Corynebacterium diphtheriae was first observed by Klebs in 1883 and was cultivated a year later by Loeffler, whose description in 1884 of the causative organism of diphtheria remains a standard. Diphtheria was a life-threatening disease throughout the world until the therapeutic use of antitoxin and the use, as a public health measure, of childhood immunization with toxoid. In Britain the use of toxoid was advocated by the Ministry of Health in the early 1920s, but it was not until 20 years later that extensive programmes of prophylaxis were carried out under the advertising campaign Diphtheria is Deadly.

Friedrich Loeffler's classical paper entitled ‘Untersuchungen über die Bedeutung der Mikroorganismen für die Entstehung der Diphtheric beim Menschen, bei der Taube und der Kalbe’ (Studies on the significance of bacteria in causing diphtheria in man, pigeons and calves), was published in 1884. In this paper and those which followed during the next few years, Loeffler described the diphtheria bacillus and its isolation in pure culture, and proved its relationship to the disease diphtheria. While the credit for the discovery of diphtheria toxin must go to Roux & Yersin (1888), Loeffler clearly predicted its existence in his original paper. Because, at autopsy, living ‘virulent’ diphtheria bacilli could only be recovered from experimental animals at the site of injection, Loeffler postulated that the bacteria must have released into the bloodstream a ‘chemical poison’ which caused the characteristic sterile haemorrhagic lesions in remote organs. He even noted early in 1888 that ‘the bacterial poison resembles in its action the poison [now known as abrin] obtained from jaquiriti seeds, which causes inflammation and the production of false membranes when placed on the mucous membranes either of men or animals’ (cited in Loeffler, 1908). Today we know the reason for this astute observation. Both abrin and diphtheria toxin block protein synthesis in sensitive eucaryotic cells (Collier, 1975; Olsnes & Pihl, 1976; Pappenheimer, 1977), albeit by different mechanisms. Almost a quarter of a century after the discovery of the diphtheria bacillus, the British Medical Research Council published a 718-page volume on diphtheria. In the first chapter Loeffler (1908) reviewed the history of the disease and reminisced at some length about his own early work. By 1908 when this book appeared, a good deal was already known about the epidemiology of diphtheria, the bacteriology of the diphtheria bacillus, its mode of spread by healthy adults and the protective effect of antitoxin. However, other than its proteinaceous nature almost nothing was known of the chemistry of diphtheria toxin or its mode of action. The interpretation of many of Loeffler's astute early observations and questions that puzzled him remained obscure and unanswerable until the discovery of lysogenic conversion to toxinogenicity by Freeman (1951) and the realization that the tox structural gene was carried by a bacteriophage (Uchida, Gill & Pappenhcimer, 1971).

The conversion of non-toxinogenic Corynebacterium diphtheriae to toxinogeny has been reviewed. The biology of converting phage and the relationship of converting phages to nonconverting phages are summarized. The significance of these findings to the natural history and evolution of diphtheria is assessed.

The incidence of diphtheria has declined in North America during the last fifty years until it is now an uncommon disease. This general pattern is similar to that seen in other developed countries with well-organized immunization programmes, but certain noteworthy characteristics have been observed in recent years: foci of infection lingered in two population groups of low socio-economic status, in both of which the skin has been an important reservoir. In central areas of certain cities, endemic diphtheria, chiefly cutaneous, has occurred amongst indigent adult males living in unhygienic conditions; and in the native Indian population of Northern Canada diphtheria infection has been endemic in infants and children, many of the infections being of the skin or ear and toxic disease being uncommon. During the last few years, diphtheria outbreaks have not been reported in urban areas and possibly endemicity is now restricted to northern native populations. The number of infections detected in these northern endemic areas is steadily decreasing.

A letter of inquiry was sent to 21 countries in Europe to ascertain their experience of diphtheria during the last 20 years. An analysis of the 15 replies showed that all relied on childhood vaccination and that this had reduced the annual incidence of the disease to a very low level. There was mention of three epidemics during the last ten years, and three countries identified several cases of skin diphtheria, mostly in patients who had contracted infection abroad.

