YilltoaVTITRU!TI IN MALAYA TTY :COT CUON8L A ,%S. HOBSON, M.D., M.R.C. (19to Medical Specialist, iiritish Unitary Hos-ital) rinrqra, ,uela Lumpur. CONTENTS. 1. JR.4;FAJli, 2, INTRODUCTION. RIME OP LIVITOSPIROSIS IN I ALAYA 4. CLINICAL MATERIAL.... 9 5. SOURCE OP INFECTION... 10 6. CLINICAL PICTURE 12 P? 7. COMPLICATIONS.. .... .. ..... •••••••• ........ • 8. LABORATQRy I NITS STIOATION3 11 9. DIMREATIAL DIAGNOSIS 10. TREATVNT El)PENICILLIN • . 27 b) RENAL FAILURE . A t ( 0 ) GiMRAL 29 11. PROGNOSIS .... 33 12. POST-WORM FINDINGS '31/- 13. GENERAL DISCUSSION a)CLINICAL PICTURE. ..... .. *IN • II• 39 b)BLOOD ''RE; SURE........ ...... 39 COMFTICATIONS ii-0 DIAGNOSIS. LABORATORY IN1U.STIGATIONS • 9- 3 71ROGNOSIS 14-11- 14. SPalTAL DISCUSSIONS ENICILLIN iti V TIIINTMTHaMY'' .• . S-C c) RENAL PATHOLOGY.... PATHOGENESIS OP RENAL [,'AILURE fi e) PRWENTION OF RENAL FAILURE G i- 15. SUMMARY. 69 16. REFERENCES . .. ..... .. 70 17. A '!'ENDIX A.LABORATORY FINDINGS 73 B.CASE RgOORDS PREFACE. It is since (-)rld :or IT that ellaya has become one of the malor overseas stntions for the British Army. s is only to be expected, the incidence of disese affecting service personnel will tend to vary from the well annotated pre-1939 era, when India was the main overseas base. It is essential that this change of incidence should be noted, and clinical details of any common disease affecting personnel serving in the country should be carefully recorded for the benefit of future serving medical. officers. This especially arol_les to the present day, when such a large proportion of the R.A.M.C. is composed of National Oervice Officers, who in the majority of cases have not served previously overseas and require information t;cut t disef*ses they may be taped upon to treat. It is with this object in mind, tlit I hove tal,:en the opportunity of describing leptospirosis as seen !among service personnel in Malaya. The clinical material which formed the basis for this paper consisted of 27 eases which were admitted under my care during 1950, to the British Military Hospital, Kinrara, near Kuala Lumpur. Owing to the lac% of facilities for the carrying out of leptospiral agglutination tests and the repeated failure to demonstrwte leptospira by guinea pig inoculations, the cases were diagnosed. on clinical grounds alone, However. :.era rInd successful blood c'ultures from similar cases have been sent to the U.K.- for examination by rr. J. Q. Broom p,t the elloome Research Institution, London. Re has identified some of the leptospiral strains, thus confirming the general clinical diagnosis of these cases (1951). Recently Bucklc!nd (1951) has succeeded in transmitting the disease to -hamsters (cricetus auratus) after failing with guinea pigs. The complete clinical picture, complications and prognosis are discussed and comparison made with the renorts of previous Malayan writers. The differential diagnosis of the disease as seen service personnel Is fully discussed. Treatment with penicillin was employed and from the records stntintical evidence is elicited to suggest that the nntibiotic has no effect upon the duration of fever, but does iminish the incidence of febrile relapse. The,pathogenesis of renal failure in leptonnirosis is discussed in the light of the recent advances in knowledge about acute tubular necrosis; and possible oreventitive treatment suggested. A detailed list of laboratory findings which include modern biochemical investirations„ he8 been appended, to provide a record for puroses of comparison, ACKNODGMfOTS. I would like to express my appreciation of the invaluable assistance 71ven to me, in the maintenance of 3 detailed case sheets, by tlajor (now Lieut. Col.) R.M. VANUEIUN, R.A..C. who served as my assistant medical officer; to Major (now Dr.) J.B. L.D., t4.R.0.".0 for the many laboratory investir!ations and the post-mortem examinations: to the many ?:.A.R.A.U.C. Officers and R.A.M.C. Orderlies (some F:tilayan) who nursed so many of the cases heck to complete health. T wish to thank the Director-enernl, Meilical rervlces, for permirmion to utilize the necessary clinical records for this thesis. 2. INTR(DUOTION. wince 1886, when a German -physician named described four cases Of an acute febrile illnest, associ!vted with laundice, haemorrhages and splenic enlargement, the syndrome has been associated with his name by later observers. The disease was recognised in various parts of the world. In japan, in 191), IAADA isolated a spirochsete-like organism from cp,ses of the disease. This discovery was confirmed a year later by two R.A.W..O Officers - Stokes-and- Ryle (1916). These Officers isolated a similar organism, from cases occurring among troops of the British -army in Flanders. Noguchl (1917) considered that the morphology of this new organism was sufficiently characterstio to -warrant the creation of a new genus which he named Leptospira. tlince