S. K. Kabra

Clinical outcomes in typhoid fever: adverse impact of infection with nalidixic acid-resistant Salmonella typhi

BackgroundWidespread use of fluoroquinolones has resulted in emergence of Salmonella typhi strains with decreased susceptibility to fluoroquinolones. These strains are identifiable by their nalidixic acid-resistance. We studied the impact of infection with nalidixic acid-resistant S. typhi (NARST) on clinical outcomes in patients with bacteriologically-confirmed typhoid fever.MethodsClinical and laboratory features, fever clearance time and complications were prospectively studied in patients with blood culture-proven typhoid fever, treated at a tertiary care hospital in north India, during the period from November 2001 to October 2003. Susceptibility to amoxycillin, co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone were tested by disc diffusion method. Minimum inhibitory concentrations (MIC) of ciprofloxacin and ceftriaxone were determined by E-test method.ResultsDuring a two-year period, 60 patients (age [mean ± SD]: 15 ± 9 years; males: 40 [67%]) were studied. All isolates were sensitive to ciprofloxacin and ceftriaxone by disc diffusion and MIC breakpoints. However, 11 patients had clinical failure of fluoroquinolone therapy. Infections with NARST isolates (47 [78%]) were significantly associated with longer duration of fever at presentation (median [IQR] 10 [7-15] vs. 4 [3-6] days; P = 0.000), higher frequency of hepatomegaly (57% vs. 15%; P = 0.021), higher levels of aspartate aminotransferase (121 [66–235] vs. 73 [44–119] IU/L; P = 0.033), and increased MIC of ciprofloxacin (0.37 ± 0.21 vs. 0.17 ± 0.14 μg/mL; P = 0.005), as compared to infections with nalidixic acid-susceptible isolates. All 11 patients with complications were infected with NARST isolates. Total duration of illness was significantly longer in patients who developed complications than in patients who did not (22 [14.8–32] vs. 12 [9.3–20.3] days; P = 0.011). Duration of prior antibiotic intake had a strong positive correlation with the duration of fever at presentation (r = 0.61; P = 0.000) as well as the total duration of illness (r = 0.53; P = 0.000).ConclusionTyphoid fever caused by NARST infection is associated with poor clinical outcomes, probably due to delay in initiating appropriate antibiotic therapy. Fluoroquinolone breakpoints for S. typhi need to be redefined and fluoroquinolones should no longer be used as first-line therapy, if the prevalence of NARST is high.

Chikungunya Infection in Children

Chikungunya fever is caused by Chikungunya virus (CHIK) and spread by Aedes aegypti and Aedes albopictus. The median incubation period is 2 to 4 days. Vertical transmission of disease from mother to child has also been documented. Clinical manifestations are very variable, from asymptomatic illness to severe debilitating disease. Children are among the group at maximum risk for severe manifestations of the disease and some clinical features in this group are distinct from those seen in adults. Common clinical features include: abrupt onset high grade fever, skin rashes, minor hemorrhagic manifestations, arthralgia/ arthritis, lymphadenopathy, conjunctival injection, swelling of eyelids and pharyngitis. Unusual clinical features include: neurological manifestations including seizures, altered level of consciousness, blindness due to retrobulbar neuritis and acute flaccid paralysis. Watery stools may be seen in infants. Treatment is symptomatic. Generally non- steroidal anti-inflammatory drugs are avoided. Paracetamol may be used for pain and fever. However, NSAIDS may be required for relief of severe arthralgia during convalescent phase.

