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two hospitals in Nigeria, where 14 out of 37 patientswith Lassa fever were nurses or physicians.’ 1There is at present no way of immunising people

against Lassa fever and treatment is controversial.Convalescent plasma has been advocated for treatmentbut results have been conflicting. 1,2,5,6 A possibleexplanation for the differences has emerged from theexcellent trials of convalescent plasma in treatment ofthe closely related Argentine haemorrhagic fever. 7These trials have shown conclusively that the level ofneutralising antibody against Junin virus is critical indetermining the outcome. When patients were treatedduring the first 8 days of illness with convalescentplasma containing high levels of neutralising antibody,the case-fatality rate was reduced from 20-30% to1-3%. These observations in Argentine haemorrhagicfever may well be applicable to Lassa fever because inanimals infected with Lassa virus the degree ofprotection and suppression of viraemia conferred byconvalescent plasma depends on the level of

neutralising antibody in the plasma and bears norelation to the level of immunofluorescent antibody.Moreover, these vital neutralising antibodies did notdevelop in therapeutic concentrations until late inconvalescence, usually 90-180 days after the onset ofillness. Convalescent plasma obtained within 32-45days contained such low levels of neutralising antibodythat it gave no protection. This work in animals showsthe importance of matching the source of the plasmawith the strain of Lassa virus. Plasma from Liberia wasnot as effective as plasma from Sierra Leone in

protecting animals inoculated with a Sierra Leoneanstrain of the virus.4 In a retrospective survey of 37patients with Lassa fever in Nigeria, those whoreceived plasma within 11 days of onset seemed to havea lower case-fatality rate and to recover more quickly.The treated and control groups were not, however,strictly comparable, and levels of neutralising antibodyin the plasma were not determined. No untowardeffects were noted in the plasma-treated cases,’ but inArgentine haemorrhagic fever the use of convalescentplasma has been associated with a high incidence of lateneurological complications.8Arenaviruses are not sensitive in vitro to beta-

fibroblastic interferon. In rhesus monkeysexperimentally infected with Machupo virus ofBolivian haemorrhagic fever, treatment with polyICLC was successful in inducing the production ofinterferon but had no effect on the course of the illness.9Interferon is very unlikely to be useful in either Lassa

5 Leifer E, Gocke DJ, Bourne H. Lassa fever, a new disease of man from West Africa. II.Report of a laboratory acquired infection treated with plasma from a person recentlyrecovered from the disease. Am J Trop Med Hyg 1970; 19: 677-79.

6. Clayton AJ. Lassa immune serum. Bull WHO 1977; 55: 435-39.7. Enria DA, Briggiler AM, Fernandez NJ, Levis SC, Maiztegui JI. Importance of doses

of neutralising antibodies in treatment of Argentine haemorrhagic fever. Lancet1984, ii: 255-56.

8 Maiztegui JI, Fernandez NJ, de Damiland AJ. Efficacy of immune plasma in treatmentof Argentine haemorrhagic fever and association between treatment and lateneurological syndrome. Lancet 1979; ii: 1216-17

9 Stephen EL, Scott S, Eddy GA, Levy HB. Effects of interferon on togavirus andarenavirus infections of animals. Texas Rep Biol Med 1977; 35: 449-52.

or Argentine haemorrhagic fever because theconcentrations of alpha-interferon are naturally high inboth. Interferon levels have been studied in greater

"

detail in Argentine haemorrhagic fever; they fall

rapidly after successful use of convalescent plasma. 10Ribavirin, a nucleoside with broad activity against

both DNA and RNA viruses, has proved effective inprotecting rhesus monkeys inoculated with Lassavirus. In this trial all eight treated monkeys survivedwhereas six out of ten controls died." In further

experiments on cynomolgus monkeys a comparisonwas made between treatment with ribavirin or plasmaalone and also with a combination of the two. Monkeyswere protected when either ribavirin or plasma wasadministered within the first 4 days after inoculation.When treatment was delayed for 7 days ribavirinproved superior; four out of eight animals receivingribavirin survived whereas only one out of six treatedwith plasma survived. Results of combined treatmentwere even more impressive, for all the infected animalssurvived, even when treatment was delayed until the10th day and the monkeys were seriously ill. 12Ribavirin is now being tried for Lassa fever in SierraLeone with promising results. The toxic effects areslight-mainly reversible anaemia and transient

