Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from POSTGRADUATE MED. J. '(1966), 42, 247 Annual Review INFECTIOUS DISEASES ANNUAL REVIEW OF SIGNIFICANT PUBLICATIONS HOBART A. 'REIMANN, M.D. Hahnemann Medical College and Hospital, Philadelphia, Pa. 19102, U.S.A. KNOWLEDGE of infectious diseases advanced as be the agent of choice for meningitis caused by usual during 1965. Evaluation of many newly pneumococci, H. influenzae and meningococci"l. introduced antimicrobic drugs continued. Their Trhe proper use of the new penicillins was out- great number, however, confuses physicians as lined,,a. Cephalothin l(Keflin) was active against to which ones to use, and some of them are no nonindole-producing Proteus, less so against better than the older ones. Much antimicrobic Klebsiella, Esch. coli and paracolon bacilli. therapy still is misapplied. An anthelmintic Pseudomonas was resistant. Seventy-six per cent agent successfully controlled a number of of patients infected by pneumococci, strepto- diseases. Antiviral drugs were sought. Attention cocci, nonpenicillinase-producing staphylococci, was given to rubella, its effect on the fetus and and the sensitive gram-negative just named were its persistence in the body. Hemorrhagic fevers successfully treated. A rash occurred in three of in Asia and South America received intensive 103 patients7. The drug has no particular advan- investigation. The causal relation of viruses, tage over other agents8. 'Motile strains of mycoplasmas and toxoplasmas to cancer and Klebsiella-Aerobacter were resistant to cephalo- leukemia in man remained obscure. Electron thin and cephaloridine, but sensitive to many microscopy disclosed new information in micro- other antimicrobics. Tihe opposite applied to biology and disease. The importance of urinary non-motile strains. The bacilli rapidly acquired copyright. tract infections at all stages of life was re- resistance9. Colistin sulfate failed to rid sal- emphasized. 'Recognition of infections caused monellas from 40 per cent of carriers. Bacilli by "atypical" *tubercle bacilli that resist anti- were suppressed duriing therapy'0. Colistin is microbic therapy served to extricate them fronm potentially nephrotoxic. Lincomycin was effec- classic;tuberculosis. Disturbed faunal and avian tive against staphylococci, pneumococci and ecology incident to population shifts in some hemolytic streptococci and is usefull against regions favoured an increase in the incidence of bacteria resistant to penicillin or erythromycin, encephalitis, hemorrhagic fever and Rocky and for patients allergic to those agents. Entero- Mountain spotted fever. Inapparent attacks of cocci, meningococci, gonococci and gram nega- http://pmj.bmj.com/ several epidemic diseases were observed and tive bacilli were unaffected by lincomycin". their significance was recognised. A vibrio Lincomycin was said to be as effective as peni- different from V. comma caused epidemics in cillin for the treatment of streptococcal pharyn- the Far East. gitiS12. Nalidixic acid (Negram) is effective for the treatment of urinary tract infections caused Antimicrobic Agents by Esch. coli., Proteus and other gram nega'tive bacilli. Resistance to it develops'3. on October 1, 2021 by guest. Protected New Antimicrobic Agents. Nafcillin' and Thliabendazolle, a broad spectrum anthelmin- cloxacillin2 were as effective as methicillin, tic, was effective for the treatment of infections oxacil!in, and cephalosporin in the treatment of caused by Strongyloides, Enterobius, Ancylo- staphylococcal infections. Nafcillin was used stoma, Ascaris, and Necator, without serious successfully in many cases of staphylococcal toxic effects'4. Successful treatment of cutaneous pneumonia, sepsis, arthritis and 'pyelonephritis larva migrans was described in four papers in in oral dosage of 4 to 8 grams daily.3 The over- the May 1965 issue of Archives of Dermatology. all death-rate of patients treated with nafcillin It was ineffective for Taenia solium or saginata was 38 per cent. All strains of staphylococci and weakly effective in trichiuriasis'5. Borrelidin were sensitive. Cloxacillin was not active against and vivomycin derived from streptomycin were enterococci. AmpiciHin was not as effective as said to be antiviral agents'6. Cycloguanil pamo- chloramphenicol for treating typhoid.4 The drug ate '(Camolar) was said to have been successful was as good as tetracyline for the prolongedl in the treatment of 26 of 30 patients with dermal treatment of chronic bronchitis5 and was said to leiishmaniasisl7. Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 248 POSTIGRADUATE MEDICAL JOURNAL April, 1966 Antimicrobic Therapy and Prophylaxis. A Penicillin G is 'the most active, cloxacillin, oxa- physician recommended the intravenous injec- cillin, cephalothin, and erythromycin less so, tion of 10 million units of penicillin every two and ampicillin and nafcil'lin the least30. In hours -to prevent surgical wound infectionsl8. England, 31 per cent of strains of hemolytic Should this be done, from 20 to 40 million units streptococci resisted tetracycline, particularly (12 to 24 grams) would be administered in a those present in aural and wound exudates and short period, mostly unnecessarily. Year-around dermal infections. Indiscriminate use of the administration of single injections of ,benzathine drug may have induced resistance'1. In a survey penicillin to new recruits satisfactorily controlled of Philadelphia hospitals, I ascertained what hemolytic streptococcalinfections and prevented huge amounts of antimicrobic drugs are dis- ensuing rheumatic fever'9. Should this plan be pensed. In an average month in one 500-bed applied routinely to all civilians, question arises hospital, 12 pounds of penicillin were prescribed if the harm therefrom, as yet inapparent, would -and the total cost per month of all antimicrobics overbalance the prevention of the few instances was about $16,000 (f5,714). 'Much effort is of rheumatic fever that occur and if such wasted by requesting unnecessary tests for general prophylaxis is justifiable. For example. microbic sensitivity. The reported results may after an epidemic of streptococcosis in 1953, be misleading or erroneous especiaUly from an only one case of acute rheumatic fever was over-burdened laboratory32 and poor submitted detected, -and none of the victims 'had evidence specimens. of chronic nephritis20. Many physicians still are concerned with the Antimicrobic agents are of no value for "blood-brain-barrier" and the small amount of prophylaxis against bacterial invasion during drug that enters spinal fluid. It i's far more acute viral respiratory tract infections2' 22 nor important, however, for the agent to attack the in unconscious patients23. As examples of un- microbe in 'the meninges, not in the spinal fluid, necessary prophylaxis and therapy, "vigorous" for which intravenous or intramuscular injection

antimicrobic therapy was applied in a patient is necessary. copyright. with esophageal stricture caused by an escha- Antimicrobic-sensitive bacteria may acquire rotic24 and in a patient with massive epistaxis. resistance by growth in the presence of other Prophylactically -administered agents rarely pre- resistant ones. Apparently, resistance may be vent bacterial superinvasion, and that which "caught" by exposure. Whether the change does occur may be even more difficult to treat22. can occur in vivo is unknown. Sixty-one per In guinea pigs injected with 50,000 units of cent of 450 strains of Salmonella resisted one or penicillin, the cecal flora was greatly reducedt more antimicrobic agents33. within 12 hours but later, a 10-million-fold The occasional beneficial effect of antimicro- increase in coliform bacteria occurred acoom- bic therapy in addition to the administration of http://pmj.bmj.com/ panied by severe cecitis, ileitis and lymphadeni- folic acid suggested that infection may play a tis and ibacteremia. This is an example of super- role in the cause of -tropical sprue4. infection resulting from disturbed normal A symposium on antimicrobic drugs was flora25. published in the November, 1965 issue of the A protracted outbreak of multiple drug-resis- American Journal of Medicine. tant Salmonella edinburgh infection iamong in- Harmful Ef#ects of Antimicrobic Drugs. fants was ascribed to previous unwise routine doses of Large penicillin caused anemia 'by on October 1, 2021 by guest. Protected use of antimicrobics26. Strains of staphylococci destroying erythrocytes35. Penicillin and its have become resistant to neomycin and bacitra- homologues caused nephropathy35a. Anaphylac- cin. These antimicrobics when used topically toid shock after oral therapy resulted in severe may induce microbic resistance27. neurologic residua.3 . After therapy for three Penicillin remains the drug of choice for months, oxacillin depressed the marrow and pneumococcoses. If the patient is sensitive there- caused hepatic dysfunction37. Chloramphenicol to, erythromycin is indicated. Cephaloridine, in dosage more than 50 mg./Kg./day regularly ampicillin, nafcillin, oxacillin, cephalothin, caused toxic amounts to accurmulate in the cloxacillin and tetracycline also are effective in blood. Depression of the.bone marrow occurred that order28. The method of treatment of when 25 jLg./ml. were attained. In two of 20 staphylococcosis was outlined in detail by Fin- patients, daily doses of two 'to six grams caused land29. Hemolytic streptococci have not become toxic changes in the marrow that disappeared resistant to antimicrobics excepting, in a few When the drug was stopped38. Chloramphenicol instances, to itetracycline. Anyway, tetracyclines caused optic atrophy39. Tetracycline rarely are not the agents of choice for treatment. causes anaphylaxis, 'but did so in a patient who Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from April, 1966 REIMANN: Infectious Diseases 249 was hypersensitive to penicillin40. Tetracycline in the control group contracted adenoviral infec- therapy also may incite candidiasis, photosen- tions52. Infection did not spread to antibody- sitivity, discolouration of teeth, and if decom- free persons in close contact wilth vaccinees. posed, may cause severe toxicity. Deteriorated Serologic studies of 269 recruits in Norway tetracycline caused severe nephropathy4l and disclosed a high incidence of infection with nep'hrogenic diabetes insipidus42. As for any adenovirus 4, but little or no respiratory disease. other antimicrobic, tetracyclines should be pre- Evidently, the epidemic was largely inappar- scribed in amount and duration not exceeding ent53. A severe epidemic first mistaken for that necessary to control infection. Sodium measles affected about 80 children in an insti- cephalothin caused an anaphylactoid reaction tute. Nineteen children had viral pneumonia, after its first intramuscular injection in a patient 12 had enteritis, 15 had encephalitis, and four who was hypersensitive to penicillin43. Colisti- died54. methate caused respiratory depression and mus- Rhinovirus. Nine serotypes of rhinovirus were cular weakness44. Orally administered neomycin isolated from 19 different victims of the com- was the probable cause of audio- and nephro- mon cold. A group of four new types appeared toxicity45. As a result of topical application, 26 in 1964. Viruses of different types were extant per cent of 1,538 patients were found to be in a season, but for short periods a 'single type sensitized to neomycin45a. Question was raised predominated. From the same group of students if antimicrobic therapy during early pregnancy with colds, two herpes simplex viruses and one in 85 women caused 12 malformed infants and adenovirus were isolated. The 'latter caused 13 abortions40. Among 26 victims of systemic severe febrile illness55. For unknown reasons, vasculitis, antimicrobic drugs were the cause in rhinoviruses like mycoplasmas cause disease less 47 Long-acting sulfonamide drugs probably often 'in infants and children than in adults. caused 116 cases of the Stevens-Johnson syn- They were isolated from 16 pneumonic infants drome (mucocutaneous fever)47a. and children and from those without pneu-

monia50. Volunteers inoculated with one rhino- copyright. virus were inoculated with another strain two Viral Infection of the Respiratory Tract to 16 weeks later. Those reinoculated two Influenza. Despite an official optimistic fore- weeks lIater with either virus were not ill. cast for 1964-65, influenza viruses A and A2 Evidently protection was afforded by both the caused intense local outbreaks in the United homologus and heterologus infection, but not States and in Europe, and even affected vac- after 16 weeks57. The hope of preparing an cinated persons. The antigenic nature of the effective vaccine is dimmed by the great variety viruses changes so rapidly that specific vaccines of serotypes; a vaccine specific for one strain can not be prepared quickly enough48. For the of rhinovirus protected volunteers against the http://pmj.bmj.com/ 1965-66 season, another recently isolated A2 homologus one, but not against others. Immu- strain will be added to A, A1, A2 and B strains nity lasted 12 to 18 months. Mineral oil or other now used49. Each component added to a vaccine adjuvants failed to increase immunogencity-5. diminishes the amount and effectiveness of the Interferon failed to have a protective effect others and one antigen may interfere with when given to volunteers infected with rhino- another. Interferon was present in the nasophar- virus, Coxsackie A21 and parainfluenza I yngeal secretions of volunteers infected with A. viruses59. virus50. Reoviruses, so far, have been regarded as on October 1, 2021 by guest. Protected Volunteers were infected with a strain of unimportant causes of respiratory tract infec- influenza virus derived from horses. Pretreat- tion. Studies of 406 persons, however, disclosed ment with an inactivated influenza virus failed evidence of infection with Type 2 in 88 per cent to interfere with subsequent experimental infec- and with Type 1 in 49 per cent60. Either the tion with A2 virus. Persons with high specific infection was mainly inapparent or the diagnosis antibody titer were infected with the virus, of overt disease seldom was made. and some with low titer or none at all 'resisted Respiratory Syncytial Virus. R.S viruses, for experimenital infection5l. some reason, attack infants and children more Adenovirus. Adenovirus Type 4 fed to per- often and more severely than older persons. In sons caused symptomless enteric infection with- Holland, 28 per cent of 88 children were infec- out involvement of the respiratory tract. Anti- ted. Complement-fixing antibody appeared in body appeared in the blood of all vaccinees. The four of six with bronchiolitis and in one third of procedure successfully immunized against infec- those with pneumonia. All recovered and anti- tion during an epidemic. Thirty-two of 132 men body in the blood decreased rapidly"'. One Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 250 POSTGRADUATE MEDICAL JOURNAL April, 1966 wonders how bronchiolitis can be distinguis-hed marized knowledge of viral and other non- clinically from pneumonia. In Finland, RS virus bacterial "atypical" pneumonias74. caused 15 per icent of acute infections in child- Mycoplasma. Although they are not regarded ren62. Bronchiolitis or pneumonia occurred in as true viruses, mycoplasmas as causes of 22 infants less than one year old. A commercial disease in man had been known and studied vaccine is in preparation. for decades especially by Dienes and Kliene- Serum tests indicated that 72 per cent of a berger, but attracted little attention. After German population had been exposed to RS Eaton's and Liu's observations relating Myco- virus. The lowest percentage (37 per cent) was plasma pneumoniae to pneumonia, it now is in seven-to-12-month-old infants. After the age recognized as important. in 1938, some patients of six years, 84 per cent had neutralizing anti- with pneumonia then regarded as of viral origin, body';3 and this may account for the lesser undoubtedly were infected with Mycoplasma. frequency and milder disease as age advances. At the same time, others had only pharyngitis An immunofluorescent technique is reliable for and a few had severe systemic disease also the typing of iRS virus in about 24 hours';'. without pulmonic involvement75. Various Myco- Coxsackie Viruses. Coxsackie B3 virus caused plasmas inhabit the body including M. hominis, an epidemic in a nursery in the summer. Infec- M. pneumoniae, M. orale and M. salivarium. tions varied from inapparent ones to brief Volunteers who inhaled M. hominis Type 1 illness with fever, enanthem, trhinorrhea and developed a febrile pharyngitis76. pharyngitis6;5. A2, virus caused a mild vesicular Eleven per cent of 614 respiratory tract infec- eruption of the hands and feet, and a maculo- tions in Prague were caused by M. pneumoniae papular rash on the buttocks of 21 children. especially in older children and young adults77. Two infants died. Two variant forms of A21 M. pneumoniae was isolated from the inflamed virus administered by aerosolization to volun- ear of a child with a mild respiratory tract teers resulted in a mild, febrile respiratory tract infection78. Infection involved only three child- infection67. Two strains of Coxsackie A21 virus ren in an institution, one of whom had pneu-copyright. inhaled by volunteers caused febrile bronchitis monia79. Occasionally, the microbe or a related and two of 16 had