57 Feb., 1949 j EDITORIAL

nostic titre is 1 in 1(30 but a rise in titre from 1 in 20 or 1 in 1 is significant (Rivers, loc. cit.). Indian Medical Gazette Even a titre of 1 in 100 may be accepted (War Office, loc. cit.). (8) Para-amino-benzoic acid given in the first week of the has a favourable influence on the course of the disease. DDT will kill all lice' on a FEBRUARY (9) dusting powder patient. The dusting is repeated after a week. (10) A subject recovered from classical is immune to the murine and vice versa. TYPHUS typhus 2. Murine causal is While the classical is now a typhus.?Its agent typhus R. mooseri which is borne the matter of almost ancient in medicine, by rat-, history same which other forms of this of fevers have been Xenopsylla cheopis (the spccics group The are endemic within the last 20 or so. fhe carries ). synonyms recognized years urban of latest information about the latter was obtained typhus, typhus, shop typhus Malaya, flea and rat typhus : there arc at least during the World War II only. It was of typhus 6 names. military importance and remained a hush-hush affair so far as the general, non-service, medical The causal agent is capable of causing an after a few human profession was concerned. Details have been epidemic passages through lice from released only recently and have appeared in and is serologically indistinguishable serum of books (War Office, 1946; Rivers, 1948; Stitt, R. prowazeki, the the patient reacting Clough and Branham, 1948; Gradwohl, 1948). with OX19 similarly. The agent multiplies in the gut of the flea the insect louse is harmed Twelve their Nomenclature, Causal without harming (the Fevers, the of the which con- Agents, Vectors, etc. by agent ) tinues discharging it in its ffeces. The has been divided into 12 levels group From rat to rat the agent is carried by the named and described as follows :? same flea and by rat louse Polyplax spinubsus. 1. Classical epidemic typhus.?The causal The infected rats can impart infection to man agent is Rickettsia prowazeki, louse borne, lhe by infecting food with their urine. A human war synonyms are jail fever, camp fever, fever, case cannot transmit the disease to other persons famine fever, ship fever, hospital fever, petechial direct. morbus fever, liungaricus, typhus mstorique, The disease is milder than the tabardillo epidemic typhus typhus exanthematique, detoypho, and has been reported recently from Bombay and fleckfieber. There are at least 14 names. (Soman, 1947) and Calcutta (Lowe, 1946; The only items to which attention has been Krislman et cil., 1949; Chaudhuri and Ohakra- drawn recently are: (1) The mind of the varti, 1949). is far from inactive; the 'patient really imagination conjures up the most frightful 3. Drill's disease.?The present opinion on and fancies to which implicit belief is attached, this form of typhus fever is that it is a of which a distinct recollection may remain after recrudescence of the in a sub- ' epidemic typhus recovery (Murchison, 1862, quoted by Rivers, ject who had it previously. Such a patient can loc. reveals cit.). (2) The electron microscope start an epidemic. The causal agent resembles that rickettsiae, like vaccine and bacteria, that of the epidemic typhus and not of the appear to have a limiting membrane surround- . In America the nomenclature ing the protoplasm in which are embedded of Brill's disease is used for fever found in granules. (3) Macchiavello's method of staifnng immigrants from Europe only. Further observa- is the most for rickettsise. satisfactory method tions on the recrudescence are necessary. Smears are (?') fixed lightly by heat, (?) stained for 3 to 5 minutes with 0.25 per cent basic fuchsm 4. The of Rocky Mountain of in distilled water, (in) dipped quickly in 0.25 to America.?The causal agent is Dermacen- 0.5 per cent citric acid in distilled water, (iv) troxenus rickettsi, also known as Rickettsia placed in running tap water, {v) Hooded with 1 rickettsi, R. brasiliensis and R. typhi. It is per cent methylene blue in distilled water for a tick borne and about a dozen ticks have been few seconds, (vi) washed briefly in running tap incriminated under the leadership of Derma- water, and [vii) dried with filter paper. (4) centor andersoni. The infection is trans- About 10 per cent of cases and many experimental ovarian. This is contracted in the forest by animals do not develop agglutinins for proteus small rodents or other mammals. OX19. (5) There is no evidence of a true exo- The other names are mountain toxin produced by the rickettsia?. (6) Infection fever, typho- malarial fever, bull fever, black blue with will of course produce fever, disease spotted fever, Sao Paulo mural agglutinins, and some subjects may have them typhus, Minas Geraes fever and Tobia fever. There are without any known cause. The titre naturally at least 9 names. in these cases will be constant. (7) The diag- THE INDIAN 58 MEDICAL GAZETTE [Feb., 1949

