1.
PLoS One. 2020 Mar 10;15(3):e0229355. doi: 10.1371/journal.pone.0229355. eCollection 2020.
Genetic diversity and evolutionary analysis of human respirovirus type 3 strains isolated in Kenya using complete hemagglutinin-neuraminidase (HN) gene.
Abstract
Human respirovirus type 3 (HRV3) is a leading etiology of lower respiratory tract infections in young children and ranks only second to the human respiratory syncytial virus (HRSV). Despite the public health importance of HRV3, there is limited information about the genetic characteristics and diversity of these viruses in Kenya. To begin to address this gap, we analyzed 35 complete hemagglutinin-neuraminidase (HN) sequences of HRV3 strains isolated in Kenya between 2010 and 2013. Viral RNA was extracted from the isolates, and the entire HN gene amplified by RT-PCR followed by nucleotide sequencing. Phylogenetic analyses of the sequences revealed that all the Kenyan isolates grouped into genetic Cluster C; sub-clusters C1a, C2, and C3a. The majority (54%) of isolates belonged to sub-cluster C3a, followed by C2 (43%) and C1a (2.9%). Sequence analysis revealed high identities between the Kenyan isolates and the HRV3 prototype strain both at the amino acid (96.5-97.9%) and nucleotide (94.3-95.6%) levels. No amino acid variations affecting the catalytic/active sites of the HN glycoprotein were observed among the Kenyan isolates. Selection pressure analyses showed that the HN glycoprotein was evolving under positive selection. Evolutionary analyses revealed that the mean TMRCA for the HN sequence dataset was 1942 (95% HPD: 1928-1957), while the mean evolutionary rate was 4.65x10-4 nucleotide substitutions/site/year (95% HPD: 2.99x10-4 to 6.35x10-4). Overall, our results demonstrate the co-circulation of strains of cluster C HRV3 variants in Kenya during the study period. This is the first study to describe the genetic and molecular evolutionary aspects of HRV3 in Kenya using the complete HN gene.
2.
Trauma Surg Acute Care Open. 2020 Feb 4;5(1):e000398. doi: 10.1136/tsaco-2019-000398. eCollection 2020.
Attenuation of MODS-related and ARDS-related mortality makes infectious complications a remaining challenge in the severely injured.
Abstract
INTRODUCTION:
The recent decrease in multiple organ dysfunction syndrome (MODS)-associated and adult respiratory distress syndrome (ARDS)-associated mortality could be considered a success of improvements in trauma care. However, the incidence of infections remains high in patients with polytrauma, with high morbidity and hospital resources usage. Infectious complications might be a residual effect of the decrease in MODS-related/ARDS-related mortality. This study investigated the current incidence of infectious complications in polytrauma.
METHODS:
A 5.5-year prospective population-based cohort study included consecutive severely injured patients (age >15) admitted to a (Level-1) trauma center intensive care unit (ICU) who survived >48 hours. Demographics, physiologic and resuscitation parameters, multiple organ failure and ARDS scores, and infectious complications (pneumonia, fracture-related infection, meningitis, infections related to blood, wound, and urinary tract) were prospectively collected. Data are presented as median (IQR), p<0.05 was considered significant.
RESULTS:
297 patients (216 (73%) men) were included with median age of 46 (27-60) years, median Injury Severity Score was 29 (22-35), 96% sustained blunt injuries. 44 patients (15%) died. One patient (2%) died of MODS and 1 died of ARDS. 134 patients (45%) developed 201 infectious complications. Pneumonia was the most common complication (50%). There was no difference in physiologic parameters on arrival in emergency department and ICU between patients with and without infectious complications. Patients who later developed infections underwent more often a laparotomy (32% vs 18%, p=0.009), had more often pelvic fractures (38% vs 25%, p=0.02), and received more blood products <8 hours. They had more often MODS (25% vs 13%, p=0.005), stayed longer on the ventilator (10 (5-15) vs 5 (2-8) days, p<0.001), longer in ICU (11 (6-17) vs 6 (3-10) days, p<0.001), and in hospital (30 (20-44) vs 16 (10-24) days, p<0.001). There was however no difference in mortality (12% vs 17%, p=0.41) between both groups.
CONCLUSION:
45% of patients developed infectious complications. These patients had similar mortality rates, but used more hospital resources. With low MODS-related and ARDS-related mortality, infections might be a residual effect, and are one of the remaining challenges in the treatment of patients with polytrauma.
LEVEL OF EVIDENCE:
Level 3.
STUDY TYPE:
Population-based cohort study.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
3.
Ann Transl Med. 2020 Feb;8(3):39. doi: 10.21037/atm.2019.10.40.
Clinical outcomes of ceftazidime-avibactam in lung transplant recipients with infections caused by extensively drug-resistant gram-negative bacilli.
Abstract
BACKGROUND:
Infections produced by extensively drug-resistant (XDR) gram-negative bacilli (GNB) in solid organ transplant (SOT) are an important cause of morbidity and mortality. Ceftazidime/avibactam (CAZ-AVI) is a novel β-lactam/β-lactamase combination antibiotic with anti-GNB activity, but experience in real clinical practice with CAZ-AVI in lung transplant (LT) recipients is limited.
METHODS:
We conducted a retrospective study of patients with XDR-GNB infection who received at least 3 days of CAZ-AVI in the Department of Lung Transplantation Between December 2017 and December 2018 at China-Japan friendship hospital (CJFH). The general information, clinical manifestations, laboratory examinations, treatment course, and outcomes were summarized.
