PCV7-induced changes in pneumococcal carriage and invasive disease burden in Alaskan children.

BACKGROUND: Changes in pneumococcal serotype-specific carriage and invasive pneumococcal disease (IPD) after the introduction of pneumococcal conjugate vaccine (PCV7) could inform serotype epidemiology patterns following the introduction of newer conjugate vaccines. METHODS: We used data from statewide IPD surveillance and annual pneumococcal carriage studies in four regions of Alaska to calculate serotype-specific invasiveness ratios (IR; odds ratio of a carried serotype's likelihood to cause invasive disease compared to other serotypes) in children <5 years of age. We describe changes in carriage, disease burden, and invasiveness between two time periods, the pre-PCV7 period (1996-2000) and the late post-PCV7 period (2006-2009). RESULTS: Incidence of IPD decreased from the pre- to post-vaccine period (95.7 vs. 57.2 cases per 100,000 children, P<0.001), with a 99% reduction in PCV7 disease. Carriage prevalence did not change between the two periods (49% vs. 50%), although PCV7 serotype carriage declined by 97%, and non-vaccine serotypes increased in prevalence. Alaska pre-vaccine IRs corresponded to pooled results from eight pre-vaccine comparator studies (Spearman's rho=0.44, P=0.002) and to the Alaska post-vaccine period (Spearman's rho=0.28, P=0.029). Relatively invasive serotypes (IR>1) caused 66% of IPD in both periods, although fewer serotypes with IR>1 remained in the post-vaccine (n=9) than the pre-vaccine period (n=13). CONCLUSIONS: After PCV7 introduction, serotype IRs changed little, and four of the most invasive serotypes were nearly eliminated. If PCV13 use leads to a reduction of carriage and IPD for the 13 vaccine serotypes, the overall IPD rate should further decline. NOTE: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Migration of persons between households in rural Alaska: considerations for study design.

INTRODUCTION: Recent epidemiologic research studies in rural Alaska have examined risk factors for infectious diseases collected at the household level. Examples include the health effects of in-home piped water and household air quality. Because the exposure is measured at the household level, it is necessary to determine if participants remained in the same house throughout the course of follow-up. METHODS: We used data from a pneumococcal nasopharyngeal carriage study in 8 rural Alaska villages [3 regions; average number of persons: 642 (min 210, max 720 per village) to quantify changes in household membership and individual movements from 2008 to 2010. We define a household as a group of individuals living in a home together. Because the same households participated in carriage surveys over several years, we could determine changes on an annual basis. We calculated the percentage of households with a ≥ 1 person change in household members from year to year. Additionally, we present the percentage of individuals that changed households during consecutive years. RESULTS: In 3 regions of Alaska, the average household size was 5 persons. Between 2008 and 2009, 50% (250/497) of households had a change in their membership (≥ 1 person in-migrated or out-migrated). Fifty-three percent of households experienced some migration of their members between 2009 and 2010. A total of 27 and 15% of households had a change of ≥ 2 and ≥ 3 persons, respectively. The percentage of households with movement was similar among the 3 rural regions and varied from 42 to 63% between villages. At the individual level, an average of 11% of persons changed households between years. The group with the most movement between houses was persons 18-29 years of age (19%), and least movement was in 5-10 and 50-64 years of age (6%). There was no difference in movement by gender. CONCLUSIONS: In rural Alaska, 52% of households experienced movement of members between years and 11% of individuals change households. These are important demographic figures to consider when planning and designing studies that measure an epidemiological exposure at the household level. Power and sample size calculations should account for the loss to follow-up associated with in- and out-migration of individuals from households.

Haemophilus influenzae serotype a invasive disease, Alaska, USA, 1983-2011.

Before introduction of Haemophilus influenzae type b (Hib) vaccines, rates of Hib disease in Alaska's indigenous people were among the highest in the world. Vaccination reduced rates dramatically; however, invasive H. influenzae type a (Hia) disease has emerged. Cases of invasive disease were identified through Alaska statewide surveillance during 1983-2011. Of 866 isolates analyzed for serotype, 32 (4%) were Hia. No Hia disease was identified before 2002; 32 cases occurred during 2002-2011 (p<0.001). Median age of case-patients was 0.7 years; 3 infants died. Incidence of Hia infection (2002-2011) among children <5 years was 5.4/100,000; 27 cases occurred in Alaska Native children (18/100,000) versus 2 cases in non-Native children (0.5/100,000) (risk ratio = 36, p<0.001). From 12/2009 to 12/2011, 15 cases of Hia disease occurred in southwestern Alaska (in children <5 years, rate = 204/100,000). Since introduction of the Hib conjugate vaccine, Hia infection has become a major invasive bacterial disease in Alaska Native children.

