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Epidemiology and incidence of plague in the world, 1958-79.

During the period 1958 - 79, 46 937 cases of human plague were recorded in the world, but the general downward tendency of plague incidence remained, remembering that 40 484 human cases were recorded in 1950. The current incidence of plague is an indication of the epidemicity of plague in its natural foci. In general, during the period under consideration, plague manifestations followed the universally recognized laws of the epidemicity of the disease. Anthroponotic bubonic plague-the most epidemic form of plague-was noted rarely and in limited areas. A considerable proportion of human plague cases occurred in southern Viet Nam, where the defoliation carried out over vast areas during the military operations is thought to have been one cause of the high incidence.Despite the general downward trend in plague incidence, 30 countries of the world were affected by the disease. Therefore, continuous epidemiological surveillance for plague remains an urgent task confronting the health authorities of the countries having known or potential natural foci.

Africa↗

Salmonella-based plague vaccines for bioterrorism.

Yersinia pestis, the causative agent of plague, is an emerging threat as a means of bioterrorism. Accordingly, the Working Group on Civilian Biodefense, as well as the Centers for Disease Control and Prevention, has specified Y. pestis as a prime candidate for use in bioterrorism. As the threat of bioterrorism increases, so does the need for an effective vaccine against this potential agent. Experts agree that a stable, non-invasive vaccine would be necessary for the rapid large-scale immunization of a population following a bioterrorism attack. Thus far, live Salmonella-based oral vaccines show the most potential for this purpose. When delivered via a mucosal route, Salmonella-based plague vaccines show the ability to protect against the deadly pneumonic form of plague. Also, mass production, distribution, and administration are easier and less costly for attenuated Salmonella-based plague vaccines than for plague vaccines consisting of purified proteins. Most attenuated Salmonella-based plague vaccines have utilized a plasmid-based expression system to deliver plague antigen(s) to the mucosa. However, these systems are frequently associated with plasmid instability, an increased metabolic burden upon the vaccine strain, and highly undesirable antibiotic resistance genes. The future of Salmonella-based plague vaccines seems to lie in the use of chromosomally encoded plague antigens and the use of in vivo inducible promoters to drive their expression. This method of vaccine development has been proven to greatly increase the retention of foreign genes, and also eliminates the need for antibiotic resistance genes within Salmonella-based vaccines.

Antigens, Bacterial↗

Plague. A clinical review of 27 cases.

We reviewed the medical records of 27 patients with plague seen at the Gallup (NM) Indian Medical Center between 1965 and 1989. Nineteen patients had bubonic plague and eight had septicemic plague. Three patients with septicemic plague and three with bubonic plague died. The patients presented with five different clinical pictures. Ten patients presented with classic signs of plague, five with the appearance of an upper respiratory tract infection, five with a nonspecific febrile syndrome, four with the appearance of a gastrointestinal or urinary tract infection, and three with the appearance of meningitis. Blood cultures were positive in 24 of 25 cases, and bubo aspirate cultures were positive in 10 of 13 cases. All six patients who died were under 30 years old, and all the deaths were related to a failure to treat initially with an antibiotic appropriate for plague. Plague is a treatable disease, but clinicians must have a high index of suspicion and give appropriate antibiotics at the earliest possible time to patients whose presentation suggests plague.

Adolescent↗

Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona.

Plague, primarily a disease of rodents and their infected fleas, is fatal in 50% of infected humans if untreated. In the United States, human cases have been concentrated in the southwest. The most common modes of plague transmission are through flea bites or through contact with infected blood or tissues; however, primary pneumonic plague acquired from cats has become increasingly recognized. We report on the case investigation of a patient, presumably exposed to a plague-infected cat in Colorado, who presented with gastrointestinal symptoms, and subsequently died of primary pneumonic plague. Public health officials should be vigilant for plague activity in rodent populations, veterinarians should suspect feline plague in ill or deceased cats, and physicians should have a high index of suspicion for plague in any person who has traveled to plague enzootic areas.

Adult↗

Plague in a complex of white-tailed prairie dogs and associated small mammals in Wyoming.

