Prophylaxis Of Plague Research Articles

Susceptibilities of Yersinia pestis to Twelve Antimicrobial Agents in China

Objective: Streptomycin is the preferred choice for therapy of plague in China and other countries. However, Yersinia pestis exhibiting plasmid-mediated antimicrobial agent–resistant traits had been reported in Madagascar. In this study, we evaluated the susceptibility of traditional or newer antimicrobial agents used for treatment and/or prophylaxis of plague. Methods: Following Clinical and Laboratory Standards Institute (CLSI) recommendations, the susceptibility of 12 antimicrobial agents was evaluated by the agar microdilution method in 1,012 strains of Y. pestis isolated from 1943 to 2017 in 12 natural plague foci in China. Results: One clinical Y. pestis isolate (S19960127) was found to be highly resistant to streptomycin, while the strain was still sensitive to other 11 antibiotics, that is, ciprofloxacin, ofloxacin, kanamycin, chloramphenicol, ampicillin, ceftriaxone, cefuroxime, trimethoprim-sulfamethoxazole, tetracycline, spectinomycin and moxifloxacin. The remaining 1,011 Y. pestis strains in this study demonstrated susceptibility to the above-mentioned 12 antimicrobial agents. Conclusion: Antimicrobial sensitivity surveillance of Y. pestis isolates, including dynamic monitoring of streptomycin resistance during various clinical plague treatments, should be carried out routinely.

150. Updated Clinical Guidelines for Treatment and Prophylaxis of Plague

BackgroundPlague still occurs naturally in the western United States, Latin America, Asia, and Africa. Yersinia pestis, the causative agent of plague, is a Tier 1 bioterrorism agent due to its potential for aerosol release and high fatality rates. Recommendations for treatment and post-exposure prophylaxis (PEP) of plague were published in 2000 and included limited first-line options for treating plague, namely streptomycin or gentamicin. Doxycycline or ciprofloxacin were recommended for PEP. However, since 2000 new human clinical data and animal data have become available, and the FDA has approved additional antimicrobials for plague. MethodsCDC developed updated, evidence-based guidelines for treatment and prophylaxis of plague using a comprehensive process. To collect evidence on relative efficacy of various antimicrobials for treatment of plague, the guidelines team conducted systematic literature reviews and analyzed U.S. surveillance data. Results of these investigations were published in Clinical Infectious Diseases in 2020. We also hosted several meetings with subject matter experts and clinical organizations (IDSA, AAP, etc.), federal agencies, and others to review relevant data and gather individual input on treatment and prophylaxis of plague. ResultsThe forthcoming plague guidelines will include several important updates. First-line treatment options have been expanded to include ciprofloxacin, levofloxacin, and moxifloxacin in addition to streptomycin and gentamicin. For PEP, levofloxacin and moxifloxacin are now first-line options in addition to doxycycline and ciprofloxacin. Trimethoprim-sulfamethoxazole is now one of several new alternative options for PEP. The updated guidelines also include recommendations for treatment of clinical forms of plague other than pneumonic. Additional special populations such as immunocompromised persons and neonates are also covered. ConclusionPlague remains a threat, both as a naturally occurring disease and as a potential bioterrorism weapon, and preparedness and early recognition are key to effective response. The updated clinical guidelines will be a useful tool for clinicians to manage antimicrobial treatment and PEP for plague. Disclosures All Authors: No reported disclosures

Efficiency of human plague vaccination in tuvinian natural plague focus. Message 2: dynamics of immune status indicators after revaccination

