Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from POSTGRAD. MED. J., (1965), 41, 536 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.

VIRUSES and viral diseases were the subjects chemically from penicillin and can be used of continued intensive study in the past year. against penicillin-resistant staphylococci, and Attempts to prepare vaccines for the prevention for patients sensitive to penicillin. It is not of specific infections, especially of the res- absorbed when given orally. Neutropenia may piratory tract, have not had much success be induced2. because of the complexities involved. No Sodium colistimethate (Coly-mycin) 2 to 2.5 important curative agents were discovered, nor mg./kg. every 12 hours injected intravenously has a causal relation of viruses to cancer in cured five of eight patients infected with man been proved. Many new antimicrobic Pseudomonas. Smaller dosage was necessary agents, or old ones with new names, were tested. when the renal function was impaired. It may As causes of disease and death, gram negative be neurotoxic, cause apnea and must be used bacillary infections now displace those formerly with caution in the presence of chronic caused by gram cocci, as a result of disease, renal positive debilitating impairment, hypoxicProtected by copyright. iatrogenic impairment of host-resistance and states, and if muscle relaxants, corticosteriods, other factors. The incidence of venereal diseases narcotics or sedatives are given at the same and of tuberculosis increased. Meningococcal time4. meningitis, the one disease for which anti- The activity of nafcillin, ancillin, and microbic prophylaxis seemed to have the most cloxacillin was reduced in media containing value, caused serious epidemics despite efforts serum, but cephalosporin was unaffected5. to control it. Several observers found no differences in the Antimicrobics results of therapy with ampicillin, nafcillin, New Antimicrobics. According to Garrod, oxacillin, methicillin and cephalothin. The there is little to be gained by the increasingly action of lincomycin and pristinomycin was unprofitable search for new antimicrobics from said to be similar to that of ostreogramin, natural sources. Some of the recently advertised streptogramin, spectinomycin, synergistin and ones are the same as, or similar to, ones in use'. mikamycin 6, 7. An antagonism between lin- or ones hold more comycin and erythromycin interfered with their Synthetic semisynthetic may http://pmj.bmj.com/ promise. effect on staphylococci8. Lymecycline was said Two new broad spectrum antimicrobics to be as effective as tetracycline for treating especially for the control of gram negative chronic bronchitis. Hamycin was active against bacillary infections were discussed in three Cryptococcus neoformans and H. capsulatum papers in the Journal of the American Medical in inoculated mice'0. Ethambutol may be Association of September 14th, 1964. Gent- effective against tubercle bacilli refractory to amycin is active against Pseudomonas, less so other agents". Several years must pass before again Proteus and Staphylococcus. It resembles the value of any of these agents can be judged. on September 28, 2021 by guest. streptomycin, neomycin, kanamycin and paro- As if the names for new products mentioned so momycin chemically, its antibacterial action is far are not confusing enough, these also have about the same and it occasionally causes been coined: quinacillin, everinomycin, almar- deafnessla. Cephalothin (Keflin), a semisynthetic cetin, pediamycin, viractin, monicamycin, broad spectrum agent has a similar range of enteromycin, seligomycin, xanthomycin, rubi- action and is less toxic even in patients with flavin, antimycin, oligomycin, tolfanate and renal failure. It was ineffective against others'2. There is no limit for new alphabetic Pseudomonas and enterococci. It differs combinations. Antimicrobic It is regretted that reprints of this article are not Therapy. The administration available. Copies of the Journal can be obtained of huge amounts of antimicrobics given "just price 10s. 6d. post free from the publishers or usual to be sure" is deprecated. But recent studies agents. showed that penicillin in doses of 20 to 60 Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 537 million units (12 to 36 grams) a day given occasionally were found. Other untoward intravenously cured many gram negative effects also occur. The subject was discussed bacillary infections. The amount in the serum in two papers in the Annals of Internal reached 737 units/ml. Cerebral irritation Medicine of August, 1964. Actinomycin D was occurred in patients with renal failure or central teratogenic in rats23. neural disease. Obviously, the sensitivity of Broad spectrum antimicrobics decrease the gram negative bacilli to penicillin should be rate at which colon bacilli are killed by human determined. Those inhibited by 78 units/mi. serum, probably by inhibiting bacterial meta- or less are classed as sensitive; resistant ones bolism and impairing the lytic action of serum. resist 625 units/mi. and are uncontrollable'3. The matter may be of therapeutic import24. Thirteen patients with bacterial endocarditis The same amount of antimicrobics entered the were treated successfully with propicillin blood after intraperitoneal injection as from (phenoxypenicillin) or ampicillin given orally. injection by other parenteral routes. The Infections with Str. viridans responded better method may be used in place of intravenous than those caused by Str. fecalis4. Penicillin and intramuscular injection25. given prophylactically during cardiac cathe- In regard to indiscriminate antimicrobic terization had no influence on the incidence therapy, Harris wrote that something has of subsequent bacteremia. Its use therefore is weakened clinical judgment: physicians who unwarranted'5. prescribe digitalis or quinidine (which are The therapeutic effect of penicillin combined poisons) with the utmost caution, pounce avidly with sulfonamides is unpredictable. Increased, on chloramphenicol and other antimicrobics for indifferent or decreased antimicrobial effect may minor illnesses. They would always make tests follow. If the combination is used, full doses of sensitivity before injecting tetanus antitoxin, of each are indicated. Semisynthetic penicillin but not before giving penicillin whose danger Protected by copyright. alone or combined with penicillin G and other in causing a reaction is as great26. Antimicrobic- antimicrobics was said to be of therapeutic induced diseases were described in a book27. value against infection with isoniazid-resistant Viral Infections tubercle bacillil7. Respiratory Tract Infections. Sir Christopher Acute pericarditis occurred as a hypersen- Andrewes, who with Smith and Laidlaw, dis- sitive reaction to penicillin'8, and oxacillin covered the virus of influenza in 1933, has also caused hepatitis'9. Huge doses of penicillin contributed to the knowledge of common colds. caused severe anemia in two patients20. In a review, he points out the complex, poorly Pencilloyl-polylysine introduced as an agent to understood epidemiology of these ubiquitous detect sensitivity to penicillin, itself caused a infections. Respiratory tract viruses no doubt generalized eruption after the injection of a spread from person to person by the airborne skin-test dose21. route, but various determinant factors operate Airborne contamination with penicillin of to cause seem made in epidemics. Meteorologic changes many products large pharmaceutical to be important at times, but a wide range of http://pmj.bmj.com/ plants is a serious problem. It would be stresses, including chilling, may disturb the difficult to recall such products now on the host-parasite relationship enough to permit the market and to destroy the ones in reserve. invasion of microbes. The operation of viral Chloramphenicol suppressed the formation interference and of interferon itself probably of antibodies in vitro and in experimental play a role28. By indirect methods, droplets animals. Therapeutic doses in eight patients bearing the viruses were expelled in greatest suppressed antibody formation after the amount by sneezing. Most of them fell to the injection of tetanus toxoid in six and was ground and about 10% were small enough to be on September 28, 2021 by guest. hemotoxic in four22. Chloramphenicol applied airborne. Saliva contained very little virus. to the conjunctiva caused pancytopenia in a Viruses die soon after shedding29. Four papers patient whose niece had succumbed to aplastic on airborne infections pertaining especially to anemia after oral therapy23. The reason for the those acquired in laboratories and in hospitals topical use of the agent is unclear. appeared in the October, 1964, American Amphotericin B should be used only when Journal of Public Health. Methods for their actually needed. The blood urea was increased control were outlined. in amount in 93% of 81 patients during treat- Rhinoviruses. Fifty-three types of rhinovirus ment. The renal function was persistently are known and there are many others. Rhino- reduced in 7 of 16 patients who received more viruses of 46 types were isolated from 10% than 4 g., and in six of 36 who were given less. of infected adults and from 5% of children. Tubular lesions and deposits of calcium Children were more severely affected, and half Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 538 POSTGRADUATE MEDICAL JOURNAL September, 1965 of them had viral pneumonia30. Adult volun- current viruses failed to prevent infection among teers inoculated with rhinovirus usually had 90 children against influenza A as compared coryza, but several had tracheobronchitis31. with 90 control subjects. Antibody induced in The multiplicity of specific types and the con- the blood in titer higher than 1: 64 was not stant changes in the human population explain protective43. Oil-adjuvant vaccine was shown why some persons have repeated colds in a to evoke antibody that persisted as long as season. Little hope was held for the preparation 16 months", but in accordance with the pre- of effective vaccines32. Hilleman discussed the ceding sentence, the protective value of problem of vaccination against a variety of measurable antibody in the blood is of little viral infections33. Perhaps the introduction significance. In another institution, an outbreak orally of viruses into the enteric tract in of influenza A2 affected children who had specially coated containers may elicit immunity been vaccinated with a polyvalent vaccine five without causing respiratory tract symptoms or months before. The number of illnesses among illness. Epidemiologic and antimicrobic pro- the vaccinees was slightly less than in non- phylactic efforts have failed as preventive immunized children45. Encephalopathy appeared measures. 12 hours after a child had received a polyvalent Adenoviruses. Adenovirus Types 4 and 7 vaccine46. caused sharp, localized, winter epidemics among U.S. Public Health Service officials predicted military personnel over a 4-year period84. The no widespread epidemics of influenza this year. antibody titer for adenovirus rose in several From past experience, one wonders how trust- victims of respiratory tract infection and acute worthy such predictions are. Influenza A2 was thyroiditis suggesting that the virus was the rampant in the United States and in Europe cause of both. Pharyngitis, cough and fever in the winter of 1964-196547. often accompany epidemics of keratocon- By a specific immunofluorescent technique,Protected by copyright. junctivitis caused by Type 8 virus each summer influenza virus was detected in bronchial in Taiwan36. epithelium 8 hours after the inoculation of Apprehension was raised lest contamination mice, mostly in the cytoplasm and occasionally with an oncogenic hybrid offspring of a mating intranuclearly. Virus reached a maximum between adenovirus Type 7 and SV40 virus amount in tissue in two to three days and used in vaccine may occur. This raises the progressively invaded the bronchi, bronchioles, further question whether vaccination against alveolar ducts and alveoli. Fluorescence usually mild infections is desirable or necessary. vanished after seven days48. The distribution of adenovirus 7 vaccine has A parainfluenza virus liberated a pyrogen been stopped for the time being. from granulocytes in the blood that caused the RS Virus. Respiratory syncytial virus caused fever of infection49. A lysozymic or antibody- two winter epidemics in a nursery for premature like microbic-inhibiting substance was demon- infants. Coryza usually lasted one to eight days strated in mucosal before secretion years ago by respiratory distress began37. Pneumonias Fleming. Recent studies of nasal secretionhttp://pmj.bmj.com/ occurred in 9 of 14 sick infants. RS Virus disclosed that its viral neutralizing activity caused 60% of pneumonias among infants and correlated with the presence of specific antibody children in Newcastle38. Antibody against the to each of several viruses tested. During virus was present in 66% of 329 persons, respiratory tract infection, antiviral substance chiefly in adults39. Neutralizing antibody was was in the found in 25% of persons of all ages, and after chiefly gamma 2-globulins5o. four the rose 8340. From 210 students with acute respiratory seasons, percentage to RS tract infections, two kinds of viruses were virus is related to measles virus and cause only on September 28, 2021 by guest. an exanthem. may recovered. In 122, serologic evidence of influenza B was present in 16 and of respiratory Reovirus caused hepatitis, encephalitis, myo- syncytial virus in five51. To account for the carditis and pneumonia in children. In one large percentage of unidentified infections, either victim, virus was recovered from the brain the technique used was faulty, immune bodies and feces41. failed to or unknown ECHO virus Type 25 is an enterovirus, and appear, microbes await a strain isolated from feces caused febrile discovery. respiratory tract infections in Study of 300 other students with acute inoculated adult volunteers42. intranasally pharyngitis-tonsillitis disclosed hemolytic strep- tococci to be the cause in about 25%, as Influenza. A commercially prepared poly- recorded in previous surveys. Viruses were valent vaccine that contained antigens to the causal in 38%, and 36% were of undetermined Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 539 origin. Surprisingly, the virus of herpes simplex A hemagglutination test for the detection of was implicated in 13%. Coxsackie, influenza, antibody for Mycoplasma pneumonie is simpler parainfluenza and adenoviruses accounted for to perform than the immunofluorescent pro- three to five per cent of infections. Twenty-three cedure60. Antibody against the microbe was of 86 patients, regarded as having a viral demonstrated in titer of 1:256 or higher in infection also harbored hemolytic streptococci. five victims of mucocutaneous fever (Stevens- Specific diagnosis of the six different infections Johnson syndrome), a disease often characterized mentioned seldom could be made clinically by a viral-like pneumonia61. Because Myco- because of many features in common. A few plasma (PPLO) has no rigid cell wall, it is points of differentiation were helpful: Exudate, pleomorphic and hard to see microscopically. cervical adenitis and leukocytosis were present Question was raised if it is a virus, a fungus, in 26% of streptococcal infections and in 14% or a bacterium that has lost its wall and of the others. General aching was present in therefore is not an independent microbe62. A 3.4% of patients with streptococcosis, as com- newly recognized Mycoplasma caused fatal pared with 23% during viral infections. septicemic disease in puppies63. Penicillin therapy failed to shorten the course Psittacosis caused 24 cases of pneumonia in of any of the infections and broad spectrum Scotland from 1950 to 1963. Several victims agents seemed to prolong illness. Penicillin is contracted the infection from pigeons or indicated: (1) if the patient has had rheumatic budgerigars. In 1963, 54% of pigeons in fever, glomerulonephritis or repeated attacks of Glasgow were found to be infected, but streptococcal sore throat, (2) in the presence of apparently they were not a source of disease exudate, severe inflammation, otitis media or in man64. Antimicrobics added to food for leukocytosis higher than 13,000/u. mm., (3) parakeets and other birds was said to minimize for severe sore throat in the absence of the risk of spreading psittacosis65. Protected by copyright. rhinorrhea, hoarseness or cough, and (4) if A peculiar form of pneumonia occurred in other chronic disease exists. Cultures of the six patients who had renal transplants and exudate and other tests to identify the cause were treated with azothioprine and prednisone should be made in any event52. as immunosuppressants. Cold agglutination of Pneumonias. Specific pneumonia occurs in erythrocytes occurred in five. The disease, one-third of victims of varicella, but in less than uninfluenced by antimicrobics, lasted 12 to 34 3% of those with herpes zoster. Twenty-two days. Necropsy in one disclosed Pneumocystis cases of the latter were reviewed53. carinii and cytomegalic inclusion disease66. Mycoplasma Pneumonice. Two reports Others may have been caused by Mycoplasma. emphasize the frequency of respiratory tract Cytomegalovirus was recovered post mortem infections caused by Myco. pneumonice, with from the lungs of four recipients of renal and without pneumonia54 55. One paper per- homografts67. The disorders represent maladies petuates the outmoded term "primary atypical induced by