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The publication of Mr Norman Longmate’s book King Cholera in November 1966 served as a reminder of the terrible scourge which afflicted this country on no less than four separate occasions during the nineteenth century. While this volume was, no doubt—as the ‘blurb’ on its dust-jacket affirms—‘an important contribution to social history’, so far as the part which the Church played during those critical years, the half was not told in its pages. In this short paper it will be my task to try to repair this omission in regard to just one of the four major outbreaks of the disease in England, the last in fact, that of the year 1866; and to say something of the response made by churchmen and women to the cholera outbreak of a century ago.

Suitable mesenteric glands were selected from virus hogs, the glands carefully dissected out of mesentery, covered with 10 times their weight of absolute alcohol, and placed at 37 C. over night. The alcohol was then decanted off, the glands thoroughly ground with sterile sand, and the alcohol again added to the ground glands. The preparation was then placed at 37 C. for 8 days and thoroughly shaken each day. At the end of this period the preparation was filtered through an ordinary, white, folded filter paper. The filtrate, which measured 670 c.c, was evaporated by the aid of an electric fan to a somewhat pasty, deeply yellow mass. This mass was partly dissolved in 225 c.c. of ether and set aside to sediment. The ether was decanted from the sediment and allowed to evaporate to a volume of 15 c.c. To this 15 c.c. were added 75 c.c. (5 times its volume) of acetone. A heavy, flocculent precipitate immediately formed, which was allowed to settle, whereupon the supernatant liquid was decanted. Twenty-five cubic centimeters of methylic alcohol were added to the precipitate. The methylic alcohol dissolved a portion of the precipitate, leaving, however, a deeply yellow, sticky mass undissolved. After sedimentation the methylic alcohol, decanted and diluted 1:10 with normal salt solution (1.5 c.c), was used as antigen in amounts varying from 0.01 c.c. to 0.03 c.c. with, in each case, 0.05 c.c. immune serum, 0.045 c.c. complement, 0.1 c.c. hemolysin, and 0.5 c.c. red blood corpuscles. The antigen, immune serum, and complement were mixed and placed at 37 C. for 1 hour, whereupon the hemolysin and corpuscles were added and the whole placed at 37 C. for 2 hours. Complete hemolysis followed in every case. The test for complement absorption was negative. This test was repeated with 10 times the dose of antigen used in the first test, and the result was again negative.

A controlled comparison of furazolidone and tetracycline in the treatment of cholera indicates that, in either dosage used, furazolidone reduced total stool volume by 50% and duration of diarrhoea by 40%. These results are comparable to those achieved with tetracycline, which was given in presently recommended dosage. Both furazolidone and tetracycline significantly reduced the rate of stool output within 18 to 24 hours of starting antibiotic treatment. Furazolidone was significantly less effective than tetracycline in rapidly and consistently terminating vibrio excretion. One convalescent carrier of cholera vibrios was identified among control patients; none was identified among patients treated with either tetracycline or furazolidone. All Vibrio cholerae strains tested were sensitive to tetracycline and furazolidone, but larger concentrations of the latter were required to achieve inhibition of growth. It is concluded that tetracycline remains the antibiotic of choice in cholera but that furazolidone would be a useful adjunct to cholera therapy when tetracycline is unobtainable or if strains of V. cholerae with clinically significant resistance to tetracycline should be encountered.

