Lower extremity arterial plaque in patients with type 2 diabetes mellitus: A cross-sectional study of 25-(OH)D3 and other risk factors.

OBJECTIVE: The occurrence of chronic vascular complications in individuals with type 2 diabetes mellitus(T2DM) is influenced by multiple factors. This study aims to analyze the correlation between serum 25-(OH)D3 levels and other risk factors with the formation and severity of arterial plaques in the lower extremities, and explore its role in clinical diagnosis and treatment. METHODS: A total of 628 Chinese patients with T2DM were included in this study. Based on the intima-media thickness (IMT) and plaque echogenicity measured by lower extremity vascular ultrasound, the patients were divided into the no plaque group(NP), low-risk plague group(LP), moderate-risk plague group(MP), and severe-risk plague group(SP). Based on 25-(OH)D3 levels, patients were categorized as vitamin D deficient group (VDD，25-(OH)D3 ≤ 20 ng/mL), vitamin D insufficient group (VDI，25-(OH)D3 between>20 ng/mL and < 30 ng/mL), and vitamin D sufficient group (VDS，25-(OH)D3 ≥ 30 ng/mL). The correlation between the severity of lower extremity arterial plaques and serum 25-(OH)D3 levels was analyzed, as well as the risk factors for lower extremity arterial plaque formation in patients with T2DM. RESULTS: The levels of 25-(OH)D3 in patients with arterial plaques were significantly lower than those in the NP (p = 0.002). Additionally, with the increasing severity of lower extremity arterial plaques, 25-(OH)D3 levels also decreased significantly (p = 0.01). The proportion of patients with sufficient 25-(OH)D3 levels was highest in NP, while the proportion of deficient and insufficient groups was higher in LP (p<0.001). Multivariate logistic regression analysis showed that low levels of 25-(OH)D3 were an independent risk factor for lower extremity arterial plaques in T2DM patients. Compared to patients with 25-(OH)D3>20 ng/mL, the odds ratios for the formation of moderate-risk plaques were 2.525 (95 % CI: 1.45-4.39) in patients with 25-(OH)D3 ≤ 20 ng/mL, and 2.893 (95 % CI: 1.59-5.26) for the formation of high-risk plaques. CONCLUSION: Serum 25-(OH)D3 levels may be correlated with the occurrence and severity of lower extremity arterial plaques in patients with T2DM. Low serum 25-(OH)D3 concentration is a risk factor for lower extremity vascular lesions.

The invasive pathogen Yersinia pestis disrupts host blood vasculature to spread and provoke hemorrhages.

Yersinia pestis is a powerful pathogen with a rare invasive capacity. After a flea bite, the plague bacillus can reach the bloodstream in a matter of days giving way to invade the whole organism reaching all organs and provoking disseminated hemorrhages. However, the mechanisms used by this bacterium to cross and disrupt the endothelial vascular barrier remain poorly understood. In this study, an innovative model of in vivo infection was used to focus on the interaction between Y. pestis and its host vascular system. In the draining lymph nodes and in secondary organs, bacteria provoked the porosity and disruption of blood vessels. An in vitro model of endothelial barrier showed a role in this phenotype for the pYV/pCD1 plasmid that carries a Type Three Secretion System. This work supports that the pYV/pCD1 plasmid is responsible for the powerful tissue invasiveness capacity of the plague bacillus and the hemorrhagic features of plague.

Regarding pandemics: Ibn Jatima from Almería anticipates the physiopathological concept of multi-organ failure in the 14th century.

In 1348, a pandemic known as Black Death devastated humanity and changed social, economic and geopolitical world order, as is the current case with SARS-CoV-2 coronavirus. The doctor of the Nasrid Kingdom of Granada, Ibn-Jatima from Almeria, wrote "Treatise on the Plague", in which it may be found epidemiological and clinical similarities between both plagues. In the context of Greco-Arab medicine, he discovered respiratory and contact contagion of Pestis and attributed its physiopathology to a lack of pulmonary cooling of the innate heat, generated in the heart and carried by the blood humor. The process described was equivalent to the oxygen transport system. Furthermore, it was supposed to generate toxic residues, such as free radicals, leading to an irreversible multiple organ failure (MOF), considered a mortality factor as in Covid-19. Due to its similitude, it would be the first antecedent of the MOF physiopathological concept, a finding that enriches the scientific and historical heritage of our clinical specialty.

Influenza virus infection augments susceptibility to respiratory Yersinia pestis exposure and impacts the efficacy of antiplague antibiotic treatments.

