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E K Mulholland

Publications and source records attributed to E K Mulholland.

At least 19 recordsLinked to original sources
PubMed2006

As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries.

Human blood agar (HuBA) is widely used in developing countries for the isolation of bacteria from clinical specimens. This study compared citrated sheep blood agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep blood agar (DSBA) for the isolation and antibiotic susceptibility testing of reference and clinical strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Reference and clinical strains of all organisms were diluted in brain heart infusion and a clinical specimen of cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology, and colony size were recorded. Susceptibility testing for S. pneumoniae and S. pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar plates. For all organisms, the colony numbers were similar on all agars. Substantially smaller colony sizes and absent or minimal hemolysis were noted on HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were similar for the two sheep blood agars; however, larger zone sizes were displayed on HuBA, and quality control for the reference strain failed on HuBA. For S. pyogenes, larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an acceptable alternative for the isolation of these organisms. The characteristic morphology is not evident, and hemolysis is poor on HuBA; and so HuBA is not recommended for use for the isolation or the susceptibility testing of any of these organisms. CSB MHA may be suitable for use for the susceptibility testing of S. pneumoniae.

Agar↗
PubMed2006

Pneumococcal nasopharyngeal carriage and patterns of penicillin resistance in young children in Fiji.

BACKGROUND: Little is known about nasopharyngeal carriage and the patterns of antibiotic resistance of pneumococci in Pacific nations. We set out to document pneumococcal nasopharyngeal carriage and associated risk factors, antimicrobial resistance and serotypes in healthy children in Fiji. METHODS: A cross-sectional survey of healthy children aged 3-13 months was conducted. Nasopharyngeal (NP) swabs were collected from each child and processed according to standard methods. Antimicrobial resistance was determined by disk diffusion and confirmed by E-testing. Serotyping was performed by the Quellung reaction. RESULTS: Of 440 consecutive NP swabs taken, 195 were S. pneumoniae-positive (carriage rate 44.3%). Higher rates were found in the indigenous Fijian population. Penicillin non-susceptibility was found in 11.4% of isolates, with one isolate demonstrating high-level resistance. Cotrimoxazole resistance was common (20.3%) and no isolates were chloramphenicol-resistant. Multi-drug resistance was uncommon. The commonest serotypes were 6A (13.2%), 23F (8.3%), 19F (7.4%) and 6B (6.2%). Thirty per cent were included in the 7-valent pneumococcal conjugate vaccine (PCV), 54.3% if cross-reacting strains were included. Being indigenous Fijian or having symptoms of acute respiratory infection were independent risk factors for carriage. CONCLUSIONS: Pneumococcal NP carriage is common in Fijian children. Penicillin resistance has been documented for the first time in Fiji and, as a result, first-line treatment for meningitis has been altered. Being indigenous Fijian is a risk factor for disease, although the reasons for this are unclear. A low proportion of carriage serotypes are covered by the existing 7-valent PCV.

Carrier State↗
PubMed2005

Chest X-ray-confirmed pneumonia in children in Fiji.

OBJECTIVE: To calculate the incidence and document the clinical features of chest X-ray- (CXR-) confirmed pneumonia in children aged between 1 month and 5 years living in Greater Suva, Fiji. METHODS: A retrospective review was undertaken of children aged between 1 month and 5 years with a discharge diagnosis suggesting a lower respiratory tract infection (LRTI) admitted to the Colonial War Memorial Hospital in Suva, Fiji, in the first 10 days of each month from 1 January 2001 to 31 December 2002. Clinical data were collected and CXRs were reread and classified according to WHO standardized criteria for CXR-confirmed pneumonia. FINDINGS: Two hundred and forty-eight children with LRTI met the inclusion criteria. CXRs were obtained for 174 (70%) of these cases, of which 59 (34%) had CXR-confirmed pneumonia. The annual incidence of CXR-confirmed pneumonia was 428 cases per 100,000 children aged between 1 month and 5 years living in Greater Suva. If a similar proportion of the children for whom CXRs were unavailable were assumed to have CXR-confirmed pneumonia, the incidence was 607 per 100,000. The incidence appeared to be higher in Melanesian Fijian than Indo-Fijian children. The case-fatality rate was 2.8% in all children with LRTI, and 6.8% in those with CXR-confirmed pneumonia. CONCLUSION: This is the first study to document the incidence of CXR-confirmed pneumonia in a Pacific Island country, and demonstrates a high incidence. A significant proportion of hospital admissions of children with LRTI are likely to be preventable by the introduction of pneumococcal conjugate vaccine.

