Management of Dengue: An Updated Review

Dengue is an important public health problem with a wide clinical spectrum. The World Health Organization classifes dengue into probable dengue, dengue with warning signs, and severe dengue. Severe dengue, characterized by plasma leakage, severe bleeding, or organ impairment, entails signifcant morbidity and mortality if not treated timely. There are no defnitive curative medications for dengue; management is supportive. Judicious fuid resuscitation during the critical phase of dengue is the cornerstone of management. Crystalloids are the initial fuid of choice. Prophylactic platelet transfusion is not recommended. Organ involvement in severe dengue should be carefully looked for and managed. Secondary hemophagocytic lymphohistiocytosis is a potentially fatal complication of dengue that needs to be recognized, as specifc management with steroids or intravenous immunoglobulin may improve outcomes. Several compounds with anti-dengue potential are being studied; no anti-dengue drug is available so far.

Aetiological agents for pulmonary exacerbations in children with cystic fibrosis: An observational study from a tertiary care centre in northern India

Background & objectives: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF). The infection occurs with a unique spectrum of bacterial pathogens that are usually acquired in an age-dependent fashion. The objective of this study was to find out the aetiological agents in respiratory specimens from children with CF during pulmonary exacerbation and relate with demographic variables. Methods: In this observational study, airway secretions from children (n=104) with CF presenting with pulmonary exacerbations were collected and tested for bacteria, fungi, mycobacteria and viral pathogens using appropriate laboratory techniques. The frequencies of isolation of various organisms were calculated and associated with various demographic profiles. Results: Bacteria were isolated in 37 (35.5%) and viral RNA in 27 (29.3%) children. Pseudomonas was the most common bacteria grown in 31 (29.8%) followed by Burkholderia cepacia complex (Bcc) in three (2.8%) patients. Among viruses, Rhinovirus was the most common, identified in 16 (17.4%) samples followed by coronavirus in four (4.3%). Fungi and mycobacteria were isolated from 23 (22.1%) and four (3.8%) children, respectively. Aspergillus flavus was the most common fungus isolated in 13 (12.5%) children. Interpretation & conclusions: Pseudomonas was the most common organism isolated during exacerbation. Non-tuberculous mycobacteria were not isolated, whereas infection with Bcc and Mycobacterium tuberculosis was observed, which could probably have a role in CF morbidity. Polymicrobial infections were associated with severe exacerbations.

Current antibiotic use in the treatment of enteric fever in children

Background & objectives: Antimicrobial resistance is a major challenge in the treatment of typhoid fever with limited choices left to empirically treat these patients. The present study was undertaken to determine the current practices of antibiotic use in children attending a tertiary care hospital in north India. Methods: This was a descriptive observational study in children suffering from enteric fever as per the case definition including clinical and laboratory parameters. The antibiotic audit in hospitalized children was measured as days of therapy per 1000 patient days and in outpatient department (OPD) as antibiotic prescription on the treatment card. Results: A total of 128 children with enteric fever were included in the study, of whom, 30 were hospitalized and 98 were treated from OPD. The mean duration of fever was 9.5 days at the time of presentation. Of these, 45 per cent were culture positive with Salmonella Typhi being aetiological agent in 68 per cent followed by S. Paratyphi A in 32 per cent. During hospitalization, the average length of stay was 10 days with mean duration of defervescence 6.4 days. Based on antimicrobial susceptibility ceftriaxone was given to 28 patients with mean duration of treatment being six days. An additional antibiotic was needed in six patients due to clinical non-response. In OPD, 79 patients were prescribed cefixime and additional antibiotic was needed in five during follow up visit. Interpretation & conclusions: Based on our findings, ceftriaxone and cefixime seemed to be the first line of antibiotic treatment for typhoid fever. Despite susceptibility, clinical non-response was seen in around 10 per cent of the patients who needed combinations of antibiotics.