hyperbilirubinaemia.13The best current treatment for Lassa fever thus

seems to be a combination of ribavirin andconvalescent plasma containing neutralising antibodyin high concentration. Whenever possible the source ofthe plasma should match the strain of the virus. Ifneutralising antibody cannot be measured then plasmafor therapeutic purposes should be obtained at leastthree months after the onset of illness in the donor.Treatment should be started as early as possible,preferably within the first week of illness; the outcomealso depends greatly on the quality of nursing care andsupportive therapy. 14

TO EACH ACCORDING TO HIS RISK

NATIONALLY planned health services are usually basedupon some notion of "social justice" in health-that is, thedistribution of health resources according to need. Thedifficulties of distribution are at their most acute in the

developing countries where needs are enormous and facilitiesto meet them often hopelessly inadequate. In thesecircumstances the main task is to identify the most pressingdisorders for which relief is feasible. Unfortunately the

10. Levis SC, Saavedra MC, Ceccoli C, et al. Endogenous interferon in Argentinehemorrhagic fever. J Infect Dis 1984; 149: 429-33.

11. Jahrling PB, Hesse RA, Eddy GA, et al. Lassa virus infection of rhesus monkeys:pathogenesis and treatment with ribavirin. J Infect Dis 1980; 141: 580-89.

12. Jahrling PB, Peters JC, Stephen EL. Enhanced treatment of Lassa fever by immuneplasma combined with ribavirin in cynomolgus monkeys. J Infect Dis 1984; 149:420-27.

13. Canonico PG. Ribavirin. In: Hahn FE, ed. Antibiotics, vol 6. New York: Springer-Verlag, 1983: 161-86.

14. Emond RTD, Bannister B, Lloyd G, Southee TJ, Bowen ETW A case of Lassa fever:clinical and virological findings. Br Med J 1982; ii: 1001-02.

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concepts of social justice and need do not withstand closeanalysis and are of little aid to the planners of health serviceprovision. However, in a recent publication from the WorldHealth Organisation’ a pragmatic approach is proposed. Itsuggests that the risks of various undesirable events, such as a

poor outcome to pregnancy, should serve as a proxy for need

by both individuals and whole communities.The authors of this report start from two indices beloved

by epidemiologists-relative risk and attributable risk. Theformer is the ratio of the probability of manifesting anoutcome (eg, a disease) if exposed to some risk factor to theprobability of the same outcome if not exposed to the riskfactor. So, ifheavy smokers have a ten times greater chance ofgetting lung cancer than non-smokers then the relative riskfor smokers is said to be ten. A high relative risk fromexposure to the risk factor, in our example cigarette smoking,does not of itself prove a causal connection between risk factorand disease but is a strong piece of circumstantial evidence infavour of this hypothesis. However, in the context of serviceplanning, rather than aetiological research, no supposition ofa causal connection need be entertained. It does not matter.

Suppose that some single factor, such as lack of a householdwater supply, predicts a poor outcome for pregnancy. Thenno one need be concerned whether the lack of water itself isthe dominant reason for the poor outcome, but rather thisshould be seen as indicating a host of associated factors whichmay be connected with poverty and poor nutrition as well

possibly as poor hygiene. The point is that a high-risk motherwill have been identified and resources may be channelled toher. These may include medical care, nutritional

supplements, or improved sanitation, but at the time ofidentification one need not assume that the identifying factorhas direct aetiological significance. This approach, perhapswith some combination or scoring of "risk factors", enablesus to identify both communities and individuals at high risk.It becomes possible to place priorities upon risks and to directresources where the "need" is highest. For instance,pregnant women may be passed, according to the size of theirrisk scores, only as far as is necessary along a chain of servicesstarting with the village birth attendant and ending at theprovincial hospital.The second measure of risk, attributable risk, may be

