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2.
JAMA Netw Open ; 5(1): e2142210, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34994793

RESUMO

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.


Assuntos
COVID-19/epidemiologia , Pessoal de Saúde , Reinfecção , SARS-CoV-2 , Adulto , COVID-19/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Imunogenicidade da Vacina , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Atenção Terciária , Vacinas de Produtos Inativados/administração & dosagem , Vírion/imunologia , Adulto Jovem
3.
Indian J Pediatr ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855068

RESUMO

OBJECTIVES: To elicit antibiotic prescribing patterns across Indian Pediatric Intensive Care Units (PICU) and assess attributes of the antibiotic stewardship programs. METHODS: A link to a web-based questionnaire was sent by email to pediatric intensivists across India. RESULTS: Responses were received from 62 PICUs. Majority of respondents were from private hospitals [49/62 (79.5%)]. The most commonly reported infection requiring PICU admission was community-acquired pneumonia [by 39 (62.9%) PICUs] followed by gastroenteritis [26 (41.9%)], and meningitis [15 (24.1%)]. The blood culture positivity rates varied among participating PICUs with 37 centers (59.6%) reporting low blood culture positivity yield (< 40%). Majority of the respondents acknowledged using a 7-d course of antibiotics even in culture-negative sepsis. Most common empiric antibiotics prescribed for community-acquired infections were beta-lactam monotherapy. The typical beta-lactam prescribed was ceftriaxone. However, for hospital-acquired infections (HAI), such as suspected catheter-related bloodstream infection (CLABSI) and suspected ventilator-associated pneumonia (VAP), a higher number of respondents-39/62 (61.9%) and 33/62 (53.2%), respectively, prescribed combination antibiotics (ß-lactam + vancomycin). Forty-two units (67.7%) reported having an antibiotic stewardship program in their PICUs, while twenty-nine (45.1%) centers stated having formulary restrictions. Ten (16.1%) centers had pre-authorization policy for certain antibiotics. CONCLUSION: A rather diverse pattern of prescribing and administration practices exists across different Indian PICUs. While antibiotic stewardship programmes are established in most centers, formulary restriction and pre-authorisation of antibiotic prescribing were reported by few units. Regular surveillance studies are needed to bring uniformity in antibiotic policy and select appropriate empiric therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34888654

RESUMO

OBJECTIVE: Early aggressive therapy using biologicals is increasingly being used in Juvenile Idiopathic Arthritis (JIA) for early disease remission. Pulse-steroids are used in induction regimes for rheumatic disorders such as systemic lupus erythematosus and systemic JIA; however, no controlled studies demonstrate their use in non-systemic JIA. The objective of the present study was to evaluate the efficacy and safety of pulse dexamethasone therapy in children with treatment-naive non-systemic JIA as early aggressive therapy in resource-limited settings. METHODS: 60 treatment-naive children with non-systemic JIA with an active joint count of ≥ 5 and/or involvement of hip or cervical joints were randomised to receive either pulse dexamethasone (3 mg/kg/day, max : 100 mg/d) or placebo (normal saline) for three consecutive days during each visit at 0, 6 ± 2, 12 ± 2 weeks; along with standard therapy (methotrexate and NSAIDs). The use of oral bridge steroids was permissible for persistent severe disease as per pre-defined criteria. The primary outcome was ACR-Pedi 70 response at 16 ± 2 weeks after enrolment in the two groups. RESULTS: The proportion of children achieving ACR-Pedi 70 in the two groups, at last follow-up was 11/30 (36.7%) in pulse dexamethasone arm vs 11/28 (39.3%) in the placebo arm (p-value 0.837, RR 0.93, 95% CI 0.48-1.80). We did not observe any significant difference in the proportion of children requiring bridge steroids. Adverse events were comparable in the two groups. CONCLUSION: The addition of pulse dexamethasone to standard treatment may not add any advantage in improving ACR-Pedi 70 scores at medium-term follow-up. TRIAL REGISTRATION: Clinical Trial Registry-India www.ctri.nic.in CTRI/2018/08/015151.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34921660