The only items to which attention has been bite and regional . A rash drawn are : The disease can be lately (1) may be present. in animals. In duplicated exactly experimental The causal is Dermacentroxenus the guinea-pigs the lesions in the brain and agent rickettsi var. borne ticks not necess- scrotum do not differ appreciably from those pipperi by arily on domestic animals and pets. found in experimental typhus and are more intense. (2) Most of the natural hosts show The Weil-Felix reaction is positive with 0X19, only inapparent infection. (3) Most large 0X2 and also OXK. This is rather an domestic animals are insusceptible. (4) In important point in India where tick typhus plasma tissue cultures the rickettsise show pre- (vide infra) and are known to ference for the nuclei of the cells. (5) The occur. } rickettsise are too to Berkefeld and N big pass 7. Rickettsial pox.?The described or candles or Seitz filter Red and recently W pads. (6) rickettsial disease in New York white blood cells from infected (Greenberg, guinea-pigs Klein and Huebner, 1947) is character- retain their even after Pelliteri, infectivity repeated ized a firm red papule which and brain and in by (i) develops washings; spleen suspended into a vesicle and dries to form a black retain their for a if scab, glycerol infectivity year (h) an chill and fever about a week stored at 7?C. Weil-Felix reaction does not abrupt later, (7) and a few days later still a the disease from (iii) maculo-papular distinguish epidemic typhus. rash. The nodules are affected. of 0X19 is than that regional lymph Usually agglutination higher The general rash also becomes vesicular and of but the reverse be the 0X2; occasionally may then forms black scabs. The disease is on the case. are not useless |? (8) Sulphanilamides only whole mild. in treatment but probably harmful. (9) Treat- j The causal is R. akari which mite ment with serum from rabbits hyperimmunized agent is borne. The mite concerned is with infected ticks or inoculated yolk sac is use- I Allodermanyssus on the ful. (10) Para-amino-benzoic acid is also sanguineus found house mice (Mus useful. (11) While the infection in man usually | mus cuius). occurs in those handling livestock and game, Weil-Felix reaction is negative. women and children be occasionally may Rickettsial pox is related to the In- [ Rocky infected by ticks on domestic pets. (12) Mountain fever in that guinea-pigs recovered fected unfed ticks exhibit 2 in phases biting from the pox are partially immune to the fever. {i) a phase of immunization, and (ii) a phase of infection. The rickettsias in starving tick 8. North .?This need activation by a meal of blood. The animal j mild febrile disease has been described from bitten first is immunized and the one bitten later Australia. It is caused by a rickettsia probably fever is infected. The same difference is shown by I transmitted by ticks. Q is another name. infected tick's eggs : Fresh eggs infect while It also occurs in the U.S.A. The.causal agent dried eggs immunize. (13) Tick tissue, from is R. burneti. a tick fajces are crushed tick, and fresh capable Weil-Felix reaction is negative with 0X19, of causing infection through an abrasion. 0X2 and OXK. (14) There is no proved satisfactory repellent There is some cross resistance this which will prevent tick attachment. between fever on the one hand and the South African tick fever and murine on the other. 5. Boutenneuse fever.?This is an acute fever typhus of the Mediterranean basin. The synonyms arc 9. Tick bite rickettsial fever in India.?A lievre escheronodulaire, cxantheime typhorde spotted-fever-like illness was described some dothiendermic exanthema infectiet esteral, aigue, time ago (Megaw, 1921) in the United Provinces. exanthematous fever of Conor epidemique, fever, Later similar cases were reported from Mysore and Brucli. There are at least 7 names. It is (Ileilig and Naidu, 1941, 1942). characterized by maculo-papular rash on palms and soles and black spot usually at the site of 10. Tick bite rickettsial fever in Russia.? a tick bite. Such infections have been reported (Rivers, loc. cit.). The causal agent is Dermacentroxenus conori, similar to D. rickettsi borne by the dog tick, Weil-Felix reaction has been commonly Rhipicephalus sanguineus. positive with 0X19. Rickettsia have been iso- lated from naturally infected ticks. The Weil-Felix reaction may be positive with both 0X19 and 0X2 in equal titre. Italicized headings 4 to 10 deal with which in the same group with Rocky The disease to be more fall appears widespread Mountain Hence the than is believed. of spotted fever: details, generally Kenya typhus India is nowhere near East Africa is identical with boutenneuse fever. although geographically the region of the typical disease. The tick R. pulchellus may also be a vector. 11. Scrub typhus.?'Seldom has a disease 6. South .?This is a emerged from comparative obscurity to notoriety mild fever with a local lesion at the site of the tick so rapidly as has scrub typhus' (Megaw, 1945). Feb., 1949] EDITORIAL 59