iatrogenically impaired resistance. pneumonia" that should not have been coined The virus was found in 1% of 200 well children. http://pmj.bmj.com/ in the first place. Myco. pneumoniae infections Among 20 symptomless virus-positive children, are nonseasonal, but they accompanied a winter 14 had hepatomegaly, and five had spleno- epidemic of adenoviral pneumonia54. These are megaly. The virus was isolated from nine of circumstances that I described in 1938 before 23 children with chronic hepatic disease7a. either agent was known. An agent was recovered Other Viral Infections that in retrospect probably was Myco. Rubella. Rubella, absent for 22 years, caused pneumonice. The historic aspects of these a in Alaska as described in two large epidemic on September 28, 2021 by guest. earliest observations were recited56. papers in the J.A.M.A. of February 22nd, 1965. Cold agglutination occurred in eight patients Virus was recovered 13 days before the rash who had meningoencephalitis and mild upper appeared and for 6 days afterward. Inapparent respiratory symptom without pneumonia. Two and mild infections were common, and 40%/ had mucocutaneous fever (Stevens-Johnson of patients had no rash. Rubella virus isolated syndrome)57. In 1944, I reported severe non- from seven patients during an epidemic in pneumonic disease in a patient whose cold- Texas was pleomorphic by electronmicroscopy. agglutination titer rose to 1: 20,00058. During Some victims had classic rubella, others had the course of infection, Myco. pneumonie severe arthritis. Clinical differentiation from causes cold-agglutination of erythrocytes by ECHO virus infection may be impossible and altering the I antigen that evokes erythrocytic the name rubecho disease was applied to an auto-antibody59. outbreak in Africa. Nine months later more Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 540 POSTGRADUATE MEDICAL JOURNAL September, 1965 than 30 infants were born with congenital a diagnostic problem, until it was shown that defects68. close contact and dermal abrasions favored Rubella virus was isolated up to 41 weeks infection with herpes simplex virus as "Herpes after birth from three malformed infants whose gladiatorum"79. mothers had been infected in first trimester69. Fatal herpes simplex necrotizing pneumonia Virus survived in utero in mothers for at least of an infant was acquired during passage 36 weeks70. Four nurses contracted rubella by through the birth canal of the mother with handling congenitally infected infants some of primary herpetic vulvovaginitis. Gammaglobulin whom shed virus for months after birth70. injected into the mother before delivery had During an epidemic, the injection of gamma- no effect8°. Herpes simplex cervicitis was caused globulin seemed to prevent rubella as compared by sexual contact with recurrent herpetic penile with control persons71. In other studies, lesions81. Herpes viral pneumonia and toxo- gammaglobulin failed to prevent rubella in plasmic encephalitis were fatal in a patient with mothers and in experimentally infected Hodgkin's disease treated with prednisone, children72. For the present, it may be wise not alkylating agents and roentgen rays. Herpes to rely on gammaglobulin as a protective agent. virus is an occasional unsuspected cause of About 17% of pregnant women have no viral pneumonia82. Herpes simplex in a 9-year- demonstrable antibody for rubella73. The old boy was said to have caused 17 episodes salivary gland virus caused 1% to 3% of birth of psychosis during three years, coincident with defects. Unfortunately, the infection usually is vesicles on the oral mucosa and encephalitis83. inapparent in adults and is undetectable without Viral Hepatitis. Among 737 military men special investigation74. exposed to hepatitis after eating food con- Measles. In a region of Alaska where measles taminated an infected food-handler, 96 were by Protected by copyright. had not occurred since 1942, 164 persons investigated. In most of these, hepatic functional received live measles vaccine and gamma- tests gave abnormal results and biopsy of the globulin. About 7% of them reacted with liver of 68 showed histologic evidence of fever and 6% had a rash. The failure of hepatitis in 51. Only three were icteric84. Thirty antibody to increase in titer in seroimmune cases of inapparent hepatitis discovered by persons indicated that durable immunity had laboratory tests during a routine study of followed a natural attack of the disease75. The Koreans also portrayed symptomless infection85. immunity evoked by one injection of an By using sensitive procedures for detecting improved vaccine persisted for 30 months. hepatitis, infection by transfusion occurred Reactions thereto occurred in 5% of vaccinated oftener than believed. Among 56 patients who children76. had received blood, 10 had evidence of in- At a symposium on virology in Florida, apparent infection, but none was icteric. In Smorodintzev reported success in vaccination two, evidence of hepatitis appeared within six against mumps with live attenuated virus weeks, and in two others hepatic disturbance applied transnasally. The vaccine can be persisted 10 months. The rate of inapparenthttp://pmj.bmj.com/ administered with antimeasles vaccine, but not to overt infection was estimated as 1:10086. with gammaglobulin which neutralizes mumps The three articles just referred to have examples virus. of transient inapparent infections that account Contrary to previous opinion, the incubation for undetected carriers who serve as sources period of infectious mononucleosis instead of of infection. The number of cases of hepatitis being four to 15 days was 34 to 39 days in in the United States reached a peak in 1960-61 seven patients77. At a recent meeting of the but has declined. The next 7-year cyclic peak on September 28, 2021 by guest. American Association for the Advancement of may occur in 1968. Science, Schneider described evidence that a Viral hepatitis affects other tissues besides virus caused the disease. The agent was said the liver. Inflammation and granulomas were to have been isolated in tissue cultures from detected in specimens of gastric and intestinal the blood and from the liver of patients. A mucosa and of the kidneys. Mild anemia and benign infection resembling infectious mono- hemolytic anemia occasionally were observed87. nucleosis, presumably viral in origin, was Since 1961, 87 cases of hepatitis occurred in transmitted to nine patients by the transfusion persons in close contact with chimpanzees or of blood after open cardiac surgery. Symptoms other primates88. The mode of infection sug- appeared after three or four weeks78. gested airborne transmission which seems Herpes Simplex. Constitutional symptoms possible, but thus far is unproved. and dermal lesions among five wrestlers posed There are three or more serotypes of the Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 541 causal hemovirus. Inoculation with tissue-cell caused by orally administered antipolio cultures caused hepatitis in four of 15 volun- vaccines. It was not possible always to deter- teers. Hepatitis has a spectrum of severity mine if vaccines caused infection. Fifty-seven ranging from inapparent infection to fatal suspected cases, mostly in adults, occurred 4 jaundice. Hemoviruses are prevalent in healthy to 28 days after vaccination. For that reason a persons without their having had known suggestion was made, but with dissent, not to hepatitis89. If epidemic hepatitis and serum vaccinate persons more than 18 years of age, hepatitis are caused by the same viruses, but except under circumstances of unusual risk. differ clinically according to the portal of entry, The danger of vaccine causing serious infection one wonders why gammaglobulin protects is minmal, considering the millions of persons against one and not the other. so treated98. Concurrent enteroviral infections Strain WW-55 virus caused mild hepatitis in interfere with the action of polio vaccine99. inoculated West African monkeys, the first In a study of the cause of sudden unexpected time that this has been accomplished90. Treat- death of infants, ECHO viruses Types 7 and ment of plasma with propiolactone and 22 were isolated from 7 of 10 babies'00. Whether ultraviolet radiation was said to eliminate the or not the viruses were pathogenic was danger of transmission of the virus91. Several uncertain. Enteroviruses were "typed" success- authorities do not believe that the viruses of fully by complement-fixation. The technic was hepatitis have been isolated. reliable and correlated with neutralization As in the case of viral hepatitis just men- tests'01. The clinical aspects of enteroviral tioned, there has been a tendency to regard infections in general were reviewed by many viruses as specifically unitropic, but Altman'02. evidence accrues that other tissues also are Viral Dysentery. Bacteria were the chief affected. The myocardium, the gastrointestinal causes of diarrhea among 214 Puerto Rican Protected by copyright. and neural system may be invaded by entero- children. Coxsackie and ECHO viruses were respiratory and varicella viruses; herpes zoster isolated from 22% and specific immune bodies may be disseminated especially in victims of appeared in the blood of most. Mixed viral, lymphoma and in those treated with cortico- bacterial and parasitic flora were present in steroids92; and various tissues are involved in 23%103. mice inoculated with the virus of lymphocytic "Epidemic collapse" affected 404 pupils in choriomeningitis93. Disturbed renal function three schools in Coventry in 1964. The features and viruria occurred in victims of mumps. were frontal headache, nausea, vertigo, collapse The virus may cause renal lesions94 and induce abdominalgia, sore throat, cough and vomiting. occasional transitory nephritis. To see if the Diarrhea occurred in only 11%. A virus was kidneys were the site of viral multiplication, suspected as the causel04. This infection also and to account for viruria, attempts were made is called epidemic nausea and vomiting and to recover viruses from the kidneys of children seems to be similar to epidemic viral dysentery at necropsy. From 158 specimens, 84 yielded except for the infrequency of diarrhea'05. http://pmj.bmj.com/ viruses, but the number decreased with Meningoencephalitis. St. Louis encephalitis increasing age of the subject. Cytomegalo-, virus exists in human serum, in domestic adeno-, measles, varicella and Coxsackie viruses pigeons, mice and in mosquitoes of South and were recovered. In five instances, the isolated Central America, the West Indies and Florida virus probably was related to the disease of the as reported on in seven papers in the May, child. The others probably were commensals95. 1964, issue of the American Journal of Tropical when vaccination was Medicine. An of St. Recently, antismallpox epidemic Louis encephalitis on September 28, 2021 by guest. widespread in England and Wales, 185 persons occurred for the first time in Pennsylvania and had eczema vaccinatum. More than half of New Jersey. Sixty-four cases and five deaths them were accidentally inoculated and 6% died. were reported, but many more mild cases, no Vaccination may be hazardous in hypersensitive doubt, were undiagnosed and uncounted. people96. Acute genual arthritis occurred 12 Reoviruses were recovered from the stools days after vaccination against smallpox. The of three children with encephalitis and hepatitis. virus of vaccinia was present in the synovial The viruses could not be proved to be the fluid97. Doubt has been cast on the need for cause except for the presence of virus Type 1 routine general vaccination in the United States. in the stools and in the brain in one fatal case Enteroviral Infection. Apprehension was with myocarditis and interstitial pneumonia'06. raised by the occurrence of 87 reported cases Herpes simplex virus was recovered from the of poliomyelitis-like illness associated with or brain of a child with encephalitis'07. 542 POSTGRADUATE MEDICAL JOURNAL September, 1965Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from Two adults had three or four attacks, and account for the disease, he suggests that a two children had two attacks of meningoence- dengue virus acquired unusual pathogenicity by phalitis at intervals of four months to eight genetic transformation"8. If the Junin or years. Coxsackie B5 and B2, and ECHO Machupo viruses are similar to the Asian 1 and 7 apparently were the causes. The same viruses, and if all are members of the dengue virus or different ones may cause successive group, it is likely that they are antigenically infections'o8. related, but not necessarily mutant forms. Road building in Liberia favored the spread An accidental infection in a laboratory of the tsetse fly from endemic areas of Gambian worker with the virus of louping-ill had features encephalitis. The flies now are a dangerous similar to Kyasanur Forest disease and Omsk roadside hazard'00. hemorrhagic fever"9. Thrombocytopenia and Eight of 520 bats in New England had bleeding are common to each, but also to evidence of infection with rabies virus, but dengue and other viral diseases. only 3 seemed sick at the time of study. The In a flurry of papers, thrombocytopenia and authors were apprehensive of the spread of purpura were described as peculiar to dengue'20, infection to other forms of wild-lifeT0. It is mumps121, rubella'22, and infectious mono- more likely, however, that rabies was always nucleosisl23. A diminution of circulating plate- endemic in the region and is not apt to "spread" lets during pneumococcal pneumonia and anew. Rodents rarely transmit rabies to man. compensatory thrombocytosis shortly after were Among 50,000 rabid animals only 199 (0.42%) described 40 years ago'24, and during typhus were rodents; 82 were squirrels"'. Attempts in 1929125. Similar changes induced in inoculated are underway to collect serum from vaccinated animals resulted in purpura. Thrombocytopenia veterinarians as a substitute for hyperimmune apparently is a common occurrence during horse serum that causes serious reactions. infectious diseases. Protected by copyright. Apparently many persons receive antirabic Newly Recognized and Unusual Viral vaccine unnecessarily. An estimated 30,000 Diseases. Knowledge of epidemic neuromyas- people were so treated annually. In August a bite thenia of unknown cause was reviewed126. A by a skunk caused the first reported case in "new" or hitherto undescribed dermatosis was the United States in 1964. Immediate vaccina- characterized by fever, leukocytosis and painful tion failed to prevent death. In Brazil dermal plaques with dense infiltration of improperly prepared vaccine caused fatal post- neutrophil cells. Tetracycline had no thera- vaccinal encephalomyelitis in 18 of 66 peutic effect but cortisone caused rapid persons"2. One wonders if more persons die improvement127. A peculiar epidemic infection from vaccination than from rabies. Inapparent with a papulo-vesicular rash on the hands and attacks and mild rabies never have been feet, called "Summer-term blains" affected 90 observed in man. Nevertheless, according to of 488 school-girls in England. A virus was Bell's experiments, recovery is possible since suspected as the cause but none was isolatedl28. 