The last 30 years have been changes in emphasis in the study of streptococci and streptococcal diseases. Earlier work concentrated mainly on the sources and methods of cross-infection and descriptive epidemiology of Streptococcus pyogenes in its major manifestations of respiratory, cutaneous and invasive infection and in the complications of rheumatic fever (RF), scarlet fever (SF) and post-streptococcal glomerulonephritis (PSGN).

Selective decontamination of the digestive tract was developed following the observation that the digestive tract normally has considerable resistance to colonization by newly ingested bacteria. The research that eventually led to selective decontamination was performed because in the late 1960s and early 1970s, the need for prophylaxis against Gram-negative infections in immuno-compromized patients became evident. At that time, the relatively small number of antibiotics available for therapy of serious infections often lead to treatment failure. To introduce the subject of selective decontamination, this paper, therefore, starts with a short historical overview of the kind of infectious agents as well as the antibiotics available in the 1960s; particularly regarding the type and treatment of infections in severely compromised patients. The fact that the possibilities in infectious diseases were limited was the reason for our experimental search for ways of successful prophylactic treatment with minimal risk of development of resistance.

It is well known that severe neutropenia, as usually seen in patients with acute leukaemia, aplastic anaemia or secondary to aggressive chemotherapy, predisposes to infections with Gram-negative enteric bacilli, Pseudomonas aeruginosa, Staphylococcus aureus, and to fungal infections. Infection with anaerobes, in contrast, is rare in patients with haematologic malignancy [1]. The spectrum of bacterial pathogens in this patient population has recently broadened, and now includes coagulase-negative staphylococci, viridans group streptococci, and, occasionally, coryneforms and other rather unusual opportunistic organisms. All these microorganisms originate either from the patient's own microflora, especially from the digestive tract, or from the hospital environment after having colonized the patient during the hospital stay [2]. Studies have shown that the incidence of fever during periods of severe neutropenia approaches 100%, and most of these fever episodes actually represent bacterial infection. For more than 20 years, methods for the prevention of bacterial and fungal infections have been under investigation in patients with profound neutropenia. These included decontamination trails, oral or systemic antimicrobial prophylaxis, strict reverse isolation and maintenance of germ-free conditions [3–8], prophylactic granulocyte transfusions [9], and, more recently, the application of haemopoietic growth factors [10, 11]. The method which remains the most widely used is oral antimicrobial prophylaxis, especially with agents for so-called selective decontamination of the intestinal tract.

This report is based on a study of acute infections of the upper respiratory tract in 1965 and detailed records of such infections in 1963 and 1964. A change from illnesses mainly yielding viruses to illnesses mainly yielding group A streptococci was noted around the age of 5 years. A positive culture for group A streptococci in patients over 4 years of age was highly correlated with a complaint of sore throat and with serological evidence of streptococcal infection. A bimodal age distribution curve for pharyngitis associated with a positive culture for group A streptococci was consistently noted. The incidence was highest in children aged 5–9 but a second smaller peak occurred among adults in the 30–39 age group. The evidence suggests that being female increases the risk of acquiring group A streptococci and of experiencing sore throat.

In an uncompleted study in 1965 microscopic haematuria in the second or third week after acute pharyngitis was found four times more often in patients with either microbiological or clinical evidence of dual infection with both group A streptococci and a virus than in patients with evidence only of infection with group A streptococci.

Prospective studies of the role of viruses in the aetiology of transient haematuria and of acute post streptococcal glomerulonephritis are feasible in general practice and would be most productive if concentrated in children 5–9 years of age.

Nosocomial infection in intensive care unit (ICU) practice is a common problem and is associated with abnormal carriage of Gram-negative aerobic bacilli in the gastrointestinal tract, resulting in endogenous infections. Selective decontamination of the digestive tract (SDD) is a regimen aimed at preventing or eradicating this abnormal carriage.

A large number of trials examining SDD in ICU practice have been published, the vast majority showing a significant reduction in the incidence of nosocomial, Gram-negative infection. However, the impact on morbidity and mortality is much less certain. A recent meta-analysis has suggested a 10–20% reduction in mortality (3–6% absolute difference) with SDD. A discussion of these results is presented together with potential criticisms of SDD.

