1. The incidence produced during 1926 by two epidemics of diphtheria, in a remote and unsalted country district, was equivalent to 30 years of the London endemic morbidity.

2. The cases arose in two distinct groups. An autumn outbreak with a definite concentration of infection on the school age, and probably disseminated by droplet infection, followed by an epidemic in the succeeding spring which was more severe, probably milk-borne, and in which the frequency of cases was higher among infants and adults than school children.

3. The effect of a long drive over bad roads caused a deterioration of the diluted toxin which was used for a Schick test investigation. The use of this toxin led at first to false conclusions regarding the immunity of the children, since it only caused reactions in the most susceptible members of the community.

4. As a result of retesting with a fully potent toxin it was estimated that the figure of 40 per cent. susceptible which was found with the weak toxin would have been about 80, if full strength toxin had been used.

5. The attempt to immunise actively those children who had reacted to the weak Schick toxin was found to have failed in 72 per cent. of a group which was retested 7 months later. The prophylactic course was identical with one which had succeeded in inducing Schick immunity, within 4 months, in 100 per cent. of the susceptible children in the Dunedin orphanages.

6. The slow rate of immunisation at Kaitangata is attributed to two causes, (a) the low original herd immunity of the district, (b) the selection by the weak toxin of only the most sensitive reactors which were almost certainly the most “unresponsive” members of the total Schick positive population.

7. By a comparison of the rate of response to a small dose of toxin-anti-toxin mixture, in those positive Schick reactors (a) who had, and (b) who had not, received previous prophylactic injections, it was shown that the principle of “primary and secondary” antigenic stimuli held good for human subjects, as well as for experimental animals.

8. Careful examination of the known data led to the conclusion that the air-borne autumn epidemic had increased the herd immunity of the population, in spite of the fact that the subsequent milk-borne spring outbreak produced as high a morbidity and a more severe type of diphtheria.

9. The practical lessons which may be learnt from this study are: (a) That unless a special buffered diluent is used, the toxin used for Schick testing must be freshly diluted near the place where it is to be used, (b) Active immunisation of remote unsalted communities against diphtheria requires more time, and more intensive courses of prophylactic, than areas where diphtheria has been endemic for some years, (c) In such places with a low original herd immunity, it is essential, even more than in endemic centres, never to omit retesting those who have been inoculated, in order to be certain that any attempt made to induce active immunity to diphtheria may be successful. (d) Estimations of the relative efficiency of diphtheria prophylactics, which are based on the rapidity with which samples of children become immune, are worthless unless all the observations have been made in the same environment on groups having the same original herd immunity, (e) An immunity, good enough to withstand droplet infection in a day school environment, may be broken down by massive doses of diphtheria bacilli in milk.

10. The study of outbreaks of disease in communities which are not too large to prevent a complete supervision of the whole population and environment, enable one to visualise imaginary mechanisms of infection very much more easily than in large populous areas, where so many more factors have to be left unexamined, or remain unsuspected. The hypotheses, perhaps better termed surmises, which the facts suggest, are only intended to be purely tentative and temporary. Their practical value is that they indicate to the investigator a plan of campaign and suggest what to look for, in the lucky event of his ever again meeting with a similar combination of circumstances. In epidemiology in general, as illustrated by this particular instance, opportunities arise and pass, often never to recur, and much is missed, or left undone that might have been done, if only the knowledge and hints gained during the passage of the epidemic itself had been known before its advent.

Reactions so far reported after the use of oil emulsion (OE) foot-and-mouth disease (FMD) vaccines in pigs have been infrequent and quick to resolve themselves. Although tentatively ascribed to anaphylaxis, these reactions have received little attention and their mechanism of causation has not been established conclusively.

Household aggregation of cases, one possible characteristic of person-to-person transmitted disease, was formally tested in one epidemic of variola minor by using a pair statistic. A significant result was found for all households as well as for households grouped by the type of environment, or by the phase of the epidemic growth in time. Secondary attack rates, when related to household size (number of susceptibles) showed only a marginal trend in rural households but no trend in urban or semi-rural households.

A computer program was written to analyse oligonucleotide patterns displayed by gel electrophoresis following restriction endonuclease digestion of human cytomegaloviral DNA, and was applied to an epidemiological study of the transmission of infection in a hospital special care baby unit, with regard to infant-to-infant and mother-to-infant transmission.

The program calculates the molecular weight of oligonucleotides from their mobilities, using a cubic spline curve based on the mobilities of oligonucleotides from the AD169 strain. A matching algorithm then calculates the number of unmatched fragments for each pair of viral isolates. This was used as a similarity measure which successfully distinguished mother and infant isolate pairs from epidemiologically unrelated pairs.

The program is not intended to provide fully automatic matching, but could be recommended as a screening device to pick out pairs of strains which are sufficiently similar to suggest a common source of infection, and which may warrant closer comparison. Other applications are discussed, and the possible use of densitometers to automate data entry is considered.

