Epidemiological,clinical and genetic characterization of scrub typhus in patients presenting with acute febrile illness in New Delhi

PurposeScrub typhus (ST) is a zoonotic disease, caused by O. tsutsugamushi is a major cause of acute febrile illness (AFI) in India. There is a need to study the prevalence and risk factors in various regions of India.MethodsA study to estimate the prevalence and study the risk factors of ST in patients presenting with acute febrile illness (AFI) was performed. All patients underwent serology for IgM antibodies to Orientia tsutsugamushi (In Bios International Inc, Seattle, WA) as per the manufacturers’ protocol. Following this, Polymerase Chain reaction (PCR) (real time SYBR green based targeting groEL gene and conventional PCR targeting 56 ?kDa type specific antigen gene) was performed from stored serum samples.ResultsDuring the study period, 473 patients were admitted. Of these 56 (11.8%) patients were ST positive by IgM serology. The conventional PCR targeting 56 ?kDa type specific antigen gene of O. tsutsugamushi was positive in six patients while Ot groEL SYBR green based PCR) was positive in five. PCR was positive in patients who had demonstrated a higher OD value in ELISA. Conventional PCR positive amplicons were sent for Sanger sequencing and confirmed to be O. tsutsugamushi. The mean age of the patients was 49 ?± ?18.3 years and males constituted a higher number of patients (67.9%, n ?= ?38). The pathognomonic eschar was present in 7 (12.5%) patients. Phylogenetic analysis revealed that sequences clustered close to Kato-like Hualein-20 strain and Karp-like Linh DT strains. All patients were administered doxycycline in our study. Mortality was recorded in 8.9% of the patients.ConclusionsIn patients presenting with acute febrile illness, ST should be considered as a differential diagnosis, especially in post-monsoon season. Along with serology, serum can also be used as sample for PCR in an intracellular bacterium like O. tsutsugamushi.     

Evaluation of an in-house PCR for diagnosing scrub typhus along with a preliminary study of genotypic characterization of Orientia tsutshugamushi circulating in Chhattisgarh: A prospective clinico-microbiological study

PurposeScrub typhus, caused by Orientia tsutsugamushi (O. tsutsugamushi) present nonspecific clinical features during manifestation of acute undifferentiated febrile illness (AUFI) to render its early diagnosis difficult. Accordingly, this study was undertaken to assess an in-house groEL PCR versus IgM ELISA for the diagnosis of scrub typhus and to genotypically characterise the randomly selected scrub typhus positive cases.MethodsBlood samples, collected from two hundred twenty one (221) AUFI cases were subjected to groEL PCR and IgM ELISA for diagnosis of scrub typhus. Eleven randomly selected PCR positive cases were processed for DNA sequencing to determine the genetic diversity of O. tsutsugamushi in Chhattisgarh.ResultsScrub typhus prevalence of 35.2% were detected among AUFI cases using both in-house groEL PCR and IgM ELISA. PCR alone showed sensitivity, specificity, positive and negative predictive values of 66.6% (CI: 55.08–76.94), 100% (CI: 90 to 100),100% (CI: 93.15 to 100) and 57.37% (CI: 44.05 to 69.96) while for IgM ELISA, these parameters were 62.8% (CI: 51.13–73.50), 100% (CI: 90 to 100), 100% (CI: 92.75 to 100) and 54.68% (CI: 41.75 to 67.18) respectively. PCR and ELISA could detect scrub typhus in 37.2% and 33.3% cases, when tested alone. groEL PCR detected the O. tsutsugamushi throughout the course of infection. Phylogenetic analysis depicted 5 of 11 positive cases belonged to Kuroki, Japan strain of O. tsutsugamushi, followed by Gilliam and Karp strain in 4 and 2 cases respectively.ConclusionScrub typhus should be considered in differential diagnosis of AUFI. groEL PCR may aid on to IgM ELISA test for optimum laboratory diagnosis of scrub typhus by its implementation especially in seronegative cases. Predominance of Kuroki-like strain followed by Gillian and Karp strains of O. tsutsugamushi in Chhattisgarh confirm variable geographical distribution of O. tsutsugamushi and provide the baseline epidemiological data which will eventually be used to help the researchers for developing better diagnostic tests and vaccine covering the predominant genotypes.     

Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity

Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but its clinical significance is not well known. This study was designed to evaluate interstitial pneumonia as a marker of severity of the disease for patients with scrub typhus. We investigated clinical parameters representing the severity of the disease, and the chest radiographic findings for 101 patients with scrub typhus. We then compared these clinical factors between patients with and without IP. We also studied the relationship between IP and other chest radiographic findings. The chest radiography showed IP (51.4%), pleural effusion (42.6%), cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy (13.8%) and focal atelectasis (11.8%), respectively. The patients with IP (n=52) had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024), severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients without IP (n=49). The patients with IP also had higher incidences of pleural effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001), pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the patients without IP. Our data suggest that IP frequently occurs for patients with scrub typhus and its presence is closely associated with the disease severity of scrub typhus.     

