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Vaccines Mar 2024are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. and , the etiological agents of melioidosis and glanders,... (Review)
Review
are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. and , the etiological agents of melioidosis and glanders, respectively, are the two clinically relevant members of the complex (Bpc). The development of vaccines against Bpc species has been accelerated in recent years, resulting in numerous promising subunits and glycoconjugate vaccines incorporating a variety of antigens. However, a second group of pathogenic species exists known as the complex (Bcc), a group of opportunistic bacteria which tend to affect individuals with weakened immunity or cystic fibrosis. To date, there have been few attempts to develop vaccines to Bcc species. Therefore, the primary goal of this review is to provide a broad overview of the various subunit antigens that have been tested in Bpc species, their protective efficacy, study limitations, and known or suspected mechanisms of protection. Then, we assess the reviewed Bpc antigens for their amino acid sequence conservation to homologous proteins found in Bcc species. We propose that protective Bpc antigens with a high degree of Bpc-to-Bcc sequence conservation could serve as components of a pan- vaccine capable of protecting against both disease-causing groups.
PubMed: 38543947
DOI: 10.3390/vaccines12030313 -
Emerging Infectious Diseases Apr 2024In September 2021, a total of 25 patients diagnosed with COVID-19 developed acute melioidosis after (median 7 days) admission to a COVID-19 field hospital in Thailand....
In September 2021, a total of 25 patients diagnosed with COVID-19 developed acute melioidosis after (median 7 days) admission to a COVID-19 field hospital in Thailand. Eight nonpotable tap water samples and 6 soil samples were culture-positive for Burkholderia pseudomallei. Genomic analysis suggested contaminated tap water as the likely cause of illness.
Topics: Humans; Melioidosis; Thailand; COVID-19; Burkholderia pseudomallei; Water
PubMed: 38526300
DOI: 10.3201/eid3004.231476 -
BMC Veterinary Research Mar 2024Melioidosis is a serious bacterial infection caused by Burkholderia pseudomallei, a gram-negative bacterium commonly found in soil and water. It can affect both humans...
BACKGROUND
Melioidosis is a serious bacterial infection caused by Burkholderia pseudomallei, a gram-negative bacterium commonly found in soil and water. It can affect both humans and animals, and is endemic in regions such as Southeast Asia and Northern Australia. In recent years, there have been reports of an emergence of human melioidosis in other areas, including New Caledonia.
RESULTS
During standard laboratory analysis in New Caledonia in 2021, a strain of B. pseudomallei was isolated from a goat. The strain was characterized using both MLST and WGS techniques and was found to cluster with previously described local human strains from the area. In parallel, several serological tests (CFT, ELISA, Luminex (Hcp1, GroEL, BPSS1840), arrays assay and a latex agglutination test) were performed on animals from the farm where the goat originated, and/or from three other neighboring farms. Using two commercial ELISA kits, seropositive animals were found only on the farm where the infected goat originated and tests based on recombinant proteins confirmed the usefulness of the Hcp1 protein for the diagnosis of melioidosis in animals.
CONCLUSIONS
Despite the regular reports of human cases, this is the first confirmed case of melioidosis in an animal in New Caledonia. These results confirm the presence of the bacterium in the region and highlight the importance of vigilance for both animal and human health. It is critical that all health partners, including breeders, veterinarians, and biologists, work together to monitor and prevent the spread of the disease.
Topics: Humans; Animals; Burkholderia pseudomallei; Melioidosis; Multilocus Sequence Typing; Goats; New Caledonia; Goat Diseases
PubMed: 38521903
DOI: 10.1186/s12917-024-03957-5 -
Frontiers in Pharmacology 2024has been used for traditional medicines, healthy foods and tea. The chemical compositions and biological activities of fruit, stem bark and root have been widely...
has been used for traditional medicines, healthy foods and tea. The chemical compositions and biological activities of fruit, stem bark and root have been widely studied. However, the phytochemical components and the biological activities in leaves (GAL) are limited. This research aims to study the phytochemical components and the stress resistance effects of GAL in (). To investigate the chemical components and antioxidant activities of GAL extract, the ethanol extract was characterized by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS) analysis and was used to evaluate the effects of GAL extracts on longevity and stress resistance. The results revealed that the ethanol extract of GAL possesses free radical scavenging activities. Furthermore, GAL extract increased the lifespan of by 6.02%, 15.26%, and 12.75% at concentrations of 25, 50, and 100 μg/mL, respectively. GAL extract exhibited improved stress resistance under conditions of heat and hydrogen peroxide-induced stress. The survival rates of GAL extract-treated worms were significantly higher than those of untreated worms, and GAL extract reduced reactive oxygen species (ROS) accumulation. Additionally, GAL extract treatment upregulated the expression of stress resistance-associated genes, including gst-4, sod-3, skn-1, and hsp16.2. GAL extract supplementation alleviated stress and enhanced longevity by inducing stress-related genes in . The observed effects of GAL extracts may be attributed to the stimulation of oxidant enzymes mediated through DAF-16/FOXO and SKN-1/NRF2, as well as the enhancement of thermal defense in . Collectively, this study provides the first evidence of the antioxidant activities of GAL and elucidates the underlying mechanisms of stress resistance.
