Epidemic Typhus Research Articles

Inhibitors of Rickettsia prowazekii methionine aminopeptidase 1 identified from the Pandemic Response Box

Methionine aminopeptidase (MetAp) enzymes catalyze the post-translational removal of the initiator methionine residue in newly synthesized proteins, a process that is often essential in the maturation of proteins. Consequently, these enzymes serve as important targets for drug development. Rickettsia prowazekii (Rp) is an obligate coccobacillus and the causative agent of the louse-borne epidemic typhus and despite adequate treatment causes a latent infection. This research aimed to identify potential anti-rickettsial agents by screening 400 compounds from the MMV Pandemic Response Box against RpMetAp1. Overall, 19 compounds were identified that possessed IC50 values from 10 µM to 340 nM. The most potent inhibitor was MMV 1580488 (17), which was observed to have an IC50 of 340 nM. The selected hits serve as chemical leads that can be used for the development of potent inhibitors of the RpMetAp1 enzyme.

The Use of Rabbits Used to Propagate Human Lice for Research.

The globally important human diseases of trench fever, epidemic typhus, and relapsing fever are vectored by the human louse Pediculus humanus humanus. Although these conditions are epidemically quiescent at present, they persist in socially dysfunctional situations of war, deprivation, and crowding. The taxonomically closely related head louse, Pediculus humanus capitis, does not respect economic or social status and is quite common in most countries. The 2 types of lice are now recognized as conspecific ecotypes of a single species. While the body louse has been adapted for propagation in the laboratory by feeding in vivo on live rabbits, a similar animal model has not been developed for the host-specific head louse. Accordingly, research for treatment and control of the head louse has largely been performed by using laboratory-reared body lice. This review describes methods for the propagation of body lice in the laboratory and outlines at least 4 areas of research that require sufficient numbers of aged body louse cohorts produced in rabbits for use in controlled studies: 1) pediculicide development and resistance, 2) immunity and vaccine potential, 3) endosymbiotic bacteria needed by lice for nutrition, and 4) lice as vectors of human disease. The review concludes with a discussion of several ethical issues involved with the standard method of using unsedated rabbits and recommends consideration of providing sedating anesthetics for rabbits used in louse feeding procedures.

Rudolph Virchow's Upper Silesia report: the starting point for his simultaneous engagement with public health and antisemitism.

In 2023 an important anniversary took place. It regards Virchow's report on the Upper Silesia epidemic typhus, which was associated with the death of numerous Polish peasants. It is also the starting point of Virchow's political career and fight against antisemitism, which has reached fearful levels in academia. Antisemitism is not new, but the recrudescence following the October 7th massacre of Jewish and not-Jewish people is appalling and recalls Virchow's vehemence of the past a few decades before the Nazi extermination of the Shoah during the World War II.

Typhus Fever- A Diagnosis Often Missed as A Cause of Fever.

Background: In tropical countries epidemic and endemic typhus are sometimes missdiagnosed as typhoid fever. Typhus infection is emerging in the subcontinent and clinically presents as nonspecific febrile illness. So high index of clinical suspicion is essential and the objective of the study was to detect typhus infection as a cause of febrile illness. Materials &Method: This is a prospective observational study done from January to December 2019. A total 50 patients of different age groups were taken randomly who were suffering from fever for more than 7 days. All relevant investigations including CBC, Dengue serological test, Widal test, urine routine examination and C/S, blood C/S, chest x-ray were done. Patients not responding to conventional antibiotic therapy and having persistent fever were further investigated for typhus fever with Weil-Felix test. Results: Out of 50 patients 35 were male; age range was 2 to 12 years. Mean duration of fever was 10 days. Blood for CBC showed nonspecific findings, Blood culture and urine for c/s were negative for bacterial growth, dengue serological tests were negative, chest x-ray were normal (except 2 patients had pneumonia). Weil-Felix tests were positive in all cases. 12 cases were positive for both Widal test and Weil-Felix test and in 8 cases blood c/s were also positive with Weil-Felix test. Treatment changed to Doxycycline or Azithromycin in cases of typhus fever. Conclusion: Typhus fever should be taken into account in the management of febrile illness who were admitted without a confirmed cause of fever. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 54-57

Development of a Technique Using Artificial Membrane for In Vitro Rearing of Body Lice Pediculus humanus humanus.

