Clinical Microbiology Reviews[JOURNAL]
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200 papers
Congenital Syphilis: a Review of Global Epidemiology.
Gilmour LS, Walls T
Clin Microbiol Rev · 2023 Jun · PMID 36920205 · Full text
In 2007, the World Health Organization (WHO) launched a global health initiative for the elimination of mother-to-child transmission (MTCT) of syphilis. This condition is highly preventable through antenatal identificati...
In 2007, the World Health Organization (WHO) launched a global health initiative for the elimination of mother-to-child transmission (MTCT) of syphilis. This condition is highly preventable through antenatal identification of syphilis infection and treatment with penicillin during pregnancy. This review summarizes the global status of MTCT of syphilis and concludes that this condition remains a significant issue worldwide. There are large variations in case rates by region, with the highest numbers of cases in the African and Eastern Mediterranean regions, where there are also the least data available. There are also pockets of high-incidence areas within the other regions. Although the general trend is of decreasing rates over time, there are concerning indications of consistently increasing congenital syphilis cases in some areas, particularly in areas which have previously had very low case numbers. A concerted effort will be required to achieve the 2007 WHO goal of worldwide elimination of MTCT of syphilis in the near future.
Agnostic Sequencing for Detection of Viral Pathogens.
Gauthier NPG, Chorlton SD, Krajden M … +1 more , Manges AR
Clin Microbiol Rev · 2023 Mar · PMID 36847515 · Full text
The advent of next-generation sequencing (NGS) technologies has expanded our ability to detect and analyze microbial genomes and has yielded novel molecular approaches for infectious disease diagnostics. While several ta...
The advent of next-generation sequencing (NGS) technologies has expanded our ability to detect and analyze microbial genomes and has yielded novel molecular approaches for infectious disease diagnostics. While several targeted multiplex PCR and NGS-based assays have been widely used in public health settings in recent years, these targeted approaches are limited in that they still rely on knowledge of a pathogen's genome, and an untargeted or unknown pathogen will not be detected. Recent public health crises have emphasized the need to prepare for a wide and rapid deployment of an agnostic diagnostic assay at the start of an outbreak to ensure an effective response to emerging viral pathogens. Metagenomic techniques can nonspecifically sequence all detectable nucleic acids in a sample and therefore do not rely on prior knowledge of a pathogen's genome. While this technology has been reviewed for bacterial diagnostics and adopted in research settings for the detection and characterization of viruses, viral metagenomics has yet to be widely deployed as a diagnostic tool in clinical laboratories. In this review, we highlight recent improvements to the performance of metagenomic viral sequencing, the current applications of metagenomic sequencing in clinical laboratories, as well as the challenges that impede the widespread adoption of this technology.
An Overlooked and Underrated Endemic Mycosis-Talaromycosis and the Pathogenic Fungus Talaromyces marneffei.
Wang F, Han R, Chen S
Clin Microbiol Rev · 2023 Mar · PMID 36648228 · Full text
Talaromycosis is an invasive mycosis endemic in tropical and subtropical Asia and is caused by the pathogenic fungus Talaromyces marneffei. Approximately 17,300 cases of T. marneffei infection are diagnosed annually, and...
Talaromycosis is an invasive mycosis endemic in tropical and subtropical Asia and is caused by the pathogenic fungus Talaromyces marneffei. Approximately 17,300 cases of T. marneffei infection are diagnosed annually, and the reported mortality rate is extremely high (~1/3). Despite the devastating impact of talaromycosis on immunocompromised individuals, particularly HIV-positive persons, and the increase in reported occurrences in HIV-uninfected persons, diagnostic and therapeutic approaches for talaromycosis have received far too little attention worldwide. In 2021, scientists living in countries where talaromycosis is endemic raised a global demand for it to be recognized as a neglected tropical disease. Therefore, and the infectious disease induced by this fungus must be treated with concern. is a thermally dimorphic saprophytic fungus with a complicated mycological growth process that may produce various cell types in its life cycle, including conidia, hyphae, and yeast, all of which are associated with its pathogenicity. However, understanding of the pathogenic mechanism of has been limited until recently. To achieve a holistic view of and talaromycosis, the current knowledge about talaromycosis and research breakthroughs regarding growth biology are discussed in this review, along with the interaction of the fungus with environmental stimuli and the host immune response to fungal infection. Importantly, the future research directions required for understanding this serious infection and its causative pathogenic fungus are also emphasized to identify solutions that will alleviate the suffering of susceptible individuals worldwide.
