droplet dissemination and upper respiratory or digestive portals of entry, particularly since an early symtom is sore throat with pharyngitis and tonsillitis. Contamination of food, drinks and household objects must also be considered as a possible source because the virus has been found in the urine of a patient 32 days after onset, far longer than in the throat. In some instances, the disease may have resulted from infection through cuts in the skin while the patient was handling contaminated materials, as in performing an autopsy [WHITE, 1972] or in caring for patients [FRAME et al., 1970].
Three reported outbreaks of Lassa fever have been hospital-associated: persons connected with the hospital were taken ill shortly after the admission of the index case. In the initial episode [FRAME et aI., 1970] a patient who had contracted the disease from unknown sources was evacuated to a hospital several hundred miles away; two nurses who took care of the patient came down with the disease 7 and 13-14 days later, respectively.
In a second, larger outbreak [TROUP et al., 1970; CAREY et aI., 1972], 28 persons were affected over a period of about 6-7 weeks. The index case was admitted to a hospital severely ill but recovered and was discharged 16 days later. Within 2-3 1/2 weeks of this patient's admission, 18 persons were taken ill; all except 3 that could not be located had some connection with the hospital, either as patients there for treatment, hospital staff or visitors to their sick relatives. Five additional hospitalized cases developed 10-12 days later; 4 of these cases were relatives of earlier patients and are considered as tertiary infections, and the 5th was a resident physician. Four other nonhospitalized, mild cases were subsequently uncovered among family contacts.
Similar developments occurred in an outbreak at Zorzor, Liberia; 2-3 weeks after admission of the index case, 10 persons associated with the hospital, including 3 other patients and 7 hospital staff personnel, came down with the disease. The case-fatality rate was 37% [MONATH et al., 1972b].
The most recent episode that has been investigated [MONATH et aI., 1972a] occurred at Panguma, Sierra Leone, and differs from previous ones in several respects. Review of hospital records showed that cases had occurred over an extended, rather than a short period; 64 cases were uncovered between October 1970 and October 1972. The case-fatality rate among hospitalized that is, severe cases has been 36%, similar to that of previous epidemics; however, clinical and serological surveys of hospital staff showed that a relatively large number of persons had sustained the infection without severe, or even any, clinical manifestations. The mortality among all infected persons who could be identified, therefore, was about 6%. Finally, unlike previous epidemics, this was not a hospital-related outbreak; most individuals were apparently infected in the community by contact with other patients.
Attempts have been made to determine the prevalence of Lassa virus infection by conducting plaque reduction neutralization tests. A number of positive sera have been found, but whether the antibodies were associated with disease is, on the whole, unknown [HENDERSON et al., 1972]. Sera were tested from about 700 missionaries and their families who had resided in 20 African countries between 1965 and 1968; the largest groups were from Nigeria, Ethiopia, Liberia, Zaire and Kenya. Of these sera, 5 were positive, 1 from a person stationed in Nigeria, the others in Telekoro, Guinea. Four of these 5 persons had experienced, while in Africa, a severe illness with symptoms and signs compatible with Lassa fever. A second set of about 450 sera, collected in 1965-1966 in the Makundi area of Nigeria, included 10 with antibodies. A third group of about 280 sera, also from Nigeria, revealed 3 positives among 54 sera collected in 1965 from itinerant cattle-herders and 20 positives among 200 sera collected in 1969 and 1970 in the Jos plateau.
The morphological similarity and serological relationship between Lassa, LCM and Tacaribe group viruses suggested the possibility that the Lassa virus may have a rodent reservoir. Of particular weight in this respect is the similar behavior of Lassa and LCM viruses following intra cerebral inoculation into newborn and adult mice and the fact that Lassa virus persists for as long as 80 days In the urine of mice inoculated when 1 day old. When an animal infected at birth develops normally to all appearances, and sheds virus in its urine for extended periods, perhap a lifetime; and when the animal is a domestic or peridomestic pest with the potential to soil and contaminate food, house dust and household objects such a model could fit a possible natural situation. The possibility is strengthened by similar situations prevailing with the diseases caused by other arenaviruses, partIcularly Machupo and probably Junin
viruses.
Thus far, limited efforts to locate an animal reservoir have had negative results. Tissues and urine from 39 wild-caught vertebrates, including Mus musculus, M. menutoides, Mastomys natalensis and Crocidura sp., failed to yield virus on inoculation to cells in culture [CAREY et al 1972]. The same workers found no neutralizing antibodies in the sera from another 78 small mammals: 48 rodents and 2 hedgehogs collected in northern Nigeria in 1970 and 28 bats caught near Ibadan, Nigeria, in 1966. Similarly negative results have followed attempts in Liberia [MONATH et al., 1972b].
Current investigations of the recent epidemic in Sierra Leone, while supporting the view that hospitalized Lassa fever cases are an important source of infection to hospital staff and other patients, raise another epidemiological possibility Ñ infection by contact with subclinically infecte persons. The occurrence of small clusters of cases in scattered house holds, having no apparent association or common linkage with cases in other households, might be explained on the basis of unrecognized infections in persons capable of transmitting the virus to others [MONATH et al., 1972a].
Addendum
In September and October, 1972, epidemiological investigations of an outbreak of Lassa fever were conducted in Eastern Province, Sierra Leone. Small vertebrates rodents, bats, insectivores and reptiles were collected and pooled tissues (heart, lung, spleen and kidney) from each were tested for virus by inoculation into cell cultures. Of 325 specimens tested, 10 isolations identified by CF test as Lassa virus have been made, all from the same rodent species, M. natalensis [Anonymous: Morbid. Mortal. 22: 201-202,1973].