The prognostic value of serological titres for clinical outcomes during treatment and follow-up of patients with chronic Q fever

ObjectivesWe assessed the prognostic value of phase I IgG titres during treatment and follow-up of chronic Q fever.MethodsWe performed a retrospective cohort study to analyse the course of phase I IgG titres in chronic Q fever. We used a multivariable time-varying Cox regression to assess our primary (first disease-related event) and secondary (therapy failure) outcomes. In a second analysis, we evaluated serological characteristics after 1 year of therapy (fourfold decrease in phase I IgG titre, absence of phase II IgM and reaching phase I IgG titre of ≤1:1024) with multivariable Cox regression.ResultsIn total, 337 patients that were treated for proven (n = 284, 84.3%) or probable (n = 53, 15.7%) chronic Q fever were included. Complications occurred in 190 (56.4%), disease-related mortality in 71 (21.1%) and therapy failure in 142 (42.1%) patients. The course of phase I IgG titres was not associated with first disease-related event (HR 1.00, 95% CI 0.86–1.15) or therapy failure (HR 1.02, 95% CI 0.91–1.15). Similar results were found for the serological characteristics for the primary (HR 0.97, 95% CI 0.62–1.51; HR 1.12, 95% CI 0.66–1.90; HR 0.99, 95% CI 0.57–1.69, respectively) and secondary outcomes (HR 0.86, 95% CI 0.57–1.29; HR 1.37, 95% CI 0.86–2.18; HR 0.80, 95% CI 0.48–1.34, respectively).DiscussionCoxiella burnetii serology does not reliably predict disease-related events or therapy failure during treatment and follow-up of chronic Q fever. Alternative markers for disease management are needed, but, for now, management should be based on clinical factors, PCR results, and imaging results.     

XMRV,Q fever and other emerging infections: impact on management of blood safety

As a result of continuous improvement efforts, the blood supply is now extremely safe. However, emerging infections offer a real or potential challenge to such safety. Since 2003, two new tests have been implemented in the United States in order to reduce the risk of transfusion transmission of West Nile virus and Trypanosoma cruzi. In addition, Babesia microti and dengue viruses are considered to be high-priority threats. Q fever outbreaks in the Netherlands illustrate a localized threat that has been assessed and managed through human and agricultural public health measures and by selective testing of blood donors. The recently recognized gammaretrovirus XMRV has generated scientific and social controversy and illustrates a number of problems in managing blood safety policy.     

Characteristics,risk factors and outcomes of community-acquired acute kidney injury in the elderly: a prospective tertiary hospital study,Egypt

BackgroundAcute Kidney Injury (AKI) is a public health problem. Elderly present a greater predisposition to the development of AKI, either due to kidney senility, or due to high prevalence of comorbidities and polypharmacy. Considering the scarcity of studies on AKI in the elderly particularly in developing countries, this study emphasizes on the pattern and outcome of AKI in the Egyptian elderly.ObjectiveTo analyze the demographics, risk factors and outcomes of Acute Kidney Injury (AKI) in the Egyptian elderly.MethodsA total of 199 patients were included over one year and were divided into two groups; group I (79 elderly patients) and group II (120 non-elderly patients). The two groups were compared regarding demographics, risk factors and major outcomes including patient and renal survival.ResultsElderly patients showed a higher prevalence of Diabetes Mellitus and chronic kidney disease (p=0.004 and 0.005 respectively). Pre-renal causes of AKI principally dehydration represented the major risk factor (p=0.003). Sepsis and hypertension predicted mortality in the elderly (p=0.001 and 0.035 respectively).ConclusionIn our locality; the elderly is highly vulnerable to AKI. Pre-renal causes principally dehydration represent the main triggers of AKI. Sepsis and hypertension contribute to mortality in this population. Preventive strategies are crucial not only in the hospital but also at home.     

Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease

Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens.     

Causes of death among dengue patients causes of death among hospitalized adults with dengue fever in Tainan, 2015: Emphasis on cardiac events and bacterial infections

IntroductionThe 2015 dengue outbreak in southern Taiwan caused substantial mortality. We analyzed the causes of death among these patients.Materials and methodsThis retrospective study was conducted at a medical center in Tainan from August 2015 to December 2015. Dengue was diagnosed based on the detection of serum dengue NS1 antigen, IgM, or viral RNA in the blood. Causes of death were retrieved from chart reviews by three clinicians.ResultsThere were 4488 cases of dengue in the study hospital, with an in-hospital fatality rate of 1.3% (60 cases). The mean age of the 60 fatal cases was 73 years, among whom 90% were aged ≥65 years. Twenty-eight (46.7%) patients died of severe dengue, and 29 (48.3%) deaths were possibly related to dengue. Of the latter, 24 (40%) died of secondary infections. Thirteen cardiac arrest events, including out-of-hospital (5 events) and in-hospital (8) cardiac arrests in the emergency department, occurred during the dengue epidemic. Seven (53.8%) patients did not receive medical aid before the event. Of the 40 deaths that occurred within one week after hospitalization, 60% died of severe dengue. In contrast, 50% of 20 deaths that occurred one week after hospitalization were related to hospital-acquired infections, mainly pneumonia.ConclusionOf 60 fatal cases, with a predominance of elderly patients, deaths were related to severe dengue within the first week after admission and secondary infections thereafter. The absence of medical care before cardiac arrest events highlights the importance of health education for warning signs of dengue.     