Patients undergoing bone marrow transplantation become immuno-compromised for various reasons. Deep granulocytopenia, induced by conditioning (chemotherapy and total body irradiation), renders the patient at risk for serious bacterial and fungal infections. Our strategy for prevention of these infections by selective decontamination (SD) is the result of more than 15 years of clinical experience and research. The combination of antibiotics, used as standard SD (neomycin, polymyxin B, pipemidic acid and amphotericin B), with the application of local antimicrobial agents eliminates aerobic Gram-negative rods, Staphylococcus aureus and Candida spp. from the mucosal surfaces of the digestive tract, while the majority of the anaerobic flora persist and support colonization resistance (CR). The antibiotics used either are not resorbed or do not yield therapeutic serum concentrations. Antibiotics which induce therapeutic serum concentrations, such as ciprofloxacin and cotrimoxazole, are only used for SD on a limited scale. When Gram-negative rods persist despite intake of the standard regimen, ciprofloxacin is given until these persisting rods are eliminated. If the patients cannot swallow the oral regimen, i.v. cotrimoxazole is given temporarily. Streptococcal infections are prevented by the i.v. adminstration of penicillin for 14 days starting on the first day after cytotoxic treatment (conditioning for bone marrow transplantation). The combination of SD and systemic prophylaxis has been shown to be adequate; the major problem then remaining is a relatively mild catheter-associated infection with coagulase-negative staphylococci.

Over a period of 9 years in general practice temporary enlargement of the spleen was found in 29 episodes of pharyngitis or tonsillitis, in 2 episodes of acute upper respiratory tract infection other than pharyngitis and in 6 episodes of acute cervical lymphadenitis. In five patients more than one episode of illness associated with splenomegaly was recorded.

In 26 of the 37 episodes a possible aetiology was identified. Evidence only of infection with group A streptococci was found in 14 episodes, adenoviruses or coxsackie B viruses were isolated alone in 4 episodes and in 4 episodes the only finding was the presence in the blood of more than occasional atypical mononuclear cells; in 4 episodes there was evidence of both streptococcal and viral infection. Episodes with evidence of streptococcal infection only tended to be of shorter duration and to be more evenly distributed over the year than were episodes without such evidence. Temporary splenomegaly was noted also in two children with varicella (one of whom also had streptococcal infection) and in an adult with probable rubella.

Post-streptococcal complications are known to be common among Ethiopian children. Little is known, however, about the epidemiology of beta-haemolytic streptococci in Ethiopia. A total of 816 children were studied during a one-year period: 24 cases of acute rheumatic fever (ARF), 44 chronic rheumatic heart disease (CRHD), 44 acute post streptococcal glomerulonephritis (APSGN), 143 tonsillitis, 55 impetigo, and 506 were apparently healthy children. Both ARF and APSGN occurred throughout the year with two peaks during the rainy and cold seasons. The female: male ratio among ARF patients was 1·4:1 and 1:1·9 among APSGN. The monthly carrier rate of beta-haemolytic streptococci group A varied from 7·5–39%, average being 17%. T type 2 was the most frequent serotype. Marked seasonal fluctuations were noted in the distribution of serogroups among apparently healthy children. Beta-haemolytic streptococci group A dominated during the hot and humid months of February–May. Strains were susceptible to commonly used antibiotics, except for tetracycline.

Large increases in the number of cases of human food-poisoning caused by salmonella have occurred in several countries in recent years. In England and Wales the annual number of bacteriologically confirmed cases rose from 10665 in 1981 to 30112 in 1990 and it is generally accepted that these figures are underestimates. The reasons for the unprecedented increase are largely unknown but may include increases in the consumption of convenience foods, poultry, and poultry products, together with a dramatic increase in Salmonella enteritidis infections in poultry. S. enteritidis and S. typhimurium are now the predominant serotypes both in human disease and in poultry.