Poliovirus vaccination options for achieving eradication and securing the endgame.

In 1988, the World Health Assembly resolved to globally eradicate poliomyelitis. As part of a four-pronged strategy with establishment of enhanced surveillance, institution of national immunization days, strengthening routine immunization, and carrying-out mopping-up activities, oral poliovirus vaccine (OPV) was selected as the vaccine-of-choice for eradication. Massive OPV use decreased the number of polio-endemic countries from >125 countries in 1988 to only 3 in 2012 and led to a >99.9% decrease in polio incidence in the corresponding period. In this communication, we will discuss polio vaccination options to accelerate eradication, to mitigate the risks during the planned withdrawal of type 2 OPV, and to secure eradication for future generations.

Molecular characterization of Streptococcus pneumoniae serotype 12F isolates associated with rural community outbreaks in Alaska.

Outbreaks of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 12F were observed in two neighboring regions of rural Alaska in 2003 to 2006 and 2006 to 2008. IPD surveillance data from 1986 to 2009 and carriage survey data from 1998 to 2004 and 2008 to 2009 were reviewed to identify patterns of serotype 12F transmission. Pulsed-field gel electrophoresis was performed on all available isolates, and selected isolates were characterized by additional genetic subtyping methods. Serotype 12F IPD occurred in two waves in Alaska between 1986 and 2008. While cases of disease occurred nearly every year in Anchorage, in rural regions, 12F IPD occurred with rates 10- to 20-fold higher than those in Anchorage, often with many years between disease peaks and generally caused by a single predominant genetic clone. Carriage occurred predominantly in adults, except early in the rural outbreaks, when most carriage was in persons <18 years old. In rural regions, carriage of 12F disappeared completely after outbreaks. Different 12F clones appear to have been introduced episodically into rural populations, spread widely in young, immunologically naïve populations (leading to outbreaks of IPD lasting 1 to 3 years), and then disappeared rapidly from the population. Larger population centers might have been the reservoir for these clones. This epidemiologic pattern is consistent with a highly virulent, but immunogenic, form of pneumococcus.

Trends in lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general US child population.

OBJECTIVE: To describe trends in the rate of hospitalization for lower respiratory tract infection (LRTI) among American Indian/Alaska Native (AI/AN) children and the general US population of children aged <5 years. STUDY DESIGN: This was a retrospective analysis of trends and hospitalization rates for LRTI-associated hospitalizations in 1998-2008 among AI/AN children aged <5 years using the Indian Health Service direct/contract inpatient data, and also among the general population of US children aged <5 years using the Nationwide Inpatient Sample. RESULTS: The 2006-2008 LRTI-associated hospitalization rate for AI/AN children aged <5 years (21.8 per 1000/year) was 32% lower than the 1998-1999 rate, and 1.6-fold higher than the general US children rate (13.8 per 1000/year; 95% CI, 12.8-14.8). Higher rates were seen in AI/AN children aged <5 years in the Alaska and the Southwest regions of the United States (41.2 and 28.0 per 1000/year, respectively). In infants, these rates were 136.4 and 82.4 per 1000/year, respectively, exceeding the rate in the general US infant population (37.1 per 1000/year; 95% CI, 34.3-40.0). The greatest disparity in the LRTI-associated hospitalization rate between AI/AN infants and the general US infant population was seen for pneumonia, with a 3-fold higher rate in AI/AN infants (36.2 per 1000/year vs 12.7 per 1000/year; 95% CI, 11.8-13.6). CONCLUSION: The LRTI-associated hospitalization rate is higher in AI/AN children, particularly infants from Alaska and the American Southwest, compared with the general US child population. Closing this gap will require addressing housing and sanitation inequities and ensuring high immunization rates and access to care.

Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs.

In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.