applied to communities but not to individuals. It takes intoaccount the frequency of occurrence of the "risk factor" aswell as the strength of association between the risk factor andwhat it predicts. In essence it may be calculated as thedifference between the incidence of disease when the riskfactor is present and the incidence rate when the factor isabsent, these rates being based on the population at large.Thus it indicates what might be the overall outcome in thecommunity if the risk factor were totally removed from thatcommunity. So it is possible for some factor to be verystrongly linked to a particular disease among a fewindividuals but by no means to account for the bulk of thedistribution of the disease in the population. Use ofattributable risk enables planners to identify risk factors ofimportance to the many rather than the few. However, itscorrect use is predicated upon the assumption that the riskfactor is causally related to the adverse outcome in question.If that were not so then removal of the risk factor would haveno effect.

1. Backett EM, Davies AM, Petros-Barvazian A. The risk approach in health care. Withspecial reference to maternal and child health, including family planning. WHOPubl Health Papers 1984, no 76.

2. Lilienfeld AM, Lilienfeld DE. Foundations of epidemiology, 2nd ed. New York:Oxford University Press, 1980.

The WHO report shows in much detail how by applyingthese two concepts it is possible to formulate rational and fairhealth strategies. Priorities may be placed upon the risks andresources directed where need is greatest. Gathering the basicrisk data can be difficult, but the report shows how routinelycollected morbidity and mortality statistics may be cast in arisk mould. Furthermore, risk data from one community canoften be applied to another. For example, it is probably auniversally applicable observation that very low relativeincome or high blood-pressure during pregnancy places amother in peril of poor outcome.The ideas outlined here should be practicable in most

developing countries, given only a little initial assistance insetting up. The concepts are straightforward and at field-worker level they may be applied without too much concernabout their origins. But what of advanced economies? Theytoo have difficulties in matching supply to "need". TheBritish RAWP formulae3 for distributing resources amongand within health regions are an attempt at this. Perhaps therisk approach should receive more attention from establishedhealth services-though redistribution could prove moredifficult than starting from a near vacuum. We might reflectupon whether, by giving generously to the few (eg, by cardiactransplantation), we may be denying equity to the many.Even when health services are abundant, are there not glaringgaps of genuine, yet simple, need?

PRIMARY AND SECONDARY SJÖGREN’SSYNDROME

SJOGREN’S syndrome is characterised by inflammation ofthe exocrine glands, by immunological phenomena includinghypergammdglobulinaemia, a high prevalence of variousautoantibodies, and abnormalities of immunoregulation, andby a predisposition to lymphoproliferative disorders. Theclinical syndrome is caused by progressive destruction of theexocrine glands, especially the salivary and lacrimal glands,resulting in dry eyes, dry mucous membranes, and pancreatichyposecretion. The syndrome may arise as a primary diseaseentity, or in association with other autoimmune diseases,especially primary biliary cirrhosis, rheumatoid arthritis

(RA), and systemic lupus erythematosus. In this secondaryform of Sjogren’s syndrome, the association of a

polyglandular exocrine disease with a wide spectrum oforgan-specific and non-organ-specific autoimmune diseaseremains unexplained.

Clinical, serological, and genetic studies indicate that

Sjogren’s syndrome is a heterogeneous condition. In a

detailed retrospective study, Motsopoulos’ found that

parotid swelling, lymphadenopathy, purpura, Raynaud’sphenomenon, and myositis were more common in primarythan in secondary Sjogren’s syndrome. Splenomegaly,pulmonary involvement, and lymphoproliferative disordersoccurred with equal frequency, and the glands were

histologically similar. The heterogeneity has been definedmore precisely by serological and genetic studies. Attentionhas focused on four autoantibodies detected in serum from

patients with Sjogren’s syndrome. An organ-specificantisalivary duct antibody has been reported to occur in 25%of patients with primary Sjogren’s syndrome, 69% with RAand Sjogren’s syndrome, and 26% with RA alone.’ In

addition, three non-organ-specific antibodies to small nuclear

3. Department of Health and Social Security. Sharing resources for health in EnglandReport of the Resource Allocation Working Party. London: DHSS, 1976.

1. Motsopoulos HM. Sjögren’s syndrome (sicca syndrome): current issues. Ann InternMed 1980; 92: 212-26.