152
There is much talk, but no solid facts at the moment writing on the use of direct IF on the following pathological specimens for a rapid viral diagnosis even in the field. (a) White blood cells (b) Throat swabs and throat washings (c) Urinary sediment (d) Cerebro-spinal fluid of
(e) Biopsies.’
The method to aim at in catching Lassa and Marburg and Ebola is a combination of above two methods. Inoculate ’Vero’ monkey kidney cell cultures with specimens from a suspect patient, i.e. blood in the first few days is ideal, throat swabs, urine, transudates and so on. Positive results can be obtained in 48 or 72 hours. What more do you ask from a Path. Lab.? For retrospective diagnosis and mass survey serological studies slides primed with a suspension of infected kidney cells are prepared at a Central Reference Laboratory and supplied to peripheral small laboratories and to field teams. Diagnosis of infection can be done quickly, cheaply and easily by layering specimens of sera on top of the cell concentrates which may be laboratory-infected by a choice of suitable viral agents appropriate to the geographic locality eg: ,
immunologic method utilizing antibodies linked with enzymes instead of antibodies conjugated with fluorescein dyes. This ELISA (enzyme linked immunosorbent assay) test may be found practical and cheaper especially for mass surveys. RECESSIONAL ’Ex AFRICA semper aliquid novi’ Let the peoples of big centres of population in Africa, and in cities of other centres elsewhere prepare con-
tingency plans!
Let every nation that here on earth doth dwell prepare a plan to protect its people from these endemic indigenous diseases or from imported outbreaks of new disease! Let that much respected international or anization, auntie WHO, act as a benevolent dictator to cajole and guide us, to conduct and supervise us towards the common weal of our ever increasing teeming millions when danger threatens! We have been lucky that LF and MVD are not so transmissible and contagious as those horses of the Apocalypse smallpox, typhus, plague or influenza. ’Medicine is one vast alarm system’ We have been warned three times LF, MAR, EF! We have seen the writing on the wall and have so far! survived We must not be trumped by the next VHF! And let us remember above all that homo sapiens is just one other species of life-form on a planet which like all other species has to be eternally vigilant for its survival and its very existence.
~?dictatrix)
-
-
-
I
Other
tests
are
in
the
pipeline
such
as
an
PUBLIC HEALTH ASPECTS OF VIRAL HAEMORRHAGIC FEVERS IN BRITAIN N. S. PAT
GALBRAITH, M.B., M.R.C.P., D.P.H., F.F.C.M., J. R. H. BERRIE, M.B., D.P.H., M.F.C.M., FORBES, B.SC., SUSAN YOUNG, M.R.C.P. Communicable Disease Surveillance Centre, Public Health
Laboratory
IT IS IRONIC that
infectious
at
the
Service
same
time
as one
major
disease, smallpox, has been brought
under control and now almost eliminated’ others have appeared which although much less infectious give rise to public health problems in Britain; these are mainly the recently discovered viral haemorrhagic fevers, particularly Lassa fever, Marburg virus disease and Ebola virus disease.2The purpose of this paper is to review the published experience of these three diseases, to describe the increase in travel which gives rise to their public health importance in Britain, to review the control measures taken in Britain and lastly to discuss future public health action. LASSA FEVER, MARBURG DISEASE AND EBOLA VIRUS DISEASE 1. Lassa Fever (a) Reported cases 1969 to December 1977. In January 1969 a missionary nurse working in a small hospital in Lassa in North Eastern Nigeria developed a febrile illness of gradual onset characterised by malaise, muscular pains, exudative pharyngitis and haemorrhagic rash. She was flown to the Bingham Memorial Hospital in Jos where she died
about 14 days after the onset of her illness. A second who cared for this patient in Jos developed a similar illness 8 days after her first contact with the patient and also died. A third nurse who looked after the previous patients also developed the illness and was subsequently flown to New York and admitted to the Presbyterian Hospital, where a virus was isolated from her serum. She survived after a severe illness lasting two months.3 One of the virologists working with the infected tissues cultures contracted the disease but recovered following treatment with convalescent serum.44 When in the autumn of 1970 a laboratory technician, working in the same building but not in the Lassa fever laboratory, died of the disease, all work was transferred to the maximum security laboratory at the Center for Disease Control in Atlanta. The story of the initial of Lassa fever has been vividly recounted investigation by Fuller.55 Monath6reported previous episodes of Lassa fever and listed the recorded episodes between 1969 and 1975 pointing out that most of the cases were due to hospital acquired infection. Further episodes reported up until December 1977 have been added to an adaptation of his table (Table I). Altogether 386 cases were nurse
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153
Number of
Table
reported between January
TABLE I Lassa Fever Reported cases 1969-1977
adapted and
extended from
1969 and December 1977
with 104 deaths. Of the 15
episodes listed in Table I, 11I were hospital or laboratory infections, 2 were individuals who acquired the infection outside hospital (episodes 13 and 14) and 2 were in Sierra Leone (episodes 4 and 11) where there was continuing community infection with less prominent spread within hospitals. With the exception of these two reports from Sierra Leone all were circumscribed episodes of short duration.
(b) Reported importations
America 1969-1977.
into
Europe
and North
Monath, T.P.6
In the 15 recorded episodes of Lassa fever, 8 cases were transferred to Europe or North America (Table II). Five were ill and three convalescent when they travelled, and of the five who were ill, three travelled by ordinary scheduled flights. There was no known spread of infection among their passenger contacts. All eight cases were nursed in units with trained staff in infectious disease nursing, with isolation varying from &dquo;normal care for virus infection&dquo; to a high security isolation unit. 19 23 No spread of infection to nursing or clinical medical staff occurred. In episodes 12, 13 and 14 in Table II over 1,200 contacts were identified and placed under surveillance; none developed Lassa fever.
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154
Reported
cases
TABLE 11 Lassa Fever outside West Africa 1969-1977
(c) Epidemiology Monath6 reviewed the epidemiology and epizootiology of the disease. The incubation period is usually 7 to 10 days but a range of 3 to 17 days has been recorded and a wider range of 3 to 21 days has been accepted for control purposes.2 The virus causes chronic symptomless infection in the rat Mastomys natalensis and is probably transmitted to man in the rural West African villages by direct contact in rat infested huts or by indirect contact with materials or food contaminated with infected rats’ urine. Person-to-person spread may also occur in overcrowded dwellings but has been especially important within hospitals in West Africa. All the hospital-acquired infections appear to have arisen by person-to-person spread from patients suffering from the disease. the spread has been by accidental inoculation with needles or instruments, direct personal contact and close exposure to pharyngeal secretions. In the Jos outbreak airborne spread by droplet nuclei appeared to be the explanation of secondary cases from a pregnant patient with severe pulmonary
involvement.8 In the epidemic in Panguma Hospital, Sierra Leone, hospital-acquired infection was less prominent. This hospital had isolation facilities consisting of a fourbedded isolation ward and barrier nursing was routinely practised. Despite the similar conditions to the severely affected hospitals there were no outbreaks of Lassa fever; only two patients acquired the disease between 1973 and 1975 during which time 156 patients with suspected Lassa fever were admitted. There was, however, spread to the hospital staff. Of 75 staff 2 died of Lassa fever during this period, 3 others were clinically
ill with the disease but recovered and
a
further 10 had
serological evidence of infection. 17 Although in the hospital outbreaks reported the disease has usually been severe with high mortality rates (Table I) mild and subclinical infections have been reported.’2 A serological survey in Lassa showed 5.8 per cent of population had neutralizing antibodies for Lassa virus and over a period of a year 4 of 17 hospital staff showed serological evidence of infection without symptoms.24 In Sierra Leone, where Lassa Fever is endemic, about half the febrile patients attending hospital were infected although few developed serious illness.25
Lassa virus
be recovered from the sera of most the first 14 days of the illness, from throat swabs or washing from about half during this period and from urine over a prolonged period of several weeks in a few patients .26Experience in Sierra Leone and outside West Africa indicates that isolation and barrier nursing are effective in preventing the spread of infection in hospitals but occasional patients, such as the pregnant woman with severe pulmonary involvement, may be infectious by the airborne route by droplets and droplet nuclei and require the use of special isolation units or Trexler isolators2’ for containment. can
patients during
2.
Marburg Disease and Ebola Virus (a) Reported cases 1967 to 1977 In 1967
Disease
outbreak of severe illness occurred among staff in Marburg, Frankfurt and Belgrade who had been working with a consignment of African Green Monkeys (Cercopithecus aethiops) from Uganda. Twenty-five of the staff exposed to cell cultures made from the tissues of these monkeys had a febrile illness of sudden onset, with extreme malaise, an
laboratory
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155 TABLE III
Marburg Virus Disease Reported cases 1967-1977
limbs and a characteristic between the 5th and 8th day of the illness. Seven of the 25 cases died and there were 6 secondary cases all of whom recovered. In one of the secondary cases the disease was sexually transmitted. 28 The disease appeared again in South Africa in 1975 in an Australian who had been hitch-hiking in Central and Southern Africa. He died, but two secondary cases,
headache, pains in the
maculopapular rash
his travelling companion and a nurse, recovered. 21 In 1967 two very extensive outbreaks of a clinically similar disease, which were shown to be due to an antigenically different virus subsequently named Ebola virus, occurred in Southern Sudan and Northern Zaire. This disease spread swiftly but only by close prolonged household contact or contact with patients’ blood .30 A single case in a laboratory worker in England followed an accidental prick in the thumb whilst handling infected tissues .3These reported incidents are summarised in Table III.