Poliomyelitis-related case-fatality ratio in India, 2002-2006.

BACKGROUND: On the basis of studies from developed countries, the case-fatality ratio (CFR) of poliomyelitis generally ranges from 2%-5% among children <5 years of age to 10%-30% among adults. However, little information is available for poliomyelitis-related CFR in developing countries. We conducted a study to determine the CFR in India, 1 of the 4 remaining countries with endemic wild poliovirus (WPV) circulation, during outbreaks of WPV infection during 2002 and 2006 and during the inter-epidemic years of 2003-2005. METHODS: We conducted a descriptive analysis with use of data from the acute flaccid paralysis surveillance system in India. Variables analyzed included age, caregiver-reported vaccination status, date of paralysis onset, laboratory results, final case classification, and survival outcome. Our analysis also accounted for surveillance changes that occurred in 2005, impacting case definitions and final classification. RESULTS: In 2006, 45 deaths occurred among 676 WPV cases in India, yielding a CFR of 6.7%. By comparison, in 2002, there were 66 deaths among 1600 reported WPV cases (CFR, 4.2%) and during 2002-2005, CFR was 1.5%-5.2%. All 45 deaths were among 644 (95%) WPV cases in children aged <5 years (CFR, 7.0%). Among those who died, 33 (73%) were children aged <2 years (CFR, 7.1%). CONCLUSIONS: The CFR among children aged <2 years in India is high compared with previously published CFRs for young children, in part because of improved case finding through enhanced surveillance techniques. Fatal cases emphasize the lethal nature of the disease and the importance of achieving polio eradication in India.

2009 Pandemic influenza A H1N1 in Alaska: temporal and geographic characteristics of spread and increased risk of hospitalization among Alaska Native and Asian/Pacific Islander people.

Alaska Native people have suffered disproportionately from previous influenza pandemics. We evaluated 3 separate syndromic data sources to determine temporal and geographic patterns of spread of 2009 pandemic influenza A H1N1 (pH1N1) in Alaska, and reviewed records from persons hospitalized with pH1N1 disease in 3 areas in Alaska to characterize clinical and epidemiologic features of disease in Alaskans. A wave of pH1N1 disease swept through Alaska beginning in most areas in August or early September. In rural regions, where Alaska Native people comprise a substantial proportion of the population, disease occurred earlier than in other regions. Alaska Native people and Asian/Pacific Islanders (A/PI) were 2-4 times more likely to be hospitalized than whites. Alaska Native people and other minorities remain at high risk for early and substantial morbidity from pandemic influenza episodes. These findings should be integrated into plans for distribution and use of vaccine and antiviral agents.

Invasive pneumococcal disease in Alaskan children: impact of the seven-valent pneumococcal conjugate vaccine and the role of water supply.

BACKGROUND: Alaska Native (AN) children, especially those in the Yukon-Kuskokwim region (YK-AN children), suffer some of the highest rates of invasive pneumococcal disease (IPD) in the world. Rates of IPD declined after statewide introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2001, but increased in subsequent years. METHODS: Population-based laboratory surveillance data (1986-2007) for invasive Streptococcus pneumoniae infection in Alaskan children <5 years old were used to evaluate the association of IPD rates and serotype distribution with immunization, socioeconomic status, and in-home water service. RESULTS: Introduction of PCV7 vaccine resulted in elimination of IPD caused by vaccine serotypes, but was followed by increasing rates of IPD caused by nonvaccine serotypes. Among YK-AN children IPD rates dropped by 60%, but then rose due to non-PCV7 serotypes to levels 5- to 10-fold higher than rates in non-YK-AN children and non-AN children. IPD rates in YK-AN children were twice as high in villages where <10% of houses had in-home piped water compared with villages where more than 80% of houses had in-home piped water (390 cases/100,000 vs. 146 cases/100,000, P = 0.008). CONCLUSIONS: High IPD rates in Alaska are associated with lack of in-home piped water (controlling for household crowding and per capita income). The effect of in-home piped water is most likely mediated through reduced water supply leading to limitations on handwashing.

Methicillin-resistant Staphylococcus aureus-associated hospitalizations among the American Indian and Alaska native population.