Characteristics,prevalence, risk factors,and underlying mechanism of hyponatremia in elderly patients treated with antidepressants: A cross-sectional study

ObjectivesThe aims of this study were to describe the characteristics of hyponatremia in elderly users of antidepressants, to determine the prevalence and risk factors for hyponatremia, and to identify the underlying mechanisms.Study designCross-sectional study (March 2007–April 2009) with prospectively collected data. Patients were older than 60 years, used antidepressants, and had a complete geriatric assessment.Main outcome measuresSerum sodium and antidiuretic hormone levels, serum osmolality, urine sodium level, and urine osmolality were measured. The prevalence of hyponatremia (serum sodium <135 mM) as an adverse reaction to an antidepressant (AR-AD), defined with Naranjo's algorithm, was calculated. Hyponatremic patients were compared to normonatremic patients with regard to gender, age, weight, history of hyponatremia, hyponatremia-associated medications and disorders, and type and duration of antidepressant use.ResultsOf 358 eligible patients, 345 were included. The prevalence of hyponatremia as an AR-AD was 9.3%. Risk factors were a history of hyponatremia (adjusted OR 11.17, 95%CI 2.56–40.41), weight < 60 kg (adjusted OR 3.47, 95%CI 1.19–10.13), and psychosis (adjusted OR 3.62, 95%CI 1.12–11.73). Non-suppressed ADH was found in a minority of hyponatremic patients.ConclusionsIn elderly patients, the prevalence of hyponatremia as adverse reaction to all types of antidepressants was 9%. Patients with previous hyponatremia, weight <60 kg, and psychosis were at risk. Beside SIADH, the nephrogenic syndrome of inappropriate antidiuresis, in which ADH secretion was normal, is postulated as an underlying mechanism. This has consequences for treatment of antidepressant-induced hyponatremia with vasopressin receptor antagonists.     

Religious coping methods as predictors of psychological, physical and spiritual outcomes among medically ill elderly patients: a two-year longitudinal study

A total of 268 medically ill, elderly, hospitalized patients responded to measures of religious coping and spiritual, psychological and physical functioning at baseline and follow-up two years later. After controlling for relevant variables, religious coping was significantly predictive of spiritual outcome, and changes in mental and physical health. Generally, positive methods of religious coping (e.g. seeking spiritual support, benevolent religious reappraisals) were associated with improvements in health. Negative methods of religious coping (e.g. punishing God reappraisal, interpersonal religious discontent) were predictive of declines in health. Patients who continue to struggle with religious issues over time may be particularly at risk for health-related problems.     

Accuracy of comprehensive PCR analysis of nasopharyngeal and oropharyngeal swabs for CT-scan-confirmed pneumonia in elderly patients: a prospective cohort study

ObjectivesWe aimed to assess the accuracy of PCR detection of viruses and bacteria on nasopharyngeal and oropharyngeal swabs (NPS) for the diagnosis of pneumonia in elderly individuals.MethodsWe included consecutive hospitalized elderly individuals suspected of having pneumonia. At inclusion, NPS were collected from all participants and tested by PCR for the presence of viral and bacterial respiratory pathogens (index test, defined as comprehensive molecular testing). Routine diagnostic tests (blood and sputum culture, urine antigen detection) were also performed. The reference standard was the presence of pneumonia on a low-dose CT scan as assessed by two independent expert radiologists.ResultsThe diagnosis of pneumonia was confirmed in 127 of 199 (64%) included patients (mean age 83 years, community-acquired pneumonia in 105 (83%)). A pathogen was identified by comprehensive molecular testing in 114 patients (57%) and by routine methods in 22 (11%). Comprehensive molecular testing was positive for viruses in 62 patients (31%) and for bacteria in 73 (37%). The sensitivity and specificity were 61% (95% CI 53%–69%) and 50% (95% CI 39%–61%) for comprehensive molecular testing, and 14% (95% CI 82%–21%) and 94% (95% CI 86%–98%) for routine testing, respectively. Positive likelihood ratio was 2.55 for routine methods and 1.23 for comprehensive molecular testing.ConclusionComprehensive molecular testing of NPS increases the number of pathogens detected compared with routine methods, but results are poorly predictive of the presence of pneumonia. Hence, comprehensive molecular testing is unlikely to impact clinical decision-making (NCT02467192).Clinical Trials RegistrationNCT02467192.     

Effect of tocilizumab,sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis

BackgroundRandomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids.ObjectivesTo estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids.Data sourcesPubMed, Embase, Cochrane Library, and MedRxiv.Study eligibility criteriaEligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control).MethodsReviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days.ParticipantsTwenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively.ResultsAll but two studies included data with only indirect evidence for the comparison of interest.ConclusionsAmong hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.