Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

Identification of Streptococcus pneumoniae in hospital-acquired pneumonia in adults.

Hospital-acquired pneumonia (HAP) is often more severe and life-threatening than community-acquired pneumonia (CAP). The role of Streptococcus pneumoniae in CAP is well-understood, but its role in HAP is unclear. The objective of this study was to summarize the available literature on the prevalence of S. pneumoniae in HAP episodes. We searched MEDLINE for peer-reviewed articles on the microbiology of HAP in individuals aged ≥18 years, published between 2008 and 2018. We calculated pooled estimates of the prevalence of S. pneumoniae in episodes of HAP using a random-effects, inverse-variance-weighted meta-analysis. Forty-seven of 1908 articles met the inclusion criteria. Bacterial specimen isolation techniques for microbiologically defined HAP episodes included bronchoalveolar lavage, protective specimen brush, tracheobronchial aspirate and sputum, as well as blood culture. Culture was performed in all studies; five studies also used urine antigen detection (5/47; 10.6%). S. pneumoniae was identified in 5.1% (95% confidence interval (CI): 3.8-6.6%) of microbiologically defined HAP episodes (N = 20), with 5.4% (95% CI: 4.3-6.7%, N = 29) in ventilator-associated HAP and 6.0% (95% CI: 4.1-8.8%, N = 6) in non-ventilator-associated HAP. S. pneumoniae was identified in 5.3% (95% CI: 4.5-6.3%) of HAP occurring in the intensive care unit (ICU, N = 41) and in 5.6% (95% CI: 3.3-9.5%, N = 5) outside the ICU. A higher proportion of early-onset HAP (10.3%; 95% CI: 8.3-12.8%, N = 16) identified S. pneumoniae as compared with late-onset HAP (3.3%; 95% CI: 2.5-4.4%, N = 16). In conclusion, S. pneumoniae was identified by culture in 5.1% of microbiologically defined HAP episodes. The importance of HAP as part of the disease burden caused by S. pneumoniae merits further research.

Updated recommendations of the International Dengue Initiative expert group for CYD-TDV vaccine implementation in Latin America.

Dengue disease represents a large and growing global threat to public health, causing a significant burden to health systems of endemic countries. For countries considering vaccination as part of their Integrated Management Strategy for Prevention and Control of Dengue, the World Health Organization currently recommends the first licensed dengue vaccine, CYD-TDV for: individuals aged 9 years or above from populations with high transmission rates, based on either seroprevalence criteria or pre-vaccination screening strategies, and for persons with confirmed prior exposure to infection in moderate to lower transmission settings. This paper describes the main conclusions of the Sixth Meeting of the International Dengue Initiative (IDI) held in June 2018, following release of a new product label by the manufacturer, updated WHO-SAGE recommendations, additional scientific evidence on vaccine performance, and reports of experiences by implementing countries. Considerations were made regarding the need for improving the quality of epidemiological and surveillance data in the region to help define the convenience of either of the two vaccination strategies recommended by WHO-SAGE. Extensive discussion was dedicated to the pros and cons of implementing either of such strategies in Latin America. Although, in general, a seroprevalence-based approach was preferred in high transmission settings, when cost-effectivity is favorable pre-vaccination screening is a convenient alternative. Cost-effectiveness evaluations can assist with the decisions by public health authorities of whether to introduce a vaccine. Where implemented, vaccine introduction should be part of a public health strategy that includes the participation of multiple sectors of society, incorporating input from scientific societies, ministries of heath, and civil society, while ensuring a robust communication program.

The public health value of vaccines beyond efficacy: methods, measures and outcomes.

BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination. CONCLUSIONS: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions.

Evaluation of chest radiography, lytA real-time PCR, and other routine tests for diagnosis of community-acquired pneumonia and estimation of possible attributable fraction of pneumococcus in northern Togo.