pneumonia. One strain of one may be present as a commensal. virus caused febrile disease of the upper respira- In a study of 239 recruits with pneumonia, tory tract"8. In an outbreak of infectious hepa- cold agglutination of erythrocytes occurred in titis, A,o virus was present in 45 samples of the blood of 172, but other evidence of infection feces and in the blood of four patients"9. It with M. pneumoniae was present in only 4180. may have been a secondary invader or present Perhaps these microbes were not the cause in as a commensal. Coxsackie A and B viruses most cases or the agglutination reaction was were suspected as causes of congenital cardio- provoked by nonpathogenic commensal myco- http://pmj.bmj.com/ vascular defects70. plasmas. Many authors still include all pneu- A study of 1,888 patients with respiratory monias not of the typical pneumococcal lobar tract infections in England between 1961 and form as "primary" atypical pneumonias. Bac- 1964, disclosed enteroviruses, adenoviruses, terial pneumonias usually are not primary bu't rhinoviruses and parainfluenza viruses to be the are secondary to predisposing factors. ones most often isolated. Influenza and herpes A vaccine prepared against M. pneumoniae simplex viruses were obtained from 447 patients. evoked a rise in the titer of a specific antibody The microbes were not always the cause of in 25 of 30 vaccinees8". Hamsters developed on October 1, 2021 by guest. Protected disease. Hemolytic streptococci were present in pneumonitis after intrasal innoculation of M. 1287'. In another survey, viruses, chiefly respira- pneumoniae. The microbes superficially located tory syncytial virus, probably were !the cause in on the bronchial epithelial cells were visualized 62 per cent of infections in 151 children. Anti- by applying special techniques82. microbic therapy therefore is not indicated for routine therapy. Pathogenic bacteria were pres- Other Viral Infections ent as often in pneumonic patients as in healthy Knowledge of viruses, their classification and child,ren. H. inflenzae was not implicated. *their "troubles" were summarized 'by Andrewes. Staphylococci were the chief hazard72. Viruses, no doubt, affected man and other living Varicella virus caused pneumonia in 16 per things since remote antiquity83. Any "new*' cent of adults with chickenpox. In most patients, ones probably are mutants of old ones or are the pneumonia was signless, symptomless, and newly recognized. was discovered by skiagraphy as most viral Viral infections of 'the respiratory tract may pneumonias are73. Gsell reviewed and sum- predispose persons to bacterial pneumonias. Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from April, 1966 REIMANN: Infectious Diseases 251 enteric viruses may favour bacterial intestinal who had had the disease Jmore than 10 years infection, and suggestion was made that Cox- before, antibody was absent, but neutralizing sackie B viral infections may incite acute appen- substance was present.93 The virus was isolated dicitis84. Cytomegalovirus may cause disease from 32 of 50 specimens of products of con- resembling infectious mononucleosis whereini ception in women who had rubella in the first the heterophile Itest gives a negative result85. A or second trimester of pregnancy94. Virus per- newly isolated virus designated as the Darien sisted as long as 77 days after the rash"5 9 strain and identical to Wyomyia virus found in Thrombocytopenic purpura occurred in four of mosquitoes was isolated from a man with mild nine children. Steroids were administered for febrile illness in Panama. Neutralizing antibody the dubious purpose of controlling the fragility was demonstrated in 10 of 59 inhabitants of the of capillaries. The number of platelets was not area8". influenced"7. Apparently steroids did not worsen Viruses are multitropic. After vaccination, a viral disease. vaccinia virus caused unilateral genual arthri- Three of six children with rubella encephalo- tis87. Complications in the form of generalized pathy died94. The circumstance probably occurs vaccinia, eczema vaccinatum and autoinocula- in one of 5,000 cases. Rubella virus, present in tion occurred in 336 vaccinated persons. These the organs of three infants at necropsy, indica- incidents can be avoided by not vaccinating ted the persistence of a chronic state of infection victims of leukemia, agammaglobulinemia and in the congenital form of the disease"2. Serologic atopic asthma. Therapy with vaccinia immune evidence suggested that Coxsackie B4 virus globulin was helpful88. infection of mothers may be another cause of An improved antimeasles vaccine for children congenital defects"8. more than a year old induced immunity in 99 Encephalitis. Two hundred cases of St. Louis per cent of recipients without inducing commu- encephalitis were observed in Florida in 1962, nicable measles in vaccinees. Vaccination is but, no doubt, many more mild cases and in-

contraindicated in victims during other infec- apparent infections were undetected"". Clini- copyright. tions and in those with leukemia or neoplastic cally, the spectrum of severity of illness ranged disease, in patients whose resistance is impaired, from mild infection in 49; meningitis in 27; non- and during gestation. paralytic encephalitis in 137; and paralysis in Measles may be prevented or modified by the 9. Forty-three patients more than 45 years old injection of measles immune globulin if given died'"". Inapparent infections were a major within six days of exposure89. A viral inhibiting source of infection of others and these occurred factor similar to interferon appeared in the in a ratio of 39 to one case of overt diseasel". blood of 17 of 18 children six to 11 days after A detailed description of an epidemic was vaccination9". Particles resembling papova published'"2. In 1964, eight per cent of the http://pmj.bmj.com/ viruses were visualized by electronmicroscopy in population and 29 per cent of "contacts" were nuclei of demyelinized neural cells91. inapparently infected during a major epidemic Rubella. It was estimated that 30,000 ehildren in Houston, Texas, where the disease had not born during a large epidemic of rubella in the been observed in recent years. An antimosquito United States in 1964, will be congenitally defec- campaign stopped the epidemic'"'. tive. Besides the known abnormalities, many More epidemics of arthropod-borne encepha- previously unrecorded ones were described in litis may be expected. The urbanization of a symposium published in the American Journal populations and its attendant faults of sanitation on October 1, 2021 by guest. Protected of Diseases of Children, October, 1965. Inappa- favour the breeding of mosquitos and the attrac- rent maternal rubella may affect the fetus. The tion of avian carriers of the viruses. In other virus retards intrauterine and postnatal growth words, the changing nature of human society by inhibiting cellular multiplication. The virus creates a new and favourable milieu for the was present in apparently normal infants whose maintenance and dissemination of viral infec- mothers 'had no evidence of rubella infection, tions. and in others whose mothers had had the California virus encephalitis was recognized disease early in gestation92. To determine for the first time in Florida104. Six viruses cause whether maternal infection had occurred, sam- encephalitis in North America. In general, the ples of serum may be sen't to ithe Communicable cause of about 50 per cent of reported cases was Disease Centre in Atlanta for a diagnostic test. unknown. ECHO viruses mostly of Type 4 were Complement-fixing antibody appeared soon involved in 26 of 45 encephalitic patients in after the rubella rash faded and persisted for Scotland'"'. ECHO 25 virus was the chief more than eight months. In eight of 12 persons cause of another outbreak of encephalitis'06. A. Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 252 POSTGRADUATE MEDICAL JOURNAL April, 1966 caused a small outbreak of polio-like paralysis herpes simplex, it should not be used for its also in Scotland in 1959, and 15 infections in treatment"05. 