Von Prowazek Research Articles

From disease to etiology: historical aspects of Chlamydia-related diseases in animals and humans

A first description of the etiology of trachoma was published in 1907. During expeditions to Java to study the transmission of syphilis, Halberstaedter and von Prowazek infected orangutans with conjunctival scrapings from trachoma patients and such agents in conjunctival smears. They called them "chlamydozoa". J. Ritter in 1879 published the first case description of psittacosis, describing a mini-epidemic in which three of seven patients died, and identified the source of infection, determined the incubation period and the nontransmissibility of the disease from human to human. In 1895 the term psittacosis was first applied. In 1893, Nocard isolated a Gram-negative bacterium from parrots dying of psittacosis (Bacillus psittacosis). This organism was subsequently found in human or avian subjects and was later diagnosed as Salmonella. The inconsistent bacteriological findings prompted a search for a filterable virus during the pandemic of 1929-1930. Almost simultaneously, Levinthal (1930), Coles (1930) and Lillie (1930) described small, filterable bodies in infectious material called "Levinthal-Coles-Lillie (L.C.L.) bodies". Bedson first suggested the biphasic development cycle in 1932 after having studied tissues from inoculated mice. In 1935, Burnet and Rountree propagated "the virus" on the chorioallantoic membrane of embryonated chicken.

Chlamydial Infections in Children and Adolescents

1. Latha Chandran, MD, MPH* 2. Rachel Boykan, MD† 1. *Editorial Board 2. †Assistant Professor of Pediatrics, Stony Brook University Medical Center, Stony Brook, NY After completing this article, readers should be able to: 1. Describe the varied clinical manifestations of Chlamydia trachomatis infection in neonates, children, and adolescents. 2. Know the clinical manifestations of Chlamydophila pneumoniae infection. 3. List the various diagnostic criteria and methods for C trachomatis and C pneumoniae infections. 4. Discuss the treatments for C trachomatis and C pneumoniae infections. Chlamydiae are obligate intracellular organisms that cause a wide spectrum of human and animal disease, including conjunctivitis, pneumonia, and genital tract infections. C trachomatis and C pneumoniae are significant human pathogens; C psittaci is a less common cause of human disease. The earliest descriptions of what is believed to have been trachoma are found in ancient Chinese and Egyptian manuscripts. In 1907, Halberstaedter and von Prowazek found what they assumed (correctly) to be the causal agent in trachoma when they noted intracytoplasmic vacuoles with numerous particles in Giemsa-stained epithelial cells. Subsequently, similar inclusions were described in specimens taken from the eyes of babies who had ophthalmia neonatorum, from their mothers’ uteruses, and from men who had urethritis. From 1929 to 1930, outbreaks of an “atypical pneumonia” acquired from psittacine birds stimulated more research, which led to Bedson's description of the characteristic developmental life cycle of all Chlamydiales . His accurate description of “an obligate intracellular parasite with bacterial affinities” was not fully appreciated for several decades because these new agents initially were believed to be viruses. Under the 2000 taxonomy, the order Chlamydiales was divided into four families: Chlamydiaceae, Parachlamydiaceae, Waddliaceae , and Simkaniaceae . The family Chlamydiaceae was divided further into two genera, Chlamydophila and Chlamydia , based on ribosomal sequence analysis that showed less than 95% homology between Chlamydia and Chlamydophila. Chlamydophila includes the species C pneumonia, C psittaci , and nonhuman pathogens; the family Chlamydia includes C trachomatis and nonhuman pathogens. (1 …

Chlamydia Trachomatis: Milestones in clinical and microbiological diagnostics in the last hundred years

Chlamydia trachomatis an obligate intracellular, Gram-negative bacterium is the causative agent of several acute or chronic, local and systemic human diseases such as trachoma, oculogenital and neonatal infections. It was discovered in 1907 by Halberstaedter and von Prowazek who observed it in conjunctival scrapings from an experimentally infected orangutan. In the last hundred years the detection and study of the intracellular pathogens, including chlamydiae, passed through an enormous evolution. This memorial review is dedicated to these important research and diagnostic discoveries and to the scientists who significantly contributed to this evolution starting from the application of simple light microscopy through the cell culture technique, antibiotic susceptibility, antigen and antibody detection, serotyping, to the real-time nucleic acid amplification and restriction fragment lengths polymorphism analysis. Although the majority of these old and new excellent diagnostic methods have been introduced into the rutine practice, the trachoma has remained one of the leading causes of blindness, and oculogenital chlamydial infections still are the most frequent sexually transmitted bacterial diseases, furthermore lymphogranuloma venereum is a disease emerging in the developed countries at the beginning of the 21 st century.