(b) Epidemiology Although African green monkeys transmitted Marburg virus disease in the initial outbreak they have not been
shown to be a natural reservoir of the disease. The first cases in the Ebola virus epidemic in Southern Sudan occurred in workers in a cotton factory where there was heavy rodent and bat infestation but so far the limited number of animal specimens examined have not shown evidence of infection. The incubation period was from 3 to 9 days in the two outbreaks of Marburg disease but in the Ebola virus epidemic a wider range of 4 to 16 days was reported 30 and as with Lassa fever a range of 3 to 21 days is suggested for control purposes. Virological studies in Marburg34 showed virus was present in blood, urine, throat swabs and seminal fluid and high titres were found in blood at the beginning of the Ebola virus infection of a laboratory worker.3’ These diseases spread readily by contact with blood or body fluids but transmission by droplets or droplet nuclei is unlikely. Simpson3° described how with the use of good nursing
review of the reported cases of these diseases indicates that this person-to-person spread can be controlled effectively by good barrier nursing techniques and protective clothing for staff or by care in special isolation units, and that laboratory spread can be prevented by the examination of specimens by special techniques or in specially designed high security laboratories.35 There was no evidence of airborne spread by droplet nuclei except in the case of the severely ill woman with pulmonary involvement in Jos.g It appears that none of these three diseases can spread by this route from persons who are not manifesting symptoms and it is very unlikely that spread can occur in this way in the first few days of the illness in the absence of respiratory
symptoms
or
signs.
TRAVEL AND DISEASE THE VIRAL haemorrhagic fevers have become of public health importance in Britain because of the increased speed of travel and especially the increased volume of travel.
1. International Air Travel The first fare-paying passenger flight from Britain took place on July 5th 1919 from London (Hendon) to Paris (Le Bourget) in 21 hours.36 Routes to Africa and India were pioneered during the 1920’s and 1930’s but it was not until the Second World War that the route from Britain to West Africa via Lisbon was opened up. The first scheduled flights taking 21 days began in 1947 and by 1976 this had been reduced to 61 hours. Heathrow became London’s main airport and in
techniques, supplemented by protective clothing, contact infections fell dramatically in the Sudan Ebola virus
outbreak.
3. Conclusions Lassa fever, Marburg disease and Ebola virus infection are zoonoses with a high mortality rate in man in most reported incidents. In Sierra Leone many mild and subclinical infections have been reported. Person-
to-person spread
readily
occurs
particularly by
contact
with infected blood, secretions and tissues and has been especially prominent in hospitals and laboratories. A
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Figure
1
156
prevent its export and import. This new received international recognition in the revised International Health Regulations 196944and in the increased emphasis of the World Health Organization on surveillance programmes. The regulations themselves cover only plague, cholera, yellow fever and smallpox and although world surveillance of otherdiseases not included in the regulations, such as influenza, has been successful45 it is difficult to apply the principles of surveillance to the new viral haemorrhagic fevers in Africa. As Bruce-Chwatt46 has pointed out, the weakest point of the new system of surveillance is that the countries in which some of the most important diseases are endemic have the least adequate public health organizations and limited resources to implement the system. It is apparent, therefore, that until these services can be improved, the prevention of spread of the viral haemorrhagic fevers in Britain must depend on the detection and isolation of suspected cases at airports or after arrival in this country and the surveillance of contacts possibly exposed to infection. The problem of detection is complicated by the increased importation of persons suffering from other febrile illness particularly malaria and typhoid fever. Notifications of malaria rose from about 100 in the early 1960’s to 1,162 in 1976,47 a nearly twelve fold rise. There were 50 deaths between 1966 and 1976 most of which were cases of falciparum malaria from West Africa. Recorded importations of typhoid fever into England and Wales doubled between 1973 and 1977, 104 cases compared with 206, although most of these were from the Indian sub-continent. 41 measures
to
approach
Figure 2 1947 just over 63,000 passengers passed through to all destinations,3’ a figure which increased to over 23 million by 1976,38 which does not include passengers other airports serving London. In 1945 9 million passengers were carried on scheduled world airlines other than those of the USSR39 and this figure had increased to 475 million in 1976,4° (Figure 1) a more than fifty fold increase, which does not take into account the great increase of charter flights in recent years.
through
2. Air Travel, United Kingdom to and from West Africa Statistics for West Africa as a whole are not available but passenger traffic between British airports to and from commonwealth West Africa is recorded38 41 (Figure 2). There was more than a three fold increase between 1968 and 1976. Assuming about half the passengers were arrivals, the figure of 103,000 arrivals per annum or about 280 per day in 1976 is derived. This is consistent with the estimate of Emond et al42 of about 700 arrivals per day from East, Central and West Africa at London’s three main airports. 3. Quarantine and Surveillance Dorolle43 described the development of the International Sanitary Regulations to prevent the global spread of cholera, plague, yellow fever, smallpox and typhus based on the concept of quarantine, that is, the temporary isolation of the sick or of those likely to have been infected. He pointed out that the increased speed of modern travel rendered this negative approach to international disease control inadequate and he advocated the more positive approach of international surveillance, that is, the early detection of reporting of communicable disease and the implementation of
4. Conclusions International air passenger traffic on scheduled airlines has increased fifty fold since the end of the Second World War. Nearly 300 passengers now arrive daily in the United Kingdom from commonwealth West Africa and as many as 700 from East, Central and West Africa where Lassa fever, Marburg disease and Ebola virus disease occur. Their countries of origin have the least well developed public health services and are least able to implement surveillance. Prevention of international spread of these diseases must therefore depend on early detection of suspected cases at airports or after arrival in Britain and appropriate isolation and surveillance. PUBLIC HEALTH MEASURES IN BRITAIN THE PROBLEMS of importation of exotic disease as a result of increased international air traffic have long been recognised 49 but the special problems created by the appearance of the ’new’ viral haemorrhagic fevers only began to be fully appreciated in the United Kingdom in 1975, although a special isolation unit for Lassa fever had been established at the Hospital for Tropical Diseases, London, in the previous year.’9
Public Health Measures 1975 In January 1975 a British doctor suffering from a severe febrile illness was flown home to London from the Nigeria and was treated in the isolation unit at Hospital for Tropical Diseases where he died.&dquo;’ 19 The diagnosis of Lassa fever was subsequently confirmed by the isolation of virus from a blood specimen at the Center for Disease Control, Atlanta, U.S.A. The public health issues created by this event were given immediate and detailed consideration by the Department of Health and Social Security (DHSS) and resulted in the publication in 1976 of the Memorandum on Lassa Fever,’ now widely accepted as model guidelines for the
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157 of patients and for public health protection. The death of this repatriated doctor in London aroused considerable interest in the medical and lay press in early 1975,5051 but despite the active concern of DHSS and the professional and lay interest in Lassa fever no further suspected or confirmed cases came to the notice of DHSS during 1975.
