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Molecular and cellular basis of interleukin 12 activity in prophylaxis and therapy against infectious diseases.

A major goal for immunologists dealing with infectious diseases is the development of vaccines and immunotherapies that will protect patients against infection or the undesired effects of immune responses elicited by pathogens. Studies defining the function of different cytokines have contributed to the progress of new strategies to manipulate the immune response. Recent studies have demonstrated that interleukin 12 (IL-12) is a key cytokine for promoting cell-mediated immunity and initiating resistance to infection. Because IL-12 is a potent stimulator of host defense against a variety of pathogens, it holds great promise for therapeutic use. In addition, IL-12 antagonists protect the host against immunopathology and death caused by an excessive cellular immune response that can occur during acute microbial infections.

Animals↗

Diagnosis and treatment of infectious diseases in HIV-infected hosts.

Treatment of infectious diseases in patients with HIV infection is of primary importance in patient care. Viral, bacterial, parasitic, and fungal pathogens all may affect these patients. It is essential that accurate diagnoses be made and appropriate therapy be administered as early as possible.

AIDS-Related Opportunistic Infections↗

Monitoring infectious diseases using routine microbiology data. II. An example of regression analysis used to study infectious gastroenteritis.

Routine data used to study infectious diseases may contain biases which obscure trends. A 16-year series (up to 1968) of routine laboratory data was used to study patterns of incidence of infective gastroenteritis for which no laboratory diagnosis could be made. An artificial pattern was detected. This arose because GPs tended to refer a greater proportion of their patients during dysentery epidemics. Multiple regression analysis was used to separate out this effect so that the underlying trends could be observed. The seasonal pattern of undiagnosed cases showed an autumn peak. There were also early-winter epidemics of disease with little or no excretion of red blood or pus cells in the diagnostic faeces specimen. Some of the winter communicable disease among older children and adults appeared to be associated with signs of a temporary fat malabsorption in pre-school age cases. Undiagnosed cases in older children and adults were not related to the E. coli serotypes causing disease in infants during this period. The statistical method applied increased the usefulness of these routine data. Although this series of laboratory records is now more than a decade old the results of the analysis can be compared with new observations as more is learned about the epidemiology of previously unrecognized pathogens, especially rotaviruses.

Adolescent↗

Using standards and controls in molecular assays for infectious diseases.

Ten years ago, laboratory directors introducing molecular infectious disease diagnostics in the routine clinical setting had few resources to assist in their implementation and quality assurance programs. In the past 10 years, several organizations have recognized this need and have established standard reference materials, controls, external quality assessment programs, and written guidelines. It is a challenge for the clinical laboratory scientist to evaluate and incorporate these new programs and services in the context of traditional good laboratory practice and current laboratory regulations. This article presents many of the options available for control materials, proficiency programs, standard reference materials, and written guidelines. It shows where harmonization of new practice with long-standing convention and regulation is progressing and where questions remain.

Communicable Disease Control↗

Infectious diseases: statutory notification and surveillance.

The notification of infectious diseases has evolved over a number years and will continue to do as practices change or are modified. This article gives an insight into how the system for notification has developed. It outlines the process and purpose for notification and how the accumulation of data gathered can help nurses, midwives and health visitors make strategic plans for intervention and prevention of further outbreaks of disease. The nurse, midwife or health visitor has a central role to play in ensuring that diseases are notified to the 'proper officer'. Furthermore, if nurses, midwives and health visitors were given the power to notify diseases, the number of diseases notified may increase. This would result in a clearer and truer account of the number of notifiable diseases.

Data Collection↗

Social ecosystem health: confronting the complexity and emergence of infectious diseases.

The emergence and re-emergence of infectious diseases and their rapid dissemination worldwide are challenging national health systems, particularly in developing countries affected by extreme poverty and environmental degradation. The expectations that new vaccines and drugs and global surveillance would help reverse these trends have been frustrated thus far by the complexity of the epidemiological transition, despite promising prospects for the near future in biomolecular research and genetic engineering. This impasse raises crucial issues concerning conceptual frameworks supporting priority-setting, risk anticipation, and the transfer of science and technology's results to society. This article discusses these issues and the limitations of social and economic sciences on the one hand and ecology on the other as the main theoretical references of the health sciences in confronting the complexity of these issues on their own. The tension between these historically dissociated paradigms is discussed and a transdisciplinary approach is proposed, that of social ecosystem health, incorporating these distinct perspectives into a comprehensive framework.