RESUMO

BACKGROUND: Growth retardation is an important feature of celiac disease (CeD) that can lead to the failure of attainment of potential adult height. There is lack of data on the spectrum of height in treatment-naïve patients with CeD, with normal expected height at one end and short stature at the other. METHODS: We performed a retrospective analysis of a prospectively maintained database at our center, including a total of 583 treatment-naïve patients with CeD: 419 adults (183 [43.7%] males) and 164 adolescents (12-18 years) (72 [43.9%] males). The details extracted from the database included demographic details, height, weight, body mass index, clinical symptoms, biochemical parameters, anti-tissue transglutaminase antibody anti-tTG Ab) titer, and the severity of villous abnormalities (as per modified Marsh grade). The data from Indian National Family Health Survey-4 were used as comparators. RESULTS: Overall, 19.6% of adults and 57.9% of adolescents with CeD had short stature. While mean height of men with CeD was similar, women were taller than population controls. While a higher proportion of men with CeD had short stature as compared to the controls (32.2% vs. 20%, p<0.001), a lower proportion of women with CeD had short stature (9.7% vs. 18.9%, p<0.001). Higher proportion of adolescents with CeD had short stature compared to adults (57.9% vs. 19.6%, p<0.001). On multivariate analysis, adulthood was found to be associated with a lower prevalence of short stature. CONCLUSIONS: Overall, 19.6% of adults and 57.9% of adolescents with CeD had short stature. While the mean height of adult men with CeD was not significantly different from the population controls, women were taller. Adolescents with CeD were significantly shorter than their peers.

6.
Pediatr Pulmonol ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826368

RESUMO

BACKGROUND: There is a lack of studies on cystic fibrosis (CF) outcomes in children from developing countries like India. Identifying risk factors for mortality may help identify the high-risk group and plan policy management of such patients. We aimed to determine the factors associated with mortality among Indian children with CF. METHODS: In this retrospective study, we extracted demography, clinical features, laboratory and outcome data from medical records of children with CF. Bivariate and multivariate analysis was performed to identify variables associated with mortality. RESULTS: We enrolled 178 children, and there were 32 (18.0%) deaths. Median (IQR) z-score for body mass index (BMI) at last follow up was -1.5 (-2.7, -0.2) and -2.5 (-4.0, -1.6), p-value 0.039, in survived and deceased group respectively. Mean (SD) of % predicted of FEV1/FVC and FEV1 25-75 at the time of diagnosis in survived versus diseased group was 94.7 (24.1) versus 81.5 (19.1), p-value 0.063 and 56.1 (38.9) versus 45.7 (29.9), p-value 0.347, respectively. Significant factors associated with mortality included history of neonatal complications; hazard ratio (HR): 8.5 (95% confidence interval [CI]: 3.0-23.9, p < 0.001), low Z-scores for BMI at the time of diagnosis; HR: 7.1 (95% CI: 2.3-22.0, p < 0.001), FEV1/FVC at the time of diagnosis; HR: 5.1 (95% CI: 1.65-15.4, p < 0.004), and FEV1 25-75; HR: 3.6 (95% CI: 1.1-11.8, p = 0.03). CONCLUSIONS: Factors associated with increased mortality risk included neonatal complications, low BMI, and lower pulmonary function test results. Low BMI and low PFT indices can be improved upon by timely treatment of respiratory infections, better nutrition, early diagnosis, and treatment. A newborn screening program may help in early diagnosis and identification of the neonatal problem of CF.

7.
Lancet Infect Dis ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826383

RESUMO

BACKGROUND: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection. METHODS: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%. FINDINGS: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61). INTERPRETATION: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

8.
Indian J Ophthalmol ; 69(12): 3734-3739, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34827033

RESUMO

Ethambutol use may lead to permanent vision loss by inducing a dose- and duration-dependent optic neuropathy. This has been of concern to ophthalmologists and physicians both; however, ethambutol continues to be used because of its anti-mycobacterial action with relative systemic safety. Recently, the guidelines of the Revised National Tuberculosis Control Programme of India have been revised to allow for fixed dose and longer duration of ethambutol use; this is likely to result in an increase in vision-threatening adverse effects. Taking cognizance of this, neuro-ophthalmologists, infectious disease specialists, and scientists met under the aegis of the Indian Neuro-Ophthalmology Society to deliberate on prevention, early diagnosis, and management of ethambutol-related toxic optic neuropathy. The recommendations made by the expert group focus on early suspicion of ethambutol toxicity through screening at the physician's office and opportunistic screening by the ophthalmologist. Further, they focus on an early diagnosis through identification of specific clinical biomarkers and on management in way of early stoppage of the drug and supportive therapy. This statement also describes the mechanism of reporting a case of toxic optic neuropathy through the Pharmacovigilance Programme of India and emphasizes the need for spreading awareness regarding vision-threatening adverse effects among patients and healthcare workers.