Amer. Rev. resp. Dis., 1963, 88, part 2. Badger, G. F., Dingle, J. H., Feller, A. E., Hodges, R. G., Jordan, W. S., jun., and Rammelkamp, C. H., jun. (1953). Amer. J. Hyg., 58, 174. Banatvala, J. E., Anderson, T. B., and Reiss, B. B. (1964). Brit. med. J.y 1, 537. Buck, C. (1956). Amer. J. Hyg., 63, 1. Chanock, R. M., Bell, J. A., and Parrott, R. H. (1961). In Perspectives in Virology, edited by M. Pollard, 2, 126. Chapman and Hall, London. Parrott, R. H., Cook, K., Andrews, B. E., Bell, J. A., Reichelderfer, T., Kapikian, A. Z., Mastrota, F. M., and Huebner, R. J. (1958). New Engl. J. Med., 258, 207. Clarke, S. K. R., Corner, B. D., Gambier, D. M., Macrae, J., and Peacock, D. B. (1964). Brit. med. J., 1, 1536. Dimmock, N. J., and Tyrrell, D. A. J. (1962). Lancet, 2, 536. Gamble, D. R., and Kinsley, M. L. (1963). Mth. Bull. Minist. Hlth Lab. Serv., 22, 6. Gardner, P. S., Stanfield, J. P., Wright, A. E., Court, S. D. M., and Green, C A. (1960). Brit. med. J., 1, 1077. Higgins, P. G., Boston, D. G., and Ellis, E. M. (1964). Mth. Bull. Minist. Hlth Lab. Serv., 23, 93. Ellis, E. M., and Boston, D. G. (1963). Ibid., 22, 71. Holzel, A., Parker, L., Patterson, W. H., Cartmel, D., White, L. L. R Purdy, R., Thompson, K. M., and Tobin, J. O'H. (1965). Brit. mea. J., 1, 614. Kendall, E. J. C, Bynoe, M. L., and Tyrrell, D. A. J. (1962). Ibid., 2 82 Lidwell, ?. M., and Sommerville, T. (1951). J. Hyg. (Lond.), 49, 365. Peacock, D. B., and Clarke, S. K. R. (1961). Lancet, 2, 466. Sutton, R. N. P. (1962). J. Hyg. (Lond.), 60, 51. Tyrrell, D. A. J. (1963). Amer. Rev. resp. Dis., 88, part 2, p. 77. and Parsons, R. (1960). Lancet, 1, 239.

Paper discs impregnated with antiserum, lyophilized, and stored at temperatures ranging from −21 to 33 C have yielded potent and specific reagents when rehydrated 370 days later. Applications are discussed.

RECENTLY, while studying the action of culture supernatants of Vibrio cholerae and El Tor vibrio on the phospholipids of human serum, the presence of a lysolecithinase previously reported by other workers1,2 was confirmed. In addition, an enzyme which hydrolysed lecithin was found in culture supernatants of haemolytic El Tor vibrio, but could not be detected in supernatants of either V. cholerae or non-haemolytic El Tor strains. (Three such El Tor strains were obtained from the Walter Reed Army Institute of Research through the courtesy of Dr. Felsenfeld).

The experiments recorded in the present paper confirm the existence of 4 forms of the hog cholera bacillus described in a previous paper (1), namely the "normal" type strain MS and its 3 variants, MR, NS and NR. Serological evidence is also presented to show that the symbols MS, MR, NS and NR represent the similar conceptions of previous investigators who have used the letters OH, O, ØH and Ø respectively to designate variant forms of other organisms. It has been shown that the S form of the hog cholera bacillus, as the S forms of other bacteria, is more virulent for laboratory animals than the R forms. In regard to the reversibility of one form to another it was found that by transfer in broth or by passage through mice the MR form showed a tendency to revert to the original MS form. Transfer in broth and animal passage, however, failed to induce any variations in the NR or NS forms. Growth in homologous immune sera did not cause reversion to original forms but in fact provoked further dissociation of the MR to the NR form and also of the NS to the NR form. The MR form may revert to the original normal MS form or may dissociate further into the NR form and is, therefore, the most unstable of the variants. Further attempts to induce changes in the other variants were not made. The dissociation as observed may be represented thus: See PDF for Structure

In experimental work with filtrates of cultures of typhoid bacilli Shwartzman1 observed a new immunological phenomenon in 1928. This phenomenon is elicited by means of a single preparatory intradermal injection of a small amount of a given bacterial filtrate followed twenty to forty-eight hours later by an intravenous injection of the same or another bacterial filtrate. Following the second injection there appears at the site of the preparatory injection in the majority of rabbits pronounced hemorrhagic lesions which bring about necrosis and ulceration. These experiments were confirmed by Burnet,2 Gratia and Linz3 and also the author of this paper in collaboration with Appelmans.4 Gratia and Linz5 attempted to demonstrate the relationship of this phenomenon to anaphylactoid reactions described by Sanarelli6 and phenomenon of Arthus. The Shwartzman phenomenon can be elicited only with certain bacterial filtrates, including those of cholera vibrio as shown by Gratia and Linz, who employed the latter filtrates in a considerable number of experiments. The author of this paper attempted to determine whether EL Tor vibrios behave in the same manner as cholera vibrio towards the Shwartzman phe