1. The bacteriological problems involved in the production of meat and fish pastes in sealed glass jars have been studied.

2. Data are presented showing the normal flora of the raw materials used. Particular attention is drawn to the anaerobic species present in seasoning materials.

3. Bacterial contamination due to manufacturing operations is discussed.

4. The requirements of a satisfactory heat treatment are outlined, together with experimental methods of study used to overcome possible causes of failure.

5. Bacteriological examinations of 14,365 samples of paste showed that 88% were sterile: the flora of the remainder was examined.

6. Experimental evidence is presented to show that certain anaerobic spore-forming bacilli are the main possible cause of spoilage, and the significance of aerobic spore-forming bacilli has been established. An extremely heat-resistant anaerobe was isolated.

7. Routine bacteriological control of the finished products is suggested.

8. A simple, inexpensive, and rapid method of detecting anaerobic species has been devised, which can also be applied to other foodstuffs. Data are presented from the examination of a further 6110 samples using this method.

1. The participation times of a series of mixtures of horse serum and a pool of rabbit antihorse serum have been determined. The results have been presented in a table and isochrones drawn. Four distinct α procedure optima were found, suggesting that there may be at least four different antigen-antibody reactions concerned when horse serum reacts with a rabbit antihorse serum.

2. The reaction between horse serum crystalbumin and the same pooled rabbit antihorse serum has been investigated, and recorded-similarly.

3. Inhibition of precipitation was found to be more marked in the region of antigen excess than in the region of antiserum excess. Evidence is presented in support of the view that the occurrence of multiple zones may obscure this observation.

4. The results are compatible with the view that the second stage of the precipitation reaction is specific.

5. The isochrones correspond with Boyd's R type.

Information is lacking on the integrated evaluation of mortality rates in healthcare-associated infections (HAIs). Our aim was to differentiate the risk factors responsible for the incidence from those for the case-fatality rates in association with HAIs. We therefore examined the time trends of both incidence and case-fatality rates over a 20-year period at a tertiary-care teaching medical centre in Taiwan and the mortality rate was expressed as the product of the incidence rate and the case-fatality rate. During the study period the overall mortality rate fell from 0·46 to 0·32 deaths/1000 patient-days and the incidence rate fell from 3·41 to 2·31/1000 patient-days, but the case-fatality rate increased marginally from 13·5% to 14·0%. The independent risk factors associated with incidence of HAIs were age, gender, infection site, admission type, and department of hospitalization. Significant prognostic factors for HAI case-fatality were age, infection site, intensive care, and clinical department. We conclude that the decreasing trend for the HAI mortality rate was accompanied by a significant decline in the incidence rate and this was offset by a slightly increasing trend in the case-fatality rate. This deconstruction approach could provide further insights into the underlying complex causes of mortality for HAIs.

1. Salmonella typhi, strain Ty2, grown in vivo and employed as acetone-dried vaccine possessed a higher immunizing potency than the descendants of the same parent strain grown in vitro and employed as vaccine.

2. When 2 × 108in vitro-grown bacteria were employed as challenge, the immunizing effects of both types of vaccine were more marked than after administration of 2 × 108in vivo-grown bacteria as challenge.

3. The higher potency of the in vivo-grown vaccine was apparent in all experiments, whether the challenge strain was grown in vivo or in vitro.

4. Immunogenic substances were isolated from infected organs of mice and guinea-pigs, and an immunogenic substance from the peritoneal fluid of the infected guinea-pigs was concentrated by precipitation with ethanol.

A bacterial spore test has been developed which enables the efficacy of the sterilizing cycle recommended by the British Pharmaceutical Codex (1973) for bottled fluids to be accurately monitored. During a 14-month period this test detected faults in 3.3% of the sterilizing cycles, representing five distinct episodes of sterilization failure that passed unnoticed by the conventional controls of physical measurements and sterility testing. There were no failures of sterilization as detected by conventional techniques which were not indicated by the spore test.

Adult cockroaches were found to survive up to 22 weeks when provided with 1% Formalin (0·4% formaldehyde) in lieu of drinking water. Given 4% Formalin or 2% glutaraldehyde they survived up to 41 days. During the experiments eggs were laid and hatched and the offspring continued to grow. Combined with surface disinfection, this may hold out a simple method of rendering adult cockroaches gnotobiotic or even axenic.

1. The rigidity of agar gel in poured agar plates can be tested by a comparatively simple and easily repeatable method.

2. Commercial agar from different sources varies in the rigidity of gel it produces at a given concentration.

3. The rigidity of gel produced by any agar at a given concentration is affected by processing and by the mode of production of poured plates and to some extent by the diluent used.

4. The appearance of a spurious S-R change in colonies of Salmonella and Shigella on media with an increasing agar content is a measure of the rigidity of the agar gel used and not directly of the agar concentration of the medium.