Fleas were collected from white-tailed prairie dogs (Cynomys leucurus) and other small mammals trapped on six grids during a field study near Meeteetse (Wyoming, USA) in 1989 and 1990 to investigate the dynamics of plague in this rodent population. Fleas were identified and tested for Yersinia pestis by mouse inoculation. Yersinia pestis-positive fleas were found on prairie dogs and in their burrows. Flea species on prairie dogs changed from spring to late summer. White-tailed prairie dog numbers were significantly lower in the presence of Y. pestis-positive fleas; however, affected populations generally recovered 1 to 2 yr following absence of detectable plague. Grids where recovery occurred had a high proportion of juvenile male prairie dogs. Eighteen flea species were identified on small mammals, six of which were infected with Y. pestis. Some flea species were associated with a particular small mammal species, while others were found on a broad range of host species. Flea species most important in the potential interchange of Y. pestis between associated small mammals and white-tailed prairie dogs were Oropsylla tuberculata cynomuris, Oropsylla idahoensis, and Oropsylla labis. Plague cycled through the white-tailed prairie dog complex in an unpredictable manner. Each summer the complex was a mixture of colonies variously impacted by plague: some were declining, some were unaffected by plague, and others were recovering from plague population declines. These data provide insight into the dynamics of plague in white-tailed prairie dog complexes, but predicting movement of plague is not yet possible and the role of associated mammals in maintenance of plague is not understood.

Animals↗

Clinical and epidemiological observations on an outbreak of plague in Nepal.

In the autumn of 1967, plague broke out among hill people in western Nepal, a country that had not previously reported human plague. Two persons were infected from an active sylvatic focus at a grazing area 5 km from Nawra, the village where the epidemic occurred. The second patient introduced plague into the village where the rest of the cases occurred. Clinical and epidemiological evidence suggests that plague was spread both by the airborne route, resulting in 6 cases of tonsillar plague and 1 case of primary pneumonic plague, as well as by infected fleas, resulting in 17 cases of bubonic plague. Since no evidence of a rodent epizootic was uncovered in the village itself, and because of the distinct clustering of the bubonic cases, human-to-human spread of plague by infected ectoparasite vectors, presumably Pulex irritans, is thought to have occurred.This focus probably represents the most southerly boundary of the central Asian plague area yet identified.

Adolescent↗

Plague: from natural disease to bioterrorism.

Yersinia pestis is the causative agent of plague, an enzootic vectorborne disease usually infecting rodents (rats) and fleas. Humans can become infected after being bitten by fleas that have fed on infected rodents. In humans, the disease usually occurs in the form of bubonic plague. In rare cases, the infection spreads to the lungs via the bloodstream and causes secondary pneumonic plague. Person-to-person transmission has been described for pneumonic plague but is rare in primary bubonic plague. Bubonic plague can usually be treated successfully with antibiotics; however, pneumonic plague develops rapidly and carries a high fatality rate despite immediate treatment with antibiotics. Plague is also recognized as a potential agent of bioterrorism. It has been used, or considered for use, as a biologic weapon on several occasions. It is important for the medical community to be familiar with the epidemiology, diagnosis, and symptoms of plague so it can deliver an appropriate and calm response should the unthinkable happen.

Journal Article↗

Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague.

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.

Animals↗

Three days in October of 1630: detailed examination of mortality during an early modern plague epidemic in Venice.

The epidemiology of medieval and early modern European plague remains highly controversial. It now seems likely that the epidemiology was not uniform throughout either the geographic or temporal boundaries of the plague in Western Europe. The Venetian plague of 1630 was extensively documented; day-by-day records were kept, and each mortality in the city was recorded in a set format. The days 23-25 October 1630, representing a period when mortality was beginning to increase sharply, are examined. In all, 1,163 deaths were recorded. They show a large preponderance of women; a mean age of 28, but a majority of cases clumped between ages 0 and 25 years; and an unequal sex ratio among children. Further, there was an identifiable smallpox epidemic raging simultaneously with plague, and more than one-quarter of all the deaths in this period of high mortality were clearly due to nonplague causes. Deaths due to wounds and associated with violence were prominent in one parish, which suggests that in times of plague the breakdown in the normal machinery of government, in everyday patterns of life, and possibly of mental well being resulted in an even more exaggerated death toll. These factors--violence, accidents, and other epidemics--have never been so definitively tied to a European plague epidemic. In addition, there are hints that plague has a marked proclivity to kill pregnant women--their deaths far outnumber those anticipated--and that plague was very localized at a given moment within Venice itself, even during times of peak mortality.

