Charting the impact of maternal antibodies and repeat exposures on sapovirus immunity in early childhood from a Nicaraguan birth cohort.

BACKGROUND: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. METHODS: We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). RESULTS: Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. CONCLUSION: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

Epigenome-wide differential methylation and differential variability as predictors of high-grade cervical intraepithelial neoplasia (cin2+).

CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs. low-grade (≤CIN1) lesions. In ≤CIN1 (n=117) and CIN2+ (n=31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M values among nine cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDR). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR<0.05) and Gene Ontology (GO) term enrichment. Compared to ≤CIN1, CIN2+ exhibited greater methylation at CCNA1 Cluster 1 (M value difference 0.24; 95% CI 0.04, 0.43) and RARB Cluster 2 (0.16; 95% CI 0.05, 0.28), and lower methylation at CDH1 Cluster 1 (-0.15; 95% CI -0.26, -0.04). CIN2+ exhibited lower variability at CDH1 Cluster 2 (variation difference -0.24; 95% CI -0.41, -0.05) and FHIT Cluster 1 (-0.30; 95% CI -0.50, -0.09). EWAS detected 3,534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms.

Nonsecretor Phenotype Is Associated With Less Risk of Rotavirus-Associated Acute Gastroenteritis in a Vaccinated Nicaraguan Birth Cohort.

BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. METHODS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by reverse-transcription quantitative polymerase chain reaction, and saliva or blood was used to determine HBGA phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. RESULTS: Rotavirus was detected in 109 (7%) stool samples from 1689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11 [24%]) and equine-like G3P[8] (11 [24%]). The overall incidence of rotavirus-associated AGE was 9.2 per 100 child-years, and was significantly higher in secretor than nonsecretor children (9.8 vs 3.5/100 child-years, P = .002). CONCLUSIONS: The nonsecretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children.

Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.

BACKGROUND: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. METHODS: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. RESULTS: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. CONCLUSIONS: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. IMPACT: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.

Secretor Status Strongly Influences the Incidence of Symptomatic Norovirus Infection in a Genotype-Dependent Manner in a Nicaraguan Birth Cohort.

BACKGROUND: The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. METHODS: Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. RESULTS: Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted odds ratio [aOR], 0.09 [95% confidence interval {CI}, .02-.33]) or non-GII.4 viruses (aOR, 0.2 [95% CI, .07-.6]) were less likely to have severe AGE compared to GII.4-infected children. CONCLUSIONS: Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.

First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort.

BACKGROUND: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. METHODS: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. RESULTS: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. CONCLUSIONS: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines.

Testing for Sexually Transmitted Infection Using Wet and Dry Self-Collected Brush Samples Among Women in Mombasa, Kenya.

ABSTRACT: We compared detection of Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis using dry and wet self-collected samples using brushes among females who engage in sex work in Mombasa, Kenya. Detection of T. vaginalis and N. gonorrhoeae in dry and wet samples was similar, but C. trachomatis detection in dry samples appeared lower.

Health Care Provider Perceptions of Facilitators and Barriers to Human Papillomavirus Vaccination Delivery in Five Countries.

BACKGROUND: National human papillomavirus (HPV) vaccination programs could reduce global cervical cancer morbidity and mortality with support from health care providers. We assessed providers' perceptions of HPV vaccination in 5 countries. METHODS: We identified providers from 5 countries where national HPV vaccination programs were at various stages of implementation: Argentina, Malaysia, South Africa, South Korea, and Spain. Providers authorized to administer adolescent vaccines completed an in-depth survey, reporting perceptions of barriers and facilitators to initiating and completing HPV vaccination, and logistical challenges to HPV vaccination. RESULTS: Among 151 providers, common barriers to HPV vaccination initiation across all countries were parents' lack of awareness (39%), concerns about vaccine safety or efficacy (33%), and cost to patients (30%). Vaccination education campaign (70%) was the most commonly cited facilitator of HPV vaccination initiation. Common barriers to series completion included no reminder system or dosing schedule (37%), loss to follow-up or forgetting appointment (29%), and cost to patients (25%). Cited facilitators to completing the vaccine series were education campaigns (45%), affordable vaccination (32%), and reminder/recall systems (22%). Among all countries, high cost of vaccination was the most common logistical challenge to offering vaccination to adolescents (33%). CONCLUSIONS: Incorporating provider insights into future HPV vaccination programs could accelerate vaccine delivery to increase HPV vaccination rates globally.

