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PubMed2000

[The state of vector-borne diseases in Indonesia].

From epidemiological point of view, Indonesia is an extremely interesting area owing its insular structure and ecological, anthropological, cultural and economical diversity. As everywhere, vector-borne diseases are the result of complex and variable epidemiological systems, subject both to biogeographical rules and human activity. Two main arboviroses are present in Indonesia: dengue and Japanese encephalitis. Dengue appears as an endemoepidemic disease and is mostly circumscribed to urban areas. Haemorrhagic cases were first observed in 1968; since then, the incidence has been constantly increasing and the disease is now one of the principal causes of child lethality. Japanese encephalitis is a rural endemic disease transmitted by rice-field mosquitoes; its incidence remains relatively low since pigs, which are usual link-hosts for the virus, are uncommon in this mainly Muslem country. Human clinical cases are recorded from non-Muslem islands such as Bali or Irian Jaya which raises the question of immunisation for travellers. Recently, Japanese encephalitis was observed on east of the Wallace line which had been considered as the eastern cut-off line. Malaria is common throughout the country, Plasmodium vivax being the most frequent species. Some of the Anopheline vectors are related to brackish water as are coastal species; others have been favoured by rice growing. Several species bite and rest outdoors, rendering control measures complex. Moreover, chloroquine resistance is increasing in both P. falciparum and P. vivax. All three filaria species responsible for human lymphatic filariasis exist in Indonesia. Bancroft filariasis is present in rather limited foci on most of the islands; malayan filariasis is very prevalent on many islands, mostly in coastal areas, and Timor filariasis exist only on a few small islands. These parasitic diseases are cumulative and do not practically endanger the health of travellers. In the past, plague was common on Java island, but today, human cases are very rare. Scrub typhus is prevalent everywhere, as is murine typhus, being very frequent in harbour cities and one of the main causes of hospitalisation for febrile syndromes.. On the whole, the situation of several of these diseases has been worsening in Indonesia for about thirty years. Although epidemiological situations constantly evolve, two recent occurrences should be paid particular attention: -transmigration which is now a national priority and greatly facilitates the spread of many pathogens, arboviroses or chloroquine-resistant plasmodia, but also of rats, mosquitoes, etc. -deforestation due either to land-farming by Javanese transmigrants or to sudden climatic changes such as El Niño in 1997. Such deep ecological transformations may have considerable and unforeseeable consequences on the epidemiology of vector-borne diseases in Indonesia.

Animals↗

PubMed1990

[Group B streptococci in neonatal pathology: pathogenetic mechanism, diagnosis and prevention].

Group B streptococci have recently attracted the attention of researchers as the causative agents of human neonatal disease. They are currently encountered much more frequently than it was believed previously. Various types of adult pathogen carriers have been described; this accounts for the numerous sources and pathways of infection transmission, both vertical and horizontal. The transmission risk depends on many factors, vaginal colonization in the parturient being of special import. The level of the pathogen adhesion to the barrier epithelium is reflective of the tissue sensitivity to infection. Increased sensitivity of the vaginal epithelium to B streptococci adhesion in association with the intake of some contraceptives has been found. The adhesive activity of avirulent streptococci B strains is shown to be higher than in the virulent strains, which is especially important in mixed virus bacterial infections. The streptococcal infection of high mortality is underlain by activation of persisting avirulent streptococci B that manifest their pathogenicity as a result of the virus-specific modifications in the host cell membrane. During 1985-1987, in Leningrad Institute of Gynecology and Obstetrics over 80 strains of streptococci B were isolated, the leading serotypes being Ia/C, Ib/C, II/C, III/R. Only 54% of the studied pregnancies attended with the streptococcus carriage had a favourable neonatal outcome. The strain serotypes from maternal isolates and abortuses fully correlated. Further improvement of the laboratory diagnosis and means of the pathogen and its carriers identification is a current priority.

Bacterial Adhesion↗

PubMed2003

The methylerythritol phosphate pathway and its significance as a novel drug target.

Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) are the precursors for all isoprenoid compounds. Two pathways are found in Nature for their biosynthesis. The mevalonate (MVA) pathway is found in eukaryotes, algae, archae and some gram-positive bacteria. Gram-negative bacteria, plants and some gram-positive bacteria utilize the methyl erythritol phosphate (MEP) pathway. The distribution and the orthogonal nature of the pathways make the MEP pathway an attractive new target for antibiotics and herbicides. The MEP pathway is essential for bacterial viability. Inhibitors to the MEP pathway represent a "dual-use technology" because potential targets include potential biological warfare agents in addition to common human pathogens. The CDC has three categories designated for Biological Diseases/Agents. Three of the six entities designated as the highest priority (Category A) are organisms that utilize, or appear to utilize, the MEP pathway. Among the 12 second highest priority agents (Category B) listed, 8 are organisms that appear to utilize the MEP pathway. Common human pathogens that can be targeted include the organisms responsible for peptic ulcers, tuberculosis, malaria, food safety threats, and sexually transmitted diseases. There is so far only one inhibitor reported that specifically blocks the MEP pathway and is being investigated clinically. This compound, fosmidomycin, has been shown to be somewhat effective in treating Plasmodium falciparum, the parasite responsible for malaria. We foresee that new MEP pathway inhibitors will open up an entirely new class of antibiotics. An MEP pathway intermediate has also been shown to be the most potent gammadelta T cell activator.

Animals↗

PubMed1987

Setting priorities: nationwide nosocomial infection prevention and control programs in the USA.

Approximately two million nosocomial infections occur annually in patients admitted to acute-care hospitals in the USA. Factors that should be considered in setting national priorities for nosocomial infection prevention and control efforts include incidence, mortality, prolongation of stay, cost of treatment, and potential for prevention of infections at different sites. National nosocomial infection priorities in the USA cover infections caused by emerging pathogens, infections at selected sites including the bloodstream, infections in intensive-care units, infections resulting from contaminated devices and products, development of the capability to analyze surveillance data in a timely fashion, dissemination of information on effective prevention strategies to infection control personnel, and training of infection control personnel, including physicians. The mechanism used to disseminate information on effective prevention strategies is the series of CDC 'Guidelines for the Prevention and Control of Nosocomial Infections'. These guidelines address prevention of nosocomial infections at the four major sites, handwashing and environmental control issues, infection control in personnel health, and isolation precautions.

Cross Infection↗

PubMed2003

Acute bacterial rhinosinusitis in pediatric medicine: current issues in diagnosis and management.

In children, acute bacterial rhinosinusitis is a common infection and although rare, carries a potential for serious, life threatening complications. Bacterial rhinosinusitis usually follows a viral infection or allergic rhinitis. Early, effective antibacterial therapy is essential to shorten the duration of infection and illness, to diminish mucosal damage, and to prevent contiguous infectious involvement of the orbit or central nervous system. Because the signs and symptoms of acute bacterial rhinosinusitis are similar to those of viral upper respiratory tract infection, establishing an accurate diagnosis in children poses a clinical challenge. Infection with Streptococcus pneumoniae accounts for 30-66% of episodes of acute bacterial rhinosinusitis in children. Other important pathogens include Haemophilus influenzae (20-30%) and Moraxella catarrhalis (12-28%). In selecting initial antimicrobial therapy, priority should be given to drugs with activity against S. pneumoniae. The oral agents that currently offer the greatest activity against this pathogen include amoxicillin, amoxicillin-clavulanate, cefdinir, cefpodoxime proxetil, and cefuroxime axetil; all are considered appropriate for the initial treatment of acute bacterial rhinosinusitis in children. Amoxicillin is customarily used as first-line therapy for uncomplicated acute bacterial rhinosinusitis. For patients who are allergic to amoxicillin, second- or third-generation oral cephalosporins may be used as first-line therapy. Clarithromycin has been suggested as an alternative to amoxicillin or cephalosporins in beta-lactam allergic patients. Clindamycin may also be indicated as first-line treatment in patients who have culture-proven penicillin-resistant S. pneumoniae. If no clinical response occurs within 72 hours, the choice of a second-line antibiotic is governed by the drug's known antimicrobial efficacy, resistance patterns, dosing schedules, the potential for compliance, and knowledge of the patient's drug allergies. High-dose amoxicillin-clavulanate (90 mg/kg/d of the amoxicillin component) has been recommended for high-risk children (e.g. those in day care, and those who have recently received antibiotics) who show no improvement after treatment with the usual dose of amoxicillin (45 mg/kg/d). Broad-spectrum, third-generation oral cephalosporins, such as cefdinir, should be considered as second-line agents when standard therapy has failed or when patients show hypersensitivity to penicillin. Intramuscular ceftriaxone may be appropriate for patients who fail on a second course of antibiotic treatment.

