Effectiveness of 10-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in Pakistan.

OBJECTIVE: To assess the effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) against invasive pneumococcal disease (IPD) due to vaccine serotypes of Streptococcus pneumoniae post introduction of the vaccine into the routine immunization program in Pakistan. METHODS: A matched case-control study was conducted at 16 hospitals in Sindh Province, Pakistan. Children aged <5years (eligible to receive PCV10) who presented with radiographically confirmed pneumonia and/or meningitis were enrolled as cases. PCR for the lytA gene was conducted on blood (for radiographic pneumonia) and cerebrospinal fluid (for meningitis) samples to detect S. pneumoniae. The proportion of IPD due to vaccine serotypes (including vaccine-related serogroups) was determined through serial multiplex PCR. For each case, at least five controls were enrolled from children hospitalized at the same institution, matched for age, district, and season. RESULTS: Of 92 IPD patients enrolled during July 2013 to March 2017, 24 (26.0%) had disease caused by vaccine serotypes. Most case (87.5% of 24) and control (66.4% of 134) children had not received any PCV10 doses. The estimated effectiveness of PCV10 against vaccine-type IPD was 72.7% (95% confidence interval (CI) -7.2% to 92.6%) with at least one dose, 78.8% (95% CI -11.9% to 96.0%) for at least two doses, and 81.9% (95% CI -55.7% to 97.9%) for all three doses of vaccine. CONCLUSIONS: The vaccine effectiveness point estimates for PCV10 were high and increased with increasing number of doses. However, vaccine effectiveness estimates did not reach statistical significance, possibly due to low power. The findings indicate the likely impact of vaccine in reducing the burden of vaccine-type IPD if vaccine uptake can be improved.

Profile and outcomes of critically ill children in a lower middle-income country.

OBJECTIVE: To determine the clinical profile and outcome of critically ill children presenting to a paediatric ED in a lower middle-income country. METHODS: We performed a retrospective analysis of children (<14 years) presenting to the ED of the National Institute of Child Health, Karachi, between January and December 2014 who were assigned to acuity 1 (requiring immediate life-saving interventions) according to the Emergency Severity Index. Data included demographic variables, presenting complaints, interventions and outcomes in the ED. RESULTS: There were 172 162 visits during the year. Of these, 13 551 (8%) were level 1. 64% of level 1 patients were transported to the ED without ambulance service. Neonates (0-28 days) constituted 48% of level 1 children; their most frequent presenting complaints were respiratory symptoms, followed by fever and reluctance to feed. Above the neonatal age group, the most common presenting complaints were gastrointestinal symptoms (with signs of hypoperfusion), followed by seizures, reluctance to feed and respiratory symptoms. 64% of children of >28 days presenting were malnourished. Interventions included cardiopulmonary resuscitation, application of bubble continuous positive airway pressure and endotracheal intubation. Overall mortality was 13%; 63% of all deaths were in the neonatal age group. CONCLUSION: Children with the highest triage acuity represent 8% of all visits to a paediatric ED. In this group, neonates account for nearly half of all the children, and more than half of all the deaths among critically ill children came in ED. A large proportion of high-acuity children are malnourished.

Overcrowding and possible solutions for a busy paediatric emergency department.

OBJECTIVE: To quantify the extent of emergency department overcrowding in a tertiary care hospital and to identify possible solutions. METHODS: This retrospective study was conducted at the National Institute of Child Health, Karachi, and comprised data of all patients presenting to the emergency department from November 2014 to January 2015. Data was collected through the health management information system which generates daily report of patients. Patients who stayed at the emergency department for 4 or more hours were included. RESULTS: Of the 6,505 patients, 2,757(42.38%) were discharged straightaway while 2,555(39.27%) were admitted to different wards and subspecialties. Besides, 934(14.35%) patients left the department against medical advice, 147(2.25%) expired, 89(1.36%) were referred to other hospitals, 20(0.30%) were dead on arrival and 3(0.04%) left without being seen by a physician. Of those who were admitted, 1,049(41%) patients stayed for more than 10 hours before getting the main hospital bed. Mostly, the delays observed were due to delay in getting lab reports, already preoccupied ventilators and incubators in paediatric and neonatal intensive care units, not using checklist for proper re-assessment of patients and early discharge, overburdened by patients coming in just for nebulisation and intravenous or intramuscular medications, the admitting residents detain the unstable patient longer in emergency department before admission to wards. CONCLUSIONS: The emergency department of the hospital faced significant overcrowding which overwhelmed efficient standard care.

Pattern of relapse in paediatric acute lymphoblastic leukaemia in a tertiary care unit.

OBJECTIVE: To determine the frequency, site and time to relapse from diagnosis, and to see the relationship of relapse with important prognostic factors. METHODS: The prospective descriptive observational study was conducted at the National Institute of Child Health, Karachi, June 2005 to May 2007, and comprised newly-diagnosed cases of acute lymphoblastic leukaemia. Bone marrow aspiration was done on reappearance of blast cells in peripheral smear and cerebrospinal fluid. Detailed report was done each time when intra-thecal chemotherapy was given or there were signs and symptoms suggestive of central nervous system relapse. SPSS 12 was used for data analysis. RESULTS: Of the 60 patients enrolled, 4(6.6%) expired and 1(1.7%) was lost to follow-up. Of the 55(91.6%) who comprised the study sample, 35(58%) were males and 25(42%) females. Mean age of relapse was 6.8±3.27 years. Mean time to relapse from diagnosis was 1.3±0.54 years; 12(20%) patients suffered relapse, and of them 5(14%) were boys. Central nervous system relapse in 8(67%) patients was the most common site, with 3(25%) bone-marrow relapses. Out of 12 patient with relapses, 9(75%) had white blood cell count less than 50,000/cm. CONCLUSIONS: Relapse in acute lymphoblastic leukaemia was common, although treatment modalities are improving day by day.