Benchmarking↗
PubMed2004

Recent advances in pneumococcal vaccination of children.

Pneumococcal disease is a major cause of childhood morbidity and mortality worldwide. However, there is a lack of epidemiological data to describe the vaccine-preventable burden of disease. New pneumococcal conjugate vaccines offer hope of preventing infant pneumococcal disease. The efficacy of the 7- and 9-valent pneumococcal conjugate vaccine (PCV) against invasive vaccine-type pneumococcal disease in young children is between 77 and 97%. The PCV vaccine efficacy against radiological pneumonia in HIV-negative infants for the 7- or 9-valent PCV is 23-30%. The vaccine efficacy in HIV-positive infants is lower--65% against invasive vaccine-type pneumococcal disease and no significant efficacy against radiological pneumonia. The 7-valent PCV showed modest efficacy against acute otitis media (7%) but seems to be more effective in preventing recurrent or severe disease. The high cost of these new vaccines is a barrier to their widespread introduction. The development of other pneumococcal vaccine candidates with wider serotype coverage should be encouraged. These vaccines should be affordable for all countries, particularly those with the highest burden of disease. In addition, other vaccination strategies such as maternal and neonatal immunisation and combinations of fewer doses of the PCV combined with an early dose of the cheaper pneumococcal polysaccharide vaccine need to be assessed further.

Child↗
PubMed2003

High incidence of Haemophilus influenzae type b infection in children in Pacific island countries.

The Haemophilus influenzae type b (Hib) disease burden among children <5 years old in 4 Pacific island countries (PICs) was estimated. The incidence of confirmed Hib meningitis was calculated using the numbers of culture-confirmed isolates. In addition, the World Health Organization (WHO) Hib Rapid Assessment Tool (RAT) was used to estimate the true Hib meningitis incidence and the number of Hib meningitis and pneumonia cases, as well as the number of deaths due to Hib meningitis and pneumonia. The Hib meningitis annual incidence in 3 PICs was 70-84 cases per 100,000 children <5 years old. For PICs, the RAT is likely to overestimate the Hib pneumonia burden, as it assumes a 5 : 1 ratio of Hib pneumonia to Hib meningitis. The true ratio is likely to be 1 : 1. The high Hib disease burden and the relative cost-effectiveness of Hib vaccine make the introduction of Hib vaccine a good investment for PICs, costing US1000 dollars-US10,000 dollars for each death prevented--a number that ignores savings from reductions in the cost of treatment.

Bacterial Capsules↗
PubMed2001

Respiratory rate as a predictor of positive lung aspirates in young Gambian children with lobar pneumonia.

Clinical predictors of a positive bacterial culture from lung aspirate or blood culture were investigated in 90 children under 5 years of age with lobar pneumonia on whom both lung aspiration and blood culture were performed. Of the 66 children with a respiratory rate of > or = 50 breaths/min, 35 (53%) had positive bacterial lung aspirates compared with only five (21.7%) of 23 children with a respiratory rate of < 50 breaths/min (odds ratio [OR] 4.06, 95% confidence interval [CI] 1.24-15.46, p = 0.02). Of the 41 children with positive lung aspirates, 31 (76%) had negative blood cultures. In contrast with children with positive lung aspirates, there were no clinical predictors of a positive blood culture. A respiratory rate of > or = 50 breaths/min in children with radiological evidence of lobar pneumonia would support lung aspiration as a positive result is significantly more likely than in children with a lower respiratory rate.

