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After the Spanish Civil War, poor hygiene and nutritional deficiencies among a large part of Spain's population contributed to the rise of epidemic diseases. Exanthematic typhus posed a challenge to the health authorities, especially during the spring of 1941, when the epidemiological cycle of the disease and the lack of infrastructures combined to create a serious health crisis. The Franco regime, aware that this situation posed a threat to its legitimacy, promptly used social exclusion as part of its health policy against the epidemic. This article provides an in-depth analysis of the case of Valencia, a city that was behind Republican lines during the war, and therefore received successive waves of refugees as Franco's troops advanced.

The article describes how the system of medical care for wounded soldiers in Rijeka during the First World War was organized. In the Austro-Hungarian Empire the hospital care for sick and wounded soldiers, except of a military health care, was under the exclusive jurisdiction of the Red Cross. The Municipal Committee of the Hungarian Red Cross in Rijeka, established in 1881, renewed its previously suspended activity in August 1914, with the task of starting a war hospital for wounded soldiers. For this purpose, the former Hotel for emigrants, a large modern building opened in 1908, was converted. It became the center of hospital care for wounded soldiers in the city. Also, under the supervision of the Red Cross in Rijeka several smaller auxiliary dispensaries were organized. The other city health care facilities and the most of the physicians in Rijeka were included in the care for the wounded. The head of the volunteer nurses of the Red Cross was the president of the Red Cross in Rijeka, Countess Sofia Wickenburg, the wife of the governor and at the same time the president of the Red Cross city branch. The medical staff in Rijeka was particularly noted for its successful and rapid suppression of a typhus epidemic in February and March 1915. The paper is based on research of archival funds in the State Archives in Rijeka and part of the Rijeka and Zagreb press.

The year 1915 was particularly difficult; it was characterized by droughts, famines, and outbreaks of diseases including typhus.This text exposes its spread in Mexico City as well as the measures implemented to combat it, carried out before knowing the etiology of the illness, focused on cleaning up the environment and the measures undertaken afterwards with the aim of delousing people.

Objective: The Royal Army Medical Corps (RAMC) has justly regarded its relief of the appalling conditions found in the liberated Nazi concentration camp at Bergen-Belsen in April 1945 as one of its more glorious achievements. This view has, in the last decade, come under attack from historians who have, inter alia, criticised the nature and speed of the medical measures employed by the British. This has focused particularly on the management of the typhus epidemic, erroneously claimed to be the major disease killer of the survivors, and which was the catalyst for the premature German surrender of the camp to the approaching Allies about 3 weeks before the end of the war. This review examines the veracity of this statement and the nature of the evidence on which it was based., Methods: Review of all the relevant extant primary source written evidence both published and archived in major collections in London, Washington and Belsen, in addition to the relevant subsequent secondary evidence., Results: Disprove the ill-considered and scientifically flawed attempts to discredit the RAMC and demonstrate that the RAMC can be shown to have made the correct prioritising decisions in relieving starvation as well as in implementing the appropriate public health anti-typhus measures and to have acquitted itself honourably., Discussion: Underlines the pitfalls of basing sweeping conclusions on an imperfectly understood inadequate selection of the available evidence., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Materials, that summarize data of original research and scientific literature on epidemiology and problems of persistence during epidemic typhus, whose causative agent (Rickettsia prowazekii) is reactivated in the organism of the previously ill and is manifested as Brill-Zinser disease, are presented. A retrospective analysis was carried out with the data obtained by Russian (All-Union) Centre for Rickettsioses during study of epidemiologic examination maps of 5705 typhus nidi and results of 19 463 blood sera analysis during study of immunologic structure of population in the territories of the former USSR for the period from 1970 to 1992. A decrease of epidemic typhus morbidity and an increase of the fraction of Brill-Zinser disease took place as a result of pediculosis corporis control. In separate territories specific weight of Brill-Zinser disease was 48% in 1952, up to 80% in 1969, and from 1977 all the ill were previously ill. However, during the perestroika period and afterwards, due to a reduction of economic and hygienic living conditions, appearance of refugees, the immune structure regarding typhus began to change. Due to the buildup of the population migration process and the presence of risk groups (refugees, homeless) among population of regions, where local wars are waged, the enhancement of methods of epidemic typhus and Brill-Zinser disease diagnostics and pediculosis corporis eradication is necessary. Study of R. prowazekii by molecular-genetics methods is necessary for complete understanding of its mechanism of persistence.

Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine.

Rickettsia prowazekii has been tested for biological warfare due to the high mortality that it produces after aerosol transmission of very low numbers of rickettsiae. Epidemic typhus, the infection caused by these obligately intracellular bacteria, continues to be a threat because it is difficult to diagnose due to initial non-specific symptoms and the lack of commercial diagnostic tests that are sensitive and specific during the initial clinical presentation. A vaccine to prevent epidemic typhus would constitute an effective deterrent to the weaponization of R. prowazekii; however, an effective and safe vaccine is not currently available. Due to the cytoplasmic niche of Rickettsia, CD8(+) T-cells are critical effectors of immunity; however, the identification of antigens recognized by these cells has not been systematically addressed. To help close this gap, we designed an antigen discovery strategy that uses cell-based vaccination with antigen presenting cells expressing microbe's proteins targeted to the MHC class I presentation pathway. We report the use of this method to discover a protective T-cell rickettsial antigen, RP884, among a test subset of rickettsial proteins.

The article describes the measures taken against the threat of typhus epidemic in Finland during the Second World War. Comparisons between countries at war and their different typhus prevention methods are made. The main method of typhus prevention in Finland consisted of regular sauna bathing, which was culturally acceptable and very efficient when combined with heating of the clothing. The Finnish troops remained virtually louse-free by ecological and traditional methods, and thus the spread of typhus fever in the army could be prevented.

Rickettsia prowazekii, the causative agent of epidemic typhus, is an obligately intracytoplasmic bacterium, a lifestyle that imposes significant barriers to genetic manipulation. The key to understanding how this unique bacterium evades host immunity is the mutagenesis of selected genes hypothesized to be involved in virulence. The R. prowazekii pld gene, encoding a protein with phospholipase D activity, has been associated with phagosomal escape. To demonstrate the feasibility of site-directed knockout mutagenesis of rickettsial genes and to generate a nonrevertible vaccine strain, we utilized homologous recombination to generate a pld mutant of the virulent R. prowazekii strain Madrid Evir. Using linear DNA for transformation, a double-crossover event resulted in the replacement of the rickettsial wild-type gene with a partially deleted pld gene. Linear DNA was used to prevent potentially revertible single-crossover events resulting in plasmid insertion. Southern blot and PCR analyses were used to confirm the presence of the desired mutation and to demonstrate clonality. While no phenotypic differences were observed between the mutant and wild-type strains when grown in tissue culture, the pld mutant exhibited attenuated virulence in the guinea pig model. In addition, animals immunized with the mutant strain were protected against subsequent challenge with the virulent Breinl strain, suggesting that this transformant could serve as a nonrevertible, attenuated vaccine strain. This study demonstrates the feasibility of generating site-directed rickettsial gene mutants, providing a new tool for understanding rickettsial biology and furthering advances in the prevention of epidemic typhus.

