Reducing the global burden of acute lower respiratory infections in children: the contribution of new diagnostics.
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Anti-Bacterial Agents↗
Biomedical subjects
Kim Mulholland
Publications and source records attributed to Kim Mulholland.
Perspectives on the burden of pneumonia in children.
In the US at the beginning of the 20th century, the infant mortality rate was high (150/1000 live births); 19% of deaths were due to pneumonia. In the pre-antibiotic era, childhood pneumonia case fatality rates were age dependant with most deaths occurring in infants. The introduction of antibiotics in the late 1930s lowered the mortality, but in the US most of the improvements in pneumonia mortality since 1900 had already occurred, probably due to improvements in nutrition and child care. Today, efforts to control pneumonia mortality are focused on case management and vaccines. History suggests that a more holistic approach may be needed.
Age Factors↗
Pneumococcal vaccination in developing countries.
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Africa↗
Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia.
OBJECTIVE: To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. METHODS: Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants aged<2 years with suspected intussusception (533 infants in Hanoi; 51 in Melbourne). Specificity was evaluated in 638 infants aged<2 years presenting with clinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). FINDINGS: In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). CONCLUSION: The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely.
Acute Disease↗
Evaluating the post-licensure effectiveness of a group B meningococcal vaccine in New Zealand: a multi-faceted strategy.
A nationwide strategy to control a group B meningococcal disease epidemic in New Zealand using an epidemic strain-specific vaccine (MeNZB ) commenced in 2004. In the absence of randomised controlled trials investigating the efficacy of this particular vaccine, a complement of observational methods are planned to evaluate the post-licensure effectiveness of this vaccine strategy. The two main approaches involve a Poisson regression model investigating the overall impact of the MeNZB programme on disease rates over time capitalising on detailed population-based disease surveillance data and the staged roll-out of the vaccine campaign, and a case-control study that aims to estimate vaccine effectiveness in pre-school children. The studies are designed to minimise the potential biases inherent in all observational methods and provide critical data on the effectiveness of a major public health intervention.
Adolescent↗
From secondary prevention to primary prevention: a unique strategy that gives hope to a country ravaged by meningococcal disease.
New Zealand has been affected by an epidemic of group B meningococcal disease dominated by a strain defined as, B:4:P1.7b,4. Over 5550 cases and 222 deaths have been reported since 1991 in a population of 4 million people. Meningococcal disease cases notified on EpiServ database operated by Institute of Environmental Science and Research Limited through to 30 September 2004. Through the collaborative efforts of a government agency, vaccine company, university and laboratory institute, clinical trials of the Chiron produced outer membrane vesicle (OMV) strain-specific MeNZB vaccine were run in rapid succession. The delivery of MeNZB will be New Zealand's largest immunisation programme with three doses given at 6-week intervals to over 1 million people aged 6 weeks-19 year olds inclusive. Planning, co-ordinating and delivering the immunisation programme is a challenging project for the New Zealand Health Sector.
Adolescent↗
MeNZB: a safe and highly immunogenic tailor-made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain.
Clinical studies have been conducted in New Zealand evaluating the safety and immunogenicity of an outer membrane vesicle (OMV) vaccine, MeNZB, developed to control epidemic disease caused by group B meningococci, subtype P1.7b,4. MeNZB, administered in a three-dose regimen, was well tolerated and induced a seroresponse, defined as a four-fold rise (> or =titre 8) in serum bactericidal antibodies against the vaccine strain 4-6 weeks after the third vaccination, in 96% (95% confidence interval (CI): 79-100%) of adults, 76% (95% CI: 72-80%) of children, 75% (95% CI: 69-80%) of toddlers and 74% (95% CI: 67-80%) of infants receiving MeNZB. In conclusion, these findings suggest that MeNZB is safe and is likely to confer protection against systemic group B meningococcal disease caused by the epidemic strain.
Adolescent↗
Commentary: comorbidity as a factor in child health and child survival in developing countries.
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Child Welfare↗
The Gambian pneumococcal vaccine trial - implications for control of childhood pneumonia.
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Acute Disease↗
The New Zealand Meningococcal Vaccine Strategy: a tailor-made vaccine to combat a devastating epidemic.