BACKGROUND: American Indians and Alaska Natives (AI/ANs) have had documented outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infection but, to our knowledge, no studies have examined MRSA infection among this population nationally. We describe MRSA-associated hospitalizations among the approximately 1.6 million AI/ANs who receive care at Indian Health Service health care facilities nationwide. METHODS: We used hospital discharge data from the Indian Health Service National Patient Information Reporting System to determine the rate of MRSA-associated hospitalizations among AI/ANs who used Indian Health Service health care in 1996-2005 and in the comparison periods 1996-1998 and 2003-2005. Hospitalization rates among AI/ANs were examined by year, age group, sex, and region. MRSA-associated diagnoses were also examined. Rate comparisons were performed using Poisson regression analysis. Comparison of rates to those of the general United States population was made for 2003-2005 by means of the Nationwide Inpatient Sample. RESULTS: Between comparison periods, the rate of MRSA-associated hospitalization increased from 4.6 to 50.6 hospitalizations per 100,000 AI/ANs (P<.01), with increases in both sexes, all age groups, and all regions. By 2005, MRSA was the causative organism for the majority (52%) of all S. aureus-associated hospitalizations. The most common associated diagnosis was skin and soft-tissue infection, which accounted for 59% of MRSA-associated diagnoses. In 2003-2005, the age-adjusted rate among AI/ANs was 58.8 hospitalizations per 100,000 persons, compared with 84.7 hospitalizations per 100,000 persons in the general US population. CONCLUSIONS: MRSA-associated hospitalizations have increased significantly among AI/ANs served by Indian Health Service health care facilities. Clinicians should have a high index of suspicion for MRSA infection in AI/ANs, especially in those with a diagnosis of skin and soft-tissue infection.

Rapid assessment tool for Haemophilus influenzae type b disease in developing countries.

Haemophilus influenzae type b (Hib) still causes a substantial number of deaths among children in developing countries, despite the availability of effective conjugate vaccines. A major obstacle in developing a Hib vaccine has been limited awareness about the impact of Hib disease. A tool was developed to estimate the national rates of Hib meningitis and pneumonia by assessing retrospective local data over 7 to 10 days. Data from 11 countries in Africa, the Middle East, and Asia were studied and showed rates of Hib meningitis from >50 cases per 100,000 children >5 years in Ghana and Uganda to <15 per 100,000 in Iran, Jordan, and Uzbekistan. Results were affected by the quality of available data. The Hib rapid assessment tool can be useful to countries that desire a timely assessment of Hib disease rates.

Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study.

OBJECTIVE: To assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria. METHODS: From 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions. For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity. FINDINGS: During the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group. Overall, 285 children with suspected meningitis were identified. In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained. Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination. An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis. There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10%. Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins. CONCLUSION: On the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health. The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins.

Comparison of Three Selective Enrichment Methods for the Isolation of Listeria monocytogenes from Naturally Contaminated Foods.

Three selective enrichment procedures-the U.S. Food and Drug Administration (FDA) method, the U.S. Department of Agriculture (USDA) method, and the Netherlands Government Food Inspection Service (NGFIS) method-were compared for isolating Listeria monocytogenes from contaminated foods. The foods were obtained from the refrigerators of patients with culture-proven listeriosis who were identified through multistate active surveillance in a U.S. population of 19 million. The study was designed to identify foods that may be important in transmission of L. monocytogenes in sporadic cases of human listeriosis. Of 899 foods analyzed by all three methods, 121 were positive for L. monocytogenes by at least one method. The three enrichment methods detected L. monocytogenes in 65% (FDA), 74% (USDA), and 74% (NGFIS) of the foods shown to contain L. monocytogenes . The differences among the three methods were not statistically significant. However, the recovery of L. monocytogenes by a combination of any two methods (USDA-FDA 88%, USDA-NGFIS 91%, FDA-NGFIS 87%) was significantly better than that by one method alone (p < 0.02). The differences among the combinations of methods were not statistically significant. These results suggest that at least two enrichment methods must be used in combination to recover L. monocytogenes from contaminated foods with a success rate near 90%. Correlations were observed between negative results and low (<0.3 CFU/g) level of L. monocytogenes contamination for the USDA (p << 0.001) and NGFIS (p << 0.001) methods. A similar but somewhat weaker association was observed for the FDA method (p < 0.06).