Deborah Lehmann

Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children—implications for vaccine strategies

Streptococcus pneumoniae is a leading cause of fatal bacterial pneumonia in young children. Pneumococcal polysaccharide vaccines have not been promoted for use in young children because many constituent serotypes are not immunogenic in children < 2 years old. Conjugating pneumococcal polysaccharide epitopes to a protein carrier would likely increase vaccine immunogenicity in children. We reviewed published and unpublished pneumococcal serotype and serogroup data from 16 countries on 6 continents to determine geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates among children and to estimate coverage of proposed and potential pneumococcal conjugate vaccine formulas. The most common pneumococcal serotypes or groups from developed countries were, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7. Development of customized heptavalent vaccine formulas, one for use in all developed countries and one for use in all developing countries, would not provide substantially better coverage against invasive pneumococcal disease than two currently proposed heptavalent formulas. An optimal nanovalent vaccine for global use would include serotypes 1, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Geographic and temporal variation in pneumococcal serotypes demonstrates the need for a species-wide pneumococcal vaccine.

Upper respiratory tract bacterial carriage in aboriginal and non-aboriginal children in a semi-arid area of Western Australia

Background: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are associated with otitis media (OM). Indigenous children experience particularly high rates of OM. Few studies worldwide have described upper respiratory tract (URT) carriage in Indigenous and non-Indigenous children living in the same area. Aim: The aim of this study was to describe URT bacterial carriage in Aboriginal and non-Aboriginal children in the Kalgoorlie-Boulder area, Western Australia, as part of an investigation into causal pathways to OM. Methods: Five hundred four and 1045 nasopharyngeal aspirates were collected from 100 Aboriginal and 180 non-Aboriginal children, respectively, followed from birth to age 2 years. Standard procedures were used to identify bacteria. Results: Overall carriage rates of S. pneumoniae, M. catarrhalis and H. influenzae in Aboriginal children were 49%, 50% and 41%, respectively, and 25%, 25% and 11% in non-Aboriginal children. By age 2 months S. pneumoniae and M. catarrhalis had been isolated from 37% and 36% of Aboriginal children and from 11% and 12% of non-Aboriginal children, respectively. From age 3 months onward, carriage rates in Aboriginal children were 51% to 67% for S. pneumoniae and M. catarrhalis and 42% to 62% for H. influenzae; corresponding figures for non-Aboriginal children were 26% to 37% for S. pneumoniae and M. catarrhalis and 11% to 18% for H. influenzae. Non-Aboriginal children had higher carriage rates in winter than in summer, but season had little effect in Aboriginal children. Staphylococcus aureus carriage was highest under age 1 month (55% Aboriginal, 61% non-Aboriginal) and was always higher in non-Aboriginal than Aboriginal children. Conclusions: Interventions are needed to reduce high transmission and carriage rates, particularly in Aboriginal communities, to avoid the serious consequences of OM.

Predictors of neonatal sepsis in developing countries.

Background. Neonatal infections are a major cause of death worldwide. Simple procedures for identifying infants with infection that need referral for treatment are therefore of major public health importance. Methods. We investigated 3303 infants <2 months of age presenting with illness to health facilities in Ethiopia, The Gambia, Papua New Guinea and The Philippines, using a standardized approach. Historical factors and clinical signs predicting sepsis, meningitis, hypoxemia, deaths and an ordinal scale indicating severe disease were investigated by logistic regression, and the performance of simple combination rules was explored. Results. In multivariable analysis, reduced feeding ability, no spontaneous movement, temperature >38°C, being drowsy/unconscious, a history of a feeding problem, history of change in activity, being agitated, the presence of lower chest wall indrawing, respiratory rate >60 breaths/min, grunting, cyanosis, a history of convulsions, a bulging fontanel and slow digital capillary refill were independent predictors of severe disease. The presence of any 1 of these 14 signs had a sensitivity for severe disease (defined as sepsis, meningitis, hypoxemia, or radiologically proven pneumonia) of 87% and a specificity of 54%. More stringent combinations, such as demanding 2 signs from the list, resulted in a considerable loss of sensitivity. By contrast only slight loss of sensitivity and considerable gain of specificity resulted from reducing the list to 9 signs. Requiring the presence of fever and any other sign produced a diagnostic rule with extremely low sensitivity (25%). Conclusions. Physical signs can be used to identify young infants at risk of severe disease, however with limited specificity, resulting in large numbers of unnecessary referrals. Further studies are required to validate and refine the prediction of severe disease, especially in the first week of life, but there appear to be limits on the accuracy of prediction that is achievable.