Les Rickettsies : historique et actualité (1 re partie)

In early part of the last century (1910) Ricketts and von Prowazek laid the foundation of modern rickettsiology. Their pioneering works eventually led to the recognition of new species and Rickettsials infections. As soon as Rickettsia are the first strictly intracellular bacteria described, its taxonomy gathered on the basis of this criterion : a great number of kinds of bacteria will be identified only with the advent of the sequencing and the discovery of molecular clocks such as ribosomal 16S RNA and cytochrome C. Many phenotypic criterion such as morphology, tests of complement, neutralization of toxins, mouse serotyping and SDS-page proved reliable. However, gene comparison ( ompA, ompB and sca4) will make it possible to very precisely determine the species containing of the genus Rickettsia and to suggest a classification supported by high bootstrap values as well as antibiotics tests. Nevertheless, the phylogenetic position of species such Rickettsia helvetica, Rickettsia canadensis and Rickettsia bellii could not be given with precision, and the polyphasic analysis of the classification of the Rickettsia species based on genes concatenation associated with phenotypic characters available might be alternatives for Rickettsia phylogeny.

Stanislaus von Prowazek (1875–1915) Prodigy between Working Bench and Coffee House

Stanislaus von Prowazek (1875–1915) Prodigy between Working Bench and Coffee House

Plasmodium inui Is Not Closely Related to Other Quartan Plasmodium Species

Plasmodium inui (Halberstaedter and von Prowazek, 1907), a malarial parasite of Old World monkeys that occurs in isolated pockets throughout the Celebes, Indonesia, Malaysia, and the Philippines, has traditionally been considered to be related more closely to Plasmodium malariae of humans (and its primate counterpart Plasmodium brasilianum), than to other primate Plasmodium species. This inference was made in part because of the similarities in the periodicities or duration of the asexual cycle in the blood, the extended sporogonic cycle, and the longer period of time for development of the pre-erythrocytic stages in the liver. Both P. inui and P. malariae have quartan (72 hr) periodicities associated with their asexual cycle, whereas other primate malarias, such as Plasmodium fragile and Plasmodium cynomolgi, are associated with tertian periodicities (48 hr), and Plasmodiumn knowlesi, with a quotidian (24 hr) periodicity. Phylogenetic analyses of portions of orthologous small subunit ribosomal genes reveal that P. inui is actually more closely related to the Plasmodium species of the "vivax-type" lineage than to P. malariae. Ribosomal sequence analysis of many different, geographically isolated, antigenically distinct P. inui isolates reveals that the isolates are nearly identical in sequence and thus members of the same species.

Alfred Th. Leber (1881-1954): a pioneer in tropical ophthalmology. Missing in the South Seas--rediscovered in India

In spite of the brief duration of German colonial rule during that period tropical medicine enjoyed a remarkable growth and development. This is the first account of the career of the pioneer of tropical ophthalmology, Alfred Theodor Leber (1881-1954); medical history had previously reported him missing in Java after the 1st world war. His career was greatly influenced by his uncle, Theodor Leber (1840-1917), the founder of experimental ophthalmology. Alfred Leber was the one who combined teaching and research in the subjects of ophthalmology and tropical medicine. During his first expedition as a private lecturer together with von Prowazek in Samoa (1910-1911), he discovered the involvement of the eye in filarial infections with Wuchereria bancrofti (Lebers fundus). In consideration of his extraordinary work he was appointed professor at the young age of 33. After his training at the eye clinic at Berlin University under von Michel he worked as senior physician with von Hippel in Göttingen. Both Ludwig Külz and the famous painter Emil Nolde joined him on his second expedition, to New Guinea, in 1913. During his expedition in summer 1914 World War I broke out. Leber could not return to Germany. He stayed in the neutral Dutch East Indies during these years. Favoured by the ravages of war, British and Australian authorities (Military Intelligence, War Office, Defence) succeeded in seizing some of Leber's research reports and kept them under lock and key. The "Leber-Külz medical demographic New Guinea expedition on behalf of the Reich's Colonial Office" was therefore known to the public only as "Emil Nolde's travels in the South Seas".(ABSTRACT TRUNCATED AT 250 WORDS)

