Plague and Pregnancy: Why Special Considerations Are Needed.

Pregnant women are an important at-risk population to consider during public health emergencies. These women, like nonpregnant adults, may be faced with the risk of acquiring life-threatening infections during outbreaks or bioterrorism (BT) events and, in some cases, can experience increased severity of infection and higher morbidity compared with nonpregnant adults. Yersinia pestis, the bacterium that causes plague, is a highly pathogenic organism. There are 4 million births annually in the United States, and thus the unique needs of pregnant women and their infants should be considered in pre-event planning for a plague outbreak or BT event.

Plague Gives Surprises in the Second Decade of the Twenty-First Century.

From 2010 through 2019, the six leading countries by numbers of human plague cases reported to the WHO were, in order from highest to lowest, Madagascar, Congo, Uganda, Peru, Tanzania, and the United States. From these countries, there was a total of 4,547 cases, of whom 786 (17%) died. Top plague events were four outbreaks of primary pneumonic plague in Madagascar that affected 1,936 persons, including index cases, of whom 137 died. One of the outbreaks was caused by a streptomycin-resistant strain of Yersinia pestis. Person-to-person transmission occurred in a taxi, in households with family caregivers, at burial ceremonies and wakes for victims, and at a hospital where cases were treated. Unique clinical presentations in the United States included a dog owner who acquired pneumonic plague from his sick dog, a boy with septicemic plague who developed complications of osteomyelitis and arthritis that required surgery for bone removal and bone grafting, and a prairie dog handler who acquired bubonic plague from a bite by a sick prairie dog. Efficacy of antibiotics in a model of pneumonic plague in African green monkeys for use in bioterrorism revealed the most effective drugs to be gentamicin, ciprofloxacin, and levofloxacin. A recombinant vaccine containing Fraction 1 antigen and V antigen of Y. pestis designed for first responders during a bioterrorism attack and military personnel was tested for safety and immunogenicity but was not licensed for use by the end of the decade.

Progress on plague vaccine development.

Yersinia pestis (YP), the gram-negative plague bacterium, has shaped human history unlike any other pathogen known to mankind. YP (transmitted by the bite of an infected flea) diverged only recently from the related enteric pathogen Yersinia pseudotuberculosis but causes radically different diseases. Three forms of plague exist in humans: bubonic (swollen lymph nodes or bubos), septicemic (spread of YP through the lymphatics or bloodstream from the bubos to other organs), and contagious, pneumonic plague which can be communicated via YP-charged respiratory droplets resulting in person-person transmission and rapid death if left untreated (50-90% mortality). Despite the potential threat of weaponized YP being employed in bioterrorism and YP infections remaining prevalent in endemic regions of the world where rodent populations are high (including the four corner regions of the USA), an efficacious vaccine that confers immunoprotection has yet to be developed. This review article will describe the current vaccine candidates being evaluated in various model systems and provide an overall summary on the progress of this important endeavor.

Chlorine dioxide inactivation of bacterial threat agents.

AIMS: To evaluate the efficacy of chlorine dioxide (ClO(2)) against seven species of bacterial threat (BT) agents in water. METHODS AND RESULTS: Two strains of Bacillus anthracis spores, Yersinia pestis, Francisella tularensis, Burkholderia pseudomallei, Burkholderia mallei and Brucella species were each inoculated into a ClO(2) solution with an initial concentration of 2.0 (spores only) and 0.25 mg l(-1) (all other bacteria) at pH 7 or 8, 5 or 25°C. At 0.25 mg l(-1) in potable water, six species were inactivated by at least three orders of magnitude within 10 min. Bacillus anthracis spores required up to 7 h at 5°C for the same inactivation with 2.0 mg l(-1) ClO(2). CONCLUSIONS: Typical ClO(2) doses used in water treatment facilities would be effective against all bacteria tested except B. anthracis spores that would require up to 7 h with the largest allowable dose of 2 mg l(-1) ClO(2). Other water treatment processes may be required in addition to ClO(2) disinfection for effective spore removal or inactivation. SIGNIFICANCE AND IMPACT OF STUDY: The data obtained from this study provide valuable information for water treatment facilities and public health officials in the event that a potable water supply is contaminated with these BT agents.

Detection of enzootic plague foci in peninsular India.