care
Public Health Measures 1976-77 By early 1976 D.H.S.S. recommendations had been put into practice. Hospital and laboratory provision had been made,’ the main hospital provision being at Coppetts Wood Hospital covering South East England and including within its catchment area London’s airports. The first Trexler isolator to become available for patient isolation by negative pressure was in use there in 1975.27 Laboratory facilities included seven designated laboratories to undertake examinations of material to exclude such eminently treatable diseases as malaria and typhoid and a maximum security laboratory at the microbiological Research Establishment (MRE), Porton, for virus isolation and serological tests for viral haemorrhagic fevers.2The diseases were made notifiable by amending the Public Health (Infectious Diseases) Regulations, 1968 52 53,thus providing the Medical Officers for Environmental proper officers Health (MOEH) - of a local authority with statutory powers for disease control ;*&dquo;* Lassa fever on 3rd August 1976 52 and viral haemorrhagic fever and Marburg disease on 20th November 1976.53 These detailed preparations were put to good use during 1976 when there were two confirmed cases of Lassa fever and one of Ebola virus infection. The first case (Tables I and II, episode 13), who flew home to the United States via London (Heathrow), had 41 contacts in Britain .20 The second case (Tables I and II, episode 14) was initially investigated in St. Mary’s Hospital, London but later transferred to Coppetts Wood where Lassa virus was subsequently isolated from urine. 21 Three of his 300 contacts developed symptoms, two had been in the same ward and one was a laboratory technician, and were isolated. Initially one of these contacts refused isolation in hospital and the MOEH did not have statutory power to enforce isolation. However, the patient eventually agreed to enter hospital and fortunately did not develop Lassa fever. There was no spread to any of the contacts. The third case in 1976 was a scientist from MRE Porton who pricked his thumb whilst working with virus strains from the Sudan outbreak of Ebola virus infection and contracted the disease (Table III, episode 4).21 11 Because of the unknown nature of this disease at the time, extra precautions were taken to prevent spread; 29 doctors and nurses at Coppetts Wood Hospital were kept in quarantine in the hospital for at least 21 days and 50 contacts in Wiltshire were confined to their homes during 21 days surveillance. -
3. Suspected Viral Haemorrhagic Fever 1976-77 These three episodes led to a greatly increased awareness of these viral haemorrhagic fevers, the second and third episodes in particular having extensive press and television coverage in Britain. Understandably, therefore, there followed a period during which many persons arriving from West Africa with fevers or who became febrile were labelled as &dquo;suspected Lassa fever&dquo; and unnecessary &dquo;control&dquo; measures were introduced. We have attempted to assess the size of the problem of viral,-) haemorrhagic fever and suspected cases by
Figure
examining
records of
3
DHSS, MRE Porton and Cop-
petts Wood Hospital for the years 1976 and 1977. These records show that there were the three confirmed 20 21 3’ and 77 other cases in 1976, already discussed
possibility of viral haemorrhagic seriously considered and in whom subsequently this diagnosis was excluded. This included the patients reported by Emond et a1.42 Specimens for virus isolation were received by MRE Porton from 36 of the 77 patients and there was a record of 37 of them at patients fever
in whom the
was
DHSS. These 77 patients should be regarded as the minimum number in whom viral haemorrhagic fever was seriously considered because we have not consulted records or made enquiries at any designated hospitals other than Coppetts Wood Hospital, nor have we sought information from MOsEH other than specific queries about some of these 77 patients. In these 77 patients we obtained a record of the date of return to Britain, date of admission to hospital or date specimens were submitted for virus isolation (Figure 3). There was a peak incidence in both 1976 and 1977 in the late summer and early autumn. The larger peak in 1976 was probably related to the interest and anxiety following the publicity given to the case of Lassa fever in the engineer returning from Nigeria21 but the seasonal pattern evident in both years was probably associated with the incidence of malaria in West Africa and variations in the volume of air traffic. In the study of patients with suspected viral haemorrhagic fever,4z forty five per cent had a final diagnosis of
malaria. There is increased transmission of malaria in the rainy season in Nigeria,55 from about June to August but the disease is endemic throughout the year and an increased incidence in these months probably had only a small influence on the seasonal pattern of suspected viral haemorrhagic fever in Britain. The main cause is most likely to be the increased air traffic in the third quarter of each year,56 shown in Figure 4; the July to September average monthly passengers carried in each of the years 1073-76 being between 60 and 80 per cent higher than the average for the preceding quarters of the year. We have not studied the age, sex and occupation of the suspected and confirmed cases of viral haemorrhagic fever because this has already been reported by Emond et al.42 The mean age of their patients was 33 years with a range of 11 to 64 years; about two-thirds
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158
(b)
Contacts of
Suspected
Cases
Information about the surveillance of
contacts of susbe expected, less readily available than that about the contacts of confirmed cases. Nevertheless some information was available about the contacts of 33 of the 77 suspected cases. Altogether, 590 contacts were recorded and placed under surveillance; in 10 of the 33 suspected cases additional contacts were mentioned but the number was not known. In 26 suspected cases, who had 331 recorded contacts, it was possible to determine the probable duration of surveillance by taking the time interval between admission of the suspected case to a designated unit and the date on which the diagnosis of viral haemorrhagic fever was excluded. These 331 recorded contacts, all but 18 of whom were in the community, were under surveillance for a total of 4,618
pected
cases
is,
as
might
days.
It is difficult to estimate from this the total number of
of surveillance of contacts of suspected cases in Britain in 1976 and 1977 but it is unlikely to have been less than 15,000 days. This is derived by trebling the figure of 4,618 days contact surveillance already calculated for 26 suspected cases, comprising about one third of the 77 suspected cases in the records of DHSS, MRE Porton and Coppetts Wood Hospital and by taking into account the probability of other suspected cases not included in these records. It is impossible to suggest a cost for this surveillance of contacts of suspected cases because the proportion placed under close surveillance is not known, but it is nevertheless clear that this placed a considerable workload on local environmental health services. A full evaluation of the workload and cost of viral haemorrhagic fevers in Britain has yet to be undertaken. The present investigation was a retrospective study of available records held centrally about surveillance of contacts locally. Emond et a142 have given an indication of the heavy workload in a designated unit and an indication of the workload of central surveillance is given by the issue of formal letters from the Chief Medical Officer on the subject of infectious disease. There were 39 letters issued in 1976 and 1977, 23 (59 per cent) of which concerned viral haemorrhagic fever: 9 of these 23 letters were about surveillance of contacts of the three confirmed cases, 12 were about suspected cases and 2 gave general information and advice.
days
-
’
Figure were
males.
cases were
4
They pointed out that 20 per cent of the engineers or workers in the construction
and their records indicate that students and lecturers comprised another 24 per cent of their 46 confirmed and suspected cases. The predominance of these two occupational groups may reflect the large numbers in these occupations travelling between West Africa and the United Kingdom, particularly in the
industry
summer
holiday period.
4. Surveillance of Contacts 1976-77 (a) Contacts of confirmed cases. The surveillance and quarantine of contacts of the three confirmed cases in 1976 placed a considerable burden upon the staff of Coppetts Wood Hospital and the environmental health departments concerned. Altogether 341 persons were reported to be under surveillance and a further 79 in quarantine in hospital or at home for at least 21 days. Most of these 420 persons were close contacts and required daily recordings of temperature and throat examination in accordance with the recommendations of the Memorandum on Lassa fever,2 although whether this was actually carried out in all cases is not known. A detailed evaluation of the cost of one day’s surveillance of a close contact has not been undertaken but it is likely to be about £5 per contact. The 420 contacts under surveillance for 21 days had a total of 8,820 days of surveillance. From this figure and the suggested daily cost it is estimated that the cost of surveillance of contacts alone of these three confirmed cases was about
£40,000.
5. Conclusions Public health measures for the control of viral haemorrhagic fevers in Britain were developed in detail during 1975 and introduced by 1976. These included the setting up of designated hospital units, provision of special laboratory facilities and guidance on standard surveillance procedures. In 1976 there were three confirmed cases in Britain one of whom was in transit to the U.S.A.; 420 contacts of these cases were placed under surveillance. Interest and anxiety created by these cases resulted in many febrile patients recently arrived from Africa being considered suspected cases; 77 of these were identified. There was a seasonal incidence in the summer and early autumn which corresponded to the peak period of travel between West Africa and the United Kingdom and also to the season when transmission of malaria is at its highest level in Nigeria. A study of the surveillance of contacts of confirmed and suspected cases indicated a substantial workload on local environmental health services.
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159 FUTURE PUBLIC HEALTH ACTION IN BRITAIN THIS REVIEW of viral haemorrhagic fevers in Britain suggests that, despite the balanced presentation of the problem in the Memorandum on Lassa fever,’ the public health services have overreacted to the risks of community spread of these diseases and placed less emphasis on the more real risks of hospital and laboratory spread. The purpose of this section of the paper is to consider the problems created by suspecting viral haemorrhagic fever and instituting control measures and the risks of not doing so, and how these problems and risks might be reduced. 1. Problems created
by suspecting
viral
haemorrhagic
fever There
are
three main groups of problems created by viral haemorrhagic fever and instituting con-
suspecting trol measures.
(a) Problems to the patient: It might result in delay in diagnosis of other conditions, the most important and lethal of which is falciparum
malaria;&dquo;’ 11 it would
mean
unnecessary admission to
hospital and possibly subjection to high security isolation ; unjustified public reaction might result in social problems at home and at work. Problems to the hospital services The provision and expense of adequate high security hospital units with sufficient staff to care for large numbers of suspects; the provision of adequate high security laboratory facilities; the disruption of general hospital services by cases presenting in casualty departments and possibly admitted to general wards;
the difficulties caused to the ambulance services. Problems to the public health services The heavy workload and anxiety imposed on the public health services by the surveillance of contacts; the creation of unnecessary public fear and alarm; the professional and public reaction that because of frequent unconfirmed .cases there is really little risk and the standard of control measures might, therefore, fall (Crying wolf too often!). 2. Risks
of not suspecting viral haemorrhagic fever The risks of not suspecting viral haemorrhagic fever occur in two different situations, firstly, spread in the community and secondly hospital or laboratory spread. (a) Community spread The review of the reported episodes of Lassa fever, Marburg disease and Ebola virus infection shows that person-to-person spread by airborne infection is very unusual and is only likely to take place from a seriously ill patient with pulmonary involvement. It is usually unnecessary, therefore, to trace and place under surveillance remote contacts of a suspected case. Furthermore, because of the problems outlined above such public health action is undesirable. Follow up of remote contacts can only be justified if the patient was severely ill with pulmonary involvement as indicated by
symptoms, signs
or
subsequent radiological findings.