33% of his virus was mice survived after inoculation"3. Chagres isolated from persons inhttp://pmj.bmj.com/ Russian scientists believe that a variant of Panama28a. A man exposed to epizootic bovine rabies virus may cause multiple sclerosis and abortion died from pneumonia caused by an acute disseminated encephalomyelitis. Another agent of the bedsonia group similar to the virus suspected to cause amyotrophic lateral cause of the bovine disease129. sclerosis is being investigated in the U.S.A.14. Mink disease of probable viral or myco- Hemorrhagic Fevers. The hemorrhagic fevers plasmal origin caused hypergammaglobulemia of Asia seem to be caused by one or more like that of multiple myeloma. A virus of viruses possibly related to dengue virus"5. mouse lymphosarcoma caused hypergamma- on September 28, 2021 by guest. Dengue viruses were isolated from victims of globulemia, plasma cell infiltration and hemorrhagic fever in Singapore, where the amyloidosis. Amyloid nephrosis occurred in disease generally was mild except in young the late stage of lymphocytic choriomeningitis80. childrenll6. A similar disease called Machupo A virus that seemed to be the cause of human observed in South America was caused by a warts was cultivated in vitrol31. The virus of virus similar to Junin virus and probably is Venezuelan equine encephalomyelitis was transmitted by a wild rodent'7. One wonders isolated from the marrow late in the disease if this is a "new" disease or one that has when it was not found elsewhere in the body. come to attention. Hammon warned that The procedure may be applied successfully for A. egypti mosquitoes may spread infection to the diagnosis of other viral infections'82. the southern United States and elsewhere. To Miscellaneous Viral Studies. "Hospital September, 1965 REIMANN: Infectious Diseases 543 Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from infections" caused by staphylococci and salmo- antiviral activity in mice inoculated with the nellas are of serious import, but other microbes virus if given within 72 hours of infection49. also are blamed. Chief among these are the It also inhibited the growth of rubella virus'50. viruses of hepatitis, smallpox, poliomyelitis, Viractin (actidione) from Streptomyces griseus Coxsackie and ECHO disease, herpes simplex, had doubtful value for respiratory tract vaccinia and respiratory tract infections'33. infectionsl51. Sulfamethoxypyridazine was said Viruses may be transmitted by contaminated to cure trachoma'52, and a vaccine seemed to enema tubingl34. Although viruses were be effective for prevention'53. Other antiviral present only in the central neural system in agents under study are: halogenated pyrimidine seven of 48 dead infants, they have not been nucleosides for herpes viruses, hydroxybenzyl- proved to be the causes of unexplained sudden benzimidazole and guanidine for picorna deaths'35 as mentioned previously. viruses, and pteridines and cyclopin for others. More knowledge of "slow acting" viral Improvements in the diagnosis and treatment infections of animals may shed light on the of cutaneous viral infections were reviewed'54. cause of some obscure human maladies. Ovine A thiosemicarbazone (methisazone) said to diseases such as scrapie, maidi and visna, and be of value as a prophylactic agent against perhaps mink disease, are examples. They have smallpox in India, gave disappointing results characteristics resembling lupus erythematosus, in South Africa155. It has no value. rheumatoid arthritis, myeloma, polyarteritis, therapeutic multiple sclerosis, and Viruses and Neoplasia. Because of evidence 136 pneumonia encephalitis relating viruses to the cause of leukemia, the Congress of the United States authorized ten An interferon-like substance produced by million dollars to support further research for herpes simplex virus suppressed the activities these reasons: Virus-like particles were found of vaccinia, herpes and influenza viruses. in 30% of children with acute leukemia; the Protected by copyright. Because antibody to herpes simplex seems to particles were structurally the same in human have no effect on the infection or in preventing and animal leukemias; virus-like particles were it, interferon may regulate the host-virus transmitted in mouse milk to infant mice; and equilibrium37. Interferon in the crusts of a hope that vaccines to prevent leukemia may vaccinial lesions may be a nonfunctional res- be ponse to viral growth or may suppress viral developed'56. growth until an immune mechanism evolves. Electronmicroscopy disclosed discrete virus- It also like particles in human embryonic tissue infected may modify the clinical course of with material from the bone marrow of patients smallpox38. with leukemia'57, but similar particles occasion- Antiviral Agents. The antiviral activity of ally were seen in control cultures'58. Microbes IDU (5-iodo-2' deoxyuridine) may depend upon isolated from leukemic children either were the short intermolecular distance between the viruses or mycoplasmas that caused leukemia- iodine and oxygen of a carbonyl groupl39. The like disease in inoculated mice. They were not agent not only inhibited the multiplication of found in normal or leukemic adults. Con- http://pmj.bmj.com/ Rous sarcoma virus in vitro, but suppressed fusingly, similar microbes were isolated from the transformation of cells into malignant children with sarcomas and with lupus ones140. A combination of 5-bromo-deoxyuridine erythematosus'59. The usual question of the and N-methyl-isatinthiosemicarbazone eradi- presence of commensals activated by impaired cated vaccinia virus from cultured cells141. host-resistance pertains. Viral and mycoplasmal Views on the efficacy of IDU to cure vaccinial particles obtained from human leukemic tissue and herpetic keratitis and dermal are at in the herpes appeared viscera of marmosets inoculated on September 28, 2021 by guest. variance42. In experimental studies, infected therewith. A relation between the particles and rabbits that were treated improved temporarily, leukemia was not established, but similar ones but infection persisted. Similar disappointing have been found in leukemic mice, not in results ensued in patients'43. In one study, normal ones according to Domchowski's report treatment with IDU delayed healing. Another at a recent meeting. On the other hand, neither drug, tri-fluorothymidine may be of value in Girardi nor Phillips and their co-workers were therapy44. IDU failed in the treatment of able to isolate viral agents from children with herpes zoster'45, cutaneous herpes simplex146 acute leukemia or with infectious mono- and trachoma'47 and 5-fluorodeoxyuridine had nucleosis160 161. Epidemiologic research so far no affect on rubella virus in cell-cultures48. has not revealed convincing evidence of a Amantidine inhibited the growth of influenza virus-like spread of leukemia in man62, 163. virus in vitro. Therapeutically, the agent had In an attempt to "interfere" with the Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 544 POSTGRADUATE MEDICAL JOURNAL September, 1965 presumed virus of leukemia, a variety of viral not determined'76. The oncogenicity of vaccines was injected into a patient with acute adenovirus Type 12 in hamsters was inhibited leukemia. Periods of temporary clinical or prevented by the later administration of improvement occurred164. Injection of gamma- large amounts of the virus. The larger the globulin with antimicrobics had no beneficial quantity of virus inoculated initially, the fewer effect on febrile infections during acute tumor-free animals177. leukemia'65. Because adenovirus 12 induces sarcomas in A Reo virus was isolated from a patient newborn hamsters, persons who have been with Burkitt's lymphoma that seems to be infected with the virus should be observed for endemic in Africa'66. Virus-like inclusions were years. Antibody studies indicated that about present in marrow cells of three patients with 25% of children and 48% of adults have had multiple myeloma, but not in 15 other victims167. such infection, often inapparently. In one The prospects for establishing a causal role laboratory, Type 12 virus comprised only 30/ of viruses in human malignancy were outlined of all adenoviruses isolated from 7,000 patients by Hilleman'l6. Andrewes'69 and Enders157 in four years'78. suspected that some cancers in man either may According to several investigators, "there is be caused by viruses or that viruses like other no definitive information at present to relate irritants serve as incitants. any known virus to neoplasia in man'75. Inoculated SV40 virus disappeared rapidly Perhaps only a genetic portion of a virus179 is from infant hamsters but reappeared in tumors. responsible or a virus may act as an accelerator Virus was not always present and seemed not to chemical or hormonal induced neoplasias to be essential to the retention of oncogenicity. which would develop anyway'80. The problem in some is summarized in Chapters 15 to 19 of a Neutralizing antibody appeared Protected by copyright. animals, but was unrelated to the subsequent recently published bookl8. appearance of tumors'70. Cells infected with SV40 virus synthesized viral antigen and also Bacillary Infections the specific antigen of induced tumors. DNA Tuberculosis. Although a number of sana- inhibits the formation of the viral antigen and toriums for tuberculosis have been closed or serves to differentiate the two171. An X- used for other purposes, the incidence of tuber- irradiated SV40 transplant as a vaccine culosis has risen in the United States in recent prevented tumor formation in newborn hamsters years'82. Some authorities feel that since anti- inoculated with SV40 virus172. Tumor cells polio vaccine has been so successful, had BCG produced by SV40 virus in hamsters did not vaccination been widely practiced, a similar yield the virus on culture, but when seeded onto decline in tuberculosis might have ensued. sensitive indicator cells, characteristic viral Other observers recommend BCG vaccination lesions appeared. The tumor cells evidently only for special groups likely to be infected. harbored persistent viral subinfection called the Its value in protecting against late postprimary "virogenic state." Tumor cells induced by tuberculosis is doubtful. Vaccination destroyshttp://pmj.bmj.com/ adenovirus Type 12 and polyoma virus failed the value of the tuberculin test to locate sources to show viral subinfection. Evidently, basic of infection and for diagnosis'83. According to differences occur in cells transformed by Dubos, BCG vaccine evokes strong and lasting different viruses178. immunity only if the nature and quantity of a Adenoviral particles recovered from tumors standard strain of bacilli used are correct, and induced by virus Type 12 were similar to the if the vaccinees are able to produce antibody. inoculated but At best, does not the ones, were "incomplete" sug- acquired immunity prevent on September 28, 2021 by guest. gesting why the living, infectious virus could primary establishment of lesions nor does it not be isolated despite serologic evidence of its result in the immediate eradication of super- activity'74. Among a variety of viruses including infecting bacilli. Unfortunately, vaccination adenoviruses, influenza, RS, mumps, measles, may prove to have limited usefulness even in rhino-, polio, varicella and others, only unhygienic social environments'84. Thus the adenoviruses 12, 18 and especially Type 7 controversy continues. caused tumors in inoculated newborn ham- The hope for the eradication of tuberculosis stersl75. Tumors appeared after long latent is dim for several reasons: (a) failure to detect periods and were free of detectable viruses170. and report cases, (2) failure of victims to accept Adenovirus Type 12 transformed hamster cells therapeutic management, and (3) failure to in vitro to morphologically altered cells, but prevent inactive disease from reactivating85. whether the changed cells were malignant was Deaths from tuberculous meningitis have de- Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 545 dined after modem therapy, but serious sequels of the original infection or to a new exogenous are common among survivors. Among 65 of infection, indicating the need for active im- them, intracranial calcifications ensued in 21, munization in such persons. Apparently little auditory disturbance in 26, and abnormal or no active immunity ensues as the result of electroencephalograms in 47. Normal education an attack of tetanus'95 in some cases. was possible in only 35186. Active immunization against tetanus with Continued surveillance of previously un- toxoid is the method of choice. Unimmunized treated patients has not disclosed an increasing persons who need protection should be given resistance of Myco. tuberculosis to anti- human tetanus immune globulin for quick microbics. Less than 2% of strains resisted action. Tetanus antitoxin is not reliable and streptomycin and isoniazid and 2.2% resisted there is danger of reaction to equine or bovine paraaminosalicylic acid'87. serums196. The use of homologous antitetanus "Atypical" Tubercle Bacilli. These bacilli serum that has half-life 10 times longer than cause pulmonic disease, lymphadenopathy, serum from other species would eliminate the generalized infection, and destructive poly- danger'97. Penicillin protected mice against arthritis'88 indistinguishable from classic tuber- tetanus only when given within four hours after culosis. Skin testing with various tuberculins infection, but spores persisted unharmedl98. also suggests the existence of inapparent in- Nine patients with tetanus were said to be fections. Both crossreactions to various anti- cured promptly by hyperbaric oxygenation gens and multiple infections probably occur'89. therapy99. If Cl. tetani were active and were The skin reactivity of 947 white infants and suppressed by oxygen, such treatment conceiv- children indicated a higher incidence of infection ably may be effective. But the toxin presum- with nonchromogenic atypical tubercle bacilli ably is bound to neural tissue and the symptoms than with M. tuberculosis and skotochromogens. appear long after bacilli have ceased to grow Protected by copyright. Among coloured patients, the relative incidence or have disappeared. If oxygen therapy is was reversed'90. curative, its mode of action is obscure. Uncertainty persists in regard to the origin of While tracheostomy occasionally is life-sav- mycobacteria that are regarded as atypical, ing when less traumatic measures fail, serious anonymous or unclassified. Some authorities sequels may follow. Among 29 patients so believe them to be separate, distinct strains; treated, 23 lived more than three days and of and others, that they are variant forms of M. these, 18 wounds became infected, eleven by tuberculosis. Perhaps both views are valid. staphylococci and five by Pseudomonas200. In In my own experiments, culture of a strain another report, complications followed trache- of standard H37Rv for months or years on otomy in 33% of 212 patients, 6 of whom solid or in liquid media evoked several variant died201. Tracheostomy is greatly overdone. forms that had many, most, or all of the Parenteral injection of medicaments caused features of "atypical" strains'91. infection with Cl. welchii in five patients, three Leprosy. Immigrants from Indonesia in- of whom died202. When the buttocks are the site http://pmj.bmj.com/ creased the number of lepers in Holland to of injection, it is surprising that such incidents 250. Within months after arrival, supposedly are so rare. For this infection, hyperbaric cured patients had exacerbations192. Two oxygen therapy has a logical base for use patients who failed to improve after therapy against actively growing anaerobes. Some non- with a sulfone compound (Dapone) were in- cytopathogenic viruses caused cytopathic effects fected with bacilli resistant to the drug'93. in tissue cultures when subjected to 95% Capreomycin was used to control successfully oxygen under pressure, but not in air203. on September 28, 2021 by guest. infection with Myco. leprae in the foot-pads of Salmonella. An epidemic of 23 cases of mice. It may have value in treating human infection with Salmonella infantis probably victims194. came from eggs contaminated by a carrier. Tetanus. In a 10-year period, 2,130 cases The disease generally was mild, and in one of tetanus were admitted to hospitals in Bom- patient it was clinically inapparent. Despite the bay. Eleven patients (0.5%) had had tetanus indication that the bacilli were sensitive by the before; one of them three times. The intervals tube-dilution test, both tetracycline and between attacks varied from three months to chloramphenicol failed in treatment204. No one five years. All except one recovered. Six of knows why all salmonellas except S. typhosa the eleven were hypersensitive to antitetanus resist chloramphenicol. serum given for the initial attack. Recurrences In a 3-month period, 745 cases of S. newport may be due to the persistence and reactivation infection occurred. These were acquired from 546 POSTGRADUATE MEDICAL JOURNAL September, 1965Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from bakery products in Upsala. About 66 per cent pathogens were Esch. coli and Klebsiella of of victims were inapparently infected; the rest such serologic diversity that specific identifica- were sick in varying degrees of severity; and tion was impossible. Thirty-five of 45 patients one died205. Sal. typhosa phage Type A infected who had vasomotor failure died217. 26 persons in Harlow, England. The source An unexpected observation concerned a probably was contaminated corned beef. One factor in the serum of some patients with patient had fever but no symptoms, and a child chronic bacterial infection that specifically had neither fever nor symptoms yet typhoid favors an increased growth rate of the pathogen. bacilli were present in the blood of both206. Serum from a patient infected with Pseudo- Salmonella paratyphi B caused an epidemic monas allowed their rapid growth, but inhibited in Scotland, affecting 188 persons in May, 1964. the growth of Esch. coli. and Proteus218. The source probably was a confection prepared Anthrax. Anthrax as an occupational disease with artificial cream, imported eggs or canned affected 57 patients in a 10-year period in meat. Forty patients were symptomless with Massachussetts, and undiagnosed infections no inapparent infection. Four victims who had doubt occurred. Infection does not confer other chronic disease died207. immunity yet prophylactic vaccination was Ampicillin (Penbritin) was said to have con- recommended. Antimicrobics were said to have trolled typhoid in seven of eight patients 208 and been effective in therapy219. Anthrax was fatal was credited in ridding the bacilli from seven in a pipe-fitter who handled goat-hair insulation of eight carriers209. felt. Diagnosis was made when bacteremia was Hodgkins disease renders patients particularly discovered postmortem220. Several persons were susceptible to infection with M. tuberculosis and infected during an epidemic among bison in Salmonella. Three patients infected with Sal- Canada221. Anthrax still is prevalent in south- monella were observed, two of whom died20. western Iran where 25 victims were observedProtected by copyright. in Salmonella also may invade victims of hepatitis a hospital and of these four died. Many more and others whose resistance is impaired. Pet cases no doubt occur for which medical aid is chicks, dogs and turtles are sources of not sought or is not available222. infection2". Cholera. Extensive physiologic studies, pre- Shigella. A cell-free vaccine will Ibe ready viously lacking, were made. Dehydration was soon for clinical trial212. One wonders if its caused by a depletion of extracellular fluid. immunizing effect will be as poor as that from There is a normal, or greater than normal, flow cholera and typhoid vaccines. of protein-free plasma through the normal- Esch. coli. During an epidemic of enteritis appearing enteric membrane that is not among infants, E. coli was present in the resorbed. One patient required the intravenous oropharynx of many symptomless carriers. The injection of more than 60 liters (15 gallons) of carrier rate was 33 per cent in households of fluid in five days. Experiments also showed neighbouring families and 0 per cent in more that water and electrolytes can be restored remote places. Airborne transmission seemed orally when possible223. The suggestion that thehttp://pmj.bmj.com/ likely to have occurred213. The percentage of loss of fluid was the result of disturbed perme- strains of Escherichia coli resistant to neomycin ability not caused by local inflammation of increased from none in 1957-58 to 80 per cent the enteric mucosa, the use of the copper in 1961-62214. sulfate dilution method to measure plasma Pseudomonas, unlike pathogenic staphylo- viscosity, the design of the "cholera cot", a cocci and samonellas, seldom caused wide- trial of and a low death-rate spread "hospital" epidemics215. Yet, a streptomycin, of during 5°/° mentioned in the paper had all been des- on September 28, 2021 by guest. 