RESULTS:
A total of 10 patients who underwent LT at our center were included. They were all males with a mean age 51 years. Infections after LT included pneumonia and/or tracheobronchitis [n=9; 90% (9/10)], cholecystitis and blood stream infection (BSI) (n=1, patient 8). In these 10 LT recipients, the incidence of various airway complications was 70% (7/10). Carbapenem-resistant Klebsialla pneumoniae (CRKP) was the predominant pathogen, being detected in 9 patients. Multilocus sequence typing (MLST) analysis showed that all 9 CRKP isolates belonged to ST11. Six patients (6/10, 60%) started CAZ-AVI as salvage therapy after a first-line treatment with other antimicrobials. CAZ-AVI was administered as monotherapy or in combination regimens in 20% (2/10) and 80% (8/10) of patients respectively. There were no difference in temperature before and after CAZ-AVI treatment (P>0.05). White blood cell (WBC) at 7 days, and procalcitonin (PCT) at 7 days and 14 days significantly dropped (P<0.05). After 7-14 days of CAZ-AVI treatment, the PaO2/FiO2ratio (P/F ratio) significantly improved (P<0.05). Nine patients (9/10, 90%) obtained negative microbiologic culture of CRKP/CRPA, with a median time to was 6.7 days (range, 1-15 days). However, 5 patients (5/10, 50%) had relapse of CRKP/CRPA infections in the respiratory tract regardless of whether negative microbiologic culture was obtained or not. The 30-day survival rate was 100%, and the 90-day survival rate was 90% (1/10). No severe adverse events related to CAZ-AVI occurred.
CONCLUSIONS:
CAZ-AVI treatment of CRKP/ CRPA infection in LT recipients was associated with high rates of clinical success, survival, and safety, but recurrent CRKP/CRPA infections in the respiratory tract did occur.
2020 Annals of Translational Medicine. All rights reserved.
KEYWORDS:
Extensively drug-resistant bacteria; carbapenem-resistant K. pneumoniae; ceftazidime-avibactam; gram-negative bacilli (GNB); lung transplant (LT); outcomes
4.
J Assoc Physicians India. 2020 Mar;68(3):63-66.
Etiology, Clinical Profile and Outcome of Encephalopathy in Elderly.
Abstract
BACKGROUND:
Diagnosis and delay in management of encephalopathy in elderly patients is challenging due to the paucity of presenting symptoms and signs.
METHODS:
This was an observational study conducted over a period of one year (1.2.2016 to 31.1.2017) on all elderly patients presenting with encephalopathy. Their demographic profile along with clinical presentation, laboratory, imaging results and final outcome were recorded and analysed.
RESULTS:
There were 251 elderly patients who presented with encephalopathy, 110 (43.82%) of whom were females. Majority of these patients i.e. 186(74.10%) were in the age group of 60-75 years with a mean age of 70.78 years. There were 112 (44.62%) patients who presented to the hospital within 6 hours of commencement of the altered mental status (AMS). Multiple etiologies for encephalopathy were present in 75 (29.88%) patients with the commonest being neurological in 97 (38.65%) patients, infection/sepsis in 92 (36.65%) patients and metabolic in 84 (33.47%) patients. Hyponatremia was the commonest cause of metabolic encephalopathy present in 38(45.24%) patients followed by hypoglycemia in 25 (29.76%) patients. Pneumonia was the commonest infection present in 41 (44.57%) patients. There were 48(19.12%) deaths with 38(79.17%) of them having one or more co-morbidities. Early presentation to hospital (within 6 hours of commencement of symptoms), higher GCS and conscious level at presentation were the good prognostic markers of outcome in these elderly patients. However patients with septic encephalopathy were found to have worst prognosis.
CONCLUSION:
The common etiologies of encephalopathy in the elderly were neurological (38.65%) followed by infection (36.65%) and metabolic (33.47%). The mortality rate was 19.12%. Seeking medical aid within 6 hours of commencement of altered sensorium along with timely diagnosis could reduce the mortality and improve outcomes.
© Journal of the Association of Physicians of India 2011.
5.
J Assoc Physicians India. 2020 Mar;68(3):43-47.
Nasal Airway Resistance and Latent Lower Airway Involvement in Allergic Rhinitis.
Abstract
INTRODUCTION:
Allergic rhinitis (AR) and asthma are closely linked atopic conditions, often termed as one airway one disease. Nasal airflow obstruction is a cardinal symptom of AR and objective assessment of resistance to nasal airflow in rhinitis can be measured by active anterior rhinomanometry. This study was aimed at correlating the degree of resistance to nasal airflow (NAR) with the clinical severity of allergic rhinitis. In addition, it aimed at determining the proportion of patients with latent lower airway involvement in AR and studying the impact of ARIA severity grade and NAR on this value.
MATERIALS AND METHODS:
A prospective prevalence study was conducted wherein 32 patients diagnosed with allergic rhinitis underwent determination of nasal airway resistance by active anterior rhinomanometry and lung function evaluation by spirometry. If spirometry was normal; histamine challenge test was performed to check for bronchial hyper-reactivity.
RESULTS:
94% of patients with moderate- severe allergic rhinitis had significantly elevated nasal airway resistance compared to 56% of patients with mild rhinitis. (p=0.014). 71.9% of patients with allergic rhinitis but no symptoms of asthma had bronchial hyper-reactivity with a positive histamine challenge or airflow obstruction on lung functions. 87.5% patients with significantly elevated nasal airway resistance compared to 25% with lower values had lower airway involvement. (p=0.001). 94% of patients with moderate - severe rhinitis and 83% of patients with persistent rhinitis compared to 50% patients with mild and 44% with intermittent symptoms had lower airways involved. (p<0.05).