Bacteremia↗
PubMed2000

Conjugate pneumococcal vaccines: an overview.

A seven-valent conjugate pneumococcal vaccine has been shown to have dramatic efficacy against invasive pneumococcal disease and lesser efficacy against otitis media and pneumonia. This vaccine was licensed for use in infants in the United States in February 2000 and is recommended there for routine use in infants and catch-up vaccination in high-risk children. Specific regional pneumococcal vaccines are not needed; nine to 11 serotypes cover most pneumococcal disease in most parts of the world; nine- and 11-valent conjugate vaccines are currently being developed for the global market. There is evidence of serotype replacement in vaccine recipients (in both carriage and disease), which might reduce overall vaccine effectiveness. There is also evidence that vaccines may reduce rates of antimicrobial resistance in pneumococci. Studies of the burden of pneumococcal disease as well as program support are needed to assist developing countries to introduce these expensive vaccines.

Clinical Trials as Topic↗
PubMed2000

Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia.

In developing countries, endemic childhood meningitis is a severe disease caused most commonly by Streptococcus pneumoniae or Haemophilus influenzae type b (Hib). Although many studies have shown that fatality rates associated with meningitis caused by these organisms are high in developing countries, little is known about the long-term outcome of survivors. The purpose of this study was to assess the importance of disabilities following pneumococcal and Hib meningitis in The Gambia. 257 children aged 0-12 years hospitalized between 1990 and 1995 with culture-proven S. pneumoniae (n = 134) or Hib (n = 123) meningitis were included retrospectively in the study. 48% of children with pneumococcal meningitis and 27% of children with Hib meningitis died whilst in hospital. Of the 160 survivors, 89 (55%) were followed up between September 1996 and October 1997. Of the children with pneumococcal meningitis that were traced, 58% had clinical sequelae; half of them had major disabilities preventing normal adaptation to social life. 38% of survivors of Hib meningitis had clinical sequelae, a quarter of whom had major disabilities. Major handicaps found were hearing loss, mental retardation, motor abnormalities and seizures. These data show that despite treatment with effective antibiotics, pneumococcal and Hib meningitis kill many Gambian children and leave many survivors with severe sequelae. Hib vaccination is now given routinely in The Gambia; an effective pneumococcal vaccine is needed.

Child↗
PubMed1999

An evaluation of the informed consent procedure used during a trial of a Haemophilus influenzae type B conjugate vaccine undertaken in The Gambia, West Africa.

It has recently been debated whether it is possible or desirable to have one internationally recognised standard of "informed consent" or whether research ethics should be adapted to the culture and educational level of the study population. This study examined the attitudes of the Gambian people to consent to medical research, and evaluated the informed consent process used in a major efficacy trial of a Haemophilus influenzae vaccine. Consent was requested after parents had received a verbal explanation and an information sheet which described the vaccine trial in a local language. A semi-structured interview was conducted with 137 acceptors and 52 refusers. Certain points of knowledge were recalled well by the acceptors; 90% knew the purpose of the vaccine was to prevent disease, but the placebo control design was understood by only 10%. The prime motive for consenting was to receive the HIB vaccine (93%) and that for refusing was that the vaccine was experimental (35%) and might have unknown side effects (29%). Although parents took advice from researchers (50%), health workers (24%), friends (16%) and family (12%), in all cases the decision was made by one of the child's parents. Only 1% of parents sought the opinion of traditional or religious leaders. The principles of informed consent, that it should be free, autonomous and informed were affirmed by this community. Therefore, in The Gambia, the international code of informed consent is appropriate.

Adult↗
PubMed1999

Risk factors for severe respiratory syncytial virus infection leading to hospital admission in children in the Western Region of The Gambia.

