Advances in Identifying the Causes of Major Infectious Diseases

views updated

Advances in Identifying the Causes of Major Infectious Diseases

Overview

At the beginning of the twentieth century the germ theory of disease was alive and well. However, it would take time and skill to identify the specific causes of many of the infectious diseases. Robert Koch (1843-1910) and Louis Pasteur (1822-1896) had identified bacteria as the causative agents in many diseases, and scientists could stain these organisms and identify their shapes under the microscope.

Important areas developed early in the twentieth century that added to knowledge about pathogenic (disease-causing) organisms. Filterable viruses, organisms so small that they passed through a filter, were discovered in the 1890s. These viruses were so small and mysterious that many unexplained diseases were attributed to them. Also, one-celled animals, or protozoa, and a group of parasitic worms emerged as new suspects.

In 1901 the mysterious African sleeping sickness was found to be caused by a one-celled animal carried by a biting fly, the tsetse fly. Joseph Everett Dutton (1874-1905), David Bruce (1855-1931), and Aldo Castellani (1875-1971) located the trypanosome that caused this disease. In 1901 Walter Reed (1874-1905) proved that a mosquito carried the scourge of the tropics—yellow fever. In 1905 the organisms causing whooping cough, dengue fever, and measles were discovered. George Frederick Dick (1881-1967) and his wife Gladys Dick (1881-1963) found the bacteria that caused scarlet fever and developed a test for it.

These diseases caused many deaths. At the turn of the twentieth century, the average life expectancy was about 50. This meant that, of all people born in a given year, by age 50 half would be alive and half dead. The death of children and infants to a host of "childhood diseases" brought down the average life expectancy.

Background

In previous centuries the world's great plagues affected the course of history and mankind. The condition known as sleeping sickness probably originated in Africa and was noted in slaves brought from there. Thomas Winterbottom, an English doctor, first described the condition in 1803. While working in Cuba, he noted slaves with terrible fevers and enlarged glands. In 1857 the famous missionary doctor David Livingstone (1813-1873) observed how cattle died from the bite of the tsetse fly, and horses developed nagana, or stallion fever. Livingstone was the first to treat animals with arsenic compounds. These compounds eventually were used to treat humans with sleeping sickness, although the organism that caused the disease was not identified.

During the last few years of the nineteenth century, trade routes increased and people began to travel into the hot equatorial areas. In 1894 an army doctor, Sir David Bruce, and his wife went to Africa to study nagana. Drawing blood from infected horses, they looked carefully at each sample under the microscope and noted a peculiar one-celled parasite nestled among the blood cells. This parasite was later named Trypanosoma brucei (or T. brucei). Bruce also confirmed Livingstone's idea that the biting fly was the carrier.

For over 300 years yellow fever was one of the world's great plagues. The debate over whether yellow fever originated in Africa or America will probably never be solved. In the late 1800s it was discovered that the mosquito was somehow involved in the transmission of malaria. In 1881 Carlos Juan Finlay (1833-1915) of Havana proposed that mosquitoes carried yellow fever. Several scientists, using their microscopes, looked in vain.

Dengue fever is an acute, sometimes hemorrhagic fever that causes intense body pain. Also called "breakbone fever" or "Dandy fever," it makes the person very ill but is seldom fatal. In Philadelphia, during the summer of 1708, Dr. Benjamin Rush (1746-1813) first described dengue. The term "breakbone fever" refers to the fact that the joints and bones feel like they are breaking. Like malaria and yellow fever, dengue would soon be linked to the mosquito.

Among the list of major world epidemics, measles has been greatly underrated. In the last 150 years, in industrial societies, measles drew attention when the overall interest in children increased. Measles is so contagious that it is passed by casual contact, and the host may give it to someone else before the symptoms occur. It probably appeared during the Middle Ages in France. A Danish doctor, P. L. Panum (1820-1885), studied an outbreak in the Faroe Islands in 1875. He determined the exact nature of the disease, the 13-14 day incubation period, its high level of contagion, and that one attack confers lifelong immunity.

Whooping cough, also called pertussis, is characterized by a cough with a period of drawing in air or whoop. The disease was first described in 1578, but probably existed before that. About 100 years later, the Latin word "pertussis" was applied, meaning intensive cough.

Scarlet fever, also called scarlatina, was described in 1676 by English physician Thomas Syndenham as small red spots, redder than the measles.

Impact

The work of Bruce and Livingstone had described the tsetse as a carrier of sleeping sickness in animals. In 1901 Dutton, working in Gambia, examined samples of human blood from sleeping sickness victims and found a similar trypanosome. The name of this one-celled parasite was T.b. gambiense. Thrilled by the success, he launched an all-out investigation into other insect-born diseases. In 1902 his work ended when he died while investigating relapsing fever on the Congo River.