Female↗

Histopathology of experimental plague in cats.

Formalin-fixed paraffin-embedded archival tissues of seven adult cats of both sexes that died after being experimentally infected with Yersinia pestis were examined light microscopically to characterize the lesions. The cats were exposed in two groups using two routes of infection: ingestion of Y. pestis-infected rodent or a subcutaneous injection of Y. pestis to simulate a flea bite. Immunohistochemistry was performed on tissues from all organ systems from a representative cat from each group to determine the distribution of Y. pestis bacilli during infection. In all seven cats, bubonic plague lesions were seen. The lesions of pneumonic plague were present in two cats. Septicemic plague was confirmed in all seven cats by bacteriologic culture. Aggregations of bacteria were seen in lymphoid tissue in all cats and in lung tissues from the two cats with pneumonic plague. The most consistent histologic finding was necrosuppurative inflammation in the lymph nodes. Invariably, Y. pestis bacteria were present in large numbers at affected sites. Orally infected cats had more numerous lesions in the lymph nodes of the head and neck regions. These experimentally induced cases of feline plague document that cats are unique among carnivores in exhibiting bubonic, pneumonic, and septicemic plague following exposure to Y. pestis. The lesions of the orally infected cats were consistent with those previously described for naturally occurring Y. pestis infections in cats and corroborate the contention that cats most commonly contract plague by eating Y. pestis-infected rodents and not via flea bite. The histopathology of Y. pestis disease in these cats is comparable to that described for human plague.

Animals↗

A plague epizootic in the black-tailed prairie dog (Cynomys ludovicianus).

Plague is the primary cause for the rangewide decline in prairie dog (Cynomys spp.) distribution and abundance, yet our knowledge of plague dynamics in prairie dog populations is limited. Our understanding of the effects of plague on the most widespread species, the black-tailed prairie dog (C. ludovicianus), is particularly weak. During a study on the population biology of black-tailed prairie dogs in Wyoming, USA, plague was detected in a colony under intensive monitoring, providing a unique opportunity to quantify various consequences of plague. The epizootic reduced juvenile abundance by 96% and adult abundance by 95%. Of the survivors, eight of nine adults and one of eight juveniles developed antibodies to Yersinia pestis. Demographic groups appeared equally susceptible to infection, and age structure was unaffected. Survivors occupied three small coteries and exhibited improved body condition, but increased flea infestation compared to a neighboring, uninfected colony. Black-tailed prairie dogs are capable of surviving a plague epizootic and reorganizing into apparently functional coteries. Surviving prairie dogs may be critical in the repopulation of plague-decimated colonies and, ultimately, the evolution of plague resistance.

Animals↗

[Epidemiological data on the plague in Madagascar].

The first case of plague was introduced in Madagascar in 1898 in the east coast by way of boat from India. In 1921, plague reach the highlands and a large epidemic over the next twenty years. Until the beginning of the 80's, only of few case were identified, notified mostly in rural setting. However gradually it has re-emerged as a public health problem. Urban plague is located in the city of Antananarivo (resurgence in 1978 after 28 years of apparent silence) and in Mahajanga port (resurgence in 1991 after 63 years of silence). The reactivation of the Plague National Control Program from 1994 will allow better surveillance. The aim of this analysis is to update the epidemiological data on human plague in Madagascar based on reported cases obtained from the Central Lab of the Pasteur Institute of Madagascar from 1980 to 2001 (16,928 suspected cases of which 3,500 are likely positives or confirmed positives). The Plague season runs from October to March on the central highlands and July to November on the north-western coast. Sex-ratio male/female is 1.3/1, and the age-group of 5 to 25 years is more affected. The case fatality rate was 40% in the beginning of the 1980's, and decreased to 20% by the end of the 1990's. The percentage of case with pulmonary plague decrease from 15% to less than 5%. However, geographical extension is demonstrated: 4 districts in 1980, 30 districts in 1999 and 21 districts in 2001. In 2002, the diffusion of a new rapid test (reagent strip) in the primary health centres (CSB) in 42 endemic districts may help to decrease the morbidity and the letality due to plague and improve its control at the national level.