Seroepidemiology of SARS-CoV-2 infections in an urban population-based cohort in León, Nicaragua.

In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence reached 28% in the first 6 months of the country's epidemic and reached 35% 6 months later. Immune waning was uncommon. Individuals with a seropositive household member were over three times as likely to be seropositive themselves, suggesting the importance of household transmission.

Students with global experiences during medical school are more likely to work in settings that focus on the underserved: an observational study from a public U.S. institution.

BACKGROUND: Global health interest has grown among medical students over the past 20 years, and most medical schools offer global health opportunities. Studies suggest that completing global health electives during medical school may increase the likelihood of working with underserved populations in a clinical or research capacity. This study aimed to assess the association of global electives in medical school on subsequently working in global health and with underserved populations in the United States (U.S.), additionally considering students' interests and experiences prior to medical school. We also examined whether respondents perceived benefits gained from global electives. METHODS: We surveyed medical school graduates (classes of 2011-2015) from a large public medical school in the U.S. to describe current practice settings and previous global health experience. We evaluated work, volunteer, and educational experiences preceding medical school, socioeconomic status, race and ethnicity using American Medical College Application Service (AMCAS) data. We assessed the association between students' backgrounds, completing global health electives in medical school and current work in global health or with underserved populations in the U.S. RESULTS: In the 5 to 8 years post-graduation, 78% of 161 respondents reported work, research, or teaching with a focus on global or underserved U.S. POPULATIONS: Completing a global health elective during medical school (p = 0.0002) or during residency (p = 0.06) were positively associated with currently working with underserved populations in the U.S. and pre-medical school experiences were marginally associated (p = 0.1). Adjusting for pre-medical school experiences, completing a global health elective during medical school was associated with a 22% greater prevalence of working with an underserved population. Perceived benefits from global electives included improved cultural awareness, language skills, public health and research skills, and ability to practice in technology-limited settings. CONCLUSION: Medical school graduates who participated in global electives as students were more likely than their peers to pursue careers with underserved populations, independent of experiences prior to medical school. We hypothesize that by offering global health experiences, medical schools can enhance the interests and skills of graduates that will make them more likely and better prepared to work with underserved populations in the U.S. and abroad.

Association of State Legislation of Human Papillomavirus Vaccination with Vaccine Uptake Among Adolescents in the United States.

We assessed the association of state legislation with adolescent human papillomavirus (HPV) vaccination rates in states that legislated information dissemination or administration of HPV vaccination. Using insurance claims, we calculated monthly HPV vaccination rates (November 2009-December 2017) among adolescents in states that passed HPV vaccination legislation during that period: Missouri (July 2010), Kentucky (February 2012), Indiana (March 2013), Oregon (June 2013). We used segmented regression to estimate levels and trends of HPV vaccination rates, comparing pre-legislation to post-legislation segments, adjusting for seasonal vaccination patterns and changes to the vaccination recommendation among males during the study period. Indiana's legislation allowed pharmacists to administer HPV vaccination; legislation in Kentucky, Missouri, and Oregon included provisions HPV and cervical cancer education. No statistically significant increases in HPV vaccination levels or trends were observed in the post-legislation segments among adolescents overall; however, a significant post-legislation increase in vaccination trends was observed among boys in Missouri (ß = 0.16, p = 0.03). Evidence for a positive impact of legislation on HPV vaccination rates is limited. The scarcity of policies that directly facilitate or promote HPV vaccination, and the breadth of exemptions to school vaccination requirements, may limit the effectiveness of these policies. Continuing efforts to introduce and pass legislation that directly facilitates HPV vaccination, combined with promoting existing evidence-based interventions, can provide opportunities to identify the most effective strategies to increase adolescent HPV vaccination rates.