Acute Disease↗

PubMed1998

Clinical implications of nosocomial gram-positive bacteremia and superimposed antimicrobial resistance.

The coexistence of a pathogen population with an ever-increasing resistance to many antibiotics and a patient population characterized by increasingly complex clinical problems has contributed to an increase in the bloodstream infections associated with gram-positive bacteria. This serious therapeutic challenge has already been associated with an increase in infection-related morbidity and mortality, a prolongation of hospital stays, and an escalation of healthcare costs. Vancomycin resistance, long prevalent among the enterococci, has emerged in strains of Staphylococcus aureus. Several cases of infection caused by S. aureus strains with intermediate-level resistance to vancomycin (MIC=8 microg/mL) have recently been reported. As glycopeptide resistance accelerates among the gram-positive bacteria, so does the potential for adverse clinical consequences associated with bloodstream infections caused by these pathogens. The patients least able to tolerate the effects of uncontrolled bloodstream infections are also those at the highest risk for the development of infections caused by glycopeptide-resistant pathogens. In this at-risk population, a poor outcome may be anticipated if effective antibiotic therapy is unavailable. Appropriate rationing of vancomycin and other antimicrobial agents that increase the selection of antibiotic-resistant strains of gram-positive bacteria and the rapid development of novel antimicrobial agents with reliable gram-positive activity must be immediate priorities if the threat posed by glycopeptide-resistant gram-positive pathogens is to be countered.

Anti-Bacterial Agents↗

PubMed2003

Coronary atherosclerosis and somatic mutations: an overview of the contributive factors for oxidative DNA damage.

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. Genetic research on CAD has traditionally focused on investigation aimed at identifying disease-susceptibility genes. Recent evidence suggests that somatically acquired DNA mutations may also contribute significantly to the pathogenesis of the disease, underlining the similarity between atherosclerotic and carcinogenic processes. The generation of oxidative stress has been emphasized as an important cause of DNA damage in atherosclerosis. This review highlights some of the major atherogenic risk factors as likely mediators in the oxidative modification of DNA. It also examines the hypothesis that an increase in oxidative stress may derive from "oxidatively" damaged mitochondria. Accordingly, further research in this field should be given high priority, since increased somatic DNA damage could be an important pathogenic factor and an additional prognostic predictor, as well as a potential target for therapeutic strategies in coronary artery disease.

Aging↗

PubMed2002

Foods as production and delivery vehicles for human vaccines.

Vaccination is a great asset for eradication of infectious diseases in humans and animals. With the prevalence of antibiotic resistant bacterial strains and an alarming increase in new and re-emerging pathogens, the need for vaccination continues to be a high priority for mammalian diseases. In the last several years, a novel approach for developing improved mucosal subunit vaccines has emerged by exploiting the use of genetically modified plants. It has been demonstrated that plant-derived antigens are functionally similar to conventional vaccines and can induce neutralizing antibodies in mammalian hosts. Using genetically engineered plants for the production of immunogenic peptides also provides a new approach for the delivery of a plant-based subunit vaccine, i.e., oral delivery, provided these immunogenic peptides are expressed in an edible part of the plant, such as grain or fruit. Thus, food crops can play a significant new role in promoting human health by serving as vehicles for both production and delivery of vaccines.

Communicable Disease Control↗

PubMed2000

The selenium-coxsackievirus connection: chronicle of a collaboration.

This review provides a historical account of a collaboration established between a nutritionist and a virologist to investigate the interrelationship of host nutritional status and viral virulence. The parties to this collaboration consider themselves specialists in the fields of antioxidant nutrition and viral immunology, respectively. The advantages of such talent pooling are discussed (rapid startup, well-focused experimentation, ability to visualize the "big picture"), as are some of the disadvantages (limited common scientific vocabulary, proper apportioning of credit, lack of institutional infrastructure to house such efforts). The common perception that some of the most exciting science occurs when the advancing edges of two disparate disciplines intersect is borne out by this project because host nutriture was shown for the first time to influence the genetic make-up of an invading viral pathogen. Encouragement of joint cooperative ventures should have a high priority as demanded by increasingly difficult scientific problems and as desired by scientists themselves who wish to see their research progress more quickly.

Animals↗

PubMed1991

[ENT antibiotic therapy: therapeutic guidelines. Part I].