The New Zealand Meningococcal Vaccine Strategy aims to end the devastating 14-year epidemic of B:4:P1.7b,4 group B meningococcal disease in New Zealand through a mass immunisation programme to all under 20 year olds using a tailor-made vaccine (MeNZB). This paper describes the scientific rationale, development, and key components of the New Zealand Meningococcal Vaccine Strategy. A summary of the efficacy and safety data of existing outer membrane vesicle group B meningococcal vaccines is included as these data critically support the Strategy.
Disease Outbreaks↗
Clinical case definition for the diagnosis of acute intussusception.
OBJECTIVE: Because of the reported association between intussusception and a rotavirus vaccine, future clinical trials of rotavirus vaccines will need to include intussusception surveillance in the evaluation of vaccine safety. The aim of this study is to develop and validate a clinical case definition for the diagnosis of acute intussusception. METHODS: A clinical case definition for the diagnosis of acute intussusception was developed by analysis of an extensive literature review that defined the clinical presentation of intussusception in 70 developed and developing countries. The clinical case definition was then assessed for sensitivity and specificity using a retrospective chart review of hospital admissions. Sensitivity of the clinical case definition was assessed in children diagnosed with intussusception over a 6.5-year period. Specificity was assessed in patients aged <2 years admitted with bowel obstruction and in patients aged <19 years presenting with symptoms that may occur in intussusception. RESULTS: The clinical case definition accurately identified 185 of 191 assessable cases as "probable" intussusception and six cases as "possible" intussusception (sensitivity, 97%). No case of radiologic or surgically proven intussusception failed to be identified by the clinical case definition. The specificity of the definition in correctly identifying patients who did not have intussusception ranged from 87% to 91%. CONCLUSIONS: The clinical case definition for intussusception may assist in the prompt identification of patients with intussusception and may provide an important tool for the future trials of enteric vaccines.
Acute Disease↗
Hospital-based case-control study of bronchiectasis in indigenous children in Central Australia.
BACKGROUND: Childhood pneumonia has been reported to be associated with the development of bronchiectasis but there are no case-control studies that have examined this. This study examined the relationship between hospital admission for episode(s) of pneumonia and the risk of radiologically proven bronchiectasis. METHODS: A medical record-based case-control study of bronchiectasis in Indigenous children was conducted in Central Australia. Controls (183), matched to cases (61) by gender, age and year of diagnosis, were Indigenous children hospitalized with other conditions. RESULTS: There was a strong association between a history of hospitalized pneumonia and bronchiectasis [odds ratio (OR), 15.2; 95% confidence interval (95% CI) 4.4-52.7]. This was particularly evident in recurrent hospitalized pneumonia (P for trend < 0.01), severe pneumonia episodes with longer hospital stay (P for trend < 0.01), presence of atelectasis (OR 11.9; 95% CI 3.1-45.9) and requirement for oxygen (P for trend < 0.01). The overall number of pneumonia episodes, rather than its site, was associated with bronchiectasis. Although the total number of pneumonia episodes in the first year of life did not increase the risk of bronchiectasis, more severe episodes early in life did. Malnutrition, premature birth and being small for gestational age were more common findings among cases. Breast-feeding appeared to be a protective factor (OR 0.2; 95% CI 0.1-0.7). CONCLUSIONS: Although we cannot fully answer the question of why bronchiectasis is much more common in Indigenous children, we have provided strong evidence of an association between bronchiectasis and severe and recurrent pneumonia episodes in infancy and childhood.
Adolescent↗
The use of CRP for diagnosing infections in young infants < 3 months of age in developing countries.
The diagnosis of severe bacterial infection in young infants in developing countries is difficult because of the lack of sensitivity and specificity of the presenting symptoms and signs. Whether C-reactive protein (CRP) might help with the early detection of neonatal sepsis was investigated in a prospective study in The Gambia, Ethiopia and The Philippines. Infants < 3 months of age with symptoms or signs of possible sepsis were evaluated; CRP was measured and assessed for its ability to predict proven invasive bacterial infection. Of 966 children < 3 months of age, 54 had a positive blood culture, 13 a positive CSF culture, 15 a positive blood and CSF culture and 884 had negative cultures. Median (interquartile range) CRP values were 42 (9-173), 14 (6-36), 209 (135-286) and 8 (3-27) mg/L in the four groups, respectively. Taking a CRP cut-off of 10 mg/L, the sensitivity and specificity of an elevated CRP to predict a positive blood or CSF culture were 77% and 55%, respectively, and 55% and 82%, respectively, for a cut-off of 40 mg/L. CRP lacks the sensitivity and specificity to be used alone as a predictor of serious infections in young infants.