Adolescent↗

Frequency analysis of the delta32ccr5 HIV resistance allele in a medieval plague mass grave.

The 32 basepair deletion in the gene for the human chemokine receptor CCR5 (delta32ccr5) conferring resistance against HIV-1 infection is present in Caucasian populations. The mutant allele is believed to have originated by a single mutational event in historic times and to have reached its present population frequency of an average 10 % in Europe through selective pressure by a pathogenic agent. Because of their great impact on European populations, the medieval Plague epidemics have been considered as a possible candidate. To test this hypothesis, we studied the delta32ccr5-frequency in 35 individuals from a mass grave containing victims of the 14th century Plague pandemic in Lübeck, Northern Germany, and compared them to the frequency in a control group from the same burial site, dating from the time before the first Plague pandemic. If the delta32ccr5 allele conferred an at least partial resistance against the medieval Plague, its frequency would be expected to be lower in those that died in the pandemic, than it was in the local population before the arrival of the Plague. The CCR5 locus could be typed successfully for 14 Plague victims and for 20 individuals from the medieval control group. We found a delta32ccr5 allelic frequency of 14.2% and 12.5%, respectively. The difference between these figures is not statistically significant. Furthermore, they are comparable to the delta32ccr5 frequency for nowadays Northern Europe. We therefore conclude that the medieval Plague pandemic has not contributed to an increase in the allelic frequency of the mutant delta32ccr5 allele and that, if there has been a positive selection of this allele, it is likely to have occurred before the 14th century and thus before the arrival of the Plague in Europe.

Alleles↗

[Primary characterization of the properties and diagnostic value of the antigenic complex "fraction V" in a plague microbe].

The experimentally obtained antigenic complex isolated by extraction in the gradient surfactants from live and acetone-dried bacteria of the capsule-free vaccine strain EV76 of a plague microbe that had lost its ability to synthesize the diagnostic species-specific capsular antigen F1 was investigated. The antigenic complex fraction V (FV) was obtained after the fifth stage of extraction at a concentration of 1.28% of surfactants and after additional purification. The thermostable FV was found to consist mainly of protein. The protein having a molecular mass of about 43 kD predominates in the fraction. The latter is nontoxic for albino mice and antigenic. It forms a precipitate with commercial antiplague serum antibodies. FV antigenic sensitization of tanned sheep red blood cells gave rise to a diagnostic agent that specifically reacted with an antiplague serum rather than with heterologous sera against enterobacteria. The sera immunized with FV specifically reacted in the JDJFR with all the strains of the pathogen of plague irrespective of the temperature of their cultivation, including "fraction-free", which did not interact with a diagnosticum on F1. The animal sera immunized with capsule-free plague microbial strain reacted only with a FV-erythrocytic diagnosticum and they did not interact with F1 antigen-sensitized red blood cells. The erythrocytic FV diagnosticum was tested in ABNR with 130 typical and atypical plague microbial strains and with 133 strains of heterologous bacteria of different species of the family Enterobacteriaceae. The FV diagnosticum identified all the variants of a plague microbe, while the F1 diagnosticum revealed only its capsular variants. Among the heterologous bacteria, some strains of the closely related pathogen of pseudotuberculosis in those who were in the R form, rather than S form, positively reacted. The use of FV identified 2 groups of hybridomas obtained after immunization of albino mice with the capsule-free variant of a plague microbe. Some hybridomas reacted only with plague bacteria while others did with two above pathogens. The authors substantiate the expediency of using FV, its components, and obtained monoclonal plague pathogen antibodies to improve antiplague diagnosticums with an activity spectrum that exceeds that of the existing commercial F1 antigen-based diagnosticums. They also discuss the lines of further studies.

Animals↗

Use of ELISA to reveal rodent infections in plague surveillance and control programmes.

