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Current Research in Immunology 2023Plague remains endemic in many parts of the world, and despite efforts, no preventative vaccine is available. We performed a systemic review of available randomised... (Review)
Review
Plague remains endemic in many parts of the world, and despite efforts, no preventative vaccine is available. We performed a systemic review of available randomised controlled trials (RCTs) of live, attenuated, or killed plague vaccines vs. placebo, no intervention, or other plague vaccine to evaluate their efficacy, safety, and immunogenicity. Data sources included MEDLINE, Embase, and the Cochrane Library; clinical trial registers; and reference lists of included studies. Primary outcomes were efficacy, safety, and immunogenicity. Risk of bias was assessed using the Cochrane Collaborations tool. Only 2 RCTs, both on subunit vaccines, were included out of the 75 screened articles. The 2 trials included 240 participants with a follow-up of 3 months and 60 participants with a follow-up of 13 months, respectively. Safety evidence was limited, but both vaccines were well tolerated, with only mild to moderate adverse events. Both vaccines were immunogenic in a dose-dependent manner. However, given the limited data identified in this systematic review, we are unable to quantify the efficacy of vaccines to prevent plague, as well as their long-term safety and immunogenicity. More trials of plague vaccines are needed to generate additional evidence of their long-term effects.
PubMed: 37954941
DOI: 10.1016/j.crimmu.2023.100072 -
Health Security 2023Plague meningitis is a serious and often fatal manifestation of infection. In the aftermath of a bioweapon attack with , this typically rare manifestation may develop...
Plague meningitis is a serious and often fatal manifestation of infection. In the aftermath of a bioweapon attack with , this typically rare manifestation may develop in a substantial number of patients, particularly if treatment delays occur. Risk factors, clinical evolution, and optimal treatment strategies for plague meningitis are not well understood. We searched PubMed Central and other databases for reports of plague meningitis in any language. Articles containing descriptions of patients with plague meningitis and their treatment and outcomes were included. Among 1,496 articles identified in our search, 56 articles describing 84 cases from 1898 to 2015 met inclusion criteria. The median age of patients was 16 years (range 6 weeks to 64 years); 68% were male. Most patients (n = 50, 60%) developed meningitis following primary bubonic plague. Common signs and symptoms included fever (n = 56, 66%), nuchal rigidity (n = 38, 45%), and headache (n = 33, 36%); 29% (n = 24) of patients had focal neurologic deficits such as cranial nerve abnormalities. Almost all (n = 23, 96%) of the 24 patients who did not receive antimicrobials died, and 42% (n = 25) of the 59 patients treated with antimicrobials died. The case fatality rate of patients grouped by antimicrobial received was 50% (1 out of 2) for fluoroquinolones, 19% (4 out of 21) for aminoglycosides, 14% (2 out of 14) for sulfonamides, 11% (2 out of 18) for chloramphenicol, and 0% (0 out of 13) for tetracyclines. Plague meningitis most often occurs as a complication of bubonic plague and can cause focal neurologic deficits. Survival is more likely in patients who receive antimicrobials; tetracyclines, aminoglycosides, and chloramphenicol had the lowest associated case fatality rates.
Topics: Humans; Male; Infant; Female; Plague; Anti-Bacterial Agents; Chloramphenicol; Aminoglycosides; Meningitis; Disease Progression
PubMed: 36576503
DOI: 10.1089/hs.2022.0081 -
The Cochrane Database of Systematic... 2000Plague is endemic in China, Mongolia, Burma, Vietnam, Indonesia, India, large parts of Southern Africa, the United States and South America. There are three types of... (Review)
Review
BACKGROUND
Plague is endemic in China, Mongolia, Burma, Vietnam, Indonesia, India, large parts of Southern Africa, the United States and South America. There are three types of vaccines (live attenuated, killed and F1 fraction) with varying means of administration.
OBJECTIVES
The objective of this review was to assess the effects of vaccines to prevent plague.
SEARCH STRATEGY
We searched Medline, Embase, the Cochrane Controlled Trials Register and reference lists of articles. We handsearched the journal 'Vaccine' and contacted experts in the field.
SELECTION CRITERIA
Randomised trials comparing live and killed plague vaccines against no intervention, placebo, other plague vaccines or vaccines against other disease (control vaccines).
DATA COLLECTION AND ANALYSIS
Three reviewers assessed the eligibility of trials.
MAIN RESULTS
No trials were included.
REVIEWER'S CONCLUSIONS
There is not enough evidence to evaluate the effectiveness of any plague vaccine, or the relative effectiveness between vaccines and their tolerability. Circumstantial data from observational studies suggest that killed types may be more effective and have fewer adverse effects than attenuated types of vaccine. No evidence appears to exist on the long-term effects of any plague vaccine.