PubMed: 38515852
DOI: 10.3389/fphar.2024.1331627 -
MBio Apr 2024Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine...
UNLABELLED
Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine against melioidosis exists. In preclinical vaccine studies, demonstrating protection against respiratory infection in the highly sensitive BALB/c mouse has been especially challenging. To address this challenge, we have used a safe yet potent live attenuated platform vector, LVS Δ, previously used successfully to develop vaccines against the Tier 1 select agents of tularemia, anthrax, and plague, to develop a melioidosis vaccine. We have engineered melioidosis vaccines (rLVS Δ/Bp) expressing multiple immunoprotective Bp antigens among type VI secretion system proteins Hcp1, Hcp2, and Hcp6, and membrane protein LolC. Administered intradermally, rLVS Δ/Bp vaccines strongly protect highly sensitive BALB/c mice against lethal respiratory Bp challenge, but protection is overwhelmed at very high challenge doses. In contrast, administered intranasally, rLVS Δ/Bp vaccines remain strongly protective against even very high challenge doses. Under some conditions, the LVS Δ vector itself provides significant protection against Bp challenge, and consistent with this, both the vector and vaccines induce humoral immune responses to Bp antigens. Three-antigen vaccines expressing Hcp6-Hcp1-Hcp2 or Hcp6-Hcp1-LolC are among the most potent and provide long-term protection and protection even with a single intranasal immunization. Protection via the intranasal route was either comparable to or statistically significantly better than the single-deletional Bp mutant Bp82, which served as a positive control. Thus, rLVS Δ/Bp vaccines are exceptionally promising safe and potent melioidosis vaccines.
IMPORTANCE
Melioidosis, a major neglected disease caused by the intracellular bacterial pathogen , is endemic in many tropical areas of the world and causes an estimated 165,000 cases and 89,000 deaths in humans annually. Moreover, is categorized as a Tier 1 select agent of bioterrorism, largely because inhalation of low doses can cause rapidly fatal pneumonia. No licensed vaccine is available to prevent melioidosis. Here, we describe a safe and potent melioidosis vaccine that protects against lethal respiratory challenge with in a highly sensitive small animal model-even a single immunization is highly protective, and the vaccine gives long-term protection. The vaccine utilizes a highly attenuated replicating intracellular bacterium as a vector to express multiple key proteins of ; this vector platform has previously been used successfully to develop potent vaccines against other Tier 1 select agent diseases including tularemia, anthrax, and plague.
Topics: Humans; Animals; Mice; Burkholderia pseudomallei; Melioidosis; Tularemia; Anthrax; Plague; Mice, Inbred BALB C; Bacterial Vaccines; Vaccines, Attenuated; Antigens, Bacterial
PubMed: 38511933
DOI: 10.1128/mbio.00186-24 -
The American Journal of Tropical... May 2024Melioidosis, infection caused by Burkholderia pseudomallei, is characterized by robust innate immune responses. We have previously reported associations of TLR1 single...
Melioidosis, infection caused by Burkholderia pseudomallei, is characterized by robust innate immune responses. We have previously reported associations of TLR1 single nucleotide missense variant rs76600635 with mortality and of TLR5 nonsense variant rs5744168 with both bacteremia and mortality in single-center studies of patients with melioidosis in northeastern Thailand. The objective of this study was to externally validate the associations of rs76600635 and rs5744168 with bacteremia and mortality in a large multicenter cohort of melioidosis patients. We genotyped rs76600635 and rs5744168 in 1,338 melioidosis patients enrolled in a prospective parent cohort study conducted at nine hospitals in northeastern Thailand. The genotype frequencies of rs76600635 did not differ by bacteremia status (P = 0.27) or 28-day mortality (P = 0.84). The genotype frequencies of rs5744168 did not differ by either bacteremia status (P = 0.46) or 28-day mortality (P = 0.10). Assuming a dominant genetic model, there was no association of the rs76600635 variant with bacteremia (adjusted odds ratio [OR], 0.75; 95% CI, 0.54-1.04, P = 0.08) or 28-day mortality (adjusted OR, 0.96; 95% CI, 0.71-1.28, P = 0.77). There was no association of the rs5744168 variant with bacteremia (adjusted OR, 1.24; 95% CI, 0.76-2.03, P = 0.39) or 28-day mortality (adjusted OR, 1.22; 95% CI, 0.83-1.79, P = 0.21). There was also no association of either variant with 1-year mortality. We conclude that in a large multicenter cohort of patients hospitalized with melioidosis in northeastern Thailand, neither TLR1 missense variant rs76600635 nor TLR5 nonsense variant rs5744168 is associated with bacteremia or mortality.