Various respiratory viral infections in general and seasonal influenza in particular may increase the susceptibility to bacterial infections. Plague caused by Yersinia pestis endangers large populations during outbreaks or bioterrorism attacks. Recommended antibiotic countermeasures include well-established protocols based on animal studies and corroborated by effective treatment of human cases. Until now, prior exposure to viral respiratory infections was not taken into consideration when selecting the appropriate treatment for plague. Here, we show that as late as 25 days after exposure to influenza virus, convalescent mice still exhibited an increased susceptibility to sublethal doses of Y. pestis, presented with aberrant cytokine expression, and impaired neutrophil infiltration in the lungs. Increased levels of M2 alveolar macrophages and type II epithelial cells, as well as induction in metalloproteases expression and collagen and laminin degradation, suggested that the previous viral infection was under resolution, correlating with enhanced susceptibility to plague. Surprisingly, postexposure prophylaxis treatment with the recommended drugs revealed that ciprofloxacin was superior to doxycycline in mice recovering from influenza infection. These results suggest that after an influenza infection, the consequences, such as impaired immunity and lung tissue remodeling and damage, should be considered when treating subsequent Y. pestis exposure.

Single-dose combination nanovaccine induces both rapid and long-lived protection against pneumonic plague.

Yersinia pestis, the causative agent of pneumonic plague, induces a highly lethal infection if left untreated. Currently, there is no FDA-approved vaccine against this pathogen; however, USAMRIID has developed a recombinant fusion protein, F1-V, that has been shown to induce protection against pneumonic plague. Many F1-V-based vaccine formulations require prime-boost immunization to achieve protective immunity, and there are limited reports of rapid induction of protective immunity (≤ 14 days post-immunization (DPI)). The STimulator of INterferon Genes agonists cyclic dinucleotides (CDNs) have been shown to be promising vaccine adjuvants. Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have also shown to enhance immune responses due to their dual functionality as adjuvants and delivery vehicles. In this work, a combination nanovaccine was designed that comprised F1-V-loaded nanoparticles combined with the CDN, dithio-RP,RP-cyclic di-guanosine monophosphate, to induce rapid and long-lived protective immunity against pneumonic plague. All mice immunized with a single dose combination nanovaccine were protected from Y. pestis lethal challenge within 14 DPI and demonstrated enhanced protection over F1-V adjuvanted with CDNs alone at challenge doses ≥7000 CFU Y. pestis CO92. In addition, 75% of mice receiving the single dose of the combination nanovaccine were protected from challenge at 182 DPI, while maintaining high levels of antigen-specific serum IgG. ELISPOT analysis of vaccinated animals at 218 DPI revealed F1-V-specific long-lived plasma cells in bone marrow in mice vaccinated with CDN adjuvanted F1-V or the combination nanovaccine. Microarray analysis of serum from these vaccinated mice revealed the presence of serum antibody that bound to a broad range of F1 and V linear epitopes. These results demonstrate that combining the adjuvanticity of CDNs with a nanovaccine delivery system enables induction of both rapid and long-lived protective immunity against Y. pestis. STATEMENT OF SIGNIFICANCE: • Yersinia pestis, the causative agent of pneumonic plague, induces a highly lethal infection if left untreated. Currently, there is no FDA-approved vaccine against this biodefense pathogen. • We designed a combination nanovaccine comprising of F1-V antigen-loaded polyanhydride nanoparticles and a cyclic dinucleotide adjuvant to induce both rapid and long-lived protective immunity against pneumonic plague. • Animals immunized with the combination nanovaccine maintained high levels of antigen-specific serum IgG and long-lived plasma cells in bone marrow and the serum antibody showed a high affinity for a broad range of F1 and V linear epitopes. • The combination nanovaccine is a promising next-generation vaccine platform against weaponized Y. pestis based on its ability to induce both rapid and long-lived protective immunity.

Monitoring of Neutrophil Recruitment to Mice Lungs During Pneumonic Plague.

Early sensing of bacterial infection and the immediate recruitment of neutrophils to the lung is a major and decisive stage of the innate immune response to pulmonary bacterial infections. This chapter details the preparation of lung tissue suspensions from mice infected intra-nasally (I.N.) with the plague bacterium Yersinia pestis to study in vivo neutrophil responses to the infection. The samples were used for the quantification of neutrophil levels and for the characterization of the pro-inflammatory response required for neutrophil recruitment to the lung. The specific requirements for performing the procedures under Biosafety Level 3 containment and the proper handling and sterilization of the samples are discussed.

Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model.

Yersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered. In this work, we show that primary pneumonic or secondary septicemic plague can be preferentially modeled in mice by varying the volume used for intranasal delivery of Y. pestis. Low volume intranasal challenge (10µL) of wild type Y. pestis resulted in a high frequency of lethal secondary septicemic plague, with a low degree of primary lung infection and rapid development of sepsis. In contrast, high volume intranasal challenge (30µL) yielded uniform early lung infection and primary disease and a significant increase in lethality. In a commonly used BSL2 model, high volume challenge with Y. pestis lacking the pigmentation locus (pgm-) gave 105-fold greater deposition compared to low volume challenge, yet moribund mice did not develop severe lung disease and there was no detectable difference in lethality. These data indicate the primary cause of death of mice in the BSL2 model is sepsis regardless of intranasal dosing method. Overall, these findings allow for the preferential modeling of pneumonic or septicemic plague by intranasal dosing of mice with Y. pestis.

Unique Case of Disseminated Plague With Multifocal Osteomyelitis.

Plague is a disease caused by Yersinia pestis. Septicemic and pneumonic plague have a high mortality rate if untreated. Here we describe the challenges of accurately diagnosing a nonfatal pediatric case of septicemic plague with involvement of multiple organs; to our knowledge, the first documented case of multifocal plague osteomyelitis.

Plague in China 2014-All sporadic case report of pneumonic plague.

BACKGROUND: Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. CASE PRESENTATION: All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. CONCLUSIONS: Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post-exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist.

TNFα and IFNγ but not perforin are critical for CD8 T cell-mediated protection against pulmonary Yersinia pestis infection.

Septic pneumonias resulting from bacterial infections of the lung are a leading cause of human death worldwide. Little is known about the capacity of CD8 T cell-mediated immunity to combat these infections and the types of effector functions that may be most effective. Pneumonic plague is an acutely lethal septic pneumonia caused by the Gram-negative bacterium Yersinia pestis. We recently identified a dominant and protective Y. pestis antigen, YopE69-77, recognized by CD8 T cells in C57BL/6 mice. Here, we use gene-deficient mice, Ab-mediated depletion, cell transfers, and bone marrow chimeric mice to investigate the effector functions of YopE69-77-specific CD8 T cells and their relative contributions during pulmonary Y. pestis infection. We demonstrate that YopE69-77-specific CD8 T cells exhibit perforin-dependent cytotoxicity in vivo; however, perforin is dispensable for YopE69-77-mediated protection. In contrast, YopE69-77-mediated protection is severely impaired when production of TNFα and IFNγ by CD8 T cells is simultaneously ablated. Interestingly, TNFα is absolutely required at the time of challenge infection and can be provided by either T cells or non-T cells, whereas IFNγ provided by T cells prior to challenge appears to facilitate the differentiation of optimally protective CD8 T cells. We conclude that cytokine production, not cytotoxicity, is essential for CD8 T cell-mediated control of pulmonary Y. pestis infection and we suggest that assays detecting Ag-specific TNFα production in addition to antibody titers may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias.

Discovery of a leptospirosis cluster amidst a pneumonic plague outbreak in a miners' camp in the Democratic Republic of the Congo.

Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa.

A novel post-exposure medical countermeasure L-97-1 improves survival and acute lung injury following intratracheal infection with Yersinia pestis.

Yersinia pestis, a Gram-negative bacillus causing plague and Centers for Disease Control and Prevention (CDC) classified Category A pathogen, has high potential as a bioweapon. Lipopolysaccharide, a virulence factor for Y. pestis, binds to and activates A(1) adenosine receptor (AR)s and, in animals, A(1)AR antagonists block induced acute lung injury (ALI) and increase survival following cecal ligation and perforation. In this study, rats were infected intratracheally with viable Y. pestis [CO99 (pCD1( + )/Δpgm) 1 × 10( 8 ) CFU/animal] and treated daily for 3 d with ciprofloxacin (cipro), the A(1)AR antagonist L-97-1, or cipro plus L-97-1 starting at 0, 6, 24, 48, or 72 h post-Y. pestis. At 72 h post-Y. pestis, cipro plus L-97-1 significantly improved 6-d survival to 60-70% vs 28% for cipro plus H(2)O and 33% for untreated Y. pestis controls (P = 0.02, logrank test). Lung edema, hemorrhage and leukocyte infiltration index (LII) were evaluated histologically to produce ALI scores. Cipro plus L-97-1 significantly reduced lung edema, as well as aggregate lung injury scores vs controls or cipro plus H(2)O, and LII vs controls (P < 0.05, Student's unpaired t test). These results support efficacy for L-97-1 as a post-exposure medical countermeasure, adjunctive therapy to antibiotics for Y. pestis.