Topics: Humans; Plague; Plague Vaccine; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 10796565
DOI: 10.1002/14651858.CD000976 -
Malaria Journal Oct 2017Lack of valid and reliable data on malaria deaths continues to be a problem that plagues the global health community. To address this gap, the verbal autopsy (VA) method... (Review)
Review
BACKGROUND
Lack of valid and reliable data on malaria deaths continues to be a problem that plagues the global health community. To address this gap, the verbal autopsy (VA) method was developed to ascertain cause of death at the population level. Despite the adoption and wide use of VA, there are many recognized limitations of VA tools and methods, especially for measuring malaria mortality. This study synthesizes the strengths and limitations of existing VA tools and methods for measuring malaria mortality (MM) in low- and middle-income countries through a systematic literature review.
METHODS
The authors searched PubMed, Cochrane Library, Popline, WHOLIS, Google Scholar, and INDEPTH Network Health and Demographic Surveillance System sites' websites from 1 January 1990 to 15 January 2016 for articles and reports on MM measurement through VA.
INCLUSION CRITERIA
article presented results from a VA study where malaria was a cause of death; article discussed limitations/challenges related to measurement of MM through VA. Two authors independently searched the databases and websites and conducted a synthesis of articles using a standard matrix.
RESULTS
The authors identified 828 publications; 88 were included in the final review. Most publications were VA studies; others were systematic reviews discussing VA tools or methods; editorials or commentaries; and studies using VA data to develop MM estimates. The main limitation were low sensitivity and specificity of VA tools for measuring MM. Other limitations included lack of standardized VA tools and methods, lack of a 'true' gold standard to assess accuracy of VA malaria mortality.
CONCLUSIONS
Existing VA tools and methods for measuring MM have limitations. Given the need for data to measure progress toward the World Health Organization's Global Technical Strategy for Malaria 2016-2030 goals, the malaria community should define strategies for improving MM estimates, including exploring whether VA tools and methods could be further improved. Longer term strategies should focus on improving countries' vital registration systems for more robust and timely cause of death data.
Topics: Autopsy; Humans; Interviews as Topic; Malaria; Sensitivity and Specificity
PubMed: 29058621
DOI: 10.1186/s12936-017-2071-x -
Osong Public Health and Research... Feb 2022Yersinia pestis, the cause of plague and a potential biological weapon, has always been a threatening pathogen. Some strains of Y. pestis have varying degrees of...
Yersinia pestis, the cause of plague and a potential biological weapon, has always been a threatening pathogen. Some strains of Y. pestis have varying degrees of antibiotic resistance. Thus, this systematic review was conducted to alert clinicians to this pathogen's potential antimicrobial resistance. A review of the literature was conducted for experimental reports and systematic reviews on the topics of plague, Y. pestis, and antibiotic resistance. From 1995 to 2021, 7 Y. pestis isolates with 4 antibiotic resistance mechanisms were reported. In Y. pestis 17/95, 16/95, and 2180H, resistance was mediated by transferable plasmids. Each plasmid contained resistance genes encoded within specific transposons. Strain 17/95 presented multiple drug resistance, since plasmid 1202 contained 10 resistance determinants. Strains 16/95 and 2180H showed single antibiotic resistance because both additional plasmids in these strains carried only 1 antimicrobial determinant. Strains 12/87, S19960127, 56/13, and 59/13 exhibited streptomycin resistance due to an rpsl gene mutation, a novel mechanism that was discovered recently. Y. pestis can acquire antibiotic resistance in nature not only via conjugative transfer of antimicrobial-resistant plasmids from other bacteria, but also by gene point mutations. Global surveillance should be strengthened to identify antibiotic-resistant Y. pestis strains by whole-genome sequencing and drug susceptibility testing.
PubMed: 35255676
DOI: 10.24171/j.phrp.2021.0288 -
PLoS Neglected Tropical Diseases Nov 2023Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that...
BACKGROUND
Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone-no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease-how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment.
METHODOLOGY/PRINCIPAL FINDINGS
This systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints-the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days.
CONCLUSIONS/SIGNIFICANCE
This systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial's results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.
Topics: Humans; Animals; Plague; Zoonoses; Outcome Assessment, Health Care
PubMed: 37943880
DOI: 10.1371/journal.pntd.0011509 -
International Journal of Colorectal... Aug 2022Haemorrhoidal disease (HD) plagues one in every ten people, with a plethora of surgical treatment modalities, of which laser haemorrhoidoplasty (LHP) is a relatively... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of postoperative pain and symptoms control following laser haemorrhoidoplasty versus Milligan-Morgan haemorrhoidectomy for symptomatic haemorrhoids: a new standard.
