Handling patients with suspected Lassa fever entering Great Britain

Handling patients with suspected Lassa fever entering Great Britain A. W. WOODRUFF1, A special isolation unit has been created at the Hospitalfor Tropical Diseases, London, for the reception of patients arriving in Great Britain from West Africa with suspected Lassa fever. The management of such patients and the operation of the unit are described. Experience during the first eighteen months of operation has been very satisfactory and valuable lessons have been learned concerning the diagnosis and treatment of Lassa fever and the nurs ing ofpatients. Lassa fever in Great Britain has so far presented as pyrexia of unknown origin in persons arriving in the country by air from West Africa. A plan has therefore been evolved that is applied to all persons who present at the hospital with pyrexia of unknown origin and who have arrived in Britain from West Africa during the preceding seventeen days. Ap- proximately a hundred patients a year are admitted to the hospital with pyrexia and having recently been in West Africa; approximately fifty of these have been to West Africa during the seventeen days prior to their admission. Following the diagnosis of Lassa fever in one such patient in 1972, plans were made to create an isolation unit for reception of those with potentially dangerous diseases. This was done, it was brought into use eighteen months ago, and was used for the reception of the second patient brought to Britain with Lassa fever in January 1975. The unit consists of a two-bedded room provided with self- contained toilet and bathing facilities and telephone intercommunication. It is approached through two air-locked rooms and the whole unit is equipped with powerful exhaust ventilation. MANAGEMENT OF PYREXIAL PATIENTS WHO HAVE BEEN IN WEST AFRICA DURING THE PRECEDING SEVENTEEN DAYS The admitting medical officer decides, before the patient is taken to the ward, whether he should be isolated or put into an ordinary cubicle. Those with 1 Wellcome Professor of Clinical Tropical Medicine, London School of Hygiene and Tropical Medicine. Physician, Hospital for Tropical Diseases, London, England. pyrexia of unknown origin who have been in West Africa during the preceding seventeen days are isolated. Those in whom the diagnosis is known or who, although they have been to West Africa, have not been there during the preceding seventeen days, are not isolated. Patients in the group that is isolated are most likely to have, as a cause of their pyrexia, an infection with Plasmodium falciparum. The next most probable diagnosis is an upper respiratory infection of influenzal type, and following this an infective enteritis caused by Salmonella, Shigella, or other enteropathic bacteria. A third group of such febrile patients will have amoebic dysentery or amoebic abscess of the liver. The first thing that has therefore to be done is to examine a blood slide for malaria parasites. Patients are maintained in isolation until this has been carried out and until the result of the examination is known. Currently, the blood film is taken by the admitting officer, who wears gloves and a mask while doing so and who stains the film using staining materials kept inside a safety cabinet. If the blood film examination is positive and clinical evidence of non-malarial illness is absent, the patient is removed from isola- tion. If however the blood film contains no parasites, isolation is maintained and the consultant physician in charge of the ward is informed. He makes a decision as to whether there is a significant risk of Lassa fever being present or not. Experience has so far shown that those encountered in Britain with Lassa fever are most likely to be doctors or nurses who have been caring for febrile patients in hospitals situated in small towns in rural areas of West Africa. It is not uncommon, however, for clinical examina- 3403 - 717 - BULL. WORLD HEALTH ORGAN., Vol. 52, 1975 A. W. WOODRUFF tion to reveal that the risk of Lassa fever being present is virtually nil. This happened, for example, in the case of a patient recently admitted to the hospital on the day of arrival in Britain from Lagos. He had been in West Africa for two weeks and had been ill for five days with diarrhoea, and during the last two days had had a sore throat. His temperature was 37.5°C (99°F). He had no headache, or aches in the limbs or trunk, his symptoms were improving, and although he was pyrexial he was not seriously ill. Moreover he had not stayed outside of Lagos even though he had been in Nigeria. On clinical grounds therefore high-risk precautions were discon- tinued. If the consultant physician decides that there is still a risk of a dangerous viral infection being present, the consultant microbiologist is informed and specimens for further examination are collected in consultation with him and dispatched by him to the Maximal Security Laboratory, Porton, for labo- ratory tests. Routine for attending patients in the isolation unit For patients in whom the diagnosis of Lassa fever is considered possible the following procedures are followed while the investigative procedures are pro- ceeding or during subsequent management. 