Close contacts, defined as members of the patient’s household or persons who worked closely with the patient,2are those to whom there is a possibility of community spread in Britain, although the evidence suggests that this possibility is very small unless they have had contact with the patient’s blood, urine or secretions. In Marburg disease sexual transmission may also occur. Surveillance should begin as soon as possible.2Daily throat examination is of doubtful value in detecting the onset of disease and because it may increase the small risk to the examining doctors it
should be omitted as a routine, and surveillance restricted to enquiry about the contacts’ health and recording their temperatures. (b) Hospital and laboratory spread The main risk of not suspecting viral haemorrhagic fever and instituting control measures is in the possible spread in hospitals and laboratories. Eleven of the 15 episodes recorded in Table I and all of the 4 Marburg disease episodes recorded in Table III have been due to or resulted in hospital or laboratory spread of infection. The death of a laboratory worker in New York in 1970,’ whose mode of infection has not been explained, and the infection of a laboratory worker in England,3o indicate that spread can occur despite the very different laboratory and hospital conditions outside Africa. Although this is a’real risk and perhaps has not been fully appreciated in all hospitals and laboratories, it should not be exaggerated. Importation of viral haemorrhagic fever is a rare event. Emond et a141 reported that only two of their 46 suspects had viral haemorrhagic disease and one of these was the laboratory worker, who was known to have been handling infected cultures.3’ The other was a convalescent urinary excreter of Lassa virus and therefore a risk to attendants handling urine without adequate care. Woodruff et al.11 examined sera from 86 persons attending the Hospital for Tropical Diseases in London who had travelled to the United Kingdom from tropical Africa and who had suffered from pyrexial illnesses. None showed evidence of infection with Lassa or Marburg virus. 3. Recommendations to reduce the problems and risks It is possible to reduce the problems created by suspected viral haemorrhagic fever in Britain and to reduce the risks to hospital and laboratory staff in four main ways. (a) Less suspicion and less surveillance The importance of occupation and place of residence in Africa has been stressed in assessing the possibility of viral haemorrhagic fever in patients arriving in Britain.’ 19 42 Hospital and laboratory staff and persons from rural areas are the most likely suspect cases. Emond et a142 have suggested a classification of risk which we have slightly amended :Minimal risk. Arnvals from major cities, who have not worked in hospitals or laboratories. These patients with pyrexia of unknown origin should be cared for in tropical disease centres, in regional infectious disease units, in isolation units of general hospitals and barrier nursed, or if appropriate treated at home. Specimens should be sent to routine laboratories. No surveillance action is necessary. Moderate risk. Arrivals from rural areas or hospital or laboratory workers. These patients with pyrexia of unknown origin should be seen by a consultant in infectious disease before being considered a &dquo;suspected case&dquo;. Then after consultation with the MOEH admission to a designated unit and surveillance of contacts, if necessary, are arranged. Only close contacts’ should be placed under surveillance unless the patient was seriously ill with pulmonary involvement, in which event more remote contacts should be traced. Laboratory examinations to exclude malaria and other diseases should be made in high security cabinets. The Communicable Disease Surveillance Centre and Area Medical Officer should be informed. High risk. Arrivals from places or hospitals where viral haemorrhagic fever is known to be present or persons who have had contact with known patients or have been
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160
handling specimens or materials likely to be contaminated. The infectious disease consultant should be consulted immediately, the MOEH contacted and the Communicable Disease Surveillance Centre and Area Medical Officer informed. Arrangements should be made for admission to a designated unit, for virological examination of specimens in the high security laboratory and for surveillance of contacts as above. (b) A panel of clinical specialists It is important that the clinical diagnosis of suspected viral haemorrhagic fever should be made by a consultant experienced in this field. A specialist panel system should be set up analogous to the &dquo;smallpox panel&dquo; system, in which the clinician or MOEH seeks the advice of one of the specialist panel before arranging appropriate action. If the classification of risk categories above is acceptable, the clinician, if he considered it appropriate, could discuss with the MOEH the care of minimal risk patients without reference to a member of the specialist panel, but to establish the diagnosis of &dquo;suspected viral haemorrhagic fever&dquo; the specialist would have to be consulted; if appropriate, admission to a designated unit should be arranged and contact surveillance commenced. This would, of course, be the case in all suspects the specialist considered to be moderate or high risk. (c) More awareness of hospital and laboratory risk MOsEH, control of infection officers and infection control nurses should regularly bring the potential risk to hospital and laboratory staff to the attention of colleagues caring for febrile patients arriving from Central and West Africa. If patients in the category of minimal risk suspects are admitted to district general hospitals, they should be admitted to the isolation unit, the control of infection officer should be informed and should ensure appropriate precautions are taken including the reporting of staff absence and sickness. These patients should not be admitted to general wards unless no isolation unit is available and then should be barrier nursed. (d) An emergency control team The control of an outbreak of viral haemorrhagic fever in a hospital or laboratory is the legal responsibility of the MOEH, who would carry out this function with the hospital Emergencies Committee.2 In addition to the recommendations made in the Lassa fever Memorandum, there should be an emergency control team available nationally to assist locally in outbreak control. The Communicable Disease Surveillance Centre has begun to create such a team of three or four people experienced in the epidemiology, virology, medical and nursing care and the control of viral haemorrhagic fever, who could be brought together at short notice if required.
collectively
4. Conclusions The risks of community spread of viral haemorrhagic fevers have been exaggerated whereas it is the more real risks of hospital and laboratory spread that require
emphasis.
The clinical diagnosis of suspected viral haemorfever should be made only by a consultant member of a specialist panel, analogous to the smallpox panel. Surveillance should include only close contacts, except in special circumstances. General hospitals admitting febrile patients recently arrived from areas where viral haemorrhagic fever occurs and in whom there is minimal risk of these diseases should care for these patients in isolation units
rhagic
and staff should be kept aware of the possibility of these diseases. An emergency control team comprising persons experienced in the control of viral haemorrhagic fevers should be available nationally. REFERENCES 1 HENDERSON, D. A. (1973). Eradication of smallpox: The critical ahead. Proceedings of the Royal Society of Medicine 66, 493. year 2 Report (1976) Memorandum on Lassa Fever. London. HMSO. 3 FRAME, J. D., et al (1970). Lassa Fever, a new virus disease of man from West Africa. Clinical description and pathological findings. The American Journal of Tropical Medicine and Hygiene 19, 670. 4 LEIFER, E., GOCKE, D. J. and BOURNE, H. (1970). Lassa fever, a new virus disease of man from West Africa. Report of a laboratory-acquired infection treated with plasma from a person recently recovered from the disease. The American Journal of Tropical Medicine and Hygiene, 19, 677. 5 FULLER, J. G. (1974). Fever! The hunt for a new killer virus. London. Hart-Davis, MacGibbon. 6 MONATH, T. P. (1975). Lassa fever: review of epidemiology and . Bulletin of the World Health Organization, 52, 577. epizootiology 7 Center for Disease Control (1970). Lassa virus infection —
8
Pennsylvania. Morbidity and Mortality Weekly Report, 19, 123. CAREY, D. E., et al (1972). Lassa fever. Epidemiological aspects of the 1970 epidemic, Jos, Nigeria. Transactions of the Royal Society of
Tropical Medicine and Hygiene, 66, 402. et al (1974). Lassa fever in the Eastern Province of Sierra Leone 1970-1972. Epidemiologic studies. American Journal of Tropical Medicine and Hygiene, 23, 1131. WOODRUFF, A. W., et al (1973). Lassa fever in Britain: An imported case. British Medical Journal, 3, 616. 11 GILLES, H. M. and KENT, J. C. (1976). Lassa fever: retrospective diagnosis o f two patients seen in Great Britain in 1971. British 9
FRASER, D. W.,
10
Medical
4, 1173. Journal,
12 MONATH, T. P. et al (1973). A hospital epidemic of Lassa fever in Zorzor, Liberia, March-April, 1972. The American Journal of 13
Tropical
Hygiene. 22, 773. . (1974). A review of Lassa Fever outbreaks in Nigeria
Medicine and
SMITH, E. A.
