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Campylobacter EnteritisSEVEN years ago, campylobacter infections were

regarded as a rare cause of human disease. Sincethe first description by VINZENT et al. in 1947, only111 cases had been reported, mostly from the U.S.A.(The name campylobacter, meaning curved rod,was coined in 1963 when SEBALD and VÉRON2 dis-

tinguished the organisms genetically, biochemi-

cally, and serologically, from the true vibrios suchas Vibrio cholerae and V. parahaemolyticus.) In

veterinary medicine, campylobacter infections aretaken very seriously: Campylobacter fetus vener-ealis causes enzootic sterility in cattle and C. fetusintestinalis causes abortion in sheep and cattle. Inman, C. fetus intestinalis (serotype A biotype II,and serotype B) is an opportunist-that is, mostaffected patients have some predisposing factorsuch as cirrhosis, immunosuppression, neoplasm,or damage to heart-valves.3 Pregnant women andinfants are at risk. But a different group of campy-lobacters has now taken the stage, as a commoncause of enteritis in otherwise healthy people.These organisms were first recognised by KING4 in1957, who originally called them "related vibrios"because they had features in common with VIN-ZENT’S organism but were antigenically different.VERON and CHATELAIN5 saw this group as repre-sented by the two species C. jejuni and C. coli

(listed by SMIBERT in Bergey’s Manual as C. fetusss jejuní); but later work suggests that the group isheterogeneous and made up of many serotypes, sothere is much to be said for keeping the term"related campylobacters" till more is known.When KING did her work, only 12 patients with

"related"-campylobacter infection had been

reported. The most prominent symptom was

diarrhoea, but in all cases the organism was isolatedfrom blood: attempts to isolate it from fxces failedbecause of overgrowth by coliforms. Ten yearswere to pass before BuTZLER and his colleagues inBrussels overcame the problem of selecting campy-lobacters from mixed bacterial populations. Theyused a method that depended upon the ability ofcampylobacters, which are very small, to passthrough a filter that retains most other bacteria. By

1. Vinzent, R., Dumas, J., Picard, N. Bull. Acad. nat. Méd. Paris, 1947, 131,90

2. Sehald, M., Véron, M. Ann Inst. Pasteur, 1963, 105, 897.3. Butzler, J. P , Dereume, J. P., Barbier, P., Smekens, L., Dekeyser, J. Nouv.

Presse méd. 1977, 6, 1033.4. King, E O. J. inject. Dis. 1957, 101, 119.5. Veron, M., Chatelain, R. Int. J. system. Bact. 1973, 23, 122.

this means they isolated campylobacters from thefaeces of 5.1% of children with diarrhoea and 1.3%of children without diarrhoea.6 In 1977 SKIRROW7isolated "related" campylobacters from the fsecesof 57 (7.1%) of 803 unselected patients withdiarrhoea. Experience in Britain,’-1° Sweden, 12 theNetherlands,13 and elsewhere shows that the inci-dence of "related"-campylobacter infection is high-est in young children but that people of all agesmay be affected, some of the most severely ill pa-tients being adults. Reports from Africa suggestthat the organism may be very common in the tro-piCS.14 In Brussels the isolation-rate increases dur-ing the summer.15 In the United States a large out-break (about 2000 cases) has just been reported,apparently associated with consumption of waterfrom a public supply.16 As with all enteropatho-genic bacteria, carriage is compatible with health.Something under 1% of the population are carriers,and commonly they are contacts of patients withenteritis. There have been several outbreaks in nur-series and other institutions. Campylobacter enter-itis is usually an acute diarrhoeal illness which lastsseveral days, with or without fever.’ The diarrhoeais often slight but sometimes it is frankly watery ormucosanguinous and accompanied by vomiting,dehydration and electrolyte disturbance. Apartfrom diarrhoea the outstanding symptom is ab-dominal pain, which can be severe and sometimesbrings the patient to a surgical bed. The averageincubation period is thought to be about 5 days butit probably ranges from 2 to 10 days. Specific ag-glutinating antibodies appear in most patients dur-ing the illness. 7, 17 The site of infection seems to bethe jejunum and ileum: in affected children.CADRANEL et al. 18 isolated campylobacters fromileal, jejunal, and gastric aspirates, and acute in-flammation of the jejunum and ileum has been seenat laparotomy. Invasion of the bowel has been seenin chickens fed with isolates from human beings.l9