Antiviral Approaches against Influenza Virus.
Kumari R, Sharma SD, Kumar A … +8 more , Ende Z, Mishina M, Wang Y, Falls Z, Samudrala R, Pohl J, Knight PR, Sambhara S
Clin Microbiol Rev · 2023 Mar · PMID 36645300 · Full text
Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and...
Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza.
The mRNA Vaccine Technology Era and the Future Control of Parasitic Infections.
You H, Jones MK, Gordon CA … +5 more , Arganda AE, Cai P, Al-Wassiti H, Pouton CW, McManus DP
Clin Microbiol Rev · 2023 Mar · PMID 36625671 · Full text
Despite intensive long-term efforts, with very few exceptions, the development of effective vaccines against parasitic infections has presented considerable challenges, given the complexity of parasite life cycles, the i...
Despite intensive long-term efforts, with very few exceptions, the development of effective vaccines against parasitic infections has presented considerable challenges, given the complexity of parasite life cycles, the interplay between parasites and their hosts, and their capacity to escape the host immune system and to regulate host immune responses. For many parasitic diseases, conventional vaccine platforms have generally proven ill suited, considering the complex manufacturing processes involved and the costs they incur, the inability to posttranslationally modify cloned target antigens, and the absence of long-lasting protective immunity induced by these antigens. An effective antiparasite vaccine platform is required to assess the effectiveness of novel vaccine candidates at high throughput. By exploiting the approach that has recently been used successfully to produce highly protective COVID mRNA vaccines, we anticipate a new wave of research to advance the use of mRNA vaccines to prevent parasitic infections in the near future. This article considers the characteristics that are required to develop a potent antiparasite vaccine and provides a conceptual foundation to promote the development of parasite mRNA-based vaccines. We review the recent advances and challenges encountered in developing antiparasite vaccines and evaluate the potential of developing mRNA vaccines against parasites, including those causing diseases such as malaria and schistosomiasis, against which vaccines are currently suboptimal or not yet available.
Human Listeriosis.
Koopmans MM, Brouwer MC, Vázquez-Boland JA … +1 more , van de Beek D
Clin Microbiol Rev · 2023 Mar · PMID 36475874 · Full text
Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food. Clinically, listerial disease, or listeriosis, most often pres...
Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food. Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal sepsis. Invasive listeriosis is life-threatening and a main cause of foodborne illness leading to hospital admissions in Western countries. Sources of contamination can be identified through international surveillance systems for foodborne bacteria and strains' genetic data sharing. Large-scale whole genome studies have increased our knowledge on the diversity and evolution of L. monocytogenes, while recent pathophysiological investigations have improved our mechanistic understanding of listeriosis. In this article, we present an overview of human listeriosis with particular focus on relevant features of the causative bacterium, epidemiology, risk groups, pathogenesis, clinical manifestations, and treatment and prevention.
Human and Animal Fascioliasis: Origins and Worldwide Evolving Scenario.
Mas-Coma S, Valero MA, Bargues MD
Clin Microbiol Rev · 2022 Dec · PMID 36468877 · Full text
Fascioliasis is a plant- and waterborne zoonotic parasitic disease caused by two trematode species: (i) Fasciola hepatica in Europe, Asia, Africa, the Americas, and Oceania and (ii) , which is restricted to Africa and As...