42-month period, 73 premature, congenitally cribed 20 years ago after the 1945 epidemic of defective, leukemic and otherwise debilitated cholera in Chungking in a report224 to which no children were infected with Pseudomonas in reference was made. Wales. Hygienic surroundings, the use of sterile Unusual manifestations of brucellosis may instruments and parenteral medicaments or cause diagnostic perolexity. Debono observed fluids are the best measures for prevention. 18 patients whose symptoms and signs were Polymyxin was used therapeutically but without mistaken for poliomyelitis225. Chronic sup- decisive effect216. puration of the liver or spleen occurs226. Among 100 patients with bacteremia caused Plague occurred as usual in India227. An by gram negative bacilli, the urinary tract was American soldier contracted bubonic-meningitic the source of infection in 65 per cent, the skin plague in Viet-nam. Lymphogranulomatosis in 14 per cent. Fifty-five died. The commonest first was suspected. Diagnosis was made after Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 547 P.pestis was recovered from a guinea pig coccal glomerulitis in 62 persons. No evidence inoculated with spinal fluid228. of chronic renal disease was detected in 58288. The cause of "endotoxin shock" still is Previous studies had shown that permanent vague. Shock cannot be prevented by antimi- harm rarely ensued. Group B beta-hemolytic crobic prophylaxis and its treatment is unsatis- streptococci (Str. agalactae) were the commonest factory. It is probable in some instances that causes of neonatal sepsis, accounting for 25% antimicrobics, if given, may liberate endotoxin of infections239. by destroying enteric bacteria229. Early L-form colonies of Group A streptococci can diagnosis and therapy was said to have reduced be identified with their parent cocci because the death-rate from 70 per cent to 30 per cent both contain a specific M protein detectable by in a hospital230. an immunofluorescent procedure240. L-form of Although the fluorescent antibody technique Streptococcus fecalis caused fatal septicemia in does not replace cultural and other diagnostic two patients24'a. procedures, it was successful for making rapid Rheumatic Fever. Unless infection with diagnosis in epidemics of pertussis and of Group A hemolytic streptococci is treated with Ech. coli infections in a remote area231. penicillin within 24 hours of its onset, rheumatic fever can ensue. The fluorescent antibody Coccal Infections technique serves to identify streptococcal infec- Streptococci. Monthly injections of repository tion in that early period and obviates treatment penicillin to serve as both prophylaxis and of other infections not influenced by anti- therapeusis were superior to intermittent injec- microbics. Unfortunately, streptococcal infec- tions in reducing the attack rates of strepto- tions may be symptomless and undetected.241 coccal infections and rheumatic recurrences282. evidence accrued that too Previously, early Protected by copyright. Penicillin G or phenethicillin given orally are treatment of streptococcosis impairs the the drugs of choice for the treatment of acute development of immunity. hemolytic streptococcal infection in children. A review of 4.500 cases of rheumatic fever Recurrences happen, but some of them may be over a 40-year period disclosed that its inci- from exogenous reinfection, not from failure of dence has decreased somewhat and the mortality therapy. Recovery occurred promptly in most rate has decreased to a greater extent.242 A patients so treated, and in 80 per cent of those Russian investigator described the pattern of given tetracyline. Treatment with tetracyclines changes in lesions of the myocardium.243 did not result in quick cure. Treatment had to In another co-operative study, a previous be changed for victims of scarlet fever because report of the beneficial effect of therapy with streptococci were not eliminated238. The failure cortisone was not confirmed. Prednisone did of penicillin to eradicate streptococci from the not terminate the course of rheumatic activity throat in some instances may owe to the pre- any better than aspirin, but was helpful in sence there of penicillinase - producing controlling the exudative phase of severe acute staphylococci284, 235 myocarditis in critically sick patients. http://pmj.bmj.com/ The problem persists of differentiating viral Prednisone therapy therefore is not needed for pharyngitis, the commoner infection which treating acute rheumatic polyarthritis with or needs no treatment, from hemolytic strepto- without mild or questionable carditis.244 coccal sore throat which does. Methods of Staphylococci. Airborne transmission of accurate diagnosis were outlined by Stollerman. staphylococci, though it occurs, is not a com- The recommended treatment is 600,000 units mon mode of nor does bedding appear or more of benzathine G. Penicillin spread, penicillin to be a major source. Important means are on September 28, 2021 by guest. may be given orally in doses of 200,000 to the transfer of cocci from the nose to the hands 250,000 units four times daily for ten days. of attendants and to the patient, and from Erythromycin is substituted for patients sensi- infected patients to the hands of other hospital tive to penicillin26. personnel to the next person and so on. Three patients thought to have poststrepto- Results of studies also minimize the importance coccal glomerulonephritis instead had wide- of environmental reservoirs of Group A strep- spread inflammatory and necrotizing vascular tococci. Transfer was limited to intimate con- lesions. Streptococci seemed also to cause tact with carriers. Staphylococcal infections polyvasculitis, but the drugs used for therapy are more difficult to control with penicillin may have been responsible237. A follow-up study than those caused by streptococci. Tetra- was made 10 years after a unique epidemic cycline given to a carrier of staphylococci in- caused by streptococci-induced poststrepto- creased their number in his nose and in the Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 548 POSTGRADUATE MEDICAL JOURNAL September, 1965 surrounding air, and their spread to other even when treatment began on the first or persons246. second days. These studies reemphasize the During a year, 213 patients with staphylo- need to revive the procedure of type determina- coccal sepsis were admitted to a 17-bed isolation tion that is helpful in diagnosis, prognosis, unit. Only 14 died from that infection, but therapy and epidemiology. The authors recom- 14 other deaths were caused by superinvading mend specific vaccines for prophylaxis252. Con- gram negative bacilli. About half were in- sidering the relative rarity of lobar pneumo- fected with untypable staphylococci resistant coccal pneumonia, and the multitude of vac- to penicillin, tetracycline and chloramphenicol. cines available against other infections, the The types of staphylococci present in the noses procedure is impracticable excepting for small of patients were not the same as those of their epidemics of pneumococcosis in closed popula- infections. Nursing personnel did not become tions. carriers of patients' strains, nor did the carrier- Purulent menginitis in adults usually was rate increase among them. The present mor- caused by pneumococci or meningococci in a tality-rate (31%) is about the same as it was Detroit hospital between 1943 and 1963 and in the patients during 1945 (28%), before there has been no increase in the incidence of staphylococci became antimicrobic-resistant247. other gram positive or gram negative bacterial In a survey, 14 per cent of patients were infections. Despite modern therapy, the mor- infected after admission to a hospital. Staphyl- tality-rate of pneumococcal meningitis was 68 ococcus aureus was the chief cause in 34% of per cent253. The death-rate of Klebsiella these and gram negative bacilli in 22 per cent. pneumoniae meningitis was reduced from 99 Twenty-six per cent of the patients were re- per cent to 50 per cent. The infection occurred ceiving antimicrobics at the time248. Twenty-one chiefly in debilitated patients among the 153 of 25 patients with fulminating staphylococcal cases on record254. Protected by copyright. infections recovered after treatment with a For therapy, attempts often are made to combination of a semisynthetic penicillin and secure large amounts of an antimicrobic in the Fucidin249. spinal fluid255, as if the bacteria floating therein Further evidence was added to show that are harmful. Intravenous injection to achieve deliberate nasal colonization of harmless high concentration of the agent in the meningeal staphylococci prevented the invasion of hetero- tissue at the site of infection is more logical. logous virulent ones250. A staphylolytic sub- Serious outbreaks of meningococcal mening- stance was isolated from a species of itis afflicted recruits in military centres and Pseudomonas2oa. elsewhere in the western United States. Ap- parently antimicrobic prophylaxis failed and With the addition of new phages to the other methods were applied to stop the disease. standard ones, more of the currently untypable In one area, 15 of 105 victims died256. Mening- staphylococci can be classified. Type UC-18, ococcus Type 2, Group B, became resistant to for example, caused 10% of infections in a sulfonamides. A carrier-rate hospital and resisted penicillin, tetracycline and high persistedhttp://pmj.bmj.com/ streptomycin. The strain was absent in persons among persons treated orally with sulfadiazine not in hospitals251. or penicillin257. Pneumococcal Pneumonia. Between 1952 Venereal Diseases and 1963, 2,000 cases of pneumococcal pneu- Modern aspects of syphilis and other monia and 529 instances of bacteremia were treponemoses, gonorrhea, lymphogranuloma observed in a hospital, indicating the continued venereum, granuloma inguinale and nonvener- of that Pneumococcus eal diseases were discussed in several prevalence infection. genital on September 28, 2021 by guest. Types 1, 7, 8, 4, 3, 12, 14, 19, 6 and 2 in that articles in the Medical Clinics of North order were the chief causes. Type 1 infection America of June, 1964. A few points of in- was associated with bacteremia in 66 per cent terest are that about 65 per cent of untreated of cases. Type 3 gave the highest mortality, victims of syphilis have little inconvenience 51 per cent of 35 cases. The average death-rate therefrom and that both syphilis and gonorrhea without complications was 20 per cent; with have increased in incidence. Indiscriminate complications, 53 per cent and with meningitis, penicillin therapy probably has inadvertently 63 per cent. In adequately treated patients the cured patients with either infection. At present, death-rate in general was 12 per cent. Anti- most syphilitic patients are treated by private microbic treatment was not always successful. physicians and perhaps 90 per cent of cases are It had little or no effect on the outcome among not reported to health officers. The moder those destined at the onset of illness to die, treatment of syphilis was outlined. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 549 The standard serologic diagnostic tests for studies, evidence of histoplasmosis previously syphilis sometimes fail. In one study, negative undiagnosed or as an inapparent infection, was reactions were obtained in 24 proved infections. discovered in 85% of instances in the mid- The faulty result in 16 of them was caused western United States and in 12% elsewhere.268 by a positive prozone reaction258. Among 66,000 A medical student contracted histoplasmosis in Austrian soldiers who donated blood to a blood a laboratory. Studies then disclosed that 26 of bank, the VDRL test gave a positive reaction 62 exposed classmates were sensitive to the in 49. Thirty-nine of these had syphilis259. If histoplasmin, and nine had pulmonary infiltra- the test is not wholly reliable, one wonders tion.269 Direct staining of sputum is a reliable how many cases were missed or misdiagnosed. method of diagnosis.270 Soil polluted by bird Not long ago, suggestion was made that droppings and sprayed with 36 gallons per 100 syphilis gradually evolved from the prototypes square feet of a 3% solution of formaldehyde of yaws and bejel. A more recent view casts was said to have reduced the incidence of doubt on the separateness of the treponemes histoplasmosis in an epidemic area.27 of venereal syphilis, endemic syphilis, bejel According to Furcolow, attempts to control yaws and pinta. Perhaps the same microbe environmental exposure, sterilization of causes each disease and the different clinical infected foci, and vaccines have not been suc- responses may depend upon epidemiologic fac- cessful in the eradication of histoplasmosis.272 tors, the mode of transmission, the site of Amphotericin B is the drug of choice for the entry and the resistance of the human hosts. treatment of chronic histoplasmosis,273 but it The incidence of atypical forms of infection must be used cautiously. may depend upon the frequency of febrile Histoplasmosis was discovered for the first malaria in some areas of the world. Trepo- time in Cyprus in two persons who were nemes do not survive at temperatures higher infected in a cave that harbored bats.274 In Protected by copyright. than 40°C. Colombia, H. capsulatum was present in a bat's Improved methods of treatment have had no liver.275 The disease had been known for years effect on the spread of gonococcal infection. in Italy and the microbe was isolated from the Infections have increased in incidence world- soil near Bologna.276 Since 1963, 31 cases were wide and "the time has come for an entirely recognised in Montreal.277 Many Puerto Ricans new attitude to this major source of human reacted positively to the histoplasmin skin test. illness and unhappiness."260 After exposure In Japan, some agent other than H. capsulatum to infected partners, 26 of 98 men had asympto- probably accounts for the rare reactors to the matic gonorrhea that was diagnosed by the test.278 H. duboisii differs from H. capsulatum; fluorescent antibody procedure.26 Falsely in Africa lesions of the disease were in the positive results may occur in tests of carriers skin, bone and abdominal viscera, not in the of meningococci that share an antigen with the The gonococcus.262 Among 203 men with urethritis, lungs or central nervous system. Gonococcus was the cause in 139. The epidemiology of the infection there is only unknown.279 http://pmj.bmj.com/ microbe recovered from the rest was the Coccidioidomycosis in the American South- T-strain of Mycoplasma. It resisted penicillin, at the but was sensitive to tetracycline. The infection west was discussed by three essayists probably represents the "sixth" venereal disease October 9 meeting of the American College of but may be asymptomatic at times.263 No Physicians. The irregular distribution of the viruses or evidence of their presence was dis- disease in endemic areas may be explained by covered in 45 with differences in local soils and the temperature patients nongonococcal that either do or do not favor the existence of urethritis.264 Immunofluorescent staining for on September 28, 2021 by guest. the identification of Tr. pallidum and N. the fungus. The infection is clinically inapparent gonorrheae directly from smears of lesions can in 60 per cent of infected persons. Disease be done in about a minute265. The test also ranges in severity from mild respiratory tract gave positive results in 7 of 42 patients with discomfort to severe pneumonia and death. A Reiter's syndrome and negative results in chronic form occurs: Amphotericin-B is urethritis of other cause.266 Spectinomycin was effective if therapy is prolonged, but as men- said to be as effective as other antimicrobics tioned elsewhere in this review, it may be for the treatment of acute gonorrheal ure- nephrotoxic. thritis.267 The hazard of contracting coccidioidomy- cosis in the endemic aea of the St. Joaquin Mycotic Infections Valley, 1963-64, was less than that reported Histoplasmosis. In 706 routine necropsy previously. During the first year of residence, Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 550 POSTGRADUATE MEDICAL JOURNAL September, 1965 infection was evident in only 1.58% of persons Despite control programs, malaria is the in the susceptible population. Suppresion of most serious insect-borne disease in Central dust was a factor in reducing the incidence80. America. Mosquitoes have acquired resistance Among 1,895 persons who served in a to synthetic antimalarial drugs. Malaria laboratory where Coccidioides immitis was occurred among troops in Vietnam who under study during 18 years, about 10 per cent received chloroquine and primaquine, and gave evidence of having been accidentally among Cambodians who were given infected. One third of those whose skin reacted amodiaquine. Evidently, the disappointing to coccidioidin were asymptomatic. The rest had results are a serious setback in the control of had dermal lesions or respiratory tract illness281. the disease. Perhaps a return to the use of Among 22 patients with aspergillosis, 16 quinine is imminent. 