Paediatrics (RCH) - Research Publications

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    Prospective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005-2007
    Steer, AC ; Jenney, A ; Kado, J ; Good, MF ; Batzloff, M ; Waqatakirewa, L ; Mullholland, EK ; Carapetis, JR (CENTERS DISEASE CONTROL & PREVENTION, 2009-02-01)
    We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005-2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6-12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1-92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention.
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    Recommendations for treatment of childhood non-severe pneumonia
    Grant, GB ; Campbell, H ; Dowell, SF ; Graham, SM ; Klugman, KP ; Mulholland, EK ; Steinhoff, M ; Weber, MW ; Qazi, S (ELSEVIER SCI LTD, 2009-03-01)
    WHO recommendations for early antimicrobial treatment of childhood pneumonia have been effective in reducing childhood mortality, but the last major revision was over 10 years ago. The emergence of antimicrobial resistance, new pneumonia pathogens, and new drugs have prompted WHO to assemble an international panel to review the literature on childhood pneumonia and to develop evidence-based recommendations for the empirical treatment of non-severe pneumonia among children managed by first-level health providers. Treatment should target the bacterial causes most likely to lead to severe disease, including Streptoccocus pneumoniae and Haemophilus influenzae. The best first-line agent is amoxicillin, given twice daily for 3-5 days, although co-trimoxazole may be an alternative in some settings. Treatment failure should be defined in a child who develops signs warranting immediate referral or who does not have a decrease in respiratory rate after 48-72 h of therapy. If failure occurs, and no indication for immediate referral exists, possible explanations for failure should be systematically determined, including non-adherence to therapy and alternative diagnoses. If failure of the first-line agent remains a possible explanation, suitable second-line agents include high-dose amoxicillin-clavulanic acid with or without an affordable macrolide for children over 3 years of age.
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    High Burden of Impetigo and Scabies in a Tropical Country
    Steer, AC ; Jenney, AWJ ; Kado, J ; Batzloff, MR ; La Vincente, S ; Waqatakirewa, L ; Mulholland, EK ; Carapetis, JR ; Franco-Paredes, C (PUBLIC LIBRARY SCIENCE, 2009-06-01)
    BACKGROUND: Impetigo and scabies are endemic diseases in many tropical countries; however the epidemiology of these diseases is poorly understood in many areas, particularly in the Pacific. METHODOLOGY/PRINCIPAL FINDINGS: We conducted three epidemiological studies in 2006 and 2007 to determine the burden of disease due to impetigo and scabies in children in Fiji using simple and easily reproducible methodology. Two studies were performed in primary school children (one study was a cross-sectional study and the other a prospective cohort study over ten months) and one study was performed in infants (cross-sectional). The prevalence of active impetigo was 25.6% (95% CI 24.1-27.1) in primary school children and 12.2% (95% CI 9.3-15.6) in infants. The prevalence of scabies was 18.5% (95% CI 17.2-19.8) in primary school children and 14.0% (95% CI 10.8-17.2) in infants. The incidence density of active impetigo, group A streptococcal (GAS) impetigo, Staphylococcus aureus impetigo and scabies was 122, 80, 64 and 51 cases per 100 child-years respectively. Impetigo was strongly associated with scabies infestation (odds ratio, OR, 2.4, 95% CI 1.6-3.7) and was more common in Indigenous Fijian children when compared with children of other ethnicities (OR 3.6, 95% CI 2.7-4.7). The majority of cases of active impetigo in the children in our study were caused by GAS. S. aureus was also a common cause (57.4% in school aged children and 69% in infants). CONCLUSIONS/SIGNIFICANCE: These data suggest that the impetigo and scabies disease burden in children in Fiji has been underestimated, and possibly other tropical developing countries in the Pacific. These diseases are more than benign nuisance diseases and consideration needs to be given to expanded public health initiatives to improve their control.
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    As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries
    Russell, FM ; Biribo, SSN ; Selvaraj, G ; Oppedisano, F ; Warren, S ; Seduadua, A ; Mulholland, EK ; Carapetis, JR (AMER SOC MICROBIOLOGY, 2006-09-01)
    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.
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    The burden of hospitalised rotavirus infections in Fiji
    Jenney, A ; Tikoduadua, L ; Buadromo, E ; Barnes, G ; Kirkwood, CD ; Boniface, K ; Bines, J ; Mulholland, K ; Russell, F (ELSEVIER SCI LTD, 2009-11-20)
    Rotavirus is the most common cause of acute severe dehydrating diarrhoea in young children worldwide. We describe the burden of rotavirus disease and the rotavirus types causing it in the largest city in Fiji. During 2006 and 2007, 592 children under 5 years of age were admitted to hospital in Suva, Fiji with acute diarrhoea. Of the 454 children for whom a stool specimen was tested, 39% were positive for rotavirus and the predominant strain found was the serotype G3[P8]. There is a significant burden of disease due to rotavirus in Fiji and the introduction of rotavirus vaccines into the national immunization schedule may drastically reduce inpatient diarrhoeal disease.