Human lice are the only hematophagous ectoparasites specific to human hosts. They transmit epidemic typhus, trench fever and relapsing fever, diseases which have already caused millions of deaths worldwide. In order to further investigate lice vectorial capacities, laboratory-controlled live lice colonies are essential. Previously developed lice-rearing methods significantly advanced research on louse-borne diseases and louse biology. In this study, we aimed to develop a rearing technique for the Orlando (Or) strain of body lice on an artificial membrane. We tested two systems, namely the Hemotek feeding system and a Petri dish with the lice being fed through a Parafilm membrane. Lice longevity and development were drastically affected by the blood anticoagulant. Additionally, heparinised human blood on a Petri dish was the best candidate when compared to the control group (reared on a rabbit). Therefore, this strategy was applied to 500 lice. Development into adulthood was recorded after 21 days (17 days for the rabbits), and 52 eggs were deposited (240 for the rabbits). In this study, we were able to maintain one generation of body lice on an artificial membrane with comparable feeding and longevity rates to those fed on live rabbits. However, lice fecundity decreased on the artificial membrane. In vitro lice-rearing experiments will enable pathogen infection assays and pesticide bioassays to be carried out in accordance with animal welfare requirements.

Examining trends in epidemic typhus using historical texts.

Although associated with conflict, epidemic typhus was endemic across Europe into the modem period. The extent of the problem it caused is uncertain as record keeping in the most affected socioeconomic groups was rare. Google Ngram Viewer details the frequency of word usage in written language over time. The objective was to examine whether use of the word typhus reflected potential patterns in epidemic typhus. The frequency of the word 'typhus' was used in British English was studied between 1800 and 2019 and trends were examined. Clear differences in word usage were apparent; use increased throughout the 19 th century corresponding to increasing industrialization. Peaks coinciding with World Wars 1 and 2 were apparent. Strong correlations with the words "conflict", "warfare" and "industry" were seen. Mean shifts corresponded to public health legislation in the UK and the introduction of antibiotics. This study illustrates how examination of word usage can illuminate aspects of disease occurrence where official data sources are lacking.

Reviewing the pages of the first issues of «Perm medical journal»: 100th anniversary of this authoritative russian scientific edition

In 2023, we celebrate a historical date – the 100th anniversary of publishing the first issue of “Perm Medical Journal”. The first editor-in-chief was an outstanding doctor, the founder of the first surgical school, Professor V.N. Parin. The content of the first eight volumes of the journal issued from 1923 to 1930 is analyzed in the article. The first paper of the first issue of a journal was devoted to epidemic typhus and relapsing fever. The papers of great scientists, professors such as A.V. Pshenichnov, P.I. Pichugin, A.S. Lebedev, P.I. Chistyakov, V.P. Pervushin and others impress by profundity of thought. Great attention in the journal was paid to the questions of surgery and urology; these papers constituted 52% of the content of the first eight volumes. Analysis of the works belonging to V.N. Parin, D.P. Kuznetsky, V.P. Shipitsyn, B.Ya. Strelkov, A.A. Vechtomov and other authors, which were devoted to diagnostics, treatment and prevention of gastric ulcer, ventral hernias, tumors of different organs, inflammatory surgical diseases, vascular, urinary, urethral and genital injuries, rhinoplasty, show that these publications aroused interest among Russian and foreign scientists and physicians and significantly influenced a progress of medical science and practical health care.

Typhus Epidemic in the British Army on the Iberian Peninsula in the Winter of 1808/1809

Typhus Epidemic in the British Army on the Iberian Peninsula in the Winter of 1808/1809

Human rickettsial infections in India - A review.