289. 290 There is evidence were leukemic and four had cancer. Of these, that P. falciparum may resist quinine.291 20 had received corticosteriods, antimicrobics or It still is uncertain if different species of antineoplastic drugs that impaired their resis- Leishmania account for the different clinical tance282. Growth of Candida albicans was manifestations of infection as oriental sore (L. inhibited by the intact conjunctiva and extracts tropica), mucocutaneous disease (L. brazil- thereof. The inhibition was not ascribed to an liensis) and kala azar (L. donovani) or if the antimetabolic action and was not caused by microbe is the same in each and host resistance lysozyme28. designs the form the disease takes. In the Cryptococcus neoformans usually is regarded Sudan, six infected Americans were observed. as an opportunistic invader in patients whose Four of these had dermal ulcers only, and two resistance is impaired. A case was described, had classic kala azar as if they were less however, in a previously healthy youth who resistant to the same microbe. had ChloroquineProtected by copyright. apparently contracted the infection from pigeon been used as an antimalarial agent in those who droppings. He had severe hepatitis, pneumonia, had dermal lesions, but not in those severely ill, splenomegaly and lymphadenitis. In retrospect, as if the drug had a suppressive action on a transitory attack of pleurisy and pulmonic leishmania. Six persons who were not sick and invasion, suspected as tuberculous 19 months without lesions reacted positively to the dermal previously probably was cryptococcal in origin. leishmanin test, indicating that they, having a Spontaneous remission then was followed by higher degree of resistance, had been systemic dissemination. Subsequent therapy inapparently infected.292 Cutaneous leish- with amphotericin B was successful.284 maniasis is widely distributed in forested regions of Central and South America. Treatment with Protozoal and Metazoal Infections pyrimethamine was said to be effective in In 1936, 148 confirmed and presumptive therapy, but is toxic. cases of malaria were reported in the United Chagas disease caused by Trypanosoma States. P.vivax accounted for 78 cases and P. cruzi, endemic in Central and South America, falciparum for 36. On a ship from Africa re- is transmitted by several species of triatomahttp://pmj.bmj.com/ cently 40 persons had malaria. Twelve infections bugs. About 22% of Panamanians had were caused by P. falciparum of which eight serologic evidence of infection. were overt and four were inapparent. Five other Schistosomiasis affects about 5 per cent of the cases originated in the United States. Of these, world population. S. japonica causes the most two were caused iatrogenically, a third infection serious infections. With increased travel in and had been acquired years ago, and in two the from endemic regions, the infection is becoming origin was unknown.285 The fluorescent anti- more elsewhere.293 prevalent on September 28, 2021 by guest. body test gave positive results in malarial More than 600 cases of leptospirosis were infections.286 recorded in the United States since 1953. Rats Diaprim (pyrimethamine) was used success- are not the only source of infection. Farmers, fully in the prevention of infection in a hyper- veterinarians, packing-house employees and epidemic region of Gambia. None of the pro- meat inspectors are at risk. In the general tected children developed detectable antibody population, 2.6 per cent of sera from persons in contrast with untreated ones. Frequent gave positive results to serologic tests.294 reinfection also maintains specific antibody at a Ecchinococcus multicellularis infected foxes high level287. According to other investigators, and cows in midwest United States, Alaska and Camolar (cycloguanil pamoate) also afforded Canada.295 long-term protection after a single intramuscular Trichinosis among 11 diners was treated with injection.288 thialbendazole. The drug induced defervescence Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 551 of the disease and a sense of well-being in four wounds. Irradiation reduced the risk of post- victims. It failed to kill the larvae, caused operative infection of clean wounds by 25 per dermatitis and central neural disturbance and cent. The net effect in all instances, however, did not alter the eosinophilia.290 The was negligible, that is, infection occuirred in 7.4 fluorescent antibody procedure was said to have per cent of wounds in irradiated rooms and in greater diagnostic value than the precipitin test 7.5 per cent of those in control areas. Infection and the complement fixation test. It gave a rates varied from 3 to 11.7 per cent among the positive reaction within two weeks of the onset five institutions indicating that many other of disease. 297 factors play a role in the incidence of post- Another antihelmintic drug, dithiazone iodide operative infection.306 (Delvex) caused serious gastroenteric and other An account of contagious diseases among disturbances. Eight treated patients died. It the Enigli;sh pilgrims on ship-board and after should be used only for severe infection their arrival in America in the 1620's also caused by Trichiuris or Strongyloides.298 describes the ravages of smallpox among the native Amerinds. They, not having been ex- Miscellaneous posed to smallpox before, had no immunity. Urinary Tract Infection.-Urinary tract and The decimation of hostile tribes was an im- other infections caused by gram-positive portant factor in the success of the immune bacteria have declined more than 50 per cent. in or partially immune pilgrims in establishing 12 years only to be replaced by infections with permanent colonies.307 Similar circumstances, Klebsiella, Aerobacter and Proteus299. The no doubt, pertained in Polynesia after measles change in the flora probably was brought about was introduced by early explorers. therapy. The problem of The thymus gland was said to play a key by antimicrobial Protected by copyright. infection acquired in hospitals, particularly of role in the maturation of immunologic capa- the urinary tract was reviewed by Sanford.300 bilities by means of a humoral mechanism.308 The lining of the urinary bladder is naturally Electronmicroscopy of microbes is advancing able to destroy bacteria. Cystitis often heals rapidly as shown by many articles in a sym- and the urine becomes sterile.301 The intro- posium.309 An apparatus that magnifies billi- duction of a retention catheter may not cause onths of an inch is being constructed. My infection in a normal bladder.302 Measlurement own studies visualized the penetration of bacilli of specific agglutinins in the blood was said to into the enteric mucosa of rats. Apparently, helpful in the diagnosis of overt or inapparent these harmless commensals are disposed of by pyelonephritis.303 surface-action of the microvilli and superficial Infections occurred in 26 of 30 patients in tissue, and by phagocytosis or bacteriocatalysis whom renal homotransplantation was done, and in enteric epithelial cells310. contributed to the cause of death in 10. Staphylococci, Pseudomonas and other gram- REFERENCES negative bacilli were the chief causes. Infections 1. WAKSMAN, S. A. (1965): Antibiotics: The http://pmj.bmj.com/ often followed immunosuppressive therapy that Duplication Problem, Science, 147, 1396. 1 a. KLEIN, J. O., EIcKHoFF, T. C., and FINLAND, impaired the patients' defensive mechanism.304 M. (1964): Gentamycin: Activity in Vitro Protoplasts, as bacteria without cell walls, and Observations in 26 Patients, Amer. J. persist in renal tissue after apparent cure of med. Sci., 248, 528. and may account for a relapse of 2. KLEIN, J. O., et al. (l964): Cephalothin: pyelonephritis Activity in Vitro, Observation and Excretion infection. Erythromycin killed protoplasts, but in Normal Subjects and Clinical Observations

was ineffective against intact bacteria305. Proto- in 40 Patients, ibid, 248, 640. on September 28, 2021 by guest. plasts and L forms were subjects of a sym- 3. BAINES, R. D., and RIFKIND, D. (1964): Intra- summary of which appeared in venous Administration of Sodium Colisti- posium, the methate, J. Amer. med. Ass., 190, 278. Science magazine of 5 February, 1965. Their 4. PERKINS, R. L. (1964): Apnea with Intra- possible causal relation to subacute bacterial muscular Colistin Therapy, ibid, 190, 421. endocarditis, rheumatic fever, Reiter's syndrome 5. BARBER, M., and WATERWORTH, P. M. (1964): Penicillinase-Resistant Penicillins and Cepha- and other diseases was suggested. losporins, Brit. med. J., ii, 344. Other Sttudies. The value of ultraviolet 6. GEDDES, A. M., SLEET, R. A., and MURDOCH, radiation in reducing the number of bacteria J. M. (1964): Lincomycin Hydrochloride. in surgical operating rooms was studied Clinical and Laboratory Studies, ibid, ii, 670. 7. BARBER, M., and WATERWORTH, P. M. (1964): cooperatively in five hospitals. 'Differences in Antibacterial Activity of Lincomycin and the number of surviving air-borne bacteria Pristinamicin: A Comparison with Ery- varied according to the nature of the infected thromycin, ibid, ii, 603. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 552 POSTGRADUATE MEDICAL JOURNAL September, 1965

8. NOYES, R. W., et al. (1965): Drug Antagonism demiology of Respiratory Virus Infections, between Lincomycin and Erythromycin, Science, 146, 1274. Science, 147, 746. 29. BUCKLAND, F. E., and TYRRELL, D. A. J. 9. PINES, A., et al. (1964): Controlled Comparison (1964): Experiments on the Spread of Colds, of Lymecycline with Tetracycline Hydro- J. Hyg. (Lond.), 62, 365. chloride in Exacerbations of Chronic Bron- 30. HAMPARIAN, V. V., LEAGUS, M. B., and chitis, Brit. med. J., ii, 1495. HILLEMAN, M. R. (1964): Additional Rhino- 10. BENNETr, J. E., et al. (1964): In vivo Activity virus Serotypes, Proc. Soc. exp. Biol. (N.Y.), of Colloidal Hamycin, an Antifungal Anti- 116, 976. biotic, Proc. Soc. exp. Biol. (N.Y.), 117, 166. 31. CATE, T. R., et al. (1965): Production of 11. KUCK, N. A., PEETS, E. A. and FORBES, M. Tracheobronchitis in Volunteers with Rhino- (1963): Mode of Action of Ethambutol, on virus in a small-Particle Aerosol, Amer. J. Mycobacterium, Strain H37Rv, Amer. Rev. Epidem., 1, 95. resp. Dis., 87, 905. 32. HAMPARIAN, V. V. et al. (1964): Epidemiologic 12. Antimicrobial Agents and Chemotherapy, Investigations of Rhinovirus Infections, Proc. (1965): Science, 147, 522. Soc. exp. Biol. (N.Y.), 117, 469. 13. WEINSTEIN, L., LERNER, P. L., and CHEW, 33. HILLEMAN, M. R. (1964): Prospects for W. A. (1964): Clinical and Bacteriological Vaccination Against More Recently Dis- Studies of the Effect of Massive Doses of covered Respiratory Viruses, Industry and Penicillin G on Infections Caused by Gram- Trop. Health, 5, 82. negative Bacilli, New Engl. J. Med., 271, HILLEMANN, M. R. (1964): A Forward Look 525. at Viral Vaccines, with Special Reference 14. GRAY, I. R., et al. (1964): Oral Treatment of to a New Immunologic Adjuvant, Amer. Bacterial Endocarditis with Penicillins, Rev. resp. Dis., 90, 683. Lancet, ii, 110. 34. BLOOM, H. H., et al. (1964): Patterns of 15. KREIDBERG, M. B., and CHERNOFF, H. L. Adenovirus Infection in Marine Corps (1965): Ineffectiveness of Penicillin Pro- Personnel, Amer. J. Hyg., 80, 328. phylaxis in Cardiac Catheterization, J. 35. SWANN, N. H. (1964): Acute Thyroiditis Pediat., 66, 286. Associated with Adenovirus Infection, 16. WEINSTEIN, L., SAMET, C. A., and CHEW, W. H. Program Amer. Coll. Phys. Oct. 8, p. Protected by copyright. 30. (1964): Studies of the Effects of Penicillin- 36. GRAYSTON, J. T., et al. (1964): Epidemic Sulfonamide Combinations in Man, Amer. Keratoconjunctivitis on Taiwan: Etiological J. med. Sci., 248, 408. and Clinical Studies, Amer. J. trop. Med. 17. Many Drug-Resistant TB Cases Yield to New Hyg., 13, 492. Therapy Approaches (1964): Antib. News, 37. BERCOVICH, S., and TARANKO, L. (1964): Acute 1, 1. Respiratory Illness in Premature Nursery 18. SCHOENWETTER, A. H., and SILBER, E. N. Associated with Respiratory Syncytial Virus (1965): Penicillin Hypersensitivity, Acute Infection, Pediatrics, 34, 753. Pericarditis, and Eosinophilia, J. Amer. med. 38. GARDNER, P. S., ELDERKIN, F. M., and WALL, Ass., 191, 672. A. H. (1964): Serologic Study of Respiratory 19. PAS, T. A., and QuINN, E. L. (1965): Chole- Syncytial Virus Infection in Infancy and static Hepatitis Following the Administration Childhood, Brit. med. J., ii, 1570. of Sodium Oxacillin, J. Amer. med. Ass., 191, 39. HAMBLING, M. H. (1964): A Survey of Anti- 674. bodies to Respiratory Syncytial Virus in the 20. VANARSDEL, P. P., and GILLILAND, B. C. Population, ibid, i, 1223. (1965): Anemia Secondary to Penicillin 40. BEEMS, M., EGERER, R., and ANDERSON, J. Treatment, J. Lab. clin. Med., 65, 277. (1964): Respiratory Syncytial Virus Neutra- 21. E-rriNGER, E., and KAYE, D. (1964): Systemic lizing Antibodies in Persons Residing http://pmj.bmj.com/ in Manifestations After a Skin Test with Chicago, Pediatrics, 34, 761. Penicilloyl-polylysine, New Engl. J. Med., 41. JOSKE, R. A., et al. (1964): Hepatitis- 271, 1605. Encephalitis in Humans with Reovirus 22. Chloramphenicol (1964): Med. News, J. Amer. Infection, Arch. intern. Med., 113, 811. med. Ass., 190, 34. 42. KASEL, J. A., et al. (1965): ECHO Virus Type 23. ROSENTHAL, R. L., and BLACKMAN, A. (1965): 25, Infection in Adult Volunteers, Proc. Soc. ,Bone-Marrow Hypoplasia Following Use of exp. Biol. (N.Y.), 118, 381. Chloramphenicol Eye Drops, ibid, 191, 136. 43. BASHE, W. J., et al. (1964): Failure of Poly- 23a. Teratogenic Action of Actinomycin D. (1965): valent Vaccine to Provide Clinical Protection on September 28, 2021 by guest. Abstr. J. Amer. med. Ass., 191, 136. against Asian Influenza, New Engl. J. Med., 24. WAISBREN, B. A., and BROWN, I. (1964): Effect 270, 870. of Wide-Spectrum Antibiotics on Bactericidal 44. HOBSON, D., et al. (1964): Serological Studies Activity of Human Serum: In Vitro and in on Adult Volunteers Inoculated with Oil- Vivo, Amer. J. med. Sci., 248, 56. Adjuvant Asian Influenza Vaccine, Brit. med. 25. SHEAR, L., et al. (1965): Intraperitoneal Anti- J., ii, 271. biotic Administration: Rate of Absorption 45. MOFFET, H. L., GRAMBLETT, H. G., and Across Normal Peritoneum, ibid, 249, 1. DOBBINS, J. (1964): Outbreak of Influenza 26. HARRIS, C. (1964): The Physician and Drug A2 Among Immunized Children, J. Amer. Disputes, Science, 146, 717. med. Ass., 190, 806. 27. SMITH, T. J. ;(1964): Antibiotic-Induced 46. WOODS, C. A., and ELLISON, G. W. (1964): Diseases, in Diseases of Medical Progress, Encephalopathy Following Influenza Immuni- Edit., R. H. Moser, pp. 3-60. Springfield, zation, J. Pediat., 65, 745. Illinois: Charles C. Thomas. 47. Flu Outbreaks Hit 21 States (1965): AMA 28. ANDREWES, C. H. (1964): The Complex Epi- News, Mar. 22, page 1. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 553 48. NAYAK, D. P., et al. (1964): Progressive 68. PHILLIPS, C. A., et al. (1965): Isolation of Descending Influenza Infection in Mice Rubella Virus. An Epidemic Characterized Determined by Immunofluorescence, Proc. by Rash and Arthritis, J. Amer. med. Ass., Soc. exp. Biol. (N.Y.), 116, 200. 191, 615. 49. ATKINS, E., CRONIN, M., and ISACSON, P. 69. RUDOLPH, A. J., et al. (1965): Transplacental (1964): Endogenous Pyrogen Release from Rubella Infection in Newly Born Infants, Rabbit Blood Cells Incubated in vitro with ibid, 191, 843. Parainfluenza Virus, Science, 146, 1469. 70. First Trimester Rubella Isolated after Delivery 50. ARTENSTEIN, M. S., BELLANTI, J. A., and (1965): Antibiot. News, 2, 3. BUESCHER, E. L. (1964): Identification of the 70a. HARDY, J., et al. (1965): Postnatal Trans- Antiviral Substances in Nasal Secretions, mission of Ruibella Virus to Nurses, J. Amer. Proc. Soc. exp. Biol. (N.Y.), 117, 558. med. Ass., 191, 1034. 51. KAPIKIAN, A. Z., et al. (1964): A Pilot Study 71. BRODY, J. A., SEVER, J. L., and SCHIFF, G. M. of Acute Respiratory Illness on a College (1965): Prevention of Rubella by Gam- Campus, Amer. Rev. resp. Dis., 90, 175. maglobulin During an Epidemic in Barrow, 52. EVANS, A. S., and DICK, E. C. (1964): Acute Alaska, in 1964, New Engl. J. Med., 272, Pharyngitis and Tonsillitis in University of 127. Wisconsin Students, J. Amer. med. Ass., 190, 72. Gap in Rubella Defenses, Mod. Med., May 25, 699. 1964, p. 29. 53. PEK, S., and GIKAS, P. W. (1965): Pneumonia 73. SEVER, J. L., SCHIFF, G. M., and HUEBNER, due to Herpes Zoster, Ann. intern. Med., 62, R. J. (1964): Rubella Antibodies in Pregnant 350. Women, Obstet. Gynec., 23, 153. 54. FORsyTH, B. R., et al. (1965): Etiology of 74. Salivary Gland Virus may Equal Rubella Primary Atypical Pneumonia in a Military Fetal Peril (1964): Antibiot. News, 1, 1. Population, J. Amer. med. Ass., 191, 364. 75. BRODY, J. A., et al. (1964): Measles Vaccine 55. GRAYSTON, J. T., et al. (1965): Mycoplasma Field Trials in Alaska, J. Amer. med. Ass., Pneumoniae Infections, Clinical and Epide- 190, 965. miologic Studies, ibid, 191, 369. 76. New, Further Attenuated Live Measles Vaccine 56. REIMANN, H. A. (1964): Viral and Myco- Tested in 6,000 Children (1964): Med.