1. Protective clothing is put on in a specially designated changing room in the noninfectious area. 2. Personal clothing is completely removed in this room and specially provided tunic, trousers, and socks are put on. 3. In the same room these garments are covered with two pairs of disposable plastic leggings, paper gown, plastic apron, hood, mask, plastic visor, and rubber gloves. 4. On leaving the isolation unit, the staff member takes off the plastic apron, visor, mask, hood, gown, and outer leggings in the air-locked inner changing room within the infected area and places them in a specially marked plastic bag for incineration. 5. He (or she) then proceeds to the outer airlocked room where he rinses his hands in the disinfectant provided and then washes them. 6. He crosses the corridor to the changing room in the noninfective area, deposits the inner leggings into a specially marked plastic bag for incineration and deposits socks, trousers, and tunic into a separately marked container for autoclaving. He then puts on his personal clothing and immediately leaves the isolation unit. Procedures contingent upon the above routine 1. Staff may not eat, drink, or smoke within the isolation area. 2. Only specially authorized staff may enter the area; such staff are volunteers. 3. Limited visits by close relatives are allowed only under close supervision and on the terms outlined above. Special nursing conditions 1. Special conditions apply to the collection and dis- posal of excreta. Currently, excreta are mixed with Sudol to make a 1: 20 solution, allowed to stand for 1 hour and then disposed of through the toilet within the isolation unit. 2. Disposable cutlery and crockery are used and in- cinerated after use. 3. A meeting is held after the discharge of patients nursed in this unit. 4. Following clearance of the unit, final cleansing is carried out on the instructions of the local community physician. CLINICAL POINTS EMERGING FROM RECENT MANAGEMENT OF LASSA FEVER Points concerning diagnosis (a) Very considerable variation in the severity of trunk and limb pains and headache may occur between patients. Thus, one of our patients had excruciating pains of this kind while the other, a more severely ill patient, was little affected by them. Relative mildness of such pains should not, there- fore, lead to a lessening of suspicion. (b) Leucopenia is not invariable and, particularly after the fever has been present for a few days, the white cell count may become normal. Counts within the normal range were found in both patients admit- ted to the Hospital for Tropical Diseases, London, although there was evidence that in at least one of these patients leucopenia had been present earlier. (c) The condition of the throat may be such as to suggest diphtheria as a likely diagnosis. One of the two patients referred to had a very thick, adherent membrane on the throat and free bleeding occurred when this membrane was swabbed or when portions of it were removed. 718 HANDLING SUSPECTED LASSA FEVER IN GREAT BRITAIN Points concerning management of the patient during the main course of the illness The pulse may be slow in comparison with the patient's temperature, but during the terminal period of the fatal case in the London series a rising pulse rate and electrocardiographic changes were pro- minent. The latter included considerable S-T segment elevation in most leads, and were consistent with the development of myocardial damage. Evidence of such damage was found by histological examination of the myocardium after death. There is, therefore, clearly a need to support the heart and cardio- respiratory mechanism. Administration of oxygen is required, and it is possible that administration of anti-inflammatory steroids may be of benefit. Cer- tainly, correction of dehydration is necessary to prevent cardiac damage resulting from haemocon- centration, which may lead to sludging of blood in the coronary circulation and ensuing anoxia of the myocardium. In one of the two patients cared for at the Hospital for Tropical Diseases, London, the plasma sodium on admission was 126 mmol/litre. The potassium was normal being 4 mmol/litre. Bi- carbonate was somewhat reduced