Streptococcus pneumoniae (Spn) is a leading cause of community-acquired pneumonia (CAP), yet existing diagnostic tools remain inadequate. We aimed to evaluate laboratory and radiological methods for detecting pneumococcal aetiology in CAP patients and to estimate Spn prevalence in this group. All-aged patients hospitalized with clinically defined CAP in northern Togo were enrolled during 2010-2013. Latent class analysis pooled results of semi-automated blood culture (SABC), whole blood lytA real-time polymerase chain reaction (rt-PCR), serum C-reactive protein (CRP), and chest radiography (CXR) and categorized patients as likely pneumococcal or non-pneumococcal CAP. We enrolled 1684 patients; 1501 had results for all tests. CXR, SABC, lytA rt-PCR and CRP >71·2 mg/l had sensitivities of 94% [95% confidence interval (CI) 87-100], 13% (95% CI 10-16), 17% (95% CI 14-21) and 78% (95% CI 75-80), and specificities of 88% (95% CI 84-93), 100% (95% CI 99-100), 97% (95% CI 96-99) and 77% (95% CI 75-79), respectively. Pneumococcal attributable proportion was 34% (95% CI 32-37), increasing with age and in men. We estimated that Spn caused one third of CAP. Whole blood lytA rt-PCR was more sensitive than SABC; both had low sensitivity and high specificity. Conversely CXR was highly sensitive and reasonably specific; it could be a useful tool for epidemiological studies aiming to define Spn pneumonia incidence across all ages.

Maternal influenza and birth outcomes: systematic review of comparative studies.

BACKGROUND: Although pregnant women are considered at high risk for severe influenza disease, comparative studies of maternal influenza and birth outcomes have not been comprehensively summarised. OBJECTIVE: To review comparative studies evaluating maternal influenza disease and birth outcomes. SEARCH STRATEGY: We searched bibliographic databases from inception to December 2014. SELECTION CRITERIA: Studies of preterm birth, small-for-gestational-age (SGA) birth or fetal death, comparing women with and without clinical influenza illness or laboratory-confirmed influenza infection during pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed study quality. MAIN RESULTS: Heterogeneity across 16 studies reporting preterm birth precluded meta-analysis. In a subgroup of the highest-quality studies, two reported significantly increased preterm birth (risk ratios (RR) from 2.4 to 4.0) following severe 2009 pandemic H1N1 (pH1N1) influenza illness, whereas those assessing mild-to-moderate pH1N1 or seasonal influenza found no association. Five studies of SGA birth showed no discernible patterns with respect to influenza disease severity (pooled odds ratio 1.24; 95% CI 0.96-1.59). Two fetal death studies were of sufficient quality and size to permit meaningful interpretation. Both reported an increased risk of fetal death following maternal pH1N1 disease (RR 1.9 for mild-to-moderate disease and 4.2 for severe disease). CONCLUSIONS: Comparative studies of preterm birth, SGA birth and fetal death following maternal influenza disease are limited in number and quality. An association between severe pH1N1 disease and preterm birth and fetal death was reported by several studies; however, these limited data do not permit firm conclusions on the magnitude of any association. TWEETABLE ABSTRACT: Comparative studies are limited in quality but suggest severe pandemic H1N1 influenza increases preterm birth.

Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies.

Streptococcus pneumoniae serotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3 S. pneumoniae serotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%, P < 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P < 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

Impact of the Hajj on pneumococcal transmission.