Nigerian Medical Journal, 4, 216. et al (1975). Lassa fever in Onitsha, East Central . Bulletin of the World Health Organization, State, Nigeria, in 1974
14 BOWEN, G. S.
52, 599. 15 VELLA, E. E., (1976). Lassa fever. Hospital update, 2, 31. 16 FRAME, J. D., (1975). Surveillance of Lassa fever in missionaries
stationed in West Africa. Bulletin of the World Health Organisation, 52, 593. KEANE, E. and GILLES, H. M. (1977). Lassa fever in Panguma 1 , 1399. Hospital, Sierra Leone, 1973-6. British Medical Journal, 18 Report (1976). On the state of the Public Health for the year 1975. p.41. London. HMSO. 19 WOODRUFF, A. W. (1975). Handling patients with suspected Lassa fever entering Great Britain. Bulletin of the World Health Organisation, 52, 717. 20 ZWEIGHAFT, R. M. et al. (1977). Lassa fever: response to an imported case. New England Journal of Medicine, 297, 803. 21 Report (1977). On the state of the Public Health for the year 1976, p.52. London. HMSO. 22 BOWEN, G. S. (1978). Personal communication. 23 EMOND, R. T. D. (1976). Isolation for high risk patients. Postgraduate Medical Journal, 52, 563. 24 ARNOLD, R. B. and GARY, G. W. (1977). A neutralization test survey for Lassa fever activity in Lassa, Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 71, 152. 25 BRITISH MEDICAL JOURNAL (1978). Arena viruses in perspective, 1, 529. 26 MONATH, T. P. and CASALS, J. (1975). Diagnosis of Lassa fever and the isolation and management of patients. Bulletin of the World Health Organisation, 52, 707. 27 TREXLER, P. C., EMOND, R. T. D. and EVANS, B. (1977). Negative-pressure plastic isolator for patients with dangerous infections. British Medical Journal, 2, 559. 28 MARTINI, G. A. (1969). Marburg agent disease: in man. Transactions of the Royal Society of Tropical Medicine and Hygiene. 63, 295. 29 GEAR, J. S. S. et al. (1975). Outbreak of Marburg virus disease in Johannesburg. British Medical Journal, 4, 489. 30 SIMPSON, D. I. H. (1977). Marburg and Ebola virus infections: a guide for their diagnosis, management and control. Offset Publication No. 36. Geneva. World Health Organisation. 31 EMOND, R. T. D. et al. (1977). A case of Ebola virus infection. British Medical Journal, 2, 541. 32 MARTINI, G. A. (1973). Marburg virus disease. Postgraduate Medical Journal, 49, 542. 17
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Continue4t}fj page
186
There is much talk, but no solid facts at the moment writing on the use of direct IF on the following pathological specimens for a rapid viral diagnosis even in the field. (a) White blood cells (b) Throat swabs and throat washings (c) Urinary sediment (d) Cerebro-spinal fluid of
(e) Biopsies.’
The method to aim at in catching Lassa and Marburg and Ebola is a combination of above two methods. Inoculate ’Vero’ monkey kidney cell cultures with specimens from a suspect patient, i.e. blood in the first few days is ideal, throat swabs, urine, transudates and so on. Positive results can be obtained in 48 or 72 hours. What more do you ask from a Path. Lab.? For retrospective diagnosis and mass survey serological studies slides primed with a suspension of infected kidney cells are prepared at a Central Reference Laboratory and supplied to peripheral small laboratories and to field teams. Diagnosis of infection can be done quickly, cheaply and easily by layering specimens of sera on top of the cell concentrates which may be laboratory-infected by a choice of suitable viral agents appropriate to the geographic locality eg: ,
immunologic method utilizing antibodies linked with enzymes instead of antibodies conjugated with fluorescein dyes. This ELISA (enzyme linked immunosorbent assay) test may be found practical and cheaper especially for mass surveys. RECESSIONAL ’Ex AFRICA semper aliquid novi’ Let the peoples of big centres of population in Africa, and in cities of other centres elsewhere prepare con-
tingency plans!
Let every nation that here on earth doth dwell prepare a plan to protect its people from these endemic indigenous diseases or from imported outbreaks of new disease! Let that much respected international or anization, auntie WHO, act as a benevolent dictator to cajole and guide us, to conduct and supervise us towards the common weal of our ever increasing teeming millions when danger threatens! We have been lucky that LF and MVD are not so transmissible and contagious as those horses of the Apocalypse smallpox, typhus, plague or influenza. ’Medicine is one vast alarm system’ We have been warned three times LF, MAR, EF! We have seen the writing on the wall and have so far! survived We must not be trumped by the next VHF! And let us remember above all that homo sapiens is just one other species of life-form on a planet which like all other species has to be eternally vigilant for its survival and its very existence.
~?dictatrix)
-
-
-
I
Other
tests
are
in
the
pipeline
such
as
an
PUBLIC HEALTH ASPECTS OF VIRAL HAEMORRHAGIC FEVERS IN BRITAIN N. S. PAT
GALBRAITH, M.B., M.R.C.P., D.P.H., F.F.C.M., J. R. H. BERRIE, M.B., D.P.H., M.F.C.M., FORBES, B.SC., SUSAN YOUNG, M.R.C.P. Communicable Disease Surveillance Centre, Public Health
Laboratory
IT IS IRONIC that
infectious
at
the
Service
same
time
as one
major
disease, smallpox, has been brought
under control and now almost eliminated’ others have appeared which although much less infectious give rise to public health problems in Britain; these are mainly the recently discovered viral haemorrhagic fevers, particularly Lassa fever, Marburg virus disease and Ebola virus disease.2The purpose of this paper is to review the published experience of these three diseases, to describe the increase in travel which gives rise to their public health importance in Britain, to review the control measures taken in Britain and lastly to discuss future public health action. LASSA FEVER, MARBURG DISEASE AND EBOLA VIRUS DISEASE 1. Lassa Fever (a) Reported cases 1969 to December 1977. In January 1969 a missionary nurse working in a small hospital in Lassa in North Eastern Nigeria developed a febrile illness of gradual onset characterised by malaise, muscular pains, exudative pharyngitis and haemorrhagic rash. She was flown to the Bingham Memorial Hospital in Jos where she died
about 14 days after the onset of her illness. A second who cared for this patient in Jos developed a similar illness 8 days after her first contact with the patient and also died. A third nurse who looked after the previous patients also developed the illness and was subsequently flown to New York and admitted to the Presbyterian Hospital, where a virus was isolated from her serum. She survived after a severe illness lasting two months.3 One of the virologists working with the infected tissues cultures contracted the disease but recovered following treatment with convalescent serum.44 When in the autumn of 1970 a laboratory technician, working in the same building but not in the Lassa fever laboratory, died of the disease, all work was transferred to the maximum security laboratory at the Center for Disease Control in Atlanta. The story of the initial of Lassa fever has been vividly recounted investigation by Fuller.55 Monath6reported previous episodes of Lassa fever and listed the recorded episodes between 1969 and 1975 pointing out that most of the cases were due to hospital acquired infection. Further episodes reported up until December 1977 have been added to an adaptation of his table (Table I). Altogether 386 cases were nurse
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153
Number of
Table
reported between January
TABLE I Lassa Fever Reported cases 1969-1977
adapted and
extended from
1969 and December 1977
with 104 deaths. Of the 15
episodes listed in Table I, 11I were hospital or laboratory infections, 2 were individuals who acquired the infection outside hospital (episodes 13 and 14) and 2 were in Sierra Leone (episodes 4 and 11) where there was continuing community infection with less prominent spread within hospitals. With the exception of these two reports from Sierra Leone all were circumscribed episodes of short duration.
(b) Reported importations
America 1969-1977.
into
Europe
and North
Monath, T.P.6
In the 15 recorded episodes of Lassa fever, 8 cases were transferred to Europe or North America (Table II). Five were ill and three convalescent when they travelled, and of the five who were ill, three travelled by ordinary scheduled flights. There was no known spread of infection among their passenger contacts. All eight cases were nursed in units with trained staff in infectious disease nursing, with isolation varying from &dquo;normal care for virus infection&dquo; to a high security isolation unit. 19 23 No spread of infection to nursing or clinical medical staff occurred. In episodes 12, 13 and 14 in Table II over 1,200 contacts were identified and placed under surveillance; none developed Lassa fever.
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154
Reported
cases
TABLE 11 Lassa Fever outside West Africa 1969-1977
(c) Epidemiology Monath6 reviewed the epidemiology and epizootiology of the disease. The incubation period is usually 7 to 10 days but a range of 3 to 17 days has been recorded and a wider range of 3 to 21 days has been accepted for control purposes.2 The virus causes chronic symptomless infection in the rat Mastomys natalensis and is probably transmitted to man in the rural West African villages by direct contact in rat infested huts or by indirect contact with materials or food contaminated with infected rats’ urine. Person-to-person spread may also occur in overcrowded dwellings but has been especially important within hospitals in West Africa. All the hospital-acquired infections appear to have arisen by person-to-person spread from patients suffering from the disease. the spread has been by accidental inoculation with needles or instruments, direct personal contact and close exposure to pharyngeal secretions. In the Jos outbreak airborne spread by droplet nuclei appeared to be the explanation of secondary cases from a pregnant patient with severe pulmonary
involvement.8 In the epidemic in Panguma Hospital, Sierra Leone, hospital-acquired infection was less prominent. This hospital had isolation facilities consisting of a fourbedded isolation ward and barrier nursing was routinely practised. Despite the similar conditions to the severely affected hospitals there were no outbreaks of Lassa fever; only two patients acquired the disease between 1973 and 1975 during which time 156 patients with suspected Lassa fever were admitted. There was, however, spread to the hospital staff. Of 75 staff 2 died of Lassa fever during this period, 3 others were clinically
ill with the disease but recovered and
a
further 10 had
serological evidence of infection. 17 Although in the hospital outbreaks reported the disease has usually been severe with high mortality rates (Table I) mild and subclinical infections have been reported.’2 A serological survey in Lassa showed 5.8 per cent of population had neutralizing antibodies for Lassa virus and over a period of a year 4 of 17 hospital staff showed serological evidence of infection without symptoms.24 In Sierra Leone, where Lassa Fever is endemic, about half the febrile patients attending hospital were infected although few developed serious illness.25
Lassa virus
be recovered from the sera of most the first 14 days of the illness, from throat swabs or washing from about half during this period and from urine over a prolonged period of several weeks in a few patients .26Experience in Sierra Leone and outside West Africa indicates that isolation and barrier nursing are effective in preventing the spread of infection in hospitals but occasional patients, such as the pregnant woman with severe pulmonary involvement, may be infectious by the airborne route by droplets and droplet nuclei and require the use of special isolation units or Trexler isolators2’ for containment. can
patients during
2.