We discuss the variety of ear, nose and throat infections and then define the criteria for the choice of an adequate antibiotic. The importance of "supercalculated" therapy based on the results of Gram's stain is stressed, as it can save patients from over-treatment and adverse side-effects. Indications for Gram's stain in ENT as well as the value of the characteristics of the pus produced by different pathogens are described. The severity of the infection determines the choice between parenteral or oral therapy. The importance of the decision taken on the 1st and 3rd day of a severe infection is emphasised. Therapeutic principles in ENT infections are shown by grouping different infections with a similar spectrum of pathogens; also the indications for antibiotic therapy are outlined. Finally the priority of antibiotic treatment in some surgical infections is mentioned, and the peri-operative prophylaxis and treatment are described as well as the guidelines for treatment of infectious post-operative complications.

Anti-Bacterial Agents↗

PubMed1994

[Current studies on the neurobiology of chronic fatigue syndrome].

Cytokines are soluble mediators which are released by activated immune cells during infection and inflammation. The possibility that fatigue is mediated by the effects of cytokines on the central nervous system is supported by several converging lines of evidence: 1) infusions of cytokines to immunocompromised patients induce flu-like symptoms including fatigue and malaise; 2) peripheral and central injection of cytokines to laboratory rodents induce sickness behaviour; 3) symptoms of sickness behaviour occurring during experimental infections can be abrogated by administration of anti-cytokine treatments; 4) although many pitfalls in the detection of cytokines still exist, patients afflicted with the chronic fatigue syndrome have been found in some studies to display instances of excessive production of cytokines. Experimental studies have confirmed that cytokines are interpreted by the brain as internal signals for sickness. Furthermore, there is evidence that sickness is a motivation which reorganizes the organism's priorities in face of this particular threat which is represented by infectious pathogens. The elucidation of the mechanisms that are involved in these effects and in particular, the role of the cytokines which are produced in the brain in response to peripheral immune stimuli and to stressors, should give new insight on the way sickness and recovery processes are organized in the brain.

Adaptation, Psychological↗

PubMed2026

MicroRNAs in Veterinary Viral Diseases: A Comprehensive Review from Molecular Mechanisms to Clinical Translation.

MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length, that regulate post-transcriptional gene expression and have emerged as pivotal modulators of host-virus interactions. Veterinary viral diseases continue to pose substantial challenges to animal health, livestock productivity, food security, and public health, particularly due to their zoonotic potential. While miRNA research has advanced considerably, a comprehensive and critically integrated understanding of their biological functions and clinical applications across veterinary viral diseases remains incomplete. This comprehensive critical narrative synthesis addresses four overarching research questions: (1) What conserved and species-specific miRNA-mediated mechanisms govern major veterinary viral diseases? (2) What contextual factors determine antiviral vs. proviral duality? (3) To what extent do circulating miRNA signatures offer diagnostic and prognostic utility? (4) What translational barriers currently prevent clinical implementation, and how can the One Health framework help overcome them? Integrating three interconnected dimensions-molecular mechanisms, pathogen-specific responses, and translational applications-the review synthesizes evidence across PRRSV, avian oncogenic viruses (MDV, ALV), the immunosuppressive IBDV, FMD, BVDV, Ebola, Hendra, Rabies, and aquatic viral diseases. A key contribution of this review is the proposal of a four-axis contextual framework that explains the antiviral/proviral duality of miRNAs, and a 'One miRNA, One Health' convergence model with a concrete implementation roadmap. Key findings include: (a) a four-axis contextual framework (cell type, infection stage, viral strain, host-viral miRNA competition) that explains the antiviral/proviral duality; (b) virus-encoded miRNAs (v-miRNAs) as lower-risk therapeutic targets due to their absence from uninfected host genomes; (c) circulating miRNA biomarkers validated only at proof-of-concept stage (TRL 1-3), with no veterinary product yet at TRL ≥4; and (d) zoonotic conservation of miR-155, miR-146a, miR-21, and miR-122 across human and veterinary pathogens, supporting a 'One miRNA, One Health' convergence strategy. Critical short-term priorities are standardized pre-analytical protocols, open-access veterinary miRNA databases, and multicenter validation in natural infection cohorts.

Antiviral therapy↗

PubMed1988

Study on the efficacy of nosocomial infection control (SENIC Project): results and implications for the future.