Topics: Humans; Melioidosis; Male; Female; Toll-Like Receptor 1; Thailand; Middle Aged; Bacteremia; Toll-Like Receptor 5; Adult; Cohort Studies; Polymorphism, Single Nucleotide; Genotype; Burkholderia pseudomallei; Prospective Studies; Aged; Genetic Predisposition to Disease
PubMed: 38507807
DOI: 10.4269/ajtmh.23-0381 -
The Lancet. Microbe Apr 2024Melioidosis is a neglected but often fatal tropical disease. The disease has broad clinical manifestations, which makes diagnosis challenging and time consuming. To... (Observational Study)
Observational Study
BACKGROUND
Melioidosis is a neglected but often fatal tropical disease. The disease has broad clinical manifestations, which makes diagnosis challenging and time consuming. To improve diagnosis, we aimed to evaluate the performance of the CRISPR-Cas12a system (CRISPR-BP34) to detect Burkholderia pseudomallei DNA across clinical specimens from patients suspected to have melioidosis.
METHODS
We conducted a prospective, observational cohort study of adult patients (aged ≥18 years) with melioidosis at Sunpasitthiprasong Hospital, a tertiary care hospital in Thailand. Participants were eligible for inclusion if they had culture-confirmed B pseudomallei infection from any clinical samples. Data were collected from patient clinical records and follow-up telephone calls. Routine clinical samples (blood, urine, respiratory secretion, pus, and other body fluids) were collected for culture. We documented time taken for diagnosis, and mortality at day 28 of follow-up. We also performed CRISPR-BP34 detection on clinical specimens collected from 330 patients with suspected melioidosis and compared its performance with the current gold-standard culture-based method. Discordant results were validated by three independent qualitative PCR tests. This study is registered with the Thai Clinical Trial Registry, TCTR20190322003.
FINDINGS
Between Oct 1, 2019, and Dec 31, 2022, 876 patients with culture-confirmed melioidosis were admitted or referred to Sunpasitthiprasong Hospital, 433 of whom were alive at diagnosis and were enrolled in this study. Median time from sample collection to diagnosis by culture was 4·0 days (IQR 3·0-5·0) among all patients with known survival status at day 28, which resulted in delayed treatment. 199 (23%) of 876 patients died before diagnosis and 114 (26%) of 433 patients in follow-up were treated, but died within 28 days of admission. To test the CRISPR-BP34 assay, we enrolled and collected clinical samples from 114 patients with melioidosis and 216 patients without melioidosis between May 26 and Dec 31, 2022. Application of CRISPR-BP34 reduced the median sample-to-diagnosis time to 1·1 days (IQR 0·7-1·5) for blood samples, 2·3 h (IQR 2·3-2·4) for urine, and 3·3 h (3·1-3·4) for respiratory secretion, pus, and other body fluids. The overall sensitivity of CRISPR-BP34 was 93·0% (106 of 114 samples [95% CI 86·6-96·9]) compared with 66·7% (76 of 114 samples [57·2-75·2]) for culture. The overall specificity of CRISPR-BP34 was 96·8% (209 of 216 samples [95% CI 93·4-98·7]), compared with 100% (216 of 216 samples [98·3-100·0]) for culture.
INTERPRETATION
The sensitivity, specificity, speed, and window of clinical intervention offered by CRISPR-BP34 support its prospective use as a point-of-care diagnostic tool for melioidosis. Future development should be focused on scalability and cost reduction.
FUNDING
Chiang Mai University Thailand and Wellcome Trust UK.