5. The appearance of this spurious S-R change induced by rigid agar bears no relation to the agglutinability of the organism.

6. Both increased or decreased agglutinability of cultures of Salmonella and Shigella is associated with the appearance of colonies of an apparently rough morphology at a lower level of agar rigidity than that at which spurious S-R change develops in a normally agglutinable culture.

7. Without some standardization of the rigidity of the gel used in agar plates, erroneous conclusions may be drawn regarding the antigenic state of the organisms under test.

8. Samples of agar of differing gel rigidity can be blended to form a product producing a gel of a calculated 12 sec. value.

I am indebted to the Director-General, Army Medical Services, for permission to publish this article.

Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000–2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1–11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3–63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.

We estimated prevalence and incidence of liver condition outcomes, and costs to the health service of diagnosed hepatitis B virus (HBV) in Tayside, UK. HBV patients were identified from electronic virology data between 1989 and 2003. The health resource costs of HBV for surface antigen-positive (HBsAg+) patients and HBV (HBsAg+ or immune, i.e. recovered) patients were calculated. A total of 633 patients had HBV (275 HBsAg+), and were more likely to be male (62% vs. 48%), older (mean age 42·6 vs. 39·2 years) and deprived than the general population. The prevalence of immune individuals increased steadily. Post-HBV diagnosis, 24% of immune and 13% of HBsAg+ patients were diagnosed with a liver condition. The median cost per immune patient (£3023) was greater than per HBsAg+ patient (£1498) (P = 0·02). While increasing prevalence of immune HBV patients highlights an increase in screening and treatment, the costs associated with this group are high.

In the present paper we describe the results of further investigations on the morphology and staining characters of Piroplasma canis, as well as a large number of observations on the living parasites. Our previous papers (1905) contained the results of studies preliminary to the investigation of the life-history of the parasite, but further work was unavoidably interrupted owing to the difficulties attending this form of research—we unaccountably failed to transmit the disease after several passages through dogs, and met with great difficulties in rearing progeny from infected ticks. Consequently the observations had to be discontinued until, after several failures, infected ticks (Haemaphysalis leachi) capable of transmitting the disease, had been received from South Africa through the kindness of Mr C. P. Lounsbury, Government Entomologist, Cape Colony. With this fresh strain of the disease we have succeeded in demonstrating various points in the morphology of the parasite which have hitherto escaped observation, and have worked out its method of multiplication in the living blood. Further studies have also been made on the vitality of the parasite outside the body in culture fluids, but these and other studies on the cycle of development within the tick are reserved for future communications.

“White Australia,” the pleasant dream of a peculiar political party, is a subject on which a few years ago it would have been inadvisable if not unsafe to venture too unrestrained opinions. There was a time when in certain quarters the euphonious phrase was almost tantamount to a war cry. To some political dreamers it may even have been a perennial dream, full of visions of whiteness and purity, just as to us in England the mention of the “Pearly Pacific” conjures up vistas of prattling palms, wimpling waters and silvery strands. The dream is a pretty one, fitting theme for the poet and artist; Samoa and R. L. Stevenson, what a perfect juxtaposition! What delectable tales our romance weavers indulge us with! The gorgeous colouring, the wondrous life, the glorious moon, the ocean's unceasing sigh—all fine, all beautiful, all seeming perfect—but all superficial or tempered with prosaic features which mar the picture.

Nuttall was born in San Francisco, California, on 5 July 1862; the second son of Robert Kennedy Nuttall, M.D. (Aberdeen) and his wife, Magdalena, daughter of John Parrott of San Francisco. The Nuttalls were descended from an old Lancashire family, which settled in Ireland in 1707, many of its members serving as officers in the British Army. His father went to Australia, but migrated to San Francisco in 1850 and practised there till 1865. In that year the family came to Europe and remained there till 1876, the children being educated in England, France, Germany and Switzerland. Consequently, Nuttall spoke several languages, a fact which assisted him enormously in his future work and travels.

“Health is more affected by atmospheric conditions than by any other influence. From the moment the new born child utters its first cry, until life finally ceases, he is directly and immediately dependent on the atmosphere he breathes for continued existence. Records of sickness and of mortality clearly show that the nearer atmospheric conditions are to those of the open country, the better is the health of the population, and that the more these conditions are modified owing to urbanisation and industrialisation, the more pronounced is the ill-effect upon general health” (1).

Skin tests made with the toxin obtained from Tunnicliff's strain of green producing streptococcus on normal individuals, and on cases prior to and after an attack of measles did not give any definite positive evidence of the etiological relationship of this organism to measles. Further, an attack of measles did not produce any apparent increase in the antitoxic content of a patient's serum for this toxin.

The literature upon the presence of various ferments in milk is extremely large and dates back through many years. Up to the beginning of 1911, however, when the experiments described in this paper were undertaken, no observer had dealt with milk uncontaminated by bacteria.