News, Protected by copyright. plasmal Pneumonias, Dis. Chest, 46, 158. ibid, 190, 27. 57. SKOLDENBURG, B. (1965): Aseptic Meningitis 77. HOAGLAND, R. J. (1964): The Incubation Period and Meningo-Encephalitis in Cold-Agglutinin- of Infectious Mononucleosis, Amer. J. publ. Positive Infections, Brit. med. J., i, 100. Hlth., 54, 1699. 58. REIMANN, H. A. (1944): Primary Atypical 78. SMITH, D. R. (1964): Postperfusion Febrile Pneumonia of Unknown Cause: Report of Syndrome, Brit. med. J., i, 945. a Similar Disease without Pneumonia, J. 79. SELLING, B., and KILBRICK, S. (1964): An Mich. med. Soc., 43, 147. Outbreak of Herpes Simplex among Wrestlers 59. Infective Agent in Human Leukemia (1965): (Herpes Gladiatorum), New Engl. J. Med., Leading article, Brit. med. J., i, 267. 270, 979. 60. DOWDLE, W. R., and ROBINSON, R. Q. (1964): 80. WHEELER, C. E., and HUFFINEs, W. D. (1965): An Indirect Hemagglutination Test for Primary Disseminated Herpes Simplex of the Diagnosis of Mycoplasma Pneumoniae Newborn, J. Amer. med. Ass., 191, 455. Infections, Proc. Soc. exp. Biol. (N.Y.), 116, 81. NIGoGOsYAN, G., and MILLS, G. W. (1965): 947. Herpes Simplex Cervicitis, ibid, 191, 496. 61. LUDLAM, G. B., BRIDGES, J. B., and BENN, E. C. 82. CHEEVER, A. W., VALSAMIS, M. P., and (1964): Association of Stevens-Johnson RABSON, A. S. (1965): Necrotizing Toxo- Syndrome with Antibody for Mycoplasma plasmic Encephalitis and Herpetic Pneumonia Pneumoniae, Lancet, i, 958. Complicating Treated Hodgkins Disease, http://pmj.bmj.com/ 62. Virus, Fungus, or Bacterium? (1964): Science, New Engl. J. Med., 272, 26. 146, 1077. 83. SHEARER, M. L., and FINCH, S. M. (1964): 63. CARMICHAEL, L. E., FABRICANT, J., and SQuiRE, Psychosis with Recurrent Herpes, ibid, R. A. (1964): A Fatal Systemic Disease of 1964, 494. Infant Puppies Caused by Cytopathogenic 84. SPONG, F. W., et al. (1964): Anicteric Hepatitis: Organisms with Characteristics of Myco- A Population Study, Program, Amer. Coll. plasma, Proc. Soc. exp. Biol. (N.Y.), 117, Phys. Oct. 18, p. 4. 826. 85. CHUNG, W. W., et al. (1964): Anicteric

64. GRIST, N. R., and MCLEAN, C. (1964): Hepatitis in Korea. I. Clinical and Labora- on September 28, 2021 by guest. Infections by Organisms of Psittacosis Lym- tory Studies, Arch. intern. Med., 113, 526. phogranuloma Venereum Group in the West 86. HAMPERS, C. L., PRAGER, D., and SENIOR, J. R. of Scotland, Brit. med. J., ii, 21. (1964): Post-Transfusion Anicteric Hepatitis, 65. DEAN, D. J., et al. (1964): Prevention of New Engl. J. Med., 271, 747. Psittacosis, Publ. Hlth. Rep. (Wash.), 79, 101. 87. CONARD, M. E., SCHWARTZ, F. D., and YOUNG, 66. RiFKiND, D., et al. (1964): Transplantation A. A. (1964): Infectious Hepatitis - A Generalized Disease, Amer. J. Med., 37, 789. Pneumonia, J. Amer. med. Ass., 189, 808. 89. 67. HEDLEY-WHITE, E. T., and GRAIGHEAD, J. E. McLEAN, I. W. (1964): Clinical Significance (1965): Generalized Cytomegalic Inclusion of Recent Investigation of Hepatitis Viruses, Disease after Renal Homotransplantation, Postgrad. Med., 35, 481. New 90. Hepatitis Apparently Produced in an Experi- Engl. J. Med., 272, 473. mental Animal (1964): Med. News, J. Amer. 67a. HANSHAW, J. B., et al. (1965): Acquired med. Ass., 189, 33. Cytomegalovirus Infection, New Engl. J. 91. Hepatitis Risks in Blood Plasma Held Med., 272, 602. Eliminated (1964): Antibiot News, 1, 1. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 554 POSTGRADUATE MEDICAL JOURNAL September, 1965 92. MERSELIS, J. G., KAYE, D., and HooK, E. W. for Viruses that Cause Chronic Neurologic ,(1964): Disseminated Herpes Zoster. A Diseases in the U.S.S.R., Science, 147, 1114. Report of 17 Cases, Arch. intern. Med., 115. HAMMON, W. M., and SATHER, G. E. (1964): 113, 679. Virological Findings in the 1960 Hemor- 93. WILSNACK, R. E., and ROWE, W. R. (1964): rhagic Fever Epidemic (Dengue) in Thailand, Immunofluorescent Studies of the Histo- Amer. J. trop. Med. Hyg., 13, 629. pathogenesis of Lymphocytic Choriomenin- 116. GoLDsMITH, R. S., et al. (1965): Haemorrhagic gitis Virus Infection, J. exp. Med., 120, 829. Fever in Singapore, A Changing Syndrome, 94. UTZ, J. P., HoUK, V. N., and ALLING, D. W. Lancet, i, 334. (1964): Clinical and Laboratory Studies of 117. WIEBENGA, N. H., et al. (1964): Epidemic Mumps. IV. Viruria and Abnormal Renal Hemorrhagic Fever in Bolivia. II. Demon- Function, New Engl. J. Med., 270, 1283. stration of Complement-Fixing Antigen in 95. BENYESH-MELNICK, M., ROSENBERG, H. S., and Patient's Sera with Junin Virus Antigen, WATSON, B. (1964): Viruses in Cell Cultures Amer. J. trop. Med. Hyg., 13, 626. of Kidneys of Children with Congenital JOHNSON, K. M., et al. (1965): Virus Isolation Heart Malformation and other Diseases, from Human Cases of Hemorrhagic Fever Proc. Soc. exp. Biol. (N.Y.), 117, 452. in Bolivia, Proc. Soc. exp. Biol. (N.Y.), 118, 96. COPEMAN, P. W. M., and WALLACE, H. J. 113. (1964): Eczema Vaccinatum, Brit. med. J., 118. New Asian Dengue Held as Peril to U.S. ii, 906. Gulf States (1964): Antibiot. News, 1, 3 97. SILBY, H. M., et al. (1965): Acute Monarticular (Nov. 25). Arthritis after Vaccination, Ann. intern. 119. COOPER, W. C., GREEN, I. J., and FRESH, J. W. Med., 62, 347. ,(1964): Laboratory Infection with Louping- 98. PHS Recommendations on Oral Vaccine Use Ill Virus: A Case Study, Brit. med. J., ii, (1964): Washington News, J. Amer. med. 1627. Ass., 190, 15. 120. NELSON, E. R., and BIERMAN, H. R. (1964): 99. FELDMAN, R. A., HOLGUIN, A. H., and Dengue Fever: A Thrombocytopenic GELFAND, H. M. (1964): Interference in Disease? J. Amer. med. Ass., 190, 99. Poliovirus Vaccination, Pediatrics, 33, 526. 121. FAMA, P. G., PATON, W. B., and BOSTOCIC, M. I. 100. MOORE, M. L., et al. (1964): Sudden Un- (1964): Thrombocytopenic Purpura Comp-Protected by copyright. expected Death in Infancy. Isolations of licating Mumps, Brit. med. J., ii, 1244. ECHO Type 7 Virus, Proc. Soc. exp. Biol. 122. SVENNINGSEN, N. W. (1965): Thrombocytopenia (N.Y.), 116, 231. after Rubella, Acta paediat. (Uppsala), 54, 101. GNEsH, G. M., PLAGER, H., and DECHER, W. 97. (1964): Enterovirus Typing by Complement 123. CLARKE, B. F., and DAVIES, S. H. (1964): Fixation, ibid, 115, 898. Severe Thrombocytopenia in Infectious 102. ALTMAN, R. (1964): Clinical Aspects of Mononucleosis, Amer. J. med. Sci., 248, 703. Enterovirus Infection, Postgrad. Med., 35, 124. REIMANN, H. A. (1924): The Blood Platelets 451. in Pneumococcus Infection, J. exp. Med., 40, 103. GUARDIOLA-RoTGER, A., et al. (1964): Studies 553. on Diarrheal Diseases, J. Pediat., 65, 81. REIMANN, H. A., and JULIANELLE, L. A. (1925): 104. POLLOCK, G. T., and CLAYTON, T. M. (1964): The Production of Purpura by Derivatives "Epidemic Collapse": A Mysterious Out- of Pneumococcus, ibid, 43, 97. break in Three Coventry Schools, Brit. med. 125. REIMANN, H. A., Lu, G. Y. C., and YANG, C. S. J., ii, 1625. (1929): The Blood Platelets in Typhus Fever, 105. REIMANN, H. A. (1963): Viral Dysentery, Arch. Path., 7, 640. Amer. J. med. Sci., 246, 404. 126. HOLT, G. W. (1965): Epidemic Neuro- 106. JOSKE, R. A., et al. (1964): Hepatitis- myasthenia: The Sporadic Form, Amer. http://pmj.bmj.com/ J. Encephalitis in Humans with Reovirus med. Sci., 249, 98. Infection, Arch. intern. Med., 113, 811. 127. A New Dermatosis? (1964): Lead. Art, Brit. 107. KENT, T. H., and NICHOLSON, D. P. (1964): med. J., ii, 1547. Herpes Simplex Encephalitis, Amer. J. Dis. 128. WARIN, R. P., et al. (1964): Outbreaks of a Child., 108, 644. Papulo-Vesicular Exanthem on the Hands 108. KEMOLA, E., and LAPINLEIMU, K. (1964): and Feet ("Summer-term Blains"), Brit. med. Multiple Attacks of Aseptic Meningitis in J., i, 1413. the Same Individuals, Brit. med. J., i, 1087. 128a. PERALTA, P. H., SHELOKov, A., and BRODY, 109. ABEDI, Z. H., and MILLER, M. J. (1964): J. A. (1965): Chagres Virus: A New Human on September 28, 2021 by guest. Roadside Tsetse Hazard in Liberia, Amer. Isolate from Panama, Amer. J. trop. Med. J. trop. Med. Hyg., 13, 499. Hyg., 14, 146. 110. GIRARD, K. F., et al. (1965): Rabies in Bats 129. BARNES, M. G., and BRAINERD, H. (1964): in Southern New England, New Engl. J. Pneumonitis with Alveolar-Capillary Block Med., 272, 75. in a Cattle Rancher Exposed to Epizootic 111. Rabies Surveillance Unit, C.D.C. Atlanta Bovine Abortion, New Engl. J. Med., 271, (1964): The Role of Rodents in the 981. Epidemiology of Rabies Morbidity and 130. RASK-NIELSEN, R. (1964): Coombs-positive Mortality, 13, 398. Hemolytic Anemia and Generalized Amy- 112. Post-Vaccinal Rabies in Biazil (1965): Trop. loidosis in Mice Following Transmission of Med. and Hygiene News, 14, 8. Subcellular Leukemic Material, Proc. Soc. 113. Laboratory Animals Survive Inoculation with exp. Biol. (N.Y.), 116, 1154. Rabies Virus (1964): Med. World News, 131. OROSZLAN, S., and RICH, M. A. (1964): Human Sept. 11, p. 9. Wart Virus: In vitro Cultivation, Science, 114. BRODY, J. A., et al. (1965): Soviet Search 146, 531. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 555 132. SMITH, T. J., MCKINNEY, R. W., and SAWYER, 151. "Viractin" Against Upper Respiratory In- W. D. (1964): Isolation of Venezuelan fections (1964): Lead. Art, Brit. med. J., ii, Equine Encephalomyelitis Virus by Bone 1482. Marrow Culture, Proc. Soc. exp. Biol. Med., 152. MITSuI, Y., et al. (1964): Trachoma: Its 117, 271. Treatment with a Long-Acting Sulfonamide 133. MILLER, J. D. (1964): Viral Diseases as Administered Orally, Amer. J. trop. Med. Hospital Acquired Infections, Program. Hyg., 13, 488. Amer. Coll. Phys. Oct. 8, p. 11. 153. GRAYSTON, J. T., et al. (1964): Prevention of 134. MEYERS, P. A., and MAY, R. (1964): Virus Trachoma with Vaccine, Arch. environm. Transmission in Enemas, Amer. J. Roent- Hlth., 8, 518. genol., 91, 864. 154. ARTENSTEIN, M. S., and DEMIS, D. J. (1964: 135. BLATrNER, R. J. (1964): Possible Role of Virus Recent Advances in the Diagnosis and Infection in Sudden Unexpected Death, Treatment of Viral Diseases of the Skin J. Pediat., 65, 631. New Engl. J. Med., 270, 1101. 136. "Slow Viruses" Bring Sure Diseases to 155. Methisazone Disappointing in South Africa Animals; Effect on Man Suspected (1964): (1965): Internat. Comments, J. Amer. med. Antibiot. News, 1, 8. Ass., 191, 612. 137. FRUITSTONE, M. J., WADDELL, G. H., and 156. Promise and Caution in Leukemia (1964): SIGEL, M. M. (1964): An Interferon Pro- Mod. Med., 32, 26. duced in Response to Infection by Herpes 157. Viruses Could Trigger Cancer, but might not Simplex Virus, Proc. Soc. exp. Biol. (N.Y.), be a Primary Cause (1964): Med. News, 117, 804. J. Amer. med. Ass., 190, 30. 138. WHEELOCK, E. F. (1964): Interferon in Dermal 158. INMAN, D. R., WOODS, D. A., and NEGRONI, G. Crusts of Human Vaccinia Virus Vaccination. ,(1964): Viruses in Leukemia, Brit. med. J., Possible Explanation of Relative Benignity i, 929. of Variolation Smallpox, Proc. Soc. exp. 159. MURPHY, W. H., FURTADO, D., and PLATA, E. Biol. (N.Y.), 117, 650. (1964): Possible Association between 139. CAMERMANN, N., and TROTTER, J. (1964): Leukemia in Children and Virus-like Agents, 5-Iodo-2'-deoxyuridine: Relation of Structure J. Amer. med. Ass., 191, 122. Protected by copyright. to its Antiviral Activity, Science, 144, 1348. 160. PHILLIPS, C. F., et al. (1965): Failure to 140. FORCE, E. E., and STEWART, R. C. (1964): Isolate Viral Agents from Bone-marrows of Effect of 5-Iodo-2'-Deoxyuridine on Multi- Children with Acute Leukemia, Brit. med. J., plication of Rous Sarcoma in vitro, Proc. i, 286. Soc. exp. Biol. (N.Y.), 116, 803. 161. Infective Agents in Human Leukaemia (1965): 141. FURUSAWA, E., FURUSAWA, S., and CUrrING, Lead. Art, Brit. med. J., i, 286. W. (1965): Further Studies of Drug Com- 162. MILLER, R. W. (1964): Radiation, Chromo- binations for Complete Cure of DNA Virus somes and Viruses in the Etiology of Infection in Cultured Cells, Proc. Soc. exp. Leukemia, New Engl. J. Afed., 271, 30. Biol. (N.Y.), 118, 394. 163. Viruses and Leukemia (1964): Leading Articles, 142. Second Look at First Effective Antiviral Agent Lancet, i, 1259. (1964): Med. News, J. Amer. med. Ass., 164. WHEELOCK, E. F., and DINGLE, J. H. (1964): 189, 38. Observations on the Repeated Administration 143. JUEL-JENSON, B. E., and MACCALLUM, F. 0. of Viruses to a Patient with Acute Leukemia, (1964): Treatment of Herpes Simplex Lesion New Engl. J. Med., 271, 645. of the Face with Idoxuridine: Results of a 165. BODEY, J. P., et al. (1964): Use of Gamma- Double-blind Controlled Study, Brit. med. J., globulin in Infection in Acute-Leukemia