Chickens were readily infected with salmonella organisms when fed diets containing unsterilized bone-meal or provided with drinking water containing a suspension of natural salmonella infected chicken faeces. When fed diets containing avoparcin at concentrations of 10 or 100 mg/kg chickens infected in these ways excreted larger numbers of salmonellas for longer periods than did chickens fed a nonmedicated diet.

Compared with a similar survey conducted ten years previously, a survey conducted in 1982, eleven years after the implementation of legislation forbidding the routine use of feeds containing ‘therapeutic’ antibiotics, revealed a decreased incidence of resistance to tetracyclines, furazolidone and sulphonamides in Escherichia coli strains causing generalized infections in chickens in the UK; the decrease was particularly marked in the case of tetracycline resistance, 17·9% of strains in 1982 being resistant to this antibiotic compared with 31·2% in 1972.

Giving furazolidone to groups of chickens inoculated intramuscularly with O2:K1 strains of E. coli of differing degrees of furazolidone sensitivity indicated that great care is required in the performance and interpretation of laboratory tests for sensitivity to this antibiotic. Infections caused by strains that required as little as 1·25 μg/ml of furazolidone to inhibit their multiplication in laboratory tests responded poorly to furazolidone treatment; those that were inhibited by less responded well, better than to treatment with tetrac3rcline, chloramphenicol. ampicillin or trimethoprim.

The course of experimental infection in groups of 6-month-old castrated lambs with field isolates of Mycoplasma agalactiae from France was followed culturally and serologically for 7 months. Infection with an ovine field isolate following inoculation by different routes and contact exposure was compared with that caused similarly by a caprine field isolate. The prolonged infections produced were symptomless apart from limited arthritis in one animal inoculated with the isolate from sheep and increased lachrymation in another associated with the goat isolate. The ovine isolate was more virulent in that ante- and post-mortem recoveries of the organism were more consistent and the serological responses more pronounced. Serological responses varied between animals and between strain infections, and the results of the film inhibition test were more consistent than those of the complement fixation test. The limitations of both these tests for detecting carrier infections are discussed.

In vivo methods were used to study the F38-type mycoplasma in parallel with related mycoplasmas.

Three of five strains of ‘bovine serogroup 7’ with an unknown history of subculture produced mycoplasmaemia in mice inoculated intraperitoneally. A strain of ‘bovine serogroup L’ also produced mycoplasmaemia, but no evidence of similar ability could be found for single strains of Mycoplasma capricolum, M. equigenitalium and M. primatum, or for two strains of the F38-type mycoplasma.

In cross-immunization tests a bovine serogroup 7 strain (NCTC 10133) and a strain (‘Blenheim’) of the SC (small colony) type of M. mycoides subsp. mycoides were used for the purpose of challenge. Cross-protection was described as ‘complete’ or ‘partial’, depending on whether it was as great as, or less than, that produced by homologous vaccine. Although strain NCTC 10133 protected strongly, possibly completely, against Blenheim, and Blenheim gave partial protection against NCTC 10133, challenge with NCTC 10133 and Blenheim gave strikingly different results. Thus (1) F38-type strains, M equigenitalium and M. primatum all gave partial cross-protection against NCTC 10133 but not against Blenheim, (2) NCTC 10133, unlike Blenheim, was seldom susceptible to partial cross-protection by LC (large colony) strains of M. mycoides subsp. mycoides, and (3) three SC strains – which would have protected completely against Blenheim – protected only partially against NCTC 10133. NCTC 10133 and Blenheim were similar, however, in that M. capricolum and M. mycoides subsp. capri failed to cross-protect against them both.