Rickettsial infections are emerging and/or re-emerging disease that poses a serious global threat to humans and animals. Transmission to humans and animals is through the bite of the ectoparasites including ticks, fleas and chigger mites. Most of the rickettsial diseases are endemic in India, but underdiagnosed. This review is aimed at analyzing the prevalence of rickettsiosis in India and the advancement of rickettsial diagnosis. We have conducted a systematic review on the prevalence of rickettsial disease in India ranging from 1.3% to 46.6% for spotted fever, 2.4% to 77.8% for scrub typhus and 1% to 46.4% for Q fever, based on the literature published with the evidence of isolation, serological, and molecular diagnostics. Search engines Medline/PubMed, Science Direct, ProQuest, and EBSCO were used to retrieve the articles from electronic databases by using appropriate keywords to track the emergence of these rickettsial diseases in India for the period of 1865 to till date. We retrieved 153 published rickettsial articles on hospital-based studies from India that were purely made on the basis of prevalence and the laboratory parameters viz., Weil-Felix test (WF) and Rapid Immunochromatographic tests (RICT) with reference to the gold standard IFA and ELISA. More epidemiological studies are required for epidemic typhus to know the exact prevalence status of this louse-borne rickettsiosis in India. Currently, there is no confirmed specific inflammatory marker for rickettsial diseases. Moreover, serological cross-reactivity is an important aspect, and it should be investigated in endemic areas, there is also a need to include molecular diagnostic techniques for further confirmation in healthcare settings.

Associations of meteorological factors and dynamics of scrub typhus incidence in South Korea: A nationwide time-series study

Scrub typhus, also known as Tsutsugamushi disease, is a climate-sensitive vector-borne disease that poses a growing public health threat. However, studies on the association between scrub typhus epidemics and meteorological factors in South Korea need to be complemented. Therefore, we aimed to analyze the association among ambient temperature, precipitation, and the incidence of scrub typhus in South Korea. First, we obtained data on the weekly number of scrub typhus cases and concurrent meteorological variables at the city-county level (Si-Gun) in South Korea between 2001 and 2019. Subsequently, a two-stage meta-regression analysis was conducted. In the first stage, we conducted time-series regression analyses using a distributed lag nonlinear model (DLNM) to investigate the association between temperature, precipitation, and scrub typhus incidence at each location. In the second stage, we employed a multivariate meta-regression model to combine the association estimates from all municipalities, considering regional indicators, such as mite species distribution, Normalized Difference Vegetation Index (NDVI), and urban-rural classification. Weekly mean temperature and weekly total precipitation exhibited a reversed U-shaped nonlinear association with the incidence of scrub typhus. The overall cumulative association with scrub typhus incidence peaked at 18.7 C° (with RRs of 9.73, 95% CI: 5.54–17.10) of ambient temperature (reference 9.7 C°) and 162.0 mm (with RRs of 1.87, 95% CI: 1.02–3.83) of precipitation (reference 2.8 mm), respectively. These findings suggest that meteorological factors contribute to scrub typhus epidemics by interacting with vectors, reservoir hosts, and human behaviors. This information serves as a reference for future public health policies and epidemiological research aimed at controlling scrub typhus infections.

Analysis of Prevention, Detection, and Response Measures of Major Infectious Diseases by Modern Chinese Seaport Quarantine Institutions: A Case Study of Modern Tianjin Seaport Quarantine

During the late Qing Dynasty, Tianjin Customs gradually established the seaport quarantine system to prevent the spread of epidemics from Japan, Hong Kong, and the Northeast. The major infectious diseases inspected by the quarantine institution of Tianjin Port include cholera, plague, smallpox, typhus and yellow fever, of which cholera is the most frequent and influential infectious disease in modern Tianjin, followed by plague and smallpox, and no large-scale epidemics of typhus and yellow fever have been found.In the process of preventing the spreading of foreign infectious diseases, the quarantine institution of Tianjin Port has gradually developing. A set of business system has been established, which is based on ship inspection and takes preventive injection, rat flea research and disease diagnosis and treatment as the core.In conclusion,the seaport quarantine institutions in Tianjin played an active role in the prevention, detection, and response to major infectious diseases ,opened up a precedent for Chinese people to independently handle border health quarantine.Its historical practice and quarantine mode are a window for understanding the development history of quarantine infectious diseases in modern China, which has very important reference value.