The purpose of the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) was to evaluate nosocomial infection prevention and control programs in hospitals in the United States. The overall plan was to assess the surveillance and control activities in hospitals in the United States in 1970 and 1976, to measure the change in the nosocomial infection rates from 1970 to 1976 as determined from a carefully conducted retrospective chart review, and to assess the influence of changes in these programs on infection rates after controlling for other important changes that occurred during the interval. The SENIC 'bottom line' was that 32% of infections that would have occurred in the absence of well-organized infection surveillance and control programs were potentially preventable. However, only 6% of infections were actually being prevented by programs that existed in 1976. The critical components of an effective program were a balance between surveillance and control efforts, one infection control nurse for every 250 beds, a trained hospital epidemiologist, and feedback of surgical wound infection rates to practicing surgeons. In the United States, priorities for nosocomial infection prevention and control efforts include infections caused by emerging pathogens such as coagulase-negative staphylococci, enterococci, and Candida species; infections of the blood stream and surgical wounds; and infections in critical-care units. In addition, there is a critical need for timely analysis and dissemination of surveillance data and for continued training of infection control practitioners and physicians to maximize the effectiveness of prevention and control efforts.

Cross Infection↗

PubMed2026

The 2026 Bundibugyo Ebola Outbreak: A Warning for Global Preparedness for Future Epidemics.

Dear Editor, The 2026 Bundibugyo Ebolavirus (BDBV) outbreak has once again demonstrated that the threat of emerging diseases remains a major global health challenge. The outbreak, first detected in the Democratic Republic of Congo (DRC) and spread to Uganda, is not only a regional crisis but also a test of the world's preparedness for pathogens with epidemic potential. Unlike Zaire Ebolavirus (EBOV), which has benefited from effective vaccines and treatments in recent years, BDBV still lacks a licensed vaccine or specific treatment[1]. As of June 6, a total of 515 laboratory-confirmed cases and 91 deaths have been reported in DRC, while Uganda has reported 19 laboratory-confirmed cases and two deaths. The occurrence of unexplained deaths among both the community and healthcare workers, along with prior reports of an unidentified hemorrhagic fever, suggest that the outbreak has been likely originated in March 2026 or even earlier. Accordingly, the virus is believed to have spread unnoticed for several weeks before being identified through genomic sequencing in mid-May 2026[2]. The resurgence of Ebola in Africa results from a complex interaction of environmental, social, and political factors. Deforestation, the development of mining activities, the expansion of agriculture, and increased human contact with wildlife have elevated the likelihood of spillovers from wildlife reservoirs, particularly fruit bats, which are considered the most likely natural hosts of ebolaviruses. Moreover, weak disease surveillance systems and limited access to health services have delayed the identification of early cases. The similarity of the initial symptoms of Ebola to other endemic diseases in the region, such as malaria, makes early diagnosis difficult and provides ample opportunity for transmission to spread. Insecurity, misinformation, attacks on healthcare facilities, and armed conflict in the region have also posed serious challenges to the implementation of contact tracing programs and rapid response to the epidemic[3,4]. One of the most critical challenges highlighted by this outbreak is the weakness of diagnostic capacities in the affected areas. The initial 2007 outbreak of BDBV proved that delayed lab confirmation paralyzes public health responses[5]. Now, dealing with a much larger outbreak in 2026, the persistence of this challenge highlights a dangerous failure to invest in diagnostic infrastructure over the last 19 years. Many health facilities do not have access to molecular laboratories, rapid sample transport systems, and biosafety infrastructure[6]. These limitations delay the diagnosis and isolation of patients, thus perpetuating disease transmission. Investment in the development of mobile laboratories, rapid point-of-care diagnostic tests, and digital reporting systems can dramatically reduce the time to diagnosis and response to an outbreak. The BDBV outbreak shows that laboratory preparedness must be considered an essential part of global health security. Furthermore, the early detection of emerging pathogens depends not only on diagnostic technologies but also on the expertise of local scientists who are able to recognize unusual epidemiological and laboratory patterns. During the current outbreak, suspected Ebola cases initially tested negative using common diagnostic tests (designed for Zaire Ebola Virus), which delayed the identification of the BDBV. Specifically, field-based diagnostics in Bunia were calibrated exclusively to detect the EBOV responsible for recent Congolese outbreaks. Consequently, patient samples collected throughout late April and early May yielded negative results, requiring cross-country transport to Kinshasa for genomic confirmation[2]. This experience revealed a major vulnerability in outbreak preparedness: diagnostic tools designed for known threats may be ineffective in detecting less common or unexpected pathogens. Therefore, strengthening local scientific capacities, developing genomic surveillance, and expanding access to flexible and adaptable diagnostic platforms should be considered as a top priority for global health security. The lack of a licensed vaccine for BDBV was one of the most significant challenges of this epidemic. While the rVSV-ZEBOV vaccine has played a significant role in controlling Zaire ebolavirus, there is no licensed vaccine for BDBV. In response to this outbreak, efforts to develop mRNA-based vaccines, adenoviral vectors, rVSV-based vaccines, and multipotent vaccines have been accelerated[7]. However, the experience of this epidemic has shown that the development of medical products for rare diseases continues to face financial and investment constraints. This challenge highlights the need for sustained support from governments and international institutions for research and development of pathogens with epidemic potential. The 2026 Bundibugyo outbreak provides several key lessons for the global community. First, early detection and rapid diagnosis are the most important factors in containing the epidemic. The 19-year interval between the 2007 BDBV outbreak and the 2026 outbreak underscores persistent shortcomings in investment toward decentralized, pan-ebolavirus diagnostic infrastructure, with diagnostic delays hindering timely outbreak identification in both instances. Second, the trust and active participation of local communities are as important as medical interventions. Additionally, the rapid cross-border transmission dynamics between the DRC and Uganda demonstrate that blanket travel restrictions and border closures are impractical. As communities in the Great Lakes region routinely cross national borders for trade and healthcare, coordinated regional surveillance and timely information sharing are likely to be more effective than broad border closures in mitigating disease transmission[8]. Third, the protection of health workers must be a priority in preparedness plans. Fourth, a "One Health" approach is essential for simultaneous monitoring of humans, animals, and the environment. Although BDBV is not a new pathogen, the lack of licensed medical interventions and limited investment in research reflect many of the vulnerabilities associated with the concept of "Disease X."[9]. Unlike Zaire Ebola Virus, for which licensed vaccines and monoclonal antibody therapies are available, BDBV forces public health responses to rely almost entirely on non-pharmaceutical interventions such as isolation and infection control[10]. This gap reflects the structural inequity in global health research and development funding, with pathogens affecting resource-limited regions receiving insufficient attention until they spark an international emergency[2]. The BDBV outbreak proves that global epidemic preparedness cannot be pathogen-selective; it requires proactive investment in broad-spectrum countermeasures and resilient frontline health systems[8]. In conclusion, the 2026 BDBV outbreak is a serious wake-up call for the global health system. The epidemic revealed that gaps in surveillance systems, diagnostic capacities, vaccine development, and preparedness for emerging diseases persist. Investing in health infrastructure, developing Pan-Ebolavirus vaccines, strengthening laboratories, expanding the One-Health approach, and supporting research on emerging zoonotic pathogens must be at the top of global health security priorities. Otherwise, the BDBV outbreak may be just a prelude to larger crises to come.