Overcoming barriers to adolescent vaccination: perspectives from vaccine providers in North Carolina.

To capture strategies for achieving high adolescent coverage of tetanus-diphtheria-acellular pertussis (Tdap), meningococcal conjugate (MenACWY), and human papillomavirus (HPV) vaccination, we surveyed employees of 20 North Carolina (N.C.) clinics that achieved adolescent vaccination coverage higher than the state average. One employee per clinic completed a surveysummarizing clinic practices regarding adolescent vaccination; perceived barriers and facilitators to Tdap/MenACWY/HPV vaccination; and the role of "champions" who made special efforts to promote adolescent vaccination. Common perceived barriers for all vaccinations were parental opposition and logistical barriers to receiving vaccination. For HPV vaccination, employees cited parental concerns about sexual behavior and injection site pain; no school vaccination requirement; and low-perceived benefit in boys. Most clinics (80%) implemented successful changes to increase adolescent vaccination: consistently offering vaccination, tracking vaccination status using existing data, providing appointment reminders, updating providers on vaccination recommendations, and expanding vaccination hours. Strategies to improve HPV vaccination included co-administration with Tdap and MenACWY, and providing reminders to complete the vaccination series. Vaccine champions strongly recommended vaccination to parents (55%) and educated parents on vaccination recommendations (36%). Clinics in N.C.and similar settings can implement these and other low-resource strategies to overcome adolescent vaccination barriers. ABBREVIATIONS: CDC=Centers for Disease Control and Prevention; EHR=Electronic health record; HPV=Human papillomavirus; Tdap=Tetanus-diphtheria-acellular pertussis vaccine; MenACWY=Meningococcal Conjugate Vaccine; NCIB=North Carolina Immunization Branch; NCIR=North Carolina Immunization Registry; ACIP=Advisory Committee on Immunization Practices.

Awareness, Knowledge, and Travel-Related Risk Factors for Zika Virus Among Latinas Attending a Federally Qualified Health Center in Rural North Carolina.

BACKGROUND The Zika virus (ZIKV) epidemic that began in 2015 presented a risk for ZIKV infection among persons who traveled to ZIKV-affected countries. Latinas in North Carolina and their sexual partners may be exposed to ZIKV when traveling to these regions.METHODS We administered a cross-sectional survey, measuring ZIKV risk and knowledge, to a convenience sample of 262 reproductive-age Latinas attending a Federally Qualified Health Center in rural North Carolina. We described ZIKV risk and knowledge in the sample, and compared responses between those who were pregnant or recently pregnant, and those who were not pregnant. We further identified factors associated with 1) awareness of ZIKV and 2) high knowledge of ZIKV sequelae and prevention among those who were aware of ZIKV, using log-binomial regression.RESULTS Two-thirds of participants had ever heard of ZIKV, which was positively associated with educational attainment. Most participants aware of ZIKV had moderate/high knowledge of ZIKV transmission (92.5%) and symptoms (73.2%), but knowledge of preventing sexual and congenital transmission was limited. Travel was infrequent among pregnant or recently pregnant participants (5.4%) and their partners (7.1%). Despite low risk for ZIKV infection, participants were willing to practice ZIKV prevention.LIMITATIONS Our study is limited by a lack of generalizability to Latinas in other regions of the country, self-reporting bias, and lack of survey validation as an indicator of English language proficiency.CONCLUSIONS Providers should identify patients likely to become pregnant and travel to high-risk areas, inquire about partner travel history, and offer culturally appropriate ZIKV risk counseling.

Acceptability of two- versus three-dose human papillomavirus vaccination schedule among providers and mothers of adolescent girls: a mixed-methods study in five countries.

