Showing papers in "Current Opinion in Infectious Diseases in 2000"
TL;DR: The low cure rates obtained with praziquantel in a Senegalese focus of schistosomiasis can best be interpreted on the basis of epidemiological factors, and are unlikely to be connected with any drug resistance in the parasite.
Abstract: The low cure rates obtained with praziquantel in a Senegalese focus of schistosomiasis can best be interpreted on the basis of epidemiological factors, and are unlikely to be connected with any drug resistance in the parasite. Schistosome isolates obtained in Egypt from uncured patients present evidence of lower susceptibility to the drug, albeit to a rather limited extent. Similarly, laboratory schistosomes subjected to repeated passages under drug pressure are partly insensitive to the drug. Oxamniquine is at present the only available alternative to praziquantel. Research and development of new antischistosomal drugs is urgently needed.
148 citations
TL;DR: The recent clinical implications of nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity are reviewed and options for management are discussed.
Abstract: Nucleoside reverse transcriptase inhibitors suppress HIV replication by blocking reverse transcriptase, an RNAdependent DNA polymerase. These drugs can also affect cellular and mitochondrial DNA polymerases. Mitochondrial DNA polymerase g is particularly sensitive to nucleoside reverse transcriptase inhibitors, and the majority of adverse effects caused by nucleoside reverse transcriptase inhibitors are most likely caused by mitochondrial dysfunction. This article reviews the recent clinical implications of nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity and discusses options for management. Curr Opin Infect Dis 13:5‐11.
138 citations
TL;DR: In patients with hematologic malignancy or bone marrow transplant, who may experience prolonged or severe neutropenia during the course of therapy, the skin and nails should be carefully examined and consideration given to treating potential infection sites that may serve as portals for systemic dissemination.
Abstract: Fusarium species are ubiquitous and may be found in the soil, air and on plants. Fusarium species can cause mycotoxicosis in humans following ingestion of food that has been colonized by the fungal organism. In humans, Fusarium species can also cause disease that is localized, focally invasive or disseminated. The pathogen generally affects immunocompromised individuals with infection of immunocompetent persons being rarely reported. Localized infection includes septic arthritis, endophthalmitis, osteomyelitis, cystitis and brain abscess. In these situations relatively good response may be expected following appropriate surgery and oral antifungal therapy. Disseminated infection occurs when two or more noncontiguous sites are involved. Over eighty cases have been reported, many of which had a hematologic malignancy including neutropenia. The species most commonly involved include Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme (also termed F. verticillioides). The diagnosis of Fusarium infection may be made on histopathology, gram stain, mycology, blood culture, or serology. Portals of entry of disseminated infection include the respiratory tract, the gastrointestinal tract, and cutaneous sites.The skin can be an important and an early clue to diagnosis since cutaneous lesions may be observed at an early stage of the disease and in about seventy-five cases of disseminated Fusarium infection. Typical skin lesions may be painful red or violaceous nodules, the center of which often becomes ulcerated and covered by a black eschar. The multiple necrotizing lesions are often observed on the trunk and the extremities. Onychomycosis most commonly due to F. oxysporum or F. solani has been reported. The onychomycosis may be of several types: distal and lateral subungual (DLSO), white superficial (WSO), and proximal subungual (PSO). In proximal subungual onychomycosis there may be associated leukonychia and/or periungual inflammation. Patients with Fusarium onychomycosis have been cured following therapy with itraconazole, terbinafine, ciclopirox olamine lacquer, or topical antifungal agent. In other instances nail avulsion plus antifungal therapy has been successful. In patients with hematologic malignancy or bone marrow transplant, who may experience prolonged or severe neutropenia during the course of therapy, the skin and nails should be carefully examined and consideration given to treating potential infection sites that may serve as portals for systemic dissemination. When disseminated Fusarium infection is present therapy with antifungal agents has generally been disappointing with the chances of a successful resolution being enhanced if the neutropenia can be corrected in a timely manner.