Ebolavirus↗

PubMed2001

CD40 signaling converts a minimally immunogenic antigen into a potent vaccine against the intracellular pathogen Listeria monocytogenes.

Conventional vaccination strategies have failed for numerous pathogens, and the development of novel approaches to vaccine development is a major public health priority. Killed or subunit vaccines represent an attractive approach due to their safety, but they suffer from low immunogenicity and generally require adjuvants. In this study, the possibility of harnessing CD40 signaling for enhancing the immunogenicity of killed vaccines was investigated. Intravenous immunization of C57BL/6 mice with heat-killed Listeria monocytogenes (HKL) induced minimal immunity, but HKL administered together with an agonistic anti-CD40 mAb induced high levels of both CD4(+) and CD8(+) T cells capable of producing IFN-gamma following in vitro HKL stimulation. HKL/anti-CD40 vaccination elicited robust protection against subsequent Listeria challenge. Approximately 1000-fold fewer bacteria were detected in the liver and spleen of vaccinated mice, and vaccinated mice were also able to resist a normally lethal Listeria challenge. CD40-mediated adjuvant activity required endogenous IL-12 at the time of vaccination, and protection was mediated by both CD8(+) and CD4(+) T cells. Thus, CD40 signaling can deliver potent adjuvant activity for vaccination against intracellular pathogens and is particularly effective for pathogens requiring both CD4(+) and CD8(+) T cells for effective control.