1963'°7. Corticosteroid treatment in 346 patients Herpes Simplex. Herpes simplex infection of with various kinds of acute and post-infectious the vulva may be accompanied by viremia and meningoencephalitis caused a high mortality hepatic, pneumonic, neural and adrenal involve- rate and more neurologic sequels than in un- ment. After a primary attack, recurrences may treated patients'08. be provoked by menstruation or other distur- Rabies is a polio-encephalitis as determined bance. Infants may be infected during passage in a 'study of 49 cases. The site of the bite had 'through -the birth canal 117 and develop necro- no relation to the length of the incubation tizing encephalitis and retinopathy"18. The virus period or to the clinical course. Negri bodies caused encephalitis in 52 patients in a 3-year were present in 70 per cent of patients'08a. In period. In three, it was preceded by labial rabid dogs, the virus was in the saliva three days lesions"9. A herpes-like virus was present in before the onset of illness and for two days fetal and neonatal dogs that died with an acute afterwards. Therefore, recommendation was hemorrhagic disease. Virus passed through the made to shorten the time of observation of a placenta causing death in some dogs, but in bitten patient to five rather than 10 days'09. others 'the virus persisted latently like the virus In one victim, hysteria was suspected because of herpe' simplex in 'man'20. Three papers in physicians were not informed of a cat-bite three the Journal of the American Medical Associa- months previously"0. A generalized reaction to tion of November 29, 1965 described epidemics antirabies serum affected 16 per cent in of herpes gladiatorum, that is, infection acquired adults"0. Fatal post-vaccinal encephalomyelitis by contact in wrestlers. occurred in 18 of 65 persons vaccinated with an Iododeoxyuridine (IDU) applied to facial antirabies vaccine. "Fixed" virus was isolated herpes simplex was said to have reduced the from the vaccine"12. Rabies 'has increased in duration of the lesions to three days as com- incidence in Ontario because of an increased pared with nine days in control subjects'2'. T'he number of foxes as sources of infection. Fewer viruses of herpes s'implex, zoster and varicellacopyright. foxes are killed in response to a smaller demand are related 'as disclosed by cross reaction, neu- for their fur. tralization and complement fixation testsl22. Smallpox. Doubt raised about the need for Hepatitis. Two-thirds of 1,675 patients with continued routine vaccination against smallpox hepati'tis acquired the disease without exposure provoked controversy at a Pediatric Society to known sources such as jaundiced persons or meeting. In a study to detect harmful effects, transfusion of blood or other injections. One Kempe -stated t'hat no deaths from the disease hundred patients with hepatitis and an equal

occurred in 'the United States since 1948, bu't number of control subjects were questioned. http://pmj.bmj.com/ more than 200 deaths were caused by vaccina- Twenty-five infections were acquired by the tion"13. Among 2.3 'million primary vaccinees. 'transfusion of blood. Others had had a higher 1,427 complications or sequels and four deaths consumption of raw clams, and more injections occurred. An estimated 15 to 18 persons died from physicians than the controls, but the after vaccination in 1963. Vaccination is needed source in many instances was obscure. The for persons who enter endemic regions or for higher mortality rate from the serum hepatitis contacts when victims of smallpox import infec- than from infectious hepatitis, at times, may be tion and spread it in an area free of the disease. accounted for by the advanced age of the on October 1, 2021 by guest. Protected Safer methods of protection should be devised patient and of other underlying disease'23 such as chemotherapy or immune gammaglo- Hepatitis in aged patients often is mistaken for bulin. The matter was discussed at length and evidence of cancer or other disease. Six of 23 recommendations were proposed"13. A sterile patients died and four others had progressive inflammatory flare-up may appear at the site disease'24. of vaccination years afterward"4. Nonicteric serum hepatitis is ten or more Great trouble and expense ensued when a times as common as its icteric form. In a 9-year person froim Ghana suspected of having small- study of 816 patients -after transfusion, 33 had pox arrived at an airport. About 1,000 persons jaundice, an incidence of 9.2 cases per 1,000 who were nearby subsequently were sought, units of blood. The death-rate was 4.4 per cent. found and vaccinated. The alarm was unneces- The risk of infection increases with the number sary; the patient had varicella"l5. of transfusions given. The injection of gamma Because there is no evidence that antismall- globulin did not prevent infection, buit lessened pox vaccination has any effect on recurrent the relative proportion of icteric cases to non- Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from April, 1966 REIMANN: Infectious Diseases 253 icteric ones. The injection of 10 ml. of gamma- vector is involved"4. In one instance in the and another dose after a month will prevent United States, infection was transmitted from a about three-fourths of icteric serum hepatitis. stricken physician to his wife'85. globulin in the week after blood transfusion 'The case-rate was 1 per cent in treated patients Bacillary Infections -and 3.9 per cent in the controls. The supply of Salmonella. In June, 18,000 persons were gamma globulin is too limited for routine use12". infected with Salmonella typhimurium in a Two teams of investigators failed to note any Californian city. Three debilitated victims died. protection offered by the injection of gamma- Bacilli from a well polluted -the city's reservoir globul:in'26. and water supply"36. In another report, single unit transfusions In a nationwide (U.S.A.) surveillance of accounted for 17 per cent of all cases. Trans- salmonellosis, S. typhimurium and S. derby fusion of whole blood appeared to be less were most often isolated from man. S. derby hazardous than pooled plasma or fibrinogen. was usually recovered 'from persons aged 50 The onset of hepatitis was highest between 30 to 79 in whom it usually caused short, mild and 75 days after transfu,sion. The overall illness. Infection with S. heidelberg often was mortality rate was 11 per cent of 538 cases, but typhoidal, and with S. cholerae-suis it often 5.5 per cent in victims less than 40 years old127. was septicemic"3'. Five infections of the urinary Eleven cases of hepatitis *were observed in tract caused by Salmnonella were descriibed"8. persons exposed to chimpanzees'28. Several The pattern of typhoid may vary according authorities doubted that the viruses of hepatitis to geographic, climatologic and immunologic have been isolated. Another group of Italian factors and the ethnic origin of its victims, an workers reported the isolation of a causative impression I also gained in Indonesia. In virus"29. India, among 340 typhoid victims, rose-spots were absent, epistaxis was rare, and cough was Hemorrhagic Fever. Hemorrhagic fever is the chief early symptom. Circulatory collapse not new to Thailand but has -been observed often occurred, but intestinal hemorrhage andcopyright. every year since 1950 when it came to general perforation seldom did. The death-rate was attention after the Korean conflict. Question about 4 per cent"39. still arises as to 'the relationship of the virus Dysentery. In a survey of families in Scot- to dengue viruses. In the epidemics, dengue land, among 1,354 cases of diarrhea only 19 virus of different 'types and chikungunya virus per cent were of bacterial origin, and of those were present. None of the victims was of Euro- Sh. sonnei caused 84 per cent; Esch. coli, 9 per pean descent, which suggested that previously cent, Salmonellae 6 per cent, and Sh. flexneri exposed n.atives react more severely to reinfec- 0.4 per cent. Eighty per 'cent of infections were tion or that a genetic influence is operative130. of unknown cause. Coxsackie A, and ECHO 7 http://pmj.bmj.com/ Yet American troops in Korea had hemorrhagic viruses were isolated but without proof of their fever and the mortality rate was 10 per cent. relationship to diarrheas'40. Among 112 children Uremia was the chief cause of death'3'. Infec- during three years, those less than six months tion probably transmitted by A. aegypti mosqui- old were chiefly affected. Diarrhea was caused toes and ithe possilbility of its appearance in the -by bacteria alone in 25 per cent of cases, by United States was considered'32. viruses alone in 12 per cent and by mixed

