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is believed to be the result of an abnormal response bythe host-possibly the failure of cell-mediated immunity.

In the Old Word, cutaneous leishmaniasis presents amore uniform appearance and, although it goes by manypopular names (oriental sore, Biskra button, Gafsasore, Baghdad boil, Delhi boil, Jericho boil, &c.), the

epidemiological pattern follows a definite course. Theinfection begins as a zoonosis affecting the semi-desertrodents such as gerbils (or, possibly, originally lizards 10)and burrow-inhabiting sandflies; man is infected byaccident when he strays into the steppes; the disease isthen introduced into human settlements where dogs alsoharbour the parasite, and eventually rodents and dogsentirely disappear from the scene and inter-humantransmission by domestic sandflies, as in India, is thefinal result. In the pristine forests of Central and SouthAmerica, man is only exceptionally attacked, but if thecountry is disturbed either by deforestation or byrevolutions when the inhabitants take to the woods, thedisease becomes epidemic. A similar situation arose

recently in the Middle East war 11 when many cases oforiental sore appeared among the troops, and, inci-

dentally, a new reservoir (a merion) of the infection wasdiscovered.The visceral type of leishmaniasis (kala-azar) has a

similar composite picture in Latin America, Kenya andthe Sudan, Europe (even the French Riviera), the MiddleEast and the southern republics of the U.S.S.R., theIndian subcontinent, and China. There are manyzoogeographical peculiarities in the distribution of kala-azar and in its reservoirs and its vectors. Kala-azar is

usually easy to diagnose by the isolation of the organism,but if it arises in unusual circumstances it may not be

recognised immediately. For instance, cases associatedwith blood-transfusion have been reported in northernlatitudes like Sweden 12 and England, and even venerealinfection has occurred.13 The identification of theindividual species of Leishmania is much more difficult,for morphological differences do not exist and the

investigator is dependent upon complicated tests such asthat of ADLER 1 or the new haemagglutination reactionof BRAY and LAINSON.14 With the exception of espundia,leishmaniasis is usually readily cured with antimonialdrugs, but its prevention presents many problems. Onthe one hand, the synthetic insecticides like dicophane(D.D.T.) quickly destroy the domestic sandflies, as

happened fortuitously in India during the malaria-eradication campaigns; on the other hand, when thevectors are exophilic and when sylvatic reservoirs arepresent, eradication of the disease or even its controlbecomes much more difficult. The Russians 15 suc-ceeded by the large-scale poisoning of the gerbils, and theChinese by the destruction or cure of infected dogs, butin Africa and Latin America no solution has yet beenfound. MANSON-BAHR 16 attempted to immunise the10. Hoare, C. A. Proc. Int. Congr. trop. Med. Malar. 1948, 2, 1110.11. Gunders, A. E. Nature, Lond. 1968, 219, 8512. Barr, M. E. Bengtsson, Garnham, P. C. C., Huldt, G., Kostmann, R.

Proc. Int. Congr. trop. Med. Malar. 1963, 7, 315.13. Symmers, W. St. C. Lancet, 1960, i, 127.14. Bray, R. S., Lainson, R. Trans. R. Soc. trop. Med. Hyg. 1967, 61, 490.15. Latyshev, N. L, Kryukova, A. P. Trudy Voenno-med. Akad. RKKA

1941, 25, 59.16. Manson-Bahr, P. E. C. Trans. Roy. Soc. trop. Med. Hyg. 1961, 55, 550,

population in an endemic area in Kenya by vaccinationwith an avirulent strain of Leishmania donovmsi 17

derived from ground squirrels; although the method hadsucceeded in volunteers, it failed in the field, perhapsbecause the viability of the vaccine had become lost inthe course of the campaign. Nevertheless, the use ofvaccines, after further development, may well prove thebest method of prophylaxis of the visceral disease, andthis method has been successfully applied for centuriesin the Middle East for the prevention of cutaneousleishmaniasis.

Clearly leishmaniasis has immense practical import-ance and offers a challenge to the epidemiologist,immunologist, and parasitologist. It is not surprising,therefore, that the World Health Organisation 18 held alarge international symposium last year in Moscow todiscuss the subject, and that many Governments andFoundations (including British) are deeply involved inresearch.

Annotations

ANTILYMPHOCYTE SERUM

MANY preparations of antilymphocyte serum have nowbeen tested in animals and in man. Some have beenraised by immunising rabbits with mouse thymocytes.Others have been raised in horses by injecting whateverhuman lymphoid material was available, includinguntreated cadaver spleen. Sometimes the unmodifiedserum has been used, sometimes the separated globulin,after absorption with red blood-cells.

