151 Typhus, Epidemic

Epidemic typhus fever is an acute rickettsial disease transmitted among victims by the human body louse, Pediculus humanus corporis. Its characteristic Sjnnptoms include high fever, prostration, headache and body aches, and a widespread rash that covers the trunk and limbs of the body.

Because of its association with conditions of hu­man misery, typhus has been known by many names. Jail distemper and its variations — morbus carcerum, gaol fever, and jayl fever - indicate the prevalence of typhus in detention facilities. Ship fe­ver, camp fever, and famine fever reflect the poor hygiene characteristic of travel, of military expedi­tions, and of refugee populations. The characteristic rash of typhus has elicited other descriptive names, including spotted fever in English, Fleckfieber and typhus exanthematicus in German, typhus exanthe- matique in French, tifo exantemdtico and tabardillo in Spanish (the latter meaning “red cloak”), and typhus-esantematico in Italian. Although Hippo­crates applied the word typhus, from the Greek word meaning smoky or hazy, to confused or stuporous states of mind frequently associated with high fe­vers, the word was not associated with the disease as it is currently known until the eighteenth century. After murine typhus was identified, the appellation typhus historique was sometimes applied to the clas­sic, epidemic disease.

Etiology and Epidemiology

Occurring as a natural infection only in humans, epidemic typhus is caused by Rickettsia prowazekii. It is spread from host to host by the human body louse, P. humanus corporis, and less often by the human head louse, Pediculus humanus capitis. The body louse spends its entire existence in the clothes of humans. Eggs laid in the seams of the undergar­ments hatch after about 8 days, and the nymphs become adults in about 2 weeks, going through three molts.

Once typhus organisms in infected human blood are ingested by a louse, they multiply rapidly in the cells lining the louse’s intestines and are se­creted in the feces of infected lice. Since rickettsiae are not found in other tissues (such as the salivary glands) of the louse, they are transmitted to new human hosts mechanically. This is usually accom­plished by contact of infected louse feces with a small abrasion of the skin incurred when the hu­man scratches the unpleasant itch caused by feed­ing lice. The disease spreads when lice leave fe­verish or dead victims for new hosts with normal temperatures. Unlike other rickettsial organisms, R. prowazekii is not passed from generation to gen­eration in the eggs of its host arthropod. In fact, as Hans Zinsser of Harvard Medical School pointed out in his 1935 history of typhus fever, humans constitute a great threat to the health and happi­ness of these small creatures, for humans usually recover from typhus fever, whereas the disease is inevitably deadly for infected lice.

Tjrphus is widely known as a disease of cold cli­mates, appearing in epidemics that usually reach their peaks in late winter and taper off in the spring. This pattern is clearly related to the ideal conditions for multiplication of lice and their rapid transmis­sion to new hosts. Typhus flourishes when people are crowded together in unsanitary surroundings and lack fuel, circumstances that predispose them to wear the same garments day and night for months at a time.

Persons of all ages are susceptible to typhus. Mor­tality rates in untreated typhus fever vary between 5 and 25 percent, occasionally reaching 40 percent. In children under 15 years of age, however, the dis­ease is generally mild. As age increases, so does mortality.

Clinical Manifestations and Pathology

After an incubation period that may vary from 5 to 15 days, the onset of typhus is abrupt.

During the first 2 or 3 days, the fever reaches its maximum, between 102^o to 105^oF, and is sustained for another 5 days, after which it falls rapidly if the outcome is favorable. In fatal cases, however, pros­tration becomes more progressive, with neurological symptoms increasing. These may include deafness, stupor, delirium, and eventually coma preceding death. Since 1948, however, when chloramphenicol and the tetracyclines (known collectively as broad­spectrum antibiotics) were introduced, no one need die of typhus if diagnosis is made in a timely manner.

Immunology

An attack of typhus confers long immunity. Many children in regions where typhus is frequent may contract Subclinical or mild cases that protect them somewhat from a later, more severe infection. Be­cause R. prowazekii persists in the tissues of its vic­tims even after recovery from the disease, however, symptoms of the disease may reappear years later, especially under conditions of stress when a victim’s immune system is depressed. This phenomenon was noted but not recognized in 1898, when New York physician Nathan Brill described a disease fre­quently diagnosed as typhoid but having symptoms more closely related to typhus. In 1910 Brill pub­lished an exhaustive study of 221 cases, and his thor­oughness led to the designation of “Brill’s disease” as a catchall for unknown, typhus-like symptoms.

For the next two decades, moreover, because of ignorance surrounding many other rickettsial dis­eases, illnesses exhibiting typhuslike symptoms any­where in the world were often classified as Brill’s disease. In 1934 Zinsser correctly hypothesized from epidemiological data that Brill’s disease was a recru­descence of epidemic typhus in persons who had ear­lier suffered an attack of the classic disease. During the 1950s, laboratory investigations confirmed his hypothesis, and the disease was renamed Brill- Zinsser disease.