Campylobacteriosis is transmitted by ingestionand carriage in the intestine. Sometimes the

organisms enter the bloodstream, perhaps in a boutof diarrhoea or because of a change of intestinalflora or some immunological deficiency. 18 In cam-pylobacter septicaemia, the treatment of choice is

6. Butzler, J. P., Dekeyser, P., Lafontaine, Th. Antimicrob. Agents Chemother.1974, 5, 86.

7. Skirrow, M. B. Br. med. J. 1977, ii, 9.8. Dale, B. ibid. p. 318.9. Tanner, E. I. ibid. p. 579.

10. Pearson, A. D., Suckling, W. G., Ricciardi, I. D , Knill, M., Ware, E. ibid.p.955.

11. Telfer Brunton, W. A., Heggie, D. ibid. p. 956.12. Landquist, B., Kjellander, J., Kosunen, T. ibid. 1978, i, 303.13. Severin, W. P. J. Ned. T. Geneesk 1978, 122, 499.14. De Mol, P., Bosmans, E. Lancet, 1978, i, 604.15. Lauwers, S., De Boeck. M., Butzler, J. P. ibid.16. Morbid. Mortal. wkly Rep. 1978, 27, 207.17. Butzler, J. P. Lancet, 1973, ii, 858.18. Cadranel, S., Rodesch, P., Butzler, J. P., Dekeyser, P. Am. J. Dis. Child.

1973, 126, 152.19. Butzler, J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G. Proc.

int. Congr. Chemother. 1977, p. 174.

136

gentamicin. In enteritis, the infection responds tofurazolidone or erythromycin, but isolation of cam-pylobacters from the stools is not necessarily an in-dication for antibiotic treatment. Although man-to-man transmission is a common mode of spread, theinfection is undoubtedly a zoonosis. As with sal-monellosis, many species, including birds,2O har-bour these organisms. Some human infections havebeen traced to contact with poultry (live and

dressed) and to young dogs with diarrhoea. We donot yet know to what extent animals contribute tothe pool of human infection.

Testicular Infiltrates in ChildhoodLeukaemia: Harbour or Harbinger?TREATMENT of acute lymphoblastic leukaemia

(A.L.L) has revealed latent features of the disease.Meningeal leukaemia thus became a major problemin the 1960s, supposedly because the blood/brainbarrier makes the meninges a sanctuary from

chemotherapy. Eradication of occult meningealdisease has greatly improved prognosis, but newtroubles have arisen. The prognosis for boys is nowsubstantially worse than that for girls (see p. 128).Could this be related to testicular infiltration?

_

Testicular involvement in childhood leukaemiawas seldom recognised before 1960. It is rarelypresent at diagnosis, usually being seen in associ-ation with disease recurrence. Most of the patientshave A.L.L., but in less common forms of leukaemiathe risk may be higher.2 Testicular leukaemia is pri-marily a disease of prepubertal boys, though thefact that it does occur in young men treated forleukaemia and T-cell lymphoma4 suggests that itmay be seen increasingly in older patients as sur-vival improves. In 162 males treated at one hospitalbetween 1962 and 1971,5 the incidence of testicu-lar relapse was 14%. Testicular infiltration in nec-ropsy series varies from 29% to 92%.6 Clinically,testicular involvement tends to be related to

ominous features such as high initial white count,3 3

organomegaly, and age at diagnosis of under 2 orover 8. The symptomless swelling is seldom drawnto the doctor’s attention by patient or parents, and