Fascioliasis is a plant- and waterborne zoonotic parasitic disease caused by two trematode species: (i) Fasciola hepatica in Europe, Asia, Africa, the Americas, and Oceania and (ii) , which is restricted to Africa and Asia. Fasciolid liver flukes infect mainly herbivores as ruminants, equids, and camelids but also omnivore mammals as humans and swine and are transmitted by freshwater Lymnaeidae snail vectors. Two phases may be distinguished in fasciolid evolution. The long predomestication period includes the origin in east-southern Africa around the mid-Miocene, the origin in the Near-Middle East of Asia around the latest Miocene to Early Pliocene, and their subsequent local spread. The short postdomestication period includes the worldwide spread by human-guided movements of animals in the last 12,000 years and the more recent transoceanic anthropogenic introductions of into the Americas and Oceania and of into several large islands of the Pacific with ships transporting livestock in the last 500 years. The routes and chronology of the spreading waves followed by both fasciolids into the five continents are redefined on the basis of recently generated knowledge of human-guided movements of domesticated hosts. No local, zonal, or regional situation showing disagreement with historical records was found, although in a few world zones the available knowledge is still insufficient. The anthropogenically accelerated evolution of fasciolids allows us to call them "peridomestic endoparasites." The multidisciplinary implications for crucial aspects of the disease should therefore lead the present baseline update to be taken into account in future research studies.
Osteoarticular Mycoses.
Gamaletsou MN, Rammaert B, Brause B … +20 more , Bueno MA, Dadwal SS, Henry MW, Katragkou A, Kontoyiannis DP, McCarthy MW, Miller AO, Moriyama B, Pana ZD, Petraitiene R, Petraitis V, Roilides E, Sarkis JP, Simitsopoulou M, Sipsas NV, Taj-Aldeen SJ, Zeller V, Lortholary O, Walsh TJ, International Consortium for Osteoarticular Mycoses
Clin Microbiol Rev · 2022 Dec · PMID 36448782 · Full text
Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, th...
Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. osteomyelitis and arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of and Aspergillus arthritis. Relapsed infection, particularly in arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.
Monkeypox Virus Infections in Humans.
Elsayed S, Bondy L, Hanage WP
Clin Microbiol Rev · 2022 Dec · PMID 36374082 · Full text
Human monkeypox is a viral zoonosis endemic to West and Central Africa that has recently generated increased interest and concern on a global scale as an emerging infectious disease threat in the midst of the slowly rele...
Human monkeypox is a viral zoonosis endemic to West and Central Africa that has recently generated increased interest and concern on a global scale as an emerging infectious disease threat in the midst of the slowly relenting COVID-2019 disease pandemic. The hallmark of infection is the development of a flu-like prodrome followed by the appearance of a smallpox-like exanthem. Precipitous person-to-person transmission of the virus among residents of 100 countries where it is nonendemic has motivated the immediate and widespread implementation of public health countermeasures. In this review, we discuss the origins and virology of monkeypox virus, its link with smallpox eradication, its record of causing outbreaks of human disease in regions where it is endemic in wildlife, its association with outbreaks in areas where it is nonendemic, the clinical manifestations of disease, laboratory diagnostic methods, case management, public health interventions, and future directions.
Updated Review on Species: 2006-2021.
Traxler RM, Bell ME, Lasker B … +3 more , Headd B, Shieh WJ, McQuiston JR
Clin Microbiol Rev · 2022 Dec · PMID 36314911 · Full text
This review serves as an update to the previous review by Brown-Elliott et al. published in 2006 (B. A. Brown-Elliott, J. M. Brown, P. S. Conville, and R. J. Wallace. Jr., Clin Microbiol Rev 19:259-282, 2006, https://do...
This review serves as an update to the previous review by Brown-Elliott et al. published in 2006 (B. A. Brown-Elliott, J. M. Brown, P. S. Conville, and R. J. Wallace. Jr., Clin Microbiol Rev 19:259-282, 2006, https://doi.org/10.1128/CMR.19.2.259-282.2006). Included is a discussion on the taxonomic expansion of the genus, current identification methods, and the impact of new technology (including matrix-assisted laser desorption ionization-time of flight [MALDI-TOF] and whole genome sequencing) on diagnosis and treatment. Clinical manifestations, the epidemiology, and geographic distribution are briefly discussed. An additional section on actinomycotic mycetoma is added to address this often-neglected disease.