Relevance. In Russia, the live plague vaccine (LPV) is used for specific prophylaxis of plague. Immunological monitoring of humans vaccinated by LPV in order to search for informative diagnostic markers, as well as to improve the tactics of epidemiological surveillance of plague enzootic territories is an urgent area of research.The aim is to assess the parameters of cellular and humoral immunity in humans revaccinated by LPV who permanently reside on territory of the Tuvinian natural plague focus.Materials and methods. The study involved 76 volunteers from the Republic of Tuva, revaccinated by LPV. Blood sampling was performed before vaccination and 1, 3, and 6 months after revaccination. The study included the determination of cytokine production (IFN-γ, IL-4, TNF-α), specific antibodies, immunoglobulins (IgM, IgG, IgA and IgE) and lymphocyte subpopulation composition (CD3, CD4, CD8, CD16, CD19, immunoregulatory index).Results. A decrease in IgG and IgM and an increase in IgA were found after vaccination with LPV and their increase after revaccination. Correlation relationships were revealed between immunoglobulins, B cells and IL-4. Revaccination leads to an increase seroconversion. The activation of humoral immunity in humans vaccinated against plague is also evidenced by dynamics of changes in the subpopulation composition: an increase in B-lymphocytes and natural killer cells, a decrease in T-helpers and immunoregulatory index, and cellular immunity stimulation is an increase in spontaneous and induced production of pro- and anti-inflammatory cytokines.Conclusion. It has been shown that LPV is capable of causing the body’s immune restructuring and activating the cellular and humoral mechanisms of immunological protection. For a complete understanding of the development and preservation of antiplague immunity, it is necessary to continue the annual immunological monitoring of the population living on the territory of the Tuvinian natural plague focus, using additional modern research methods.

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.

SummaryThis report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.

Safety of Antimicrobials During Pregnancy: A Systematic Review of Antimicrobials Considered for Treatment and Postexposure Prophylaxis of Plague.

The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy. We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes. Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported. For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.

Human response to live plague vaccine EV, Almaty region, Kazakhstan, 2014-2015.

BackgroundIn Kazakhstan, a live plague vaccine EV 76 NIIEG has been used for plague prophylaxis since the mid-1930s. Vaccination is administered yearly among people living in plague-enzootic areas. Similar practices are used in other former Soviet Union countries. Yet, to this day, the effectiveness period of the vaccine is unknown. It is also not clear how different factors can affect the effectiveness of the vaccine over time.MethodsWe surveyed changes in antibody levels specific for F1 antigens of Yersinia pestis among vaccinated people 4, 8, and 12 months post- vaccination. Blood samples were taken from the participants of the study for producing sera, which was later analyzed using indirect hemagglutination reaction with antigenic erythrocyte assay (micromethod) for identifying antibodies to F1 Y.pestis.ResultsIn first-time-receivers of the plague vaccine, antibody titer reached the highest level of antibody that represents a conditionally protective titer after 4 months, dropped drastically after 8 months, and dropped again after 12 months. Similar results were obtained among those who have been vaccinated previously. However, in that group, the percentage of people with a level of antibody that represents a conditionally protective titer remained statistically significant even after 8 and 12 months.ConclusionBased on the results of this study, we recommend initiating vaccination campaigns for the medical and veterinary staff, as well as the general population four months prior to the springtime epizootics of plague among wild rodents.

Current State of the Problem of Vaccine Development for Specific Prophylaxis of Plague

Emergence of large-scale plague outbreaks in Africa and South America countries in the modern period, characterized by high frequency of pneumonic plague development (including with lethal outcome) keeps up the interest of scientists to the matters of development and testing of means for specific prophylaxis of this particularly dangerous infectious disease. WHO workshop that was held in 2018 identified the general principles of optimization of design and testing of new-generation vaccines effectively protecting the population from plague infection. Application of the achievements of biological and medical sciences for outlining rational strategy for construction of immunobiological preparations led to a certain progress in the creation of not only sub-unit vaccines based on recombinant antigens, but also live and vector preparations on the platform of safe bacterial strains and replicating and non-replicating viruses in recent years. The review comprehensively considers the relevant trends in vaccine construction for plague prevention, describes advantages of the state-of-the art methodologies for their safety and efficiency enhancement.