PURPOSE
Haemorrhoidal disease (HD) plagues one in every ten people, with a plethora of surgical treatment modalities, of which laser haemorrhoidoplasty (LHP) is a relatively novel option. This systematic review and meta-analysis objectively evaluated the efficacy, safety, and tolerability of LHP compared against conventional (Milligan-Morgan) open haemorrhoidectomy (CoH).
METHOD
A comprehensive search of MEDLINE, EMBASE, CENTRAL, and Google Scholar was conducted. Randomised controlled trials (RCTs) and comparative cohort studies (CCSs) which compared LHP against CoH were included, with postoperative pain as the primary outcome. Secondary outcomes included intraoperative characteristics, short- and moderate-term outcome, and complications.
RESULTS
A total of 12 studies (6 RCTs and 6 CCSs), with a total of 1824 patients, were analysed. LHP resulted in reduced postoperative pain for the first day (mean difference of 2.07 visual analogue scale units), week, and month. The mean dosage and duration of postoperative analgesia use was similarly lower, with a mean difference of 4.88 mg (morphine) and 2.25 days, respectively. Crucially, recurrence was equivocal (HR: 0.72, CI: 0.21-2.40) at a mean follow-up duration of 8.58 ± 9.55 months. LHP resulted in lower blood loss and was 12.74 min shorter on average. LHP's postoperative recovery time was 9.03 days less with equivalent or decreased risk of most short- and moderate-term complications except anal thrombosis.
CONCLUSION
Our study suggests that LHP is more tolerable than CoH, providing patients with superior postoperative quality of life at equivalent moderate-term efficacy. These findings contribute to improved understanding of LHP and its potential at enhancing the quality of HD care.
Topics: Hemorrhoidectomy; Hemorrhoids; Humans; Lasers; Pain Measurement; Pain, Postoperative
PubMed: 35906356
DOI: 10.1007/s00384-022-04225-4 -
The Cochrane Database of Systematic... Jun 2020Plague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the...
BACKGROUND
Plague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the disease. A rapid diagnostic test (RDT) could help in establishing a prompt diagnosis of plague. This would improve patient care and help appropriate public health response.
OBJECTIVES
To determine the diagnostic accuracy of the RDT based on the antigen F1 (F1RDT) for detecting plague in people with suspected disease.
SEARCH METHODS
We searched the CENTRAL, Embase, Science Citation Index, Google Scholar, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov up to 15 May 2019, and PubMed (MEDLINE) up to 27 August 2019, regardless of language, publication status, or publication date. We handsearched the reference lists of relevant papers and contacted researchers working in the field.
SELECTION CRITERIA
We included cross-sectional studies that assessed the accuracy of the F1RDT for diagnosing plague, where participants were tested with both the F1RDT and at least one reference standard. The reference standards were bacterial isolation by culture, polymerase chain reaction (PCR), and paired serology (this is a four-fold difference in F1 antibody titres between two samples from acute and convalescent phases).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. We appraised the methodological quality of each selected studies and applicability by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When meta-analysis was appropriate, we used the bivariate model to obtain pooled estimates of sensitivity and specificity. We stratified all analyses by the reference standard used and presented disaggregated data for forms of plague. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included eight manuscripts reporting seven studies. Studies were conducted in three countries in Africa among adults and children with any form of plague. All studies except one assessed the F1RDT produced at the Institut Pasteur of Madagascar (F1RDT-IPM) and one study assessed a F1RDT produced by New Horizons (F1RDT-NH), utilized by the US Centers for Disease Control and Prevention. We could not pool the findings from the F1RDT-NH in meta-analyses due to a lack of raw data and a threshold of the test for positivity different from the F1RDT-IPM. Risk of bias was high for participant selection (retrospective studies, recruitment of participants not consecutive or random, unclear exclusion criteria), low or unclear for index test (blinding of F1RDT interpretation unknown), low for reference standards, and high or unclear for flow and timing (time of sample transportation was longer than seven days, which can lead to decreased viability of the pathogen and overgrowth of contaminating bacteria, with subsequent false-negative results and misclassification of the target condition). F1RDT for diagnosing all forms of plague F1RDT-IPM pooled sensitivity against culture was 100% (95% confidence interval (CI) 82 to 100; 4 studies, 1692 participants; very low certainty evidence) and pooled specificity was 70.3% (95% CI 65 to 75; 4 studies, 2004 participants; very low-certainty evidence). The performance of F1RDT-IPM against PCR was calculated from a single study in participants with bubonic plague (see below). There were limited data on the performance of F1RDT against paired serology. F1RDT for diagnosing pneumonic plague Performed in sputum, F1RDT-IPM pooled sensitivity against culture was 100% (95% CI 0 to 100; 2 studies, 56 participants; very low-certainty evidence) and pooled specificity was 71% (95% CI 59 to 80; 2 studies, 297 participants; very low-certainty evidence). There were limited data on the performance of F1RDT against PCR or against paired serology for diagnosing pneumonic plague. F1RDT for diagnosing bubonic plague Performed in bubo aspirate, F1RDT-IPM pooled sensitivity against culture was 100% (95% CI not calculable; 2 studies, 1454 participants; low-certainty evidence) and pooled specificity was 67% (95% CI 65 to 70; 2 studies, 1198 participants; very low-certainty evidence). Performed in bubo aspirate, F1RDT-IPM pooled sensitivity against PCR for the caf1 gene was 95% (95% CI 89 to 99; 1 study, 88 participants; very low-certainty evidence) and pooled specificity was 93% (95% CI 84 to 98; 1 study, 61 participants; very low-certainty evidence). There were no data providing data on both F1RDT and paired serology for diagnosing bubonic plague.