Marburg Disease and Ebola Virus (a) Reported cases 1967 to 1977 In 1967
Disease
outbreak of severe illness occurred among staff in Marburg, Frankfurt and Belgrade who had been working with a consignment of African Green Monkeys (Cercopithecus aethiops) from Uganda. Twenty-five of the staff exposed to cell cultures made from the tissues of these monkeys had a febrile illness of sudden onset, with extreme malaise, an
laboratory
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155 TABLE III
Marburg Virus Disease Reported cases 1967-1977
limbs and a characteristic between the 5th and 8th day of the illness. Seven of the 25 cases died and there were 6 secondary cases all of whom recovered. In one of the secondary cases the disease was sexually transmitted. 28 The disease appeared again in South Africa in 1975 in an Australian who had been hitch-hiking in Central and Southern Africa. He died, but two secondary cases,
headache, pains in the
maculopapular rash
his travelling companion and a nurse, recovered. 21 In 1967 two very extensive outbreaks of a clinically similar disease, which were shown to be due to an antigenically different virus subsequently named Ebola virus, occurred in Southern Sudan and Northern Zaire. This disease spread swiftly but only by close prolonged household contact or contact with patients’ blood .30 A single case in a laboratory worker in England followed an accidental prick in the thumb whilst handling infected tissues .3These reported incidents are summarised in Table III.
(b) Epidemiology Although African green monkeys transmitted Marburg virus disease in the initial outbreak they have not been
shown to be a natural reservoir of the disease. The first cases in the Ebola virus epidemic in Southern Sudan occurred in workers in a cotton factory where there was heavy rodent and bat infestation but so far the limited number of animal specimens examined have not shown evidence of infection. The incubation period was from 3 to 9 days in the two outbreaks of Marburg disease but in the Ebola virus epidemic a wider range of 4 to 16 days was reported 30 and as with Lassa fever a range of 3 to 21 days is suggested for control purposes. Virological studies in Marburg34 showed virus was present in blood, urine, throat swabs and seminal fluid and high titres were found in blood at the beginning of the Ebola virus infection of a laboratory worker.3’ These diseases spread readily by contact with blood or body fluids but transmission by droplets or droplet nuclei is unlikely. Simpson3° described how with the use of good nursing
review of the reported cases of these diseases indicates that this person-to-person spread can be controlled effectively by good barrier nursing techniques and protective clothing for staff or by care in special isolation units, and that laboratory spread can be prevented by the examination of specimens by special techniques or in specially designed high security laboratories.35 There was no evidence of airborne spread by droplet nuclei except in the case of the severely ill woman with pulmonary involvement in Jos.g It appears that none of these three diseases can spread by this route from persons who are not manifesting symptoms and it is very unlikely that spread can occur in this way in the first few days of the illness in the absence of respiratory
symptoms
or
signs.
TRAVEL AND DISEASE THE VIRAL haemorrhagic fevers have become of public health importance in Britain because of the increased speed of travel and especially the increased volume of travel.
1. International Air Travel The first fare-paying passenger flight from Britain took place on July 5th 1919 from London (Hendon) to Paris (Le Bourget) in 21 hours.36 Routes to Africa and India were pioneered during the 1920’s and 1930’s but it was not until the Second World War that the route from Britain to West Africa via Lisbon was opened up. The first scheduled flights taking 21 days began in 1947 and by 1976 this had been reduced to 61 hours. Heathrow became London’s main airport and in
techniques, supplemented by protective clothing, contact infections fell dramatically in the Sudan Ebola virus
outbreak.
3. Conclusions Lassa fever, Marburg disease and Ebola virus infection are zoonoses with a high mortality rate in man in most reported incidents. In Sierra Leone many mild and subclinical infections have been reported. Person-
to-person spread
readily
occurs
particularly by
contact
with infected blood, secretions and tissues and has been especially prominent in hospitals and laboratories. A
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Figure
1
156
prevent its export and import. This new received international recognition in the revised International Health Regulations 196944and in the increased emphasis of the World Health Organization on surveillance programmes. The regulations themselves cover only plague, cholera, yellow fever and smallpox and although world surveillance of otherdiseases not included in the regulations, such as influenza, has been successful45 it is difficult to apply the principles of surveillance to the new viral haemorrhagic fevers in Africa. As Bruce-Chwatt46 has pointed out, the weakest point of the new system of surveillance is that the countries in which some of the most important diseases are endemic have the least adequate public health organizations and limited resources to implement the system. It is apparent, therefore, that until these services can be improved, the prevention of spread of the viral haemorrhagic fevers in Britain must depend on the detection and isolation of suspected cases at airports or after arrival in this country and the surveillance of contacts possibly exposed to infection. The problem of detection is complicated by the increased importation of persons suffering from other febrile illness particularly malaria and typhoid fever. Notifications of malaria rose from about 100 in the early 1960’s to 1,162 in 1976,47 a nearly twelve fold rise. There were 50 deaths between 1966 and 1976 most of which were cases of falciparum malaria from West Africa. Recorded importations of typhoid fever into England and Wales doubled between 1973 and 1977, 104 cases compared with 206, although most of these were from the Indian sub-continent. 41 measures
to
approach
Figure 2 1947 just over 63,000 passengers passed through to all destinations,3’ a figure which increased to over 23 million by 1976,38 which does not include passengers other airports serving London. In 1945 9 million passengers were carried on scheduled world airlines other than those of the USSR39 and this figure had increased to 475 million in 1976,4° (Figure 1) a more than fifty fold increase, which does not take into account the great increase of charter flights in recent years.
through
2. Air Travel, United Kingdom to and from West Africa Statistics for West Africa as a whole are not available but passenger traffic between British airports to and from commonwealth West Africa is recorded38 41 (Figure 2). There was more than a three fold increase between 1968 and 1976. Assuming about half the passengers were arrivals, the figure of 103,000 arrivals per annum or about 280 per day in 1976 is derived. This is consistent with the estimate of Emond et al42 of about 700 arrivals per day from East, Central and West Africa at London’s three main airports. 3. Quarantine and Surveillance Dorolle43 described the development of the International Sanitary Regulations to prevent the global spread of cholera, plague, yellow fever, smallpox and typhus based on the concept of quarantine, that is, the temporary isolation of the sick or of those likely to have been infected. He pointed out that the increased speed of modern travel rendered this negative approach to international disease control inadequate and he advocated the more positive approach of international surveillance, that is, the early detection of reporting of communicable disease and the implementation of
4. Conclusions International air passenger traffic on scheduled airlines has increased fifty fold since the end of the Second World War. Nearly 300 passengers now arrive daily in the United Kingdom from commonwealth West Africa and as many as 700 from East, Central and West Africa where Lassa fever, Marburg disease and Ebola virus disease occur. Their countries of origin have the least well developed public health services and are least able to implement surveillance. Prevention of international spread of these diseases must therefore depend on early detection of suspected cases at airports or after arrival in Britain and appropriate isolation and surveillance. PUBLIC HEALTH MEASURES IN BRITAIN THE PROBLEMS of importation of exotic disease as a result of increased international air traffic have long been recognised 49 but the special problems created by the appearance of the ’new’ viral haemorrhagic fevers only began to be fully appreciated in the United Kingdom in 1975, although a special isolation unit for Lassa fever had been established at the Hospital for Tropical Diseases, London, in the previous year.’9
Public Health Measures 1975 In January 1975 a British doctor suffering from a severe febrile illness was flown home to London from the Nigeria and was treated in the isolation unit at Hospital for Tropical Diseases where he died.&dquo;’ 19 The diagnosis of Lassa fever was subsequently confirmed by the isolation of virus from a blood specimen at the Center for Disease Control, Atlanta, U.S.A. The public health issues created by this event were given immediate and detailed consideration by the Department of Health and Social Security (DHSS) and resulted in the publication in 1976 of the Memorandum on Lassa Fever,’ now widely accepted as model guidelines for the
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157 of patients and for public health protection. The death of this repatriated doctor in London aroused considerable interest in the medical and lay press in early 1975,5051 but despite the active concern of DHSS and the professional and lay interest in Lassa fever no further suspected or confirmed cases came to the notice of DHSS during 1975.