A continuous serological and bacteriological surveillance in rodents was carried out in peninsular India i.e. Andhra Pradesh, Karnataka and Tamil Nadu to detect the role of different species of rodents in the maintenance of active enzootic plague foci. Live rodents were collected from wild and ruderal/peri-domestic situations by digging and trapping for sera and organ samples. During 1989 to 2007 serological evidence of plague was detected in different species of rodents in peninsular India. Plague antibodies were detected in 243 sera samples in three different rodent species. Sero-positivity (0.042 percent) amongst rodents tested were found in Tatera indica cuvieri (Hardwicke) followed by Rattus rattus and Bandicota bengalensis. Regular plague surveillance work enhanced the possibility of detecting and delimiting plague foci and helped in implementing necessary preventive anti plague measures to prevent the occurrence of human plague.

What's eating you? oriental rat flea (Xenopsylla cheopis).

The oriental rat flea (Xenopsylla cheopis) is an ectoparasite of small mammals and a vector of many diseases for which humans are incidental hosts. This species of flea is most widely known for carrying Yersinia pestis and Rickettsia typhi, the causative agents of the plague and murine typhus, respectively. Public health issues related to X cheopis may increase in the future as global warming expands the geographic area in which the fleas can survive. A bioterrorist attack of plague also remains a threat. Extensive research is ongoing regarding X cheopis and its interaction with the bacteria it transmits to find better ways of reducing related morbidity and mortality. Traditional control measures include extermination of small mammal hosts, insecticide use to eliminate the flea itself, and use of antibiotics to control the associated diseases. The future may include targeted insecticide usage to prevent the continued development of resistance as well as new methods of reducing transmission of flea-borne diseases that could eliminate the need for chemical insecticides all together.

Control measures of a 400-year-old plague epidemic: an example of past efficiency at controlling disease and similarities with current epidemics.

The plague caused by the bacterium Yersinia pestis, provides one of the best historical examples of pandemic infection. It can therefore be considered the first "globalized" disease, thanks also to the crowds that favoured the rebalancing of infectious agents between Europe and the Middle East. In this paper we analyse all the official documents of the time, highlighting the most effective prevention measures implemented in the city of Ferrara during the Italian plague. Historical mortality data for the 1630 Italian plague in northern Italy are first analysed. In contrast to the high rates recorded throughout the area from Milan to Florence, the mortality rate in Ferrara remained normal over the period. From the city's documents it emerged that the authorities, from the 16th century onwards, had already understood that the spread of the contagion could also occur through domestic animals, although rats are never mentioned. The strength of Ferrara's response to the "plague emergency" stems from an efficient and emergency-ready health control system, financed and supported by the "permanent surveillance team of the city and the Pontifical Legation of Ferrara - Azienda Sanitaria Pubblica" even in times of great economic difficulty for the State. Among the various measures that the city of Ferrara adopted to deal with the plague the following should be mentioned: guards at the city gates, lazarettos, safety of doctors, self-isolation and treatment of every suspicious case as if it were a real case of plague, measures to support the poorer classes of the population, veterinary and hygiene standards for the city and for housing, management of Catholic religious functions and the precepts of the Legation of Ferrara, which was under papal control, closure of churches to avoid mass gatherings, and limitations of all kinds of social and economic relations within and outside the population. The broad regimen, laid down in the 16th century, contains extremely modern health rules which are very much in line with those recommended by the WHO and the health authorities of each individual state in the current COVID-19 pandemic, even starting with hand-washing. The fight against epidemics of the past, especially the history of the plague in the 17th century, anticipates very important and valid concepts, and represents a wake-up call for the recent epidemics of emerging pathogens.

Protective immunity against plague.

Plague, an infectious disease that reached catastrophic proportions during three pandemics, continues to be a legitimate public health concern worldwide. Although antibiotic therapy for the causative agent Yersinia pestis is available, pharmaceutical supply limitations, multi-drug resistance from natural selection as well as malicious bioengineering are a reality. Consequently, plague vaccinology is a priority for biodefense research. Development of a multi-subunit vaccine with Fraction 1 and LcrV as protective antigens seems to be receiving the most attention. However, LcrV has been shown to cause immune suppression and Y. pestis mutants lacking F1 expression are thought to be fully virulent in nature and in animal experiments. The LcrV variant, rV10, retains the well documented protective antigenic properties of LcrV but with diminished inhibitory effects on the immune system. More research is required to examine the molecular mechanisms of vaccine protection afforded by surface protein antigens and to decipher the host mechanisms responsible for vaccine success.

