An Interview with Professor Manuel Varela: Dysentery and Kiyoshi Shiga

Sep 4, 2018 by

Kiyoshi Shiga

Michael F. Shaughnessy –

1) Professor Varela- we have all heard the word “dysentery” but only have a global understanding of it. Can you describe it?

The illness called dysentery represents one particular form of the gastroenteritis diseases. The word gastroenteritis is a general term that refers to the conditions in an individual in which their linings of the stomach and of the intestinal tract are experiencing the inflammatory process.

The term dysentery itself is meant to describe a serious type of gastroenteritis in which a patient is suffering from a severe form of diarrheal stool that can be accompanied by blood, pus, mucous, bacteria and water. Frequently, patients who are suffering from the dysentery may also experience cramping in the abdomen and sometimes a fever.

In general, patients will typically start to experience the classical signs and symptoms of dysentery between one and seven days after exposure to the causative microbial agent. The associated watery diarrhea excretion from the patient may be profuse. Sometimes the patient will suffer from rectal pain, vomiting, and nausea.

The dysenteric ailment may last approximately 3 to 5 days in the individual and then resolve itself of the problem in a self-limiting fashion. Occasionally, complications of dysentery may occur. These sorts of complications may include dehydration (sometimes severely), seizures brought about during fever, confusion, and neurological dysfunction, all of which may occur especially in young patients.

2) Now, what causes it, and how can it be prevented?

There are several microbial causes of dysentery. The main microbial culprits are the bacteria, viruses, and the protozoa. The chief causes of bacterial dysentery are Shigella dysenteriae and Escherichia coli. The main causes of viral dysentery include Norwalk virus and rotavirus.  A prime candidate for amoebic dysentery is the protozoan called Entamoeba histolytica. Another protozoal cause of dysentery is the ciliate called Balantidium coli.

One of the most common causes of bacterial dysentery is the Shigella dysenteriae, a Gram-negative rod-shaped microbe. This particular dysentery aliment is also referred to as the bacillary dysentery or the shigellosis.

Incidentally, some scientific investigators and clinicians have argued that these two bacteria are of the same species, both being E. coli, and with the Shigella dysenteriae now being considered a “biogroup” of the E. coli bacteria. Yet, when referring to the dysentery caused by such bacteria, scientists will often keep the Shigella denotation simply to avoid confusion with those ailments caused by classical pathogenic E. coli and to maintain a contextual perspective with the previous historical literature about the Shigella.

Independent of the microbial causative agent of dysentery, the illness is transmitted to patients by contact with other patients who have microbe-contaminated hands.  Additionally, the dysentery may be less often transmitted by the consumption of food or drink that are contaminated with fecal matter harboring the causative microbes. The technical term for these types of microbial spread between individuals is referred to as the fecal-oral route of transmission. Sometimes the patients with dysentery need not be experiencing measurable signs or observable symptoms, being asymptomatic, in order to transmit the illness to others.

With respect to the bacillary dysentery, only a relatively small number of living microbes, as few as a hundred bacterial cells, are required to initiate the illness. In this regard, the Shigella dysenteriae bacteria are understood to be rather potent in causing dysentery. Thus, bacillary dysentery may be frequently encountered in areas where personal hygiene and sanitation are poorly practiced. Good handwashing practices would go a long way towards prevention of dysentery.

3) How can it be treated?

Clinicians may often recommend that bacillary dysentery be left to run its course and resolve itself on its own. Thus, treatment may be limited to supportive care.

In serious bacillary dysentery cases, oral rehydration will be indicated. In certain situations, the physician may prescribe a prophylactic course of antibiotic administration, such as ceftriaxone, in order to prevent transmission to family members or to others in close association with the clinical dysentery patient.

As of this writing, a vaccine is in the pipeline. This new vaccine involves a live attenuated form of the bacterium commonly known as Shigella flexneri.  

4) As with most illnesses, there is a history- Who was Kiyoshi Shiga and how did he discover Shigella dysenteriae?

Dr. Kiyoshi Shiga was an eminent Japanese bacteriologist and medical physician who discovered the Shigella dysenteriae bacterium, a microbe which now holds his name. Shiga was born on the 7th day of February, in the year 1871, in Sendai, Japan, to parents Shin and Chiyo Sato. His father had been a prominent administrator but lost his standing during the Japanese Mejii Restoration era, bringing the family into serious economic adversity. Raised by relatives on his mother’s side, young Kiyoshi chose to embrace his mother’s maiden name, changing his surname to Shiga from the paternal name of Sato.

