104. Plague Meningitis - A Systematic Review of Published Cases, Antimicrobial Treatment, and Outcomes

Background Plague meningitis is a rare but serious manifestation of infection with the bacterium Yersinia pestis. The risk factors, clinical evolution, and optimal treatment strategies of plague meningitis are not well understood, and data is limited to sporadic case reports. To advance knowledge of this condition and support clinical practice recommendations, we conducted a systematic review of published cases of plague meningitis. Methods We reviewed PubMed Central, Medline, Embase, and other databases for publications on plague meningitis in any language. Articles that contained reports of patients with plague meningitis plus information on patient outcome were included. Results Among 1,090 articles identified in our search, we found 54 articles describing 83 cases eligible for inclusion. Cases occurred between 1898 and 2015; mean age of patients was 20.5 years (range 6 wks - 64 yrs) and 65% were male. Most patients lived in the United States (23%), Argentina (18%), Vietnam (12%), or China (12%). Four patients (5%) had primary plague meningitis. More than half (59%) of patients developed meningitis secondary to primary bubonic plague; the remainder developed meningitis secondary to other or unknown forms of plague. Of patients with a bubo, 51% had an axillary bubo. The most common symptoms were fever (66%), nuchal rigidity (43%), and headache (35%); 23 patients had focal neurologic deficits such as cranial nerve abnormality. Case fatality rate was 96% (n=23/24) for patients who did not receive antimicrobial treatment and 42% (n=25/59) for patients treated with antimicrobials. Case fatality rate by antimicrobial received, including patients who received multiple antimicrobial classes, was 50% for sulfonamides (n= 38), 50% for fluoroquinolones (n=2), 19% for aminoglycosides (n=21), 11% for chloramphenicol (n=19), and 0% for tetracyclines (n=14). Conclusion Plague meningitis has a high fatality rate, but antimicrobial treatment can improve patient outcomes. Having an axillary bubo may be a risk factor for developing plague meningitis – in contrast to our findings, a recent analysis found that only 24% of patients with bubonic plague had buboes in the axillary region. Additional research would be helpful to investigate this association further. Disclosures All Authors: No reported disclosures

Prejudice in Past Pandemics

Accompanying the spread of SARS-CoV-2 (COVID-19) across the globe was a proliferation in anti-Asian hate crimes and political rhetoric. These discriminatory actions mirrored the prejudice exhibited towards other groups in past pandemics, such as Jewish populations in Europe during the Black Death between 1346 and 1353. This study aimed to determine similar patterns relating to and underlying the prejudice seen in past pandemics, focusing on three categories: hate crimes, political rhetoric, and religiosity. Prejudice against Jewish people during the Bubonic plague, Immigrants in America during the 1918 Flu, and Asian Americans during COVID-19 were investigated in this study because of the historical record of existing prejudice against these groups before the start of the pandemics. Overall, this study found that there was no general pattern of hate crimes during past pandemics without accompanying political rhetoric. In addition, there was no general pattern in religiosity in the pandemics studied, suggesting that the prejudice was not fueled by religious motivations. Given the small selection of pandemics analyzed in this study, further analysis with more pandemics could present more robust conclusions.

The Vase of Ambrosia

This is an introduction to and translation of the Vase of the Deathless Ones’ Ambrosia Tantra. The Vase of Ambrosia presents itself as a treasure text that was taught by Padmasambhava in eighth-century Tibet and finally revealed five hundred years later. In the opening chapter, Padmasambhava explains that a devastating epidemic disease will spread to Tibet and ultimately kill three out of every four people in the world. Despite this dire prognosis, he also explains the medical and spiritual causes of the disease, such that the physicians and ritual specialists of the future will be able to treat their patients and protect themselves. Taken together, the Vase of Ambrosia is a scriptural cycle that represents the Tibetan experiences of and responses to the bubonic plague in the thirteenth century, and which continues to inspire Buddhist approaches to epidemic disease even today.

CsrA Enhances Cyclic-di-GMP Biosynthesis and Yersinia pestis Biofilm Blockage of the Flea Foregut by Alleviating Hfq-Dependent Repression of the hmsT mRNA

Yersinia pestis , the bacterial agent of bubonic plague, produces a c-di-GMP-dependent biofilm-mediated blockage of the flea vector foregut to facilitate its transmission by flea bite. However, the intricate molecular regulatory processes that underlie c-di-GMP-dependent biofilm formation and, thus, biofilm-mediated blockage in response to the nutritional environment of the flea are largely undefined.

Keragaman, Dominasi Tikus Silvatik, Kepadatan Pinjal dan Kewaspadaan Pes di Daerah Fokus Pes di Kecamatan Cepogo Kabupaten Boyolali

One of rodent borne diseases that exist in Indonesia is pes with flea as vector and rat as reservoir. The objective of this research were to find out the diversity, dominance of rats, the density of rat and fleas as monitoring efforts for vigilance of plague transmission. The study was conducted in September-October 2016 in Wonodoyo and Kembang Kuning village, Cepogo Sub District of Boyolali District. The research is descriptive with cross sectional approach. Samples collection were conducted by rats survey used single live trap in the silvatic area. The results showed that rats trap success in Wonodoyo village was 3.8% (38 rats) and 1,1% (11 rats) in Kembang Kuning village. Four kind of silvatic rats were Rattus exulans, R. tiomanicus, Niviventer fulvescens and Maxomys surifer. Most of the rats caught (73.68%) in Wonodoyo Village were infested with fleas, while in Kembang Kuning Village it was 27.27%. All of fleas identified as Stivalius cognatus. The specific and general flea index value of S. cognatus in Wonodoyo Village is 2.66; Kembang Kuning Village is 0.45. Early vigilance is very important to do to prevent the transmission of bubonic plague originating from silvatic rats in Cepogo District, particularly in Wonodoyo Village.