ii, 987. Patients, J. Amer. med. Ass., 190, 1099. http://pmj.bmj.com/ 166. BELL, T. M., et al. (1964): Isolation of a 144. Viral Infections (1964): Med. News, J. Amer. Reovirus from a Case of Burkitt's med. Ass., 190, 41. Lymphoma, Brit. med. J., i, 1212. 145. MACCALLUM, D. D., JOHNSTON, E. N. M., and 167. SORENSEN, G. D. (1965): Virus-like Particles BAJA, B. H. (1964): 5 Iodo-2'-Deoxyuridine in Myeloma Cells of Man, Proc. Soc. exp. in the Treatment of Herpes Zoster, Brit. J. Biol. (N.Y.), 118, 250. Derm., 76, 459. 168. HILLEMAN, M. R. (1964): Prospects for the 146. IVE, F. A. (1964): A Trial of 5-Iodo-2'- Role of Viruses in Human Malignancy, Deoxyuridine in Herpes Simplex, Brit. J. Health Lab. Sci., i, 70. Derm., 76, 463. 169. ANDREWES, C. H. (1964): Tumour-Viruses on September 28, 2021 by guest. 147. SOWA, S., and SOWA, J. (1964): Attempted and Virus-Tumours, Brit. med. J., i, 653. Therapy of Trachoma with 5-Iodo-2'- 170. GIRARDI, A. J., HILLEMAN, M. R., and Deoxyuridine, Brit. med. J., ii, 989. ZWICKEY, R. E. (1964): Tests in Hamsters 148. MASSAB, H. F., and CocimAN, R. W. (1964): for Oncogenic Quality of Ordinary Viruses Influence of 5-Fluorodeoxyuridine on Including Adenovirus Type 7, Proc. Soc. Growth Characteristics of Rubella Virus, exp. Biol. (N.Y.), 115, 1141. Proc. Soc. exp. Biol. (N.Y.), 177, 410. LARSON, V. M., et al. (1965): Studies of 149. DAVIES, W. L., et al. (1964): Antiviral Activity Oncology of Adenovirus Type 7 Viruses in of I-Admantanamine (Amantadine), Science, Hamsters, ibid, 118, 15. 144, 862. 171. RAPP, F., MELNICK, J. L., and KITAHARA, T. 150. MASSAB, H. F., and COCHRAN, K. W. (1964): (1965): Tumor and Virus Antigens of Rubella Virus: Inhibition in Vitro by Simian Virus 40: Differential Inhibition of Amantadin Hydrochloride, Science, 145, Synthesis by Cytosine Arabinoside, Science, 1443. 147, 625. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 556 POSTGRADUATE MEDICAL JOURNAL September, 1965 172. GOLDNER, H., et al. (19%4): Interruption of 192. Leprosy in the Netherlands (1964): Geneesk. SV40 Virus Tumorigenesis Using Irradiated Gids., 42, 375. Homologous Tumor Antigen, Proc. Soc. 193. PETIT, J. H. S., and REES, R. J. W. (1964): exp. Biol. (N.Y.), 117, 851. Sulfone Resistance in Leprosy, Lancet, ii, 173. GERBER, P. (1964): Virogenic Hamster Tumor 673. Cells: Induction of Virus Synthesis, Science, 194. SHEPARD, C. C. (1964): Capreomycin: Activity 145, 833. Against Experimental Infection with Myco- 174. SMITH, R. O., and MELNICK, J. L. (1964): bacterium Leprae, Science, 146, 403. Adenovirus-like Particles from Cancers In- 195. VAKIL, B. J., MEHTA, A. J., and TULPULE, T. H. duced by Adenovirus-12 but Free of (1964): Recurrent Tetanus, Postgrad. med. J., Infectious Virus, Science, 145, 1190. 40, 601. 175. GIRARDI, A. J., LARSON, V. M., and HILLMAN, 196. SCUDDER, P. A., and MCCARROL, J. R. (1964): M. R. (1965): Further Tests in Hamsters for Current Status of Tetanus Control. Im- Oncogenic Quality of Ordinary Viruses and portance of Human Tetanus-Immune Globu- Mycoplasma, with Correlative Review, Proc. lin, J. Amer. med. Ass., 188, 625. Soc. exp. Biol. (N.Y.), 118, 173. 197. ECKMAN, IL. i(1964): Active and Passive Tetanus 176. McBRIDE, W. D., and WIERNER, A. (1964): Immunization, New Engl. J. Med., 40, 601. In vitro Transformation of Hamster Kidney 198. SMITH, J. W. G. (1964): Penicillin in the Cells by Human Adenovirus Type 12, Proc. Prevention of Tetanus, Brit. med. J., ii, Soc. exp. Biol. (N.Y.), 115, 870. 1293. 177. EDDY, B. E., GRUBBS, G. E., and YOUNG, R. D. 199. PASCALE, L., et al. (1964): Treatment of (1964) :Tumor Immunity in Hamsters In- Tetanus with Hyperbaric Oxygenation, J. fected with Adenovirus Type 12 or Simian Amer. med. Ass., 189, 408. Virus 40, Proc. Soc. exp. Biol. (N.Y.), 117, 200. GOTSMAN, M. S., and WHITBY, J. L. (1964): 575. Respiratory Infection Following Trache- 178. CRAMBLETr, H. G., and EDMOND, E. W. (1964): ostomy, Thorax., 19, 89. Adenovirus Type 12 Infection, J. Amer. med. 201. MEADE, J. N. (1964): Tracheostomy-Its Com- Ass., 188, 1086. plications and Their Management: Study of 179. GIRARDI, A. J., and HILLEMAN, M. R. (1964): 212 Cases, New Engl. J. Med., 265, 519. Host Virus Relationships in Hamsters 202. BERGGREN, R. B., et al. (1964): ClostridialProtected by copyright. Inoculated with SV40 Virus During the Myositis from Injections, J. Amer. med. Ass., Neonatal Period, Proc. Soc. exp. Biol. (N.Y.), 188, 1044. 116, 723. 203. SEGRE, D. (1964): Cytopathic Effects of 180. Tumours Caused by Viruses (1964): Lead. Normally Non-Cytopathogenic Viruses in Art. Brit. med J., i, 647. Tissue Cultures Held Under Increased 181. MEDES, G., and REIMANN, S. P. (1963): Normal Oxygen Pressure, Proc. Soc. exp. Biol. Growth and Cancer, pp. 194 to 254. Phila- (N.Y.), 117, 577. delphia and Montreal: J. B. Lipincott. 204. KOHLER, P. F. (1964): Hospital Salmonellosis, 182. A Rise in Tuberculosis (1964): Mod. Med., 32, J. Amer. med. Ass., 189, 6. 54. 205. BILLE, B. T., MELLBRIN, F., and NORDBRING, F. 183. MENZIN, A. W. (1964): Current Immunization (1964): An Extensive Outbreak of Gastro- Methods and Materials, Arch. intern. Med., enteritis Caused by Salmonella Newport. I. 107, 409. Some Observations on 745 Known Cases, 184. DUBOS, R. (1964): Acquired Immunity to Acta. med. scand., 175, 557. Tuberculosis, Amer. Rev. resp. Dis., 90, 505. 206. ASH, I., et al. (1964): Outbreak of Typhoid 185. Eradication of Tuberculosis: A Problem in Fever Connected with Corned Beef, Brit. Epidemiologicopedics (1965): Edit. J. Amer. med. J., i, 1474. med Ass., 191, 492. 207. SHARP, J. C. M., BROWN, P. P., and SANGSTER,http://pmj.bmj.com/ 186. TODD, R. M., and NEVILLE, M. B. (1964): G. (1964): Outbreak of Paratyphoid in the Sequelae of Tuberculous Meningitis, Arch. Edinburgh Area, Brit. med. J., i, 1282. Dis. Childh., 39, 213. 187. HOBBY, G. L. (1965): Primary Drug Resist- 208. UWAYDAH, M., and SHAMMA'A, M. (1964): The ance: II. Continuing Study of Tubercle Treatment of Typhoid Fever with Ampicillin, Bacilli in Veteran Population within the Lancet, i, 1242. U.S., Amer. Rev. resp. Dis., 91, 30. 209. CHRISTIE, A. B. (1964): Treatment of Typhoid Carriers with Ampicillin, Brit. med. J., i, 188. KLINENBERG, J. R., GRIMLEY, P. M., and 1609. SEEGMILLER, G. E. (1965): Destructive Poly- on September 28, 2021 by guest. arthritis Due to a Photochromogenic Myco- 210. ,HEINEMANN, H. S., et al. (1964): Hodgkin's bacterium, New Engl. J. Med., 272, 190. Disease and Salmonella typhimurium Infec- 189. JOHNsON, W. W., and SMITH, D. T. (1964): tion, J. Amer. med. Ass., 188, 632. Cross Reactions with Tuberculins on Guinea 211. Salmonella Surveillance, Comm. Dis. Center. Pigs with Single and Double Experimental U.S. Depart. H. E. and W. No. 27, (July 27) Infections with Mycobacteria, Proc. Soc. 1964. exp. Biol. '(N.Y.), 116, 1024. 2t2. Shigella Vaccine 'Ready for Clinical Trial 190. WALKER, S. H., and PATRON, L. R. (1964): (1964): Antibiot. News, i, 1. Unclassified Mycobacterial Infections in 213. BORIS, M., et al. (1964): Escherichia Coli Children, Amer. J. Dis. Child., 108, 460. Gastroenteritis, Pediatrics, 33, 18. 191. REIMANN, H. A., and MA, P. P. C. (1965): 214. ROZANSKY, R., et al. (1964): Enteropathogenic Dissociation of M. Tuberculosis and Atypical Esch. coli Infection in Infants during the Mycobacteria, Amer. Rev. resp. Dis., in Period from 1957 to 1962, J. Pediat., 64, press. 521. September, 1965 REIMANN: Infectious Diseases 557 Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 215. Hospital Infections with Pseudomonas Pyo- 238. Follow-up of an Epidemic (1964): Mod. Med., cyanea, Lead. Art. (1964): Brit. med. 1., ii, 32, 51. 1019. 239. EICKHOFF, T. C., et al. (1964): Neonatal Sepsis 216. JACOBS, J. (1964): The Investigation of an and Other Infections Due to Group B Outbreak of Pseudomonas Pyocyanea In- Beta-Hemolytic Streptococci, New Engl. J. fection in a Pediatric Unit, Postgrad. med. J., Med., 271, 1221. 40, 590. 240. KARAKAWA, W. W., RoTTA, J., and KRAUSE, 217. MAIzrEGUI, J. I., et al. (1965): Bacteremia Due R. M. (1965): Detection of M Protein in to Gram-Negative Rods, New Engl. J. Med., Colonies of Streptococcal L Forms by 272, 222. Immunofluorescence, Proc. Soc. exp. Biol. 218. Growth Rate of Bacteria i(1964): Med. News, ,(N.Y.), 118, 198. J. Amer. med. Ass., 190, 33. 240a. MATrMAN, L. H., and MATrMAN, R. E. (1965): 219. MATZ, M. H., and BRUGSCH, H. G. (1964): L Forms of Streptococcus Fecalis in Sep- Anthrax in Massachusetts: 1943 Through ticemia, Arch. intern. Med., 115, 315. 1962, J. Amer. med. Ass., 188, 633. 241. SASLAW, M. S., and VIETA, A. G. (1964): 220. Anthrax-Ohio (1964): Morbidity and Mortality. Limits to Rheumatic Fever Prevention, Weekly Report, U.S. Dept. H. E., and W., Pediatrics, 64, 552. 13, 117. 242. MASSELL, B. F., AMEZCUA, F., and PELARGONIO, 221. Outbreak of Anthrax in Northwest Territories S. (1964): Evolving Picture of Rheumatic (1964): Med. Serv. J. Can., 20, 531. Fever. Data from 40 Years at the House of 222. KOHOUT, E., SEHAT, A., and ASHRAF, M. the Good Samaritan, J. Amer. med. Ass., (1964): Anthrax: A Continous Problem in 118, 287. Southwest Iran, Amer. J. med. Sci., 247, 565. 243. ORLOVSKAIA, G. W. '(1964): Development of 223. PHILLIPS, R. A. (1964): Water and Electrolyte Pattern of Tissue Changes in Rheumatic Losses in Cholera, Fed. Proc., 23, 705. Heart, Vop. Revm., 4, 26. 224. REIMANN, H. A., et al. (1946): Asiatic Cholera. 244. Combined Rheumatic Fever Study Group Clinical Study and Experimental Theralpy (1965): A Comparison of Short-term, with Streptomycin, Amer. J. trop. Med., 26, Intensive Prednisone and Acetylsalicylic Acid 631. Therapy in the Treatment of Acute Rheu- 225. DEBONO, J. E. ,(1964): Brucellosis Simulating matic Fever, New Engl. J. Med., 272, 63.