Over two million Muslim pilgrims assemble annually in Mecca and Medina, Saudi Arabia, to complete the Hajj. The large number of people in a crowded environment increases the potential for pneumococcal carriage amplification. We evaluated pneumococcal carriage prevalence with four cross-sectional studies conducted at beginning-Hajj (Mecca) and end-Hajj (Mina) during 2011 and 2012. A questionnaire was administered and a nasopharyngeal swab was collected. The swab was tested for pneumococcus, serotype and antibiotic resistance. A total of 3203 subjects (1590 at beginning-Hajj and 1613 at end-Hajj) originating from 18 countries in Africa or Asia were enrolled. The overall pneumococcal carriage prevalence was 6.0%. There was an increase in carriage between beginning-Hajj and end-Hajj cohorts for: overall carriage (4.4% versus 7.5%, prevalence ratio (PR) 1.7, 95% CI 1.3-2.3), and carriage of 23-valent pneumococcal polysaccharide vaccine serotypes (2.3% versus 4.1%, PR 1.8, 95% CI 1.2-2.7), 13-valent pneumococcal conjugate vaccine (PCV) serotypes (1.1% versus 3.6%, PR 3.2, 95% CI 1.9-5.6), 10-valent PCV serotypes (0.6% versus 1.6%, PR 2.6, 95% CI 1.2-5.3), antibiotic non-susceptible isolates (2.5% versus 6.1%, PR 2.5, 95% CI 1.7-3.6) and multiple non-susceptible isolates (0.6% versus 2.2%, PR 3.8, 95% CI 1.8-7.9). Fifty-two different serotypes were identified, most commonly serotypes 3 (17%), 19F (5%) and 34 (5%). These results suggest that the Hajj may increase pneumococcal carriage-particularly conjugate vaccine serotypes and antibiotic non-susceptible strains, although the exact mechanism remains unknown. The Hajj may therefore provide a mechanism for the global distribution of pneumococci.

Adverse events following yellow fever preventive vaccination campaigns in eight African countries from 2007 to 2010.

BACKGROUND: Serious, but rare adverse events following immunization (AEFI) have been reported with yellow fever (YF) 17D vaccine, including severe allergic reactions, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). The frequency with which YEL-AND and YEL-AVD occur in YF endemic countries is mostly unknown. METHODS: From 2007 to 2010, eight African countries - Benin, Cameroon, Guinea, Liberia, Mali, Senegal, Sierra Leone, and Togo- implemented large-scale YF preventive vaccination campaigns. Each country established vaccine pharmacovigilance systems that included standard case definitions, procedures to collect and transport biological specimens, and National Expert Committees to review data and classify cases. Staff in all countries received training and laboratory capacity expanded. RESULTS: In total, just over 38 million people were vaccinated against YF and 3116 AEFIs were reported of which 164 (5%) were classified as serious. Of these, 22 (13%) were classified as YF vaccine reactions, including 11 (50%) hypersensitivity reactions, six (27%) suspected YEL-AND, and five (23%) suspected YEL-AVD. The incidence per 100,000 vaccine doses administered was 8.2 for all reported AEFIs, 0.43 for any serious AEFI, 0.058 for YF vaccine related AEFIs, 0.029 for hypersensitivity reactions, 0.016 for YEL-AND, and 0.013 for YEL-AVD. Our findings were limited by operational challenges, including difficulties in obtaining recommended biological specimens leading to incomplete laboratory evaluation, unknown case ascertainment, and variable levels of staff training and experience. CONCLUSIONS: Despite limitations, active case-finding in the eight different countries did not find an incidence of YF vaccine associated AEFIs that was higher than previous reports. These data reinforce the safety profile of YF vaccine and support the continued use of attenuated YF vaccine during preventive mass vaccination campaigns in YF endemic areas.

Improving influenza surveillance in sub-Saharan Africa.

PROBLEM: Little is known about the burden of influenza in sub-Saharan Africa. Routine influenza surveillance is key to getting a better understanding of the impact of acute respiratory infections on sub-Saharan African populations. APPROACH: A project known as Strengthening Influenza Sentinel Surveillance in Africa (SISA) was launched in Angola, Cameroon, Ghana, Nigeria, Rwanda, Senegal, Sierra Leone and Zambia to help improve influenza sentinel surveillance, including both epidemiological and virological data collection, and to develop routine national, regional and international reporting mechanisms. These countries received technical support through remote supervision and onsite visits. Consultants worked closely with health ministries, the World Health Organization, national influenza laboratories and other stakeholders involved in influenza surveillance. LOCAL SETTING: Influenza surveillance systems in the target countries were in different stages of development when SISA was launched. Senegal, for instance, had conducted virological surveillance for years, whereas Sierra Leone had no surveillance activity at all. RELEVANT CHANGES: Working documents such as national surveillance protocols and procedures were developed or updated and training for sentinel site staff and data managers was organized. LESSONS LEARNT: Targeted support to countries can help them strengthen national influenza surveillance, but long-term sustainability can only be achieved with external funding and strong national government leadership.