Non-Specific Prophylaxis of Plague in the Gorno-Altai High-Mountain Natural Focus in 2016

Objective of the study is to substantiate performance, assess the conditions, and analyze the results of activities on non-specific plague prophylaxis in the epizootic territory. Materials and methods. Utilized were archival data and operational reports of Altai Plague Control Station, Irkutsk RAPI, RusRAPI “Microbe”, Center of Hygiene and Epidemiology in the Republic of Altai, and Rospotrebnadzor Administration in the Republic of Altai, as well as literature sources. Spatial analysis was carried out using GIS-technologies. Results and conclusions. Concerted and coordinated activities of the Rospotrebnadzor institutions, medical and veterinary institutions, local executive authorities have allowed for complex prophylactic and anti-epidemic measures on prevention of plague dissemination and transmission in the territory of the Republic of Altai in 2016. Demonstrated has been the necessity to expand the scope and scale of operations and scientific research in the focus, deploying advanced toolkit of methods and means.

Historical and Modern Views on the Problem of Specific Plague Prophylaxis

Objective of this review is to analyze diachronically paradigm shift as regards problems of specific plague prophylaxis and appreciate contribution of the present-day scientific discoveries in the sphere of plague agent investigations and peculiarities of its interaction with host organism to the solution of topical issues of vaccine development that will be safe and tangibly effective against this particularly dangerous disease. Outlined is the historical background of the conceptual evolution concerning specific plague prophylaxis and events that are landmarked with eminent scientific discoveries by A.Yersin, French researcher and microbiologist. Given are the data on the current state of plague immune-prophylaxis both in Russia and around the world. Through the prism of the latest researches that assume application of advanced technological resource of medical sciences (molecular biology, biotechnology, bioinformatics, molecular immunology) put forward is the prospective of search and construction of safe and effective anti-plague next generation vaccines.

Analysis of the Genome Wide Sequence of Yersinia pestis strains Based on the Consecutive 680-SNP Algorithm

Designed is an optimized scheme for SNP analysis of the genome wide sequences of plague agent strains, based on the consecutive algorithm of clusterization of individual intraspesific Y. pestis groups. The scheme comprises 680 singular polymorphic nucleotides (SNPs), the usage of which provides not only for the clustering of closely related strains, but for the determination of phylogenetic bonds between groups of strains and order of their divergence from the common tree-trunk of the plague agent evolution. Based on the consecutive 680-SNP algorithm, carried out is the analysis of genome wide sequences of C-627 Y. pestis strain isolated in Central-Caucasian high-mountain focus (Russia), strain 1454 isolated in Altay mountain focus (Russia), strain 231 (708) – Aksay high mountain focus (Kirgizia), and vaccine EV NIIEG (Research Institute of Epidemiology and Hygiene) strain, applied for immunization in the Russian Federation and in a number of other countries. Identified are the genome variants of the strains: 1. ORI3 (EV NIIEG), 2. MED0 (C-627), 0.ANT3 (231(708)), 0.ANT4 (1454), and their place in the scheme of Y. pestis global variation. Evidenced is the absence of the chromosomal region responsible for pigmentation in the genome wide sequence of the vaccine strain EV NIIEG, which testifies to its safe use for specific plague prophylaxis.

YscF is a Highly Specific Marker for Evaluation of Antibody Response to Live Plague Vaccine in Humans

Live plague vaccine (LPV) was widely used to control Yersinia pestis infection in the middle of 20th century, and this vaccine still remains a choice for prophylaxis of plague. Nevertheless, human immunity to LPV was poorly investigated, and was limited mostly to examining the antibody response to the capsular antigen F1 and lipopolysaccharide of Y. pestis. In this work we tested sera from 19 individuals who received multiple immunizations with attenuated strain of Y. pestis EV NIIEG that is employed as a LPV in Russia. Sera from 15 healthy donors, which had no contact with Y. pestis or LPV were used as a control. All sera were studied for the presence of antigen-specific antibodies in immunoblot and to a panel of highly purified recombinant Y. pestis proteins. We found that donors vaccinated with EV NIIEG contained antibodies to one or a few antigens, such as YopM, LcrV, Pla, and F1, in the range of 31.6- 78.9%. However, sera of some non-vaccinated donors reacted positively with at least one of these antigens. Similar cross-reactivity was observed earlier during testing of F1/LcrV subunit vaccine in humans and non-human primates. In contrast, our study revealed that human humoral immune response to YscF was highly specific. Antibodies to this antigen were detected in sera of 10 out of 19 vaccinees, while all 15 control sera from non-vaccinated donors were negative. YscF represents a subunit of the translocation needle of the type 3 secretion system (T3SS) of Yersinia, and forms a polymeric structure. Apparently, successful human vaccination with LPV leads to the assembly of T3SS apparatus in vivo. Thus, we showed for the first time that YscF can be considered as a highly specific marker of evaluation of human immune response to live plague vaccine.