Topics: Adult; Humans; Benchmarking; Burkholderia pseudomallei; Developing Countries; Melioidosis; Pathology, Molecular; Point-of-Care Systems; Sensitivity and Specificity; Suppuration
PubMed: 38493790
DOI: 10.1016/S2666-5247(23)00378-6 -
Frontiers in Cellular and Infection... 2024Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where... (Review)
Review
Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population. The common marmoset (), a Neotropical new-world (platyrrhines) non-human primate, has gained increasing attention as an animal model for a number of diseases given its small size, availability and evolutionary proximity to humans. This review aims to (i) discuss the pros and cons of the common marmoset as an animal model by providing a brief snapshot of how marmosets are currently utilized in biomedical research, (ii) summarize and evaluate relevant aspects of the marmoset immune system to the study of infectious diseases, (iii) provide a historical backdrop, outlining the significance of infectious diseases and the importance of developing reliable animal models to test novel therapeutics, and (iv) provide a summary of infectious diseases for which a marmoset model exists, followed by an in-depth discussion of the marmoset models of two studied bacterial infectious diseases (tularemia and melioidosis) and one viral infectious disease (viral hepatitis C).
Topics: Animals; Humans; Callithrix; Disease Models, Animal; Communicable Diseases; Tularemia; Bacterial Infections
PubMed: 38465237
DOI: 10.3389/fcimb.2024.1340017 -
Heliyon Feb 2024In this work, we formulated and investigated an optimal control problem of the melioidosis epidemic to explain the effectiveness of time-dependent control functions in...
In this work, we formulated and investigated an optimal control problem of the melioidosis epidemic to explain the effectiveness of time-dependent control functions in controlling the spread of the epidemic. The basic reproduction number with control measures is obtained, using the next-generation matrix approach and the impact of the controls on is illustrated numerically. The optimal control problem is analyzed using Pontryagin's maximum principle to derive the optimality system. The optimality system is simulated using the forward-backward sweep method based on the fourth-order Runge-Kutta method in the MATLAB program to illustrate the impact of all the possible combinations of the control interventions on the transmission dynamics of the disease. The numerical results indicate that among strategies considered, strategy is shown to be the most effective in reducing the number of infectious classes compared to both strategy and strategy . Furthermore, we carried out a cost-effectiveness analysis to determine the most cost-effective strategy and the result indicated that the strategy (treatment control strategy) should be recommended to mitigate the spread and impact of the disease regarding the costs of the strategies.
PubMed: 38434022
DOI: 10.1016/j.heliyon.2024.e26487 -
Cureus Jan 2024Burkholderia infection commonly presents as bacteraemic pulmonary disease; however, it is notorious for its wide variety of presentations in chronic cases, including...
Emerging Burkholderia Musculoskeletal Infections With Delayed Diagnosis in Non-endemic Regions Affect Patient Morbidity: A Case Series of 10 Patients With a Review of the Literature.
INTRODUCTION
Burkholderia infection commonly presents as bacteraemic pulmonary disease; however, it is notorious for its wide variety of presentations in chronic cases, including musculoskeletal manifestations. It is common in patients living in endemic areas with comorbidities such as diabetes and who have chronic alcoholism. It was previously under-reported due to a low index of suspicion. Now, there is an increasing trend of diagnosis of these infections in non-endemic areas because of various factors, such as MALDI-TOF, molecular tests, and PCR.
MATERIALS AND METHODS
This is a single tertiary centre study of 10 patients, diagnosed with Burkholderia infection and treated at our institution between 2021 and 2023 and followed up for a minimum of six months. Information was collected from outpatient and inpatient records.
RESULTS
In this study, the mean age of the patients was 45 years, with eight males and two females. Out of 10, seven patients had comorbidities. However, only one patient has a history of travelling to an endemic area. All our patients were treated operatively, and the course of intervention and the planning of the surgical procedure were decided according to clinico-radiological findings. Six out of 10 patients suffering from Burkholderia species infections have a history of prolonged ICU stay, four of them tested positive for Burkholderia pseudomallei and the remaining two tested positive for Burkholderia cepacia,with a mean average time of 24.6 days. Diabetes was the most common comorbidity in 70% of the patients. The knee was the most commonly affected joint, showing involvement in 60% of patients. We have done surgical intervention in all patients. In our study, we have given IV antibiotics for a minimum of six weeks to all patients, followed by oral antibiotic therapy for three to six months on the basis of regular follow-up of clinico-haematologic parameters.
CONCLUSION
Infections caused by Burkholderia species should be considered a potential causative agent of musculoskeletal infections in non-endemic areas without prior history of travelling to endemic areas. It may present with a chronic, mild course; a high index of suspicion is required, and it is important that due suspicion translates to prompt diagnosis and appropriate treatment to mitigate the course of the disease and associated morbidities in patients.
PubMed: 38414696
DOI: 10.7759/cureus.53096