The synonyms of the disease are : tsutsuga- reaction time' in this disease. (6) Mite killer mushi. disease, mite-borne typhus, Japanese and repellent. DDT is of no value. DBP river fever, tropical typhus and rural typhus. (dibutyl-phthalate) and DMP (dimethyl- There are at least 6 names. phthalate are efficient mite killers. DBP has been used in the British Army. Two ounces of The causal agent R. orientalis also known as DBP will suffice for a man for a fortnight. All R. tsutsugamushi, R. akamushi and R. nippon- clothes are impregnated and the drug in them icum (Wilson and Miles, 1946) is transmitted lasts a fortnight; only excessive washing or by the larval mites of at least 3 species : rains remove it before that time. Benzyl Trombicula akamushi in Japan, T. deliensis in heavy benzoate promises to be a better drug. Malaya and India, and T. minor in New Guinea. The infection in the mites is trans-ovarian from 12. Trench fever.?This fever is now generally the mother as well as direct from feeding on believed to be rickettsial : Hence its inclusion jungle rodents as larvae. Only the lame feed in the typhus fevers. it has on blood. Weil-Felix reaction is of great value. Besides, militarily the same importance and the same epidemiology. The patient's serum OXK by the agglutinates Mass movements of humanity are liable to the second week. The agglutinin reaches its maxi- same risks as military movement: Hence the mum titre the end of the third week : And by in civil life of in India. The the titre from OXK is reached in this importance to-day highest are : ' synonyms Wolkman fever, His-Werner fever. the specificity' is not Unfortunately disease, shin fever, and shank fever : there are perfect : may also evoke a at least 5 names. similar response. The causal is R. borne The fever is for most of agent quintana by probably responsible louse Pedicvlvs humanus var. corporis. PUO (pyrexia of unknown origin) in India. body Two papers corroborating this statement appear The Weil-Felix reaction is negative with in this issue. It was first diagnosed in Calcutta 0X19, 0X2 and OXK. in 1935 by clinical and serological means (Afridi, During the World War II trench fever personal communication, made in consultation, harassed the German . in Russia. It in 1935). The mites at that time eluded detec- Army also broke out in Poland and was known as tion. As the fever was occurring among the the causal R. syces attention was directed to the fodder Weigl disease, agent being weigl. only, disease is identical with trench and grain for the horses and mules only. Weigl apparently fever. The only items to which attention has been drawn lately are : (1) Protective vaccines. Rickettsial Cultures and Antigens They are of three (f) mouse lung or cotton types, The organisms grow only in living cells. rat lung sac vaccine, and (iii) vaccines, (u) yolk Cultures for the of vaccines for agar tissue culture vaccine. (2) Para-amino- preparation immunization or for reactions with benzoic acid therapy. It has a definite value if serological sera of and immunized are commenced before the 7th day of illness. (3) the patients animals Chloromycetin. It has given excellent results obtained from : (?) infected tissue of insects, The appears to be use- arthropods and rodents, (ii) special tissue cul- (Editorial, 1948). drug 1 ful for all rickettsial fevers. (4) Sharply defined tures inoculated, and {Hi) yolk sac of the belts of the disease. Usually a road or a stream embryonated egg inoculated. is the dividing line. Jungle near habitation is ' Most of the rickettsise can be sedimented dangerous and secondary jungle' (land "pre- by viously cared for allowed to run wild) is centrifuging. Soluble in particularly (5) Mental processes antigens, probably protein nature, dangerous. have been obtained for R. R. mooseri and state. Said a doctor's wife recently after ^ prowazeki, ' and R. rickettsial the action on the sedi- her recovery from scrub : Races were | by typhus mented material of ether my trouble. The moment I fell asleep they diethyl (Topping, N. and M. Stitt et began : horses were on the race course, H., Shear, .T., quoted by al., racing arc suitable for goldfish in their bowl and dahlias round the loc. cit.). They complement fixation. house'. This lasted as long as the fever lasted ' a continuous dream. Writes a clinician : At one time when a great number of patients were Diagnosis being admitted to the hospital and we. were on Laboratory diagnosis presents considerable the look out for scrub typhus, it was found that difficulty. The Weil-Felix reaction is not positive if a was of patient with fever who suspected in every rickettsial condition. The agglutinin is scrub was to sit and lie did sit typhus asked up, not developed early in the disease. In some he was be a case of scrub up, found not to cases it does not develop until the convalescence. is 'the typhus' (Khan, 1947). Such combina- A rising titre rather than a high titre is looked tion of asthenia, lethargy, apathy and increased for. 60 THE INDIAN MEDICAL GAZETTE [Feb., 1949