Rota virus Diarrhea in Hospitalized Children.

OBJECTIVE: To determine the frequency and clinical features of Rota virus diarrhea in children presenting in a tertiary care hospital. STUDY DESIGN: A cross-sectional, observational study. PLACE AND DURATION OF STUDY: National Institute of Child Health, Karachi, from January to June 2007. METHODOLOGY: A total of three hundred children of either gender aged 1 month to 5 years, who presented with diarrhea of < 7 days as a primary illness were enrolled. Children with bloody diarrhea or nosocomial gastroenteritis acquired during hospitalization for other disease were not included. Detection of Rota virus in stool was done by enzyme linked immunoassay. RESULTS: Out of 300 children, 188 (63%) tested positive and 112 (37%) tested negative for Rota virus. Positive Rota virus cases in 7 - 12 months of age was (n = 34, 18.08%). Overall, 151 (80.3%) children with Rota virus were less than 3 years old. 182 (60.7%) had fever, 118 (39.3%) had vomiting and 156 (82.9%) children had both fever and vomiting. CONCLUSION: This study shows that Rota virus is a common organism causing diarrhea in children less than 3 years of age. There is a need to incorporate Rota virus vaccine in the national EPI program to decrease the disease burden as highlighted in this study.

Study of PKRBD in HCV genotype 3a infected patients in response to interferon therapy in Pakistani population.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated. RESULTS: In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones. CONCLUSIONS: The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.

Effectiveness of Haemophilus influenzae type b conjugate vaccine on radiologically-confirmed pneumonia in young children in Pakistan.

OBJECTIVE: The effectiveness of Haemophilus influenzae type b (Hib) vaccine in preventing severe pneumonia in Asian children has been questioned, and many large Asian countries yet to introduce Hib conjugate vaccine in immunization programs. The primary objective of this study was to assess Hib conjugate vaccine effectiveness (VE) on radiologically-confirmed pneumonia in children born after introduction of Hib conjugate vaccine in Pakistan. STUDY DESIGN: A matched case-control study enrolled cases of radiologically-confirmed pneumonia in several hospitals serving low-income populations during 2009-2011. Cases were matched by age and season with 3 hospital and 5 neighborhood controls. Pneumonia was diagnosed using standardized World Health Organization criteria for chest radiograph interpretation. Matched OR were estimated for VE. RESULTS: A total of 1027 children with radiologically-confirmed pneumonia were enrolled; 975 cases, 2925 hospital controls, and 4875 neighborhood controls were analyzed. The coverage for 3 doses of diphtheria-tetanus-pertussis-hepatitis B-Hib conjugate vaccine was 13.7%, 18%, and 22.7% in cases, hospital controls and neighborhood controls, respectively. Estimated Hib VE for radiologically-confirmed pneumonia was 62% with 3 doses of vaccine using hospital controls and 70% using neighborhood controls. CONCLUSIONS: Hib conjugate vaccine prevented a significant fraction of radiologically-confirmed pneumonia in children in Pakistan. Maximizing impact on child survival needs improved immunization coverage.

Frequency of nutritional rickets in children admitted with severe pneumonia.

OBJECTIVE: To determine the frequency of nutritional rickets in children hospitalized with severe pneumonia. METHOD: This study was carried out at the department of paediatric medicine at National Institute of Child Health Karachi. It is a case series done over a period of six months from 15th November 2008 to 15th may 2009. Patients admitted (n=137) with severe pneumonia were included in the study and were investigated for presence of rickets with serum calcium, phosphorus and alkaline phosphatase. Those having low to normal calcium low phosphorus and raised alkaline phosphatase were labeled as having rickets. All data collected were entered on Performa. Children with familial, vitamin D dependent/resistant rickets, secondary rickets, and cerebral palsy or on anti convulsant therapy were excluded from this study. RESULTS: Out of 137 patients, with severe pneumonia, 83 were male and 54 female. Frequency of nutritional rickets in children with severe pneumonia was observed in 101(74%) cases. Rickets was more common in 2 to 12 months of age, i.e., 79.8% (67/84) and in those children who were breast fed (85.3% vs. 40%). Frequency was higher in those children who were not exposed to sunlight. CONCLUSION: Pneumonia is a very common presentation of rickets. This study suggests that rickets may be more common in children who are breast fed and those who have less exposure to sunlight.

1-(5a,5b,8,8,11a,13b-Hexamethyl-eicosa-hydro-1H-cyclo-penta-[a]chrysen-3-yl)-1-ethanone.

The title compound, C(29)H(48)O, is a triterpenoid isolated from Adiantum incisum forssk. In the crystal structure, the asymmetric unit contains two independent mol-ecules which are not significantly different. Each mol-ecule contains four six-membered rings, all adopting chair conformations, and a five-membered ring in an envelope conformation. In the mol-ecular structure, non-classical intra-molecular C-H⋯O hydrogen bonds are observed.