PURPOSE: The World Health Organization revised its human papillomavirus (HPV) vaccination recommendations to include a two (2-) dose schedule for girls aged ≤ 15 years. We investigated acceptability of 2- versus 3-dose schedule among adolescent vaccination providers and mothers of adolescent girls in five countries. METHODS: Adolescent vaccination providers (N = 151) and mothers of adolescent girls aged 9-14 years (N = 118) were recruited from Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preference for a 2- versus 3-dose HPV vaccination schedule via quantitative surveys. Mothers' attitudes towards a 2-dose schedule were assessed through focus group discussions. RESULTS: Most adolescent providers preferred a 2- over a 3-dose HPV vaccination schedule (overall: 74%), with preference ranging from 45.2% (South Africa) to 90.0% (South Korea). Lower cost, fewer clinic visits, and higher series completion were commonly cited reasons for 2-dose preference among providers and mothers. Safety and efficacy concerns were commonly cited barriers to accepting a 2-dose HPV vaccination schedule among providers and mothers. Mothers generally accepted the reduced schedule, however requested further information from a trusted source. CONCLUSIONS: Adolescent vaccination providers and mothers preferred the 2-dose over 3-dose HPV vaccination schedule. Acceptability of a 2-dose HPV vaccination could be improved with additional information to providers and mothers on HPV vaccination safety and efficacy.

Epstein-Barr Virus, High-Risk Human Papillomavirus and Abnormal Cervical Cytology in a Prospective Cohort of African Female Sex Workers.

BACKGROUND: High-oncogenic-risk human papillomavirus (hrHPV) is necessary, although insufficient, to promote cervical cancer. Like HPV, Epstein-Barr virus (EBV) is a common pathogen with the capacity to promote epithelial neoplasms. We examined the association between cervical EBV, hrHPV, and cytology in female sex workers in Nairobi, Kenya. METHODS: Women (n = 332) with known cervical cytology and hrHPV mRNA results were evaluated for cervical EBV DNA by conventional polymerase chain reaction. Prevalence ratios (PRs) were calculated to assess the relationships between EBV, hrHPV, and cervical cytology. Prospective analyses used risk ratios and time-to-event analyses to determine the association of EBV with hrHPV clearance and with abnormal cytology outcomes. RESULTS: Baseline prevalence of hrHPV and EBV was 29% and 19%, respectively. Higher EBV prevalence was found among women with older age, HIV, hrHPV, abnormal cytology, Mycoplasma genitalium infection, smoking habits, younger age at sexual debut, and less frequent condom use. At baseline, women with EBV had a higher prevalence of hrHPV infection than did EBV-negative women (52% vs. 24%; HIV-adjusted PR [95% confidence interval], 1.8 [1.3-2.6]). Epstein-Barr virus-positive women had a higher prevalence than did EBV-negative women of high-grade precancer (15% vs. 2%) and abnormal cytology (37% vs. 15%), although HIV- and hrHPV-adjusted associations were not significant (high-grade precancer: PR, 2.0 [0.7-5.9]; abnormal cytology: PR, 1.4 [0.9-2.2]). In prospective analyses, a marginal association was observed between baseline EBV detection and delayed hrHPV clearance. CONCLUSIONS: Our data support a possible role for EBV as a high-risk marker or cofactor for HPV-mediated cervical cancer development.

The Role of Chlamydia trachomatis in High-Risk Human Papillomavirus Persistence Among Female Sex Workers in Nairobi, Kenya.