THE scientific memoirs contained in this volume are of considerable interest. Drs. Klein and Houston have investigated the behaviour of pathogenic organisms when inoculated upon various farinaceous media, and conclude that the likelihood of infection of the human subject from such source is probably remote. A number of food-stuffs were similarly examined by Dr. Klein for the presence of pathogenic organisms, with the result that none was found. Dr. Gordon has continued his studies upon the bacteriology of scarlatina, and he adduces further proof that the Streptococcus scarlatinae is a species distinct from other streptococci and that it may be the causative organism of this disease. Two papers are concerned with the behaviour of micro-organisms when inoculated into the soil. In the first, Dr. Houston inoculated soil with crude sewage, and found that on the whole the soil-microbes ousted the sewage ones and that the addition of sewage to soil resulted in a temporary increase only of the sewage microbes. In the second, Dr. Sidney Martin has continued his work upon the nature of the antagonism of the soil to the typhoid bacillus; this organism survives but a short time in the soil, being destroyed by the products of the putrefactive bacteria which exist therein. Dr. Klein also reports on the infection of cockles and mussels with the typhoid and cholera microbes, and shows that these organisms may persist in the interior of the molluscs for some time after the source of infection has been removed. The importance of rats in the dissemination of plague has induced Dr. Haldane to devise an apparatus for generating carbonic oxide gas for destroying these pests in plague-infected ships. This, is described and some experiments with it are detailed. There is also an interesting report upon research work in connection with glycerinated vaccine lymph. The volume concludes with a number of well-executed photographs illustrating the various papers. Thirteenth Annual Report of the Local Government Board, 1900–1. Supplement containing the Report of the Medical Officer for 1900–1. (London: Eyre and Spottiswoode, 1902.)

HREE experiments are reported in this paper. Experiment A was a study to determine the efficacy of aluminum hydroxide gel as an adjuvant in killed fowl cholera vaccine. Expriment B was designed to determine (1) if this vaccine would stimulate and maintain a high degree of immunity for 52 weeks, and (2) if the stress of mixing vaccinated males from different flocks at time of challenge would affect their resistance to fowl cholera. Experiment C was a study to determine if birds could be immunized against fowl cholera and withstand exposure to virulent cultures of Pasteurella multocida while infected with fowl pox virus. A method for production of an effective water-in-oil emulsified fowl cholera veccine was presented in a previous paper.'

1. Previous work on the antigenic structure of the cholera group of vibrios is experimentally reviewed, and the data amplified and systematised.2. The cholera group is defined as consisting of vibrios with similar biochemical characters and having a common heat-labile antigenic component.3. The heat-stable antigens are divisible into:(a) A considerable number of specific antigens, best demonstrated by O sera and H-O suspensions, which serve as a basis of classification into O subgroups.(b) A non-specific component, demonstrable with O sera and O suspensions.4. The first subgroup contains all the standard cholera vibrios from central laboratories, and the majority of other epidemic strains. We consider that it represents the only class of vibrios known for certain to cause epidemic cholera.5. The races of this subgroup I are further divisible into two (or perhaps three) “types”, as established by Japanese workers, according to differences in their subsidiary O antigens.6. The haemolytic “El Tor” vibrios are serologically diverse. The term “El Tor” should, as Shousha suggests, be reserved for those that have the same specific O component as the standard cholera vibrios.7. For the identification of the undoubted cholera vibrios a standard subgroup I O serum is recommended in conjunction with the haemolytic test. The serum should contain both the main and the subsidiary antigens of the subgroup.8. As a working rule it is suggested that bacteriological proof of “cholera” or a cholera carrier should rest on the isolation of a non-haemolytic vibrio with the specific O antigen of subgroup I.The studies and observations on which this paper is based were conducted while one of us (K. V. V.) was holding a Fellowship of the International Health Division of the Rockefeller Foundation.Our thanks are due to Mr P. Bruce White for constant help and advice, and to the numerous bacteriologists in various lands who have kindly supplied us with cultures and sera.