AUTHORS' CONCLUSIONS
Against culture, the F1RDT appeared highly sensitive for diagnosing either pneumonic or bubonic plague, and can help detect plague in remote areas to assure management and enable a public health response. False positive results mean culture or PCR confirmation may be needed. F1RDT does not replace culture, which provides additional information on resistance to antibiotics and bacterial strains.
Topics: Adult; Antigens, Bacterial; Child; Confidence Intervals; Cross-Sectional Studies; False Negative Reactions; False Positive Reactions; Humans; Plague; Sensitivity and Specificity; Time Factors; Yersinia pestis
PubMed: 32597510
DOI: 10.1002/14651858.CD013459.pub2 -
Pathogens (Basel, Switzerland) Jan 2021Rodents carry many ectoparasites, such as ticks, lice, fleas, and mites, which have potential public health importance. Middle Eastern countries are hotspots for many... (Review)
Review
Rodents carry many ectoparasites, such as ticks, lice, fleas, and mites, which have potential public health importance. Middle Eastern countries are hotspots for many emerging and re-emerging infectious diseases, such as plague, leishmaniasis, Crimean Congo hemorrhagic fever, and Q fever, due to their ecological, socioeconomic, and political diversity. Rodent ectoparasites can act as vectors for many of these pathogens. Knowledge of rodent ectoparasites is of prime importance in controlling rodent ectoparasite-borne zoonotic diseases in this region. The current systematic review and meta-analysis performs a comprehensive synthesis of the available knowledge, providing an evidence-based overview of the ectoparasites detected on rodents in Middle Eastern countries. Following a systematic search in Pubmed, Scopus, and Web of Science, a total of 113 published articles on rodent ectoparasites were studied and analyzed. A total of 87 rodent species were documented, from which , , and were found to be the most common. Fleas were the most reported ectoparasites (87 articles), followed by mites (53), ticks (44), and lice (25). , , , and were the most commonly described fleas, lice, mites, and ticks, respectively. Based on the reviewed articles, the median flea, louse, mite, and tick indices were highest in Israel (4.15), Egypt (1.39), Egypt (1.27), and Saudi Arabia (1.17), respectively. Quantitative meta-analysis, using a random-effects model, determined the overall pooled flea prevalence in the Middle East as 40% (95% CI: 25-55, = 100%, < 0.00001), ranging between 13% (95% CI: 0-30, = 95%, < 0.00001) in Iran and 59% (95% CI: 42-77, = 75%, < 0.00001) in Israel. The overall pooled louse prevalence was found to be 30% (95% CI: 13-47, = 100%, < 0.00001), ranging between 25% in Iran (95% CI: 1-50, = 99%) and 38% in Egypt (95% CI: 7-68, = 100%). In the case of mites, the pooled prevalence in this region was 33% (95% CI: 11-55, = 100%, < 0.00001), where the country-specific prevalence estimates were 30% in Iran (95% CI: 4-56, = 99%) and 32% in Egypt (95% CI: 0-76, = 100%). For ticks, the overall prevalence was found to be 25% (95% CI: 2-47, = 100%, < 0.00001), ranging from 16% in Iran (95% CI: 7-25, = 74%) to 42% in Egypt (95% CI: 1-85, = 100%). The control of rodent ectoparasites should be considered to reduce their adverse effects. Using the One Health strategy, rodent control, and precisely control of the most common rodent species, i.e., , , and , should be considered to control the rodent-borne ectoparasites in this region.
PubMed: 33572506
DOI: 10.3390/pathogens10020139 -
Clinical Infectious Diseases : An... May 2020The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for...
BACKGROUND
The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy.
METHODS
We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes.
RESULTS
Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported.
CONCLUSIONS
For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.
Topics: Abortion, Spontaneous; Anti-Infective Agents; Child; Female; Humans; Infant, Newborn; Male; Plague; Pregnancy; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 32435799
DOI: 10.1093/cid/ciz1231