The first laboratory diagnostic test for typhus grew out of a chance observation in 1916 by Vien­nese physician Edmund Weil and his English col­league Arthur Felix that a strain of Bacillus proteus was agglutinated by the sera of typhus patients. Later studies revealed that the phenomenon was a chance antigenic “fit,” but the Weil-Felix reaction, as it came to be called, provided a laboratory tool that became useful in several rickettsial diseases. In 1941 a more specific complement-fixation test was developed, and during the 1970s a variety of new techniques have improved the sensitivity and accu­racy of laboratory diagnosis.

Distribution and Incidence

In all areas of the world where public health and sanitation measures have been rigorously enforced, the incidence of typhus has declined dramatically. Cases may erupt in urban slums, and the disease remains a threat to many isolated rural regions. Re­porting of cases is poor in many regions of the world where typhus is most prevalent. Map VIIL151.1 shows the worldwide distribution of epidemic typhus during World War II. A recent study indicates that the major areas where typhus-infected lice are wide­spread have been reduced to three: the Himalayan region of Asia, the Andean regions of South America, and the hom of Africa, especially famine-ridden Ethiopia.

Map VIII.151.1. Outline map of the world (c. World War II), showing the approximate geographic distri­bution of epidemic (exanthematic) louse-borne typhus, murine (en­demic) flea-bome typhus, and Brill’s disease. (From Stanhope Bayne-Jones, in U.S. Army Medical Department 1964, 177.)

History and Geography

Antiquity Through The Sixteenth Century As a disease having a human reservoir, epidemic typhus has undoubtedly existed for centuries. Al­though it has been speculated that certain ancient plagues were probably typhus, the first contempo­rary accounts of a disease that may well have been typhus appeared near the end of the fifteenth cen­tury. In 1489-90 during the civil wars of Granada, Spanish physicians described a typhus-like disease that killed 17,000 Spanish soldiers - six times the number killed in combat with the Moors.

In the early sixteenth century, a similar malady appeared in Italy. During the French siege of Naples in 1528, an apparent typhus epidemic may have altered the subsequent course of European history. The French were at the point of decisive victory over the forces of Charles V when the disease appeared and struck down 30,000 French soldiers, forcing the remnants of the army to withdraw. In 1546 Girolamo Fracastoro (Fracastorius), who had observed the epi­demics in Italy, published the first clear description of what he termed a “lenticular or punctate or petechial” fever also characterized by headache and general malaise.

In the Balkan regions, where German, Italian, and French troops assembled to combat the Turks, many soldiers were struck by typhus even before they reached the battlefield.

Early to Mid-Nineteenth Century

Typhus increased dramatically in the early nine­teenth century. In 1812 Napoleon’s catastrophic expe­dition to Russia was plagued by typhus. Between 1816 and 1819, moreover, a great epidemic of the dis­ease struck 700,000 people in Ireland, whose popula­tion was only 6 million. For several decades, however, confusion characterized medical understanding of the disease. By the late eighteenth century, the medi­cal nosologist Boissier de Sauvages had begun using the word typhus to describe the neurological symp­toms of typhus, but few attempts were made to distin­guish pathologically between typhus and typhoid fe­ver, which also produced a red rash. Even into the twentieth century, confusion between typhoid and ty­phus was perpetuated in the nomenclature. In many European countries, the former was known as typhus abdominalis and the latter as typhus exanthematicus.

In 1837 Philadelphia physician William Wood Ger­hard, who had studied the distinctive intestinal le­sions of typhoid as a student of Pierre Louis in Paris, noted their absence in victims of typhus fever, which had been epidemic in Philadelphia the previous year. Gerhard’s work, however, was not immediately embraced by physicians who clung to older theories of the unity of fevers. It was not until mid-century that additional pathological and epidemiological re­search, especially by William Jenner and Austin Flint, convinced most American physicians that ty­phus and typhoid were distinct disease entities.

The European revolutions of 1848 spawned typhus epidemics in eastern Europe, as did warfare in Ethio­pia. During a particularly severe typhus epidemic in Upper Silesia, the German physician and politician Rudolph Virchow published a radical assessment of the epidemic that subsequently cost him his govern­ment post. Observing that the disease afflicted the poor, the uneducated, and the unclean, Virchow called for democracy, education, and public health measures as the proper “treatment” of the epidemic.

Late Nineteenth Century Through World War I Although typhus itself subsided during the latter half of the nineteenth century, the advent of the germ theory of disease during the 1870s spurred bacteriologists to search for a microbial cause for the classic scourge. In 1909, exploiting recent discover­ies about the role of insect and other arthropod vec­tors of microorganisms, Charles Nicolle, director of the Institut Pasteur in Tunis, North Africa, demon­strated that the body louse was the vector of typhus. The following year, Howard Taylor Ricketts, who was investigating typhus in Mexico City, described small bacteria he found in the blood of typhus vic­tims, in infected lice, and in lice feces. Before Rick­etts could confirm his observations, he contracted typhus and died. In 1916 the Brazilian Henrique da Rocha Lima described similar organisms, which he named Rickettsia prowazekii, the genus name after Ricketts and the species name after Polish re­searcher Stanislaus von Prowazek, who had also died from a laboratory-acquired typhus infection.