Serologic Markers for Long-Term Immunity in Humans Vaccinated with Live Yersinia pestis EV NIIEG

Live plague vaccines have saved thousands of human lives in the 20th century and have continued to be used in Russia and other countries of the former Soviet Union for prophylaxis of plague. A live attenuated Y. pestis EV strain line NIIEG is used for the routine annual vaccination of plague workers, as well as people from the groups at risk. This vaccination can offer immunity against both bubonic and pneumonic plague. However, serologic markers of the human response to vaccination with EV NIIEG are poorly investigated. It is not clear whether other antigens, in addition to the established capsular antigen F1 and lipopolysaccharide, can elicit specific and long-lasting antibody responses in vaccinees. In this study, a humoral immunity to a panel of recombinant Y. pestis-specific antigens, such as F1, Pla, LcrV, YopM and YscF, was examined in volunteers, who received multiple annual immunizations with EV NIIEG during the period of 5 to 30 years. To evaluate a long-term immune response to these antigens, we chose a cohort of donors, who had their last immunization 4-30 years ago. The immunoblotting technique revealed that sera of 14 out of 17 donors contained antibodies to at least one of the tested antigens. As expected, the occurrence of anti-F1 antibodies was detected in a large group of vaccinees (57%). In contrast, the presence of specific antibodies to either LcrV or YscF was less pronounced (26% and 36%, respectively), and only two donors possessed anti-YopM (10%). Surprisingly, we found that sera of the vast majority of volunteers (82%) gave positive reaction with the outer membrane protease Pla, specific to Y. pestis. This analysis will provide insights into the correlates of immunity elicited in humans by live plague vaccine, aid in the search for markers of exposure to plague, and help to develop new diagnostic protocols.

Lack of antimicrobial resistance in Yersinia pestis isolates from 17 countries in the Americas, Africa, and Asia.

Yersinia pestis is the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance in Y. pestis was reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392 Y. pestis isolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.

To 110th Anniversary of the Federal Public Health Institution Astrakhan Plague Control Station

Presented is a historical essay on the work of one of the oldest Russian anti-plague institutions - Astrakhan Plague Control Station. Noted is the fact that specialists of this institution made a substantial contribution to the development of the theory of plague natural focality and other contagious infections, as well as to the provision for and implementation of measures for epidemiological surveillance and prophylaxis of plague and other particularly dangerous infectious diseases in the territory of the North-West Caspian sea region.

Lovastatin protects against experimental plague in mice.

BackgroundPlague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model.MethodologyLovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg) every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates.Conclusions/SignificanceLovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5%) and lovastatin-treated mice (3/15; 20%) was significant (P<0.004; Mantel-Haenszel test). Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

Resistance of Yersinia pestis to antimicrobial agents.

Since the beginning of the 1990s, the number of human cases of plague has been rising, and outbreaks are reappearing in various countries after decades of quiescence. Plague is therefore categorized as a reemerging disease. Until recently, Yersinia pestis was considered as uniformly susceptible to agents that are active against gram-negative bacteria. The isolation in Madagascar of two multidrug-resistant strains of Y. pestis, one resistant to all of the antimicrobial agents recommended for treatment and prophylaxis of plague and the other resistant to a smaller array of drugs, is worrisome. The demonstration that horizontal gene transfer in the flea midgut may be the source of antibiotic-resistant Y. pestis strains is of great concern and indicates that such a clinically ominous event may occur again. There is also concern that a biological attack with Y. pestis might employ a natural or engineered antimicrobial-resistant strain. Surveillance of antibiotic resistance in Y. pestis should therefore become systematic worldwide.