CONCLUSION:
Significantly greater proportion of patients with moderate-severe and persistent allergic rhinitis had elevated nasal airway resistance values. 72% patients with allergic rhinitis had lower airway involvement despite having no symptoms of asthma, prevalence being greater in patients with severe and persistent disease. Proportion of patients with lower airway hyper-responsiveness is significantly higher among patients with raised nasal airway resistance as determined by rhinomanometry. This study thus concludes that measurement of nasal airway resistance determined by active anterior rhinomanometry is a good objective tool to measure severity of nasal obstruction in allergic rhinitis with good correlation with the ARIA clinical severity grade .It may also be a promising tool to identify allergic rhinitis patients who are at a higher risk of having latent lower airway involvement.
© Journal of the Association of Physicians of India 2011.
6.
Crit Care. 2020 Mar 4;24(1):77. doi: 10.1186/s13054-020-2805-y.
Cortisol total/CRP ratio for the prediction of hospital-acquired pneumonia and initiation of corticosteroid therapy in traumatic brain-injured patients.
Comment on
- PMID:
- 32131877
- PMCID:
- PMC7057606
- DOI:
- 10.1186/s13054-020-2805-y
- [Indexed for MEDLINE]
7.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Jan;34(1):88-91. doi: 10.13201/j.issn.1001-1781.2020.01.022.
[Application status and prospect of botulinum toxin A in otorhinolaryngological treatment].
[Article in Chinese]
Abstract
Botulinum toxin A is a kind of neurotoxin produced by clostridium botulinum, and has been applied for nearly thirty years in China.The target of BTX-A is to selectively cleave the synaptosome-associated protein of 25 KD molecular mass, commonly abbreviated SNAP-25, thereby inhibiting neurotransmitter release and causing chemodenervation. The potential application of botulinum toxin A in treating the spasmodic dysphonia, hemifacial spasm, tinnitus, rhinitis has been confirmed both in clinical practice and previous studies. This paper is to review comprehensively the application status and the prospect of botulinum toxin A in otorhinolaryngological treatment.
Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
KEYWORDS:
botulinum toxin A; otorhinolaryngological disease; treatment
8.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Jan;34(1):19-22;27. doi: 10.13201/j.issn.1001-1781.2020.01.005.
[Recent clinical advances in refractory chronic sinusitis].
[Article in Chinese]
Abstract
Refractory chronic sinusitis is one of the difficult diseases in otolaryngology. Lots of research have been conducted on the pathogenesis and treatment of the refractory chronic sinuses. Many guidelines, including abroad, have provided descriptions and treatment guidelines for the disease, but the definition and diagnostic criteria of refractory chronic sinusitis still need to reach a consensus. Therefore, this article summarizes the latest research status of refractory chronic sinusitis.
Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
KEYWORDS:
sinusitis; therapy
9.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Jan;34(1):13-18. doi: 10.13201/j.issn.1001-1781.2020.01.004.
[Advances in the endotypes of chronic rhinosinusitis].
[Article in Chinese]
Abstract
The pathogenesis of chronic rhinosinusitis（CRS） is complex. There are differences in the clinical manifestations and therapeutic effects of CRS dominated by different causes. At present, there is a lack of uniform classification standards in clinical practice. In this paper, the research progress in the endotype of CRS in recent years was discussed.
Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
KEYWORDS:
Th cell; endotype; genetics; microbiome; rhinosinusitis
10.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Jan;34(1):5-9. doi: 10.13201/j.issn.1001-1781.2020.01.002.
[Clinical study of Chinese Medicine fumigation combined with "Zhuyuan Decoction" in the treatment of chronic rhinosinusitis].
[Article in Chinese; Abstract available in Chinese from the publisher]
Abstract
Objective:To investigate the clinical efficacy of "Zhuyuan soup" by combination with fumigation and oral administration on chronic rhinosinusitis（CRS）, further exploring effective Chinese medicine for the disease, and giving full play to the unique advantages of external treatment of traditional Chinese medicine. Method:By using randomized and positive drug controlled methods, patients with moderate-to-severe chronic rhinosinusitis were randomly divided into western medicine group and traditional Chinese medicine group, 30 cases in each group. In the western medicine group, the nasal spray hormone Budesonide was used, and the patients in the traditional Chinese medicine group were treated with the traditional Chinese medicine prescription"Zhuyuan soup"by combination with fumigation and oral administration. All of the above patients were followed up for 2 weeks, and 1 course for 1 month. Visual analogue scores were taken at each follow-up, and CT and nasal endoscopy were performed before and after treatment. Result:The total effective of "Zhuyuan soup" group was 67.1%, which was higher than that of western medicine group（59.6%）, but there was no statistically significant difference（P>0.05）. After treatment, there were no significant differences between the two groups with regard to the symptom of nasal congestion, dizziness, facial pain or fullness, dysosmia, nasal discharge or postnasal drip, total sensation, total symptom score（P>0.05）. According to the total symptom score, the effect of the two groups of patients was not significantly correlated with the gender, age, course of disease, alcohol and tobacco hobbies, previous medication and surgery（P>0.05）. Based on the results of the study, we found that the Chinese medicine group is superior to the western medicine group in improving the total feeling of the disease, dizziness or headache, facial pain or fullness, and postnasal drip, olfactory disorder. Conclusion:Both traditional Chinese medicine and western medicine are effective methods for treating chronic rhinosinusitis. Clinically, individualized comprehensive treatment should be carried out according to the patient's condition. The above methods may be applied alone or in combination with Chinese and Western medicine. Further optimization and improvement of the combination of traditional Chinese and Western medicine in chronic sinusitis can help improve the clinical efficacy and satisfaction of patients, which deserves further study.
Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
KEYWORDS:
Zhuyuan soup; efficacy; fumigation; sinusitis
11.
Pediatr Crit Care Med. 2019 Dec;20(12):1211-1212. doi: 10.1097/PCC.0000000000002141.
The authors reply.
Comment on
- Outcomes of Children With Bronchiolitis Treated With High-Flow Nasal Cannula or Noninvasive Positive Pressure Ventilation. [Pediatr Crit Care Med. 2019]
- High-Flow Nasal Cannula Versus Noninvasive Ventilation: A Matter of Confusion. [Pediatr Crit Care Med. 2019]
12.
Pediatr Crit Care Med. 2019 Dec;20(12):1210-1211. doi: 10.1097/PCC.0000000000002110.
High-Flow Nasal Cannula Versus Noninvasive Ventilation: A Matter of Confusion.
Comment in
- The authors reply. [Pediatr Crit Care Med. 2019]
Comment on
13.
Vet Q. 2019 Dec;39(1):161-167. doi: 10.1080/01652176.2019.1697013.
Role for migratory domestic poultry and/or wild birds in the global spread of avian influenza?
- PMID:
- 31752591
- PMCID:
- PMC6913625
- DOI:
- 10.1080/01652176.2019.1697013
- [Indexed for MEDLINE]
14.
Environ Pollut. 2020 Feb;257:113424. doi: 10.1016/j.envpol.2019.113424. Epub 2019 Oct 18.
Particulate air pollution in Ho Chi Minh city and risk of hospital admission for acute lower respiratory infection (ALRI) among young children.
Abstract
High levels of air pollutants in Vietnam, especially particulate matters including PM2.5, can be important risk factors for respiratory diseases among children of the country. However, few studies on the effects of ambient air pollution on human health have been conducted in Vietnam so far. The aim of this study is to examine the association between PM2.5 and hospital admission due to acute lower respiratory infection (ALRI) among children aged < 5 years old in Ho Chi Minh city, the largest city of Vietnam. Data relating PM2.5 and hospital admission were collected from February 2016-December 2017 and a time series regression analysis was performed to examine the relationship between PM2.5 and hospital admission including the delayed effect up to three days prior to the admission. We found that each 10 μg/m3 increase in PM2.5 was associated with an increase of 3.51 (95%CI: 0.96-6.12) risk of ALRI admission among children. According to the analysis, male children are more sensitive to exposure to PM2.5 than females, while children exposed to PM2.5 are more likely to be infected with acute bronchiolitis than with pneumonia. The study demonstrated that young children in HCMC are at increased risk of ALRI admissions due to the high level of PM2.5 concentration in the city's ambient air.
Copyright © 2019 Elsevier Ltd. All rights reserved.
KEYWORDS:
Air pollution; Children health; Hospital admission; Lag effect; Respiratory infection
15.
PLoS One. 2019 Oct 16;14(10):e0220951. doi: 10.1371/journal.pone.0220951. eCollection 2019.
Risk factor profiles and clinical outcomes for children and adults with pneumococcal infections in Singapore: A need to expand vaccination policy?
Martinez-Vega R1, Jauneikaite E2,3, Thoon KC4,5, Chua HY1, Huishi Chua A1, Khong WX1, Tan BH6, Low Guek Hong J6, Venkatachalam I6, Anantharajah Tambyah P7, Hibberd ML2, Clarke SC3, Ng OT1,8,9.
Abstract
Invasive pneumococcal infection is a major cause of morbidity and mortality worldwide despite the availability of pneumococcal vaccines. The aim of this study was to re-evaluate the clinical syndromes, prognostic factors and outcomes for pneumococcal disease in adults and children in Singapore during the period before and after the introduction of the pneumococcal vaccine. We retrospectively analyzed a large cohort of patients admitted to the four main public hospitals in Singapore with S. pneumoniae infection between 1997 and 2013. A total of 889 (64% of all isolates identified in the clinical laboratories) cases were included in the analysis; 561 (63.1%) were adult (≥16 years) cases with a median age of 62 years and 328 (36.9%) were paediatric cases with a median age of 3 years. Bacteraemic pneumonia was the most common syndrome in both groups (69.3% vs. 44.2%), followed by primary bacteraemia without pneumonia (14.3% vs. 13.4%), meningitis (6.4% vs. 7.6%) and non-bacteraemic pneumonia (5.2% vs. 21%). The major serotypes in adults were 3, 4, 6B, 14, 19F and 23F whereas in children they were 14, 6B and 19F, accounting both for nearly half of pneumococcal disease cases. No particular serotype was associated with mortality or severity of the pneumococcal disease. Overall mortality rate was 18.5% in adults and 3% in children. Risk factors for mortality included acute cardiac events in adults, meningitis in children and critical illness and bilateral pulmonary infiltrates in both adults and children. Penicillin resistance was not associated with increased mortality. Our results agree with global reports that the course of pneumococcal disease and its clinical outcome were more severe in adults than in children. The main serotypes causing invasive disease were mostly covered by the vaccines in use. The high mortality rates reflect an urgent need to increase vaccination coverage in both adults and children to tackle this vaccine-preventable infection.
- PMID:
- 31618204
- PMCID:
- PMC6795432
- DOI:
- 10.1371/journal.pone.0220951
- [Indexed for MEDLINE]
16.
PLoS One. 2019 Oct 15;14(10):e0222925. doi: 10.1371/journal.pone.0222925. eCollection 2019.
Introduction of quality management in a National Reference Laboratory in Germany.