The differential agglutination has been In scrub typhus the mouse infection test establish mentioned under every fever and may be ultimately appears to the diagnosis. summarized as follows : Ascites is a constant feature ancl smears from the peritoneum arc positive. All infected mice, do not sicken. scrotal Disease however, Guinea-pig Reaction reaction provides the distinction between this form of typhus and others. Typically the 1. Classical epidemic typhus 0X19 + + + + swelling is deep in murine typhus, superficial 0X2 + in Rocky Mountain spotted fever, absent in OXK scrub typhus and usually absent in classical 2. Murine typhus .. 0X19+H?h typhus. For inoculation washed rbc suffice. 0X2 + . Rats and mice can harbour the infection in OXK brain only. 3. Brill's disease .. 0X19 + + + The use of 0X2 does not appear to be very 0X2 + helpful on the whole. OXK In the war laboratories, rickettsial agglutina- 4. Rocky Mountain spotted tion tests with the antigens themselves have fever .. .. 0X19 -j?f- given differentiation between epidemic and 0X2 + murine typhus, a differentiation not possible OXK-++ with Weil-Felix reaction. The preparation of the however is not When 5. Boutenneuse fever .. 0X19 -f-f- antigens easy. standard are 0X2 + antigen suspensions available for all rickettsial infections more definite OXK + + diagnosis and inter-relationship between the infections will bite 6. South African tick be possible. Complement fixation will also be fever .. .. 0X19 -|?f- with suitable antigens, in 0X2 possible although + endemic areas it is not likely to give "much OXK ++ information. Presumably normal individuals in 7. Rickettsial pox endemic areas in the U.S.A. have given strong in weak dilutions of 8. North Queensland tick reactions their sera and 1946). .. .. 0X19 (Johnson Damson, typhus / 0X2 OXK A Point in Epidemiology 9. Tick bite rickettsial fever It appears quite possible that scrub typhus in India has been introduced into India recently, after fever the and during the World War 10. Tick bite rickettsial J ' in Russia II : Otherwise spread of fever' from Hindu places of pilgrimage would have attracted atten- 11. Scrub .. 0X19 typhus tion. half such are situated in 0X2 Nearly places No such spread has ever attracted OXK + jungles. + + attention. In the past PUO in the Army in 12. Trench fever .. 0X19 India has not been associated with manoeuvres 0X2 and bivouacs. Whether the fever now detected OXK will thrive or die out the next few years will show. The fact of its dying out will lend to the view of recent introduction. These reactions are based on Topley and support Wilson's Principles of Bacteriology and Immu- If the disease fails to thrive it will not bo nology, 1946, Memoranda on Medical Diseases the only disease so affected.. Adverse tellural in Tropical and Sub-tropical Areas, 1946, Stitt's influence in India on the causal agents of many Practical Bacteriology, Hematology and Para- diseases which cripple and kill elsewhere is sitology, 1948, and Gradwohl's Clinical Labora- striking (Greval, 1946). 1948. tory Methods and Diagnosis, Regarding When suitable soluble antigens are available, the relative intensity of the reaction the agree- it will be possible to look for endemicity by ment is not perfect. Even nomenclature of the examining sera routinely by complement fevers varies slightly. Sao Paulo rural typhus fixation with these antigens from samples left of the Memoranda, for instance, is merged into over after the Wassermann reaction. the Rocky Mountain spotted fever of Stitt. The results of Weil-Felix test should be Other Rickettsia- correlated with the clinical findings. The re- There are rickettsial other than those action has been found positive in the course of respons- other diseases like undulant fever, enteritis, ible for human diseases. Some cause diseases in in or with- and (Wilson and Miles, animals, others live arthropods, with loc. cit.). out causing inconvenience to the hosts. MEDICAL NEWS 61 Feb., 1949]