Persistent Borrelia burgdorferi Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models.
Verschoor YL, Vrijlandt A, Spijker R … +5 more , van Hest RM, Ter Hofstede H, van Kempen K, Henningsson AJ, Hovius JW
Clin Microbiol Rev · 2022 Dec · PMID 36222707 · Full text
Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi group, which are transmitted by tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations...
Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi group, which are transmitted by tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations of Lyme borreliosis are diverse and treated with oral or intravenous antibiotics. In some patients, long-lasting and debilitating symptoms can persist after the recommended antibiotic treatment. The etiology of such persisting symptoms is under debate, and one hypothesis entails persistent infection by a subset of spirochetes after antibiotic therapy. Here, we review and appraise the experimental evidence from animal studies on the persistence of B. burgdorferi sensu lato infection after antibiotic treatment, focusing on the antimicrobial agents doxycycline and ceftriaxone. Our review indicates that some animal studies found sporadic positive cultures after antibiotic treatment. However, this culture positivity often seemed to be related to inadequate antibiotic treatment, and the few positive cultures in some studies could not be reproduced in other studies. Overall, current results from animal studies provide insufficient evidence for the persistence of viable and infectious spirochetes after adequate antibiotic treatment. Borrelial nucleic acids, on the contrary, were frequently detected in these animal studies and may thus persist after antibiotic treatment. We put forward that research into the pathogenesis of persisting complaints after antibiotic treatment for Lyme borreliosis in humans should be a top priority, but future studies should most definitely also focus on explanations other than persistent B. burgdorferi sensu lato infection after antibiotic treatment.
The Changing Paradigm of Drug-Resistant Tuberculosis Treatment: Successes, Pitfalls, and Future Perspectives.
Dookie N, Ngema SL, Perumal R … +3 more , Naicker N, Padayatchi N, Naidoo K
Clin Microbiol Rev · 2022 Dec · PMID 36200885 · Full text
Drug-resistant tuberculosis (DR-TB) remains a global crisis due to the increasing incidence of drug-resistant forms of the disease, gaps in detection and prevention, models of care, and limited treatment options. The DR-...
Drug-resistant tuberculosis (DR-TB) remains a global crisis due to the increasing incidence of drug-resistant forms of the disease, gaps in detection and prevention, models of care, and limited treatment options. The DR-TB treatment landscape has evolved over the last 10 years. Recent developments include the remarkable activity demonstrated by the newly approved anti-TB drugs bedaquiline and pretomanid against Mycobacterium tuberculosis. Hence, treatment of DR-TB has drastically evolved with the introduction of the short-course regimen for multidrug-resistant TB (MDR-TB), transitioning to injection-free regimens and the approval of the 6-month short regimens for rifampin-resistant TB and MDR-TB. Moreover, numerous clinical trials are under way with the aim to reduce pill burden and shorten the DR-TB treatment duration. While there have been apparent successes in the field, some challenges remain. These include the ongoing inclusion of high-dose isoniazid in DR-TB regimens despite a lack of evidence for its efficacy and the inclusion of ethambutol and pyrazinamide in the standard short regimen despite known high levels of background resistance to both drugs. Furthermore, antimicrobial heteroresistance, extensive cavitary disease and intracavitary gradients, the emergence of bedaquiline resistance, and the lack of biomarkers to monitor DR-TB treatment response remain serious challenges to the sustained successes. In this review, we outline the impact of the new drugs and regimens on patient treatment outcomes, explore evidence underpinning current practices on regimen selection and duration, reflect on the disappointments and pitfalls in the field, and highlight key areas that require continued efforts toward improving treatment approaches and rapid biomarkers for monitoring treatment response.
The Microbial Etiology of Community-Acquired Pneumonia in Adults: from Classical Bacteriology to Host Transcriptional Signatures.
Gadsby NJ, Musher DM
Clin Microbiol Rev · 2022 Dec · PMID 36165783 · Full text
All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification o...