Abstract
BACKGROUND:
High quality diagnostic services are crucial for tuberculosis (TB) diagnosis, treatment and control. A strong laboratory quality management system (QMS) is critical to ensuring the quality of testing and results. Recent initiatives to improve TB laboratory quality have focused on low and middle-income countries, but similar issues also apply to high-income countries.
METHODS AND FINDINGS:
Using a multipronged approach reviews of facilities, equipment, processes (purchasing, pre-analytic, analytic and post-analytic), staff, health and safety, documentation, information management and organization based on the ISO 15189 and the twelve quality system essentials were conducted between October 2015 and January 2016 at the National TB Reference Laboratory in Germany. Outcome assessment included proportion of smear positive slides, proportion of contaminated liquid cultures and DNA contamination rates before and after implementation of QMS. The odds ratio for these outcomes was calculated using a before/after comparison. Reviews highlighted deficiencies across all twelve quality system essentials and were addressed in order of priority and urgency. Actions aimed at improving analytical quality, health and safety and information management were prioritised for initial implementation in parallel with each other. The odds ratio for a sample to be tested as microscopically positive increased by 2.08 (95%CI 1.41-3.06) comparing the time before with the time after implementation of quality managed fluorescence microscopy. Liquid culture contamination rates decreased from 23.6- 7.6% in April-July 2016 to <10% in November 2017-March 2018. The proportion of negative controls showing evidence of DNA contamination decreased from 38.2% in 2013 to 8.1% in 2017, the corresponding odds ratio was 0.14 (95%CI 0.07-0.29).
CONCLUSION:
This study showed marked improvement on quality indicators after implementation of a QMS in a National TB Reference Laboratory. The challenges and lessons learned in this study are valuable not just for high-income settings, but are equally generalizable to other laboratories.
- PMID:
- 31613905
- PMCID:
- PMC6793863
- DOI:
- 10.1371/journal.pone.0222925
- [Indexed for MEDLINE]
17.
PLoS One. 2019 Oct 10;14(10):e0223991. doi: 10.1371/journal.pone.0223991. eCollection 2019.
Alteration of humoral, cellular and cytokine immune response to inactivated influenza vaccine in patients with Sickle Cell Disease.
Nagant C1, Barbezange C2, Dedeken L3, Besse-Hammer T4, Thomas I2, Mahadeb B5, Efira A4, Ferster A3, Corazza F1.
Abstract
INTRODUCTION:
Patients suffering from Sickle Cell Disease (SCD) are at increased risk for complications due to influenza virus. Annual influenza vaccination is strongly recommended but few clinical studies have assessed its immunogenicity in individuals with SCD. The aim of this study was to explore the biological efficacy of annual influenza vaccination in SCD patients by characterizing both their humoral and cell-mediated immunity against influenza antigen. We also aimed to investigate these immunological responses among SCD individuals according to their treatment (hydroxyurea (HU), chronic blood transfusions (CT), both HU and CT or none of them).
METHODS:
Seventy-two SCD patients (49 receiving HU, 9 on CT, 7 with both and 7 without treatment) and 30 healthy controls were included in the study. All subjects received the tetravalent influenza α-RIX-Tetra® vaccine from the 2016-2017 or 2017-2018 season.
RESULTS:
Protective anti-influenza HAI titers were obtained for the majority of SCD patients one month after vaccination but seroconversion rates in patient groups were strongly decreased compared to controls. Immune cell counts, particularly cellular memory including memory T and memory B cells, were greatly reduced in SCD individuals. Functional activation assays confirmed a poorer CD8+ T cell memory. We also document an imbalance of cytokines after influenza vaccination in SCD individuals with an INFγ/IL-10 ratio (Th1-type/Treg-type response) significantly lower in the SCD cohort.
CONCLUSION:
SCD patients undergoing CT showed altered immune regulation as compared to other treatment subgroups. Altogether, the cytokine imbalance, the high regulatory T cell levels and the low memory lymphocyte subset levels observed in the SCD cohort, namely for those on CT, suggest a poor ability of SCD patients to fight against influenza infection. Nevertheless, our serological data support current clinical practice for annual influenza vaccination, though immunogenicity to other vaccines involving immunological memory might be hampered in SCD patients and should be further investigated.
- PMID:
- 31600331
- PMCID:
- PMC6786629
- DOI:
- 10.1371/journal.pone.0223991
- [Indexed for MEDLINE]
18.
PLoS One. 2019 Oct 10;14(10):e0223806. doi: 10.1371/journal.pone.0223806. eCollection 2019.
Early and long-term outcomes of coronary artery bypass surgery with and without use of heart-lung machine and with special respect to renal function - A retrospective study.
Merkle J1, Sunny J1, Ehlscheid L1, Sabashnikov A1, Weber C1, Eghbalzadeh K1, Djordjevic I1, Liakopoulos O1, Choi YH1, Wahlers T1, Zeriouh M1.
Abstract
The aim of our study was to compare early and long-term outcome of patients undergoing either on-pump or off-pump coronary artery bypass grafting with special focus on impairment of renal function. Five hundred ninety-three consecutive patients undergoing coronary artery bypass grafting were retrospectively analyzed. They were assigned either to on-pump (n = 281) or to off-pump (n = 312) group. Early and long-term outcomes were analyzed with special focus on renal function. Basic demographics and preoperative characteristics did not differ between groups (p>0.05) as well as postoperative renal parameters (p>0.05). Postoperative odds ratios (OR) of off-pump group in comparison to on-pump group were higher without reaching significance in terms of incidence of gastrointestinal complications and pneumonia (OR = 2.23 and 1.61, respectively) as well as hazard ratios (HR) on long-term follow-up for mortality and incidence of myocardial infarction (HR = 1.50 and 2.29, respectively). Kaplan-Meier estimation analysis also revealed similar results for both groups in terms of mid- and long-term survival (Breslow p = 0.062 and Log-Rank p = 0.064, respectively) and for incidence of myocardial infarction (Breslow p = 0.102 and Log-Rank p = 0.103, respectively). Our study suggests that use or not use of coronary artery bypass did not influence postoperative renal function. Odds of early outcomes were similar in both groups as well as incidence of myocardial infarction and mortality in long-term follow-up.