Bartonella henselae infection in diverse clinical conditions in a tertiary care hospital in north India

Background & objectives: Bartonella henselae causes infections which closely resemble febrile illness and chronic diseases such as tuberculosis and haematological malignancies. There are not many studies on Bartonella infections from India. The present study was undertaken to diagnose B. henselae infection in diverse clinical conditions in a tertiary care hospital in north India. Methods: A total of 145 patients including those with fever and lymphadenopathy, infective endocarditis and neuroretinitis were enrolled in the study. Whole blood, serum and lymph node aspirate and valvular vegetations if available, were obtained. Samples were plated on chocolate agar and brain-heart infusion agar containing five per cent fresh rabbit blood and were incubated at 35°C for at least four weeks in five per cent CO2with high humidity. Immunofluorescent antibody assay (IFA) was done for the detection of IgM antibodies in the serum using a commercial kit. Whole blood was used to perform polymerase chain reaction (PCR) for the citrate synthase gene (gltA). Results: IFA was positive in 11 of 140 (7.85%) patients and PCR was positive in 3 of 140 (2.14%) patients. Culture was negative in all the cases. A higher incidence of Bartonella infection was seen in patients with fever and lymphadenopathy (n=30), seven of whom were children. In ophthalmological conditions, four cases were IFA positive. Interpretation & conclusions: The present study shows that the threat of Bartonella infection is a reality in India. It is also an important treatable cause of fever and lymphadenopathy in children. Serology and PCR are useful tests for its diagnosis. Clinicians should consider Bartonella infection in the differential diagnosis of febrile illnesses and chronic diseases.

Role of Glycemic control and Lipid profile in management of Diabetic complications

Background: Diabetes mellitus is one of the most common endocrine disorders affecting about 6% of the world’s population. Diabetes mellitus is the leading cause of end stage renal disease (ESRD), a major cause of non-traumatic amputations, responsible for preventable blindness and a leading cause of cardiovascular mortality. Objective: The objective of the study was to assess the glycemic control by estimation of glycated hemoglobin (HbA1c), and lipid profile in patients of Diabetes mellitus without complications and in Diabetes mellitus with complications like neuropathy, retinopathy and nephropathy and compare with controls. Material and methods: The present study comprised of 100 clinically diagnosed and confirmed cases of type 2 Diabetes mellitus attending and admitted in RNT Medical College and Hospital, Udaipur, Rajasthan, India. Glycosylated hemoglobin (HbA1c), Total Cholesterol, Triglycerides, HDL-Cholesterol, LDLCholesterol and VLDL-Cholesterol were calculated in all groups using Friedewald’s formula. Result: Our study showed that HbA1c levels were significantly higher (p<0.01) in all groups of patients as compared to controls. The increase in Serum Cholesterol, Triglyceride, LDL-Cholesterol, VLDL-Cholesterol and decrease in HDL-Cholesterol levels were statistically significant (p<0.01) in Diabetic retinopathy and Diabetic nephropathy group as compared to controls, whereas in Diabetic neuropathy group and in Diabetes mellitus without complication, the increase in Serum Cholesterol, Triglyceride, LDL-Cholesterol, VLDL-Cholesterol and decrease in HDL-Cholesterol levels was not statistically significant as compared to controls. Conclusion: Our study revealed that poor glycemic control and dyslipidemia are associated with Diabetic complications like neuropathy, retinopathy and nephropathy. Estimation of glycosylated hemoglobin and lipid profile helps in predicting the development of microvascular complications.

Correlation of Thyroid Hormones with FSH, LH and Prolactin in Infertility in the Reproductive Age Group Women

Introduction: Measurement of prolactin and thyroid hormones, especially thyroid stimulating hormone (TSH), has been considered an important component of infertility work up in women. Thyroid dysfunctions interfere with numerous aspects of reproduction and pregnancy. Aim: To correlate thyroid hormones level with FSH, LH and prolactin in infertility in the reproductive age group women. Materials and methods: This study includes 100 infertile women who attended infertility clinic of our institute along with 50 fertile women as a control group between age group of 20 to 40 years. Out of 100 infertile women, 70 were of primary infertility and 30 of secondary infertility. Thyroid hormones and infertility hormones level is measured from all participants by chemiluminance immunoassay. Results: Prolactin and TSH were positively correlated with each other. They were also negatively correlated with LH, FSH and T3 in infertile groups. Therefore we can say that hyperprolactinemia and hypothyroidism plays key role in etiopathogenesis of infertility. Conclusion: There was a higher crude prevalence of hypothyroidism and hyperprolactinemia in the infertile women as compared to the fertile ones in the control group.

Mortality and Other Outcomes in Relation to First Hour Fluid Resuscitation Rate: A Systematic Review.