All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, , Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized ("typical") bacterial pathogens as well as a role for commensal bacteria ("normal respiratory flora"). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.
Genotypic Resistance Testing of HIV-1 DNA in Peripheral Blood Mononuclear Cells.
Chu C, Armenia D, Walworth C … +2 more , Santoro MM, Shafer RW
Clin Microbiol Rev · 2022 Dec · PMID 36102816 · Full text
HIV-1 DNA exists in nonintegrated linear and circular episomal forms and as integrated proviruses. In patients with plasma viremia, most peripheral blood mononuclear cell (PBMC) HIV-1 DNA consists of recently produced no...
HIV-1 DNA exists in nonintegrated linear and circular episomal forms and as integrated proviruses. In patients with plasma viremia, most peripheral blood mononuclear cell (PBMC) HIV-1 DNA consists of recently produced nonintegrated virus DNA while in patients with prolonged virological suppression (VS) on antiretroviral therapy (ART), most PBMC HIV-1 DNA consists of proviral DNA produced months to years earlier. Drug-resistance mutations (DRMs) in PBMCs are more likely to coexist with ancestral wild-type virus populations than they are in plasma, explaining why next-generation sequencing is particularly useful for the detection of PBMC-associated DRMs. In patients with ongoing high levels of active virus replication, the DRMs detected in PBMCs and in plasma are usually highly concordant. However, in patients with lower levels of virus replication, it may take several months for plasma virus DRMs to reach detectable levels in PBMCs. This time lag explains why, in patients with VS, PBMC genotypic resistance testing (GRT) is less sensitive than historical plasma virus GRT, if previous episodes of virological failure and emergent DRMs were either not prolonged or not associated with high levels of plasma viremia. Despite the increasing use of PBMC GRT in patients with VS, few studies have examined the predictive value of DRMs on the response to a simplified ART regimen. In this review, we summarize what is known about PBMC HIV-1 DNA dynamics, particularly in patients with suppressed plasma viremia, the methods used for PBMC HIV-1 GRT, and the scenarios in which PBMC GRT has been used clinically.
Paracoccidioidomycosis: Current Status and Future Trends.
Hahn RC, Hagen F, Mendes RP … +6 more , Burger E, Nery AF, Siqueira NP, Guevara A, Rodrigues AM, de Camargo ZP
Clin Microbiol Rev · 2022 Dec · PMID 36074014 · Full text
Paracoccidioidomycosis (PCM), initially reported in 1908 in the city of São Paulo, Brazil, by Adolpho Lutz, is primarily a systemic and neglected tropical mycosis that may affect individuals with certain risk factors aro...
Paracoccidioidomycosis (PCM), initially reported in 1908 in the city of São Paulo, Brazil, by Adolpho Lutz, is primarily a systemic and neglected tropical mycosis that may affect individuals with certain risk factors around Latin America, especially Brazil. Paracoccidioides brasiliensis , a classical thermodimorphic fungus associated with PCM, was long considered to represent a monotypic taxon. However, advances in molecular taxonomy revealed several cryptic species, including Paracoccidioides americana, P. restrepiensis, P. venezuelensis, and P. lutzii, that show a preference for skin and mucous membranes, lymph nodes, and respiratory organs but can also affect many other organs. The classical diagnosis of PCM benefits from direct microscopy culture-based, biochemical, and immunological assays in a general microbiology laboratory practice providing a generic identification of the agents. However, molecular assays should be employed to identify isolates to the species level, data that would be complemented by epidemiological investigations. From a clinical perspective, all probable and confirmed cases should be treated. The choice of treatment and its duration must be considered, along with the affected organs, process severity, history of previous treatment failure, possibility of administering oral medication, associated diseases, pregnancy, and patient compliance with the proposed treatment regimen. Nevertheless, even after appropriate treatment, there may be relapses, which generally occur 5 years after the apparent cure following treatment, and also, the mycosis may be confused with other diseases. This review provides a comprehensive and critical overview of the immunopathology, laboratory diagnosis, clinical aspects, and current treatment of PCM, highlighting current issues in the identification, treatment, and patient follow-up in light of recent species taxonomic developments.