Thirty-two strains of an infectious filterable agent, with properties that establish it as a virus, have been isolated from a malady of cats. This disease can be readily recognized and differentiated from other feline diseases by blood studies, which make apparent the characteristic profound leucopenia and marked relative lymphocytosis in the absence of thrombopenia and appreciable anemia. (Because the cytological pictures of the bone marrow and blood are essentially similar to those which characterize human agranulocytosis, we have named the disease under study "infectious feline agranulocytosis.") The cytological reaction to the presence of the virus is further characterized by proliferation of the reticuloendothelial cells of the lymph nodes and spleen, and by the formation of intranuclear inclusion bodies in the cells of the gastro-intestinal mucosa, lymph nodes, and bronchial mucosa. The etiological agent, the virus of infectious feline agranulocytosis, is pathogenic for cats when given by the oral, intragastric, cutaneous, subcutaneous, intraperitoneal, intravenous, and intranasal routes; it can be recovered at the height of the disease from the blood, spleen, liver, lung, intestinal mucosa, nasal secretions, nasal mucosa and turbinates, feces, and urine. The virus appears to be limited in its pathogenicity to the feline species. We found that a variety of animals, as represented by albino Swiss mice, guinea pigs, domestic rabbits, and ground squirrels (Citellus richardsonii Sabine), failed entirely to react to the injection of massive doses of virus. Repeated attempts at infection of these animals regularly failed when the intranasal, intraperitoneal, subcutaneous, and intramuscular routes of inoculation were employed for single doses. The same was true when from four to six transfers in "blind" serial tissue passages were made. Moreover, attempts to propagate the virus on the chorio-allantoic membrane of the developing chick were unsuccessful. The significance of the facts is discussed in the paper that follows.

During the quarter of a century which has elapsed since the discovery by Prof. Koch of the comma bacillus of cholera, research work has benn almost confined to the bacteriology of the subject. Unfortunately, with the exception of M. Haffkine’s prophylactic inoculations, which are now very little used even in india, this line of work has done little or nothing to help the practitioner who is confronted with the treatment of this terrible disease. No powerful antitoxic serum of practical value has been produced, and even if such should still be obtained, many patients value has been produced, even if such should still be obtained, many patients come under treatment in such a state of collapse that no medicine can be absorbed, even if retained. The old controversy between the evacuant conserative methods of treatment has long since ended in the practically universal adoption of the latter, although as late as 1866 Dr. George Johnson advocated castor oil, denying that there was any relationship between the amount of fluid lost from the body and the mortality, while he strenuously opposed the use of intravenous saline injections to replace it. There is still much difference of opinion about the latter treatment, for although all who have used transfusion testify to the remarkable immediate improvement in the pulse and general condition, yet this is commonly of such brief duration that many think it only severs to needlessly prolong the agony of the patient, so that of recent years it has been only exceptionally resorted to in India.

Coproantibodies [1] in experimental cholera have been investigated to assess the effectiveness of oral vaccination [1-3], but the levels of intestinal antibody have been difficult to measure and to correlate with protective effects of the cholera vaccine. Recently, the canine species has been used as an animal model for experimental cholera because the syndrome of fluid and electrolyte loss can be produced [4]. Also, the lack of demonstrable gastrointestinal histopathology in this canine model [5] makes further analogy with the human illness possible. Since the dog is a useful experimental model and is subject to many of the diseases that occur in man, we have been interested in the canine immunological system, particularly in describing the immunoglobulins in serum [6, 7] and in external secretions [8, 9]. This paper will include a discussion of the immunoglobulin content of normal canine intestinal secretions and will quantitate the concentrations of these copro-immunoglobulins. An isolation procedure for recovery of the copro-immunoglobulins, particularly secretory IgA, will be outlined; in addition, some of the physical properties of the IgA molecule and its polypeptide-chain components will be examined.

Although hog cholera has been the subject of extensive investigation by immunological methods, little has appeared in the literature concerning the nature of the specific virus, aside from the discovery of DeSchweinitz and Dorset1 that the causal agent is filtrable through Berkefeldt and Chamberlain candles. This paper records certain observations made with the virus in the course of an experimental study.The virus in the blood of hog cholera withstands rapid desiccation over sulphuric acid, unslacked lime or other hygroscopic agents in vacuo at O° C., without its infectiousness and antigenic property being apparently affected. The resulting virus-powder may be kept in sealed glass containers for years and probably indefinitely without loss in viability, virulence and antigenicity. Though the virus in the powdered form keeps indefinitely, after it is redissolved in a suitable solvent such as normal physiological salt solution, it loses in viability and antigenic property at the same rate and under like co...