Chlamydia trachomatisinfections and their importance to the gynaecologist

SummaryIn 1907 Halberstaedter and von Prowazek described intracytoplasmic inclusions in the conjunctival scrapings of orang-utans that had been infected with material from patients with trachoma. Subsequently, they described similar inclusions in conjunctival epithelial cells from infants with ophthalmia neonatorum (1909) and these findings were confirmed by others. Heyman (1910) observed inclusions in cells from the cervical smear of the mother, and the urethral smear of the father, of an infant suffering from what today is known as inclusion blenorrhoea. The inclusions were thought to be a form of the organism responsible for the disease (Schachter and Dawson, 1978). The name ‘chlamydia’ originated from Halberstaedter's and von Prowazek's description in 1907 as ‘mantled animals’. There is, in fact, no mantle but the name chlamydia has remained.

Chlamydial Infections

Chlamydia trachomatis was first described by Halberstadter and Von Prowazek in 1907, as a characteristic intracytoplasmic inclusion in the conjunctival scrapings from a patient with trachoma. Although the organism was identified as the etiologic agent of trachoma and inclusion conjunctivitis in the neonate, a full understanding of its nature was not feasible until C trachomatis was first successfully propagated in cell cultune in 1965. This technical innovation greatly facilitated investigation of the biology and the epidemiology of chlamydial infections in man. C trachomatis is now recognized to be one of the most prevalent sexually transmitted diseases in the United States today. It is responsible for 40% to 50% of cases of nongonococcal urethritis (NGU) in men and a large reservoir of genital infection, largely asymptomatic, in women. In the United Kingdom, where NGU is a reportable disease, NGU is now more prevalent than gonorrhea and is considered to be the most important male veneral disease. The cervical infection in women is of special importance to pediatricians as the infection may be transmitted to the infant during parturition, leading to both ocular and respiratory disease. A thorough understanding of the microbiology and epidemiology of C trachomatis is an important prerequisite for appreciating the clinical features, diagnostic methods, and management of these infections by pediatricians.

Trachoma: Prevention and Treatment

Giambattista Bietti, Professor of Ophthalmology at the University of Rome, and Georges H. Werner, virologist from Vitry-sur-Seine, France, have collaborated to produce a timely monograph on the clinical, epidemiologic, therapeutic, and microbiologic aspects of trachoma. Dr. Bietti is a world authority on the disease. He is President of the International Organization Against Trachoma and has published many important papers on all phases of research on trachoma and related diseases. Dr. Werner is well known for his many virologic contributions on this and other diseases. The two authors have reviewed the world literature on trachoma (which is estimated to affect 400 million people) and have made useful analyses on the basis of their own experience.The monograph opens with an historical survey of the microbiology of trachoma. It begins with Halberstaedter's and von Prowazek's demonstration in 1907 of the cytoplasmic inclusions that bear their names, and continues with a complete discussion of the morphologic and biologic properties of the trachoma agent for which the generic names, Bedsonia and Chlamydia, have been proposed.

AN AID IN DETECTING TRACHOMA-LIKE INCLUSION BODIES IN THE CONJUNCTIVA

IN 1907, while in Java to investigate the immunology of syphilis, Halberstadter and von Prowazek 1 discovered the inclusion bodies associated with trachoma. This observation was the first demonstration of such bodies in the eye. A few investigators have expressed the belief that the infectious agent of trachoma is a rickettsial body. 2 In support of this view, Cuenod and Nataf 2b claimed the passage of the agent through the louse onto a normal conjunctiva, with the production of clinical trachoma. Halberstadter-Prowazek inclusion bodies are observed in the conjunctival scrapings in cases of certain ocular infections. Although trachoma is the most important of these, similar bodies are also seen in cases of inclusion conjunctivitis, psittacosis and lymphogranuloma venereum. 3 Whether, as Lindner 4 stated, these bodies constitute the agent causing trachoma or whether they are the by-products of a tissue reaction to this agent is not clear. What does seem