The history of louse-borne typhus and geomedizine

The experience of World War I made popular the concept of medical geography (geomedicine in English, geomedizine in German), which became part of Nazism's philosophy of national welfare, safety, and solidarity. The Nazis used it to create propaganda to show some groups as rats, vermin, and Untermenschen (subhumans). In this way, more than 10 million people were killed under the Nazi regime: 6 million Jews, plus more than 5 million Gypsies, Jehovah's Witnesses, and other individuals who were not part of the German theory of “master race.” The Germans’ fear of typhus that spread in the Wehrmacht was so immense that during the occupation, Polish doctors used this phobia to organize a resistance movement. Contemporarily, the scope of geographic medicine encompasses the following research areas: spatial differentiation of disease incidents and the process of disease diffusion, geographic inequalities in the population's health level, and morbidity determinants among the inhabitants of developing countries. In the first half of the 19th century, it played an essential role in the activities aimed against epidemics of infectious diseases, including louse-borne typhus (epidemic typhus), cholera, and typhoid, linking these diseases to cultural determinants. Under the influence of this idea, the concept of doctor-hygienist emerged, and social medicine began to evolve.

Domestic researchers who have made important contributions to the study of digestive system diseases: images in art. Maks Moiseyevich Gubergrits

A few main directions can be distinguished in the scientific and practical activities of M. M. Gubergrits. Even his first studies contributed to the history of the development of domestic cardiology. He continued the work started by V. P. Obraztsov on the III normal heart sound, studied changes in heart tones and the formation of a gallop rhythm, the rhythm of a neurasthenic quail, was one of the first to evaluate the clinical significance of the electrocardiographic technique, and tried to use it for better understanding the effect of certain drugs on the heart. He described disorders of the cardiovascular system in severe infectious diseases (epidemic typhus, relapsing fever, and typhoid fever) and thrombosis of the splenic vein. An important part of the scientific activity of M. M. Gubergrits was the pain problem. An outstanding humanist scientist could not ignore this human suffering from various diseases. He was interested not only in the origin of pain in diseases of the heart, liver, and kidneys but also in pain as a general problem of physiology and pathology. However, he most clearly revealed himself as a talented clinician in gastroenterology by constantly combining thoughtful observation at the patient’s bedside with clinical and physiological experimentation. Back in 1929, in his work on the mechanism of gastric secretion, he established the effect of mechanical irritation of the gastric mucosa on the secretion of gastric juice. He described a unique palpatory symptom of a bigastric stomach (changes in the position of the lower border of the stomach, re‑determined by splashing noise). He had a keen interest in peptic ulcer disease. His studies on pancreatic physiology and pathology have retained their value to the present day: data on excretory function, the adaptability of exocrine function to different diets, the possibility of a partial violation of this function (dyspancreatism), as well as the organ’s functional study technique developed in his clinic. M. M. Gubergrits described the pain zone in the pathology of the head and body of the pancreas. In addition, he described concomitant diseases of the liver and pancreas and the liver’s involvement in the pathological process in gastric, duodenal, and large intestinal diseases. The studies by M. M. Gubergrits on the clinical picture of pancreatic diseases played a significant role in the further research. To a large extent, his statements on the diagnosis of pancreatitis have retained their significance. He emphasized the importance of such symptoms as pathological hunger, thirst, polyuria, weight loss, pain in the epigastric area, sometimes jaundice, diarrhea with creatorrhea and steatorrhea, and changes in the blood and urine.

Integrating core subtractive proteomics and reverse vaccinology for multi-epitope vaccine design against Rickettsia prowazekii endemic typhus.

