87

Influenza apart, there is no recent parallel to thisemergence of a new virus causing a pandemic. Itseems that, at the beginning, there were two epidemicfoci-Ghana and Indonesia. One suggestion is thatthe Moslem pilgrimage, an epidemiological commondenominator of the two countries, may have played apart in the initial spread. In India the disease wasrumoured to have been imported by Moslems. Onthe whole, the outbreak was severer in the tropicsthan in the temperate zone. In the tropics, community-wide spread is probably favoured by poor sanitation.In the more developed countries outbreaks havetended to centre on eye clinics. A.H.C. is likely to be acommon eye infection in future, and a careful look-out must be kept for neurological complications.

SUBCLINICAL LEAD POISONING

INORGANIC-LEAD poisoning is usually thought of asa disease characterised by constipation, abdominal

colic, fatigue, headache, myalgia, anxmia, reticulo-

cytosis, and’ basophilic stippling. In severe forms

peripheral-nerve involvement may cause muscle

paralysis. The most feared complication, encephalo-pathy, is nowadays rarely seen in adults but is typicalof childhood poisoning. Clinical lead poisoning is

widely believed not to happen when the blood-leadconcentration is below 80 Lg. per 100 ml., and thismay well be true; but it does not follow that lowerlevels are without effect-as with many other con-ditions, lead poisoning can be subclinical. Haem

synthesis, for example, may be impaired in the absenceof symptoms. This impairment results from enzymeinhibition and shows as depression of erythrocytedelta-aminolaevulinic dehydratase (A.L.A.-D.), increasedexcretion of its substrate delta-aminolsevulinic acid

(A.L.A.) and of type-lll coproporphyrin (c.p.) into theurine, and accumulation of protoporphyrin ix in

erythrocytes. Erythrocyte A.L.A.-D. is partiallyinhibited at lead levels as low as 20 g. per 100 ml.or less-an effect which can ’be seen even in the

general urban population.l Increases in A.L.A. and c.p.excretion become measurable at blood-lead levels ofsome 40 ug. per 100 ml.

2

Subclinical neurotoxic effects caused by lead areless well established. Lately subclinical neuropathywas demonstrated by neurophysiological methods inneurologically symptomless lead workers, 3, 4 but a

causal relation between the nerve damage and blood-lead levels has yet to be shown. The presence orabsence of neurophysiological findings such as reducednerve conduction velocity and electromyographicabnormalities seem, indeed, to be quite unrelated tothe severity of total lead effect as judged by commonlyused criteria. 4 Subclinical encephalopathy is anotherlead effect for which the dose-response relationship is

1. Hernberg, S., Nikkanen, J. Lancet, 1970, i, 63.2. Selander, S., Cramér, K. Br. J. ind. Med. 1970, 27, 28.3 Catton, M. J., Harrison, M. J. G., Fullerton, P. M., Kazantzis, G.

Br. med. J. 1970, ii, 80.4. Seppalainen, A. M., Hernberg, S. Br. J. ind. Med. 1972, 29, 443.

unknown: David et al. suggest that hyperactivity maybe a manifestation of this in children. They notedsignificantly higher blood-lead levels in hyperactivechildren than in control children. But only 8 out of 62hyperactive children had a history of earlier lead

poisoning. That subclinical brain damage mayappear in the absence of overt poisoning is also

suggested by another study where lead workers weretested psychologically. 6 Although the workers werewithout clinical neurological symptoms, they showedvarious abnormalities compared with unexposedcontrols. The most prominent were slowness of

performance, psychomotor disturbances, slight intel-ligence defects, and personality changes. Clearly,neurological effects must be taken more seriouslythan the reversible early hsematological abnormalities.

Thinking in black and white terms is out of date,and the grey area of subclinical lead poisoning is

especially important now that lead is recognised as apublic-health hazard. In view of the enormous

number of published reports on lead toxicology, it isastonishing how little attention this area hasreceived. The need for further work is urgent, andinvestigators should use modern epidemiological andclinical methods and should not be restricted to well-known, specific manifestations of lead toxicity. Therehave been reports, for example, suggesting quitenon-specific effects such as inhibition of phago-cytosis,7 mitotic disturbances, and shortening of life-span in laboratory animals.9 These and other possiblemanifestations of lead toxicity certainly deserveattention. Dose-response relationships need to beestablished for as many effects as possible; and hereit should be recognised that susceptibility to leadtoxicity varies and depends on a number of factorsincluding age, season of year, calcium and phos-phorus intake, iron deficiency, dietary protein,vitamins, alcohol intake, presence of other metals, andcoexisting disease.1 The analytical accuracy of blood-lead determinations also deserves serious attention.

Inter-laboratory comparisons in the U.S.A. and

Europe 11,12 have revealed alarming methodologicalerrors. According to the latest, 12 involving 22

toxicological laboratories in the Common Market,values measured from the same blood-samples showeda ninefold range, and more than 30% of the resultswere classified as completely unacceptable. It is

quite evident that such a poor level of analyticalaccuracy makes interpretation of dose-responserelationships impossible. The magic borderline of80 ug. per 100 ml. should also be re-evaluated in the

light of these findings.

5. David, O., Clark, J., Voeller, K. Lancet, 1972, ii, 900.6. Hanninen, H. Cited by Hernberg, S. International Symposium on

Environmental Health Aspects of Lead, Amsterdam, Oct. 2-6,1972, paper 58.

7. Bingham, E. in Trace Substances in Environmental Health; vol.III, p. 83. Columbia, Miss., 1969.

8. Schwanitz, G., Lehnert, G., Gebhart, E. Dt. med. Wschr. 1970,95, 1636.

9. Schroeder, H. A., Tipton, I. H. Archs envir. Hlth, 1968, 17, 965.10. Goyer, R. A., Mahaffey, K. R. Environm. Hlth Persp. 1972, no. 2,

p. 73.11. Donovan, D. T., Vought, V. M., Rakow, A. B. Archs envir. Hlth,

1971, 23, 111.12. Berlin, A., del Castilho, P., Smeets, J. International Symposium on

Environmental Health Aspects of Lead, Amsterdam, Oct. 2-6,1972, paper 92.