care
Public Health Measures 1976-77 By early 1976 D.H.S.S. recommendations had been put into practice. Hospital and laboratory provision had been made,’ the main hospital provision being at Coppetts Wood Hospital covering South East England and including within its catchment area London’s airports. The first Trexler isolator to become available for patient isolation by negative pressure was in use there in 1975.27 Laboratory facilities included seven designated laboratories to undertake examinations of material to exclude such eminently treatable diseases as malaria and typhoid and a maximum security laboratory at the microbiological Research Establishment (MRE), Porton, for virus isolation and serological tests for viral haemorrhagic fevers.2The diseases were made notifiable by amending the Public Health (Infectious Diseases) Regulations, 1968 52 53,thus providing the Medical Officers for Environmental proper officers Health (MOEH) - of a local authority with statutory powers for disease control ;*&dquo;* Lassa fever on 3rd August 1976 52 and viral haemorrhagic fever and Marburg disease on 20th November 1976.53 These detailed preparations were put to good use during 1976 when there were two confirmed cases of Lassa fever and one of Ebola virus infection. The first case (Tables I and II, episode 13), who flew home to the United States via London (Heathrow), had 41 contacts in Britain .20 The second case (Tables I and II, episode 14) was initially investigated in St. Mary’s Hospital, London but later transferred to Coppetts Wood where Lassa virus was subsequently isolated from urine. 21 Three of his 300 contacts developed symptoms, two had been in the same ward and one was a laboratory technician, and were isolated. Initially one of these contacts refused isolation in hospital and the MOEH did not have statutory power to enforce isolation. However, the patient eventually agreed to enter hospital and fortunately did not develop Lassa fever. There was no spread to any of the contacts. The third case in 1976 was a scientist from MRE Porton who pricked his thumb whilst working with virus strains from the Sudan outbreak of Ebola virus infection and contracted the disease (Table III, episode 4).21 11 Because of the unknown nature of this disease at the time, extra precautions were taken to prevent spread; 29 doctors and nurses at Coppetts Wood Hospital were kept in quarantine in the hospital for at least 21 days and 50 contacts in Wiltshire were confined to their homes during 21 days surveillance. -
3. Suspected Viral Haemorrhagic Fever 1976-77 These three episodes led to a greatly increased awareness of these viral haemorrhagic fevers, the second and third episodes in particular having extensive press and television coverage in Britain. Understandably, therefore, there followed a period during which many persons arriving from West Africa with fevers or who became febrile were labelled as &dquo;suspected Lassa fever&dquo; and unnecessary &dquo;control&dquo; measures were introduced. We have attempted to assess the size of the problem of viral,-) haemorrhagic fever and suspected cases by
Figure
examining
records of
3
DHSS, MRE Porton and Cop-
petts Wood Hospital for the years 1976 and 1977. These records show that there were the three confirmed 20 21 3’ and 77 other cases in 1976, already discussed
possibility of viral haemorrhagic seriously considered and in whom subsequently this diagnosis was excluded. This included the patients reported by Emond et a1.42 Specimens for virus isolation were received by MRE Porton from 36 of the 77 patients and there was a record of 37 of them at patients fever
in whom the
was
DHSS. These 77 patients should be regarded as the minimum number in whom viral haemorrhagic fever was seriously considered because we have not consulted records or made enquiries at any designated hospitals other than Coppetts Wood Hospital, nor have we sought information from MOsEH other than specific queries about some of these 77 patients. In these 77 patients we obtained a record of the date of return to Britain, date of admission to hospital or date specimens were submitted for virus isolation (Figure 3). There was a peak incidence in both 1976 and 1977 in the late summer and early autumn. The larger peak in 1976 was probably related to the interest and anxiety following the publicity given to the case of Lassa fever in the engineer returning from Nigeria21 but the seasonal pattern evident in both years was probably associated with the incidence of malaria in West Africa and variations in the volume of air traffic. In the study of patients with suspected viral haemorrhagic fever,4z forty five per cent had a final diagnosis of
malaria. There is increased transmission of malaria in the rainy season in Nigeria,55 from about June to August but the disease is endemic throughout the year and an increased incidence in these months probably had only a small influence on the seasonal pattern of suspected viral haemorrhagic fever in Britain. The main cause is most likely to be the increased air traffic in the third quarter of each year,56 shown in Figure 4; the July to September average monthly passengers carried in each of the years 1073-76 being between 60 and 80 per cent higher than the average for the preceding quarters of the year. We have not studied the age, sex and occupation of the suspected and confirmed cases of viral haemorrhagic fever because this has already been reported by Emond et al.42 The mean age of their patients was 33 years with a range of 11 to 64 years; about two-thirds
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158
(b)
Contacts of
Suspected
Cases
Information about the surveillance of
contacts of susbe expected, less readily available than that about the contacts of confirmed cases. Nevertheless some information was available about the contacts of 33 of the 77 suspected cases. Altogether, 590 contacts were recorded and placed under surveillance; in 10 of the 33 suspected cases additional contacts were mentioned but the number was not known. In 26 suspected cases, who had 331 recorded contacts, it was possible to determine the probable duration of surveillance by taking the time interval between admission of the suspected case to a designated unit and the date on which the diagnosis of viral haemorrhagic fever was excluded. These 331 recorded contacts, all but 18 of whom were in the community, were under surveillance for a total of 4,618
pected
cases
is,
as
might
days.
It is difficult to estimate from this the total number of
of surveillance of contacts of suspected cases in Britain in 1976 and 1977 but it is unlikely to have been less than 15,000 days. This is derived by trebling the figure of 4,618 days contact surveillance already calculated for 26 suspected cases, comprising about one third of the 77 suspected cases in the records of DHSS, MRE Porton and Coppetts Wood Hospital and by taking into account the probability of other suspected cases not included in these records. It is impossible to suggest a cost for this surveillance of contacts of suspected cases because the proportion placed under close surveillance is not known, but it is nevertheless clear that this placed a considerable workload on local environmental health services. A full evaluation of the workload and cost of viral haemorrhagic fevers in Britain has yet to be undertaken. The present investigation was a retrospective study of available records held centrally about surveillance of contacts locally. Emond et a142 have given an indication of the heavy workload in a designated unit and an indication of the workload of central surveillance is given by the issue of formal letters from the Chief Medical Officer on the subject of infectious disease. There were 39 letters issued in 1976 and 1977, 23 (59 per cent) of which concerned viral haemorrhagic fever: 9 of these 23 letters were about surveillance of contacts of the three confirmed cases, 12 were about suspected cases and 2 gave general information and advice.
days
-
’
Figure were
males.
cases were
4
They pointed out that 20 per cent of the engineers or workers in the construction
and their records indicate that students and lecturers comprised another 24 per cent of their 46 confirmed and suspected cases. The predominance of these two occupational groups may reflect the large numbers in these occupations travelling between West Africa and the United Kingdom, particularly in the
industry
summer
holiday period.
4. Surveillance of Contacts 1976-77 (a) Contacts of confirmed cases. The surveillance and quarantine of contacts of the three confirmed cases in 1976 placed a considerable burden upon the staff of Coppetts Wood Hospital and the environmental health departments concerned. Altogether 341 persons were reported to be under surveillance and a further 79 in quarantine in hospital or at home for at least 21 days. Most of these 420 persons were close contacts and required daily recordings of temperature and throat examination in accordance with the recommendations of the Memorandum on Lassa fever,2 although whether this was actually carried out in all cases is not known. A detailed evaluation of the cost of one day’s surveillance of a close contact has not been undertaken but it is likely to be about £5 per contact. The 420 contacts under surveillance for 21 days had a total of 8,820 days of surveillance. From this figure and the suggested daily cost it is estimated that the cost of surveillance of contacts alone of these three confirmed cases was about
£40,000.
5. Conclusions Public health measures for the control of viral haemorrhagic fevers in Britain were developed in detail during 1975 and introduced by 1976. These included the setting up of designated hospital units, provision of special laboratory facilities and guidance on standard surveillance procedures. In 1976 there were three confirmed cases in Britain one of whom was in transit to the U.S.A.; 420 contacts of these cases were placed under surveillance. Interest and anxiety created by these cases resulted in many febrile patients recently arrived from Africa being considered suspected cases; 77 of these were identified. There was a seasonal incidence in the summer and early autumn which corresponded to the peak period of travel between West Africa and the United Kingdom and also to the season when transmission of malaria is at its highest level in Nigeria. A study of the surveillance of contacts of confirmed and suspected cases indicated a substantial workload on local environmental health services.
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159 FUTURE PUBLIC HEALTH ACTION IN BRITAIN THIS REVIEW of viral haemorrhagic fevers in Britain suggests that, despite the balanced presentation of the problem in the Memorandum on Lassa fever,’ the public health services have overreacted to the risks of community spread of these diseases and placed less emphasis on the more real risks of hospital and laboratory spread. The purpose of this section of the paper is to consider the problems created by suspecting viral haemorrhagic fever and instituting control measures and the risks of not doing so, and how these problems and risks might be reduced. 1. Problems created
by suspecting
viral
haemorrhagic
fever There
are
three main groups of problems created by viral haemorrhagic fever and instituting con-
suspecting trol measures.