The Sato-Shiga family household moved to Tokyo, Japan, where Shiga entered high school. In the year 1892, Shiga began medical studies at the School of Medicine, housed at the Tokyo Imperial University.  While a medical student, Shiga was reported to have listened to the great Prof. Shibasaburo Kitasato give a seminar on his work dealing with his bacteriological studies on the Clostridium tetani and the associated antitoxin. Dr. Kitasato had just become extremely famous for his co-discovery of the causative bacterial agent of the Black Death, a plague-causing microbe named Yersinia pestis.

Dr. Shiga took his medical doctorate in 1896 and moved to the Institute for Infectious Diseases where he was charged at first with providing care to tuberculosis and diphtheria patients.  Dr. Shiga subsequently entered the research laboratory of the famous Dr. Kitasato, who then served as Dr. Shiga’s research mentor. In the lab, Dr. Shiga sought to study the microbial cause of the so-called “red diarrhea” which we now know to be the dysentery, as the apt description “red” denotes the bloody stool condition inherent in dysentery.

In his laboratory, Dr. Shiga examined the red stool specimens from about three dozen hospitalized dysentery patients, all of whom had acquired the ailment during a massive dysentery outbreak that occurred at the time. He isolated and cultured bacteria in the laboratory. Dr. Shiga then performed several classical microbiological tests on his patients’ clinical isolates of bacteria. 

First, he stained the bacterial isolates from the red stool specimens with the famous Gram stain, and found Gram-negative rods in their stool samples. Next, he examined the fermentation properties of the clinical isolates and found that a bacterium in each of his samples had fermented the sugar glucose, also known as dextrose, converting them into acid metabolites. 

The dysenteric bacterial isolates were also shown by Dr. Shiga to be negative for the indole test, indicating that his bacteria did not metabolize the amino acid tryptophan. His bacteria also did not ferment the sugar-alcohol called mannitol into acid end-products.

Lastly, Dr. Shiga showed that his bacteria agglutinated on glass slides when in the presence of blood serum taken from convalescing dysentery patients in the ward.  This agglutination test was demonstrated by Dr. Shiga to be a good diagnostic test for the bacillary form of the dysentery.

Dr. Shiga published his historic findings in 1899 as a single author, while acknowledging the help of his famous mentor, Dr. Kitasato, in the publication. Dr. Shiga’s microbiological characterization of the dysentery bacillus is still considered relevant in modern times.

5) What is the current status of this thing we call “dysentery” and whatever happened to Kiyoshi Shiga?

In the U.S. alone, cases of bacillary dysentery may number on the order of half-a-million, annually. On a worldwide scale, the numbers of bacillary dysentery cases that occur on an annual basis are staggering—an estimated 90 million yearly cases!  The vast majority of bacillary dysentery cases occur in young children.

Dr. Shiga’s 1899 discovery of the causative agent for the dreadful bacillary dysentery brought him worldwide acclaim. In 1900, he married his wife, Ichiko, and together the couple had eight offspring.

After his tenure in Dr. Kitasato’s laboratory, Dr. Shiga then moved to Germany where he worked in Dr. Paul Ehrlich’s laboratory. In Germany, Dr. Shiga studied the chemotherapy potential for the ailment called trypanosomiasis, also known as the African sleeping sickness, which is caused by the vector-borne protozoan called by the genus name Trypanosoma

In 1905, Dr. Shiga moved back to the Institute for Infectious Diseases with Dr. Kitasato, but both scientists later resigned in protest after institutional reorganization by the Japanese government proved to be untenable for them and others. Drs. Shiga and Kitasato then established the Kitasato Institute where Dr. Shiga became a division director. 

In 1920, Dr. Shiga then became professor at the Keio University, housed in Tokyo. At about the same time, Dr. Shiga moved to Korea to become the director of the National Hospital, in Seoul. In 1926, he moved to Seoul University to become its first dean of the associated medical school. In 1929, Dr. Shiga then became president of Seoul University but left the post in 1931, returning to the Kitasato Institute conducting research.

In 1936, he had been invited to deliver a keynote address at Harvard University for its 300-year anniversary celebrations. The speech was a tribute to Dr. Shiga that was warmly welcomed by him.

During World War II, Dr. Shiga’s wife had died of cancer at a relatively young age, and his oldest son died tragically while en route to her funeral services. To make matters worse, Dr. Shiga’s home in Tokyo had been destroyed by allied bombings. In his later years, he wrote an autobiography, and he wrote another biography about Dr. Paul Ehrlich. He died on the 25th day of January in the year 1957, at 85 years of age.

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