108 citations
TL;DR: Teeth are coated with a biofilm that contains periodontal pathogens that have the potential to modulate the course of systemic diseases such as atherosclerosis and to contribute to low birthweight and preterm labor.
Abstract: Teeth are coated with a biofilm that contains periodontal pathogens. Pathogens express virulence factors which enable them to invade and replicate within epithelial cells and to invade the underlying connective tissue. This stimulates production of prostaglandins and cytokines that induce tissue loss. In addition, these bacteria have the potential to modulate the course of systemic diseases such as atherosclerosis and to contribute to low birthweight and preterm labor.
83 citations
TL;DR: Although many antimicrobial biomaterials have shown promising activity in vitro, few anti-infective prosthetic devices manufactured from these materials have yet achieved any degree of success in clinical trials.
Abstract: Although many antimicrobial biomaterials have shown promising activity in vitro, few anti-infective prosthetic devices manufactured from these materials have yet achieved any degree of success in clinical trials. Controversy surrounds the exploitation of antibiotics in these materials and the microbiological methods that have been used in the clinical trials on the devices.
78 citations
TL;DR: Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that the authors must live with the old vaccines or not vaccinate.
Abstract: Anthrax vaccination has become a ‘hot’ topic. On the one hand, fears that Iraq holds secret caches of anthrax-based weaponry, that other countries may be developing or may have developed similar devices, or that hard-line groups may make their own anthrax-based devices for bioterrorist attacks have focused official attention on the need for means of protection, principally, though, for the military. On the other hand, the unsolved issues of the Gulf War illnesses have left elements of doubt in the minds of some as to the possible role of anthrax (among other) vaccines in this syndrome, and have drawn attention to the shortage of pre-clinical, clinical, pharmacological and safety data on the existing UK and US anthrax vaccines. In the middle are those hotly debating the US and Canadian policies of mandatory anthrax immunization for military personnel or, in the case of the UK policy of voluntary immunization, simply voting with their feet. Compounding matters have been the publicized failures of the US vaccine production facility and the less publicized UK problems of supply. Meanwhile, those in genuine at-risk occupations are left unsure whether, if they can get the vaccine at all, they really want it. Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that we must live with the old vaccines or not vaccinate.
78 citations
TL;DR: The molecular biology of trichomonads is still in its infancy, but analysis of genes, genomic structure and transcriptional mechanisms suggest that trichomoads combine both prokaryotic and eukaryotic features.
Abstract: Trichomonas vaginalis is emerging as a major pathogen of men and women and is associated with serious health consequences. Advances in diagnosis and treatment are presented. The complexity of trichomonad pathogenesis is illustrated in the interaction of this parasite with human cells, tissues and the immune system. It is now becoming evident that the interaction of trichomonads with the host is frequently modulated by environmental signals. The molecular biology of trichomonads is still in its infancy, but analysis of genes, genomic structure and transcriptional mechanisms suggest that trichomonads combine both prokaryotic and eukaryotic features. Evidence for the ancient divergence of trichomonads from other eukaryotic lineages is discussed.
75 citations
TL;DR: During the period under review, several studies have been reported that confirm the impact of antifungal prophylaxis and the emergence of non-albicans Candida spp.
Abstract: Infections caused by Candida spp. are frequent and serious in oncology patients. Over the past decade, the introduction of azole antifungals as prophylactic agents, and other factors have caused a shift in the species of Candida that cause infection. During the period under review (June 1999 to June
37 citations
TL;DR: There is increasing evidence of involvement of C. pneumoniae infection in bronchial asthma, and the role of this agent in immunocompromised patients has also begun to be appreciated.
Abstract: Chlamydia pneumoniae is a significant cause of both upper and lower respiratory tract infections. The spectrum of diseases ranges from asymptomatic infection to serious disease, including severe pneumonia and exacerbations of chronic bronchitis requiring mechanical ventilation. There is increasing evidence of involvement of C. pneumoniae infection in bronchial asthma, and the role of this agent in immunocompromised patients has also begun to be appreciated.