A variety of hemrorrhagic fever first noted in bacterial-viral infecti'on in 12 per cent. Various on October 1, 2021 by guest. Protected Argentina in 1958 and 'later in Bolivia may be types of adenovirus, Coxsackie, ECHO and related to the Far Eastern infection"33. A sym- myxoviruses were isolated. Eighty-two per cent posium on the diseases as they occur in the of viral isolations were made in summer. At Americas was published in the September, 1965 present, the causes of 60 per cent of acute issue of the American Journal 'of Tropical diarrheal disease have not ,been discovered. Medicine. As mentioned previously in the case On the basis of probable cause, only three of of St. Louis encephalitis, an artificial distur- 74 cases of infantile diarrhea needed anti- bance of mammalian ecology favoured epi- microbic therapy'4'. demics of Bolivian hemorrhagic fever. During Sonne shigellosis is responsible for most an antimalaria campaign, DDT was used widely. bacillary dysentery in England. Streptomycin Cats poisoned by DDT died, thus permitting a is the therapeutic agent of choice, but more household invasion of a mouse4like rodent, the expensive drugs such as nalidixic acid and source of 'human infection. Their virus-bearing paromomycin are effective, if streptomycin urine is deposited on food or in water. No insect resistance is encountered'42. Shigella flexneri Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 254 POSTGRADUATE MEDICAL JOURNAL April, 1966 dysentery occurred in eight of 17 persons in At a !recent conference in Washington, Myco. contact with a dysenteric pet money'43. Shigellas leprae was said never to have been cultivated, rarely are found in the blood stream. In three yet Garbutt reported success in tissue culture"4. children with shigellar dysentery, sepsis was Leprosy became overt in a soldier who had caused by Esch. coli and Aerobacter. Malnu- left New Caledonia 20 years ago"'. trition often provides opportunity for -the Tetanus immune globulin prepared from invasion of nonpathogenic commensal bacilli'44. human plasma is 'effective in preventing tetanus Many strains of Shigellla resisted sulfadiazine when given at the itime of injury. It now is which no longer should be used for treatment. available commercially. Immunization with Ampicillin and colistimethate, kanamycin and toxoid stilil is desirable"". Six victims of tetanus neomycin are most effective in vitro and may recovered after therapy with 3,000 to 5,000 be of value for oral administration to patients145. international units of human tetanus hyper- Electron microscopic observations disclosed immune globulin"57. A repository type of what appeared to be the phagocytosis of penicillin injected promptly after injury was commensal bacilli by the intestinal epithelial said to be of value in preventing tetanus cells of rats as a physiological process wi,thout providing the strain of bacillus is sensitive to inflammation. Suggestion was made that penicillin"58. Toxins derived from nine strains shigellas and vibrios similarly may enter the of Cl. tetani were the same. Evidently, a mucosa, cause inflammation, decompose and specific neuro'toxin is shared by all strains"9. liberate their toxins'46. ShigeHla bacilli fed to guinea pigs penetrated the intact en-teric Tuberculosis. For 45 years, J. A. Myers led epithelium and reached Ithe tunica propria in one of 'the few continuous studies to determine a few hours. An exudative inflammatory the natural history of untreated tuberculosis. reaction preceded degenerative changes in the This is no longer possible since the introduction villi with loss of cytoplasmic comiponents and of modern therapy. His observations have microvilli'47. Studies in tissue culture disclosed established facts that corrected preconceived

ideas and theories. One of the contributions copyright. mycoplasmas stuck to cytoplasmic surfaces, was that the primary infection almost always their penetration of cells, and areas of is benign and needs no treatment because the necrosis148. Electron microscopy has opened a available drugs are not germicidal, antimicrobic- new field in microbiology. resistant bacilli may emerge, therapy gives a Other Bacillary Infections false sense of security, it does not influence Vaccination against whooping cough failed the course of infection, and drugs control the -to prevent an epidemic. The isolat-ion of Bord. few infections that develop later. Specific pertussis serves better to discover the cause of sensitization and allergy account for 'the an outbreak than for diagnosis in individual occurrence and nature;of subsequent acute and http://pmj.bmj.com/ patients. Whooping occurred in only 20 per chronic 'tuberculosis. A step to eradicate cent iof patients with paroxysmal cough. A tuberculosis is to prevent or postpone the previous attack of pertussis gave no immunity'49. initial infection throughout life for all persons'60. Clostridium botulinum Type F, caused an An epidemic of a viral respiratory tract outbreak of botulism in Denmark. That type infection apparently impaired resistance and has not been found in the United States, but favoured an outbreak of 'tuberculosis involving

was isolated from marine sediment 1,646 82 Eskimos. About 50 per cent of school on October 1, 2021 by guest. Protected meters deep in the Pacific Ocean near Oregon'50. children had active disease'"'. Phlyctenular An antianthrax vaccine is available for keratoconjunctivitis -among Eskimos usually is distribution'51. One wonders how reliable it is. caused by tubercle -bacilli and can be preven'ted Pseudomonas aeruginosa, usually disregarded by the use of isoniazid'"'. as an unimportant commensal, caused an out- A small epidemic occurred among 153 Negro break of 14 infections in a neurosurgical ward. school children, 25 of whom were previously A contaminated shaving-brush probably was non'reactive to tuberculin, but later reacted the source. Twenty other specific types of the positively'63. Another outbreak involved 27 bacillus were isolated from the environment'52. medical students and hospital personnel in a Listeria monocytogenes was reported as the 2-year period. The source was undetected'"4. cause of an aortic ianeurism in an 'aged diabetic In iaged persons, the supposed first tuber- woman153. The aneurism may have exi'sted for culous infection often is a reactivation of years and the site subsequently may have been previously unrecognized disease rather than a invaded by an opportunistic microbe. reinfection or a primary infection. The Ghon Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from April, 1966 REIMANN: Infectious Diseases 255 complex was present in 72 per cent of 66 aged a temporary state but may be a constitutional patients'5. or an acquired anomaly related to the develop- Tuberculosis persists as a hazard to public ment of sarcoidosis'.77 health. In the United States, an estimated Pasteurellosis. Six or more cases of bubonic 50,000 new cases and 9,000 deaths occur plague and one death were diagnosed in South- annually. About 75 per cent of new infections western United States where sylvatic plague develop in 35 million tuberculin-positive has always been endemic in rodents178. A persons, especially among the poor classes, the bacillus isolated from rabbits in Alaska at first aged, and the chronically ill"i;. Persons with was identiified as Past. pestis, but proved to be arrested tuberculosis should be given 300 mg. Past. pseudotuberculosis" . In 1932, 1 called of isoniazid daily for a year or two0'17. The attention to the similarity and possible relation- indications for prophylactic treatment were ship of the two bacilli just mentioned to Past. outlined1 8. On the other hand, prophylaxis tularensis'80. Past. hemolytica, multicida and with isoniazid was not so successful as pneumotropica also are pathogenic for Man'8-. previously reported. In Japan, among 1,000 Past. pseudotuberculosis was said to have persons who were treated, eight were infected caused erythema nodosum in seven children as compared with 11 who received a placebol'9. who were cured by antimicrobic therapy'82. Among 365 men treated for tuberculous Cholera. All that is called cholera isn't meningitis, the death-rate diminished from 70 cholera, as noted by many observers in the per cent to 20 per cent between 1946 and 1958 past. Olther infections, including viral dysentery after isoniazid was used for treatment. Residual and malnutrition may cause similar loss of fluid effects ensued in 25 per cent and more often in from the enteric tract by altering vascular or Negroes'70. epithelial permeability without demonstrable During a year's survey, the increase of lesions in the mucosa. Lesions, probably toxic primary resistance in strains of Myco. tuber- in nature, however, were present in the heart, culosis to streptomycin rose from 3.10/% to bronchi, muscles, and parenchymatous organs copyright. 5.6%/,,; to para-aminosalicylic acid, from 2.9°/, in victims of cholera'83. Cholera is a unique to 6.8%; anid to isoniazid from 3.9%°to 7.8%. disease. Vibrios do not enter the system and Among 196 strains of "atypical" tubercle the cause of the huge losses of fluid is bacilli, one was sensitive to isoniazid, one to unexplained. Possibly, la circulating toxin para-aminosallicylic acid and 64 to strepto- released in the bowel wall affects the hypo- mycin7 . thalamus and results in an autonomic vascular "Atypical" Tubercle Bacilli. In Australia, disturbance of the epithelium.