During World War I, military forces on both sides of the conflict acted on Nicolle’s discovery, institut­ing delousing procedures to combat typhus. These included bathing and steam-treating clothing to kill lice. Among poor civilian populations in war-tom eastern Europe, where such preventive measures were not enforced, the disease continued to exact a high rate of mortality. In 1915 Serbia was particu­larly hard hit, and typhus settled with a vengeance on Russia and Poland after 1918. Typhus research in Poland after World War I, sponsored by the League of Red Cross Societies, confirmed Rocha Lima’s asser­tion that R. prowazekii was the cause of typhus. Even so, because rickettsiae could not be cultured on lifeless media like ordinary bacteria, their etiologic relationship to typhus and other rickettsial diseases was not firmly established until the late 1930s.

Postwar Period Through World War II

During the 1920s and 1930s, empirical research on a vaccine against typhus was hampered because the organisms could not be grown in necessary quanti­ties outside of living cells. Displaying ingenuity in the face of this limitation, researchers prepared vac­cines from infected lice intestines, from lice feces, and from the typhus-infected lungs of rats. Then in 1937 U.S. Public Health Service investigator Herald R. Cox discovered that rickettsiae grew luxuriously in the yolksacs of fertile hens’ eggs. This method simplified vaccine production and made it commer­cially feasible just as the onset of World War II again raised concern about large-scale typhus epidemics.

The threat of typhus was a key factor in Allied military plans during World War II, and in 1942 Presi­dent Franklin D. Roosevelt created an extraordinary body, the U.S.A. Typhus Commission, to combat ty­phus wherever it might threaten the U.S. military efforts. The so-called Cox vaccine was administered to all Allied military personnel, and although experi­ence during the hostilities indicated that it did not actually prevent the disease, it clearly ameliorated its course. Intensive research on antilouse agents by government and private groups, moreover, demon­strated that lice could be effectively controlled by dichlorodiphenyl-trichloroethane, more commonly called DDT. This powder could be applied with a “blowing machine” to puff it under clothes without their owners having to remove them. The method was not only faster, it was also accepted by even the most modest civilians. DDT also proved to be highly effec­tive in the typhus epidemic that occurred during the winter of 1943-4 in Naples, Italy. With astonishing rapidity, the nascent epidemic collapsed. Within two decades, however, the ability of lice to become resis­tant to DDT had been documented. In addition, the chemical’s ecological hazards were found unaccept­able, and it is no longer widely used to prevent typhus.

Prophylaxis and control of typhus with the Cox vaccine and with DDT during World War ∏ reduced typhus from a major threat to a mere nuisance among Allied troops. Only 104 cases occurred among U.S. military personnel, with no deaths. In contrast, severe epidemics occurred among civilians in North Africa, Yugoslavia, the German concentra­tion camps, Japan, and Korea.

Mid-Twentieth Century to Present

In 1948 the tetracyclines and chloramphenicol, known together as broad-spectrum antibiotics, were discovered to be effective treatments for rickettsial diseases. Since the late 1940s, efforts to combat ty­phus have depended almost exclusively on these anti­biotics. In 1980 concern about the limited efficacy and side effects of the Cox vaccine halted its produc­tion, and at the present writing, no typhus vaccine is commercially available. Recent research, moreover, has indicated that the humoral immunity stimu­lated by all existing rickettsial vaccines is less impor­tant than is cell-mediated immunity. At present, genetic engineering techniques are being employed in research on a more effective vaccine.

Since 1950, typhus has been reported most fre­quently from the horn of Africa, from the high plains of the Andes in South America, and from the Himal­ayan regions of Asia - all areas characterized by rural poverty and cold weather. In one survey of Bolivian army recruits, for example, 80 percent had antibodies against the disease. Another study in a Bolivian village near the Peruvian border found mild typhus in children often confused with measles. Typically, the disease was more severe in afflicted adults than in children.

In Ethiopia, with its frequent famines, thousands of cases of typhus have been documented in recent years, especially in refugee camps. Similar ecologi­cal and sociological conditions in neighboring coun­tries suggest that the disease may also be wide­spread in them but masked by poor reporting. Reli­able statistics are also virtually impossible to obtain from the Himalayan regions of Asia.

Since Nicolle’s identification of the body louse as the vector of typhus, the slogan “no lice, no typhus” has been the watchword of public health efforts against this disease. But as Hans Zinsser noted in 1935, typhus will always remain a smoldering threat, ready to break out at any time that war, famine, or other catastrophes remove the public health barriers against it.

Victoria A. Harden

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