In 1903 a new outbreak of sleeping sickness occurred in Uganda. David Bruce and Aldo Castellani, an Italian tropical disease expert, arrived to search for a connection. Examining spinal fluid, Castellani found another tiny parasite, and Bruce realized he'd found another form of sleeping sickness. He called this strain T. b. rhodesiense.

Stopping the disease then meant destroying the flies and restricting infected people and cattle. This proved to be very difficult because of African traditions.

Since there was no cure, in the 1920s people were advised to cover up completely in the hot tropical climate. In 1922 Bayer, a German pharmaceutical house, found that an arsenic compound called tryparsamide was effective, although it had side effects. Another drug, suramin sodium, was found effective for treatment in the disease's early stages. Sleeping sickness is still found in parts of sub-Saharan Africa, but aggressive programs to eradicate the tsetse and protect humans by using a preventive treatment have it under control.

Carlos Chagas (1879-1934), a Brazilian physician, found the reduviid bug, or "kissing bug," spreads a form of sleeping sickness in Central and South America. The host is the armadillo and possum. It is called the kissing bug because it bites the tender places on the face. In 1900 Carlos Finlay told Walter Reed, an army doctor, of his idea that the mosquito caused yellow fever. They joined with a group called the Yellow Fever Experiment that planned a simple experiment. One group of volunteer soldiers would live in a screened house among dirty blankets and remains of yellow fever victims. The common thinking was that the disease was spread in this way. Another group would live in clean housing without screens. The result showed that the soldiers with the screens stayed healthy; the mosquito-bitten soldiers came down with yellow fever.

By the 1900s researchers knew that agents smaller than bacteria, called viruses, could be passed through a filter. When investigators put the serum of yellow fever victims through such a filter, they found that it kept its potency. The Reed commission found that yellow fever was not only carried by a mosquito, but was a virus. After showing this connection, Reed then developed a plan that freed Havana from the disease in just a year.

When Reed died in 1902 he was succeeded by William Crawford Gorgas (1845-1920), who commanded the dramatic campaign against yellow fever during the construction of the Panama Canal. Ferdinand de Lesseps (1805-1894) had started cutting a canal through the narrow isthmus in 1881, but had failed because many workers had died of malaria and yellow fever. In 1904 Gorgas convinced the government to follow the Havana example and start an intensive war against the mosquito. Mosquito-proof buildings, netting, spraying, and draining stagnant pools were part of the plan. The last fatal case of yellow fever during the canal's construction occurred in 1906, and the canal was completed in 1914. During the 1930s, a vaccine was created and the scourge that devastated not only the tropics, but major places in the Untied States, was ended.

Dengue fever, a disease found in hot, humid climates, must be watched even today because control is most difficult. A 1906 study reports that an experiment involving human volunteers showed dengue is carried by several varieties of Aedes mosquitoes. In 1907 the disease was shown to be caused by a virus.

Dengue played an important part in the Pacific theater during World War II, especially in the Philippines. Even if dengue did not kill, it could incapacitate soldiers, causing them to be off-duty for weeks. Because of the four subtypes, a vaccine has never been developed, and a person must have all four to develop immunity. Late in the 1940s DDT was found to be effective in controlling the mosquito. However, during the 1970s this chemical was found to cause illeffects, and no effective replacement has since been found.

Three infectious diseases—measles, diphtheria, and scarlet fever—had been major problems, especially for children. Deaths from these diseases declined as the twentieth century progressed and new emphasis was placed on children's health. Since no drug affects measles, the only treatment is bed rest, protection of the eyes, and steam to help breathing. A measles vaccine was later developed.

Whooping cough leads to serious complications like convulsions and brain damage. In 1906 two bacteriologists at the Pasteur Institute were studying how bacteria destroys the red blood corpuscles. Jules Bordet (1870-1961) and Octave Gengou developed tests for many diseases. They isolated the bacterium that causes whooping cough, now called Bordatella pertussis. Their work laid the foundation for the vaccine that would be introduced in the early 1960s.

George and Gladys Dick investigated the cause of scarlet fever and, in 1923, isolated the streptococcus bacterium that causes the disease. Building on the study of others in the field of toxins, they prepared a toxin used for immunization. In 1924 they developed a skin test to determine susceptibility to scarlet fever.

Infectious diseases have had a devastating effect on human beings. Identifying the insect vectors of yellow fever, dengue, and sleeping sickness has enabled those at risk to target the carriers, using eradication and good hygiene. Identifying "childhood" diseases like measles, scarlet fever, and whooping cough led to better containment through quarantine. It would not be until the latter half of the twentieth century that vaccines would cut down on incidences of such diseases in the industrial nations.

EVELYN B. KELLY