The survival and growth of toxigenic Vibrio cholerae 01 in water under various conditions of salinity, pH, temperature and cation composition and concentration were studied in an extensive series of laboratory experiments. Inter- and intra-strain variation in stress response (of 01 and non-01 strains) and the ability of V. cholerae to adapt to stressful environments were also studied. Toxigenic V. cholerae 01 were able to survive for at least 70 days at 25 °C in solutions of sea salt. The optimal salt concentration was 2·0% though all solutions in the range 0·25–3·0% gave good support. Substrains with enhanced capacity to persist at sub-optimal salinity (0·1%) were demonstrated. A great degree of inter-strain variation in stress response at low salinity (0·05%) was found among 59 strains, and this variation was unrelated to serogroup (01 or non-01), source (clinical or environmental) or country of origin (Tanzania or Bangladesh). At optimal salinity, inter-strain variation was less and 18 out of 20 strains remained viable at high concentrations for at least 40 months at 25 °C. V. cholerae 01 could not survive beyond 45 days at 4 °C and optimal salinity, either with or without nutrients. The optimal pH range for survival at 25 °C was 7·0–8·5 at optimal salinity, and 7·5–9·0 at low salinity. V. cholerae 01 require Na+ for survival in the absence of nutrients, and for enhanced growth in their presence. The presence of Ca2+ or Mg2+, in addition to Na+, further enhanced survival. These, and other results reported in this paper, suggest that toxigenic V. cholerae 01 are able to survive for extended periods in warm water containing no nutrients but having a salinity of 0·25–3·0% and a pH of around 8·0. With added nutrients and under the same conditions, rapid growth is possible. The implications of these findings for the identification of putative aquatic reservoirs of V. cholerae 01, and for the epidemiology of cholera, are considerable.

In a series of 519 intravenous cannulae with valved injection side-ports the incidence of cannula-related local inflammation was 25·2% and bacteraemia 0·2%. Severe local inflammation was associated with a longer mean duration of cannulation, 59·4 v. 81·4 h (P = <0·05). There was no significant association between the presence of local inflammation and microbial colonization of either the intravascular segment of the cannula, the adjacent skin, or the side-port. The data suggest that colonization of the cannulae was usually secondary to prior skin colonization. Side-port colonization did not, predispose to cannula colonization. Organisms colonizing the side-port were biologically different and were possibly derived from the skin of medical attendants. In the final 157 patients, randomized to receive either isopropyl alcohol or 0·5% chlorhexidine in 70% spirit skin preparation, there was no difference in the incidence of either local inflammation or microbial colonization.

Operating in ultraclean air and the prophylactic use of antibiotics have been found to reduce the incidence of joint sepsis confirmed at re-operation, after total hip or knee-joint replacement. The reduction was about 2-fold when operations were done in ultraclean air, 4·5-fold when body-exhaust suits also were worn, and about 3- to 4-fold when antibiotics had been given prophylactically. The effects of ultraclean air and antibiotics were additive. Wound sepsis recognized during post-operative hospital stay was, however, reduced by these measures only when it had been classed as major wound sepsis. This was reported after 2·3% of operations done without antibiotic cover in conventionally ventilated operating rooms.

Joint sepsis was much more frequent after wound infection and especially after major wound sepsis, although most cases of joint sepsis were not preceded by recognized wound sepsis. This was particularly noticeable after major wound sepsis associated with Staphylococcus aureus; after 37 such infections the same species was subsequently found in the septic joint of 11 patients. The sources of wound colonization with Staph. aureus, when this was not followed by joint sepsis, appeared to differ widely from those where joint sepsis occurred later. Operating-room sources could bo found for most of the latter and the risk of infection appeared to be similar with respect to any carrier in the operating room whether a member of the operating team or tho patient. For wound colonization that was not followed by joint sepsis, operating-room sources could only be inferred for fewer than half and of these more than one half appeared to be related to strains carried by the patient at the time of operation.

