Tammy Zulz

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.

Epidemiology of Haemophilus influenzae serotype a, North American Arctic, 2000-2005.

Serotype a is now the most common seen in the North American Arctic; highest rates occur in indigenous children.

International circumpolar surveillance system for invasive pneumococcal disease, 1999-2005

Disease rates are high among indigenous persons in Arctic countries, and PCV7 has resulted in decreased rates in North American children.

International Circumpolar Surveillance, An Arctic Network for the Surveillance of Infectious Diseases

Hospitals, public health agencies, and reference laboratories work together to detect and control infectious disease in Arctic regions.

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 during1983–2011. 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.

Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska.

BACKGROUND Alaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction. METHODS Pneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005-2008 and post-PCV13 time period April 2010-December 2013; excluding Jan 2009-March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009. RESULTS Among Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5-17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18-44 years (39%, P<0.001); this decline was similar in AN and non-AN persons (38%, P=0.016, 43%, P=0.014, respectively). CONCLUSIONS Forty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005-2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18-44 years.

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.

Epidemiology of bacterial meningitis in the North American Arctic, 2000–2010

OBJECTIVE To determine the incidence of meningitis caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in the North American Arctic during 2000-2010. METHODS Surveillance data were obtained from the International Circumpolar Surveillance network. We defined a case of bacterial meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae as a culture-positive isolate obtained from a normally sterile site in a resident with a meningitis diagnosis. RESULTS The annual incidence/100,000 persons for meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae among all North American Arctic residents was: 0.6, 0.5, and 1.5, respectively; the meningitis incidence among indigenous persons in Alaska and Canada (indigenous status not recorded in Greenland) for those three bacteria was: 2.1, 0.8, and 2.4, respectively. The percentage of pneumococcal isolates belonging to a 7-valent pneumococcal conjugate vaccine serotype declined from 2000-2004 to 2005-2010 (31%-2%, p-value <0.01). During 2005-2010, serotype a caused 55% of H. influenzae meningitis and serogroup B caused 86% of meningococcal meningitis. CONCLUSIONS Compared with all North American Arctic residents, indigenous people suffer disproportionately from bacterial meningitis. Arctic residents could benefit from the development of an H. influenzae serotype a vaccine and implementation of a meningococcal serogroup B vaccine.

Molecular Characterization of Streptococcus pneumoniae Serotype 12F Isolates Associated with Rural Community Outbreaks in Alaska

ABSTRACT 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.

Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013

ABSTRACT The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n = 8), 5.8% (n = 20), and 1.2% (n = 4) of the isolates, respectively. A total of 51 emm types were identified, of which emm1 (11.1%) was the most prevalent, followed by emm82 (8.8%), emm49 (7.8%), emm12 and emm3 (6.6% each), emm89 (6.2%), emm108 (5.5%), emm28 (4.7%), emm92 (4%), and emm41 (3.8%). The five most common emm types accounted for 41% of isolates. The emm types in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development.