Objective: To determine the effect of different regimen of first hour fluid administration rates on mortality and severe consequences of impaired circulation in 2 to 60 months old children with impaired circulation. Design: Systematic review of randomized controlled trials. Data sources: Various databases including PubMed, Cochrane Library and EMBASE were searched. Results: We found only two relevant trials; one was excluded as there was no comparator arm. Only one study (The FEAST Trial) compared boluses with maintenance fluid alone in children with severe febrile illness and one or more signs of impaired perfusion. The 48-hour mortality was more in the bolus group (RR 1.45, 95% CI 1.13,1.86). The quality of evidence is rated as ‘moderate’. For the children who met the WHO criteria for shock (severely impaired circulation) (n=65 children), those receiving boluses had higher mortality (RR 2.40, 95% CI 0.84, 6.88); the quality of evidence was rated as ‘very low’. Conclusions: A single large randomized controlled trial conducted in low-resource settings indicates that administration of fluid bolus is associated with higher mortality in comparison to the maintenance fluids alone in children with severe febrile illness and one or more signs of impaired perfusion. The findings are not generalizable to contexts with different severity of and different causes of shock and in centers with better facilities. There is urgent need for research in different settings to determine the optimal rate of fluid resuscitation in the first hour in children presenting with impaired circulation, particularly with severely impaired circulation.

Prevalence and Risk Factors for Allergic Bronchopulmonary Aspergillosis in Indian Children with Cystic Fibrosis.

Objectives: Allergic bronchopulmonary aspergillosis (ABPA) is a common complication in patients with cystic fibrosis. This crosssectional study was planned to determine the prevalence and risk factors for ABPA in Indian children with cystic fibrosis. Methods: Clinical evaluation, spirometry, chest radiograph, sputum, total IgE, specific IgE for Aspergillus fumigatus, IgG precipitins and skin prick tests were done in 33 CF patients. Results: Prevalence of allergic bronchopulmonary aspergillosis was 18.2% (95% CI 6.9% - 35.4%): allergic bronchopulmonary aspergillosis was higher in patients with low cystic fibrosis score, age >12 years, atopy, and eosinophilia. Conclusion: Prevalence of ABPA is higher in Indian children with cystic fibrosis.

Multiple locus sequence typing of Salmonella Typhi, isolated in north India - a preliminary study.

Background & objectives: In India enteric fever is a major public health problem and Salmonella Typhi is the most common aetiologic agent. Any control strategy for such infections depends to a large extent on the understanding of the disease and relatedness of strains across the world. Multi locus sequence typing (MLST) is one such method of genotyping of bacteria based upon housekeeping genes of known function and chromosome position. MLST data of pathogens are important to determine the molecular evolution by a stable and reproducible method. This study was undertaken to determine the sequence types of representatives S. Typhi isolates obtained from enteric fever patients in a tertiary care centre in north India, over a period of 20 years (1990-2010). Methods: A total of 30 representative isolates of S. Typhi identified by biochemical and serological tests were subjected to multi locus sequence typing (MLST). Seven housekeeping genes of known function and chromosome position were used for the typing by MLST. Sequencing was carried out by using an automated DNA sequencer and results were analyzed to generate phylogenetic tree. Results: MLST pattern grouped S. Typhi into two sequence types- ST1 and ST2. ST1 was predominantly present followed by ST2. Interpretation & conclusions: By MLST the presence of both sequence types, ST1 and ST2, was found in S. Typhi isolates in our region. Predominately ST1 was present followed by ST2. These preliminary results corroborate the global distribution of both sequence types of S. Typhi and also emphasize for the continuous screening of S. Typhi.

Association between reproductive factors and breast cancer in an urban set up at central India: A case-control study.

Background: Epigenetic changes, geography and environmental factors do surpass the genetic factors in the development of breast cancer. This study investigates the association of reproductive factors with the breast cancer in this context. Objective: To detect the association of reproductive risk factors with breast cancer in an urban set up at central India. Study Design: Matched paired community-based case-control study. Materials and Methods: The study was conducted for a period of a year from October 2008 to August 2009 in Bhopal (MP). Demographic data and reproductive risk factor related information were collected using structured questionnaire. Data analysis was done by Epi-info and SPSS 16. Results: History of using oral contraceptive pills (OR = 3.02, 95% CI: 1.28-7.11), history of not having breastfeeding (OR = 3.62, 95% CI: 1.29-10.16) and family history of breast cancer (OR = 3.98, 95%CI: 1.06-14.826) were associated significantly with the occurrence of breast cancer in multivariate analysis. Conclusions: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.

Intermittent or Daily Short Course Chemotherapy for Tuberculosis in Children: Meta-analysis of Randomized Controlled Trials.