During tho follow-up period, which averaged about 2¼ years with a maximum of four years, there were, in addition to the 86 instances of deep joint sepsis confirmed at re-operation, 85 instances in which sepsis in the joint was suspected during this period but was not confirmed, because re-operation on the joint was not done. The incidence of suspected joint sepsis was, like that of confirmed joint sepsis, less after operations done in ultraclean air: 1/2·5, or with prophylactic antibiotics, 1/2·3

Although re-operation was more frequent on tho knee-joint than on the hip, and pain after the initial operation was more frequent after knee operations, there was no evidence that this was the result of any increased risk of infection.

There was some indication of an increased risk of joint sepsis and of major wound sepsis, after operations on patients with rheumatoid arthritis compared with other diagnoses. The increase could have been as much as twofold but, because of the small numbers involved, the statistical limitations of the study render these differences only marginally significant.

When wound washout samples had been obtained from the surgical wound after the insertion of the prosthesis the risk of subsequent joint sepsis was found to be considerably greater for those patients from whose wounds larger numbers of bateria were isolated than from those of other patients at the same hospital.

Milk samples from 251 nursing mothers were screened for enterotoxigenic staphylococci. The incidence of staphylococci in milk samples was 71·3%. Two hundred and sixteen strains were isolated from 179 mothers. Eighty-six (39·8%) of the 216 strains were found to be toxigenic. Enterotoxin type A (SEA) predominated, with 41 strains (19·0%) elaborating it. Twenty-one strains (9·7%) produced enterotoxin B (SEB) while only eight (3·7%) produced enterotoxin C (SEC). Ten strains (4·6 %) produced all three types. Enterotoxigenic strains usually produced coagulase, thermonuclease and alpha haemolysin.

In this series breast-feeding alone was more common than combined breast and bottle feeding, especially among mothers less than 30 years old. The incidence of reported infantile diarrhoea decreased with increasing age of the mother. Of 16 babies with diarrhoea, 10 (62·5%) had mothers whose milk yielded staphylococci. Six of these were toxigenic. Although no direct relationship between enterotoxigenic staphylococci in the milk of nursing mothers and infantile diarrhoea could be demonstrated, these findings reveal a potential health risk to these infants.

Swabs of rectal faeces were obtained daily for 28 days from 90 calves reared in five batches during the summer of 1983. The calves were purchased unweaned in markets and fed a milk-substitute diet. Salmonella typhimurium phage type DT204c was isolated from calves in four batches and Salmonella newport from one. When the data from the 90 calves were considered together the incidence of salmonellas, excretion rose to peak between 5 and 7 days after purchase before declining to low levels during the fourth week. Salmonella was isolated from 55 (61%) calves; 30 were positive on up to four occasions while 21 and 4 animals respectively were positive between 5 and 11 and 15 and 20 times. In the majority of animals infection was probably subclinical since treatment with antibacterial drugs and excretion of S. typhimurium coincided in four calves only.

Two groups of calves, one of three and the other of two animals, were purchased in markets and reared initially on a commercial veal unit for 1 month and 4 months respectively. They were then moved to the Veterinary School, Langford, and kept for a further 6 and 4 months respectively. The animals were sampled weekly and a continual turnover in the strains forming the majority Escherichia coli faecal flora was demonstrated for all calves. Antibacterial-drug resistance, as measured by an Antibiotic Resistance Index (ARI), increased after arrival on the veal unit and persisted at high levels during the whole of their stay. After moving to Langford the ARI fell. Initially there was a reduction in the average number of resistance determinants per resistant strain and then, after a delay of up to 8 weeks, by an increase in the proportion of isolates that were fully sensitive. The source of the sensitive strains was not ascertained, although their appearance was not associated specifically with either weaning or turning out to pasture.