460 patients shed altypical mycoibacteria, but Cholera-like disease in an endemic area of http://pmj.bmj.com/ they caused pulmonic or lymph no,de infections cholera was caused by a vibrio different from in only 78. Antimicrobilc drugs were of little classic V. comma. Such microbes may be value in therapy 72. Mycobacterium kansasii mistaken for paracolon bacilli. Infection in- (group 1 atypical mycobacteria) caused genual duced the development of a specific agglutinin. arthritis. Excisio,n of infected tissue and The vibrios were not found in healthy isoniazid therapy were curative'73. Myco. persons"4. Non-vibrio cholera is usually milder kansasii caused a granulomratous dermal lesion than cholera, but differential diagnosis cannot that ihas persisted for 22 years. Therapy with be made clinically. In one study, no known on October 1, 2021 by guest. Protected streptomycin was partially successful"74. A pathogen was recovered from most victims with nonphotochromogenic mycobacterium caused profuse watery diarrhea'85. The possibility of disseminated infection'7'a. viral dysentery was not mentioned. It is In my laboratory, a strain of Myco. probable that clinical cholera is a syndrome tuberculosis, after prolonged cultivation, gave ;of multiple cause, including malnutrition. rise to variant forms, some of which had the El Tor vibrios, usually regarded as of low characteristics of so-called atypical tubercle virulence, caused epidemics of severe cholera bacilli 5. Question had been raised as to that began in Indonesia and later appeared in whether such strains were separate and distinct Iraq, Iran, Afghan'istan and the Soviet Union'8". from the classic form or mutants thereof. Undue panic and unnecessary travel restrictions Probably both views hold". ensued. Mass vaccination was applied even Victims of sarcoidosis seldom react to the though vaccine is of doubtful value. Infection tuberculin test, even after recovery from the is not apt to spread further in regions of good disease. The lack of reactivity therefore is not sanitation. Persons infected in endemic areas Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 256 POSTGRADUATE MEDICAL JOURNAL April, 1966 may, of course, travel elsewhere and sicken who had hemolytic streptococci usually of in remote places. Group A in their throat were not treated with The value of anticholera vaccine is con- antimicrobics. There were no complications, troversial, but a new vaccine was said to be no rheumatic fever nor nephritis. Among 82 effective. Cholera occurred in 6.1 per 1,000 of patients averaging 17 years old, penicillin was control victims, but in only 1.7 of vaccinees'8 . given prophylactically and 79 others received Analysis of the symptoms in 325 cases showed placebo pills. There were no significant that the course of cholera was not significantly differences in the number of streptococcal altered by vaccination'88. The effectiveness of infections or the number of rheumatic recur- vaccine is weak and of short duration189. rences in either group'97. According to another A single indigenous case of cholera occurred study among 161 patients, one half who received in the United States. None of the persons with penicillin daily for about two years had no whom the patient had had contact was fewer intercurrent streptococcal infections (22 infected'90. The patient "recovered soon after per cent) than those who received a placebo. being placed on antibiotic therapy" (Post hoc, The attack 'rate for rheumatic recurrence was ergo propter hoc?). No antimicrobic has proved 0.7 per cent in the treated group and 1.4 per value in treatment. Two persons were accident- cent in the control subjects'98. Evidently, the ally infected in a research laboratory in value 'of prophylaxis is questionable. The Washington. decline in the incidence and severity of rheumatic fever may owe to a decrease in the Coccal Infections virulence of Group A streptococci. Pneumonia. In a group of families, 39 per The results of a ten-year study of rheumatic cent of members were carriers of pneumococci. fever were published in the British Medical Types 3 and 19 predominated. Except Type 8, Journal of Sept. 11, 1965, in the Canadian none !of the usual types that cause lobar Medical Association Journal and in Circulation. pneumonia was present'91. Necrotizing pneu- Treatment with three regimens, namely ACTH, copyright. monia caused by gram negative bacilli has cortisone and aspirin gave similar results. The increased in incidence chiefly in persons whose prognosis in patients without initial carditis resistance was impaired and after the use of was excellent, less so for those with carditis equipment for inhalation therapy, tracheostomy whose hearts were normal previously, and was and tracheal cathetersl92. poor for those with pre-existent cardiac injury. After years of disuse, transthoracic needle The status of the heart at the beginning of aspiration of the lung again was recommended treatment, the rate of recurrences of rheumatic to discover the cause of pneumonias underlying fever and the sex of the patient must be other severe disease. In several instances, considered in the evaluation of any form of http://pmj.bmj.com/ sputumrcultures were misleading. The aspirated therapy. Rheumatic fever is clinically the same material disclosed the pathogen and occasionally whether it occurs in tropical or temperate led to appropriate 'antimicrobic therapyl93. climates'99. Hemolytic Streptococci. During a six-year Contrary to some opinions, in adults, carditis study of school children, the average annual may occur in the initial attack of rheumatic carrier-rate was 8.8 per cent. In a low-income fever. Polyarthritis was present in 34 of 35 group, the rate averaged 19 per cent without patients and carditis in eight. Chorea, nodules on October 1, 2021 by guest. Protected seasonal variation. Nontypable Group A and erythema marginatum did not appear. Two streptococci comprised about 83 per cent of patients died200. As had been surmized, strains'94. Streptococci cause impetigo half as streptococci played no role in the occurence of often as staphylococci, but mixed infections valvulitis after rheumatic fever begins. Therapy probably are common, Serologic evidence of with penicillin during rheumatic fever had no streptococcal infection was detected in 76 of influence on valvular involvement201. 303 children with impetigoy95 Endocarditis. The incidence and survival Among 1,125 children with acute pharyngitis, rate for -bacterial endocarditis has not improved Str. hemolyticus was present in 342. Types 12 in 20 years despite the advances in antimicrobic and 4 accounted for 46 per cent. Four children therapy. There ihas been a relative decrease with Type 4 infection had hematuria. Two had in the incidence of cardiac disease as an under- nephritis caused by Type 12196. lying cause and an increase in the number of Rheumatic Fever. As reported at a meeting, cases in old persons wi'th calcific and vascular 785 children with non-exudative pharyngitis disease. Nonhemolytic streptococci still are the Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from April, 1966 RELMANN: Infectious Diseases 257 chief causes, but the number of staphylococcal Urinary Tract Infection. Among 252 patients infections has increased. Surprisingly, the with chronic pyelonephritis, bacteriuria ceased incidence of gram negative bacillary or mycotic in 80 per cent during therapy, but only one- infections did not increase202. The over-all third remained free of infection for three years. cure rate in one series of patients was 40 Relapses were caused by the isame microbe or per cent for acute endocarditis and 87 per cent by reinfection with another. Hypertension, renal for subacute disease. A review of the records failure, and structural anomalies were pre- of 337 victims of subacute bacterial endocarditis disposing factors213. Combinations of anti- observed between 1924 and 1963 disclosed that microbics were less effective therapeutically than staphylococci 'have exceeded streptococci as single agents. Recurrences responded to causes. Post-cardiotomy infection is a new treatment as well as the initial infection. inciting factor and caused four per cent of cases. Sulfonamides were the least effective drugs. Congenital cardiac disease provided grounds While preimmunization protected against for bacterial invasion in six per cent of patients