Reassessment of Historical Clinical Trials Supports the Effectiveness of Phage Therapy.
Marongiu L, Burkard M, Lauer UM … +2 more , Hoelzle LE, Venturelli S
Clin Microbiol Rev · 2022 Dec · PMID 36069758 · Full text
Phage therapy has become a hot topic in medical research due to the increasing prevalence of antibiotic-resistant bacteria strains. In the treatment of bacterial infections, bacteriophages have several advantages over an...
Phage therapy has become a hot topic in medical research due to the increasing prevalence of antibiotic-resistant bacteria strains. In the treatment of bacterial infections, bacteriophages have several advantages over antibiotics, including strain specificity, lack of serious side effects, and low development costs. However, scientists dismissed the clinical success of early clinical trials in the 1940s, slowing the adoption of this promising antibacterial application in Western countries. The current study used statistical methods commonly used in modern meta-analysis to reevaluate early 20th-century studies and compare them with clinical trials conducted in the last 20 years. Using a random effect model, the development of disease after treatment with or without phages was measured in odds ratios (OR) with 95% confidence intervals (CI). Based on the findings of 17 clinical trials conducted between 1921 and 1940, phage therapy was effective (OR = 0.21, 95% CI = 0.10 to 0.44, value < 0.0001). The current study includes a topic review on modern clinical trials; four could be analyzed, indicating a noneffective therapy (OR = 2.84, 95% CI = 1.53 to 5.27, value = 0.0009). The results suggest phage therapy was surprisingly less effective than standard treatments in resolving bacterial infections. However, the results were affected by the small sample set size. This work also contextualizes the development of phage therapy in the early 20th century and highlights the expansion of phage applications in the last few years. In conclusion, the current review shows phage therapy is no longer an underestimated tool in the treatment of bacterial infections.
Controlled Human Infection Models To Accelerate Vaccine Development.
Choy RKM, Bourgeois AL, Ockenhouse CF … +3 more , Walker RI, Sheets RL, Flores J
Clin Microbiol Rev · 2022 Sep · PMID 35862754 · Full text
The timelines for developing vaccines against infectious diseases are lengthy, and often vaccines that reach the stage of large phase 3 field trials fail to provide the desired level of protective efficacy. The applicati...
The timelines for developing vaccines against infectious diseases are lengthy, and often vaccines that reach the stage of large phase 3 field trials fail to provide the desired level of protective efficacy. The application of controlled human challenge models of infection and disease at the appropriate stages of development could accelerate development of candidate vaccines and, in fact, has done so successfully in some limited cases. Human challenge models could potentially be used to gather critical information on pathogenesis, inform strain selection for vaccines, explore cross-protective immunity, identify immune correlates of protection and mechanisms of protection induced by infection or evoked by candidate vaccines, guide decisions on appropriate trial endpoints, and evaluate vaccine efficacy. We prepared this report to motivate fellow scientists to exploit the potential capacity of controlled human challenge experiments to advance vaccine development. In this review, we considered available challenge models for 17 infectious diseases in the context of the public health importance of each disease, the diversity and pathogenesis of the causative organisms, the vaccine candidates under development, and each model's capacity to evaluate them and identify correlates of protective immunity. Our broad assessment indicated that human challenge models have not yet reached their full potential to support the development of vaccines against infectious diseases. On the basis of our review, however, we believe that describing an ideal challenge model is possible, as is further developing existing and future challenge models.
Sensitivity to Vaccines, Therapeutic Antibodies, and Viral Entry Inhibitors and Advances To Counter the SARS-CoV-2 Omicron Variant.