Adjuvants, Immunologic↗

PubMed1999

In vitro evaluation of G1: a novel antimicrobial compound.

G1 (1-[5-bromofur-2-il]-2-bromo-2-nitroethene) is a novel antimicrobial compound developed in Cuba with reported broadspectrum activity against Gram-positive and -negative bacteria, yeasts and fungi. A compound of this nature may have considerable therapeutic potential. We tested the in vitro activity of this novel compound against 3595 organisms using microbroth dilution. The following are MIC50, MIC90 and range respectively for some of the microorganisms tested: E. coli 16, 16, 4 32; Klebsiella sp. 16, 16, 8 32; Citrobacter sp. 16, 16, 8 16; Enterobacter sp. 16, 16, 8-16; Proteus sp. 16, 16, 8-16; Coagulase-negative staphylococci 16, 32, 4-32; Enterococcus sp. 16, 32, 2-32; Staphylococcus aureus 8, 16, 4-16; Streptococcus agalactiae 4, 8, 4 8; Streptococcus pyogenes 4, 8, 0.25-16; Candida albicans 2, 2, 1-4; Candida tropicalis 4, 4, 2-4; Candida sp. 2,4, 1-4. MIC values appear lower for Gram-positive microorganisms and yeasts. G1 appears to be a novel antimicrobial agent with broad spectrum activity against bacterial and fungal pathogens. Defining the activity of this compound against multi-resistant bacteria is a priority.

Anti-Bacterial Agents↗

PubMed2001

Prophylaxis and treatment of influenza virus infection.

Influenza virus infections remain an important cause of morbidity and mortality. Furthermore, a recurrence of pandemic influenza remains a real possibility. There are now effective ways to both prevent and treat influenza. Prevention of infection is most effectively accomplished by vaccination. Vaccination with the inactivated, intramuscular influenza vaccine has been clearly demonstrated to reduce serious morbidity and mortality associated with influenza infection, especially in groups of patients at high risk (e.g. the elderly). However, the inactivated, intramuscular vaccine does not strongly induce cell-mediated or mucosal immune responses, and protection induced by the vaccine is highly strain specific. Live, attenuated influenza vaccines administered intranasally have been studied in clinical trials and shown to elicit stronger mucosal and cell-mediated immune responses. Live, attenuated vaccines appear to be more effective for inducing protective immunity in children or the elderly than inactivated, intramuscular vaccines. Additionally, novel vaccine methodologies employing conserved components of influenza virus or viral DNA are being developed. Preclinical studies suggest that these approaches may lead to methods of vaccination that could induce immunity against diverse strains or subtypes of influenza. Because of the limitations of vaccination, antiviral therapy continues to play an important role in the control of influenza. Two major classes of antivirals have demonstrated ability to prevent or treat influenza in clinical trials: the adamantanes and the neuraminidase inhibitors. The adamantanes (amantadine and rimantadine) have been in use for many years. They inhibit viral uncoating by blocking the proton channel activity of the influenza A viral M2 protein. Limitations of the adamantanes include lack of activity against influenza B, toxicity (especially in the elderly), and the rapid development of resistance. The neuraminidase inhibitors were designed to interfere with the conserved sialic acid binding site of the viral neuraminidase and act against both influenza A and B with a high degree of specificity when administered by the oral (oseltamivir) or inhaled (zanamivir) route. The neuraminidase inhibitors have relatively low toxicity, and viral resistance to these inhibitors appears to be uncommon. Additional novel antivirals that target other phases of the life cycle of influenza are in preclinical development. For example, recombinant collectins inhibit replication of influenza by binding to the viral haemagglutinin as well as altering phagocyte responses to the virus. Recombinant techniques have been used for generation of antiviral proteins (e.g. modified collectins) or oligonucleotides. Greater understanding of the biology of influenza viruses has already resulted in significant advances in the management of this important pathogen. Further advances in vaccination and antiviral therapy of influenza should remain a high priority.

Amantadine↗

PubMed2002

[DNA technology for diagnosis and characterization of agricultural animal pathogenic viruses].

Use of recombinant DNA for the development of diagnostic and therapeutic and preventive drugs became one of the priority trends in modern experimental veterinary. This paper discusses modern methods of virus analysis based on the DNA technologies: restriction mapping, nucleic acid hybridization, and polymerase chain reaction. Examples of utilization of these methods for clinical diagnosis and research of animal viruses are offered.

Animal Diseases↗