During the years of World War I, several severe typhus epidemics were seen in Erzurum and nearby cities. A total of 164 health officers, 125 of whom were physicians, struggled against the epidemic in the region but also they lost their lives due to typhus. Vaccination against typhus was one of the means of fighting the epidemic. However, there were some claims that a small group of Turkish physicians injected typhus-contaminated serum into Armenian civilians during World War I, and that this should be accepted as a form of biological warfare against Armenian civilians. The purpose of this article is to set out how, by whom, and on whom, and under what conditions the typhus vaccination was applied in order to reveal the truth in terms of the evidence found in historical documents. The typhus vaccine was prepared from blood taken from febrile patients affected by the disease. After the blood of the patients were defibrinated and inactivated at 60 degrees C for an hour, it was used. As the amount of blood needed to prepare the vaccine was so great, the amount of available vaccine was always insufficient to meet the demand. Hence, the prepared vaccine was only applied to those which had the higher risk of contracting typhus such as physicians and nurses. The vaccine prepared by The Third Army Health Commander Dr. Tevfik Salim was first applied to nine officers, five of whom were physicians, and among whom were Dr. Haydar Cemal and Dr. Salahattin on March 28, 1915 in Hasankale, Erzurum. Furthermore, the same vaccine was applied to people in the vicinity by Dr. Alaattin in Erzurum, Dr. Abdulhalim Asim in Bayburt, Dr. Izak in Sivas and Dr. Mihran in Hasankale. Ali Ihsan Sabis and Fevzi Cakmak, who were high ranking officers, were among those who volunteered to have the vaccination. The Third Army Health Commander Dr. Tevfik Salim ordered that the vaccine should not be applied without blood inactivation. Despite this order, Dr. Hamit Osman, who had a mental illness, applied the vaccination without inactivating the blood to some people. Among those were physicians of the Red Crescent Hospital together with soldiers who were nursing in the hospitals in Erzincan. Dr. Hamdi Suat inactivated the blood by leaving it at -16 degrees C for 24-48 hours, and instead of giving a single dose, he applied three-doses with 3-day-intervals, followed by a one more dose, which he called "the vaccine for absolute immunization" to the same people after 10-23 days. This "vaccine for absolute immunization" was actually typhus-contaminated blood which had not been inactivated. It should be noted that he injected himself with the same form of vaccine. In his article published in German in 1916 and in Turkish in 1917, he stated that he injected "the vaccine for absolute immunization" to some subjects 'condemned to death'. Dr. Haydar Cemal claimed, in a newspaper dated December 23, 1918, that the people reported as subjects 'condemned to death' were indeed Armenians, and that the innocent Armenians marked out for deportation were inoculated with the blood of typhus fever patients, and that he eyewitnessed all these events. As a result of his claims, the Interior Ministry demanded an immediate investigation, and at the end of that investigation it was understood that Dr. Haydar Cemal and Dr. Hamdi Suat had never worked together in Erzincan at the time Dr. Haydar Cemal claimed. All the claims were refuted by the investigating committee and nobody was charged. During a severe typhus epidemic, Turkish physicians injected the typhus vaccine for the purpose of "saving a life from the fire". The typhus vaccine was prepared using the available scientific knowledge of the time. No racial or religious discrimination against the people vaccinated had been proved. According to the sources, the claim that some Turkish physicians used the blood of patients with typhus as a means of biological warfare does not reflect the historical truth.

Because of their unique biological characteristics, such as environmental stability, small size, aerosol transmission, persistence in infected hosts, low infectious dose, and high associated morbidity and mortality, Rickettsia prowazekii and Coxiella burnetii have been weaponized. These biological attributes would make the pathogenic rickettsiae desirable bioterrorism agents. However, production of highly purified, virulent, weapon-quality rickettsiae is a daunting task that requires expertise and elaborate, state-of-the art laboratory procedures to retain rickettsial survival and virulence. Another drawback to developing rickettsial pathogens as biological weapons is their lack of direct transmission from host to host and the availability of very effective therapeutic countermeasures against these obligate intracellular bacteria.

Rudolph Weigl gained a high estimation for his spectacular invention of the first efficient vaccine against typhus fever. Although born a German native speaker, he changed into a great Pole with Polish education and upbringing in a patriotic atmosphere. His scientific career developed in the Universities of Lvov, Cracow and Poznan. For him, academic employment was a constant exploration of practical truths and a response to human needs, and this remained a deep obligation during his lifetime. His vaccine saved millions, particularly during World War II. Despite many nominations, he was never awarded the Nobel Prize.