VIRUS DISEASES OF SKIN, WITH SPECIAL REFERENCE TO ELEMENTARY AND INCLUSION BODIES

Virus diseases of plants and animals have always played an important role in human economy. The earliest triumphs of preventive medicine were achieved in this field before the nature of such diseases was understood. Their extraordinary capacity to flame up into world-wide epidemics makes their study of primary interest during a world war. The dermatologist has an excellent right to a special interest in virus diseases. The first successful attempt to produce artificial immunity was in smallpox. Most of the infectious exanthems are of virus or rickettsial origin. Pioneer work by Guarnieri, Paschen, von Prowazek, Lipschutz and others on the histology of virus diseases was made possible by the easy accessibility of cutaneous lesions. The intensive study of the cytologic changes caused by the viruses of herpes simplex, herpes zoster, molluscum contagiosum, varicella, variola and others by outstanding students of virus diseases testifies to the opportunity offered by diseases of

A RICKETTSIA-LIKE ORGANISM OF THE CONJUNCTIVAL EPITHELIUM OF PIGS

In 1907 Halberstädter and von Prowazek first described the cellular inclusions associated with trachoma. In 1909 Stargardt¹found similar inclusions in cases of blenorrhoea neonatorum ; indeed, the bodies of inclusion blenorrhea cannot be distinguished from those of trachoma on morphologic grounds. Leber and von Prowazek²in 1912 published a report on a disease of man, probably trachoma, in the South Sea islands and called the inclusions Lyozoon atrophicans, a species of Chlamydozoa. Shortly after these discoveries were made Uhlenhuth and Böing,³in 1910, stated that they had found bodies in the conjunctival epithelium of pigs and that these bodies closely resembled the inclusions of trachoma and blenorrhoea neonatorum. From this time onward various German workers⁴linked these structures, closely or loosely, with the virus of swine fever or hog cholera. These hazy perceptions still persist in many quarters. Von Buzna,⁵however, failed to detect the

The Carbohydrate Matrix of the Epithelial-cell Inclusion in Trachoma

Although the inclusions found in trachoma were first described by Von Prowazek and Halberstaedter in 1907, since then very little has been done to discover the nature and composition of these bodies. This microchemical study of the Von Prowazek-Halberstaedter inclusion body found in the cytoplasm of epithelial cells from trachomatous conjunctivae indicates that this inclusion contains a high concentration of some carbohydrate. The evidence would seem to indicate that this carbohydrate is glycogen. The carbohydrate is a matrix in which are suspended or embedded the so-called initial bodies of Lindner and the elementary bodies of Von Prowazek. The questions raised from this study are: 1. What is the origin of the carbohydrate? 2. Why does it not quickly diffuse throughout the cytoplasm in preparations made to study fresh unfixed cells? 3. What is the significance of the fact that the inclusions found in inclusion-body blennorrhea apparently have the same composition as the inclusions found in trachoma? 4. What is the relationship of the so-called elementary bodies of Von Prowazek and the initial bodies of Lindner to the carbohydrate matrix in which they are embedded? 5. If the carbohydrate of the trachoma inclusion is a cytoplasmic reaction to irritation from a visible or invisible virus, then do any of the other known virus diseases produce inclusions which are concentrations of glycogen? Read before the St. Louis Ophthalmic Society, October 25, 1935.

Cytological studies on the viruses of fowl-pox and vaccinia

Although, as is well known, the ultra-microscopic viruses are invisible in histological preparations, yet characteristic bodies occur within certain of the cells of animals infected with such organisms. The origin and nature of these so-called “virus bodies” has been the subject of much controversy. By some they have been regarded as the actual parasite, or at least as phases in its life cycle. To von Prowazek they were dual in character consisting of microorganisms embedded in material produced by the reaction of the cytoplasm of the infected cell. Still other observers regarded such bodies as products of cellular disintegration. In a former paper (Findlay and Ludford (1926)) we have referred to the various views held by writers in this field and have made a survey of the literature of the subject in the form of a pictographic review. We shall, therefore, only mention previous work in this field, in so far as it directly concerns our personal observations. A conspicuous fault of much of the earlier work has been the unsatisfactory histological technique employed, especially the nature of the fixative. The earlier cytological work was carried out with fixatives, which although satisfactory for the subsequent demonstration of nuclear structures were very destructive to the cytoplasm. This is particularly unfortunate since most of the virus bodies occur in the ground cytoplasm of cells. We have endeavoured to rectify this source of error in our work by employing fixatives, which have been proved to fix the cells in such a manner as to give an appearance as nearly as possible identical with their structure, as seen in the living cells.