Objective: To compare the effectiveness of intermittent with daily chemotherapy (both containing rifampicin) in childhood tuberculosis (age ≤16yrs) in achieving cure/ significant improvement. Design: Systematic Review and Meta-analysis. Methods: MEDLINE and the Cochrane Library were searched for randomized trials of antitubercular regimens containing rifampicin, in children 16 yrs or less with tuberculosis. Two reviewers independently assessed trial eligibility and quality. Data from full articles of selected studies were independently extracted by two authors and analyzed. The odds ratio was obtained for the pooled data in two groups (intermittent and daily therapy). Outcome variables: Cure/significant improvement, relapse rate and adverse events. Results: Four randomized controlled trials comparing twice weekly and daily therapy including 466 children (pulmonary 439; extrapulmonary 27) met the inclusion criteria. Baseline data were comparable. On quality assessment, 3 studies scored 2 and one study scored 3 out of 5 points. Per protocol analysis showed that children receiving intermittent regimen were less likely to be cured than those receiving daily therapy (OR 0.27; 95% CI: 0.14, 0.51). The results of intention to treat analysis suggest similar trend towards lower cure rates with twice weekly regimen (OR 0.66; 95% CI: 0.23-1.84). Conclusion: Twice weekly intermittent short course therapy is less likely to cure tuberculosis in children as compared to daily therapy. There is a need for better quality randomized controlled trials for assessing efficacy of alternate schedule for intermittent therapy for childhood tuberculosis.

Anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis.

Objective. Prevalence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in Indian patients with juvenile idiopathic arthritis (JIA). Methods. Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 78 patients with JIA which included all 3 major subtypes of the disease: pauciarticular, polyarticular afld systemic onset. Values above 5 relative units were taken as positive. Associations between antiCCP antibodies and clinical and laboratory and radiological parameters were determined. Results. Anti-CCP antibodies were positive in only 2 of 34 (5.9%) patients with pauciarticular JIA and 3 of 17 (17.6%) of systemic,.pnset JIA, whereas it was positive in 13 of 27 (48.1%) of polyarticular JIA patients (p < 0.001). Furthermore, it was seen that among patients with polyarticular JIA, RF-lgM positive patients had higher rate of anti-CCP antibody positivity with 7 of 8 (87.5%) patients having positive anti-CCP antibody (p<0.001). Similarly, patients with erosions (11/19; p<0.001) and deformities (5/-10; p<0.001) were found to have significant association with anti-CCP antibody positivity. Conclusion. Anti-CCP antibodies could be detected more frequently in the sera of JIA patients with severe manifestations like- erosions and deformity. It was also more significantly associated with seropositive polyarticular JIA than other types. It can be presumed from these results that anti-CCP antibodies can be used as a marker to predict severe course of JIA at the onset to guide optimal aggressive therapy.

Salmeterol vs. formoterol: a comparison of rapid bronchodilator effect in a randomized controlled trial.

We conducted this double blind randomized controlled trial to compare the rapid bronchodilator effect of salmeterol and formoterol in 60 children with stable asthma. Participants were randomized to receive either salmeterol (50 microg) (n=31) or formoterol (24 microg) (n=29) by metered dose inhaler and spacer. Spirometry was performed at baseline, at 30 minutes, and at 60 minutes. Bronchodilatation was assessed by changes in FEV(1) at 30 and 60 minutes. Baseline parameters were comparable in the two groups. There was no significant difference in the FEV(1) at 30 and 60 minutes between two groups. We conclude that salmeterol and formoterol both cause bronchodilator response at end of 60 minutes and are not different with regards to their rapid bronchodilator response.

Management of unresponsive asthma.

Difficult asthma is defined as asthma that is not controlled despite treatment with> 800 micro g budesonide or equivalent per day. Poor control is defined as the need for bronchodilators more than three times a week, school absence of more than five days a term, or one episode or more of wheezing each month. Common causes of poor response to treatment include; wrong diagnosis, inappropriate medications or improper inhalation technique, poor adherence to medications and co-morbidity. Steroid resistant asthma is uncommon and estimated to be 1 in 1000-10000 asthmatic patients. If there is no functional improvement to prednisolone 2 mg/kg/day for 2 weeks with adherence checked by measuring serum prednisolone and cortisol levels, a fibreoptic bronchoscopic examination with bronchoalveolar lavage and large airway biopsy should be considered. Eosinophilic inflammation identified on the biopsy in a child who is unresponsive to prednisolone may benefit from alternative anti-inflammatory treatments such as cyclosporin. Neutrophilic infiltration in biopsy may benefit with macrolide antibiotics, 5-lipogenase inhibitors or theophyllines.