32 citations
TL;DR: Knowledge gained in the molecular biology of IL-10 and its complex immune effects in experimental infection models are leading to new insights into therapeutic manipulation ofIL-10 in patients with systemic inflammatory diseases.
Abstract: Interleukin-10 is the most potent anti-inflammatory cytokine yet identified. It has multiple actions affecting the innate immune system as well as humoral and cellular immune responses. It occupies a pivotal role in the regulation of the immune response to microbial pathogens in health and disease. Knowledge gained in the molecular biology of IL-10 and its complex immune effects in experimental infection models are leading to new insights into therapeutic manipulation of IL-10 in patients with systemic inflammatory diseases.
28 citations
TL;DR: During the past 2 years some new therapeutic approaches for nosocomial pneumonia and modifications to established therapies have been described, such as optimal pharmacodynamic evaluations, monotherapy versus combination therapy, computer-assisted management programmes and antibiotic rotations.
Abstract: Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection. Supine body position in mechanically ventilated patients, and cardiopulmonary resuscitation and continuous sedation are significant risk factors for developing nosocomial pneumonia. During the past 2 years some new therapeutic approaches for nosocomial pneumonia and modifications to established therapies have been described, such as optimal pharmacodynamic evaluations, monotherapy versus combination therapy, computer-assisted management programmes and antibiotic rotations.
TL;DR: Only when this economic barrier can be lowered will new drugs emerge for use against sleeping sickness, as most representatives of the pharmaceutical industry believe that selling drugs to the victims of sleeping sickness will not yield sufficient income to justify expenses needed for the development of novel reagents.
Abstract: Problems associated with the current therapies of sleeping sickness include toxicity, resistance and a lack of a guaranteed supply. However, no new formulations are close to gaining a licence for clinical use and relatively few compounds have been shown to be effective in experimental systems. Many potentially good biochemical targets for drugs have been identified. Some of these have been validated and lead compounds have been developed. However, the biology of trypanosomes means that various pharmacological demands must be met in developing new trypanocides for clinical use. Foremost among these problems is the blood-brain barrier, across which trypanocides must cross to reach parasites in the cerebrospinal fluid.The principal problem, however, relates not to biological difficulties, which are technically surmountable, but to economics. Put simply, most representatives of the pharmaceutical industry believe that selling drugs to the victims of sleeping sickness will not yield sufficient income to justify expenses needed for the development of novel reagents. Only when this economic barrier can be lowered will new drugs emerge for use against sleeping sickness.
TL;DR: The carriage of most E. coli virulence determinants on pathogenicity islands, plasmids or phages allows the rapid evolution of these pathotypes, which need to be monitored closely.
Abstract: Enteropathogenic and enterohaemorrhagic Escherichia coli are important causes of bacterial gastroenteritis with the potential for progression to more serious syndromes, especially in the case of enterohaemorrhagic E. coli. Consequently, recent developments in molecular epidemiology and treatment regimens have focused on enterohaemorrhagic E. coli, while the similar initial pathogenic mechanisms of both enterohaemorrhagic and enteropathogenic E. coli continue to be investigated in detail. The carriage of most E. coli virulence determinants on pathogenicity islands, plasmids or phages allows the rapid evolution of these pathotypes, which need to be monitored closely.
TL;DR: Clinical trials should provide guidance as to the utility of antibiotics in the treatment or prevention of coronary artery disease and new insights into the pathogenesis of infection with C. pneumoniae have been reported.
Abstract: A body of evidence supports an association between Chlamydia pneumoniae and atherosclerosis. Recent prospective, seroepidemiologic studies have refined estimations of relative risk. Advances in diagnostic testing with the polymerase chain reaction have created a potential opportunity to screen for infected individuals. New insights into the pathogenesis of infection with C. pneumoniae have been reported, many of which are relevant to the development of atherosclerotic plaque. Clinical trials have now been initiated and should provide guidance as to the utility of antibiotics in the treatment or prevention of coronary artery disease.
TL;DR: This review considers infections that are of particular emerging importance and the forces that drive the emergence, submergence and re-emergence of infectious diseases are varied.