Did the Justinianic Plague Truly Reach Frankish Europe around 543 AD?

This article focuses on the episodes of bubonic plague recorded around 543 AD in Frankish Europe which on re-reading appear doubtful. Beginning in 541 and for two centuries, the Justinianic plague ravaged the Mediterranean area over several successive waves. The first mentions concern Egypt; the plague then spreads northward to Constantinople and almost concomitantly or shortly afterward moves westward until it reaches Western Europe. For this last region, the main source is Bishop Gregory of Tours, who in both his historical and his hagiographic writings, provides numerous data on the first outbreaks that raged in Frankish Europe, episodes to which he was a contemporary (even if for the first, he was still in early childhood). According to Gregory, around 543, bubonic plague ravaged several areas under Frankish rule. However, among others, intertextual, contextualized and chronological analyses strongly suggest that these events were in fact fictional. Gregory seems to have wanted to balance during epidemics of plague, the behavior of two bishops of Clermont that were totally opposed. In the episode of 571, when plague struck the episcopal city, the unworthy Bishop Cautinus, to escape disease, had fled the city in cowardice. In the other episode, through the intercession of Gregory's paternal uncle, the virtuous Gallus, the immediate predecessor of Cautinus and that of a saint specific of the paternal branch, the city, including the diocese, was spared from the plague. Other references to similar events in which, through saints, the plague is driven out, or territories are protected from it are also dated arbitrarily from this period. Furthermore, unlike the episode of 571, the plague of 543 is never considered a punishment for sin; moreover, no miraculous healing of plague patients is recorded. Contemporary texts from other authors of Frankish Europe, although they are rare, do not mention any epidemic around 543 - especially the Vita of Caesarius of Arles, written shortly after the death of this bishop (from 542 to 547-9) by several hagiographers - while two of Gregory’s texts, which are repeated almost verbatim, indicate that the province of Arles was the region most affected. This fact underscores the decisive contribution that hagiographic texts can make in the analysis of facts considered to be historical. Finally, the dramatic deteriorations in the health situation described in Gregory’s reports could have a background of truth and be the consequence of the climatic cooling observed from 536, likely due to volcanic eruptions, but did not involve the bubonic plague.

PsaF is a membrane-localized pH sensor that regulates psaA expression in Y. pestis

The Yersinia pestis pH 6 antigen (PsaA) forms fimbria-like structures and is required for full virulence during bubonic plague. High temperature and low pH regulate PsaA production and while recent work has uncovered the molecular aspects of temperature control, the mechanisms underlying the unusual regulation by pH are poorly understood. Using defined growth conditions, we recently showed that high levels of PsaE and PsaF (two regulatory proteins required for expression of psaA ) are present at mildly acidic pH, but these levels are greatly reduced at neutral pH, resulting in low psaA expression. In prior work, the use of translational reporters suggested that pH had no impact on translation of psaE and psaF , but rather affected protein stability of PsaE and/or PsaF. Here, we investigated the pH-dependent post-translational mechanisms predicted to regulate PsaE and PsaF stability. Using antibodies that recognize the endogenous proteins, we showed that the amount of PsaE and PsaF is defined by a distinct pH threshold. Analysis of histidine residues in the periplasmic domain of PsaF suggested it functions as a pH-sensor and indicated that the presence of PsaF is important for PsaE stability. At neutral pH, when PsaF is absent, PsaE appears to be targeted for proteolytic degradation by regulated intramembrane proteolysis. Together, our work shows that Y. pestis utilizes PsaF as a pH sensor to control psaA expression by enhancing the stability of PsaE, an essential psaA regulatory protein. IMPORTANCE Yersinia pestis is a bacterial pathogen that causes bubonic plague in humans. As Y. pestis cycles between fleas and mammals, it senses the environment within each host to appropriately control gene expression. PsaA is a protein that forms fimbria-like structures and is required for virulence. High temperature and low pH together stimulate psaA transcription by increasing the levels of two essential integral membrane regulators, PsaE and PsaF. Histidine residues in the PsaF periplasmic domain enable it to function as a pH-sensor. In the absence of PsaF, PsaE (a DNA binding protein) appears to be targeted for proteolytic degradation, thus preventing expression of psaA . This work offers insight into mechanisms that bacteria use to sense pH and control virulence gene expression.

Calamitas terrena ou Poena divina : Une approche éliadienne de la peste dans le roman Sortez vos morts de Bruno Leydet

"Calamitas terrena or Poena divina: An Eliadian Approach to the Plague in the Novel Sortez vos morts by Bruno Leydet. The article proposes a dichotomous analysis of the outbreak of the Black Plague in Marseille (1720), described by French writer Bruno Leydet in the novel Sortez vos morts, which appeared in 2005. According to the grid established by Mircea Eliade, the analysis is built on two levels: the sacred and the profane. The religious as well as the modern perception of the disease and the use of a relevant lexis allow the bubonic plague to transgress the historical space, passing into the literary one. The plague epidemic in southern France is, in our view, not only a manifestation of the divine will to punish the sinful souls of the dead, but also the incarnation of greed and vicious side of the human being. Keywords: plague, Bruno Leydet, Mircea Eliade, holy, unholy "