[Role of activation of lipid peroxidation in pathogenesis of experimental plague intoxication].

Activation of lipid peroxidation, increasing during the elevation of clinical symptoms of Y. pestis intoxication and hypoxic syndrome development, is the efferent link in cytopathogenic effects of toxic and enzymatic factors of this microorganism. Absolute or relative insufficiency of enzymatic mechanisms of blood antioxidant protection systems is the main pathogenic factor in lipid components of biomembrane destruction leading to the haemorrhagic syndrome development in Y. pestis intoxication.

Levofloxacin cures experimental pneumonic plague in African green monkeys.

BACKGROUND: Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. METHODS AND RESULTS: Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3-145 (mean = 65) 50% lethal (LD(50)) doses of Y. pestis strain CO92. Telemetered body temperature >39 °C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a "humanized" dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53-165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. CONCLUSION: Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen.

Fatal laboratory-acquired infection with an attenuated Yersinia pestis Strain--Chicago, Illinois, 2009.

On September 18, 2009, the Chicago Department of Public Health (CDPH) was notified by a local hospital of a suspected case of fatal laboratory-acquired infection with Yersinia pestis, the causative agent of plague. The patient, a researcher in a university laboratory, had been working along with other members of the laboratory group with a pigmentation-negative (pgm-) attenuated Y. pestis strain (KIM D27). The strain had not been known to have caused laboratory-acquired infections or human fatalities. Other researchers in a separate university laboratory facility in the same building had contact with a virulent Y. pestis strain (CO92) that is considered a select biologic agent; however, the pgm- attenuated KIM D27 is excluded from the National Select Agent Registry. The university, CDPH, the Illinois Department of Public Health (IDPH), and CDC conducted an investigation to ascertain the cause of death. This report summarizes the results of that investigation, which determined that the cause of death likely was an unrecognized occupational exposure (route unknown) to Y. pestis, leading to septic shock. Y. pestis was isolated from premortem blood cultures. Polymerase chain reaction (PCR) identified the clinical isolate as a pgm- strain of Y. pestis. Postmortem examination revealed no evidence of pneumonic plague. A postmortem diagnosis of hereditary hemochromatosis was made on the basis of histopathologic, laboratory, and genetic testing. One possible explanation for the unexpected fatal outcome in this patient is that hemochromatosis-induced iron overload might have provided the infecting KIM D27 strain, which is attenuated as a result of defects in its ability to acquire iron, with sufficient iron to overcome its iron-acquisition defects and become virulent. Researchers should adhere to recommended biosafety practices when handling any live bacterial cultures, even attenuated strains, and institutional biosafety committees should implement and maintain effective surveillance systems to detect and monitor unexpected acute illness in laboratory workers.

Septic shock and nonpulmonary organ dysfunction in pneumonic plague: the role of Yersinia pestis pCD1- vs. pgm- virulence factors.

OBJECTIVE: Pneumonic plague resulting from Yersinia pestis induces swiftly lethal sepsis and is a major concern as a weapon of bioterrorism. However, the role of specific plasmid-encoded vs. chromosomal Y. pestis virulence factors in the pathogenesis of acute lung injury, shock, and nonpulmonary dysfunction is unclear. We hypothesized that the pathophysiology of pneumonic plague resulting from expression of proteins encoded by the thermally regulated pCD1 plasmid differs from cardiopulmonary and inflammatory changes attributable to the chromosomal pgm gene locus. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university medical center. SUBJECTS: Conscious, chronically catheterized male Sprague-Dawley rats (total n=104). INTERVENTIONS: Rats were intratracheally infected with 109 colony-forming units of Y. pestis attenuated strains CO99 (pCD1+/DeltaApgm) or KIM6+ (pCD1-/pgm+) and evaluated over 6 days. Serial evaluations of vital signs, cardiorespiratory parameters, blood cultures, inflammatory biomarkers, and organ function were obtained, as well as organ histopathology and cytokine production. MEASUREMENTS AND MAIN RESULTS: Despite equivalent endotoxin contents between the inocula, CO99-infected animals had a median survival of 3 days with greater nonpulmonary organ injury, microbial growth, serum alanine aminotransferase, and liver microvascular permeability vs. KIM6+-infected animals (p<.05). Parallel differences occurred in serum tumor necrosis factor-alpha levels. Notably, 75% of CO99 rats developed fatal hypotension after developing nonpulmonary organ damage. CONCLUSION: These results suggest that progression to lethal sepsis with augmented liver injury during plague pneumonia requires factors encoded by the pCD1 plasmid but not chromosomal proteins present within the pgm gene locus.