BACKGROUND: Little is known about risk factors for persistent high-risk human papillomavirus (hrHPV) infection in low-income settings, and prior research has not quantified the relative duration of hrHPV infections stratified by risk factors. We compared the duration of hrHPV infection among female sex workers (FSWs) by exposure to sexually transmitted infections (STIs), using a highly sensitive biomarker assay. METHODS: From 2009 to 2011, 350 FSWs enrolled in this longitudinal study. Every 3 months, sociodemographic and sexual behavior data were collected via questionnaire, and APTIMA assays were used to detect the rRNA of Chlamydia trachomatis (CT), Neisseria gonorrhea, Trichomonas vaginalis, Mycoplasma genitalium, and messenger RNA of the E6/E7 oncoproteins expressed by hrHPV. Among 173 FSW who were infected with hrHPV during the observation period, accelerated failure time models estimated time ratios (TRs) for duration of hrHPV infection, comparing FSW infected with STIs at baseline to STI-uninfected FSWs. RESULTS: Median follow-up time was 26.2 months (interquartile range, 18.8-27.5 months). The median duration of hrHPV infection among all FSWs was 9.3 months (95% confidence interval [CI], 9.3-11.5). The duration of hrHPV infection among FSW infected with CT at baseline was greater than that among FSWs who were uninfected (adjusted TR, 1.7; 95% CI, 1.2-2.6). Among FSWs who were coinfected with hrHPV and CT at baseline, the adjusted TR was 3.4 (95% CI, 2.5-5.4) compared with FSWs infected with hrHPV only. No other STI was associated with hrHPV duration. CONCLUSIONS: Recent or concurrent CT infection was associated with prolonged hrHPV infection among a cohort of Nairobi FSWs. Management of CT could reduce risk for hrHPV persistence.

Transmission Patterns of Norovirus From Infected Children to Household Members in León, Nicaragua.

Norovirus is a common and highly transmissible gastrointestinal pathogen. Among 34 Nicaraguan households with a norovirus-infected child, 48% experienced norovirus transmission within 1 week, infecting 18% of household members; GII norovirus was more commonly transmitted than GI. Pediatric norovirus vaccines could prevent both index cases and transmission to close contacts.

Correction: Association between breastfeeding, host genetic factors, and calicivirus gastroenteritis in a Nicaraguan birth cohort.

[This corrects the article DOI: 10.1371/journal.pone.0267689.].

Putting health metrics into practice: using the disability-adjusted life year for strategic decision making.

BACKGROUND: Implementing organizations are pressured to be accountable for performance. Many health impact metrics present limitations for priority setting; they do not permit comparisons across different interventions or health areas. In response, Population Services International (PSI) adopted the disability-adjusted life year (DALY) averted as its bottom-line performance metric. While international standards exist for calculating DALYs to determine burden of disease (BOD), PSI's use of DALYs averted is novel. It uses DALYs averted to assess and compare the health impact of its country programs, and to understand the effectiveness of a portfolio of interventions. This paper describes how the adoption of DALYs averted influenced organizational strategy and presents the advantages and constraints of using the metric. METHODS: Health impact data from 2001-2011 were analyzed by program area and geographic region to measure PSI's performance against its goal of doubling health impact between 2007-2011. Analyzing 10 years of data permitted comparison with previous years' performance. A case study of PSI's Asia and Eastern European (A/EE) region, and PSI/Laos, is presented to illustrate how the adoption of DALYs averted affected strategic decision making. RESULTS: Between 2007-2011, PSI's programs doubled the total number of DALYs averted from 2002-2006. Most DALYs averted were within malaria, followed by HIV/AIDS and family planning (FP). The performance of PSI's A/EE region relative to other regions declined with the switch to DALYs averted. As a result, the region made a strategic shift to align its work with countries' BOD. In PSI/Laos, this redirection led to better-targeted programs and an approximate 50% gain in DALYs averted from 2009-2011. CONCLUSIONS: PSI's adoption of DALYs averted shifted the organization's strategic direction away from product sales and toward BOD. Now, many strategic decisions are based on "BOD-relevance," the share of the BOD that interventions can potentially address. This switch resulted in more targeted strategies and greater program diversification. Challenges remain in convincing donors to support interventions in disease areas that are relevant to a country's BOD, and in developing modeling methodologies. The global health community will benefit from the use of standard health impact metrics to improve strategic decision making and more effectively respond to the changing global burden of disease.