Communicable Diseases, Emerging↗

Dynamics and management of infectious disease in colonizing populations.

The introduction of chronic, infectious diseases by colonizing populations (invasive or reintroduced) is a serious hazard in conservation biology, threatening the original host and other spillover species. Most research on spatial invasion of diseases has pertained to established host populations, either at steady state or fluctuating through time. Within a colonizing population, however, the spread of disease may be influenced by the expansion process of the population itself. Here we explore the simultaneous expansion of a colonizing population and a chronic, nonlethal disease introduced with it, describing basic patterns in homogeneous and structured landscapes and discussing implications for disease management. We describe expected outcomes of such introductions for three qualitatively distinct cases, depending on the relative velocities at which the population and epidemic expand. (1) If transmissibility is low the disease cannot be sustained, although it may first expand its range somewhat around the point of introduction. (2) If transmissibility is moderate but the wave-front velocity for the population, vp, is higher than that for the disease, vd, the disease wave front lags behind that of the population. (3) A highly transmissible disease, with vd > vp, will invade sufficiently rapidly to track the spread of the host. To test these elementary theoretical predictions, we simulated disease outbreaks in a spatially structured host population occupying a real landscape. We used a spatially explicit, individual-based model of Persian fallow deer (Dama mesopotamica) reintroduced in northern Israel, considering a hypothetical introduction of bovine tuberculosis. Basic patterns of disease expansion in this realistic setting were similar to our conceptual predictions for homogeneous landscapes. Landscape heterogeneity, however, induced the establishment of population activity centers and disease foci within them, leading to jagged wave fronts and causing local variation in the relative velocities at which the population and epidemic expanded. Based on predictions from simple theory and simulations of managed outbreaks, we suggest that the relative velocities at which the population and epidemic expand have important implications for the impact of different management strategies. Recognizing which of our three general cases best describes a particular outbreak will aid in planning an efficient strategy to contain the disease.

Animals↗

SARS: a new infectious disease for a new century.

BACKGROUND: A new infectious disease swept the world in early 2003, causing restrictions on international travel and economic downturn in affected countries. OBJECTIVE: This article aims to provide an overview of the epidemic of severe acute respiratory syndrome (SARS). DISCUSSION: SARS is caused by a new coronavirus thought to be of animal origin. The virus induces symptoms of atypical pneumonia, clinically indistinguishable from similar syndromes. The severity is such that a 15% mortality rate has been reported. No treatment has yet been identified as reliably successful. Transmission is by droplet spread, requiring close contact. Stringent infection control precautions in health care institutions, broad isolation measures in affected communities and international surveillance with barrier restrictions to travel have led to termination of the epidemic. As of July 11, 2003, 8437 people in 32 countries have been affected, with 813 deaths reported.

Australia↗

[Experiences of prevention and treatment of infectious diseases in Chinese Soviet Republic].

Many kinds of infectious diseases had been prevalent during the Chinese Soviet Republic period. Experiences were accumulated during the fighting against these diseases, and high attention paid by the government including the party, the military and the administration, and strengthening of legislation for prevention and treatment works, with the Red Army as the main task force for the work, and the great mass actively involved in this work, with active propaganda for its prevention and treatment.

Government↗

Infectious complications in patients with hematological malignancies consulted by the Infectious Diseases team: a retrospective cohort study (1997-2001).

In order to identify the characteristics of patients with hematological malignancies (HM) in the presence/suspicion of any accompanying infectious disease, and to find the predictors of mortality in this group, hospital charts of patients with HM consulted by the Infectious Diseases (ID) team for signs/symptoms of any infection between January 1, 1997 and December 31, 2001 were retrospectively reviewed. A total of 1,132 consultations were done for 641 patients: 59.4% of the patients were male and the mean (+/-standard deviation) age of the study participants was 47.9+/-1.4 years. The most common underlying diseases were non-Hodgkin's lymphoma (30.9%), acute myelogenous leukemia (26.2%), and multiple myeloma (10.9%). Clinically and microbiologically documented infections and fever of unknown origin were observed in 43.3%, 38.1%, and 18.5% of the participants, respectively. Bloodstream infections were detected in 134 episodes (20.9%): 56.5% were caused by gram-negative microorganisms. In logistic regression analysis, the presence of pneumonia (OR 7.56, 95% CI 4.84-12.486), invasive fungal infection (OR 4.12, 95% CI 1.78-9.55), relapse or recent diagnosis of the underlying disease (OR 2.82, 95% CI 1.53-5.21) and neutropenia (OR 2.70, 95% CI 1.70-4.31) were identified as statistically significant predictors of mortality.

