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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.

This chapter discusses the role of pentamethylenediamine (cadaverine/PMD) in the pathogenesis of cholera infection. The production of PMD in experimental animal infection and its role in the pathogenesis of cholera has been examined. In view of the localization of cholera infection to the intestines, experiments were undertaken to study the appearance of PMD in vivo during cholera infection and its formation in vitro from intestinal extracts and other sources. PMD was detected and estimated in all these experiments by paper chromatography. PMD was produced by different strains of V. cholerae from all the intestinal extracts tried, viz., that of mouse, guinea-pig, rabbit and monkey. Mouse intestines were found to be the best. However, only monkey intestinal extract was studied in detail because larger quantities could be obtained for work. A 20% to 50% extract was found to be good. It was found that if extracts were prepared from the intestines whose mucosa had been scraped off gently with a scalpel, only small amounts of PMD were formed. If the entire mucosa was completely scraped off, no PMD was formed.

Since 1961 cholera El Tor has been sweeping through the Far East, and this dissemination of the disease has stimulated research not only in the countries afflicted but also in Europe and the Americas. New laboratories and workers have entered the field and many fresh ideas and concepts have emerged. The time seemed ripe, therefore, to survey the most important papers published since 1959, when the literature on cholera was thoroughly reviewed by Pollitzer, for the benefit both of those engaged in research and of those concerned with public health practice.This review covers history and incidence, causative agents (including the "classical", "El Tor" and "incomplete" forms), pathophysiology, diagnosis, treatment, mode of spreading and control measures (with particular reference to public health education and the International Sanitary Regulations). An annex, intended for laboratory use, contains selected procedures for the isolation and identification of cholera vibrios.

The identity of the El Tor vibrio is a controversial question that the usual methods of bacteriological investigation have as yet failed to settle. In this paper, the author presents the results of a study of the interrelationships between El Tor vibrios, true cholera vibrios and water vibrios, as revealed by the behaviour of the vibrios in the bile system and in the small intestine of experimental animals.The vibrios investigated included two strains isolated at the El Tor quarantine station on the Sinai Peninsula in 1934, two strains isolated at Makassar, Celebes, during a cholera epidemic in 1937 and identified as "El Tor" vibrios, four strains of true cholera vibrios and five strains of water vibrios. On the whole, the behaviour of the El Tor and Makassar vibrios was similar, closely resembling that of the cholera vibrios and differing markedly from that of the water vibrios. The author therefore considers that the strains of El Tor and Makassar vibrios examined are varieties of Vibrio cholerae and suggests that carriers of such strains should be subjected to the same measures as carriers of true cholera vibrios.

This paper is a report on an attempt to study seasonal variations in endemic cholera in West Bengal by statistical analysis of monthly mortality records over a 21-year period. The annual death-rates have been calculated for each month in each district and the average of the seven lowest rates in each district is plotted diagrammatically to show the seasonal endemicity.BY THIS MEANS THREE GROUPS OF DISTRICTS ARE DISTINGUISHED: one of high, one of variable, and one of low or no endemicity. The statistical analysis suggests that cholera experience in West Bengal is not, as is sometimes contended, dependent on the intensity of infection in Calcutta.It is felt that the method described might to advantage be applied to other areas where cholera is endemic and would be helpful in selecting the most suitable times for carrying out control measures.

Recently I picked up a piece of paper, apparently cut from some medical journal for the purpose of reinforcing a binding, and my eye caught the statement, by some one who apparently wrote as an authority, that "until now no remedy for cholera has been discovered," "all bad cases die [sic], in spite of remedies." The writer also expressed the opinion that the patients who recover would recover without medicine. About the same time I learned that cholera was spreading in Europe and that there was panic in places. These things lead me to feel that I have been remiss in my duty as a physician in not putting definitely before the profession the results of treatment of cholera in Van during an epidemic of six weeks' or more duration in the early part of this year. As the only foreign physician within a week's journey in any direction, my

REFERRING to the paper read before the French Academy (as reported in your last issue) on copper as a preservative against cholera, it may be worth while to stale that when visiting the great copper mines at Fahlun in Sweden (probably the oldest and largest in the world) I was informed that cholera had never appeared there, and that so well was the fact known that on the last visitation of cholera in Sweden some members of the Royal family took up their abode in Fahlun to escape the disease. The atmosphere was there loaded with copper fumes to such an extent that not a trace of vegetation was visible on the hills surrounding the town; so that this really seems to confirm by experience on a large scale the theory alluded to.

T'HE MAIN epidemiological features of endemic cholera have been long known, with some of the original observations dating back nearly a century. The available information has been reviewed extensively by Pollitzer (1), and unless otherwise stated, all references are taken from this monograph. By the end of the 19th century, the areas of endemicity had been clearly defined, the nature of the countryside in which it was found was described, the relationship of the disease to the weather, especially the monsoon, had been noted, and the inability of IVibrio cholerae to survive for long periods in water containing large numbers of competing organisms and the potentialities of the village tanks, or ponds of surface water, in spreading infection had been observed. The fact that the cholera vibrio could withstand a very high pH had been discovered and indeed utilized in isolating the organism in pure culture. However, efforts to provide an explanation for these features have so far been unsuccessful. In this paper we have reexamined and confirmed some of these epidemiological features and offer a theory and supporting data to explain them. The theory is that the tanks of water are, in fact, the main means of spread of the infection; the seasonal fluctuations of the disease and possibly the limitations of the endemic area are the results of fluctuations in the pH of the tank water. Examination of a number of tanks over a period of a year has shown that in sunny weather the pH commonly rises from about 7.07.5 in the morning to as high as 10.0 and occasionally to 10.5 in the afternoon. But when it rains this rise is prevented, and the pH may fall below 7.0. These fluctuations are the result of the activity of the algae in the water which liberate either carbon dioxide or oxygen according to the intensity of the light available. This range of pH's would give an advantage to the vibrio in the water over other intestinal organisms and permit them to survive, and, through natural selection, may have been responsible for producing the alkaline-resisting capacities of the organism.

It is two years since the first reports appeared dealing with the new antibiotic choloramphenicol (chloromycetin®). These first papers 1 described laboratory experiments in which the antibiotic was shown to inhibit the growth in vitro of a wide range of bacteria and, of greater interest at that time, to have a chemotherapeutic effect in a number of experimental rickettsial and virus infections. In addition, chloramphenicol was found to have two other characteristics which promised to make it useful in the treatment of patients. These were (1) its low toxicity for animals and (2) its capacity to elicit as satisfactory results when given by the oral route as by the parenteral route. It was quickly shown that the new drug was essentially nontoxic for normal men and that relatively simple technics revealed the presence of appreciable levels of active drug in the blood and urine of such persons following oral administration