Haemophilus influenzae Type b Vaccine Immunogenicity in American Indian/Alaska Native Infants.

Objectives: American Indian and Alaska Native (AI/AN) infants historically experienced a disproportionate burden of invasive Haemophilus influenzae type b (Hib) disease, especially early in life. PedvaxHIB vaccine is preferentially recommended for AI/AN infants because it elicits protective antibody levels postdose 1. Vaxelis, a hexavalent vaccine that contains the same Hib conjugate as PedvaxHIB but at lower concentration, is recommended for US children, but postdose 1 Hib immunogenicity data are needed to inform whether a preferential recommendation should be made for AI/AN infants.

serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.

Carriage prevalence and genomic epidemiology of among Native American children and adults in the Southwestern USA.

Native American individuals in the Southwestern USA experience a higher burden of invasive disease than the general population. However, little is known about carriage in these communities. A cross-sectional study was conducted to determine the carriage prevalence, risk factors and genomic epidemiology of among Native American children (<5 years, =121) and adults (≥18 years, =167) in the Southwestern USA.

Evaluation of indoor PM concentrations in a Native American Community: a pilot study.

Background: Indoor air pollution is associated with adverse health effects; however, few studies exist studying indoor air pollution on the Navajo Nation in the southwest U.S., a community with high rates of respiratory disease.

Frequency-dependent selection can forecast evolution in Streptococcus pneumoniae.

Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products.

High Burden of Among Native American Individuals on the White Mountain Apache Tribal Lands.

Background: This study was done to determine the burden of invasive on the White Mountain Apache Tribal lands.

Methods: Active population and laboratory-based surveillance for invasive infections was conducted from May 2016 to April 2018. A case was defined as a Native American individual living on or around the White Mountain Apache Tribal lands with isolated from a normally sterile body site.

Efficacy, safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: A phase IIb randomized study.

Background: Native American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs.

Methods: In this phase IIb, double-blind, controlled trial, 6-12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12-15 months.

Association of Laboratory Methods, Colonization Density, and Age With Detection of Streptococcus pneumoniae in the Nasopharynx.

Culture-based methods for detecting Streptococcus pneumoniae in the nasopharynx lack sensitivity. In this study, we aimed to compare the performance of culture and molecular methods in detecting pneumococcus in the nasopharynx of healthy individuals and to evaluate the associations of age and colonization density with detection. Between 2010 and 2012, nasopharyngeal specimens were collected from healthy individuals living on Navajo Nation and White Mountain Apache Tribal lands in the United States.

The burden of Staphylococcus aureus among Native Americans on the Navajo Nation.

Introduction: Native Americans in the southwestern United States have a higher risk for many infectious diseases and may be at higher risk for Staphylococcus aureus due to the high prevalence of risk factors for S. aureus. Recent data on invasive S.

Water quality, availability, and acute gastroenteritis on the Navajo Nation - a pilot case-control study.

The Navajo Nation includes approximately 250,000 American Indians living in a remote high desert environment with limited access to public water systems. We conducted a pilot case-control study to assess associations between acute gastroenteritis (AGE) and water availability, use patterns, and quality. Case patients with AGE and non-AGE controls who presented for care to two Indian Health Service hospitals were recruited.

The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use.

Identifying transmission routes of Streptococcus pneumoniae and sources of acquisitions in high transmission communities.

Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2-8 years old typically acquire in their own or surrounding communities.

Norovirus and Sapovirus Epidemiology and Strain Characteristics among Navajo and Apache Infants.

Norovirus and sapovirus are important causes of acute gastroenteritis (AGE) among American Indian infants. We investigated the prevalence and molecular epidemiology of norovirus and sapovirus in American Indian infants who have historically experienced a high burden of AGE compared to other US populations. Stool samples were collected from 241 children with AGE (cases) and from 343 infants without AGE (controls) ≤9 months of age from 2002-2004.

Association of Pneumococcal Protein Antigen Serology With Age and Antigenic Profile of Colonizing Isolates.

Background: Several Streptococcus pneumoniae proteins play a role in pathogenesis and are being investigated as vaccine targets. It is largely unknown whether naturally acquired antibodies reduce the risk of colonization with strains expressing a particular antigenic variant.

Methods: Serum immunoglobulin G (IgG) titers to 28 pneumococcal protein antigens were measured among 242 individuals aged <6 months-78 years in Native American communities between 2007 and 2009.