- PMID:
- 31600308
- PMCID:
- PMC6786630
- DOI:
- 10.1371/journal.pone.0223806
- [Indexed for MEDLINE]
19.
Microb Pathog. 2019 Nov;136:103702. doi: 10.1016/j.micpath.2019.103702. Epub 2019 Aug 28.
Identification of genomic loci associated with genotypic and phenotypic variation among Pseudomonas aeruginosa clinical isolates from pneumonia.
Abstract
In this work, a genotype-phenotype survey of a highly diversified Pseudomonas aeruginosa collection was conducted, aiming to detail pathogen-associated scenarios that clinicians face nowadays. Genetic relation based on RAPD-PCR of 705 isolates, retrieved from 424 patients and several clinical contexts, reported an almost isolate-specific molecular-pattern. Pneumonia-associated isolates HB13 and HB15, clustered in the same RAPD-PCR group, were selected to evaluate the genomic background underlying their contrasting antibiotic resistance and virulence. The HB13 genome harbors antibiotic-inactivating enzymes-coding genes (e.g. aac(3)-Ia, arr, blaVIM-2) and single-nucleotide variations (SNVs) in antibiotic targets, likely accounting for its pan-resistance, whereas HB15 susceptibility correlated to predicted dysfunctional alleles. Isolate HB13 showed the unprecedented rhl-cluster absence and variations in other pathogen competitiveness contributors. Conversely, HB15 genome comprises exoenzyme-coding genes and SNVs linked to increased virulence. Secretome analysis identified signatures features with unknown function as potential novel pathogenic (e.g. a MATE-protein in HB13, a protease in HB15) and antibiotic resistance (a HlyD-like secretion protein in HB13) determinants. Detection of active prophages, proteases (including protease IV and alkaline metalloproteinase), a porin and a peptidase in HB15 highlights the secreted arsenal likely essential for its virulent behavior. The presented phenotype-genome association will contribute to the current knowledge on Pseudomonas aeruginosa pathogenomics.
Copyright © 2019 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antimicrobial resistance; Comparative genomics; Genotype profiling; Pseudomonas aeruginosa; Virulence factors; epidemiological study
20.
PLoS One. 2019 Aug 6;14(8):e0220443. doi: 10.1371/journal.pone.0220443. eCollection 2019.
Networks of face-to-face social contacts in Niakhar, Senegal.
Abstract
We present the first analysis of face-to-face contact network data from Niakhar, Senegal. Participants in a cluster-randomized influenza vaccine trial were interviewed about their contact patterns when they reported symptoms during their weekly household surveillance visit. We employ a negative binomial model to estimate effects of covariates on contact degree. We estimate the mean contact degree for asymptomatic Niakhar residents to be 16.5 (95% C.I. 14.3, 18.7) in the morning and 14.8 in the afternoon (95% C.I. 12.7, 16.9). We estimate that symptomatic people make 10% fewer contacts than asymptomatic people (95% C.I. 5%, 16%; p = 0.006), and those aged 0-5 make 33% fewer contacts than adults (95% C.I. 29%, 37%; p < 0.001). By explicitly modelling the partial rounding pattern observed in our data, we make inference for both the underlying (true) distribution of contacts as well as for the reported distribution. We created an estimator for homophily by compound (household) membership and estimate that 48% of contacts by symptomatic people are made to their own compound members in the morning (95% CI, 45%, 52%) and 60% in the afternoon/evening (95% CI, 56%, 64%). We did not find a significant effect of symptom status on compound homophily. We compare our findings to those from other countries and make design recommendations for future surveys.
- PMID:
- 31386686
- PMCID:
- PMC6684077
- DOI:
- 10.1371/journal.pone.0220443
- [Indexed for MEDLINE]
21.
Am J Kidney Dis. 2019 Jul;74(1):23-35. doi: 10.1053/j.ajkd.2019.01.025. Epub 2019 Mar 19.
Cost-effectiveness of Pneumococcal Vaccination Among Patients With CKD in the United States.
Ishigami J1, Padula WV2, Grams ME3, Chang AR4, Jaar B1, Gansevoort RT5, Bridges JFP6, Kovesdy CP7, Uchida S8, Coresh J1, Matsushita K9.
Abstract
RATIONALE & OBJECTIVE:
Pneumococcal vaccine is recommended for adults 65 years and older and those younger than 65 years with clinical indications (eg, diabetes, lung/heart disease, kidney failure, and nephrotic syndrome). Its cost-effectiveness in less severe chronic kidney disease (CKD) is uncharacterized.
STUDY DESIGN:
Cost-effectiveness analysis.
SETTING & POPULATION:
US adults aged 50 to 64 and 65 to 79 years stratified by CKD risk status: no CKD (estimated glomerular filtration rate≥60mL/min/1.73m2 and urinary albumin-creatinine ratio<30mg/g), CKD with moderate risk, CKD with high risk, and kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2) or nephrotic-range albuminuria (urinary albumin-creatinine ratio≥2,000mg/g). Data sources were the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, Centers for Disease Control and Prevention, and the Atherosclerosis Risk in Communities (ARIC) Study.
