Typhus vaccine (Inventions)

The invention: the first effective vaccine against the virulent typhus disease.

The person behind the invention:

Hans Zinsser (1878-1940), an American bacteriologist and immunologist

Studying Diseases

As a bacteriologist and immunologist, Hans Zinsser was interested in how infectious diseases spread. During an outbreak of typhus in Serbia in 1915, he traveled with a Red Cross team so that he could study the disease. He made similar trips to the Soviet Union in 1923, Mexico in 1931, and China in 1938. His research showed that, as had been suspected, typhus was caused by the rickettsia, an organism that had been identified in 1916 by Henrique da Rocha-Lima. The organism was known to be carried by a louse or a rat flea and transmitted to humans through a bite. Poverty, dirt, and overcrowding led to environments that helped the typhus disease to spread.
The rickettsia is a microorganism that is rod-shaped or spherical. Within the insect’s body, it works its way into the cells that line the gut. Multiplying within this tissue, the rickettsia passes from the insect body with the feces. Since its internal cells are being destroyed, the insect dies within three weeks after it has been infected with the microorganism. As the infected flea or louse feeds on a human, it causes itching. When the bite is scratched, the skin may be opened, and the insect feces, carrying rickettsia, can then enter the body. Also, dried airborne feces can be inhaled.
Once inside the human, the rickettsia invades endothelial cells and causes an inflammation of the blood vessels. Cell death results, and this leads to tissue death. In a few days, the infected person may have a rash, a severe headache, a fever, dizziness, ringing in the ears, or deafness. Also, light may hurt the person’s eyes, and the thinking processes become foggy and mixed up. (The word “typhus” comes from a Greek word meaning “cloudy” or “misty.”) Without treatment, the victim dies within nine to eighteen days.
Medical science now recognizes three forms of typhus: the epidemic louse-borne, the Brill-Zinsser, and the murine (or rodent-related) form. The epidemic louse-borne (or “classical”) form is the most severe. The Brill-Zinsser (or “endemic”) form is similar but less severe. The murine form of typhus is also milder then the epidemic type.
In 1898, a researcher named Brill studied typhus among immigrants in New York City; the form of typhus he found was called “Brill’s disease.” In the late 1920′s, Hermann Mooser proved that Brill’s disease was carried by the rat flea.
When Zinsser began his work on typhus, he realized that what was known about the disease had never been properly organized. Zinsser and his coworkers, including Mooser and others, worked to identify the various types of typhus. In the 1930′s, Zinsser suggested that the typhus studied by Brill in New York City had actually included two types: the rodent-associated form and Brill’s disease. As a result of Zinsser’s effort to identify the types of typhus disease, it was renamed Brill-Zinsser disease.


Making a Vaccine

Zinsser’s studies had shown him that the disease-causing organism in typhus contained some kind of antigen, most likely a poly-saccharide. In 1932, Zinsser would identify agglutinins, or antibodies, in the blood serum of patients who had the murine and classical forms of typhus. Zinsser believed that a vaccine could be developed to prevent the spread of typhus. He realized, however, that a large number of dead microorganisms was needed to help people develop an immunity.
Zinsser and his colleagues set out to develop a method of growing organisms in large quantities in tissue culture. The infected tissue was used to inoculate large quantities of normal chick tissue, and this tissue was then grown in flasks. In this way, Zinsser’s team was able to produce the quantities of microorganisms they needed.
The type of immunization that Zinsser developed (in 1930) is known as “passive immunity.” The infecting organisms carry antigens, which stimulate the production of antibodies. The antigens can elicit an immune reaction even if the cell is weak or dead.
“B” cells and macrophages, both of which are used in fighting disease organisms, recognize and respond to the antigen. The B cells produce antibodies that can destroy the invading organism directly or attract more macrophages to the area so that they can attack the organism. B cells also produce “memory cells,” which remain in the blood and trigger a quick second response if there is a later infection. Since the vaccine contains weakened or dead organisms, the person who is vaccinated may have a mild reaction but does not actually come down with the disease.


Impact

Typhus is still common in many parts of the world, especially where there is poverty and overcrowding. Classical typhus is quite rare; the last report of this type of typhus in the United States was in 1921. Endemic and murine typhus are more common. In the United States, where children are vaccinated against the disease, only about fifty cases are now reported each year. Antibiotics such as tetracy-cline and chloramphenicol are effective in treating the disease, so few infected people now die of the disease in areas where medical care is available.
The work of Zinsser and his colleagues was very important in stopping the spread of typhus. Zinsser’s classification of different types of the disease meant that it was better understood, and this led to the development of cures. The control of lice and rodents and improved cleanliness in living conditions helped bring typhus under control. Once Zinsser’s vaccine was available, even people who lived in crowded inner cities could be protected against the disease.
Zinsser’s research in growing the rickettsia in tissue culture also inspired further work. Other researchers modified and improved his technique so that the use of tissue culture is now standard in laboratories.
See also Antibacterial drugs; Birth control pill; Penicillin; Polio vaccine (Sabin); Polio vaccine (Salk); Salvarsan; Tuberculosis vaccine; Yellow fever vaccine.

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