The genetic relationships between various serotypes and serogroups of meningococcal strains were investigated by restriction fragment-length polymorphism (RFLP) analysis using a number of random DNA probes and a probe containing a truncated copy of the meningococcal insertion sequence IS1106. The data were used to estimate genetic distance between all pairs of strains and to construct phylogenetic trees for meningococcal strains. B15: P1.16R strains isolated from cases of systemic meningococcal disease in two health districts with a high incidence of disease were clonal in contrast to similar strains from cases occurring in other parts of the UK. Strains from these areas, which contain a similar genomic deletion, were found to be derived from two distinct lineages within the B15: P1.16R phylogenetic group. RFLP data demonstrated that present serological typing systems for the meningoccus do not necessarily reflect true genetic relationships.

The relationship between size of the infecting dose and severity of the resulting disease has been investigated for salmonella infections by reanalysis of data within epidemics for 32 outbreaks, and comparing data between outbreaks for 68 typhoid epidemics and 49 food-poisoning outbreaks due to salmonellas. Attack rate, incubation period, amount of infected food consumed and type of vehicle are used as proxy measures of infecting dose, while case fatality rates for typhoid and case hospitalization rates for food poisoning salmonellas were used to assess severity. Limitations of the data are discussed. Both unweighted and logit analysis models are used.

There is no evidence for a dose-severity relationship for Salmonella typhi, but evidence of a correlation between dose and severity is available from within-epidemic or between-epidemic analysis, or both, for Salmonella typhimurium, S. enteritidis, S. infantis, S. newport, and S. thompson. The presence of such a relationship affects the way in which control interventions should be assessed.

Following the occurrence of a case of systemic meningococcal disease in a military camp in Norway, throat cultures and blood samples were collected from 33 healthy individuals belonging to the same troop as the patient (troop A) and from 29 individuals from a different troop (troop B) in the same camp. Serological studies showed that 91% of the recruits had bactericidal antibodies against the disease-causing strain. The isolates of Neisseria meningitidis recovered from the throat cultures were serogrouped, serotyped, and assigned to a clone on the basis of an analysis of the electrophoretic mobilities of 14 metabolic enzymes. None of the 23 carriers in troop A harboured the clone responsible for the case of disease, but 6 carried isolates of the same electrophoretic type, ET-7, which was not identified in any of the 19 carriers of troop B. Individuals in troop A were resampled 2 and 17 weeks after the meningococcal disease episode. Five of the carriers had acquired different clones and one of them changed clone twice in that period. Four of the six newly acquired clones had previously been identified in other carriers of troop A, demonstrating transmission of clones among individuals living and working in close proximity.

An outbreak of Salmonella dublin infection occurred in England and Wales in October to December 1989. Forty-two people were affected, mainly adults, and most lived in south-east England. Microbiological and epidemiological investigations implicated an imported Irish soft unpasteurized cows' milk cheese as the vehicle of infection. A case-control study showed a statistically significant association between infection and consumption of the suspect cheese (p = 0·001). Salmonella dublin was subsequently isolated from cheeses obtained from the manufacturer's premises. Initial control measures included the withdrawal of the cheese from retail sale and a Food Hazard Warning to Environmental Health Departments, as well as a press release, from the Department of Health. Subsequently, a decision was taken by the manufacturer to pasteurize milk used in the production of cheese for the UK market and importation of the cheese resumed in June 1990.

Lipopolysaceharide from serostrains of Serpulina (Treponema) hyodysenteriae for serogroups A to I was characterized using sodium dodecylsulphate polyacrylamide gel electrophoresis and silver staining. All strains had lipo-polysaccharide components ranging from 10 to 16 kDa that represented lipid A-core polysaccharide regions, and short O-antigen side chain were also recognized in certain immunoblots.

Serological reactions between lipopolysaceharide and antisera against each of these serostrains were examined by Western immunoblotting. There was relatively little antigenic cross-reactivity between LPS from the nine strains, thus confirming their suitability as serostrains.

Using cross-absorbed sera, isolates within serogroups A and E were shown to possess unique epitopes on the core lipopolysaceharide, distinct from serogroup reactivities. These isolates were therefore identified as serovars within the serogroups.

This study confirmed the usefulness of the serotyping scheme for S. hyodysenteriae, in which the bacteria can be placed into serogroups using unabsorbed sera, and into serovars within these using cross-absorbed sera.