Afriflu--international conference on influenza disease burden in Africa, 1-2 June 2010, Marrakech, Morocco.

The burden of influenza disease is to a large extent unknown for the African continent. Moreover, the interaction of influenza with common infectious diseases in Africa remains poorly described. Solid scientific evidence on the influenza disease burden in Africa is critical for the development of effective influenza vaccine policies. On 1st and 2nd June 2010 in Marrakech, Morocco, over eighty surveillance and influenza experts from 22 African countries as well as Europe and America met at the 'Afriflu' conference to discuss influenza challenges and solutions for the continent. During the meeting, participants exchanged their experiences and discussed a wide variety of topics related to influenza in Africa, including diagnosis, surveillance, epidemiology, and interventions. The meeting concluded with a pledge to improve influenza knowledge and awareness in Africa, with an emphasis on accurate determination of disease burden to help orient public health policies.

Climatic, temporal, and geographic characteristics of respiratory syncytial virus disease in a tropical island population.

Respiratory syncytial virus (RSV) is an important cause of morbidity in children worldwide, although data from equatorial regions are limited. We analysed climatic, spatial, and temporal data for children presenting to hospitals in Lombok island, Indonesia with clinical pneumonia. During the study period, 2878 children presented and 741 RSV cases were identified. In multivariate analysis with an 8-day lag, occurrence of rain was associated with 64% higher incidence of RSV disease [incidence rate ratio (IRR) 1.64, 95% confidence interval (CI) 1.13-2.38]. A 1% rise in mean relative humidity and 1 degree C increase in mean air temperature was associated with a 6% (IRR 1.06, 95% CI 1.03-1.10) and 44% (IRR 1.44, 95% CI 1.24-1.66) increase in RSV cases, respectively. Four statistically significant local clusters of RSV pneumonia were identified within the annual island-wide epidemics. This study demonstrates statistical association of monsoon-associated weather in equatorial Indonesia with RSV. Moreover, within the island-wide epidemics, localized RSV outbreaks suggest local factors influence RSV disease.

Evaluation of the Pastorex meningitis kit for the rapid identification of Neisseria meningitidis serogroups A and W135.

The recent emergence of Neisseria meningitidis W135 as a cause of epidemic bacterial meningitis and the availability of a trivalent ACW135 vaccine have created a need for accurate and timely meningococcal serogroup determination for organization of epidemic vaccine response. The sensitivity and specificity of the Pastorex meningitis kit (Bio-Rad) to identify serogroups A and W135 in the African meningitis belt was assessed using PCR testing as the gold standard. The sensitivity and specificity for serogroups A and W135 were 87 and 85%, respectively, while the specificities were 93 and 97%. The positive and negative likelihood ratios for A were 12 and 0.14 and for W135 were 33 and 0.16. The positive and negative predictive values, computed to simulate an epidemic of meningococcal meningitis with an estimated 70% prevalence of N. meningitidis among suspected cases, were 97% and 75% for A and 99% and 73% for W135. In remote locations of the African meningitis belt, latex agglutination is the only currently available test that can rapidly determine meningococcal serogroup. This study showed that latex agglutination performs well and could be used during the epidemic season to determine appropriate vaccine response.

Aetiologies and risk factors for neonatal sepsis and pneumonia mortality among Alaskan infants.

We evaluated all fatal neonatal sepsis and pneumonia cases occurring in Alaska during 1992-2000. Risk factors were evaluated using a database of all births occurring during the study period. Of 32 cases, group B streptococcus (GBS) was isolated from 21% (all 7 days of age), non-GBS Gram-positive bacteria from 50% (53% <7 days of age), and Gram-negative infections from 38% (58% <7 days of age). Infants born at <37 weeks gestation accounted for 72% of cases and had an increased risk of GBS [rate ratio (RR) 9.1, 95% confidence interval (CI) 2.0-41] and non-GBS (RR 40, 95% CI 16-101) disease. Neonatal sepsis mortality has become an outcome concentrated among pre-term infants. Aetiologies include GBS during the early neonatal period, Candida spp. during the late neonatal period, and other bacteria during both periods.