Zhou H, Møhlenberg M, Thakor JC … +5 more , Tuli HS, Wang P, Assaraf YG, Dhama K, Jiang S
Clin Microbiol Rev · 2022 Sep · PMID 35862736 · Full text
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, and spread in communities at a faster rate, re...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, and spread in communities at a faster rate, resulting in multiple waves of surge in Coronavirus Disease 2019 (COVID-19) cases. A highly mutated and transmissible SARS-CoV-2 Omicron variant has recently emerged, driving the extremely high peak of infections in almost all continents at an unprecedented speed and scale. The Omicron variant evades the protection rendered by vaccine-induced antibodies and natural infection, as well as overpowers the antibody-based immunotherapies, raising the concerns of current effectiveness of available vaccines and monoclonal antibody-based therapies. This review outlines the most recent advancements in studying the virology and biology of the Omicron variant, highlighting its increased resistance to current antibody-based therapeutics and its immune escape against vaccines. However, the Omicron variant is highly sensitive to viral fusion inhibitors targeting the HR1 motif in the spike protein, enzyme inhibitors, involving the endosomal fusion pathway, and ACE2-based entry inhibitors. Omicron variant-associated infectivity and entry mechanisms of Omicron variant are essentially distinct from previous characterized variants. Innate sensing and immune evasion of SARS-CoV-2 and T cell immunity to the virus provide new perspectives of vaccine and drug development. These findings are important for understanding SARS-CoV-2 viral biology and advances in developing vaccines, antibody-based therapies, and more effective strategies to mitigate the transmission of the Omicron variant or the next SARS-CoV-2 variant of concern.
Diagnosis, Management, and Future Control of Cholera.
Chowdhury F, Ross AG, Islam MT … +2 more , McMillan NAJ, Qadri F
Clin Microbiol Rev · 2022 Sep · PMID 35726607 · Full text
Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million cases and 143,000 deaths each year due to cholera. T...
Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million cases and 143,000 deaths each year due to cholera. The disease is transmitted fecally-orally via contaminated food or water. Severe dehydrating cholera can progress to hypovolemic shock due to the rapid loss of fluids and electrolytes, which requires a rapid infusion of intravenous (i.v.) fluids. The case fatality rate exceeds 50% without proper clinical management but can be less than 1% with prompt rehydration and antibiotics. Oral cholera vaccines (OCVs) serve as a major component of an integrated control package during outbreaks or within zones of endemicity. Water, sanitation, and hygiene (WaSH); health education; and prophylactic antibiotic treatment are additional components of the prevention and control of cholera. The World Health Organization (WHO) and the Global Task Force for Cholera Control (GTFCC) have set an ambitious goal of eliminating cholera by 2030 in high-risk areas.
Candidate Phyla Radiation, an Underappreciated Division of the Human Microbiome, and Its Impact on Health and Disease.
Naud S, Ibrahim A, Valles C … +4 more , Maatouk M, Bittar F, Tidjani Alou M, Raoult D
Clin Microbiol Rev · 2022 Sep · PMID 35658516 · Full text
Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as "ultramicrobacteria...
Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as "ultramicrobacteria" with a cell volume under 0.1 μm and were first associated with the human oral microbiota in 2007. The evolution of technology has been paramount for the study of CPR within the human microbiota. In fact, since these ultramicrobacteria have yet to be axenically cultured despite ongoing efforts, progress in imaging technology has allowed their observation and morphological description. Although their genomic abilities and taxonomy are still being studied, great strides have been made regarding their taxonomic classification, as well as their lifestyle. In addition, advancements in next-generation sequencing and the continued development of bioinformatics tools have allowed their detection as commensals in different human habitats, including the oral cavity and gastrointestinal and genital tracts, thus highlighting CPR as a nonnegligible part of the human microbiota with an impact on physiological settings. Conversely, several pathologies present dysbiosis affecting CPR levels, including inflammatory, mucosal, and infectious diseases. In this exhaustive review of the literature, we provide a historical perspective on the study of CPR, an overview of the methods available to study these organisms and a description of their taxonomy and lifestyle. In addition, their distribution in the human microbiome is presented in both homeostatic and dysbiotic settings. Future efforts should focus on developing cocultures and, if possible, axenic cultures to obtain isolates and therefore genomes that would provide a better understanding of these ultramicrobacteria, the importance of which in the human microbiome is undeniable.
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