Newer diagnostic modalities for tuberculosis

The gold standard for diagnosis of tuberculosis is demonstration of mycobacteria from various body fluids. This is often not possible in children due to pauci-bacillary nature of illness. Significant improvement in understanding of molecular biology ofMycobacterium tuberculosis has led to development of newer diagnostic techniques of tuberculosis. Polymerase chain reaction (PCR) is an emerging diagnostic tool for diagnosis of TB in children. However, its role in day-to-day clinical practice needs to be defined. A negative PCR never eliminates possibility of tuberculosis, and a positive result is not always confirmatory. The PCR may be useful in evaluating children with significant pulmonary disease when diagnosis is not readily established by other means, and in evaluating immunocompromised children (HIV infection) with pulmonary disease. In the absence of good diagnostic methods for tuberculosis, a lot of interest has been generated in serodiagnosis. ELISA has been used to detect antibodies to various purified or complex antigens ofM. tuberculosis in children. Despite a large number of studies published over the past several years, serology has found little place in the routine diagnosis of tuberculosis in children, even though it is rapid and does not require specimen from the site of disease. Sensitivity and specificity depend on the antigen used, gold standard for the diagnosis of tuberculosis and the type of tubercular infection. Though most of these tests have high specificity, their sensitivity is poor. In addition, these tests may be influenced by factors such as age, prior BCG vaccination and exposure to environmental mycobacteria. The serological tests, theoretically, may not be able to differentiate between infection and disease. At present, serodiagnosis does not appear to have any role in diagnosis of childhood pulmonary tuberculosis. A new test (QuantiFERON-TB or QFT) that measures the release of interferon-gamma in whole blood in response to stimulation by purified protein derivative is comparable with the tuberculin skin testing to detect latent tubercular infection, and is less affected by BCG vaccination. It can also discriminate responses due to nontuberculous mycobacteria, and avoids variability and subjectivity associated with placing and reading the tuberculin skin test. Polymerase chain reaction based test for identification of katG and rpoB mutation which are associated with isoniazid and rifampicin resistance may help in early identification of drug resistance in mycobacterium.

Disclosure of the HIV infection status in children.

ObjectiveTo determine the perception of caregivers about the disclosure of the diagnosis of HIV infection in children.MethodsCaregivers of fifty HIV-infected children were enrolled in the study after taking written informed consent. They were interviewed using a structured questionnaire. The questionnaire included information on the demographic details, questions about the disclosure status of HIV infection in children and perceptions about the disclosure of status to child.ResultsOnly 7 out of the 50 children (14%) were aware of their HIV status while 43/50 (86%) were unaware; as reported by their guardians/ parents. Only 6 percent children (3/50) were given factual information about the disease while 68% (34/50) were given no information. Majority of caregivers felt mid-teenage as the appropriate age for disclosing the HIV infection status and that the parents were the appropriate persons to reveal the infection status (21/50, 42%).ConclusionThere is need to develop and implement guidelines for disclosure of HIV infection status to HIV-infected children in resource limited settings.

Profile of Childhood Poisoning at a Tertiary Care Centre in North India

ObjectivesTo determine the profile and outcome (discharge from emergency room after observation, admission or death) of pediatric patients presenting with acute poisoning to a tertiary care centre in north India.MethodsWe retrospectively reviewed the last 2 year (July, 2004 to July, 2006) hospital records of pediatric emergency room to profile all cases of pediatric poisoning during that period and noted their outcome. All cases age ≤ 12 years with definite history of poisoning were included.Results111 patients presented to the pediatric emergency during the study period. Mean age of our patients was 3.12 ± 2.04 yrs (SD). Majority of our patients (63.9%) was in the 1–3 yr age group. Males outnumbered females by a factor of two; majority of our patients resided in urban areas. Kerosene (27.9%), drugs (19.8%) and insecticides (11.7%) were the agents most frequently implicated. Almost all (96.9%) ingestions were accidental in nature. Thirty six patients (32.4%) were asymptomatic after 6 hr of observation in the emergency ward; 75 patients (67.6%) developed symptoms related to toxic ingestion. The common serious symptoms included altered sensorium, respiratory distress, seizures, ataxia, hypotension, cyanosis and burns; three patients required intubation and mechanical ventilation. Almost one third of our patients underwent gastric lavage; no patient with kerosene poisoning or any other inappropriate indication underwent the same.ConclusionThe trends for pediatric poisoning noted at our centre are not very different from those observed in hospital-based studies conducted more than a decade ago, despite the rapid socioeconomic development in our country. In sharp contrast to developing countries, where majority of poisonings are due to common non-toxic household products, most of our patients require hospitalization because of severe symptoms related to dangerous nature of toxins ingested. Consultation with the poison cell results in improved patient management.

Vasopressin infusion in children with catecholamine‐resistant septic shock

Aim: To describe use of vasopressin infusion for catecholamine‐refractory septic shock in children. Methods: We report successful use of vasopressin infusion in three children with septic shock, in whom hypotension and poor perfusion persisted despite use of multiple infusions of vasopressors and inotropes. Results: All three had a rapid improvement in hypotension and perfusion after starting vasopressin infusion, allowing tapering of other infusions. Two children recovered completely.