Epidemiological investigation into an outbreak of food poisoning in 17 patients caused by Salmonella enteritidis phage-type 4 demonstrated a highly significant association with consumption of custard, retailed in custard slices and trifles from a bakery on one day. The bakery had changed their recipe for custard 2 weeks earlier to include fresh shell eggs and had not followed earlier national advice on cooking eggs for human consumption. The case-control study supports earlier work associating Salmonella enteritidis phage-type 4 infection with consumption of uncooked or lightly cooked shell eggs.

One hundred and three known sexual-contact pairs of patients with culture-proven gonorrhoea who attended St Mary's Hospital, London between May 1989 and February 1991 were identified. All isolates from these patients were serotyped and auxotyped and compared for type concordance within sexual-contact pairs. Serotype was concordant in 80 (78%) of 103 sexual-contact pairs, auxotype in 88 (85%) and auxotype/serovar (A/S) class in 66 (64%) on the first screening. All pairs of isolates showed concordance in both serotype and auxotype when typing was repeated using a single set of serotyping reagents and of auxotyping media. Seventeen serovars. 9 auxotypes and 36 A/S classes were found in this population. Our results suggest that both serotyping and auxotyping may be used as markers to allow tracing of sexual-contact pairs, but that a single set of reagents should be used to ensure maximum reliability.

In the summer of 1991 a human outbreak of Salmonella enteritidis infection occurred following a barbecue in which about 100 persons were involved. Eggs, supplied by one or more of 10 different layer farms, were the most probable source of the infection. To identify the S. enteritidis-positive flocks, an immunoassay was used to detect salmonella serogroup D-specific antibodies in the yolk of hens eggs. Antibody titres in the eggs from two layer farms, farm A and B, clearly exceeded the titres found in randomly collected eggs. Further investigations on farm A and B yielded high antibody titres in the eggs from flocks A1, A2 and B2, and low titres in the eggs from flock B1. S. enteritidis was isolated from the faecal samples of flocks A1, A2 and B2, whereas no salmonella was detected in the faecal samples of flock B1. The flocks present on both farms originated from the same breeder flock.

Among 63 Staphylococcus aureus isolates (one isolate per one patient) counted from infections (from August to November 1991) in hospital T., eight exhibited resistance to fluoroquinolones. Seven of these quinolone-resistant isolates were multiply- and methicillin-resistant S. aureus (QR-MRSA). The results of phage-, plasmid- and genotyping (pulsed field electrophoresis) revealed that six different strain-clones of these MRSA were spread in the hospital. In vitro spontaneous mutants resistant to fluoroquinolones are 1–-100-fold more frequent in MRSA than in other S. aureus when selected on isosensitest-agar containing 1 μg/ml of ciprofloxacin. However, the same mutant frequencies were found in strain 8325–4 with and without the mecA-determinant. The resistance phenotype was stable over 30 generations of subculture in nutrient broth as well in natural quinolone resistant MRSA as in mutants of other types of S.aureus selected in vitro. The phenotypic association of quinolone resistance and MRSA is rather likely due to a higher frequency of spontaneous resistant mutants which are present in natural populations of MRSA. Data of chemotherapy prior to the isolation of 8. aureus show that three of seven patients from whom QR-MRSA were isolated were treated with a quinolone. In eight cases of infections with non-MRSA and quinolone treatment the isolated S. aureus strains were in vitro sensitive to quinolones.

The DNAs of Shigella sonnei or Shigella dysenteriae type 1 strains isolated in outbrealis of shigellosis or in sporadic cases were analysed by restriction fragment length polymorphism (RFLP). Southern blots of the DNAs of 36 S. sonnei isolates digested by 8 restriction enzymes were hybridized with an Escherichia coli rRNA probe. The S. sonnei strains were unexpectedly diverse in their RFLP. Antibiotypes of the same isolates showed clusters of strains corresponding to the various outbreaks. On the other hand, RFLP analysis suggested concomitant multiple sources of infection rather than a common source and thereby introduced a new insight in the epidemiology of shigellosis. RFLP was also used to trace S. dysenteriae type 1 transmission in a recent cluster of clinical cases. Although antibiotic resistance patterns indicated the presence of more than one strain, RFLP analysis showed that the six isolates were identical clones and suggested the loss of an R episome after one person-to-person passage.