5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study.

BACKGROUND: Bacterial meningitis is an important cause of morbidity and mortality in developing countries, but the duration of treatment is not well established. We aimed to compare the efficacy of 5 and 10 days of parenteral ceftriaxone for the treatment of bacterial meningitis in children. METHODS: We did a multicountry, double-blind, placebo-controlled, randomised equivalence study of 5 versus 10 days of treatment with ceftriaxone in children aged 2 months to 12 years with purulent meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type B, or Neisseria meningitidis. Our study was done in ten paediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam. We randomly assigned children who were stable after 5 days of treatment, through site-balanced computer-generated allocation lists, to receive a further 5 days of ceftriaxone or placebo. Patients, their guardians, and staff were masked to study-group allocation. Our primary outcomes were bacteriological failure or relapse. Our analysis was per protocol. This study is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN38717320. FINDINGS: We included 1004 of 1027 children randomly assigned to study groups in our analyses; 496 received treatment with ceftriaxone for 5 days, and 508 for 10 days. In the 5-day treatment group, two children (one infected with HIV) had a relapse; there were no relapses in the 10-day treatment group and there were no bacteriological failures in either study group. Side-effects of antibiotic treatment were minor and similar in both groups. INTERPRETATION: In children beyond the neonatal age-group with purulent meningitis caused by S pneumoniae, H influenzae type b, or N meningitidis who are stable by day 5 of ceftriaxone treatment, the antibiotic can be safely discontinued. FUNDING: United States Agency for International Development.

Frequency of isolation of various subtypes and antimicrobial resistance of Shigella from urban slums of Karachi, Pakistan.

OBJECTIVES: Shigellosis remains a major public health problem in developing countries. Antimicrobial resistance has complicated the empirical treatment. Knowledge of serotypes is crucial in vaccine development, as cross-protection between various serotypes is limited. Therefore we conducted a prospective study to determine the frequency of isolation of Shigella serotypes and antimicrobial resistance. METHODS: Stool samples from 8155 individuals, collected through a surveillance study conducted in four slums of Karachi from January 2002 to March 2004, were cultured. RESULTS: Shigella was isolated in 394 (4.8%) of 8155 patients presenting with diarrhea. Two hundred and forty-two (62%) isolates were Shigella flexneri, 72 (18%) were Shigella sonnei, 43 (11%) were Shigella boydii, and 37 (9%) were Shigella dysenteriae. Thirteen S. flexneri serotypes were identified, of which the most frequent were 2a (38), 6 (37), and 1b (25), followed by 2b (23). Only 22 (5.6%) Shigella isolates were found to be pan-susceptible. Large proportions of isolates were resistant to co-trimoxazole (89% S. flexneri, 81% S. dysenteriae, 80% S. sonnei, and 56% S. boydii) and ampicillin (87% S. flexneri, 68% S. dysenteriae, 35% S. boydii, and 4% S. sonnei). CONCLUSIONS: Concurrent circulation of multiple strains with high resistance is worrying and mandates surveillance at the national level to facilitate the control of shigellosis.

Incidence of acute respiratory infections in children 2 months to 5 years of age in periurban communities in Karachi, Pakistan.

OBJECTIVE: To measure the incidence of acute respiratory infections and burden of respiratory pathogens in children aged two months to five years. METHODS: Four periurban communities in Karachi were selected for the study. The children, identified with fever and cough during community surveillance at regular intervals, were referred to especially established study clinics. These children were diagnosed to have "no pneumonia", "pneumonia" and "severe pneumonia" as per IMCI guidelines. To identify the causative organisms, children with pneumonia and severe pneumonia were investigated with oropharyngeal swabs and blood culture. RESULTS: Acute respiratory infection was seen in 5884 children during 1st February 2002 to 31st January 2003. Of these, 1097 children had pneumonia and severe pneumonia, with an incidence 440.3/1000 children per year for Acute Respiratory Infections and 82.1/1000 children per year for pneumonias. Haemophilus influenzae, Streptococcus pneumoniae and Klebsiella pneumoniae were isolated from 10.9%, 3.7% and 8.5% of oropharyngeal swabs respectively. Extrapolating from the results of this study, the total number of cases of pneumonias in children aged less than five years in Pakistan is estimated to be 213,116 per year due to H. influenzae, and 71,864 per year due to S. pneumoniae. CONCLUSION: Incidence of acute respiratory infections in children varies in different communities and is a common cause of morbidity.

Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047].

OBJECTIVE: To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. METHODS: A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. RESULTS: The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. CONCLUSION: This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future.

Enhanced disease surveillance through private health care sector cooperation in Karachi, Pakistan: experience from a vaccine trial.

INTRODUCTION: In research projects such as vaccine trials, accurate and complete surveillance of all outcomes of interest is critical. In less developed countries where the private sector is the major health-care provider, the private sector must be included in surveillance systems in order to capture all disease of interest. This, however, poses enormous challenges in practice. The process and outcome of recruiting private practice clinics for surveillance in a vaccine trial are described. METHODS: The project started in January 2002 in two urban squatter settlements of Karachi, Pakistan. At the suggestion of private practitioners, a phlebotomy team was formed to provide support for disease surveillance. Children who had a reported history of fever for more than three days were enrolled for a diagnosis. RESULTS: Between May 2003 and April 2004, 5540 children younger than 16 years with fever for three days or more were enrolled in the study. Of the children, 1312 (24%) were seen first by private practitioners; the remainder presented directly to study centres. In total, 5329 blood samples were obtained for microbiology. The annual incidence of Salmonella typhi diagnosed by blood culture was 407 (95% confidence interval (95% CI), 368-448) per 100 000/year and for Salmonella paratyphi A was 198 (95% CI, 171-227) per 100 000/year. Without the contribution of private practitioners, the rates would have been 240 per 100 000/year (95% CI, 211-271) for S. typhi and 114 (95% CI, 94-136) per 100 000/year for S. paratyphi A. CONCLUSION: The private sector plays a major health-care role in Pakistan. Our experience from a surveillance and burden estimation study in Pakistan indicates that this objective is possible to achieve but requires considerable effort and confidence building. Nonetheless, it is essential to include private health care providers when attempting to accurately estimate the burden of disease in such settings.

Helicobacter pylori colonization in infants in a peri-urban community in Karachi, Pakistan.

BACKGROUND: The prevalence and incidence of Helicobacter pylori in children in Pakistan is not known. OBJECTIVES: To measure the prevalence and age of acquisition of Helicobacter pylori infection/colonization in infants in a peri-urban community in Karachi, Pakistan. SETTING: Field based epidemiologic study in a peri-urban community in Karachi, Pakistan. METHODS: Infants aged 1 to 3 months were recruited from a birth cohort from the community. C-urea breath test (C-UBT) was performed on recruitment, and the test was repeated at 2, 3, 6, and 9 months of age. RESULTS: One hundred forty-eight infants were recruited and had C-UBT on 319 occasions over a period of 2 years. Two hundred thirty-one=(72%) tests were positive: 80% (49/61) infants at 1 month of age, 79% (33/42) at 2 month of age, 76% (92/121) at 3 month of age, 58% (37/64) at 6 months of age, and 67% (20/30) at 9 months of age. CONCLUSIONS: The study reveals an early colonization/infection of infants and a high prevalence of Helicobacter pylori in a peri-urban community in Karachi, Pakistan.