Mountain plover responses to plague in Montana.

Plague is a bacterial (Yersinia pestis) disease that causes epizootic die-offs in black-tailed prairie dog (Cynomys ludovicianus) populations in the North American Great Plains. Through their grazing and burrowing, prairie dogs modify vegetation and landscape structure on their colonies in ways that affect other grassland species. Plague epizootics on prairie dog colonies can have indirect effects on species associated with colonies. The mountain plover (Charadrius montanus) preferentially nests on black-tailed prairie dog colonies and is thus negatively impacted by the loss of prairie dogs. We studied the effects of plague and colony spatial characteristics on the occupancy of 81 prairie dog colonies by nesting plovers in Phillips County, Montana, during a 13-year period (1995-2007). We used a robust design patch occupancy model to investigate how colony occupancy and extinction and colonization rates were affected by plague history, colony size, and colony shape. Here extinction and colonization rates refer to the probability that a colony loses/gains plovers in a subsequent nesting season, given that it had/lacked plovers in that breeding season. Colony occupancy was best explained by a model with no annual variation or plague effects. Colony extinction rates were driven by a combination of a quadratic of colony area, a 3-year plague response, and a measure of colony shape. Conversely, colonization rates were best explained by a model with a 4-year plague response. The estimated annual proportion of colonies occupied by plovers was 0.75 (95% confidence interval = 0.57-0.87). Estimated extinction probability ranged from a low of 0.07 (standard error [SE] = 0.02) in 2002 to a high of 0.25 (SE = 0.03) in 1995; colonization probability ranged from 0.24 (SE = 0.05) in 2006 to 0.35 (SE = 0.05) in 2000. Our results highlight how a bird that depends on prairie dogs for nesting habitat responds to plague history and other spatial characteristics of the colony. Ultimately, this information will broaden our understanding of the impact of plague on species other than the host.

Herpesvirus latency confers symbiotic protection from bacterial infection.

All humans become infected with multiple herpesviruses during childhood. After clearance of acute infection, herpesviruses enter a dormant state known as latency. Latency persists for the life of the host and is presumed to be parasitic, as it leaves the individual at risk for subsequent viral reactivation and disease. Here we show that herpesvirus latency also confers a surprising benefit to the host. Mice latently infected with either murine gammaherpesvirus 68 or murine cytomegalovirus, which are genetically highly similar to the human pathogens Epstein-Barr virus and human cytomegalovirus, respectively, are resistant to infection with the bacterial pathogens Listeria monocytogenes and Yersinia pestis. Latency-induced protection is not antigen specific but involves prolonged production of the antiviral cytokine interferon-gamma and systemic activation of macrophages. Latency thereby upregulates the basal activation state of innate immunity against subsequent infections. We speculate that herpesvirus latency may also sculpt the immune response to self and environmental antigens through establishment of a polarized cytokine environment. Thus, whereas the immune evasion capabilities and lifelong persistence of herpesviruses are commonly viewed as solely pathogenic, our data suggest that latency is a symbiotic relationship with immune benefits for the host.

Gentamicin and tetracyclines for the treatment of human plague: review of 75 cases in new Mexico, 1985-1999.

Streptomycin, an antimicrobial with limited availability, is the treatment of choice for plague, a fulminating and potentially epidemic disease that poses a bioterrorism concern. We evaluated the efficacy of gentamicin and tetracyclines for treating human plague. A medical record review was conducted on all 75 patients with plague who were reported in New Mexico during 1985-1999. Fifty patients were included in an analysis that compared streptomycin-treated patients (n=14) with those treated with gentamicin and/or a tetracycline (n=36). The mean numbers of fever days, hospital days, and complications and the number of deaths did not differ between patients treated with streptomycin and those treated with gentamicin. One patient who received tetracycline alone experienced a serious complication. Gentamicin alone or in combination with a tetracycline was as efficacious as streptomycin for treating human plague. The efficacy of a tetracycline alone could not be determined from the study.