BACKGROUND: Acute lower respiratory tract infections (ALRI) are the major cause of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) infection is the most important viral cause of severe ALRI but only a small proportion of children infected with this virus develop severe disease. To identify possible risk factors for severe RSV infection leading to hospital admission we have carried out a case-control study of Gambian children with RSV infection admitted to hospital. METHODS: In all, 277 children admitted to three hospitals in the Western Region of The Gambia with lower respiratory tract infection due to RSV were compared with 364 control children matched for age and location of residence who had not been admitted to hospital with an ALRI during the RSV season. A detailed questionnaire covering a wide range of potential social, environmental and nutritional risk factors was administered to the child's guardian. RESULTS: Cases came from larger or more crowded compounds than controls; increased risk was particularly associated with greater numbers of children in the age group 3-5 years living in the compound (odds ratio [OR] for > or =2 children in the age group 3-5 years = 9.1, 95% CI: 3.7-28). Cases were more likely to have a sibling who had died (OR = 3.4, 95% CI: 1.7-7). Controls were more likely to have been exposed to smoke from cooking fires (OR for the mother of cases cooking at least once daily = 0.31, 95% CI: 0.14-0.7). Other protective factors were father's nationality and some professions. Vegetables were included in the diet of controls more frequently than in that of cases (OR = 0.16, 95% CI: 0.06-0.46). Mothers of cases complained of asthma more frequently than mothers of controls, but the number of asthmatic mothers was small (4.2 versus 0.5%, P = 0.05). CONCLUSIONS: Risk factors for severe RSV infection identified in this study are not amenable to public health interventions. Prevention of severe infection is likely to require the development of an effective vaccine.

Case-Control Studies↗
PubMed1999

Chloramphenicol pharmacokinetics in infants less than three months of age in the Philippines and The Gambia.

BACKGROUND: The broad antimicrobial spectrum and affordable price of chloramphenicol make it an attractive first line treatment option for children with severe illnesses in developing countries. Little is known, however, about its pharmacokinetics in young infants in these settings. METHODS: We studied infants younger than 3 months of age hospitalized in Manila, Philippines and The Gambia with possible severe bacterial infections likely to benefit from treatment with chloramphenicol. Infants in the first week of life received intramuscular doses of 25 mg/kg chloramphenicol once daily, twice daily in the second through fourth week of life and three times daily from 5 to 12 weeks of age. Blood samples were taken at 0.5, 1, 2 and 3 h after the first dose, 1 h before the second dose and before the repetition doses on subsequent days. In the Philippines a second group of infants was treated with oral chloramphenicol according to the same dosage schedule. RESULTS: Thirty-eight infants received intramuscular chloramphenicol, and 20 received oral drug. Intramuscular administration resulted in therapeutic concentrations (10 to 25 microg/ml) in 73 to 86% of children in each of the three age groups in the first 6 h and in 50 to 80% on Days 2 and 3. Between 33 and 38% of children had potentially toxic values on Days 2 and 3. In contrast, after oral administration, only about one-half of the children reached therapeutic values in serum at any time up to Day 3 after start of treatment. CONCLUSIONS: Intramuscular chloramphenicol can be used as a second line drug for the treatment of severe infections in infants younger than 90 days of age, where third generation cephalosporins are not available. It quickly achieves therapeutic values in a high proportion of children. However, severe infections should not be treated with oral chloramphenicol in this age group, because therapeutic serum concentrations were inconsistently achieved.

Administration, Oral↗
PubMed1999

Etiology of serious infections in young Gambian infants.