at 23 mmol/litre. Monitoring of electrolytes and of electrocardio- graphic changes may be of considerable value in making decisions concerning the management of patients. Such monitoring carries with it contingent requirements for the provision of laboratory facili- ties and apparatus for taking electrocardiograms in the isolation unit. Points concerning the management of contacts The procedure that has been followed for the contacts of those looking after the two patients so far admitted to the Hospital for Tropical Diseases, London, has been that normal activities are permit- ted as long as the individual remains asymptomatic. We have acted on the working hypothesis that even if viraemia did occur in an asymptomatic person the chance of it being transmitted to others from an asymptomatic person is very remote. This policy has so far been justified by events, for no secondary cases of Lassa fever developed from the two patients nursed in London. Two specimens of sera taken at intervals varying between 4 and 7 weeks were ob- tained from 4 doctors and 12 nurses who had looked after the last patient admitted. These sera were kindly examined for the presence of Lassa antibodies at the Communicable Disease Center, Atlanta, and no such antibodies were found in any of them. Similar paired sera were also examined from a further 37 persons who had had remote contact with the pa- tient or with laboratory samples from the patient and antibodies were not found in any of these. There would therefore have been no justification for the isolation in quarantine of any of these contacts. These results also indicate that the measures that were taken in looking after this patient did contain the infection. The patient most recently admitted in London developed his illness at a time when upper respira- tory infection and influenza were common in Bri- tain; it is therefore not surprising that 12 people who had had either close or remote contact with the patient became unwell during the 17 days subsequent to their last contact. All such patients were isolated; if afebrile they were barrier-nursed but if febrile full security precautions were put into effect. In every case, the ultimate diagnosis was an upper respiratory infection and paired sera from none of these patients exhibited Lassa antibodies. At the time of their illness there was, as is to be expected, considerable anxiety concerning them. Clearly, contingent isola- tion facilities for contacts must be made available when patients with Lassa fever are encountered. The plan that was worked out in conjunction with Dr T. Monath was that convalescent plasma would not be administered to contacts who became unwell unless they had been febrile for at least 3 days. Such a plan would, it is believed, use the limited available supplies of convalescent plasma optimally, both with regard to therapeutic effectiveness and conservation of supplies of plasma. In conclusion, emphasis needs to be given to the need for plans to be made, possibly with the help of an international agency, for convalescent plasma to be collected, stored, and made available in increasing amounts at selected centres. Of even greater im- portance is the need to encourage research into the production of an effective vaccine against Lassa fever. Use of such a vaccine would obviate a vast amount of human effort and anxiety in handling patients with Lassa fever. It is greatly to be hoped that national and international bodies will be en- couraged by this meeting to support in full any research needed for the production of such a vac- cine. 719 A. W. WOODRUFF RltSUMIt MESURES PRISES A L EGARD DES CAS SUSPECTS DE FIlVRE DE LASSA A L'ENTREE EN GRANDE-BRETAGNE La fievre de Lassa en Grande-Bretagne se manifeste sous la forme d'une pyrexie d'origine inconnue chez des voyageurs qui arrivent par avion d'Afrique occidentale. La presence possible de cette maladie doit donc etre envi- sagee chez tous les sujets qui presentent un etat febrile et qui se trouvaient en Afrique occidentale dans les 17 jours precedant leur entree en Grande-Bretagne. Des mesures ont et6 prises pour assurer la protection des autres malades de l'hopital ou sont admises ces personnes ainsi que du personnel charge de les examiner. Elles sup- posent notamment le port de vetements protecteurs et l'isolement (du materiel et des locaux sont prevus A cet effet) dans les cas oii l'origine de la pyrexie n'est pas aisement identifiable. Les causes les plus frequentes de maladie fdbrile chez des personnes ayant sejourne en Afrique sont le paludisme, les infections des voies respi- ratoires superieures, les infections A Salmonella et a Shigella et les infections amibiennes. Au sujet du diag- nostic, il