SummaryDifferent fractions of plasma proteins were determined by paper electrophoresis in 16 patients suffering from cholera, in 11 cases of tetanus, 10 cases of meningitis, 10 cases of small pox and 22 normal subjects. Total protein was lower than normal in all diseases studied except tetanus. Albumin was lower and fibrinogen was higher in all diseases as compared to normal values. Of the globulins, cholera cases had low α, increased β and normal γ-globulins. β-globulin contained β1 and β2 fractions not seen in normal persons. In patients suffering from small pox α- and γ-globulin fractions were normal but γ-globulin fraction which increased, contained γ1 and γ2-fractions. In patients suffering from meningitis and tetanus all the globulin fractions increased but in meningitis these increased values were not statistically significant. The implication of these changes has been discussed.

The term “air sac” infection has become associated with an exudative process occurring in the abdominal and thoracic air sacs of birds with chronic respiratory disease (CRD). It is this aspect of CRD infection which has been of the greatest concern to the commercial grower since it is the mortality and morbidity accompanying “air sac” manifestation that is of primary importance. “Air sac” infection can, however, be observed in a number of other diseases, such as infectious bronchitis, cholera, paratyphoid and Newcastle disease. The typical appearance of birds with “air sac” infection has been described by Wasserman et al. (1952), who suggested that the terms CRD and “air sac” infection are not synonymous since the latter is caused by a bacterial infection. Luginbuhl et al. (1954) observed that bacteria and fungi play a major complicating role in the pathogenesis of poultry respiratory diseases. This present paper reports briefly on the …

lumen of the bowel; with multiplication and consequent accumulation of endotoxin, possibly in part liberated by autolysis, symptoms appear. It is probable that the infrequent invasion of the deeper tissues plays no significant part in the pathogenesis of the disease. It is characteristic of this kind of infection that the microorganism remains essentially outside the body, and invasion of the tissues, with consequent exposure to the action of antibody in the case of the immune animal, is not a necessary preliminary to the development of the disease. Cholera, and related infections such as bacillary dysentery, thus differ sharply from typhoid fever, and the titration of serum antibody would appear to be at best an indirect measure of effective prophylactic immunity. It is possible that immunity to cholera is dual in nature, including an antitoxic immunity to the vibrio endotoxin, and an antibacterial immunity. The former has been discussed elsewhere (Burrows, Matyer, Wagner and McGann, 1944; Burrows, Wagner and Mather, 1944) in a preliminary way in connection with the endotoxin and will be considered in more detail in a subsequent paper. A functional antibacterial immunity developed during the course of the disease

Excerpt To the Editor:I read with interest the paper by Pierce and associates: Replacement of water and electrolyte losses in cholera by an oral glucose-electrolyte solution.Ann. Intern. Med. 70: 1...

A pandemic of El-Tor-type cholera began in south-east Asia during 1961. Many members of the medical profession, as well as government officials and the public, were confused by the relationship between the disease caused by the El Tor organism and classic Asiatic cholera. The authors observed large numbers of cholera patients admitted to San Lazaro Hospital, Manila, early in the Philippine epidemic, and in the present communication they draw attention to certain clinical and epidemiological features of so-called El Tor cholera. The paper not only describes the patients and the epidemic, but also suggests some of the treatment needs during such an epidemic. No indication was found that the disease caused by the classic cholera vibrio is different from that which is designated the El Tor variant.

Two of the main features of human cholera-induction of diarrhoea and confinement of the infection to the lumen of the intestinal tract-may be reproduced in three experimental models: (a) the streptomycin-treated, starved guinea-pig; (b) the intestinal loop in the adult rabbit; and (c) the suckling rabbit. In this paper the author compares the two last-mentioned models with his earlier work in guinea-pigs.Intestinal antibody (coproantibody) was highly protective, while circulating antibody had little or no effect, in all three models. The protective coproantibody was specific for the heat-stable vibrio antigens. It did not affect the growth of vibrios in the intestine, and its function may possibly be regarded as antitoxic rather than antibacterial. Oral vaccination protected adult rabbits against challenge by the loop technique. Heat-killed vaccine was as effective in this respect as live vaccine.The author feels that the present uncertainty concerning the protective value of cholera vaccination may be due to the fact that conventional vaccine is designed to induce high serum titres only. He considers that since oral vaccine has been shown to induce and maintain the production of coproantibody in human volunteers, a field trial should be carried out to determine whether coproantibody is as protective in man as it has proved to be in the experimental models.