Abstract: The emergence of novel infectious diseases, and the re-emergence of others, is not new. The global ecosystem is constantly changing, influencing the micro- and macroenvironments in which humans and their microbial companions reside and interact. Sometimes the environmental circumstances favour the pathogen and there is an unexpected increase in disease activity or emergence of a new infection. Alternatively, pathogenicity factors are acquired by the microbe, allowing new diseases to emerge or old diseases to increase in importance. The forces that drive the emergence, submergence and re-emergence of infectious diseases are varied, but the influence that humans have on the global ecosystem is often of central importance. This review considers infections that are of particular emerging importance.
TL;DR: The Gram-negative bacterium Salmonella enterica has evolved different strategies to subvert normal host cellular functions, which allow it to enter into and proliferate within host cells.
Abstract: The success of a pathogen depends on its capacity to enter a host, circumvent host defense barriers and establish infection. The Gram-negative bacterium Salmonella enterica has evolved different strategies to subvert normal host cellular functions, which allow it to enter into and proliferate within host cells.
TL;DR: Key questions, such as what is the optimal time of switch for specific infections, and can conditions such as osteomyelitis and endocarditis be efficaciously treated with oral therapy, need to be answered and clinicians will be able to practise evidence-based infection management incorporating sequential antimicrobial therapy.
Abstract: Antimicrobials are an important source of hospital expenditure. Traditionally, severe bacterial infections have been treated initially with intravenous antibiotics, followed by physician-directed switch to oral therapy. Unfortunately this approach results in unnecessary prolongation of intravenous t
TL;DR: Direct and mycological examinations are sufficient to make a diagnosis and to differentiate P. marneffei from other opportunistic fungi, although advances in serodiagnosis may potentially enhance understanding of the pathogenesis and identification of early asymptomatic cases.
Abstract: From an almost unknown disease 15 years ago, Penicillium marneffei has emerged to become one of the most common opportunistic fungal pathogens among HIV-infected patients in the endemic area of southern China and northern Thailand. The mode of infection is primarily airborne, with the reticuloendothelial system as the main target. Penicilliosis is a fatal disease and systemic antifungals are the mainstay of therapy. Direct and mycological examinations are sufficient to make a diagnosis and to differentiate P. marneffei from other opportunistic fungi, although advances in serodiagnosis may potentially enhance understanding of the pathogenesis and identification of early asymptomatic cases.
TL;DR: Newborns and young infants are at increased risk of severe or prolonged infections, and recent advances in understanding of the host immune response in this age group, coupled with the development of molecular genetic tools, have paved the way for a new generation of preventive vaccines.
Abstract: Newborns and young infants are at increased risk of severe or prolonged infections. Recent advances in our understanding of the host immune response in this age group, coupled with the development of molecular genetic tools, have paved the way for a new generation of preventive vaccines.
TL;DR: The year under review has seen a remarkable proliferation of papers on d Dengue, four prospective studies have been carried out across the dengue belt, many groups have been pushing at the question of pathogenesis ofdengue haemorrhagic fever, and a breakthrough has been achieved in the development of a mouse model for human denguing fever.
Abstract: The year under review has seen a remarkable proliferation of papers on dengue. Four prospective studies have been carried out across the dengue belt, many groups have been pushing at the question of pathogenesis of dengue haemorrhagic fever, and a breakthrough has been achieved in the development of a mouse model for human dengue haemorrhagic fever.
TL;DR: During the past year, two agents have been released that have activity against multidrug-resistant Gram-positive pathogens such as quinupristin/dalfopristin and linezolid, and although neither agent is a panacea, these recently released agents offer new options for therapy.
Abstract: Multidrug-resistant Gram-positive pathogens such as vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative staphylococci account for a significant number of nosocomial infections, and new options for therapy have been lacking. During the past year, two agents have been released that have activity against these organisms: quinupristin/dalfopristin and linezolid. Although neither agent is a panacea, these recently released agents offer new options for therapy.