faut savoir que la gravite des symptomes de la fievre de Lassa est extremement variable et que l'on n'observe pas toujours de leucopenie. Le personnel et les autres contacts sont mis sous surveillance pendant le jour mais ne sont pas isol6s tant qu'ils restent entierement asymptomatiques. DISCUSSION LEHMANN-GRUBE: I have never seen a Lassa fever patient, so I depend on the reports of eye witnesses. When I first heard and read about Lassa fever, it appeared to be a very severe disease and very dangerous to handle. Thus, when it was proposed that a physician who had con- tracted Lassa fever in Nigeria should be brought into Germany, I opposed this measure on the ground that it would probably be more useful to use the money to build a hospital in Africa to treat the patient there. Nevertheless, he was brought to Germany. I have sub- sequently discussed this question with several people here and it appears that Lassa fever is not as dangerous as was at first thought, so I am rather confused and uncertain what to advise in future cases of this kind. Is Lassa fever an extremely severe disease or not? Is transmission to others to be feared or not? WOODRUFF: Lassa fever is certainly a severe disease, one that clearly has a considerable lethality. It looks as though it is not perhaps all that transmissible, provided reasonable care is taken. I would not myself be very happy if a relative of mine were isolated in a small hospital where there was no equipment for the monitor- ing of electrolytes and a lack of the other facilities needed for the general care of the patient. I think there is a strong case for transferring these patients, but perhaps the most important consideration is that, whether you like it or not, they are going to be admitted as pyrexias of unknown origin. EVANS: Professor Woodruff has given a very clear de- scription of the way in which we have agreed to handle cases of pyrexia of unknown origin arriving in Britain from West Africa. To complete the picture, we ought to say what has also been agreed about cases that are definitely known to be Lassa fever. If a patient known to have Lassa fever were to be transferred to Britain, he would not, in fact, go to Professor Woodruff's unit but to a high security isolation hospital in North London, where Professor Woodruff would help take care of him. Similarly, if a definite case were to turn up in Professor Woodruff's unit, it would be transferred to the high security unit in the isolation hospital. So what Professor Woodruff has described is the " triage " arrangement that has been worked out to deal with cases of pyrexia of unknown origin. Similar arrangements exist elsewhere in Britain, and there are also arrangements for ambu- lance cover and the surveillance of contacts, both inside and outside the hospital. I wonder whether Professor Woodruff, or anyone else here, can tell us how serious is the question of airborne transmission of Lassa virus to people who are not in close contact. We know that a patient can infect others in the same ward. Is there any evidence that that patient could infect anybody out- side the building or in an adjacent building? We are obviously wondering whether we can rely on natural ventilation or whether we should always aim in Britain to provide virus-stopping filters in the exhaust air? WOODRUFF: I think that there is evidence of airborne transmission. I think there was a suspicion in Jos, Nigeria, that airborne transmission had led to a person being infected outside the hospital while waiting to be seen as an outpatient. Is that true, Dr Monath? MONATH: Yes. WOODRUFF: I personally think that the dilution factor is such that the risk of transmission by air from exhaust ventilation is extremely small. COLES: I agree with that, the risk must be very small. Dr Wulff has done antibody studies on all the staff at Nixon Hospital in Segbwema, Sierra Leone. It is obvious that we have been dealing with this disease 720 HANDLING SUSPECTED LASSA FEVER IN GREAT BRITAIN for some time, although we may not have recognized it as Lassa fever. Of 64 hospital workers, only 4 had complement-fixing antibodies; one of those was a nurse who works on an ordinary ward, one was a physician (myself) and the other two worked in the operating theatre where they were exposed to blood. It appears that airborne transmission presents a small risk. CASALS: It is not very easy, it seems to me, in view Of what we know from the different outbreaks, to evaluate the real risks of airborne transmission. In each of the nosocomial outbreaks there have been cases of probable or possible infection by this route. What we are dealing with is the variable behaviour of a phenomenon with a proven potential. 721