Ludwik Fleck is remembered for his monograph published in German in 1935. Reissued in 1979 as Genesis and development of a scientific fact Fleck's monograph has been claimed to expound relativistic views of science. Fleck has also been portrayed as a prominent scientist. The description of his production of a vaccine against typhus during World War II, when imprisoned in Buchenwald, is legendary in the scholarly literature. The claims about Fleck's scientific achievements have been justified by referring to his numerous publications in international scientific journals. Though frequently mentioned, these publications have scarcely been studied. The present article discusses differences in interpretation and evaluation of science in relation to the background of the interpreters. For this purpose Fleck's scientific publications have been scrutinized. In conjunction with further sources reflecting the desperate situation at the time in question, the results of the study account for a more restrained picture of Fleck's scientific accomplishments. Furthermore, based on the review of the latter, certain demands characterizing good science could be articulated. The restricted possibilities of those not trained in science or not possessing field specific knowledge, evaluating science are discussed, as are also formal aspects of scientific papers and questions related to research ethics.

Typhus exanthematicus in Bosnia and Herzegovina held in endemic areas from which especially quickly began spread after 1945. That year, in 1945, one hundred epidemics of typhus fever appeared, with the highest incidence rate in Europe of 215.04 per 1,000. Directions of unique program in the world were to eradicate lice of the body, but also establish monitoring of the recidivism, Brill-Zinsser disease. Since 1971, typhus exanthematicus (classical typhus) hasn't appeared in Bosnia and Herzegovina, so epidemic typhus can considered as an eradicated communicable disease.

Rickettsia prowazekii, the etiologic agent of louse-borne typhus, is listed as a category B agent under the select agent list of the United States Centers for Disease Control and Prevention. R. prowazekii was placed on the select agent list due to its potential to cause epidemic, high mortality in untreated and/or misdiagnosed cases, and ease of spread in vulnerable populations. Historically, R. prowazekii vaccines using crude antigen and/or inactivated rickettsia were partially protective but have been accompanied with undesirable toxic reactions and difficulties in standardization. The availability of the genome sequence of R. prowazekii allowed us to select genes that encode proteins with potential in immuno-protection against this human pathogen. We successfully PCR-amplified a group of genes involved in invasion (invA), cell division (fts), protein secretion (sec gene family), and virulence (ompA and ompB, virB gene family, cap and tlyA and tlyC). The generated PCR products were cloned into the Gateway cloning system and the cloned products will be introduced into Vical VR 1020-DV and VR 1012-DV DNA vaccine plasmids. Twenty-four target genes from R. prowazekii have been PCR amplified, of which fifteen have been introduced into the pENTR/SD/D-TOPO entry cloning vector.

Information about changes in the modern taxonomy of intracellular bacteria conditionally united within the nomination of "Rickettsioses" is presented in the paper. Due to a total hobby related with keeping home animals (pets), cats and dogs, apart from the cattle, joined the natural ecological cycles of rickettsioses stimulation. The morbidity of rickettsioses of the acaroid group has been persistently growing; like in case with other pathologies (Lyme's disease) involving the acaroid transfer factor, its obvious "urbanization" is pronounced. Absolute and relative morbidity indices in respect to rickettsioses, which are epidemiologically important for Russia, are presented. The modern knowledge database concerning the rickettsioses makes it possible to control the epidemic process for this infection category. It is noteworthy, that Prowazek's rickettsiosis of its both forms (i.e. the epidemic and relapsing ones), which does not have an independent cycle of circulation of its stimulator in wild nature, and unlike the acaroid group rickettsioses, turned into a socially controllable infection. It will be totally eliminated, during 10-15 years, both in Russia and the CIS countries. The practitioners are well supplied with a variety of drugs of tetracycline and fluorine-quinol groups, which makes it possible to arrest the infection process in patients rapidly and effectively and to prevent the lethal cases. A low incidence rate of rickettsioses, including Q fever, within the general infection morbidity, and taking into consideration the availability of methods for effective therapy and prevention, makes one consider a comprehensive vaccination against the discussed group of infections to be irrational. Obviously, such vaccination must be still applied in respect to a limited number of persons from among high-risk groups and for two or three varieties of rickettsioses only (i.e. Prowazek's rickettsioses, Rocky Mountain spotted fever and Q fever). Live vaccines, obtained on the basis of attenuated and recombined strains (which have a full-scale set of specific antigens), are recommended.