The Changing Epidemiology of Invasive Pneumococcal Disease in Aboriginal and Non-Aboriginal Western Australians from 1997 through 2007 and Emergence of Nonvaccine Serotypes

BACKGROUND. In 2001, Australia introduced a unique 7-valent pneumococcal conjugate vaccine (7vPCV) 2-, 4-, and 6-month schedule with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster for Aboriginal children, and in 2005, 7vPCV alone in a 2-, 4-, and 6-month schedule for non-Aboriginal children. Aboriginal adults are offered 23vPPV but coverage is poor. We investigated trends in invasive pneumococcal disease (IPD) in Western Australia (WA). METHODS. Enhanced IPD surveillance has been ongoing since 1996. We calculated IPD incidence rates for Aboriginal and non-Aboriginal Australians before and after introduction of 7vPCV. RESULTS. A total of 1792 cases occurred during the period 1997-2007; the IPD incidence rate was 47 cases per 100,000 population per year among Aboriginal people and 7 cases per 100,000 population per year in non-Aboriginal people. After introduction of 7vPCV, IPD rates among Aboriginal children decreased by 46% for those <2 years of age and by 40% for those 2-4 years of age; rates decreased by 64% and 51% in equivalent age groups for non-Aboriginal children. IPD rates decreased by >30% in non-Aboriginal people 50 years of age but increased among Aboriginal adults (eg, from 59.1 to 109.6 cases per 100,000 population per year among those 30-49 years of age). Although IPD due to 7vPCV serotypes decreased in all age groups, IPD incidence due to non-7vPCV serotypes increased, and it almost doubled among Aboriginal adults 30-49 years of age (from 48.3 to 97.0 cases per 100,000 population per year). Among non-Aboriginal children, 37% of IPD is now due to serotype 19A. CONCLUSIONS. IPD incidence rates have decreased markedly among children and non-Aboriginal adults with a 3-dose infant 7vPCV schedule. However, IPD due to non-7vPCV serotypes has increased and is of particular concern among young Aboriginal adults, for whom an intensive 23vPPV campaign is needed. An immunization register covering all age groups should be established.

Equity and child-survival strategies

Recent advances in child survival have often been at the expense of increasing inequity. Successive interventions are applied to the same population sectors, while the same children in other sectors consistently miss out, leading to a trend towards increasing inequity in child survival. This is particularly important in the case of pneumonia, the leading cause of child death, which is closely linked to poverty and malnutrition, and for which effective community-based case management is more difficult to achieve than for other causes of child death. The key strategies for the prevention of childhood pneumonia are case management, mainly through Integrated Management of Childhood Illness (IMCI), and immunization, particularly the newer vaccines against Haemophilus influenzae type b (Hib) and pneumococcus. There is a tendency to introduce both interventions into communities that already have access to basic health care and preventive services, thereby increasing the relative disadvantage experienced by those children without such access. Both strategies can be implemented in such a way as to decrease rather than increase inequity. It is important to monitor equity when introducing child-survival interventions. Economic poverty, as measured by analyses based on wealth quintiles, is an important determinant of inequity in health outcomes but in some settings other factors may be of greater importance. Geography and ethnicity can both lead to failed access to health care, and therefore inequity in child survival. Poorly functioning health facilities are also of major importance. Countries need to be aware of the main determinants of inequity in their communities so that measures can be taken to ensure that IMCI, new vaccine implementation and other child-survival strategies are introduced in an equitable manner.

Infection is the major component of the disease burden in aboriginal and non-aboriginal Australian children: a population-based study.

Background: Infection accounts for the majority of pediatric mortality and morbidity in developing countries, but there are limited data on the infectious diseases burden in children from developed countries. We investigated reasons for hospitalization before age 2 years in a birth cohort of Western Australian Aboriginal and non-Aboriginal children. Methods: Data on live births between January 1990 and December 2000, and corresponding deaths and hospitalizations in the first 2 years of life, were obtained through linked population-based data. Results: Almost half the cohort of 270,068 children were hospitalized at least once. Aboriginal children had significantly higher admission rates (2196 vs. 779 per 1000 live births), stayed longer and were more likely to die in hospital than non-Aboriginal children. Infections (mainly respiratory and gastrointestinal) were the most common reason for hospitalization, accounting for 34% of all admissions, with higher rates in Aboriginal (1114 per 1000 live births) than non-Aboriginal children (242 per 1000) (P < 0.001). Over time, admission rates for infections declined in Aboriginal children but increased in non-Aboriginal children. Aboriginal children were admitted 14 times more often for pneumonia than non-Aboriginal children. Conclusions: Infections are the leading cause of hospitalization in children under 2 years of age. The continuing heavy burden of serious infections, borne disproportionately by Aboriginal children, needs to be alleviated. Public health interventions such as the development and universal implementation of vaccines for respiratory syncytial virus, rotavirus and influenza are needed, while adequate funding must be committed to Indigenous health services and training.

Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract

Abstract Otitis media (OM) is a major burden for all children, particularly for Australian Aboriginal children. Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and viruses (including rhinovirus and adenovirus) are associated with OM. We investigated nasopharyngeal microbial interactions in 435 samples collected from 79 Aboriginal and 570 samples from 88 non-Aboriginal children in Western Australia. We describe a multivariate random effects model appropriate for analysis of longitudinal data, which enables the identification of two independent levels of correlation between pairs of pathogens. At the microbe level, rhinovirus infection was positively correlated with carriage of S. pneumoniae, H. influenzae and M. catarrhalis, and adenovirus with M. catarrhalis. Generally, there were positive associations between bacterial pathogens at both the host and microbe level. Positive viral–bacterial associations at the microbe level support previous findings indicating that viral infection can predispose an individual to bacterial carriage. Viral vaccines may assist in reducing the burden of bacterial disease.