THE RESISTANCE OF SPIROCHETES TO THE ACTION OF HEXAMETHYLENETETRAMINE DERIVATIVES AND MERCURIAL AND ARSENIC COMPOUNDS

The majority of the 76 new compounds possessed spirocheticidal powers ranging between 1: 1,000 (30) to 1:2,500 (14), while only 2 attained the power of 1:5,000, 1 of 1: 25,000, and 2 of 1: 50,000. On the other hand, 8 killed the spirochetes in a dilution of 1: 750, 10 in 1:500, 7 in 1:250. 1 in 1: 100, and 1 in 1:50. It may be mentioned that the 2 (M1, M4) of 1:50,000 and 1 (M7) of 1:25,000 belong to the mercury compounds, and that mercuric chloride kills the organisms in a dilution of 1: 100,000 under the same experimental conditions. It is also interesting to compare some of the more common chemicals and therapeutic reagents. Phenol is spirocheticidal in a dilution of 1: 2,500, lysol in 1: 5,000, formalin in 1: 750, salvarsan in 1: 7,500, and neosalvarsan in 1: 2,500. Thus, of the new compounds there are at least 14 which have the same spirocheticidal power in vitro as has neosalvarsan. It is of interest to note that nine compounds possessing the 1:1,000 spirocheticidal power showed only one-tenth of the antiseptic action when tested upon Bacillus dysenteriae and Streptococcus, while some showed an even greater difference in this respect. Nos. 16, 21, 29, 218, and 244 were effective in a dilution of 1:2,500 for spirochetes and in a 1:100 or lower dilution for the bacteria just referred to. Preparations 46 and 84 appear to exert about the same effect both on the spirochetes and the bacteria, neither being very strong. Atoxyl killed the spirochetes in a 1:50 dilution. One of the most striking results was obtained with various hemolytic substances. Neufeld and von Prowazek found that spirochetes, unlike bacteria in general, are highly susceptible to the lytic action of sodium taurocholate and saponin, and they considered that this phenomenon was of differential diagnostic value in determining plant and animal organisms. Their observations were confirmed by Gonder, who found, however, that spirochetes, especially treponemata, offer a great deal of resistance at the beginning, but finally undergo lysis, with their cell bodies swollen up or macerated. In the present experiment we have found that these substances not only bring about cytolysis of the spirochetes in higher concentrations, but also kill them without causing a gross destruction of the cells in very high dilutions; thus, sodium cholate in 1: 5,000, sodium glycocholate and taurocholate in 1: 2,500 each, saponin in 1:7,500. Sodium oleate, one of the most powerful hemolytic agents killed the spirochetes in 1: 7,000, and cobra lecithide and native cobra venom in a dilution of 1:1,000 each. Neither sodium nor potassium iodide displayed any marked spirocheticidal property (1: 10 only), while iodine in the form of Lugol's solution was able to kill them at 1:75.

THE CULTIVATION OF TRICHOMONAS OF THE HUMAN MOUTH (TETRATRICHOMONAS HOMINIS)