Acute Anterior Poliomyelitis, Lancet, i, 1132. 245. RAMMELKAMP, C. H., MORTIMER, E. A., and Protected by copyright. 226. SpiNK, W. W. (1964): Chronic Suppuration WOLINSKY, E. (1964): Transmission of with Brucellosis, Amer. J. med. Sci., 247, 129. Streptococcal and Staphylococcal Infections, 227. Plague Outbreak in Madras (1964): Brit. Med. Ann. intern. Med., 60, 753. News, Apr. 17. 246. EHRENKRANZ, N. J. (1964): Person to Person 228. FEELEY, E. J., and KRIZ, J. J. (1965): Plague Transmission of Staphylococcus Aureus, Meningitis in an American Serviceman, J. New Engl. J. Med., 271, 252. Amer. med. Ass., 191, 412. 247. BULLOCK, W. E., et al. (1964): A Staphy- 229. WEIL, M. H., SHUBIN, H., and BIDDLE, M. lococcal Isolation Service. Epidemiologic and '(1964): Shock Caused by Gram-Negative Clinical Studies Over One Year, Ann. intern. Organisms, Ann. intern. Med., 60, 384. Med., 60, 777. "Endotoxin Shock" (1964): Editorial, J. Amer. 248. KISLACK, J. W., EICKHOFF, T. C., and FINLAND, med. Ass., 190, 847. M. (1964): Hospital Acquired Infection and 230. OvERHOTr, E. L., and GRAMES, G. M. (1964): Antibiotic Usage in the Boston City Hospital Gram-Negative Septicemia, Milit. Med., 129, -January, 1964, New Engl. J. Med., 271, 181. 834. 231. NELSON, J. D., ,HEMPSTEAD, B., TANAKA, R., 249. JENSEN, K., and LASSEN, H. C. A. (1964): and PAULS, F. P. (1964): Fluorescent Anti- Fulminating Staphylococcal Infections Treated

body Diagnosis of Infections, J. Amer. med. with Fucidin and Penicillin or Semisynthetic http://pmj.bmj.com/ Ass., 188, 1121. Penicillin, Ann. intern. Med., 60, 790. 232. FEINSTEIN, A. R., et al. (1965): Prophylaxis 250. BORIS, M., et al. (1964): Bacterial Interference: of Recurrent Rheumatic Fever, Ineffective- Protection of Adults Against Nasal Staphy- ness of Intermittent "Therapeutic" Oral lococcus Infection after Colonization with lPenicillin, J. Amer. med. Ass., 191, 451. Heterologous S. aureus Strain, Amer. J. Dis. 233. BREESE, B. B., DISNEY, F. A., and TALPEY, Child., 108, 252. W. B. (1964): Streptococcal Infection in 250a. ZYSKIND, J. W., PATrEE, P. A., and LACHE, M. Children, Amer. J. Dis. Child, 107, 232. (1965): Staphylolytic Substance from a 234. MICHAEL, T. M., MICHAEL, J. B., and MASSELL, Species of Pseudomonas, Science, 147, 1458. B. F. (1964): Production of Penicillinase by 251. KUNDSIN, R. B., WALTER, C. W., and MORIN, on September 28, 2021 by guest. Staphylococci in the Throat, Amer. J. med. P. (1964): Staphylococcus Aureus C-18: Sci., 248, 152. Agent of Nosocomial Infections, Science, 235. KUNDSIN, R. B., and MILLER, J. M. (1964): 145, 1322. Significance of the Staphylococcus Aureus 252. AUSTRIAN, R., and GOLD, J. (1964): Pneu- Carrier State in the Treatment of Disease mococcal Bacteremia with Especial Reference Due to Group A Streptococci, New Engl. J. to Bacteremic Pneumococcal Pneumonia, Med., 271, 1395. Ann. intern. Med., 60, 759. 236. STOLLERMAN, G. A. (1964): Sore Throat-A 253. WILSON, F. M., and LERNER, A. M. (1964): Diagnostic and Therapeutic Dilemma, J. Etiology and Mortality of Purulent Men- Amer. med. Ass., 189, 145. ingitis at the Detroit Receiving Hospital, 237. FORDHAM, C. C., et al. (1964): Polyarteritis New Engl. J. Med., 271, 1235. and Acute Post-Streptococcal Glomerulone- 254. SOCIA, J. L., DiBENEDErrO, R., and CROCCO, J. phritis, Ann. intern. Med., 61, 89. (1964): Klebsiella Pneumoniae Meningitis. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from 558 POSTGRADUATE MEDICAL JOURNAL September, 1965 Report of a Case and Review of the 276. SoTGiu, G., and MAzzoNI, A. (1965): Histo- Literature, Arch. intern. Med., 113, 569. plasma Capsulatum: Occurrence in Soil from 255. PLORDE, J. J., GARCIA, M., and PETERSDORF, the Emilia-Romagna Region of Italy, R. G. (1964): Studies on the Pathogenesis Science, 147, 624. of Meningitis: IV. Penicillin Levels in the 277. LEzNon', A., et al. (1964): Histoplasmosis in Cerebrospinal Fluid in Experimental Montreal during the Fall of 1963, with Meningitis, J. Lab. clin. Med., 64, 960. Observations on Erythema Multiforme, 256. EIcKHoFF, T. C., and FINLAND, M. (1965): Canad. med. Ass. J., 91, 1154. Changing Susceptibility of Meningococci to 278. SHIMA, S. (1964): Histoplasmin Sensitivity in Antimicrobial Agents, New Engl. J. Med., Japan, Dis. Chest., 46, 692. 274, 395 279. CocKsHOTr, W. P., and LucAs, A. 0. (1964): 257. PASCOE, D. J., and LuFKIN, C. D. (1964): Histoplasmosis Duboisii, Quart. J. Med., 33, Meningococcal Disease Due to a Sulfadiazine 223. Resistant Strain, Pediatrics, 34, 124. 280. DRIPS, W., and SMITH, C. E. (1964): 258. SPANGLER, A. S., et al. (1964): Syphilis with Epidemiology of Coccidioidomycosis, A a Negative Blood Test Reaction, J. Amer. Contemporary Military Experience, J. Amer. med. Ass., 189, 87. med. Ass., 190, 1010. 259. KAIL, F., and STEPPERT, A. (1964): Cases of 281. JOHNSON, J. E., et al. (1964): Laboratory- Syphilis Detected by the VDRL Test in acquired Coccidioidomycosis, A Report of Blood Donors of the Austrian Army During 210 Cases, Ann. intern. Med., 60, 941. the Years 1960 to 1963, Wien. klin. Wschr., 282. CARBONE, P. P., et al. (1964): Secondary 76, 605. Aspergillosis, Ann. intern. Med., 60, 556. 260. The Spread of Gonorrhoea (1964): Leading 283. KozINN, P. J., CAROLINE, L., and TASaHIAN, Articles, Lancet, ii, 511. C. L. (1964): Conjunctiva Contains Factor 261. PARISER, H., FARMER, A. D., and MARINO, Inhibiting Growth of Candida albicans, A. F. (1964): Asymptomatic Gonorrhea in Science, 146, 1479. Men, Sth. med. I. (Bgham., Ala.), 57, 688. 284. PROCKNOW, J. J., et al. (1965): Cryptococcal 262. Detection of Gonorrhea Antibody Obscured Hepatitis Presenting as a Surgical Emergency, in Meningitis Carriers, (1964), Antibiot. J. Amer. med. Ass., 191, 269. News, 1, 5. 285. Malaria Surveillance, 1963 Annual Summary,Protected by copyright. 263. SHEPARD, M. C., et al. (1964): Possible Role Comm. Dis. Center, Atlanta, Ga. of T-Strain Mycoplasma in Nongonococcal 286. COLLINS, W. F., JEFFRY, G. M., and SKINNER, Urethritis, J. Amer. med. Ass., 188, 729. J. C. (1964): Fluorescent Antibody Studies 264. MORTON, R. S., GILLESPIE, E. H., and WILSON, in Human Malaria, Amer. J. trop. Med. M. A. (1964): Virus Culture Studies in Non- Hyg., 13, 1; ibid., 13, 256; ibid., 13, 777. Gonococcal Urethritis, J. clin. Path., 17, 114. 287. VOLLER, A., and WILSON, H. (1964): Immuno- 265. KELLOGG, D. S., and DEACON, W. E. (1964): logical Aspects of Population under A New Rapid Immunofluorescent Staining Prophylaxis against Malaria, Brit. med. J., Technique for Identification of Treponema ii, 551. pallidum and Neisseria Gonorrheae, Proc. 288. Long-Term Protection against Malaria (1964): Stc. exp. Biol. (N.Y.), 115, 963. Mod. Med., Aug. 3, p. 54. 266. HESS, E. V., HUNTER, D. K., and ZIFF, M. 289. MOST H. (1965): The Pendulum in Malaria (1965): Gonococcal Antibodies in Acute Chemotherapy: From Quinine to Chloro- Arthritis, J. Amer. med. Ass., 191, 531. quine and Back to Quinine? Milit. Med., 129, 267. TIEDEMAN, J. H., HACKNEY, J. F., and PRICE, 587. E. V. (1965): Acute Gonorrheal Urethritis 290. Setback in Malaria Battle (1964): Mod. Med., in Men, J. Amer. med. Ass., 191, 89. Aug. 3, p. 54. 268. BAKER, R. D. (1964): Histoplasmosis in 291. LEOTERS, L. G., et al. (1965): Apparenthttp://pmj.bmj.com/ Routine Autopsies, Amer. J. clin. Path., 41, Refractoriness of Ohloroquine, Pyrimetha- 457. mine and Quinine in Strains of Plasmodium 269. MURRAY, J. P., and HOWARD, D. (1964): Falciparum from Vietnam, Milit. Med., 130, Laboratory-Acquired Histoplasmosis, Amer. 168. Rev. resp. Dis., 89, 631. 292. CAHILL, K. M. (1964): Leishmaniasis in the 270. WOODS, L. P., TINSLEY, E. A., and DIVELEY, Sudan Republic, Amer. J. trop. Med. Hyg., W. L. (1964): Sputum Diagnosis of Histo- 13, 794. plasmosis, J. thorac. cardiovasc. Surg., 48, 293. CARPENTER, C. B., MOZLEY, P. D., and LEwIS,

761. N. G. (1964): Schistosomiasis Japanica on September 28, 2021 by guest. 271. Formaldehyde Flushes Fields Harboring Involvement of the Female Genital Tract, Histoplasma (1964): Antibiot. News, 1, 8. J. Amer. med. Ass., 188, 647. 272. FURCOLOW, M. L. (1965): Environmental 294. GOLDBERG, H. S., BLENDEN, D. C., and LoGUE, Aspects of Histoplasmosis, Arch. environm. J. T. (1965): Leptospirosis in Random and Hlth., 10, 4. Select Populations, Arch. Environm. Hlth., 273. Histoplasmosis Co-operative Study, V.A.- 10, 21. Armed Forces Co-operative Study on 295. MAGATH, T. B. (1965): Ecchinococcus Multi- Histoplasmosis, Amer. Rev. resp. Dis., 89, cellularis in a Beef Cow from the Middle 641. West, Science, 147, 632. 274. STOKER, D. G. (1964): Histoplasmosis in 296. KEAN, B. H., and HOSKINS, D. W. (1964): Cyprus: Report of Two Cases, Brit. med. J., Treatment of Trichinosis with Thiabendazole, ii, 793. J. Amer. med. Ass., 190, 852. 275. MARINKELLE, C. J., and GROSE, E. (1965): 297. LABZOFFSKY, N. A., et al. (1964): Fluorescent Histoplasma Capsulatum from the Liver of Test for Trichinosis, Canad. med. Ass. J., 90, a Bat in Colombia, Science, 147, 1039. 920. Postgrad Med J: first published as 10.1136/pgmj.41.479.536 on 1 September 1965. Downloaded from September, 1965 REIMANN: Infectious Diseases 559 298. Letter, Eli Lilly Co., Sept. 4, 1964. Pyelonephritis, J. Amer. med. Ass., 190, 299. A Change in the Urine (1964): Mod. Med., 1107. 32, 40. 306. SEELEY, S. F. (1964): Influence of Ultraviolet 300. SANFORD, J. P. (1964): Hospital Acquired Light on Post-operative Infection, Editorial, Urinary-Tract Infections, Ann. intern. Med., J. Amer. med. Ass., 189, 574. See also Ann. 60, 903. Surg. 1964: 160, No. 2 Suppl., pp. 9-192. 301. Bladder has Own Defenses against Bacterial Invaders (1964): Med. World News, 5, 26. 307. WOOD, P. H. (1964): Sickness and Settlement. 302. Cox, C. E., and HINMAN, F. (1965): Retention Disease as a Factor in the Early Colonization Catheterization and the Bladder Defense of New England, The Pharos of Alpha Mechanism, I. Amer. med. Ass., 191, 171. Omega Alpha Soc., 27, 98. 303. PERCIVAL, A., BRUMFITr, W., and DELOUVOIS, 308. MILLER, J. F. A. P. (1964): The Thymus and J. (1964): Serum-Antibody Level as an the Development of Immunologic Respon- Indication of Clinically Inapparent Pye- siveness, Science, 144, 1544. lonephritis, Lancet, ii, 1027. 309. Electronmicroscopy, Fifth International Con- 304. RiFKiND, D., et al. (1964): Infectious Diseases gress, S. S. Breese, Edit., Vol. 2, New York Associated with Renal Homotransplantation, and London: Academic Press. J. Amer. med. Ass., 189, 397. 310. REIMANN, H. A., (1965): Microbic Phagocytosis 305. KALMANSON, G. M., and GUZE, L. B. (1964): by Enteric Epithelial Cells, J. Amer. med. Role of Protoplasts in Pathogenesis of Ass., 192, 1130. Protected by copyright. http://pmj.bmj.com/ on September 28, 2021 by guest.