Susceptibility of pneumococcal carriage isolates to penicillin provides a conservative estimate of susceptibility of invasive pneumococci.

OBJECTIVE Because of its practical importance for public health monitoring in developing countries, we aimed to determine whether susceptibility to penicillin of pneumococci isolated from the upper respiratory tract (URT) is representative of the susceptibility of pneumococci causing pneumonia in children. METHOD The serogroup distribution and minimum inhibitory concentration of penicillin for 56 and 90 isolates from blood and cerebrospinal fluid, respectively, were compared with those of 833 pneumococcal carriage isolates from Papua New Guinean children. These included 154 and 98 strains from bacteremic and nonbacteremic hospitalized patients with pneumonia, respectively, 350 from outpatients with respiratory infections and 176 and 55, respectively, from children in a community-based study who were healthy or sick with pneumonia. RESULTS Proportions of pneumococci intermediately resistant to penicillin were comparable in the URT and blood (60%) in 1985 through 1987 when serogroup distributions in the two sites were similar. However, penicillin resistance was higher in the URT (75%) than blood (44%) in 1980 through 1984 when the less frequently carried, less resistant serogroups (1 to 5, 7 to 12, 45 and 46) accounted for a high proportion of bacteremic strains. CONCLUSIONS URT isolates from any group of sick or healthy children could provide a conservative estimate of antimicrobial susceptibility of invasive strains and is a practical way of monitoring susceptibility as well as evaluating the continued effectiveness of standard antibiotic therapy. If there was cause for concern, it would then be necessary to examine invasive isolates.

Benefits of swimming pools in two remote Aboriginal communities in Western Australia: intervention study

Abstract Objective To determine the health impact of swimming pools built with the aim of improving quality of life and reducing high rates of pyoderma and otitis media. Design Intervention study assessing prevalence of ear disease and skin infections before and at six monthly intervals after opening of swimming pools. Setting Two remote Aboriginal communities in Western Australia. Participants 84 boys and 78 girls aged < 17 years. Main outcome measures Changes in prevalence and severity of pyoderma and perforation of tympanic membranes with or without otorrhoea over 18 months after opening of pools. Results In community A, 61 children were seen before the pool was opened, and 41, 46, and 33 children were seen at the second, third, and fourth surveys. Equivalent figures for community B were 60, 35, 39, and 45. Prevalence of pyoderma declined significantly from 62% to 18% in community A and from 70% to 20% in community B during the 18 months after the pools opened. Over the same period, prevalence of severe pyoderma fell from 30% to 15% in community A and from 48% to 0% in community B. Prevalence of perforations of the tympanic membrane fell from 32% in both communities to 13% in community A and 18% in community B. School attendance improved in community A. Conclusion Swimming pools in remote communities were associated with reduction in prevalence of pyoderma and tympanic membrane perforations, which could result in long term benefits through reduction in chronic disease burden and improved educational and social outcomes.

Crowding and other strong predictors of upper respiratory tract carriage of otitis media-related bacteria in Australian aboriginal and non-aboriginal children

Background: Streptococcus pneumoniae, Moraxella catarrhalis, and nontypeable Haemophilus influenzae is associated with otitis media (OM). Data are limited on risk factors for carriage of these pathogens, particularly for Indigenous populations. We investigated predictors of nasopharyngeal carriage in Australian Aboriginal and non-Aboriginal children. Methods: Nasopharyngeal aspirates were collected up to 7 times before age 2 years from 100 Aboriginal and 180 non-Aboriginal children. Longitudinal modeling estimated effects of environmental factors and concurrent carriage of other bacteria on the probability of bacterial carriage. We present a novel method combining the effects of number of household members and size of house into an overall crowding model. Results: Each additional household member increased the risk of carriage of S. pneumoniae (odds ratio [OR] = 1.45 per additional Aboriginal child in a 4-room house, 95% confidence interval [CI]: 1.15–1.84; OR = 2.34 per additional non-Aboriginal child, 95% CI: 1.76–3.10), with similar effect sizes for M. catarrhalis, and nontypeable Haemophilus influenzae. However, living in a larger house attenuated this effect among Aboriginal children. Daycare attendance predicted carriage of the 3 OM-associated bacteria among non-Aboriginal children. Exclusive breast-feeding at 6 to 8 weeks protected against Streptococcus aureus carriage (OR = 0.42, 95% CI: 0.19–0.90 in Aboriginal children and OR = 0.49, 95% CI: 0.25–0.96 in non-Aboriginal children). OM-associated bacteria were more likely to be present if there was concurrent carriage of the other OM-associated species. Conclusions: This study highlights the importance of household transmission in carriage of OM bacteria, underscoring the need to reduce the crowding in Aboriginal households.