BACKGROUND: Despite improvements in infant mortality rates in many developing countries including The Gambia, neonatal mortality remains high and many neonatal deaths are caused by infection. The study described in this paper was conducted to determine the bacterial and viral etiology of serious infections in Gambian infants younger than 91 days old. METHODS: At a first level health facility 497 infants with symptoms that could indicate serious infection were enrolled, of whom 239 with 1 or more signs of serious infection and 55 with no signs were investigated, yielding 17 cases with positive bacterial cultures of blood and/or cerebrospinal fluid. At a nearby pediatric referral hospital 198 infants were seen and 182 were investigated, yielding 35 positive bacterial cultures. RESULTS: There were 15 culture positive cases of meningitis caused by Streptococcus pneumoniae (7), Streptococcus pyogenes (2), Enterobacter cloacae (2), Escherichia coli (1), Haemophilus influenzae type b (1), Streptococcus agalactiae (1) and Salmonella spp. (1). Six of these children died. Thirty-three infants without meningitis had positive blood cultures for Staphylococcus aureus (17), S. pneumoniae (3), Salmonella spp. (5), E. coli (3), other enterobacteria (4) and S. agalactiae (1), of whom 14 died. Nasopharyngeal aspirates from 438 children were investigated for common respiratory viruses. Respiratory syncytial virus was found in 51, influenza A in 46, influenza B in 22, parainfluenza in 26 and adenovirus in 16. Respiratory syncytial virus and influenza A isolates were found most frequently toward the end of the wet season. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was studied in 320 infants recruited during the first year. Of these 184 (58%) were positive for S. pneumoniae and 141 (44%) were positive for H. influenzae, 18 of which were type b. Infants with a bacterial isolate from blood or cerebrospinal fluid were more likely than the rest to die, whereas those with a viral isolate were less likely to die. CONCLUSIONS: The most important causes of serious infections in young Gambian infants are Staphylococcus aureus, S. pneumoniae and Salmonella spp.

Bacteria↗
PubMed1999

Etiology of pneumonia, sepsis and meningitis in infants younger than three months of age in Ethiopia.

METHODS: Within a multicenter study coordinated by WHO, an investigation of the etiologic agents of pneumonia, sepsis and meningitis was performed among infants younger than 3 months of age seen at the Ethio-Swedish Children's Hospital in Addis Ababa for a period of 2 years. Of the 816 infants enrolled 405 had clinical indications for investigation. RESULTS: There were a total of 41 isolates from blood cultures from 40 infants. The study showed that the traditionally known acute respiratory infection pathogen Streptococcus pneumoniae was most common in this extended neonatal age group, found in 10 of 41 blood isolates. Streptococcus pyogenes was a common pathogen in this setting (9 of 41 blood isolates), whereas Salmonella group B was found in 5 of 41 isolates. Streptococcus agalactiae, which is a common pathogen in developed countries, was absent. A study of the susceptibility pattern of these organisms suggests that a combination of ampicillin with an aminoglycoside is adequate for initial treatment of these serious bacterial infections, but the combination is not optimal for the treatment of Salmonella infections. Among 202 infants on whom immunofluorescent antibody studies for viruses were performed based on nasopharyngeal aspirates, respiratory syncytial virus was found in 57 (28%) infants, and Chlamydia trachomatis was isolated in 32 (15.8%) of 203 infants.

Bacteria↗
PubMed1999

Long-term morbidity and mortality following hypoxaemic lower respiratory tract infection in Gambian children.

Acute lower respiratory infections (ALRI) are the main cause of death in young children worldwide. We report here the results of a study to determine the long-term survival of children admitted to hospital with severe pneumonia. The study was conducted on 190 Gambian children admitted to hospital in 1992-94 for ALRI who survived to discharge. Of these, 83 children were hypoxaemic and were treated with oxygen, and 107 were not. On follow-up in 1996-97, 62% were traced. Of the children with hypoxaemia, 8 had died, compared with 4 of those without. The mortality rates were 4.8 and, 2.2 deaths per 100 child-years of follow-up for hypoxaemic and non-hypoxaemic children, respectively (P = 0.2). Mortality was higher for children who had been malnourished (Z-score < -2) when seen in hospital (rate ratio = 3.2; 95% confidence interval (CI) = 1.03-10.29; P = 0.045). Children with younger siblings experienced less frequent subsequent respiratory infections (rate ratio for further hospitalization with respiratory illness = 0.15; 95% CI = 0.04-0.50; P = 0.002). Children in Gambia who survive hospital admission with hypoxaemic pneumonia have a good prognosis. Survival depends more on nutritional status than on having been hypoxaemic. Investment in oxygen therapy appears justified, and efforts should be made to improve nutrition in malnourished children with pneumonia.