(a) Problems to the patient: It might result in delay in diagnosis of other conditions, the most important and lethal of which is falciparum
malaria;&dquo;’ 11 it would
mean
unnecessary admission to
hospital and possibly subjection to high security isolation ; unjustified public reaction might result in social problems at home and at work. Problems to the hospital services The provision and expense of adequate high security hospital units with sufficient staff to care for large numbers of suspects; the provision of adequate high security laboratory facilities; the disruption of general hospital services by cases presenting in casualty departments and possibly admitted to general wards;
the difficulties caused to the ambulance services. Problems to the public health services The heavy workload and anxiety imposed on the public health services by the surveillance of contacts; the creation of unnecessary public fear and alarm; the professional and public reaction that because of frequent unconfirmed .cases there is really little risk and the standard of control measures might, therefore, fall (Crying wolf too often!). 2. Risks
of not suspecting viral haemorrhagic fever The risks of not suspecting viral haemorrhagic fever occur in two different situations, firstly, spread in the community and secondly hospital or laboratory spread. (a) Community spread The review of the reported episodes of Lassa fever, Marburg disease and Ebola virus infection shows that person-to-person spread by airborne infection is very unusual and is only likely to take place from a seriously ill patient with pulmonary involvement. It is usually unnecessary, therefore, to trace and place under surveillance remote contacts of a suspected case. Furthermore, because of the problems outlined above such public health action is undesirable. Follow up of remote contacts can only be justified if the patient was severely ill with pulmonary involvement as indicated by
symptoms, signs
or
subsequent radiological findings.
Close contacts, defined as members of the patient’s household or persons who worked closely with the patient,2are those to whom there is a possibility of community spread in Britain, although the evidence suggests that this possibility is very small unless they have had contact with the patient’s blood, urine or secretions. In Marburg disease sexual transmission may also occur. Surveillance should begin as soon as possible.2Daily throat examination is of doubtful value in detecting the onset of disease and because it may increase the small risk to the examining doctors it
should be omitted as a routine, and surveillance restricted to enquiry about the contacts’ health and recording their temperatures. (b) Hospital and laboratory spread The main risk of not suspecting viral haemorrhagic fever and instituting control measures is in the possible spread in hospitals and laboratories. Eleven of the 15 episodes recorded in Table I and all of the 4 Marburg disease episodes recorded in Table III have been due to or resulted in hospital or laboratory spread of infection. The death of a laboratory worker in New York in 1970,’ whose mode of infection has not been explained, and the infection of a laboratory worker in England,3o indicate that spread can occur despite the very different laboratory and hospital conditions outside Africa. Although this is a’real risk and perhaps has not been fully appreciated in all hospitals and laboratories, it should not be exaggerated. Importation of viral haemorrhagic fever is a rare event. Emond et a141 reported that only two of their 46 suspects had viral haemorrhagic disease and one of these was the laboratory worker, who was known to have been handling infected cultures.3’ The other was a convalescent urinary excreter of Lassa virus and therefore a risk to attendants handling urine without adequate care. Woodruff et al.11 examined sera from 86 persons attending the Hospital for Tropical Diseases in London who had travelled to the United Kingdom from tropical Africa and who had suffered from pyrexial illnesses. None showed evidence of infection with Lassa or Marburg virus. 3. Recommendations to reduce the problems and risks It is possible to reduce the problems created by suspected viral haemorrhagic fever in Britain and to reduce the risks to hospital and laboratory staff in four main ways. (a) Less suspicion and less surveillance The importance of occupation and place of residence in Africa has been stressed in assessing the possibility of viral haemorrhagic fever in patients arriving in Britain.’ 19 42 Hospital and laboratory staff and persons from rural areas are the most likely suspect cases. Emond et a142 have suggested a classification of risk which we have slightly amended :Minimal risk. Arnvals from major cities, who have not worked in hospitals or laboratories. These patients with pyrexia of unknown origin should be cared for in tropical disease centres, in regional infectious disease units, in isolation units of general hospitals and barrier nursed, or if appropriate treated at home. Specimens should be sent to routine laboratories. No surveillance action is necessary. Moderate risk. Arrivals from rural areas or hospital or laboratory workers. These patients with pyrexia of unknown origin should be seen by a consultant in infectious disease before being considered a &dquo;suspected case&dquo;. Then after consultation with the MOEH admission to a designated unit and surveillance of contacts, if necessary, are arranged. Only close contacts’ should be placed under surveillance unless the patient was seriously ill with pulmonary involvement, in which event more remote contacts should be traced. Laboratory examinations to exclude malaria and other diseases should be made in high security cabinets. The Communicable Disease Surveillance Centre and Area Medical Officer should be informed. High risk. Arrivals from places or hospitals where viral haemorrhagic fever is known to be present or persons who have had contact with known patients or have been
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160
handling specimens or materials likely to be contaminated. The infectious disease consultant should be consulted immediately, the MOEH contacted and the Communicable Disease Surveillance Centre and Area Medical Officer informed. Arrangements should be made for admission to a designated unit, for virological examination of specimens in the high security laboratory and for surveillance of contacts as above. (b) A panel of clinical specialists It is important that the clinical diagnosis of suspected viral haemorrhagic fever should be made by a consultant experienced in this field. A specialist panel system should be set up analogous to the &dquo;smallpox panel&dquo; system, in which the clinician or MOEH seeks the advice of one of the specialist panel before arranging appropriate action. If the classification of risk categories above is acceptable, the clinician, if he considered it appropriate, could discuss with the MOEH the care of minimal risk patients without reference to a member of the specialist panel, but to establish the diagnosis of &dquo;suspected viral haemorrhagic fever&dquo; the specialist would have to be consulted; if appropriate, admission to a designated unit should be arranged and contact surveillance commenced. This would, of course, be the case in all suspects the specialist considered to be moderate or high risk. (c) More awareness of hospital and laboratory risk MOsEH, control of infection officers and infection control nurses should regularly bring the potential risk to hospital and laboratory staff to the attention of colleagues caring for febrile patients arriving from Central and West Africa. If patients in the category of minimal risk suspects are admitted to district general hospitals, they should be admitted to the isolation unit, the control of infection officer should be informed and should ensure appropriate precautions are taken including the reporting of staff absence and sickness. These patients should not be admitted to general wards unless no isolation unit is available and then should be barrier nursed. (d) An emergency control team The control of an outbreak of viral haemorrhagic fever in a hospital or laboratory is the legal responsibility of the MOEH, who would carry out this function with the hospital Emergencies Committee.2 In addition to the recommendations made in the Lassa fever Memorandum, there should be an emergency control team available nationally to assist locally in outbreak control. The Communicable Disease Surveillance Centre has begun to create such a team of three or four people experienced in the epidemiology, virology, medical and nursing care and the control of viral haemorrhagic fever, who could be brought together at short notice if required.
collectively
4. Conclusions The risks of community spread of viral haemorrhagic fevers have been exaggerated whereas it is the more real risks of hospital and laboratory spread that require
emphasis.
The clinical diagnosis of suspected viral haemorfever should be made only by a consultant member of a specialist panel, analogous to the smallpox panel. Surveillance should include only close contacts, except in special circumstances. General hospitals admitting febrile patients recently arrived from areas where viral haemorrhagic fever occurs and in whom there is minimal risk of these diseases should care for these patients in isolation units
rhagic
and staff should be kept aware of the possibility of these diseases. An emergency control team comprising persons experienced in the control of viral haemorrhagic fevers should be available nationally. REFERENCES 1 HENDERSON, D. A. (1973). Eradication of smallpox: The critical ahead. Proceedings of the Royal Society of Medicine 66, 493. year 2 Report (1976) Memorandum on Lassa Fever. London. HMSO. 3 FRAME, J. D., et al (1970). Lassa Fever, a new virus disease of man from West Africa. Clinical description and pathological findings. The American Journal of Tropical Medicine and Hygiene 19, 670. 4 LEIFER, E., GOCKE, D. J. and BOURNE, H. (1970). Lassa fever, a new virus disease of man from West Africa. Report of a laboratory-acquired infection treated with plasma from a person recently recovered from the disease. The American Journal of Tropical Medicine and Hygiene, 19, 677. 5 FULLER, J. G. (1974). Fever! The hunt for a new killer virus. London. Hart-Davis, MacGibbon. 6 MONATH, T. P. (1975). Lassa fever: review of epidemiology and . Bulletin of the World Health Organization, 52, 577. epizootiology 7 Center for Disease Control (1970). Lassa virus infection —
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Pennsylvania. Morbidity and Mortality Weekly Report, 19, 123. CAREY, D. E., et al (1972). Lassa fever. Epidemiological aspects of the 1970 epidemic, Jos, Nigeria. Transactions of the Royal Society of
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Nigerian Medical Journal, 4, 216. et al (1975). Lassa fever in Onitsha, East Central . Bulletin of the World Health Organization, State, Nigeria, in 1974
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52, 599. 15 VELLA, E. E., (1976). Lassa fever. Hospital update, 2, 31. 16 FRAME, J. D., (1975). Surveillance of Lassa fever in missionaries
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