As an infectious disease, typhus has triggered many epidemics during the course of wars and caused thousands of death all through the ages. The French physician Charles Nicolle (1886-1936) defined its agent as a louse transferring the disease from man to man in 1909 and was awarded the Nobel Prize in 1928. Many cases were reported during the 1st World War both in the European and the Ottoman armies; and one of the most severe epidemics broke in the Caucasian front; a great number of civilians and soldiers died at winter in 1914 and 1915. Lice had to be destroyed in order to prevent the epidemic, but etuves in the Caucasian front was too few to achieve it. Clothes were cleansed in ovens by means of a method proposed by Dr. Abdülkadir Noyan (1886-1977). On March 28, 1915 the first typhus vaccination, obtained from the infected blood of the patients, was applied by Dr. Tevfik Salim (Saklam) (1882-1963). In 1916 Dr. Ahmet Fikri Tüzer discovered a disinfection apparatus called "buğu sandiği" (vapour box) which was widely used in the Caucasian front after 1917. This apparatus was highly useful in controlling the typhus epidemics. 164 health officers lost their lifes in the Caucasian front between 1914-1918, in addition, 7310 military casualties were recorded from 1915 to the end of the war.

In tropical regions of Africa, frequently subject to social and political upheavals, there is an ever-present threat of typhus epidemics, as shown by the recent typhus outbreak in Burundi in 1997. Epidemic typhus should be systematically suspected in certain epidemiological conditions: famine, war, high-density populations (refugee camps, prisons), the presence of body louse in the clothing, and in the presence of certain clinical findings: severe infectious syndrome (temperature above 38 C), severe pain and muscle weakness, with coughing and severe neurological signs. The rapid diagnosis and treatment of typhus are essential. The prognosis has improved, thanks to the specific antibiotics that are currently available, particularly doxycycline, prescribed as a single oral dose of 200 mg for adults or of 100 mg for children. However, the prognosis still depends to a large extent on the speed of diagnosis. Typhus epidemics could be effectively predicted and limited if the measures for control of the body louse recommended by the World Health Organization were applied in the areas with the most favorable epidemiological conditions.

Body lice are vectors of three bacteria which cause human disease: Rickettsia prowazekii, the agent of epidemic typhus; Bartonella quintana, the agent of trench fever; and Borrelia recurrentis, the agent of relapsing fever. A recrudescence of body lice is being observed as the numbers of individuals living under social conditions which predispose individuals to infestation have increased. Because this phenomenon may lead to the reemergence of infections transmitted by body lice, we aimed to assess the occurrence and prevalence of the three agents described above in more than 600 body lice collected from infested individuals in the African countries of Congo, Zimbabwe, and Burundi, in France, in Russia, and in Peru. The presence of the three bacteria in each louse was determined by specific PCR amplification, and the identities of the organisms detected were confirmed by determination of the nucleotide base sequences of the amplification products. Using this approach, we were able to confirm the presence of R. prowazekii in lice collected from refugees in Burundi, among whom typhus was epidemic, and the presence of B. quintana in lice collected from all locations except the Congo. B. recurrentis was never found. Molecular approaches are convenient tools for the detection and identification of bacterial DNA in body lice and for the epidemiological study of louse-borne bacteria from countries where no medical and biological laboratory facilities are available.