Incidence and etiological agents of bacterial meningitis among children <5 years of age in two districts of Romania.

To expand upon the limited comprehensive population-based data for childhood bacterial meningitis in Eastern Europe, the present study was conducted in the Iasi and Constanta districts of Romania. From March 2000 through March 2002, children <5 years of age hospitalized for bacterial meningitis were enrolled in a prospective surveillance study. A total of 56 cases of bacterial meningitis were identified, including 37 due to Neisseria meningitidis (22 per 100,000 per year), 13 due to Haemophilus influenzae type b (7.6 per 100,000 per year), and six due to Streptococcus pneumoniae (3.5 per 100,000 per year). Of the 31 meningococcal isolates that were serotyped, 12 were serogroup A, eight were serogroup B, and 11 were serogroup C. Among all cases of bacterial meningitis, 25 occurred in children <1 year of age, including those due to meningococci (n=14), H. influenzae type b (n=7), pneumococci (n=3), and Klebsiella pneumoniae (n=1). In Romania the incidence of H. influenzae type b meningitis is similar to that found in other areas of Southern and Eastern Europe during the pre-vaccination era, and the incidence of meningococcal meningitis is one of the highest yet found in Europe. An unexpectedly high proportion of these meningococcal meningitis cases is due to serogroup A. Disease burden could be substantially reduced through the introduction of H. influenzae type b conjugate vaccine and, when available, meningococcal conjugate vaccine protective against serogroups A, B and C.

Over-representation of Samoan/Pacific Islanders among patients with methicillin-resistant Staphylococcus aureus (MRSA) infections at a large family practice clinic in Anchorage, Alaska, 1996-2000.

Two pediatricians in Anchorage observed that among patients of Samoan/Pacific Islander (S/PI) descent, bacterial wound cultures that grew Staphylococcus aureus often yielded methicillin-resistant isolates. The Alaska Section of Epidemiology performed chart reviews of patients that visited a large family practice clinic in Anchorage, Alaska, from 1996 through April 2000, and who were diagnosed with a skin infection. Eight of 204 patients were identified with culture-confirmed MRSA infections. Eighty percent (4 of 5) of S/PI patients had resistant isolates compared with 12% (4 of 34) of non S/PI patients (Yates corrected chi2 = 8.61, p-value = 0.003). Although subject to limitations, these data support similar findings documented by other studies that suggest MRSA infections disproportionately affect persons of S/PI origin. This study also suggests that it would be prudent to reduce the threshold of clinical suspicion for obtaining a skin culture among S/PI patients in Alaska, and avoid beta-lactam antibiotics until culture results are received.

Worldwide variation in the incidence of Haemophilus influenzae type b meningitis and its association with ampicillin resistance.

Some areas of the world are known to have a low incidence of Haemophilus influenzae type b meningitis, although the reasons for this are unknown. Furthermore, no complete evaluation of the worldwide variation in the incidence of Haemophilus influenzae type b meningitis has been published. In the current study, the published medical literature was reviewed to identify all studies conducted in the absence of routine childhood Haemophilus influenzae type b conjugate vaccination that reported an incidence of Haemophilus influenzae type b meningitis among children less than 5 years of age. To test the hypothesis that antibiotic use may have influenced the incidence of meningitis, incidence rates were correlated with antibiotic resistance. Seventy-one articles reported an incidence of childhood Haemophilus influenzae type b meningitis (median, 21 cases per 100,000 population per year; range, 1-95 cases per 100,000 population per year), with Asia and central/southern Europe reporting lower incidences than other areas (median, 5 and 11 cases per 100,000 per year, respectively). Within these regions of low incidence, the proportion of cerebrospinal fluid specimens that had a leukocyte count or glucose or protein level suggestive of bacterial meningitis but from which no organism was identified was low, indicating that there was no large reservoir of Haemophilus influenzae type b meningitis that went undetected by the laboratory. Study-specific incidence rates of meningitis correlated with the proportion of isolates resistant to ampicillin (or producing beta-lactamase) (R2=0.35. P=0.0014). The incidence of Haemophilus influenzae type b meningitis is substantially lower in some areas of the world than others, but this difference is unlikely to be related primarily to laboratory methodology. In contrast, antibiotic use may contribute to the observed differences in incidence.