experimental infection, it failed when there was in previous years and in 18 per cent now. The uropathy. Immunity apparently played little mortality rate had been 100 per cent, but role in recovery, but may determine the kind between 1950 and 1963, 30 per cent. It was of microbes that cause reinfection215. Many 51 per cent in a recent group largely as a result infections of the urinary tract become chronic of cardiac failure or of unknown causes203. When the ca-usative microbes are not eradicated, Endocarrditis caused by Str. fecalis ensued despite the introduction of antimicrobic agents. in three patients after urologic manipulation201. Because bacterial protoplasts resist therapy Endocarditis, inapparent for long periods, may and survive in infected kidneys, perhaps the be the source of infection of aneurisms of old procedure of "forcing" fluids to reduce cerebral blood vessels205. medullary hypertonicity still has value in- Staphylococci. Staphylococci not conforming therapy216. Revised concepts of urinary tract infection in children and its management were to the 22 known types caused serious outbreaks copyright. in a hospital. A newly classified strain caused reviewed by Allen217. infections chliefly in patients who had received Premature births occurred in 13 per cent of broad spectrum antimicrobic drugs and in women with renal infection as compared with elderly and debilitated ones. The o,utbreak five per cent in its iabsence. Among 4,000 subsided when treatment with neomycin was women in early pregnancy, six per cent had restricted200. Other epidemics in Australia and bacteriuria that often persisted for six months elsewhere may have been caused by a strain after delivery. Antimicrobic therapy reduced similar to the newly classified one207. As had the incidence of pyelonephritis to two of 72 been shown before, in infants the deliberate patients as compared with one-third who http://pmj.bmj.com/ application of nonpathogenic staphylococci received a placebo. Among 111 women who blocked an epidemic caused by a pathogenic had bacteriuria during pregnancy, the condition strain apparently by bacterial interference208. persisted in 90. Pyelographic abnormalities Coagulase-negative Staphylococcus albus were present in 61 of 131. Evidently, caused wound infection in 53 of 1,200 patients. asymptomatic badteriuria often persists and may Recovery occurred without antimicrobic indicate active renal infection218. T'he ;tetra-

therapy. Five of 12 strains were sensitive to zolium test was said to be of value as a on October 1, 2021 by guest. Protected penicillin. Infection is especially serious in screening procedure to discover significant postcardiotomy and in debilitated patients209. bacteriuria in healthy persons, but not as a Gonococcal Arthritis. Gonococcal arthritis substitute for bacteriologic examination219. seldom occurs in children, yet six cases, five In another study, 4.5 per cent of 481 gravid of -them in girls, were observed. Seventeen women had bacteriuria, only six of whom had other chilldren had gonococcosis. The source not 'had bacteniuria previously. It was present was unknown except for evidence of gonorrhea most often in those more than 30 years old, in in the families of three patients210. The infection multiparas and in Negresses. All -but a few with arthritis has increased in incidence in cases of post-partum infection occurred in women and is easily mistaken for rheumatic patients who 'had been infected before delivery fever. Pregnancy and menstruation seem to or who had been catheterized220. The infection favour its development211. Gonorrheal sal- rate is not surprising since some degree of pingitis, lepididymitis, arthritis and sepsis have hydronephrosis occurs temporarily in almost not decreased in incidence212. all gravid women. Suprapubic puncture of Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 258 258 POSTGRADUATE MEDICAL JOURNAL A pril, 1966 ,the bladder, a procedure that 'had been dis- poultry and to other birds as well. Mediastinal carded, was useful in detecting bacteriuria in involvement caused dysphagia in three women whose urine may be contaminated by patients230. In Montreal, histoplasmosis was infective vaginal discharges. Bladder urine transferred from a donor to the irecipient of a often was sterile when bacteria were present renal homograft. This is the first reported in midstream specimens of urine221. example of person-to-person transmission of L-forms or protoplasts, as variant forms of histoplasmosis231. Coccidioidomycosis trans- bacteria, were detected in the urine of 19 per mitted in a plaster cast was referred to in the cent of patients with chronic urinary tract 1965 Review of Infections. infection. Those forms may revert to the parent strain during antimicrobic therapy and Infective Agents and Neoplasia may account for persistent infection222. As studies progress, the problem becomes Syphilis. The incidence of syphilis continues more and more complex. An unsolved question to increase in the United States. Last year is why viruses can be related to onoogenesis in nearly 23,000 infectious patients were reported, animals, but not conclusively in man232? the highest number since 1950. The inclusion Mycoplasmas were isolated from benign of many unreported cases no doubt would tumours in children233 and were detected in 19 raise the figure. Seventeen per cent of cases of 35 patients with lymphomas234 235. They may were in teen-aged persons. The incidence of be commensals without pathogenicity236" Simi- late and late latent infection has decreased larly toxoplasmas have been suspected as causes steadily. of neoplasms and evidence of their presence With the assistance of health officials, a was demonstrated in 71 of 126 patients237. physician traced the spread of syphilis from Bacteria of the tribe Mimae, formerly known a patient to 45 others in widely scattered places. as the Morax-Axenfeld bacillus and by a variety The chain of infection involved 365 persons of other names, usually are opportunistic inva- during five months. The attack rate in one ders. In one study they were isolated from 65 city was 346 per 100,000 population, which patients with neoplastic disease. Infections often copyright. is seven times the usual incidence223. A followed the use of intravascular catheters236. syphilitic mother transmitted infection to her Lymphocytic choriomeningitis virus that con- offspring for nine years. Of her eight children, taminates 'tumours in 'hamsters is a source of five had congenital disease and the last child misleading conclusions. The virus also may was unaffected. With each succeeding preg- infect laboratory personnel239. Newcastle disiease 224 nancy, the effect on the fetus was less severe . virus apparently is oncolytic or antineoplas- The efficacy of penicillin as a therapeutic tic240. agent has been questioned. Treponemes per- sisted in patients treated for late syphilis, but Miscellaneous http://pmj.bmj.com/ the possibility of re-infection was not Pneumocystis carinii caused pneumonia usu- eliminated225. ally discovered by skiagraphy in 12 victims of Histoplasmosis. In a 17-month period, 42 neoplasms241. The infection occurs chiefly in persons in South Carolina had erythema persons debilitated by other conditions, but multiforme, erythema nodosum or both, two healthy persons in a family were infected probably caused by H. capsulatum. A few had by contact with another member who died from