Adolescent↗

The Widal slide agglutination test, a valuable rapid diagnostic test in typhoid fever patients at the Infectious Diseases Hospital of Jakarta.

The Widal slide agglutination test was evaluated as a rapid diagnostic test in typhoid fever patients at the Infectious Diseases Hospital, Jakarta, Indonesia from 1980-1982. The results of the test can be available within 45 minutes of patient admission. The study showed that, among 229 patients with Salmonella typhi-positive typhoid fever and 179 control fever patients, when the Widal O antibody titer was greater than or equal to 1:20 the sensitivity was 53%, the specificity 98%, the positive predictive value 96%, and the negative predictive value 68%. A negative Widal test (O antibody titer less than 1:20) does not provide useful information, but when the O antibody titer is greater than or equal to 1:20 the clinician at the Infectious Diseases Hospital of Jakarta can be 96% certain that the patient has typhoid fever.

Adolescent↗

Data base design for infectious disease control.

This paper presents an overview of a problem requiring the design of a decision support system (DSS) to be used for infectious disease control at a Veterans Administration hospital. An overview of the DSS selected for this application is presented. The major design question addressed is that of determining the data base schema. An automated network data base design technique is presented along with a description of its use in actually designing a data base required for monitoring infectious disease control. This technique can generate data bases containing large numbers of data items and set relationships, while maintaining several useful properties within the data structure.

Communicable Disease Control↗

Mesophilic aeromonads in human disease: current taxonomy, laboratory identification, and infectious disease spectrum.

The importance of the genus Aeromonas in human disease has recently become better appreciated through the use of improved methodologies for the recovery and identification of aeromonads from biologic specimens and as a result of medical studies aimed at determining the clinical significance of these bacteria when isolated from localized and invasive infections of humans. Taxonomic schemes currently allow for the identification of six Aeromonas species (five mesophilic and one psychrophilic), four of the five mesophilic species having been recovered from infectious processes or isolated from clinical material of human origin. Two major categories of human illness attributed to Aeromonas species have been observed: acute gastroenteritis in both pediatric and adult populations and disseminated disease (e.g., bacteremia) in persons with underlying hematologic malignancies or hepatic dysfunctions. Although the role of mesophilic aeromonads as important agents of bacterial gastroenteritis remains unconfirmed because of the inability to fulfill Koch's postulates (no animal model), several lines of compelling clinical and laboratory evidence indicate that these microorganisms are significant enteric pathogens.

Aeromonas↗

Risks of antipyretics in young children with fever due to infectious disease.

The objective of this study was to determine whether paracetamol (acetaminophen) affects the outcome of children with fever due to bacterial infectious disease. A total of 208 outpatients aged 6 months to 15 years with pyrexia due to bacterial infection who had been examined at the Fujimoto Children's Hospital from March 1992 to May 1992. The number of antipyretic doses of paracetamol (10 mg/kg) a day received within 3 days of illness in the patients with acute fever (> or = 38 degrees C) was investigated. In this study, the patients were divided into two groups: (i) the pneumonia group, which consisted of 101 patients who were subsequently diagnosed as having pneumonia during their illness and (ii) the control group, which consisted of 107 patients who were subsequently diagnosed as having illness with fever that did not progress to pneumonia. The mean number of daily doses was significantly higher for the pneumonia group (2.52 +/- 0.80) than for the control group (1.37 +/- 0.72, P < 0.001). There was no significant difference between the pneumonia group and the control group in body temperature during acute fever (38.7 +/- 0.65 vs 38.8 +/- 0.54 degrees C). The data suggest that frequent administration of antipyretics to children with infectious disease may lead to a worsening of their illness.

Acetaminophen↗

Bioterrorism and emerging infectious disease - antimicrobials, therapeutics and immune-modulators. SARS coronavirus.