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    Immunogenicity following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine
    Russell, FM ; Balloch, A ; Tang, MLK ; Carapetis, JR ; Licciardi, P ; Nelson, J ; Jenney, AWJ ; Tikoduadua, L ; Waqatakirewa, L ; Pryor, J ; Byrnes, GB ; Cheung, YB ; Mulholland, EK (ELSEVIER SCI LTD, 2009-09-18)
    The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received zero, one, two, or three doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following three PCV doses, geometric mean concentration (GMC) to all seven serotypes were > or = 1.0 microg/mL, and >85% of children achieved antibody levels > or = 0.35 microg/mL at 18 weeks. Following two doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with three doses. Following a single dose, significant responses were seen for all serotypes post-primary series compared with the unvaccinated. By 12 months, differences between two and three doses persisted for serotype 14 only. Although GMC following three doses are higher than after two doses, the differences were small. A single dose may offer some protection for most serotypes.
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    Prevention of otitis media by vaccination
    Russell, F ; Mulholland, K (ADIS INT LTD, 2002-01-01)
    Otitis media (OM) is one of the commonest infections in childhood and a frequent reason for prescribing antibacterials in infancy. However, the increase in prevalence of antibacterial-resistant respiratory bacterial pathogens has not been matched by the development of new antibacterial agents. Bacterial vaccine strategies aim to prevent OM directly and to reduce nasopharyngeal carriage of pneumococci, thereby reducing the likelihood of developing acute OM. Complete protection against OM would require an approach targeting both bacterial and viral agents. Immunisation with a pneumococcal conjugate vaccine provides protection against acute OM caused by pneumococcal serotypes included in the vaccine, reduces serotype-specific pneumococcal carriage, and reduces carriage of penicillin-resistant pneumococci. However, an increase in non-vaccine serotype OM has been observed in vaccinated children, which may limit the overall effectiveness of this vaccine. New vaccines targeting non-typable Haemophilus influenzae and Mycoplasma catarrhalis are in the early stages of development. Efficacy studies with influenza vaccine have shown the most promising results to date in terms of overall reduction in OM episodes. A more substantial reduction in the burden of OM in childhood would require a combination of vaccines that are effective against the bacterial and viral pathogens involved and that can be administered early in infancy.
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    High incidence of Haemophilus influenzae type b infection in children in Pacific Island countries
    Russell, FM ; Carapetis, JR ; Mansoor, O ; Darcy, A ; Fakakovi, T ; Metai, A ; Potoi, NT ; Wilson, N ; Mulholland, EK (UNIV CHICAGO PRESS, 2003-12-15)
    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.
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    Chest x-ray-confirmed pneumonia in children in Fiji
    Magree, HC ; Russell, FM ; Sa'aga, R ; Greenwood, P ; Tikoduadua, L ; Pryor, J ; Waqatakirewa, L ; Carapetis, JR ; Mulholland, EK (WORLD HEALTH ORGANIZATION, 2005-06-01)
    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.
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    An epidemiological study of RSV infection in the Gambia
    Weber, MW ; Milligan, P ; Sanneh, M ; Awemoyi, A ; Dakour, ER ; Schneider, G ; Palmer, A ; Jallow, M ; Oparaogu, A ; Whittle, H ; Mulholland, EK ; Greenwood, BM (WORLD HEALTH ORGANIZATION, 2002-01-01)
    OBJECTIVE: To describe the epidemiology of respiratory syncytial virus (RSV) infection in a developing country. METHODS: The work was carried out in three hospitals for primary cases and in the community for secondary cases in the western region of the Gambia, West Africa. RSV infection was diagnosed by immunofluorescence of nasopharyngeal aspirate samples in children younger than two years admitted to hospital with acute lower respiratory infection (ALRI). Routine records of all children with ALRI were analysed, and the incidence rates of ALRI, severe RSV-associated respiratory illness and hypoxaemic RSV infections were compared. A community-based study was undertaken to identify secondary cases and to obtain information about spread of the virus. FINDINGS: 4799 children with ALRI who were younger than two years and lived in the study area were admitted to the study hospitals: 421 had severe RSV-associated respiratory illness; 55 of these were hypoxaemic. Between 1994 and 1996, the observed incidence rate for ALRI in 100 children younger than one year living close to hospital was 9.6 cases per year; for severe RSV-associated respiratory illness 0.83; and for hypoxaemic RSV-associated respiratory illness 0.089. The proportion of all ALRI admissions due to RSV was 19%. Overall, 41% of children younger than five years in compounds in which cases lived and 42% in control compounds had evidence of RSV infection during the surveillance period. CONCLUSION: RSV is an important cause of ALRI leading to hospital admission in the Gambia. Morbidity is considerable and efforts at prevention are worthwhile.