9.
Indian Pediatr ; 58(11): 1019-1023, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34837360

RESUMO

OBJECTIVE: To evaluate factors associated with risk of hospitalization in children with community-acquired pneumonia (CAP). DESIGN: Prospective cohort study. SETTING: Multi-site hospital based study. INTERVENTION: A separate acute respiratory tract infection (ARI) treatment unit (ATU) was established. The revised WHO case definition for ARI was used across all the study sites to ensure uniformity in management of ARI patients (2-59 months). Clinical history, examination findings and investigations of enrolled patients were recorded on a predesigned case record form. Children were followed up at 1 week (± 1 day). MAIN OUTCOME MEASURE: Risk factors for hospitalization among pneumonia patients. RESULTS: A total of 7026 children with the diagnosis of ARI were enrolled. Pneumonia was diagnosed in 938 (13.4%) patients (median (IQR) age: 15 (8, 25) months; 63.5% boys). Hospitalization was needed in 56.8% of pneumonia patients. On multi-variate analysis, factors associated with risk of hospitalization were: Oxygen saturation on pulse oximetry (SpO2) <92% in room air (OR 7.04; 95% CI 1.6, 30.8, P=0.01), procalcitonin level >0.5 ng/mL (OR: 7.5, 95% CI: 1.0, 57.7, P=0.05), and lower weight for height z-score (OR 0.8; 95% CI: 0.6, 0.9, P=0.02). CONCLUSION: Present study found SpO2 <92% at room air, serum procalcitonin level >0.5 ng/mL and lower weight for height z-score to be predictors for risk of hospitalization in under-five children presenting with community acquired pneumonia. These factors can be utilized to assess a child with CAP regarding the need of hospitalization.

10.
Indian Pediatr ; 58(11): 1024-1029, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34837361

RESUMO

BACKGROUND: Current WHO algorithm has retained the signs and symptoms used in the older version for classifying severity of childhood pneumonia. OBJECTIVE: To study the role of clinical features (including that of current WHO criteria), and oxygen saturation (SpO2) in the diagnosis of childhood pneumonia. STUDY DESIGN: Multicenter prospective cohort study. PARTICIPANTS: Children, 2 to 59 months of age, suffering from acute respiratory infection (ARI). OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios were calculated for clinical features, and SpO2. RESULTS: Of a total 7026 children with ARI enrolled, 13.4% had pneumonia (37% of them had severe pneumonia), according to WHO criteria. Based on any abnormality on chest x ray (CXR), 46% had pneumonia. The sensitivity and specificity of the existing WHO criteria for diagnosis of pneumonia was 56.5% and 66.2%, respectively, when compared against abnormalities in CXR. Cough and fever, each had sensitivity of >80%. Audible wheeze and breathing difficulty, each had a specificity of >80%. Sensitivity and specificity of tachypnoea were 58.7% and 63.3%, respectively. None of the clinical features alone had a sensitivity and specificity of >80%. Addition of SpO2 of <92% to chest indrawing alone or WHO criteria increased the likelihood of diagnosis of pneumonia. CONCLUSIONS: Current WHO criteria based on rapid respiratory rate and/or chest indrawing has modest sensitivity and specificity, considering CXR abnormalities as gold standard for diagnosis of pneumonia. Addition of SpO2 of <92% to chest indrawing alone or WHO criteria increases the probability of pneumonia diagnosis, and is important in the management of a child with pneumonia.

11.
Indian Pediatr ; 58(11): 1036-1039, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34837363

RESUMO

OBJECTIVE: To identify the risk factors for pneumonia and severe pneumonia in children. DESIGN: Prospective cohort study. SETTING: Five tertiary-care teaching hospitals in India. PARTICIPANTS: Children 2 to 59 months of age suffering from acute respiratory infection (ARI). MAIN OUTCOME MEASURES: Risk factors for the development of WHO defined pneumonia and severe pneumonia. RESULT: A total of 18159 children screened, and 7026 (39%) children with ARI were enrolled. According to the WHO criteria, 938 (13.4%) and 6088 (86.6%) of the enrolled children had pneumonia and no pneumonia, respectively. Out of 938 children with pneumonia, 347 (36.9%) had severe pneumonia. On univariate analysis, younger age, male gender and low weight for height, were significant risk factors for pneumonia. On multivariate analysis, one-unit increase in age in months (OR = 0.97; 95% CI: 0.97-0.98) and weight for height z-score (OR = 0.76; 95% CI: 0.72-0.79) had a protective effect. CONCLUSIONS: Young age and undernutrition (low weight for height/length) in children are significant independent risk factors for pneumonia.