Experimental Studies on the Prophylaxis of Plague by the Use of Streptomycin

Experimental Studies on the Prophylaxis of Plague by the Use of Streptomycin

Comparisons of sulfisoxazole with sulfadiazine, and thiocymetin with chloramphenicol, in chemotherapy of experimental plague in mice.

Summary In broth cultures of 10 strains of Pasteurella pestis, 3,4-dimethyl-5-sulfanilamido-isoxazole (Gantrisin, sulfisoxazole) in concentrations of 8 to 16 times less than that of 2-sulfanilamidopyrimidine (sulfadiazine) produced a similar degree of bacteriostasis. Against the same strains of plague, chloramphenicol was 16 to 32 times more inhibitory than thiocymetin. Chloramphenicol exerted a marked antibacterial action at a concentration of 2.5 microgram/ml. as compared with about the same action for 1.3 mg./ml. of sulfisoxazole. Thus in vitro chloramphenicol was about 20 times more potent than thiocymetin, 500 times more than sulfisoxazole, and 5,000 times more than sulfadiazine. Since the mechanism of action of the synthetic antibiotics differs from that of the sulfonamides, the two types of drugs are not comparable. This difference is illustrated by the fact that sulfadiazine proved to be the most effective among these chemicals for experimental plague prophylaxis in laboratory mice, whereas chloramphenicol was the best therapeutic agent. The in vivo order of efficacy was chloramphenicol, sulfadiazine, thiocymetin, and sulfisoxazole. The lower therapeutic value of sulfisoxazole compared with sulfadiazine, and of thiocymetin compared with chloramphenicol is probably due to more rapid excretion by the kidneys.

Antigenic Structure of Pasteurella pestis and the Isolation of a Crystalline Antigen.*

The present report is a summary of investigations initiated in 1942 to extend the knowledge of the antigenic structure of P. pestis, and to use this information to place plague prophylaxis on a sounder basis. The detailed experimental data will be reported at a later date. All the studies, unless otherwise stated, were performed with dried plague bacilli of the virulent “Yreka” strain. The bacilli were grown on agar for 3 days at 37°C and suspended in saline. This was precipitated by one to 2 volumes of acetone cooled to—70°C and left overnight. Repeated washings with acetone and drying in vacuo produced a bacterial powder of high antigenicity and toxicity (LD50 for 20 g mice: 20-40 μg). Extraction of the acetone-dried plague bacilli with neutral salt solutions (0.85%, 2.5% sodium chloride solutions or 0.4% sodium acetate solution) yielded a water-soluble and a water-insoluble antigenic component. The water-soluble fraction is quite toxic for mice and rats (LD50 for 20 g mice, 8-15 μg), and has a high immunogenic value for these species, but a low value for guinea pigs. The water-insoluble portion is nontoxic for mice, and produces a very poor immunogenic response in mice and rats. However, this fraction, when tested as an alum precipitate, has a high immunogenic value, equal to that of whole plague bacilli, for guinea pigs.

An experimental study on cellular immunity in Pasteurella pestis infection

1. Animals susceptible and naturally immune to plague—Bombay rats and white mice—were infected with Past, pestis and supravital study of white blood cells from the peripheral blood stream carried out. Similar studies were made on white mice injected with (a) pure envelope serum, (b) pure somatic serum, and (c) whole antiplague serum.2. Different experimental conditions produced different cell pictures with different behaviours of individual cell types, especially the polymorpho-nuclears, the monocytes and the clasmatocytes. These abnormalities were found to bear distinctive relationship to (a) active immunity, (b) passive immunity, and (c) susceptibility on the part of the experimental animal.3. The value of immunological inferences from this study in relation to plague-serum therapy and plague prophylaxis has been emphasized.4. The possibility of a better understanding of host-parasite relationships from similar studies in other bacterial infections has been pointed out.Our thanks are due to Lt.-Col. S. S. Sokhey, I.M.S., Director Haffkine Institute, for his interest in this investigation.