Rickettsia prowazekii is an intracellular, obligate, gram-negative coccobacillus responsible for epidemic typhus. Usually, the infected body louse or its excrement when rubbed into the skin abrasions transmits the disease. The infection withR. prowazekiicauses the highest death rate (> 20% without antibiotic treatment and now 1-7%), followed by epidemic typhus, which often manifests in unsanitary conditions (up to 15-30%). Conventionally, vaccine design has required pathogen growth and both assays (in vivo and in vitro), which are costly and time-consuming. However, advancements in bioinformatics and computational biology have accelerated the development of effective vaccine designs, reducing the need for traditional, time-consuming laboratory experiments. Subtractive genomics and reverse vaccinology have become prominent computational methods for vaccine model construction. Therefore, the RefSeq sequence of Rickettsia prowazekii (strain Madrid E) (Proteome ID: UP000002480) was subjected to subtractive genomic analysis, including factors such as non-similarity to host proteome, essentiality, subcellular localization, antigenicity, non-allergenicity, and stability. Based on these parameters, the vaccine design process selected specific proteins such as outer membrane protein R (O05971_RICPR PETR; OmpR). Eventually, the OmpR was subjected to a reverse vaccinology approach that included molecular docking, immunological simulation, and the discovery of B-cell epitopes and MHC-I and MHC-II epitopes. Consequently, a chimeric or multi-epitope-based vaccine was proposed by selecting the V11 vaccine and its 3D structure modeling along with molecular docking against TLR and HLA protein, in silico simulation, and vector designing. The obtained results from this investigation resulted in a new perception of inhibitory ways against Rickettsia prowazekii by instigating novel immunogenic targets. To further assess the efficacy and protective ability of the newly designed V11 vaccine against Rickettsia prowazekii infections, additional evaluation such as in vitro or in vivo immunoassays is recommended.

Historical epidemics of scrub typhus in Queensland and Papua New Guinea.

Undifferentiated febrile diseases (e.g., Mossman fever) from northern Queensland were eventually partially attributed to mite-transmitted rickettsial infections known as scrub typhus or tsutsugamushi fever. Scrub typhus became a major medical threat to military operations in Papua New Guinea during the Second World War and killed more Australian soldiers than malaria in the pre-antibiotic era. Further investigations showed scrub typhus to be an occupational disease of rural workers in north Queensland especially around Cairns and Innisfail. Occasional small epidemics of scrub typhus still occur during military exercises in Queensland, but as scrub typhus is not a reportable disease, its presence in the civilian community is largely unknown. Increased use of serological testing in patients with fever and rash illnesses after exposure in northern Queensland is likely to show that scrub typhus is a modern infection that remains treatable with antibiotics once it is identified.

Bektaşi Mücahit Alayı (Mücâhidîn-i Bektâşiyye)

Birinci Dünya Savaşı sürecinde 1915 yılı, Osmanlı açısından oldukça zorlu şartlar altında bir mücadeleyi gerektirmişti. 1915 kışı oldukça ağır geçmiş, üstelik tifüs, tifo ve dizanteri salgınından dolayı 3. Ordu oldukça güç duruma düşmüştü. Mücadeleler, Kars ve Van çevresinde yoğunlaşmış, bu sırada da Ermeni isyanları baş göstermişti. Bu olumsuz gelişmelerin devamında Ruslar, Erzurum merkezine doğru ilerleme fırsatını bulmuşlardı. Birinci Dünya Savaşı döneminde Mevlevi Mücahid Alayı gibi mücahid birlikleri oluşturularak farklı cephelerde destek sağlanıyordu. Bu minvalde Ahmed Cemaleddin Çelebi önderliğinde 1915 Nisan ayı civarı Bektaşi Mücahid Alayı oluşturulmaya başlanmış, 1915 yılı sonlarında Erzurum cephesine yönlendirilmiş, Erzurum cephesinde görev alması sağlanmıştı. Bektaşi Mücahid Alayı, 1916’nın Ocak ayı ortalarından Şubat ayı ortalarına kadar, yani yaklaşık 1 ay gibi kısa bir süre boyunca fiziksel anlamda mücadele içinde yer alır. 9. ve 11. Kolordu’nun düştüğü zor durumdan kurtarılmasında başarı sağlamışlarsa da yetersiz askeri eğitim ve yoğun çarpışmaların olduğu dönemdeki çetin kış şartlarında kısmi destek sağlayan bu alay, kısa bir süre sonra cephe gerisine kaydırılmış ve ardından lağvedilmiştir. Anahtar Kelimeler: Birinci Dünya Savaşı, Erzurum Cephesi, Bektaşi Mücahit Alayı, Mücâhidîn-i Bektâşiyye, Çelebi Cemaleddin Efendi, Sıtkı Baba, Balabanlı Gül Ağa.

Nanoparticles: A Potential and Effective Method to Control Insect-Borne Diseases.