Summary In this study 161 cholera patients were promptly rehydrated with normal saline solution alone. The mortality rate was 3.11%. Normal saline solution seemed most suitable for initial rehydration, but sodium bicarbonate and KCl solutions are recommended for intravenous or oral substitution after initial rehydration in severe cases. Prompt correction of loss of fluid and electrolytes is necessary to save the patients. Chemotherapy with phthalylsulfathiazole and chloramphenicol proved of little value clinically but appeared to limit frequency and duration of the carrier state. On the basis of the data presented in this paper it seems reasonable to suppose that the decrease in mortality rate from 8.2% in Bangkok and Dhonburi in 1958 to 5.2% in 1959 and 3.11% in this series was due largely to the effectiveness of the prompt treatment described here. Mortality may also have been held in check in part by immunization of many persons, good socioeconomic and sanitary conditions and hospital facilities.

The paper examines whether there was a greater risk of certain infectious diseases after typhoons combined with floods in Manila, which experienced three typhoons in 1970 one of which was the most disastrous ever recorded. The data on morbidity of cholera, typhoid and clinical syndromes diagnosed as gastroenteritis, pneumonia, bronchitis and influenza from routine but active collecting were statistically examined and compared for seasonal trends with those of Baguio, a town which did not experience typhoons. In spite of increased rainfall, destruction and temporary breakdown of sanitation, no significant differences attributable to the typhoons were detected in any of the studied diseases. In particular, there was no increase in typhoid nor in cholera in this cholera endemic town. The observed higher incidence of respiratory and to some extent also of gastrointestinal diseases was not statistically significant.

After freedom from cholera for over a quarter of a century, the Philippines in 1961 experienced an epidemic of cholera. The disease, shown to be caused by the El Tor strain of cholera vibrio, was clinically indistinguishable from classical Asian cholera. Studies were undertaken in Negros Occidental Province from August to October 1962 to characterize various aspects of the epidemics in this province. This paper describes the general characteristics of the epidemics in Negros Occidental from November 1961 through September 1962.Two types of epidemic occurred. The first, explosive in nature, suggested a common source of spread of infection; the second, with a more protracted course, seemed to be due to person-to-person spread of disease. In the second epidemic, a single hospitalized case in a household and a single hospitalized case in a community were the most common findings, suggesting that infection did not spread easily or, if easily spread, caused significant disease on rare occasions only.

It has been established that the vibriocidal test developed by Finkelstein [1] and modified by Mclntyre and Feeley [2] is a sensitive tool for diagnosing cholera, since a rise in vibriocidal titer is seen in most cholera patients [3-6]. This paper characterizes in detail the vibriocidal antibody response both during the acute phase of illness and for 6 months during convalescence. The vibriocidal titer response during the acute phase was studied in 47 children participating in a field trial of cholera vaccine. It was found that

Winter epidemics of bowel disturbances, characterized by an intestinal flux, have become a problem in some of our large cities during the past few months. Simulating, in some respects, in their toxemia and collapse, the symptoms engendered by the vibrio of Koch, these endemic and epidemic bowel disturbances are popularly known as "winter cholera." It is the purpose of this paper to detail observations on recurrent epidemics of so-called "winter cholera" at Escanaba, Mich., a city of approximately 10,000 inhabitants. Escanaba is situated on Little Bay de Noc, an inlet of Green Bay. The principles evolved from the study of such epidemics will serve to explain the cause of bowel disturbances that have become in some cities a very momentous problem, taxing the ingenuity of sanitarians. In the Sixth Annual Report of Mortality Statistics, published in 1905 by the Department of Commerce and Labor, Washington, D. C., the editor says

You will find a very interesting but rather sceptical paper on the supposed connection of birds leaving towns with invasions of cholera (NATURE, vol. xxviii. p. 329), by Pfarrer Hackel of Windsheim, in the monthly journal, Der zoologische Garten (Bavaria), September, 1873 (vol. xiv. P. 328), published by the Zool. Gesellschaft of Frankfort-on-Main.