Starzl’s group in Denver have given antilymphocyteglobulin, in combination with azathioprine and predniso-lone, to 53 patients who received renal homografts.19 Allthe patients had fever, and also pain, tenderness, erythema,and swelling at the injection sites. 11 had anaphylacticreactions, which led to the treatment being stopped in 8.Skin reactions and joint pain were common. In 9 patientsa thrombocytopenia of less than 50,000 per c.mm.

developed at some time during treatment. In spite of allthese drawbacks, the one-year survival of patientsreceiving homografts rose to 95%, and no deaths weredirectly associated with antilymphocyte-globulin treat-ment. Renal biopsy in the first 8 of these patients showedno evidence of serum-induced nephritis at the end offour months.20

Other clinical studies in a few patients have beenreported. The lymphocytes which Carraz et al 21 usedto raise an antiserum were obtained from thoracic-ductfistulas induced in patiems awaiting a kidney graft. Side-effects, similar to those described by Starzl, were seenin 15 treated patients, but treatment had to be stoppedin only 1 case of serum sickness. No toxic effects onthe kidney were recorded.

Yet another approach has been pursued by Tsirimbas17. Heisch, R. B. E. Afr. med. J. 1957, 34, 183.18. W.H.O. Inter-regional travelling seminar on Leishmaniasis, U.S.S.R.,

May 22-June 10, 1967.19. Kashiwagi, N., Brantigan, C. O., Brettschneider, L., Groth, C G.,

Starzl, T. E. Ann. intern. Med. 1968, 68, 275.20. Starzl, T. E., Porter, K. A., Iwasaki, Y., Marchioro, T. L., Kashiwagi,

N. in Antilymphocytic Serum (edited by G. E. W. Wolstenholmeand M. O’Connor); p. 4. London, 1967.

Brochier, J.,21. Carraz, M., Traeger, J., Fries, D., Perrin, J., Saubier, E., Brochier, J.,21. Veysseyre, C., Prevot, J., Bryon, P., Jouvenceaux, A., Archimbaud,J. P., Bonnet, P., Manuel, Y., Bernhardt, J. P., Traeger Fouillet, Y.Rev. Inst. Pasteur Lyons, 1967-68, 1, 17.

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and his colleagues 22 They raised antilymphocyte serum inhorses by immunising them either with leukxmic lympho-cytes or with thoracic-duct lymphocytes, and they gave theproduct intravenously to 6 patients with chronic lymphaticleukaemia. Although the doses were sufficient to producelymphopenia, no adverse effects were noted duringperiods of treatment up to eighteen days. This may,perhaps, have been too short a time to assess the long-term risks of renal damage or serum sickness (or ofincreased susceptibility to viral infection 23) ; but theresults are nevertheless of interest. Starzl’s group, whoare especially concerned about serum sickness, believethat their own preparation might be made safer withoutloss of potency by isolating pure yG-globulin, since thisimmunosuppressive fraction seemed to be the least likelyto provoke immune reactions against the horse globulin.Thus, the choice of preparation, its further fractionation

and absorption, and the route of administration mayall be important. Now that Lance and Medawar 24 haveshown that antilymphocyte-serum products may abolishthe immunological opposition to grafts, the further

purification and toxicity testing of different types of anti-lymphocyte serum assumes increasing interest.

TORREY CANYON: A POSTSCRIPT

THE success of the French authorities in sinking nearly30,000 tons of oil from the Torrey Canyon with powderedchalk seemed too good to be true, and, because this methodof dispersing the oil was thought by the British Govern-ment to be impractical and not very effective, 21/2 milliongallons of detergent were poured on to the beaches ofsouthern England. Although a detailed ecological andexperimental study by scientists from the Marine Bio-logical Station at Plymouth 25 has since shown that thechemicals used were highly toxic to marine life, the

application of detergents remains the officially approvedmethod for dealing with oil pollution. A team from