An Allied Micro-organism ^ bacilli] ormis, the causal agent of fever and is such a Oroya verruga peruviana, ' It has been considered closely micro-organism. ' similar' to rickettsise and rickettsia-like' (Hyman, 1946; Pinkerton, 1947). Another Micro-organism requiring Special Condition for Growth Donovania granulomatis, the causal agent of granuloma venereum, is such a micro-organism. Its primary culture succeeds only in the yolk sac of a developing chick embryo.

REFERENCES

Afridi, M. Iv. (1935) .. Personal communication. Chaudhuri, R. N., and Indian Med. Gaz., 84, 43. Chakravarti, H. (1949).

Editorial (1948) .. Ibid., 83,517. Gradwohl, R. B. H. Clinical Laboratory Methods (1948). and, Diagnosis. The C. V. * Mosby Co., St. Louis. Greenberg, M., Pelliteri, J. A. M. A., 133, 901. O., Klein, I. F., and Huebner, R. J. (1947). Greval, S. D. S. (1946). Indian Med. Gaz., 81, 254.. Heilio, R., and Naidu, Ibid., 76, 705. V. R. (1941). Idem (1942). Ibid., 77, 338. of Hyman, H. T. (1946) .. An Integrated Practice Medicine. W. B. Saunders Company, Philadelphia and London. Johnson, M. B., and Jour. Lab. Clin. Med., 31, Damson, S. R. (1946). 550.

Ivhan, N. (1947) .. Indian Med. Gaz., 82, 81. Krishnan, Iv. V., Smith, Ibid., 84, 33. R. 0. A.. Bose, P. N., Neogy, K. / N.. Ghosh Roy, B. K, and Ghosh, M. (1949). Idem (1949). Ibid., 84, 39. Idem (1949). Ibid., 84, 41. Idem (1949). Ibid., 84, 63. 171. Lowe, J. (1946) .. Ibid., 81, Megaw, J. W. D. (1921). Ibid., 56, 361. 109. Idem (1945). Brit. Med. J., ii, t Pinkerton, H. (1947). A Textbook of Medicine. Edited by R. L. Cecil.- W. B. Saunders Company, Philadelphia and London. Phila- Rivers, T. M. (194S) .. J. B. Lippincott Co., delphia and London, Montreal.

Soman, D. W. (1947) .. Indian Med. Gaz., 83, 649. Stitt, E. R., Clough, Practical Bacteriology, P. W., and Branham, Hematology and Para- S. E. (1948). sitology. H. K. Lewis and Co., London. on War Office (1946) .. Memoranda Medical in and Diseases _ Tropical Sub-tropical Areas. H. M. Stationery Office, London. Wilson, G. S., and Topley and Wilson's Prin- Miles, A. A. (1946). ciples of Bacteriology and Immunology. Edward Arnold and Co., London.