then, the genus has been expanded by the identification of many more species, some of Waich are not pathogenic to. man. The general term "leptospirosis" is now given to infections with the members of the genus; "eils" Disease being restricted by general usage to infection with L. ictero-haemorrhaglae. R:::7 11 L '~PTO `3IROnTS IN IIALATN.. The history of leptospirosis in alay to quite recent. As far as. can he ascertained, the description, by GALLOAY (1926)4 of four cases, was the first to be ottblished. He described the onset of the disease as being sudden, with a rigor, followed by headaohe, intense ,Tinacular rains, vomiting, prostr7tion and congested conjunctivae, Jaundice appeared on the fourth day and colncided with a fall of temperature. There was a trace of albumen in the urine and casts were present. During the following two days there was an aggravation of symptoms with rapid enlargement of the liver and the development of haemorrhages:5. A remission of the fever And symptoms-occurred on the 8th day or after. Two of the cases died of epistaxis and severe intestinal haemorrhages, a delirium of the uraemic type preceeding death. There was no mention of rashes, anuria or oliguria, or laboratory investimtions. iMETOFBR (1923), working at the Institute of Medical Research in Yuala TampUr, on an investigation into :4crub Typhus, demonstrated the oresence of pathogenic leptospira by guinea-pig inoculation, in the blood of a case of pyrexia of unknown origin. Fe found after such inoculation, that the guinea pigs developed fever on the twelfth. day. If killed, or at death, autopsy showed subcutaneous, pulmonary and intestinal haemorrhages. The pulmonary haemorrhages tended to be in the shape of a butterfly and leotospira could be recovered from the liver and 'oineys. He escribed 32 cases, in 13 of which,- he demonstrated. leptospl.ra in the blood b guinea-pig inoculation or by direct blocA,culture before the eighth day of the fever. In 14 wses, Teptospira were demonstrated by inoculation of the urine after the eighth da or by urine culture. Fletcher stfited that his findings led him to believe that Malayan infections were due to the following leptospira:- L. Ictero-Irtemorrhagine, 1. hebdomadis, pyrogenec,. L. mellothamby4 and erythan. An analysis of his clinical findings in the 32 canes is shown in Table I. There was one fatal case, 'oath being due to toxaemia and uraemia, LENTM'AIT (1929), described 7 canes. In six, he demonstrated leptospira by guinea-pig inoculation of blood before the eighth day of the disease or of . urine after the eighth day. He inoculated several guinea pigs daily and then re-inoculated the peritoneal fluid into a second series of •.animmls. An analysis of his clinical findinge in the 7 capes is shown in Table I. There was no mention of renal_ complication or the results of any ancillary laboratory investigations. DANARAJ (1950), reviewed 19 cases of /eptespirosin seen in Singapore General Hospital. These cases included seven which showed sJgns of meningitis. In all the cases except one, the Alurnosis was confirmed by transrnitting the disease to guinea-nigs by intra2eritoneal inoculation of blood, Ivine or cerebra-spinal fluid. In the remaining case, which proved fotni, leptospira were demonstrated in histolofJcal ctections of the kidneys and liver. An analysis of his clinical findings is shown in Table I. Chnnges in the eerebro-spinal fluid were evident in 3 cases, in which signs of meningitis were absent. Tie pointed out, that exce7t in the fatal case whch developed renal failure, meningitis only occurred in the nnicteric cases. He considered that the most important pathological finding was the elevation of the blood urea, which was found as early as the 2nd or 3rd day of the illness. In addition, Danara3 considered that the level of the blood urea was of prognostic significance, as those patients with blood levels of over 200 mgme were more ill than the remainder. TABLE T. A tale showing the percentnge incHence of the chief signs and s*ptoms derIcribed by ?4alsan dbservers, and including the present series for compariten. Author Fletcher Lewthwaite Tlanaral 'resent 1928 7929 1950 -leries To. of cases ;;-,, 7 19 77 Prostration 100. 71' Jaundice L4 14 -1 49 tuscular , T)inn 91' 36 100 67 . -uffuslon of eyes 961 86 ' 100 70 'evere Headache 25 86 74 r-T Immes•am.. Vomitinp7 47 297, + 56 4,/buminuria 100: 1003 ”. 77 Hrtemorrhages 19- NIL 26 eningism - - 22.- 22, Danaral stated that "vomiting, when present, was not severe". 4. CLINICAL MAT&RIAL. The twenty seven cases which form the basic for-this paper comprise fourteen British and thirteen Gurkha soldiers. These patients were adqtted under my care during 1950, to the nilitary Hospital at Kinrara, near IC.uala Lumpur. Three cases prove fatal, of which one was British, and two Gurkhas. As mentioned previously, the diagnosis of all the cases .