Bacteremia↗
Evidence on the use of paracetamol in febrile children.
Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature review was performed by searching Medline and the Cochrane databases for research papers on the efficacy of paracetamol in febrile illnesses in children and adverse outcomes related to the use of paracetamol. No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria. Some studies suggested that fever may have a beneficial role in infection, although no definitive prospective studies in children have been done to prove this. The use of paracetamol in therapeutic doses generally is safe, although hepatotoxicity has occurred with recommended dosages in children. In developing countries where malnutrition is common, data on the safety of paracetamol are lacking. The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful. The role of paracetamol in children with severe malaria or sepsis and in malnourished, febrile children needs to be clarified.
Acetaminophen↗
Global burden of acute respiratory infections in children: implications for interventions.
Despite dramatic advances in human health that have occurred during the 20th century, the end of the century still sees many places in the world with high child mortality rates. This is made worse by increasing inequity, such that there are still many communities in the world in which over 30% of children die before their fifth birthday. Estimates of the global burden of childhood pneumonia are based on the assumption that there is a predictable relationship between the childhood mortality rate and the proportion of that mortality that is attributable to pneumonia. As most child deaths occur at home and can only be investigated by verbal autopsy techniques, these estimates are very crude and provide only a guide to the overall burden of pneumonia. Recent estimates from the World Health Organization suggest that 1.9 million children die as a result of acute respiratory infection (ARI), mainly pneumonia, each year. For a number of reasons, this is likely to be an underestimate. Estimates of the morbidity burden attributable to pneumonia are also very approximate, as studies have used different and nonstandardized definitions of pneumonia. These estimates were originally used to assist with planning of ARI intervention activities and for advocacy to draw attention to the problem of ARI. Recently, the introduction of new vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus) raised the prospect of prevention of pneumonia by vaccination. For reasons outlined in this paper, great caution must be exercised before using existing pneumonia burden estimates to predict mortality savings that may accompany the introduction of these vaccines into developing countries.
Child↗
Global burden of pediatric respiratory illness and the implications for management and prevention.
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Child, Preschool↗
Prevention of otitis media by vaccination.
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.
Child, Preschool↗
Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomised vaccine-probe trial.
BACKGROUND: Most studies of Haemophilus influenzae type b (Hib) disease in Asia have found low rates, and few Asian countries use Hib vaccine in routine immunisation programmes. Whether Hib disease truly is rare or whether many cases remain undetected is unclear. METHODS: To estimate incidences of vaccine-preventable Hib pneumonia and meningitis among children younger than 2 years in Lombok, Indonesia, during 1998-2002, we undertook a hamlet-randomised, controlled, double-blind vaccine-probe study (818 hamlets). Children were immunised (WHO schedule) with diphtheria, tetanus, pertussis (DTP) or DTP-PRP-T (Hib conjugate) vaccine. Vaccine-preventable disease incidences were calculated as the difference in rates of clinical outcomes between DTP and DTP-PRP-T groups. Analyses included all children who received at least one vaccine dose. FINDINGS: We enrolled 55073 children: 28147 were assigned DTP-PRP-T and 26926 DTP. The proportion of pneumonia outcomes prevented by vaccine ranged from less than 0 to 4.8%. Calculated incidences of vaccine-preventable Hib disease (per 10(5) child-years of observation) for outcome categories were: substantial alveolar consolidation or effusion, less than zero (-43 [95% CI -185 to 98]); all severe pneumonia, 264 (95% CI less than zero to 629); all clinical pneumonia, 1561 (270 to 2853); confirmed Hib meningitis, 16 (1.4 to 31); meningitis with cerebrospinal-fluid findings consistent with a bacterial aetiology, 67 (22 to 112); and admission for suspected meningitis or presenting to a clinic with convulsions, 158 (42 to 273). INTERPRETATION: Hib vaccine did not prevent the great majority of pneumonia cases, including those with alveolar consolidation. These results do not support a major role for Hib vaccine in overall pneumonia-prevention programmes. Nevertheless, the study identified high incidences of Hib meningitis and pneumonia; inclusion of Hib vaccine in routine infant immunisation programmes in Asia deserves consideration.
Bacterial Capsules↗