Relating Pneumococcal Carriage Among Children to Disease Rates Among Adults Before and After the Introduction of Conjugate Vaccines.

The use of pneumococcal conjugate vaccines (PCVs) in children has a strong indirect effect on disease rates in adults. When children are vaccinated with PCVs, other serotypes that are not targeted by the vaccine can increase in frequency (serotype replacement) and reduce the direct and indirect benefits of the vaccine. To understand and predict the likely impacts of serotype replacement, it is important to know how patterns in the transmission of serotypes among children relate to disease rates in adults.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage Among American Indians.

Background: Community-wide impact of pneumococcal conjugate vaccines (PCV) is conferred by reductions in vaccine-type nasopharyngeal carriage. We evaluated the impact of PCV13 on carriage of PCV13-specific types (1, 3, 5, 6A, 7F and 19A) and 6C among American Indians.

Methods: A nasopharyngeal specimen was collected from community members of all ages between January 2010 and April 2012 (3 months before and 24 months after PCV13 introduction).

Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: a phase 3 randomised double-blind placebo-controlled trial.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections.

Methods: This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation.

Nasopharyngeal carriage and transmission of Streptococcus pneumoniae in American Indian households after a decade of pneumococcal conjugate vaccine use.

Background: Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV) use. Few studies document pneumococcal household dynamics in the routine-PCV7 era.

Methods: We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008.

Seasonal drivers of pneumococcal disease incidence: impact of bacterial carriage and viral activity.

Background: Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses.

Methods: We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012.

Comparative immunogenicity of 7 and 13-valent pneumococcal conjugate vaccines and the development of functional antibodies to cross-reactive serotypes.

Background: Protection against disease or colonization from serotypes related to those in pneumococcal conjugate vaccines (i.e. cross-protection) vary by serotype; the basis for this variation is not understood.

A prospective study of agents associated with acute respiratory infection among young American Indian children.

Background: Native American children have higher rates of morbidity associated with acute respiratory infection than children in the general US population, yet detailed information is lacking regarding their principal clinical presentations and infectious etiologies.

Methods: We pursued a comprehensive molecular survey of bacteria and viruses in nasal wash specimens from children with acute respiratory disease collected prospectively over 1 year (January 1 through December 31, 2009) from 915 Navajo and White Mountain Apache children in their second or third year of life who had been enrolled in an efficacy study of a respiratory syncytial virus monoclonal antibody in the first year of life.

Results: During the surveillance period, 1476 episodes of disease were detected in 669 children.

Lack of nonspecific protection against all-cause nonrotavirus gastroenteritis by vaccination with orally administered rotavirus vaccine.

Objectives: Acute gastroenteritis (AGE) is recognized as a global, common threat to child survival, especially in developing countries. Rotavirus, in particular, has been implicated as a leading cause of severe AGE; however, there are numerous other pathogens that also cause AGE. Several studies have demonstrated that oral vaccination against rotavirus has generated the unanticipated benefit of protecting against AGE caused by nonrotavirus pathogens.

Epidemiologic and clinical features of other enteric viruses associated with acute gastroenteritis in American Indian infants.

Objective: To investigate the viral etiology, through the use of molecular methods, of acute gastroenteritis (AGE), which is a considerable public health burden in Native American infants.

Study Design: From March 2002 through February 2004, AGE and non-diarrheal stools were collected from Navajo and White Mountain Apache infants who received placebo during a rotavirus vaccine trial. Case (n=247) and control (n=344) specimens were tested for enteric adenovirus, astrovirus, norovirus, rotavirus, and sapovirus with real-time polymerase chain reaction.

Efficacy of a pentavalent human-bovine reassortant rotavirus vaccine against rotavirus gastroenteritis among American Indian children.

Background: Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general U.S.

Impact of more than a decade of pneumococcal conjugate vaccine use on carriage and invasive potential in Native American communities.

Background: We assessed the impact of 12 years of pneumococcal conjugate vaccine (PCV7) use on pneumococcal nasopharyngeal carriage and serotype-specific invasive disease potential among Native Americans.

Methods: Families were enrolled in a carriage study from 2006 to 2008; nasopharyngeal specimens and risk factor information were collected monthly for 7 visits. Pneumococcal carriage prevalence was compared with that before (1998-2000) and during (2001-2002) PCV7 introduction.