The analysis of the results of prolonged observations on the prophylactic immunization of employees working with R. prowazekii is presented. The necessity of the differentiated approach to the determination of the immunization schedule and the choice of vaccine is shown. The presence of specific antibodies (Ab) and the level of their titers have been found to be related to the degree of anti-infectious protection. The following characteristics indicate the presence of profound immunological transformation in vaccinees: complement-fixing Ab in titers 1:10 and more and/or immunofluorescent Ab in titers not below 1:180, Ab to protein in the hemagglutination test in titers not below 1:1000. These specific Ab and the level of their titers can be registered after the second injection of live combined typhus vaccine E and the third injection of chemical typhus vaccine. Cases of laboratory infection and their relationship to the character of immunization and the intensity of contacts with R. prowazekii virulent strains are discussed. Attention is drawn to the strict observance of professional safety rules.

During the first period of the independence of Poland, just after the first World War (1919-1921), the fight against ramped epidemics of acute infectious diseases was a main priority. The most important task of the Ministry of Public Health was the organization of the control of infectious diseases, and especially typhus. In 1919, the government named the Central Anti-Typhus Committee. However, the Committee was a collective institution without necessary competences and resources and its efforts to control typhus epidemics have been unsuccessful. At the end of 1919, there was a dramatic spread of typhus especially in the eastern parts of the country, still suffering from the war. In March 1920, the Central Anti-Typhus Committee has been replaced by the Extraordinary Epidemic Commissariat which has been endowed with special, emergency staff and resources. The Commissariat was headed by Prof. Emil Godlewski, who was soon nicknamed "tyhus tsar"; for the most affected regions competent regional commissars were appointed. The legal ground of the Extra ordinary Epidemic Commissariat was the parliament bill on 14th July 1920. This body took over from the Public Health Minister responsibilities for the fight against epidemics. The work of Commissariat had stopped the epidemics and improved epidemical status of Poland which could be seen from 1923 onwards.

The International Committee of the Red Cross investigated an outbreak of fever of unknown origin in Ngozi prison, Burundi, which resulted in a crude mortality rate of 2.61% in January 1996. A definite diagnosis of epidemic typhus caused by Rickettsia prowazekii was established by enzyme-linked immunosorbent assay using specific antigens. Control measures included complete cleansing of the prison with cyfluthrine, shaving and dusting all prisoners with permethrin 0.5% dusting powder, and replacement of all mattresses and clothes. All prisoners and guards received a single dose of doxycyline (100 mg) simultaneously. The crude mortality rate dropped abruptly to 1.27% in February 1996 and remained at or below 0.5% from March onwards. Health authorities and medical agencies working in Burundi need to consider epidemic typhus in the differential diagnosis of fever of unknown origin in order to be able to take appropriate control measures in time.

This paper provides an overview of the development of typhus vaccines between the first and second world wars. It is shown that there was a shift in the classification of the causal Rickettsiae from being classed as bacteria to being conceptualised as a type of virus. This 'paradigm switch' stimulated interest in the possibility of producing an effective medicine.

The article substantiates epidemiological expediency of complex (associated) immunization of servicemen and population against typhoid, typhus and plague in polyetiological zones of these infections, and also in cases of simultaneous proliferation of these diseases. For simultaneous preventive vaccination against these infections a complex immunization scheme was experimentally substantiated and clinically approved. It is based on national commercial vaccines and ensures a simultaneous administration of 2-3 vaccine preparations by hypodermic syringe or jet injection. Typhoid and typhus vaccines are injected under one shoulder-blade, and plague vaccine is injected under another shoulder-blade. This complex vaccine is harmless, moderately reactogenic, develops expressing immunity which have the same protective features as monovaccines alone. This scheme is recommended for use in anti-epidemic practice.

The immunogenic properties and protective activity of basic protein I and tris-soluble antigens isolated from R. prowazekii were analyzed in comparison with those of chemical typhus vaccine on the model of anti-infectious immunity in guinea pigs. The analysis revealed that purified protein I has protective activity for guinea pigs, which is less pronounced in protein I from strain E with weak pathogenicity than protein I from strains EVir and Breinl. The activity and immunogenic properties of tris-soluble antigens, especially antigen I, are comparable with those of chemical typhus vaccines in the parameters under study.