Characterization of Pseudomonas aeruginosa isolated from chronically infected children with cystic fibrosis in India

BackgroundPseudomonas aeruginosa is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). With chronicity of infection, the organism resides as a biofilm, shows multi-drug resistance, diversifies its colony morphology and becomes auxotrophic. The patients have been found to be colonized with multiple genotypes. The present work was carried out to characterize P. aeruginosa isolated from children with cystic fibrosis using phenotypic and genotypic methods.ResultsWe studied 56 patients with CF attending the Pediatric Chest clinic at All India Institute of Medical Sciences, New Delhi, India during August 1998-August 2001. These patients were regularly followed up at the clinic. Out of 56 patients, 27 were culture positive for P. aeruginosa where 8 were chronically infected (Group1) and 19 were intermittently colonized with the organism (Group2). Patients under Group1 had significantly higher rates of hospitalization, death and colonization with different colony morphotypes (p < 0.05). The isolates from Group1 patients were the positive producers of extended spectrum beta lactamase. A total of 5 auxotrophs were recovered from 2 patients where one was chronically infected with P. aeruginosa and the other was a recently enrolled patient. The auxotrophs had the specific requirement for methionine and arginine. Molecular typing revealed 33 ERIC-PCR (E1-E33) and 5 PCR-ribotyping (P1-P5) patterns. By ERIC-PCR, 4 patients were colonized with 2–4 genotypes and the remaining 23 patients were colonized with the single genotype.ConclusionWith chronicity of infection, P. aeruginosa becomes multidrug resistant, diversifies its colony morphology, acquires mucoidity and shows auxotrophy for amino acids. The chronically infected patients can be colonized with multiple genotypes. Thus in a particular clinical set up, high index of suspicion should be there for diagnosis of CF patients so as to prevent the delay in diagnosis and management of CF patients.

Long-term daily high and low doses of azithromycin in children with cystic fibrosis: A randomized controlled trial

BACKGROUND Long-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration are not very well studied in children with CF. METHODS A randomized controlled trial was conducted to compare the effect of two doses of azithromycin (5mg/kg/day and 15mg/kg/day) on FEV(1) and pulmonary exacerbations in children with cystic fibrosis. Enrolled children were randomly allocated to receive daily azithromycin (5mg/kg/day or 15mg/kg/day) for 6months. Clinical assessment and FEV(1) measurement were performed monthly. RESULTS 56 children (28 in high dose group and 28 in low dose group) were enrolled. 47 (24 and 23 children in low and high dose groups) completed 12months of follow up. There was no difference in clinical scores, FEV(1), pulmonary exacerbation rates between two groups at baseline, 6months and at 12months. Per protocol analysis revealed that pulmonary exacerbation increased after discontinuing AZM and there was significantly more increase after 12months of enrolment in children getting high dose azithromycin. There was no improvement in FEV(1) in either group at the end of treatment period. Children tolerated daily low as well as high dose AZM well for 6months. There was no significant side effect of azithromycin. CONCLUSION In this randomized controlled trial, we did not find differences in the effect of 2 doses (5mg/kg/day or 15mg/kg/day) of AZM on change in percentage predicted FEV(1), clinical scores, Pseudomonas colonization rates, pulmonary exacerbations and need for antibiotics. There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6months after discontinuing azithromycin.

Suicide among children and adolescents in south Delhi (1991–2000)

Objective : Suicide among youth is of great concern and a subject requires thorough study to formulate prevention strategy. In this paper the incidence and trends of suicide among children and adolescent of South Delhi have been reported.Methods : A retrospective analysis was carried out on 222 cases of suicidal deaths pertaining to age group of 10–18 years, the postmortem examination on the body of which were conducted in Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, New Delhi during the period from 11st January 1991 to 311st December 2000. The particular of cases were analyzed according to age group, sex, method used and causes of committing suicide.Results : Out of 222 cases 123(55.4%) were of girls (Female : Male 1.24:1). Commonest age group involved was 15–18 years in both the sexes. Commonest method used for committing suicide was hanging (57% in girls, 49.5% in boys) followed by poisoning (37.4% in girls, 49.5% in boys).Conclusion : Methods used to commit suicide are widely available and are difficult to restrict. Therefore, suicide prevention strategy based on risk factors could be more effective rather than limiting the access to methods.

Exosome-enclosed microRNAs in exhaled breath hold potential for biomarker discovery in patients with pulmonary diseases.

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