HISTORY OF TUBERCULOSIS TREATMENT

HISTORY OF TUBERCULOSIS TREATMENT
J. Sauret Valet, Departamento de Neumología, Hospital de la Santa Creu i Sant Pau, Barcelona
The present chemotherapy treatment for tuberculosis is one of the most
spectacular achievements of medicine. Since 50 years ago, when the only effective
treatment methods were surgically collapsing the lung and sanatoriums, we have
advanced to a very different treatment of drug regimens which are easy to use,
have low toxicity, and are effective in every case.
Nevertheless, humankind had to travel a long way and pay a high price to reach this
goal. We will try to summarize the most significant periods of this slow process.
To discuss the first treatment attempts for Tuberculosis, we begin when it is was
first classified as a specific disease. Hypocrites (460-370 BC) and the Kos School
established the concept of tuberculosis, or consumption, and described it as a
morbid process characterized by progressive debilitation, coughing, hemoptysis, and
suppurating lung lesions. All chronic pleural pulmonary infections, however, fall under
this definition.
Supporters of Hypocrites thought the answer for a cure was found in nature, at
least for the beginning stages of the disease. The main goal of the doctor treating
Tuberculosis was to avoid hindering natural cures. Continual rest, a balanced diet,
and abstaining from anything in excess including sex were considered crucial. A wellbalanced
diet and drinking a large amount of milk from a cow, goat, or woman by
itself or mixed with honey, were also important. For centuries, milk was practically
considered the cure for tuberculosis.
Proactive measures included bloodletting to drain contaminated blood from the
infected lung, thoracic poultices, “sandácara” pollen (from Cupressaceae plants),
drinking wine to induce coughing and suppurating from lung lesions, and thoracentesis
preformed with a sharp knife to drain fluid from the lung.
Religious remedies in sanctuaries, dedicated to the worship of the god Asclepius also
played an important role in tuberculosis treatment. Some anathemas from grateful
tuberculosis patients have been found.
Roman medicine contributed few advances; for centuries, Romans were skeptical of
medical figures, whose actions were dictated by the pater familias. When the need
for treatment eventually became apparent, the Romans incorporated the doctrine of
Greek schools without any modifications.

In the 2 nd century AC, Galileo suspected tuberculosis was contagious (also believed
by Aristotle) and began to understand that resting the infected lung, like any other
type of ulcer, was essential to healing. Similar to prior treatments, Galileo
recommended placing the patient in a clean underground room and administering
tisana (medicinal drink made with peeled barley) and a mix of plants with soothing
properties for coughing. Traveling to the sea and to Egypt (for the dry climate)
were considered beneficial to start the healing process.
During the Middle Ages, after the invasion of the Eastern barbarians, the most
important medical advances included founding of the first orphanage, hospital, and
medical school and advances in treatment were scarce. The famous Flos Medicinae
along with loosely translated aphorisms continued to place much importance on milk
(from a goat was better than a donkey) mixed with salt and honey:
Lac, sal miel i unge; bibat contra consumptus abunde.
Lac nutrit, sal traducit, lac melli lisquecit.
Lac si caprium, melius tamen est asinimum.
An interesting therapy called “cure by regal touch” was started in the Middle Ages
and persisted until the 19 th century. This privilege given to some kings (especially
French and English) was to cure certain illnesses by placing their hands over the
patient while reciting the phrase “the king touches you and God cures you.” The
first news of healing came in the 11 th century, by Robert the Pious in France and
Edwards the Confessor in England. Large crowds from every European country would
come for the day chosen for the king’s healing. Scrofula was the preferred illness
for “the touch.” It was not the only one; after some time, various monarchies
became specialized. For example, the “specialty” of the Hungarian king was jaundice,
the Spanish king specialized in insanity, Olaf of Norway in goiters, and the kings of
England and France specialized in Scrofula and epilepsy.
The Arabs, familiar with the texts of Hypocrites, Aristotle, and Galileo, assimilated
with the classic beliefs: rest and a good diet were most important in tuberculosis
treatment. In addition, infusion of rose petals could lead to extraordinary healing,
according to Avicena.
Revisionism during the Renaissance period impacted medicine and Galileo’s theories
were abandoned as the indisputable truth little by little. The first anatomicpathological
studies were started but advances in tuberculosis treatment were still
scarce. Every type of plant with expectorant or soothing qualities was tested in
various formulas and unconventional explanations. For example, Lungwort plants