To assess its potential applications in plague surveillance and control programmes, an enzyme-linked immunosorbent assay (ELISA) that captures the specific Yersinia pestis F1 antigen was used to determine the amounts of this antigen present in samples of blood and spleens from laboratory rats with acute plague, in the buboes of rats with chronic plague, and in tissues from the carcasses of rats that had died from plague. In rats with acute plague, bacteria and F1 antigen were detected in samples of blood 2-4 days after the rats had been subcutaneously inoculated with virulent Y. pestis. Although F1 antigen was not detected in blood samples at the onset of bacteraemia, average antigen levels of 10,240 ng/ml for blood clots and 4829 ng/ml for sera were detected during severe bacteraemia. Immediately after the rats died from acute plague, antigen levels in their spleens of up to 410 micrograms/g of tissue were detected. For rats with chronic plague, ELISA antigen levels of 1600 ng/g to 51 micrograms/g were detected in buboes that contained viable plague bacilli. In samples of spleen, liver, kidney and heart from rat carcasses, F1 antigen was detected up to 20 days after death. In contrast, it was possible to isolate Y. pestis bacilli from these samples only up to 6 days after death.

Animals↗

Comparison of serological and bacteriological methods in the confirmation of plague infections.

A recent, defined outbreak of bubonic plague in a remote area of the central highlands of Viet-Nam provided an opportunity to undertake studies of antibody production during the course of infections with Pasteurella pestis (Yersinia pestis). The haemagglutination (HA) test of Chen & Meyer, modified to a microtechnique, was used in studies of patients with clinical plague, and in studies of unvaccinated, asymptomatic contacts of plague patients.HA antibody was demonstrated in the sera of nearly 45% of the unvaccinated, asymptomatic contacts of plague patients, and a large proportion of these exhibited 4-fold or greater rises in titre during the outbreak. In 6 of the 16 clinical plague cases, the diagnosis could not be confirmed by bacteriological methods; however, 5 of the 6 exhibited HA antibody in sera collected on admission or in second sera collected 9-14 days later or in both. Of the 5 with positive sera, 4 had very mild clinical illnesses (pestis minor). These findings were in sharp contrast to those among the 8 surviving, bacteriologically confirmed cases, most of whom had clinically very severe illnesses. Only 1 of the 8 had demonstrable plague HA antibody in acute and early convalescent sera; however, all of the latter on whom follow-up studies could be obtained exhibited HA antibody in sera collected 1-1(1/2) months later.These findings indicate that natural active immunization with P. pestis was occurring during the outbreak, and further, that developing immunity from earlier subclinical infections may have accounted for amelioration of clinical signs and symptoms, as well as for failure to isolate P. pestis in patients with pestis minor.HA tests may be particularly useful in confirming the diagnosis of plague if employed with sera collected 3-6 weeks after the onset of illness. The HA test would appear also to provide a highly reliable tool in surveys for plague in areas of unknown endemicity.

Follow-Up Studies↗

Observations on the current status of plague endemicity in the western Usambara mountains, north-east Tanzania.

Epidemiological investigations were executed at 6 locations in the western Usambara mountains in north-east Tanzania from November 1980 to May 1982. Rodent, human and dog sera were checked for agglutinating plague antibodies, using the passive haemagglutination test. Fraction I plague antigen was similarly tested for in rodent organ macerates. Bubo aspirates and rodent organ-smears were microscopically examined for plague bacilli. A total of 257 rodents and 191 fleas were collected. Rattus rattus, Praomys natalensis and Arvicanthis niloticus were the commonest rodent species. Flea ectoparasites mostly comprised of Xenopsylla brasiliensis and Dinopsyllus lypusus. Specific plague antibodies were detected in 2.8%, 10% and 2.9% of the rodents examined in November 1980, November 1981 and May 1982 respectively. Similarly, plague antibodies were found in 0.6%, 1.2% and 0.5% of the human sera tested in September 1981, November 1981 and May 1982 respectively. All the dog sera were negative. The results suggested past contact with plague and existence of a persistent plague focus in the area. Health education for villagers, maintenance of a plague surveillance programme and regular seminars for medical and health personnel in the area were recommended in order to prompt early detection, reporting and control of an outbreak.

Animals↗

Peripatetic plague.

Cases of plague continue to occur in various parts of the world, including the western United States, where plague is endemic among the wild rodent population. In 1980, a case of plague acquired in New Mexico and hospitalized in Nebraska illustrated the problem of plague occurring in persons traveling from the state in which they become infected to another state. Nine cases of plague in travelers were identified among the 166 cases of plague reported in the United States from 1950 to 1980. Physicians should be aware of natural plague foci in the western United States and should obtain a travel history from patients with an illness clinically compatible with plague.

Adolescent↗