TL;DR: The sequence of the Treponema pallidum genome was completed in July 1998, yielding a wealth of new information regarding the enigmatic spirochete that causes syphilis and related treponematoses.
Abstract: The sequence of the Treponema pallidum genome was completed in July 1998, yielding a wealth of new information regarding the enigmatic spirochete that causes syphilis and related treponematoses. By providing the sequences and predicted functions of over 1000 genes, the genome sequence will greatly facilitate research on the genetic characteristics, physiology, antigenic structure, and pathogenesis of this organism. These advances are, in turn, expected to promote the refinement of conditions for in-vitro culture, an improvement of diagnostic tests, the development of effective vaccines, and an improved understanding of treponemal disease pathogenesis and manifestations.
TL;DR: Current knowledge on chloroquine's antimalarial mode of action and the genesis of the resistant phenotype in the human malarial parasite Plasmodium falciparum are summarized.
Abstract: For 40 years scientists have hotly debated the questions of how chloroquine kills malarial parasites and how resistance to this once first-line antimalarial drug has evolved. While an end to these debates is not in sight, as a result of the complexity of the subject, new findings have come forward that give the discussion a new direction. In this paper we will summarize current knowledge on chloroquine's antimalarial mode of action and the genesis of the resistant phenotype in the human malarial parasite Plasmodium falciparum, with special emphasis on the most recent developments in this field.
TL;DR: Data are beginning to emerge that firmly link bacterial inflammation and progressive disease with physiological and functional disability, and new trial designs need to address an integrated outcome analysis, with the assessment of long-term benefit and pharmaco-economic monitoring.
Abstract: Acute exacerbations of chronic bronchitis are one of the major public health challenges. New data suggest that they will remain so for many years. Although the role of bacteria in the initiation and maintenance of bronchial inflammation, both during and between exacerbations, is well recognized, studies of the long-term effects of therapy are few and inadequate, and the nature of the relationship with disease progression is largely unknown. Data are beginning to emerge that firmly link bacterial inflammation and progressive disease with physiological and functional disability. Methods are being developed to provide integrated, uncomplicated and reproducible assessments of health-related quality of life. These may prove fundamental to the proper investigation of new treatment modalities. Among the newer antibacterial agents, fluoroquinolones have received most investigative attention, regrettably usually without providing clinical confirmation of their obvious superiority in vitro and of their pharmacokinetic and related pharmacodynamic properties. New trial designs need to address an integrated outcome analysis, with the assessment of long-term benefit and pharmaco-economic monitoring. More antibacterial agents are available at the millennium than ever before. After 50 years, it would be preferable if we knew a little more about their role in this complex disease.
TL;DR: Evidence from recent studies involving both animal models and inflammatory bowel disease patients is presented which supports a role for bacteria in the aetiology and pathogenesis of Crohn's disease and ulcerative colitis.
Abstract: The cause of inflammatory bowel disease is unknown, but both environmental and genetic factors are implicated. This review presents evidence from recent studies involving both animal models and inflammatory bowel disease patients, which supports a role for bacteria in the aetiology and pathogenesis of Crohn's disease and ulcerative colitis.
TL;DR: No data currently exist directly comparing triple therapy regimens based on the three leading PI-sparing agents, efavirenz, nevirapine or abacavir, but the superiority of ef Cavirenz over indinavir based regimens was also observed in comparative data in this patient subset.