Association between sudden infant death syndrome and prone sleep position, bed sharing, and sleeping outside an infant crib in Alaska.

OBJECTIVE: To determine the contribution of prone sleeping, bed sharing, and sleeping outside an infant crib to sudden infant death syndrome (SIDS). METHODS: We conducted a retrospective descriptive study of all SIDS cases in Alaska from January 1, 1992, through December 31, 1997. Reviewed data sources included maternal and infant medical records, autopsy reports, birth and death certificates, police and state trooper death scene investigations, and occasionally home interviews. RESULTS: The death certificate identified SIDS as a cause of death for 130 infants (cause-specific infant mortality rate: 2.0 per 1000 live births). Among infants for whom this information was known, 113 (98%) of 115 were found in the prone position, sleeping outside an infant crib, or sleeping with another person. By contrast, 2 (1.7%) were found alone and supine in their crib (1 of whom was found with a blanket wrapped around his face). Of 40 infants who slept with a parent at the time of death, only 1 infant who slept supine with a non-drug-using parent on an adult nonwater mattress was identified. CONCLUSION: Almost all SIDS deaths in Alaska occurred in association with prone sleeping, bed sharing, or sleeping outside a crib. In the absence of other risk factors, SIDS deaths associated with parental bed sharing were rare.

Perinatal care regionalization and low birth weight infant mortality rates in Alaska.

OBJECTIVE: The purpose of this study was to determine the extent to which the failure of non-tertiary care hospitals to appropriately triage and refer pregnant women and newborns contributes to low birth weight infant death in Alaska. STUDY DESIGN: Birth certificates from 1993 to 1997 were reviewed for all 2809 infants who were born at less than 2500 g. Death certificates and maternal and infant medical charts were reviewed for all 168 infant deaths that occurred during this time. RESULTS: Mother-infant pairs who received all care at Alaska's single tertiary care center had a lower mortality rate than those who received some care at a non-tertiary care center (risk ratio, 1.5; 95% confidence interval, 0.86-2.6). Despite this, only 4% of deaths among low birth weight infants (all <1500 g) were associated with care decisions at non-tertiary centers; none of these deaths involved intentional inappropriate retention of infants or mothers. CONCLUSION: Further emphasizing perinatal care regionalization (including for infants 1500-2499 g birth weight) is unlikely to substantially decrease low birth weight infant mortality rates.

Comparison of cost-effectiveness of preventive and reactive mass immunization campaigns against meningococcal meningitis in West Africa: a theoretical modeling analysis.

For epidemic meningitis control in sub-Saharan Africa, the World Health Organization recommends a strategy of emergency vaccination with meningococcal A + C polysaccharide vaccine when epidemic thresholds are exceeded. An alternative strategy for areas without effective surveillance systems is mass preventive campaigns before outbreaks occur. A model was formulated to simulate epidemics and to compare the cost-effectiveness of these two strategies for the district of Matam, Senegal, where an actual preventive campaign was performed during 1997. The preventive strategy prevented 59% of the cases compared to 49% for the emergency strategy. The cost per case prevented was US$59 for the preventive strategy and US$133 for the reactive strategy, and the preventive strategy saved US$0.20 per habitant. Preventive meningococcal vaccination through mass campaigns prevented more outcomes at a lower cost, provided that the occurrence of an epidemic could be predicted within 3 years and that the vaccination coverage rates for the preventive and standard strategies were > 70% and < 94%, respectively. Sub-Saharan African countries without effective surveillance systems should consider mass preventive campaigns while awaiting an affordable conjugate vaccine.