Acute Disease↗
PubMed1998

Development of a clinical prediction model for an ordinal outcome: the World Health Organization Multicentre Study of Clinical Signs and Etiological agents of Pneumonia, Sepsis and Meningitis in Young Infants. WHO/ARI Young Infant Multicentre Study Group.

This paper describes the methodologies used to develop a prediction model to assist health workers in developing countries in facing one of the most difficult health problems in all parts of the world: the presentation of an acutely ill young infant. Statistical approaches for developing the clinical prediction model faced at least two major difficulties. First, the number of predictor variables, especially clinical signs and symptoms, is very large, necessitating the use of data reduction techniques that are blinded to the outcome. Second, there is no uniquely accepted continuous outcome measure or final binary diagnostic criterion. For example, the diagnosis of neonatal sepsis is ill-defined. Clinical decision makers must identify infants likely to have positive cultures as well as to grade the severity of illness. In the WHO/ARI Young Infant Multicentre Study we have found an ordinal outcome scale made up of a mixture of laboratory and diagnostic markers to have several clinical advantages as well as to increase the power of tests for risk factors. Such a mixed ordinal scale does present statistical challenges because it may violate constant slope assumptions of ordinal regression models. In this paper we develop and validate an ordinal predictive model after choosing a data reduction technique. We show how ordinality of the outcome is checked against each predictor. We describe new but simple techniques for graphically examining residuals from ordinal logistic models to detect problems with variable transformations as well as to detect non-proportional odds and other lack of fit. We examine an alternative type of ordinal logistic model, the continuation ratio model, to determine if it provides a better fit. We find that it does not but that this model is easily modified to allow the regression coefficients to vary with cut-offs of the response variable. Complex terms in this extended model are penalized to allow only as much complexity as the data will support. We approximate the extended continuation ratio model with a model with fewer terms to allow us to draw a nomogram for obtaining various predictions. The model is validated for calibration and discrimination using the bootstrap. We apply much of the modelling strategy described in Harrell, Lee and Mark (Statist. Med. 15, 361-387 (1998)) for survival analysis, adapting it to ordinal logistic regression and further emphasizing penalized maximum likelihood estimation and data reduction.

Chi-Square Distribution↗
PubMed1998

Respiratory syncytial virus infection in tropical and developing countries.

Little is known about the epidemiology of respiratory syncytial virus (RSV) infection in tropical and developing countries; the data currently available have been reviewed. In most studies, RSV was found to be the predominant viral cause of acute lower respiratory tract infections (ALRI) in childhood, being responsible for 27-96% of hospitalised cases (mean 65%) in which a virus was found. RSV infection is seasonal in most countries; outbreaks occur most frequently in the cold season in areas with temperate and Mediterranean climates and in the wet season in tropical countries with seasonal rainfall. The situation on islands and in areas of the inner tropics with perennial high rainfall is less clear-cut. The age group mainly affected by RSV in developing countries is children under 6 months of age (mean 39% of hospital patients with RSV). RSV-ALRI is slightly more common in boys than in girls. Very little information is available about the mortality of children infected with RSV, the frequency of bacterial co-infection, or the incidence of further wheezing after RSV. Further studies on RSV should address these questions in more detail. RSV is an important pathogen ill young children in tropical and developing countries and a frequent cause of hospital admission. Prevention of RSV infection by vaccination would have a significant impact on the incidence of ALRI in children in developing countries.

Age Distribution↗