Insects act as vectors to carry a wide range of bacteria and viruses that can cause multiple vector-borne diseases in humans. Diseases such as dengue fever, epidemic encephalitis B, and epidemic typhus, which pose serious risks to humans, can be transmitted by insects. Due to the absence of effective vaccines for most arbovirus, insect control was the main strategy for vector-borne diseases control. However, the rise of drug resistance in the vectors brings a great challenge to the prevention and control of vector-borne diseases. Therefore, finding an eco-friendly method for vector control is essential to combat vector-borne diseases. Nanomaterials with the ability to resist insects and deliver drugs offer new opportunities to increase agent efficacy compared with traditional agents, and the application of nanoagents has expanded the field of vector-borne disease control. Up to now, the reviews of nanomaterials mainly focus on biomedicines, and the control of insect-borne diseases has always been a neglected field. In this study, we analyzed 425 works of the literature about different nanoparticles applied on vectors in PubMed around keywords, such as"nanoparticles against insect," "NPs against insect," and "metal nanoparticles against insect." Through these articles, we focus on the application and development of nanoparticles (NPs) for vector control, discussing the lethal mechanism of NPs to vectors, which can explore the prospect of applying nanotechnology in the prevention and control of vectors.

Novel inhibitors of Rickettsia prowazekii methionine aminopeptidase from the Malaria Box

Methionine aminopeptidases (MetAp) are dinuclear metalloenzymes found in both prokaryotes and eukaryotes that catalyze the hydrolysis of the N-terminal methionine residue from nascent proteins, an important post-translational modification, which makes it an attractive target for drug discovery. Rickettsia prowazekii (Rp) is an obligate pathogen and causative agent of epidemic typhus and typhus fever. In our ongoing search for anti-rickettsial agents we screened 400 compounds from the Malaria Box for inhibition of RpMetAp1 and discovered 12 compounds that inhibited the enzyme with IC50 values ranging from 800 nM to 22 μM. These inhibitors are from eleven different chemical series and represent leads that can be used to discover more potent and efficacious anti-rickettsial agents.

Urban Crisis and Epidemic Typhus in Madrid at the Beginning of the Twentieth Century

Summary During the nineteenth century, epidemic typhus was one of the main public health problems resulting from industrialisation and urbanisation processes in Europe. It became an illness intricately linked to poverty, famine, the labour crisis and residential overcrowding. In Spain, it reached a significant peak in the first decade of the twentieth century, and Madrid was its uncontested epicentre. Between 1903 and 1910, the Spanish capital was hit by two waves of epidemic typhus. Their causes were associated with the fault lines drawn in the city’s structure during the previous decades. The origins of both epidemics, the resources deployed to control them and their socio-spatial spread can be linked to the gaps in urban policies in Madrid in comparison with the transformations that the city underwent after the middle of the nineteenth century.

Immunoinformatics design of multi-epitope vaccine using surface cell antigen OmpB and heat shock protein GroEL against rickettsioses

Rickettsioses, caused by intracellular bacteria of the rickettsia genus, pose a global health threat, particularly affecting underserved communities. Delays in diagnosis and treatment due to limited healthcare access result in severe cases and fatalities. To address this, a multi-epitope vaccine targeting OmpB and GroEL proteins in epidemic and endemic typhus rickettsia was developed using immunoinformatics techniques. T-cell and B-cell epitopes were predicted from OmpB and GroEL proteins, resulting in 5 CTL, 4 HTL, and 4 B-cell epitopes. These epitopes were linked appropriately and combined with suitable adjuvants to construct the vaccine. The vaccine's physicochemical properties and tertiary structure were validated within acceptable ranges. Molecular docking analysis demonstrated favorable binding with TLR4 receptors and MHC molecules, further confirmed by molecular dynamics simulation. Immune simulation analysis predicted T-cell, IFN, and IL-2 responses upon vaccine administration. The vaccine sequence was then optimized and cloned into a plasmid vector pET-23a(+) at the Hind and AlwNI restriction sites. In this in silico experiment, a multi-epitope vaccine derived from OmpB and GroEL proteins is presented, the first validation steps of which have been completed. Subject to successful in vivo studies, this vaccine could prove to be a promising therapeutic strategy against rickettsiosis and address a critical public health challenge.