Abstract: The current standard of care for initial antiretroviral therapy is a combination of 2 nucleoside analogues with a third agent, a protease inhibitor (PI), a non-nucleoside reverse transcriptase inhibitor or a third nucleoside analogue. Recent data heralding the arrival of potent PI-sparing regimens for initial anti-retroviral therapy and concerns regarding PI-related metabolic disturbances have led to significant shifts in treatment practices. Protease inhibitor-sparing regimens with optimal antiviral activity may have several advantages over PI-based therapy for initial or prolonged therapy. These advantages include more convenient, non-food dependent dosing regimens, lower tablet volume, fewer drug interactions, central nervous system penetration and the maintenance of PIs as an option for second line therapy. However, no data currently exist directly comparing triple therapy regimens based on the three leading PI-sparing agents, efavirenz, nevirapine or abacavir. All these agents have been compared in randomized controlled studies in treatment naive patients to triple therapy with the PI indinavir. In these studies, similar responses to indinavir were observed with nevirapine or abacavir regimens, whereas superiority was observed with efavirenz. Limited data in high viral load patients treated with nevirapine based regimens currently exist. However, the superiority of efavirenz over indinavir based regimens was also observed in comparative data in this patient subset. PI-sparing approaches appear generally well tolerated with few individuals discontinuing in clinical studies due to adverse drug events. The majority of adverse events with efavirenz and nevirapine occur within the first month, are predictable and are manageable without therapy interruption. Similarly, apart from a rare (3%) hypersensitivity reaction, which requires therapy cessation without rechallenge, adverse effects with abacavir are uncommon.
TL;DR: Since CD8+ T cells recognize antigen in the context of class I molecules, the identification of a human leucocyte antigen class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8- T lymphocytes in the immunopathogenesis of Psoriasis.
Abstract: Psoriasis occurs with at least undiminished frequency in HIV infected individuals. The behaviour of psoriasis in HIV disease is of interest, both in terms of pathogenesis and therapy, because of the background of profound immunodysregulation. It is paradoxical that, while drugs that target T lymphocytes are effective in psoriasis, the condition should be exacerbated by HIV infection. Antiretroviral therapy may improve psoriasis in tandem with improvement in the overall clinical and virological condition of the patient. The aetiopathogenesis of psoriasis is unknown but genetic and environmental factors are thought to be involved. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4+ versus CD8+ T lymphocytes. Current opinion favours an autoimmune basis for psoriasis, although the precipitating activating signal(s) within psoriatic plaques remains unknown. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. Since CD8+ T cells recognize antigen in the context of class I molecules, the identification of a human leucocyte antigen class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8+ T lymphocytes in the immunopathogenesis of psoriasis. HLA-Cw*0602 could act as a cross-reactive target for cytotoxic T lymphocytes responding to processed peptides from microorganisms. Human retrovirus-5 is a recently described, partially characterized retrovirus and has been implicated in the pathogenesis of psoriatic arthropathy but not psoriasis.
TL;DR: This review attempts to reduce the gap between the overwhelming amount of information coming recently from laboratory research and the sparse contributions resulting from clinical and epidemiological investigations of the second parasitic cause of death resulting from a protozoan parasite.
Abstract: Invasive amoebiasis, the infection of humans by Entamoeba histolytica associated with dysentery and liver abscess, is still a major cause of morbidity and mortality in developing countries. This review attempts to reduce the gap between the overwhelming amount of information coming recently from laboratory research and the sparse contributions resulting from clinical and epidemiological investigations of the second parasitic cause of death resulting from a protozoan parasite.
TL;DR: Research activity should focus in developing early diagnostic tools and drugs which would be able to effectively treat tuberculosis cases for shorter periods of time in the new millennium.
Abstract: Tuberculosis remains one of the leading infectious disease killers globally. A significant reservoir of infected individuals and disease activity remains, particularly in the countries of the world which have the least economic resources to treat latent and active disease. This has set the stage, ov
TL;DR: In this paper, the authors report that most changes are being seen in the diagnosis of fungal infections, particularly aspergillosis, and the way in which it is being incorporated into treatment strategies.
Abstract: Patterns of bacterial infection have remained fairly static with Gram-positive bacteria predominating, although this varies between institutions and between patient populations. Similarly, antimicrobial resistance rates differ widely and reflect antibiotic use and exposure. Hence, each institution should devote microbiological resources to maintain surveillance and employ vigilance so that antimicrobial treatment protocols can be adapted to meet any new challenges. Most changes are being seen in the diagnosis of fungal infections, particularly aspergillosis, and the way in which it is being incorporated into treatment strategies.