The purpose of this meeting was to provide a forum for expert presentations and discussion about the threats of bioterrorism and emerging infectious diseases, and to address the issues relating to epidemics, prevention of infection and treatment of some of these emerging infectious diseases classified as potential agents of bioterror. Included in the talks were state-of-the-art presentations about infectious clone technology and recombinant viruses, pathogen and receptor interactions at the cellular and molecular level, genomic responses to infection, and new information on antiviral mechanisms of action. Severe acute respiratory syndrome (SARS) and progress toward understanding the epidemic was addressed, and other sessions were presented concerning immune therapy and immunopotentiation of disease, siRNA and gene silencing, host responses to pathogen infections, as well as the use of genetic engineering to circumvent and direct the immune response. Many discussions were held and data were presented about possible compounds and new drugs that may have antiviral properties, yet there were few discussions of any available new drugs. This report addresses reverse genetics of SARS virus, as well as its epidemiology, and a host of different recent approaches to developing antivirals effective against SARS, including some potential vaccine candidates. Also presented are hypotheses about the human immune response to SARS infection, as well as immune therapies against botulinum and anthrax toxins. This report also addresses antiviral approaches exploiting siRNAs, and different aspects of the host immune response to many of the different dangerous pathogens discussed at this meeting. Finally, approaches to circumventing and directing the immune response using genetic engineering will be reported.

Adjuvants, Immunologic↗

Impediments to global surveillance of infectious diseases: consequences of open reporting in a global economy.

Globalization has led to an increase in the spread of emerging and re-emerging infectious diseases. International efforts are being launched to control their dissemination through global surveillance, a major hindrance to which is the failure of some countries to report outbreaks. Current guidelines and regulations on emerging and re-emerging infectious diseases do not sufficiently take into account the fact that when developing countries report outbreaks they often derive few benefits and suffer disproportionately heavy social and economic consequences. In order to facilitate full participation in global surveillance by developing countries there should be: better and more affordable diagnostic capabilities to allow for timely and accurate information to be delivered in an open and transparent fashion; accurate, less sensationalist news reporting of outbreaks of diseases; adherence by countries to international regulations, including those of the World Trade Organization and the International Health Regulations; financial support for countries that are economically damaged by the diseases in question. The article presents two cases--plague in India and cholera in Peru--that illuminate some of the limitations of current practices. Recommendations are made on measures that could be taken by WHO and the world community to make global surveillance acceptable.

Cholera↗

The H*1 hematology analyzer. Its performance characteristics and value in the diagnosis of infectious disease.

The performance characteristics and the value of data provided by the H*1 Automated Blood Cell Analyzer in the diagnosis of infectious disease are assessed. Data produced by the machine are precise over a wide range of complete blood cell counts and differential white blood cell (WBC) parameters. It is capable of accurately quantifying WBCs greater than 4000/mm3 (4 X 10(9)/L); red blood cells (RBCs), greater than 2.5 X 10(6)/mm3 (2.5 X 10(12)/L); and platelets greater than 1 X 10(3)/mm3 (1 X 10(9)/L). There is good agreement between the neutrophils and lymphocytes quantified by the standard microscopic count and the automated system; however, cells that are generally present in low incidence, namely, monocytes, basophils, and eosinophils, are less well correlated. The microscopic band cell count provides the greatest test efficiency in the diagnosis of infection. None of the unique parameters generated by the H*1 differential analyzer proved to have neither a test efficiency nor a diagnostic index greater than that of the absolute WBC count in the diagnosis of infection. The "left shift" in the leukocyte differential count as detected by the H*1 relates poorly to the presence of band neutrophils in the specimen. It is concluded that the state-of-the-art automated leukocyte differential count can dramatically reduce workload, but offers no advantage over the traditional differential WBC count in the diagnosis of infectious disease. Its potential value in the diagnosis of other conditions, particularly hematologic diseases, and in the sequential monitoring of infections in individual patients were not addressed by the present study.

Evaluation Studies as Topic↗

Prospects for a group A streptococcal vaccine: rationale, feasibility, and obstacles--report of a National Institute of Allergy and Infectious Diseases workshop.

Infections due to group A streptococci (GAS) represent a public health problem of major proportions in both developing and developed countries. Currently available methods of prevention are either inadequate or ineffective, as attested to by the morbidity and mortality associated with this ubiquitous pathogen worldwide. Advances in molecular biology have shed new light on the pathogenesis of GAS infections and have identified a number of virulence factors as potential vaccine targets. Therefore, the National Institute of Allergy and Infectious Diseases convened an expert workshop in March 2004 to review the available data and to explore the microbiologic, immunologic, epidemiologic, and economic issues involved in development and implementation of a safe and effective GAS vaccine. Participants included scientists and clinicians involved in GAS research, as well as representatives of United States federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, Department of Defense, and National Institute of Allergy and Infectious Diseases), the World Health Organization, and the pharmaceutical industry. This report summarizes the deliberations of the workshop.

Developed Countries↗