INTERVENTION(S):
Vaccination compared to no vaccination.
OUTCOMES:
Incremental cost-effectiveness ratios based on US dollars per quality-adjusted life-year (QALY).
MODEL, PERSPECTIVE, & TIMEFRAME:
Markov model, US health sector perspective, and lifetime horizon.
RESULTS:
The prevalence of pneumococcal vaccination in NHANES 1999 to 2004 was 56.6% (aged 65-79 years), 28.5% (aged 50-64 years with an indication), and 9.7% (aged 50-64 years without an indication), with similar prevalences across CKD risk status. Pneumococcal vaccination was overall cost-effective (<US $100,000/QALY) for adults aged 65 to 79 years (US $15,000/QALY) and 50 to 64 years (US $38,000/QALY). Among those aged 50 to 64 years, incremental cost-effectiveness ratios were lowest for kidney failure or nephrotic-range albuminuria (US $1,000/QALY), followed by CKD with high risk (US $17,000/QALY), CKD with moderate risk (US $25,000/QALY), and no CKD (US $43,000/QALY). Pneumococcal vaccination was cost-effective among adults aged 50 to 64 years with CKD even when assuming the lowest vaccine efficacy or 50% higher vaccine costs.
LIMITATIONS:
Some model parameters were based on data from the general population. Analysis did not consider costs associated with kidney disease progression.
CONCLUSIONS:
Uptake of pneumococcal vaccination should be improved in general. Our results also suggest the cost-effectiveness of expanding its indication to younger adults with CKD less severe than kidney failure or nephrotic syndrome.
Copyright © 2019. Published by Elsevier Inc.
KEYWORDS:
Chronic kidney disease (CKD); albuminuria; chronic kidney failure; chronic renal insufficiency; cost-effectiveness; glomerular filtration rate (GFR); infection; infectious disease; invasive pneumococcal disease; pneumococcal disease; pneumococcal pneumonia; pneumococcal vaccine; proteinuria; streptococcus pneumonia; vaccination
Comment in
- A New Indication for Pneumococcal Vaccination? [Am J Kidney Dis. 2019]
22.
Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e01989-18. doi: 10.1128/AAC.01989-18. Print 2019 Apr.
Dose Optimization of Colistin Combinations against Carbapenem-Resistant Acinetobacter baumannii from Patients with Hospital-Acquired Pneumonia in China by Using an In Vitro Pharmacokinetic/Pharmacodynamic Model.
Abstract
Colistin-based combination therapy has become an important strategy to combat the carbapenem-resistant Acinetobacter baumannii (CRAB). However, the optimal dosage regimen selection for the combination with maximum efficacy is challenging. Checkerboard assay was employed to evaluate the synergy of colistin in combination with meropenem, rifampin, fosfomycin, and minocycline against nine carbapenem-resistant A. baumannii isolates (MIC of meropenem [MICMEM], ≥32 mg/liter) isolated from Chinese hospital-acquired pneumonia (HAP) patients. A static time-kill assay, in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, and semimechanistic PK/PD modeling were conducted to predict and validate the synergistic effect of the most efficacious combination. Both checkerboard and static time-kill assays demonstrated the superior synergistic effect of the colistin-meropenem combination against all CRAB isolates. In the in vitro PK/PD model, the dosage regimen of 2 g meropenem daily via 3-h infusion combined with steady-state 1 mg/liter colistin effectively suppressed the bacterial growth at 24 h with a 2-log10 decrease, compared with the initial inocula against two CRAB isolates. The semimechanistic PK/PD model predicted that more than 2 mg/liter colistin combined with meropenem (2 g, 3-h infusion) was required to achieve the killing below the limit of detection (<LOD; i.e., 1 log10CFU/ml) at 24 h with an MICMEM of ≥32 mg/liter. Colistin combined with meropenem exerted synergistic killing against CRAB even with an MICMEM of ≥32 mg/liter and MIC of colistin (MICCST) of ≤1 mg/liter. However, it is predicted that a higher concentration of colistin combined with meropenem was crucial to kill bacteria to <LOD. Our study provides important PK/PD information for optimization of the colistin and meropenem combination against CRAB.
Copyright © 2019 American Society for Microbiology.
KEYWORDS:
Acinetobacter baumannii ; PK/PD modeling; carbapenem resistance; colistin; combination therapy; meropenem
23.
AIDS Care. 2019 Oct;31(10):1311-1318. doi: 10.1080/09540121.2019.1576845. Epub 2019 Feb 7.
Combining surveillance systems to investigate local trends in tuberculosis-HIV co-infection.
Abstract
Alameda County has some of the highest human immunodeficiency virus (HIV) and tuberculosis (TB) case rates of California counties. We identified TB-HIV co-infected patients in 2002-2015 by matching county TB and HIV registries, and assessed trends in TB-HIV case rates and estimated prevalence ratios for HIV co-infection. Of 2054 TB cases reported during 2002-2015, 91 (4%) were HIV co-infected. TB-HIV case rates were 0.29/100,000 and 0.40/100,000 in 2002 and 2015, respectively, with no significant change (P = 0.85). African-American TB case-patients were 9.77 times (95% confidence interval [CI] 5.90-16.17) more likely than Asians to be HIV co-infected, and men 2.74 times (95% CI 1.66-4.51) more likely co-infected than women. HIV co-infection was more likely among TB case-patients with homelessness (6.21, 95% CI 3.49-11.05) and injection drug use (11.75, 95% CI 7.61-18.14), but less common among foreign-born and older case-patients (both P < 0.05). Among foreign-born case-patients, 42% arrived in the U.S. within 5 years of TB diagnosis. TB-HIV case rates were low and stable in Alameda County, and co-infected patients were predominantly young, male, U.S.-born individuals with traditional TB risk factors. Efforts to reduce TB-HIV burden in Alameda County should target persons with traditional TB risk factors and recently arrived foreign-born individuals.