were suggested as treatment by Paracelso because of their similar physical
appearance to a healthy lung.
Hygienic and dietary measures were still stringent, especially concerning sexual
activities. A professor in Pauda, Juan Bautista Da Monte (1498-1552) skeptically
vowed to find the cure to Tuberculosis for his young and beautiful wife. The most
notable person of this period was Jerónimo Fracastro (1478-1553) from Verona and
author of the theory in seminaria contagiosum. Fracastro suspected that
tuberculosis and other diseases were contagious via seminaria, or bacteria, which
penetrate a breathing organism and are absorbed and transported through the blood
to the bowls.
During the 16 th and 17 th centuries, sulfur, arsenic, mercury, and every type of plant
from the New World such as quinine (tea), cocoa, and tobacco were all thoroughly
tested and none were found to be useful.
The concept that Tuberculosis was contagious was believed in countries on the
Mediterranean coast (Spain and Italy). In the 18 th century, some cities adapted
advanced prophylactic laws which included obligatory notification of cases, isolation
of patients, alienation, and burning the personal belongings of deceased patients.
These laws were made into official ordinances in 1751 by Fernando XI for all of his
kingdom. Shortly after, they were also enforced with a few modifications by the
duke of Tuscany and by the king of Naples. Unfortunately, the Napoleon conquerors
tried to denounce the ordinances since there were few others in Europe who
believed that tuberculosis was a contagious disease.
This treatment was implemented with few major changes well into the 19 th century.
In 1865, Villemin inoculated tuberculosis and in 1880-1882 R. Koch isolated and
cultivated the bacteria responsible for tuberculosis. Tuberculosis could then be
categorized as an infectious-contagious disease, the basis for an anti-tuberculosis
solution.
Nevertheless, various medications such as arsenic, tannin, iodine, tar inhalants,
creosote, and alcohol continued to be used ineffectively. Leudet curiously theorized
in 1864 that “tuberculosis is less frequent in professional drinkers that in abstinent
subjects.”
Doctors recommended trips to exotic locations (for wealthy patients) in search of an
impossible cure. For example, trips to Rome or Venice were popular at one time
under the presumption that malaria emanations of the cities were beneficial; malaria
was already considered an antagonist disease to tuberculosis.

In 1860, Hermann Brehmer from Germany started the first center in Göbersdorf to
cure tuberculosis by rest. He believed that the mountain fresh air and over-feeding
in an establishment more like a luxury hotel than a hospital would strengthen the
patient. His student, Peter Dettweiter, founded a famous center in Falkenstein in
1876 and was the first to use the name sanatorium for his establishments.
Treatment in sanatoriums quickly spread throughout Europe and America mainly
because of modifications that made them accessible to patients of any class. Until
the advent of chemotherapy, sanatoriums were the best alternative to treatment,
especially in the beginning stages of the disease.
Studies by Toussaint demonstrated changes in tuberculosis lesions when spontaneous
pneumothorax is produced. In 1888, an Italian, Carlo Forlanini preformed the first
intentional spontaneous pneumothorax using a needle to puncture the pleual cavity
and then administering nitrogen. At the same time a North American surgeon, J.B.
Murphy, preformed a similar experiment using a thick trocar to make an incision in
the thoracic cavity.
Collapsing the lung quickly became important because the surgical procedure was
more explicit than any others previously explained. Collapsing lungs using more
technical surgery was started shortly after. In 1907, Friedrich preformed the first
thoracoplasty with extensive alveolar resectioning at the expense of serious
alterations to the thoracic cavity and high mortality. In the following years, the
procedure was slowly perfected and preformed with less harm. Toward 1930,
pulmonary tuberculosis had been converted to a surgical disease and these new
techniques form the basis of modern thoracic surgery today.
In 1920, a microbiologist, A. Calmette, and his veterinarian student, C. Guerin, spent
three years cultivating bacteria and eventually found a bovine species of bacteria
with rare virulence that could possibly be developed into active immunity against
tuberculosis. The BCG vaccine was a great hope to many but because of its
widespread use, actually became an obstacle for the powerful impact of modern
chemotherapy. In fact, the observations by A. Fleming in 1929 about the
antibacterial properties of molds initiated spectacular changes in the treatment of
infectious-contagious diseases.
A few years after the discovery of penicillin, Selman A. Waksman demonstrated that
small fungi of the genus Streptomyces griseus inhibit the growth of m.tuberculosis
cultures because of a substance called streptomycin. The massive industrial
production of streptomycin in 1946 produced the first effective chemotherapy

against tuberculosis. It was then discovered that streptomycin was not the
miraculous drug that was hoped for; a few months after apparent healing, the
patients’ lesions were reopened because the bacteria had developed mutant strains
resistant to antibiotic action.
J. Lehman isolated para-amino-salicylic acid in 1944 and later discovered isonaizid, a
hydrazine from isonicotinic acid. Administration of isonaizid with streptomycin
solved the problem of resistance and finally achieved the long-lived dream of
mankind: to find a chemotherapy treatment to cure all the cases and visceral regions
of tuberculosis. Despite its advantages, a serious inconvenience to the
effectiveness of the treatment was the need to administer the drugs for 12-18
months to ensure sterilization.
In 1966, the Italian Pietro Sensi isolated rifamycin S from fungus of the genus
Streptomyces mediterranii. It was supposedly a new treatment revolution to be
verified upon experimental studies because its actions against all types of bacteria
complimented the specific activity of pyrazinamide against intercellular bacteria.
These findings were the basis of shortened chemotherapy treatment of 6 months.
They were tested in a clinical study in east Africa between 1972 and 1976 and were
recommended as initial treatment for tuberculosis.
AIDS and the recent increase of resistance and multi-resistance to rifampicin and
isonaizid in some third-world countries and poor districts of large urban regions has
had a negative impact on chemotherapy tuberculosis treatment. We cannot let our
guard down and we need economic support for the research of new drugs and
synthetic vaccines to confront the challenge of tuberculosis in the 21 st century.