Plymouth, lately returned from France, found no evidencethat the sunken oil had interfered with the fisheries thereor with fishing gear. 26 Even the crustacean fishing-grounds,which might reasonably have been expected to be sus-ceptible to contamination, escaped damage. The most

surprising finding was that the oil itself had disappeared.The areas in which the oil was sunk were carefully markedat the time, and, although some of the oil could haveshifted to other areas, it is unlikely that 30,000 tons of itcould have vanished in this way. A more plausibleexplanation (and one which gains support from the lackof interference with the fisheries) is that the pollutant wasrapidly broken down by bacterial action, which hadpresumably taken care of the small amounts of oil thatwere continually being washed up even before the ToreyCanyon ran aground. Bacteria work fastest on finelydivided material, and to ensure success with sunken oil itmight be wise in future to add oil-degrading bacteria tothe powdered chalk. The biologists’ earlier reportshowed that the use of detergents was a mistake: theirfollow-up of the French oil-sinking experiment confirmsthat the British Government should reassess its policy fordealing with oil pollution.22 Tsirimbas, A. D., Pichlmayr, R., Hornung, B., Pfisterer, H., Thierfelder,

S., Brendel, W., Such, W. Klin. Wschr. 1968, 46, 583.23. Hirsch, M. S., Murphy, F. A. Lancet, July 6, 1968, p. 37.24 Lance, E. M., Medawar, P. B. ibid. 1968, i, 1174.25. Smith, J. E. Torrey Canyon ’ Pollution and Marine Life. London,

1968. See Lancet, 1968, i, 735.26 Guardian, July 18, p. 18.

HEXACHLOROPHANE IN THE NURSERY

THOUGH the decline in Britain in recent years ofneonatal infections (particularly by staphylococci) maybe due in part to more effective antibiotics, the widespreaduse of antiseptic agents such as hexachlorophane hasprobably been important as well. Hexachlorophane is themost useful of the chlorinated bis-phenols. It has highbacteriostatic activity, but it requires a long time to killmicroorganisms. It is more effective against gram-positive than gram-negative bacteria, and there is someevidence that it may even encourage the growth of coli-form bacilli.1 This point is of particular importance inthe light of evidence presented on p. 177 by ProfessorForfar and his colleagues, and elsewhere by Light et al.of Cincinnati, that, although the introduction of hexa-chlorophane bathing of infants has resulted in a steepfall in colonisation by Staphylococcus aureus, there hasbeen a significant increase in the incidence of infectionsfrom which grari-i-negative bacteria are cultured.

This inverse connection between gram-negative organ-isms and Staph. aureus is an example of the bacterialinterference which is being increasingly recognised.O’Grady and Wittstadt 3 demonstrated a similar linkbetween carriage of Staph. aureus and micrococci,diphtheroids, and coliform organisms in the nose.

Several epidemiological inquiries have demonstrated anincrease in Pseudomonas aeruginosa infections associatedwith a decrease in the incidence of Staph. aureus infec-tions. McCabe 4 has found that prior infection of chickembryos with avirulent staphylococci protected themagainst subsequent challenge with virulent staphylococciand against gram-negative organisms.

Bacteria sometimes synthesise enzymes which inhibitthe growth of other organisms; for example, staphylococcielaborate staphylococcins which inhibit the growth ofother staphylococci. 5 Some other examples of interfer-ence may be the result of competition between groups oforganisms for essential substances such as nicotinamide. 6The mechanisms underlying the inverse relationshipbetween colonisation by Staph. aureus and gram-negativeorganisms in hexachlorophane-bathed infants are un-

known, but Professor Forfar and his associates suggestthat reduction of gram-positive organisms may leaveroom for gram-negative organisms to grow and colonisesuitable sites, such as the umbilicus and mucous mem-branes. But the possibility of direct stimulation of growthof gram-negative organisms by hexachlorophane cannotbe ruled out.

An increase in gram-negative infections is obviouslyundesirable, and our contributors this week therefore

suggest that it would be reasonable to extend the local

antiseptic effect of hexachlorophane against gram-positive bacteria by using at the same time an agenteffective against enterobacteria, such as chlorhexidine.The strict surveillance of neonatal infections andthe organisms responsible must continue, for, what-ever antibacterial agent is used, resistant strains ofbacteria present in the environment may be selected byits use.

1. Stratford, B. C. Med. J. Aust. 1963, i, 309.2. Light, I. J., Sutherland, J. M., Cochran, M. L., Sutorius, J. New

Engl. J. Med. 1968, 278, 1243.3. O’Grady, F., Wittstadt, F. B. Am. J. Hyg. 1963, 77, 187.4. McCabe, W. R. J. clin. Invest. 1967, 46, 453.5. Reeves, P. Bact. Rev. 1965, 29, 25.6. Ribble, J. C. J. clin. Invest. 1965, 44, 1091.