KEYWORDS:
AIDS-related opportunistic infections; California; HIV; Tuberculosis; public health surveillance
24.
Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e01964-18. doi: 10.1128/AAC.01964-18. Print 2019 Apr.
A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.
Francis J#1, Zvada SP#1, Denti P2, Hatherill M3, Charalambous S4, Mungofa S5, Dawson R6, Dorman S7, Gupte N7, Wiesner L1, Jindani A8, Harrison TS8, Olagunju A9, Egan D10, Owen A10, McIlleron HM1.
Abstract
Rifapentine is a rifamycin used to treat tuberculosis. As is the case for rifampin, plasma exposures of rifapentine are associated with the treatment response. While concomitant food intake and HIV infection explain part of the pharmacokinetic variability associated with rifapentine, few studies have evaluated the contribution of genetic polymorphisms. We evaluated the effects of functionally significant polymorphisms of the genes encoding OATP1B1, the pregnane X receptor (PXR), constitutive androstane (CAR), and arylacetamide deacetylase (AADAC) on rifapentine exposure. Two studies evaluating novel regimens among southern African patients with drug-susceptible pulmonary tuberculosis were included in this analysis. In the RIFAQUIN study, rifapentine was administered in the continuation phase of antituberculosis treatment in 1,200-mg-once-weekly or 900-mg-twice-weekly doses. In the Daily RPE study, 450 or 600 mg was given daily during the intensive phase of treatment. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics of rifapentine and to identify significant covariates. A total of 1,144 drug concentration measurements from 326 patients were included in the analysis. Pharmacogenetic information was available for 162 patients. A one-compartment model with first-order elimination and transit compartment absorption described the data well. In a typical patient (body weight, 56 kg; fat-free mass, 45 kg), the values of clearance and volume of distribution were 1.33 liters/h and 25 liters, respectively. Patients carrying the AA variant (65.4%) of AADAC rs1803155 were found to have a 10.4% lower clearance. HIV-infected patients had a 21.9% lower bioavailability. Once-weekly doses of 1,200 mg were associated with a reduced clearance (13.2%) compared to that achieved with more frequently administered doses. Bioavailability was 23.3% lower among patients participating in the Daily RPE study than in those participating in the RIFAQUIN study. This is the first study to report the effect of AADAC rs1803155AA on rifapentine clearance. The observed increase in exposure is modest and unlikely to be of clinical relevance. The difference in bioavailability between the two studies is probably related to the differences in food intake concomitant with the dose. HIV-coinfected patients had lower rifapentine exposures.
Copyright © 2019 Francis et al.
KEYWORDS:
AADAC ; SLCO1B1 ; pharmacogenetics; population pharmacokinetics; rifapentine; tuberculosis
25.
Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e01834-18. doi: 10.1128/AAC.01834-18. Print 2019 Apr.
Early Detection of Emergent Extensively Drug-Resistant Tuberculosis by Flow Cytometry-Based Phenotyping and Whole-Genome Sequencing.
O'Donnell MR1,2,3, Larsen MH4, Brown TS5, Jain P4, Munsamy V6, Wolf A7, Uccellini L7, Karim F6, de Oliveira T8, Mathema B2, Jacobs WR4, Pym A6.
Erratum in
Abstract
A critical gap in tuberculosis (TB) treatment is detection of emergent drug resistance. We hypothesized that advanced phenotyping with whole-genome sequencing (WGS) will detect low-frequency Mycobacterium tuberculosis drug resistance. We assessed a reporter mycobacteriophage (Φ2GFP10) in vitro to detect drug-resistant subpopulations and predict M. tuberculosis bactericidal activity in this pilot study. Subsequently, we prospectively studied 20 TB patients with serial Φ2GFP10, Xpert MTB/RIF, and M. tuberculosis culture through end of treatment. WGS was performed, and single nucleotide polymorphisms (SNPs) were examined to detect mixed infection in selected M. tuberculosis isolates. Resistant M. tuberculosis isolates were detected at 1:100,000, and changes in cytometry-gated events were predictive of in vitro M. tuberculosis bactericidal activity using the Φ2GFP10 assay. Emergent drug resistance was detected in one patient by Φ2GFP10 at 3 weeks but not by conventional testing (M. tuberculosis culture and GeneXpert). WGS revealed a phylogeographically distinct extensively drug-resistant tuberculosis (XDR-TB) genome, identical to an XDR-TB isolate from the patient's spouse. Variant lineage-specific SNPs were present early, suggesting mixed infection as the etiology of emergent resistance with temporal trends providing evidence for selection during treatment. Φ2GFP10 can detect low-frequency drug-resistant M. tuberculosis and with WGS characterize emergent M. tuberculosis resistance. In areas of high TB transmission and drug resistance, rapid screening for heteroresistance should be considered.
Copyright © 2019 American Society for Microbiology.
KEYWORDS:
South Africa; extensively drug-resistant tuberculosis; heteroresistance; phage; tuberculosis; whole-genome sequencing
26.
J Epidemiol. 2019 Aug 5;29(8):279-281. doi: 10.2188/jea.JE20180177. Epub 2018 Nov 10.
Commentary: Test-Negative Design Reduces Confounding by Healthcare-Seeking Attitude in Case-Control Studies.
KEYWORDS:
health conscious behavior; hospital-based case-control study; selection bias
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