Trichomonades from the mouth were studied by Steinberg who proposed to group them into three distinct types; namely, Trichomonas elongata, Trichomonas caudata, and Trichomonas flagellata. Doflein (3) regards them as probably identical with Trichomonas hominis. Opinions differ as to whether or not Trichomonas vaginalis Donné and Trichomonas hominis Grassi are the same species. Lynch, for instance, believes that they are the same species, while von Prowazek (4), Bensen (5), and others (6, 7) insist that they are different types. Bensen's view seems to be well supported by the difference alleged to be found between the mode of encystment in the two trichomonades, were it not for the fact that our knowledge about the so called cyst of trichomonades is still obscure. According to Alexeieff (8) many of the so called cysts were evidently blastomyces contained in the cell body of the trichomonas. An autogamy alleged to take place in cysts as described by Bohne and von Prowazek (9) has not been confirmed by Dobell (10). And Wenyon (11) contends that it has never been found possible to produce any development of these cysts outside the body on the warm stage as can be done with the cysts of Entamoeba coli. Therefore, it is still premature to take the process of encystment into consideration as far as the classification of trichomonas is concerned. On the other hand, Rodenwaldt (12) seems to think that there are many species of trichomonas in the human intestines, and Wenyon has described a new trichomonas from the human intestines (Macrostoma mesnili Wenyon). Further cultural studies in the morphology and biology of these organisms must be carried out in order to solve these problems. In the light of modern investigations there are five subgenera to be included under the genus Trichomonas Donné. They are as follows: (1) Protrichomonas Alexeieff, with three anterior flagella, without an undulating membrane. (2) Trichomastix Biitschli) with three anterior flagella and a trailing flagellum (Schleppgeissel) without an undulating membrane. (3) Trichomonas Donné, with three anterior flagella and an undulating membrane. (4) Macrostoma Alexeieff, Amend, Wenyon (11), with three anterior flagella and an undulating membrane wedged in a deep groove (peristome). (5) Tetratrichomonas Parisi (13), with four anterior flagella and an undulating membrane. As far as our culture trichomonas from the human mouth is concerned, it has been shown that it is not strictly a trichomonas and that it should be classed under the subgenus Tetratrichomonas.

BACTERIOLOGICAL AND CLINICAL STUDIES OF AN EPIDEMIC OF KOCH-WEEKS BACILLUS CONJUNCTIVITIS ASSOCIATED WITH CELL INCLUSION CONJUNCTIVITIS

1. There are cases in which epithelial cell inclusions may alone be present in the conjunctival smears. In such cases no other pathogenic organisms, such as the Koch-Weeks bacillus or the pneurnococcus, can be demonstrated in smears or cultures. 2. The conjunctiva can become simultaneously infected with the inclusion bodies and Koch-Weeks bacilli or other organisms. 3. In cases of acute or subacute conjunctival inflammations due to mixed infections the clinical features of each infection may be present. The course of the inflammation is, however, more prolonged. 4. Within recent years, the Koch-Weeks bacillus has only seldom been found in our routine examinations. 5. The epidemic studied was of a severe type. 6. Clinically it is practically impossible to distinguish pneurnococcal conjunctivitis from the Koch-Weeks conjunctivitis. Bacteriological examination of smears and cultures is the only means by which the etiological diagnosis can be definitely established. 7. Conjunctivae of certain species of monkeys are susceptible to the von Prowazek inclusion bodies, but not to the hemoglobinophilic bacilli isolated from cases of epidemic conjunctivitis. 8. The injection of conjunctival scrapings containing the von Prowazek cell inclusions into the testicles of rabbits produces no cell inclusions in the latter, while the injection of a pure culture of the hemoglofcinophilic bacilli causes an acute inflammation accompanied by numerous clumps of the organisms, simulating the von Prowazek bodies at certain stages of their evolution. 9. There exists an apparent morphological similarity between the degenerated forms of this variety of the hemoglobinophilic bacilli and the cell inclusions, both in cultures and in experimental orchitis in the rabbit. But, as a rule, the elementary bodies of the latter are much smaller and more sharply defined than the smallest granules of the former, while the initial bodies are bigger, more intensely stainable, and less definite in their contour than the hemoglobinophilic bacilli found in the infected conjunctivae.

A preliminary communication on the life history of Trypanosoma balbianii

Trypanosoma balbianii , Certes, is a primitive member of the family of the Trypanosomidæ, and occurs in great numbers as a parasite in the gut of the oyster, where it may be present, either swimming freely in the fluid contents or enclosed within the crystalline style, when this structure is present. The species has been worked at by Certes and Lustrae, the latter of whom describes the presence of an undulating membrane and the external features of the process of division. The nucleus is, however, described by neither author. The material used in prosecuting this research was obtained from oysters fished from the Adriatic Sea, off the coast of Rovigno, but the parasite also occurs in the oysters of Schleswig-Holstein and the north coast of France. This distribution is thus a wide one. The research has been carried out under the guidance of Dr. von Prowazek, my great indebtedness to whom I here take the opportunity of expressing.