abnormal skiagraphic shadows in the lungs. leukemia and cariniosis242. Therapy with penta- on October 1, 2021 by guest. Protected Most infections occurred near a golf-course midine isothionate was thought to be curative under construction from which the spores of in a hypogammaglobulinemic child243. the fungus were spread by air226. Destruction Toxoplasma caused lymphadenitis in six of a starling roost caused an epidemic of otherwise healthy persons. Infection can ibe histoplasmosis. Twenty-eight patients were recognized by isolating the microbe and proving detected, 'two died and 29 per cent of children its activity by serologic tests. Persistent lym- in the community reacted to the histoplasmin phadenitis is the commonest form of acquired test227. Two men acquired histoplasmosis 'by infection244. Fourteen per cent of 2,080 recruits digging around a bat-infested tree stump. had specific antibody in their blood245. Toxo- H. capsulatum was isolated from three 'bats plasmic myocarditis and ventricular fibrillation and 'from the soil228. The fungus ialso was were fatal in a leukemic patient246. present in bats in Panama229. Evidently, Septicemia with varieties of bacteria occurred H. capsulatum is in the bat's gut, is shed in in 52 of 420 leukemic patients chiefly with feces and enters the soil. This may apply to bacilli and candida. All but four died247. Victims Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from April, 1966 REIMANN: Infectious Diseases 259 of leukemia also are subject to infection with no illness attributable to the procedures were the cytomegalic inclusion virus. Diagnosis usu- discovered, but 19 had abnormal blood-globu- ally is made postmortem. There is no effective lins and other elements. Since 1902 it was therapy248. known that long-continued immunization of Infectious diseases usually are caused by a horses often resulted in hyperglobulinemia and single bacterium. In a 10-year review of blood amyloidosis. Similar increases of globulins also cultures from 633 patients, several bacteria induce amyloidosis in immunized persons. In were present in 52 (7.8 per cent). Most of the the technicians studied, there was no evidence patients were debilitated. Esch. coli, Staph. of amyloidosis, probably because of the small aureus, Ps. aeruginosa, Proteus, Klebsiella, Str. adiounts of antigens injected and their wide fecalis, and anaerobic streptococci were chiefly temporal spacing258 involved in combinations or in succession. Three reports should eliminate much unneces- During antimicrobic therapy, one bacterirum may sary therapy for trivial disorders. Treatment be controlled, but a different resistant one may with tetracyclines had no effect on acne. Place- 249 become invasive . bos occasionally seemed to hasten healing259. During a 3-week period, an unusual outbreak Bacteriophage-lysed vaccine failed to influence of pneumonia was fatal for 12 of 80 adult staphylococcal furunculosis260. Bacteiial-vaccine patients in a psychiatric hospital. Several istaff therapy was less effective than placebos in re- members were also affected. The cause was not ducing the incidence of wheezing, infections, known. Klebsiella was suspected, but these and infectious episodes in patients with "infec- usually are secondary opportunistic invaders tious" asthma2'. Questions still remain whether and infection rarely is contagious250. Acantha- or not the bacteria are present as normal flora, *noeba apparently caused four rapidly fatal and whether asthma is caused by allergy to cases of pyogenic meningitis in Australia. In- bacteria. fection may have occurred by the olfactory Remains of bacteria two billion years old route251. were visualized by electron microscopy in rocks Among 315 persons in Montana, about 50 per from Ontario 2. Fossils of algae were presentcopyright. cent were inapparently infected with Q fever. in precarmbrian -limestone in Australia263. Con- No overt illness was observed in the enzootic taminant bacteria allso were cultivated from region252. The incidence of Rocky Mountain meteorites264 and from coal265. The problem spotted fever is increasing in the south-eastern was discussed criitically 'by Urey2t'i'. United States, probably because of conditions The threat of using biological weapons for favourable for ticks and infected animals on warfare received further attention,267 but one abandoned farms. The actual incidence of the wonders what microbe could be disseminated disease no doubt is greater than the number

successfully against an enemy, and which would http://pmj.bmj.com/ of recognized and reported cases253. An unusual not harm an aggressor as well. Nevertheless, outbreak of typhus affected more than 26 the danger must be anticipated even though children in eastern Switzerland254. preimmunization is impracticable and there are Trichinellosis has decreased from about 18 no vaccines ;or other preventive measures per cent to less than four per cent in the United against many infections. States because of better feeding of swine and the modern processing of pork255. Thiabendazole REFERENCES 1. EICKHOFF, T. C., KISLAK, J. W., and FINLAND. given to pigs tended to destroy the l'arvas256. M. (1965): Clinical Evaluation of Nafcillin on October 1, 2021 by guest. Protected A review of the history and new develop- in Patients with Severe Staphylococcal ments in the United States about leptospirosis Disease, New Engl. J. Med., 272, 699. and an analysis of 483 cases appeared in the 2. KISLAK, J. W., EICKHOFF, T. C., and FINLAND, M. (1965): Cloxacillin: Activity in Vitro October 14 and 21 issues of the New England and Absorption and Urinary Excretion in Journal of iMedicine. Infection with L. pomona Normal Young Men, A mer. J. med. Sci.. often is mistaken for other diseases, Agglutina- 249, 636. tion tests of 29,000 samples of serum gave 3. NYDAL, IB. C., and HIALL, W. H. (1965): The Treatment of Staphylococcal Infection with positive results in 0.5 per cent. Persons exposed Nafcillin with a Discussion of Staphylococ- to contaminated water, livestock 'handlers and cal Nephritis, Ann. intern. Med., 63, 27. meat processers chiefly are at risk257. 4. MANDRIQUEZ, L., et al. (1965): Clinical Trials Studies were made over a long period on with Ampicillin in Typhoid Fever and Para- typhoid A, Brit. med. J., ii, 152. technicians employed in microbiologic labora- 5. PROTIVINSKY, R. (1965): Chemotherapy of tories who had been immunized with a variety Chronic Bronchitis: Experiences with Ampi- of vaccines and antitoxins. Among 76 persons, cillin, Munch. med. Wschr., 107, 1950. Postgrad Med J: first published as 10.1136/pgmj.42.486.247 on 1 April 1966. Downloaded from 260 POSTGRADUATE MEDICAL JOURNAL April, 1966 6. Ampicillin Seen as Choice Initial Meningitis 24. DANZIG, IL. IS., and LOEBEL, A. S. (1965): Drug, i(1965): Antibiot. News, 2, 5. Clinitest-Tablet Ingestion and Stricture of the 6a. PETERSDORF, R. G., and TURK, M. (1966): Esophagus, J. Amer. med. Ass., 192, 1092. The New Penicillins and Their Proper Use, 25. FARRAR, W. E., and KENT, J. H. (1965): Enteri- Ann. intern. Med., 64, 207. tis and Coliform Bacteria in Guinea Pigs 7. TURK, M., et al. (1965): Laboratory and Clini- Given Penicillin, Amer. J. Path., 47, 629. cal Evaluation of a New Antibiotic-Cepha- 26. HIRSCH, W., et al. (1965): Salmonella Edin- lothin, Ann. intern. Med., 63, 199. burgh Infection in Children, Lancet, ii, 828. 8. Evaluation of a New Antibiotic: Sodium 27. Staphylococci Resistant to Neomycin and Baci- Cephalothin i(Keflin), (1965): Council on tracin, Lead. Art. (1965): Lancet, ii, 421. Drugs, J. Amer. med. Ass., 194, 182. 28. KISLAK, J. W., et al. i(,1965): Susceptibility of 9. BENNER, E. J., et al. ( 1965): Natural and Pneumococcus to Nine Antibiotics, Amer. J. Acquired Resistance of Klebsiella-Aerobacter med. Sci., 250, 264. to Cephalothin and Cephaloridine, Proc. Soc. 29. FINLAND, M. (1965): Staphylococcal Infections exp. Biol. (N.Y.), 119, 536. and Antistaphylococcal Antibiotics, Med. 1 0. GOTOFF, S. P., and LEPPER, M. H. (1965): Tms. (N.Y.), 93, 101 i(Feob.). Treatment of Salmonella Carriers with Colis- 30. EICKHOFF, T. C., and FINLAND, M. ((1965): In tin Sulfate, Amer. J. med. Sci., 249, 399. Vitro Susceptibility of Group A Beta Hemo- 11. A New Antibiotic. Lincomycin (Lincocin) lytic Streptococci to 18 Antibiotic3, Amer. J. (1965): Council of Drugs, J. Amer. med. med. Sci., 249, 261. Ass., 194, 545. 31. ROBERTSON, M. H. i(1965): Beta Hemolytic 12. JACKSON, H., et al. (1965): Group A 13-Hemo- Streptococci in Southwest Essex with Parti- lytic Streptococcal Pharyngitis-Result of cular Reference to Tetracycline Resistance, Trcatment with iLincomycin, J. Amer. med. Brit. med. J., ii, 569. Ass., 194, 1189. 32. Testing of Sensitivity to Antibiotics, (1965): 13. A New Bacterial Agent for Infections of the Lead. Art., Lancet, i, 641. Genitourinary Tract. Nalidixic Acid (Neg 33. "Infective" Resistance to Antibiotics. (1965): Gram), Council on Drugs, (1965): J. Amer. Lead. Art., Lancet, i, 1149. Transferable med. Ass., 192, 628. OKUN, H., and HARLIN, Antibiotic Resistance,(1965): Lead Art., Brit. H. C. (1965): Study of Nalidixic Acid; med. J., i, 1325. Intvest. Urol., 2, 409. 34. SHEEHY, T. W., et al. (1965): Tropical Sprue 14. MOST, H., et al. (1965): The Treatment of in North Americans, J. Amer. med. Ass.,

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