Bacterial contamination of floors and other surfaces in the operating suite has been investigated by contact impression plates during the past five years. Colony counts of the floors of operating rooms, cleaned with disinfectant, were 3·3 c.f.u./10 cm2; on the floors of semi-clean and dirty areas, cleaned with detergent, colony counts were 44·8 and 71·4 c.f.u./10 cm2 respectively. The highest colony counts of 487·4 c.f.u./10 cm2 were found in the dressing rooms, the floors of which were covered with carpets, cleaned with a vacuum cleaner. Mean bacterial numbers on surfaces of various equipment in operating rooms, cleaned with disinfectant, were 2·8 c.f.u./10 cm2. Bacterial numbers on surfaces decreased markedly from 253·2 to 11·9 c.f.u./10 cm2 following the use of disinfectant. Bacterial species found from various surfaces were mainly coagulase-negative staphylococci, derived from human beings. In the light of these findings the regular use of disinfectant for cleaning of the floors and other surfaces in operating rooms is advisable.

Airborne contamination in an operating suite was studied with a slit sampler, settle plates and a light-scattering particle counter. In conventional operating rooms there was a significant difference between the empty rooms and rooms in use; the mean total bacterial count by a slit sampler changed from 1·1 in empty to 42·5 c.f.u./m3 in use (39 times increase), the settle plates count changed from 1·5 to 17·4 c.f.u./m2/min (12 times increase), and the mean total particle count changed from 56·9 to 546·7/1 (10 times increase) respectively. The increase was caused mainly by persons present in the room.

Another difference was found between zones in the operating suite; the bacterial count in the clean area doubled in the semi-clean area and further doubled in the dirty area in slit sampler count as well as settle plates count, and particle count in the clean area increased by 14 times in the semi-clean and dirty areas. This difference resulted from the different quality of the ventilating system.

Air cleanliness of operating rooms in use by persons present in the room dropped to a level between the clean and the semi-clean area in spite of the high quality of the ventilating system.

Bacterial species identified were mostly coagulase negative staphylococci and micrococci.

Our study indicates that reduction of airborne contamination in an operating suite is accomplished by the combination of an efficient ventilating system and the restriction of the number of persons present in the room.

The efficacy of three anticoagulant rodenticides for use against the Indian field mouse, Mus booduga, was evaluated in the laboratory. The poisons, namely warfarin, bromadiolone and brodifacoum, were all found to be toxic enough at the concentrations normally used against other commensal and field rodents. With brodifacoum (0·00125%), bromadiolone (0·005%) and warfarin (0·025%), 83% of the animals died respectively after 1, 1 and 6 days' feeding. It is suggested that brodifacoum and bromadiolone might be more economical than warfarin for use in practical rodent control.

The detectability of peste des petits ruminants (PPR) viral antigen in both ante-mortem secretions and necropsy samples from experimentally infected goats was investigated by both the agar gel precipitation test (AGPT) and counterimmunoelectrophoresis (CIE). Viral antigen was detected from 42·6% of the samples tested by the AGPT and 80–3% by CIE. The detection of viral antigen in a high proportion of the ocular and nasal secretions as well as the faeces and buccal scrapings, particularly from those collected within seven days of the onset of fever, by both techniques, would seem to obviate the need for lymph node biopsies or post-mortem samples in order to make a diagnosis of PPRV infection.

This paper uses the techniques of time series analysis (autocorrelation and spectral analysis) to examine oscillatory secular trends in the incidence of infectious diseases and the impact of mass vaccination programmes on these well-documented phenomena. We focus on three common childhood diseases: pertussis and mumps (using published disease-incidence data for England and Wales) and measles (using data from England and Wales, Scotland, North America and France). Our analysis indicates highly statistically significant seasonal and longer-term cycles in disease incidence in the prevaccination era. In general, the longer-term fluctuations (a 2-year period for measles, 3-year periods for pertussis and mumps) account for most of the cyclical variability in these data, particularly in the highly regular measles series for England and Wales. After vaccination, the periods of the longer-term oscillations tend to increase, an observation which corroborates theoretical predictions. Mass immunization against measles (which reduces epidemic fluctuations) magnifies the relative importance of the seasonal cycles. By contrast, we show that high levels of vaccination against whooping cough in England and Wales appear to have suppressed the annual cycle.