Can throat swab after physiotherapy replace sputum for identification of microbial pathogens in children with cystic fibrosis?

OBJECTIVE: To compare cultures throat swab after physiotherapy with results of sputum culture in identification of lower airway pathogens in children with cystic fibrosis. METHODS: 387 samples of sputum cough swabs, throat swab and throat swab after physiotherapy were collected from 48 patients of cystic fibrosis and cultured for aerobic bacteria. The results of cultures of cough swabs, throat swab and throat swab after physiotherapy were compared with results of sputum culture. RESULTS: There was good concordance between culture results of sputum and other methods. Over all concordance was 70%, 81% and 92% with cough swab, throat swab and throat swab after physiotherapy. Sensitivity for isolation of Pseudomonas aeruginosa by throat swab, cough swab and throat swab after physiotherapy was 40%, 42% and 82% respectively. Specificity for isolation of Pseudomonas by throat swab, cough swab and throat swab after physiotherapy was 99%, 100% and 99% respectively. Sensitivity for isolation of Staphylococcus aureus by throat swab, cough swab and throat swab after physiotherapy was 57%, 50% and 100% respectively. Specificity for isolation of Staphylococcus by throat swab, cough swab and throat swab after physiotherapy was 99% for all these methods. CONCLUSION: It is concluded that throat swab after physiotherapy in a child with CF can be used reliably for identification of lower airway pathogens.

An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis.

An indigenously developed method for sweat collection and titration method for estimation of chloride was validated. The mean difference in estimated chloride value from the known strength of saline in 50 samples was -1.04 +/- 4.13 mEq/L (95% CI: -0.07 to 2.28). The mean difference in the estimated chloride values between two observers when the test was performed on known strengths of saline solution was -2.5 +/- 4.24 mEq/L (95% CI: -3.67 to 1.33). The inter observer variability between two observers when the test was performed on sweat samples obtained from 50 individuals was -1.12 +/- 4.34 mEq/L (95% CI: -2.23 to 0.8 ). Sweat weight of more than 100 mg could be collected in first attempt in 602 of 757 (80%) patient with an average sweat weight of 230 mg. This inexpensive method of sweat collection and chloride estimation has acceptable accuracy and repeatability and can be used in resource poor setting for making a diagnosis of cystic fibrosis.

Risk factors for severe acute lower respiratory tract infection in under-five children.

BACKGROUND: Acute lower respiratory infection (ALRTI) is the leading cause of death in children below five years of age. Identification of modifiable risk factors of severe ALRTI may help in reducing the burden of disease. METHODS: A hospital based case control study was undertaken to determine risk factors associated with severe lower respiratory tract infection (LRTI) in under-five children. A case definition of severe ALRTI as given by World Health Organization (WHO) was used for cases. Healthy children attending Pediatrics out patient department for immunization during study period were enrolled as controls. Details of potential risk factors in cases and controls were recorded in pre-designed proforma. RESULTS: 512 children including 201 cases and 311 controls were enrolled in the study. On stepwise logistic regression analysis it was found that lack of breastfeeding (OR: 1.64; 95 percent CI: 1.23-2.17); upper respiratory infection in mother (OR: 6.53; 95 percent CI: 2.73-15.63); upper respiratory infection in siblings (OR: 24; 95 percent CI: 7.8-74.4); severe malnutrition (OR: 1.85; 95 percent CI: 1.14-3.0); cooking fuel other than liquid petroleum gas (OR: 2.5; 95 percent CI: 1.51-4.16); inappropriate immunization for age (OR: 2.85; 95 percent CI 1.59-5.0) and history of LRTI in the family (OR 5.15, 95 percent CI 3.0-8.8) were the significant contributors of ALRTI in children under five years. Sex of the child, age of the parents, education of the parents, number of children at home, anemia, inadequate caloric intake, type of housing were not documented to be significant risk factors of ALRTI. CONCLUSION: Lack of breast-feeding, upper respiratory infection in mother, upper respiratory infection in siblings, severe malnutrition, cooking fuel other than liquid petroleum gas, inappropriate immunization for age and history of LRTI in the family were the significant risk factors associated with ALRTI