14.
RNA Biol ; : 1-8, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747322

RESUMO

By analysis of lncRNA expression profiles of macrophages in response to Mycobacterium tuberculosis (Mtb) infection, we identified novel highly expressed transcripts, unique in encompassing a protein coding transcript- Cytidine Monophosphate Kinase 2 (CMPK2) and a previously identified lncRNA- Negative Regulator of Interferon Response (NRIR). While these transcripts (TILT1, 2,3 - TLR4 and Infection induced Long Transcript) are induced by virulent Mtb as well as lipopolysaccharide (LPS) early, lack of/delayed expression in non-viable Mtb/BCG infected cells, respectively, suggest an important role in macrophage responses. The elevated expression by 3 hr in response to fast growing bacteria further emphasizes the importance of these RNAs in the macrophage infection response. Overall, we provide evidence for the presence of multiple transcripts that form a part of the early infection response programme of macrophages.Abbreviations: IFN: Interferon; NRIR: negative regulator of interferon response; CMPK2: cytidine/ uridine monophosphate kinase; LPS: lipopolysaccharide; LAM: Lipoarabinomannan; PIMs: Phosphatidylinositol Mannosides; TILT1, 2,3: TLR4 and Infection induced Long Transcript; TLR4: Toll-like receptor 4; Mtb: Mycobacterium tuberculosis; BCG: Mycobacterium bovis BCG; MDMs: human monocyte derived macrophages.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34750905

RESUMO

AIM: To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality. METHODS: In a prospective cohort study, critically ill children (1 month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated. RESULTS: Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR) = 2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR = 1.525, 95% CI: 1.142, 2.037) and haematological (OR = 1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR = 1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality. CONCLUSIONS: Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade.

16.
J Glob Health ; 11: 04062, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737862

RESUMO

Background: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. Methods: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. Results: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). Conclusions: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.


Assuntos
Regras de Decisão Clínica , Pneumonia , Criança , Saúde da Criança , Humanos , Malaui , Índice de Gravidade de Doença
17.
Cell Microbiol ; 23(12): e13395, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34619004

RESUMO

Zinc-dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life-cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV-inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA-mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection. TAKE AWAYS: Dengue virus utilises cellular zinc homeostasis during replication of its RNA. ZIP8 upregulates free zinc levels during dengue virus replication. Enhanced viremia associates with elevated intracellular free zinc in dengue.

18.
Crit Care Med ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612847

RESUMO

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

19.
Rheumatol Int ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665296

RESUMO

To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5-18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.

20.
Front Pediatr ; 9: 667726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513756

RESUMO

Diagnosis of intra-thoracic tuberculosis (ITTB) in children is difficult due to the paucibacillary nature of the disease, the challenge in collecting appropriate specimens, and the low sensitivity of smear microscopy and culture. Culture and Xpert MTB/RIF provide higher diagnostic yield in presumptive TB in adults than in children. Current study was designed to understand poor yield of diagnostic assays in children. Children with presumptive ITTB were subjected to gastric aspirates and induced sputum twice. Samples were tested by Ziehl-Neelsen stain, Xpert MTB/RIF-assay, and MGIT-960 culture. Subjects were grouped as Confirmed, Unconfirmed, and Unlikely TB, and classified as progressive primary disease (PPD, lung parenchymal lesion), and primary pulmonary complex (PPC, hilar lymphadenopathy) on chest X-ray. Of children with culture-positive TB 51/394 (12.9%), culture-negative TB 305 (77.4%), and unlikely TB 38 (9.6%), 9 (2.3%) were smear positive, while 95 (24.1%) were Xpert-MTB/RIF positive. Xpert-MTB/RIF detected 40/51 culture confirmed cases (sensitivity 78.4% and NPV 96.3%). Culture was positive in more children presenting as PPD (p < 0.04). In culture-negative TB group, Xpert positivity was seen in 31% of those with PPD and 11.9% in those with PPC (p < 0.001). Conclusion: Xpert-MTB/RIF improved diagnosis by 2-fold and increased detection of MDR-TB. Both liquid culture and Xpert-MTB/RIF gave higher yield in children with lung parenchymal lesions. Children with hilar lymphadenopathy without active lung parenchymal lesions had poor diagnostic yield even with sensitive nucleic acid amplification tests, due to paucibacillary/localized disease, suggesting possible utility of invasively collected samples in early diagnosis and treatment.

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