20. Peckham, M. C. Diseases of Poultry. Ames Iowa State University, 1972.1. Pinkel, D. Cancer, 1971, 27, 247.2. Sullivan, M. P., Hrgovcic, M. in Clinical Pediatric Oncology (edited by

W. W. Sutow and others); p. 371. St Louis, 1977.3. Nies, B. A., Bodey, G. P., Thomas, L. B., Brecher, G., Freireich, E. J. Blood,

1965, 26, 133.4. Bloomfield, D. D., Frizzera, G., Gajl-Peczalska, K., Brunning, R., Kersey,

J. Proc.Am. Soc. clin. Oncol. 1978, 19, 378.5. Prieto, C., Hustu, O., Aur, R. J. A., Simone, J. Proc. Am. Ass. Cancer Res.

1975, 16, 178.6. Stoffel, T. J., Nesbit, M. E., Levitt, S. H. Cancer, 1975, 35, 1203.7. Steinfield, A. D. Radiology, 1976, 120, 681.

it can arise at any time-sometimes as late as 7

years after diagnosis, and after treatment has

stopped. When the testes become involved duringtreatment the patient will usually have other poorprognostic features, and within a few months dis-ease can be expected in bone-marrow, central ner-vous system, and elsewhere, with short survivalthereafter.6 The most important group are thosepatients with an otherwise good prognosis in whomtesticular leukaemia is the sole manifestation of

relapse. In this group the condition is usually diag-nosed in the first year after completion of chemo-therapy. Almost half the patients in the latestM.R.C. report9 had testicular relapse as the sole in-itial recurrence. The overall incidence was 13%.However, if the testis is a sanctuary site like the

meninges and is protected by a blood/testis barrier,then the actuarial risk to patients who might other-wise have achieved a long remission is 30%.

There are difficulties in interpreting the data. Anapparent excess of testicular relapse in those on theUKALL 11 schedule randomised to receive cyclo-phosphamide could be due to the dropping of spinalradiotherapy as part of their central-nervous-sys-tem prophylaxis. More importantly, the resultscould also be due to a secular trend, since increas-ing awareness of the problem of testicular diseasehas changed the diagnostic threshold. Testicularrelapse could easily have been overlooked when itoccurred in association with haematological relapse,since new or more intensive chemotherapy willoften cause shrinkage of the testicular swelling.Control of testicular infiltrates by chemotherapy isalso evident from the clustering of cases in the firstfew months after treatment is stopped; whateverthe duration of chemotherapy. This sensitivity tochemotherapy challenges the sanctuary theory. Aretesticular infiltrates the source or merely a signal offurther systemic disease? The question is critical tothe planning of treatment.

NIEs et a1. investigated 15 patients who died inapparent complete remission of their leukaemia andfound extramedullary disease in 10. 3 of the 4males had testicular infiltrates, but these 3 (allmore than 20 years old) all had leukxmic infiltratesin other organs. MATHÉ et al. 10 found evidence ofleukaemia in 12 of 31 patients apparently in com-plete remission. 4 had disease in at least one of thesix bone-marrow sites biopsied, 4 had liver infil-trates, 4 had C.N.S. involvement, and 2 had renalinvolvement. Testicular disease was found in only1 of the 13 males who had biopsies. SHARP et al. n

8. Finklestein, J. Z., Dyment, P. G., Hammond, G. D. Pediatrics, 1969, 43,1042.

9. Report of M.R.C. Working Party on Childhood Leukæmia. Br. med. J. 1978,i, 334.

10. Mathé, G., Scharwzenberg, L., Mery, A. M., Cattan, A., Scheider, M.,Amiel, J. L., Schlumberger, J. R., Poisson, J., Wajcner, G. ibid. 1966, i,640.

11. Sharp, H. L., Nesbit, M. E., D’Angio, G. J., Krivit, W. Cancer, 1967, 20,1403.