[The development of peroxosolvate-based composites and the evaluation of their effectiveness against extremely dangerous infective pathogens].

The article contains the results of the test of PFK-M composition bactericidal activity against a range of extremely dangerous infective pathogens. The preparation proved to be highly effective for the disinfection of surfaces, sanitary and technical equipment, linen, dishes, and medical utensils contaminated by plague, cholera, and anthrax pathogens. The study found that the antimicrobial activity of the preparation increased after heating and lowered when the object to be disinfected was contaminated with protein admixtures. According to the results of the disinfectological expertise, the preparation was recommended for practical application.

Observations on the endemicity of plague in Karatu and Ngorongoro, northern Tanzania.

Commensal and field rodents and wild small carnivores were live-trapped in five villages of Karatu district and one settlement in the Ngorongoro Conservation Area in Ngorongoro district in Tanzania. Blood samples were taken and serologically tested for plague, using the Blocking ELISA technique. Some domestic dogs and cats in the Karatu villages were aseptically bled and similarly tested for plague. Fleas were collected from the examined animals and from randomly selected residential houses. A total of 241 rodents, 1 Crocidura spp, 43 dogs, 12 cats and 4 slender mongooses were involved in the survey. Of the rodents, 14.5% were infested with fleas, which comprised of Xenopsylla brasiliensis (45.8%) and Dinopsyllus lypusus (54.2%), with an overall population density of 0.2 fleas/animal. Thirty one (72.1%) of the dogs were infested with fleas, all of which were Ctenocephalides spp. Thirty five (63.3%) houses were infested with fleas whose population was composed of Ctenocephalides spp, Pulex irritans, Tunga penetrans and Echinophaga gallinacea. Infected rodents were found in all the villages while the infected dog was found at Rhotia-Kati. Nineteen (11%) of the rodents and one (2%) dog harboured specific plague antibodies. It was broadly concluded that sylvatic plague was endemic in Karatu district and Ngorongoro Conservation Area and that outbreaks of the disease can occur in the area any time if and when relevant conditions become favourable. Prompt application of appropriate preventive and control measures and survey for substantiating the status in the Lake Manyara National Park, which is adjacent to some of the infected villages, are recommended.

A decade of plague epidemiology and control in the western Usambara mountains, north-east Tanzania.

Outbreaks of human plague have been occurring in the Western Usambara mountains since 1980, involving many cases and deaths. Epidemiological surveys and control activities were carried out from June 1980 to May 1990. Rodents were trapped live, identified and serologically tested for plague, using the passive haemagglutination and passive haemagglutination inhibition tests. Rodent fleas were collected, processed, identified and counted. House fleas were caught with light traps and similarly treated. People and domestic carnivores were serologically tested for the disease. Various plague control measures were undertaken. A total of 2433 animals, 2254 rodent fleas and 1366 house fleas were collected. Average indices of rodent and house fleas were 0.93 and 5.38 respectively. Rattus rattus and Mastomys natalensis were the most abundant rodent species. Xenopsylla brasiliensis and Dinopsyllus lypusus were their commonest flea ectoparasites while Pulex irritans was the major house flea. Of 2044 rodent, 1880 human and 176 dog sera tested, 5.5%, 0.5% and 6.3% respectively were positive. It was concluded that plague was active in the focus despite the control measures and that common reservoirs and efficient vectors were present. It was suggested that dogs were probably involved in the epidemiology of the disease, that P. irritans was not susceptible to the insecticide used and that the flea was probably involved in murine plague transmission. Bacteriological research on the causative agent to establish the nature of its long persistence in the area and maintenance of a surveillance service are recommended.

Role of immune response in Yersinia pestis infection.

Yersinia pestis (Y. Pestis) is an infamous pathogen causing plague pandemics throughout history and is a selected agent of bioterrorism threatening public health. Y. pestis was first isolated by Alexandre Yersin in 1894 in Hong Kong and in the following years from all continents. Plague is enzootic in different rodents and their fleas in Africa, North and South America, and Asia, including the Middle/Far East and ex-USSR countries. Comprehending the multifaceted interaction between Y. pestis and the host immune system will enable us to design more effective vaccines. Innate immune response and both components (humoral and cellular) of adaptive immune response contribute to host defense against Y. pestis infection, but the bacterium possesses different mechanisms to counteract the immune response. The review aims to analyze the role of immune response versus Yersinia pestis infection and to highlight the various stratagems adopted by Y. pestis to escape the immunological defenses.