The Potential Benefits of Delaying Seasonal Influenza Vaccine Selections for the Northern Hemisphere: A Retrospective Modeling Study in the United States.

BACKGROUND: Antigenic similarity between vaccine viruses and circulating viruses is crucial for achieving high vaccine effectiveness against seasonal influenza. New non-egg-based vaccine production technologies could revise current vaccine formulation schedules. We aim to assess the potential benefit of delaying seasonal influenza vaccine virus selection decisions. METHODS: We identified seasons where season-dominant viruses presented increasing prevalence after vaccine formulation had been decided in February for the Northern Hemisphere, contributing to their antigenic discrepancy with vaccine viruses. Using a SEIR (susceptible-exposed-infectious-recovered) model of seasonal influenza in the United States, we evaluated the impact of updating vaccine decisions with more antigenically similar vaccine viruses on the influenza burden in the United States. RESULTS: In 2014-2015 and 2019-2020, the season-dominant A(H3N2) subclade and B/Victoria clade, respectively, presented increasing prevalence after vaccine decisions were already made for the Northern Hemisphere. Our model showed that the updated A(H3N2) vaccine could have averted 5000-65 000 influenza hospitalizations in the United States in 2014-2015, whereas updating the B/Victoria vaccine component did not substantially change influenza burden in the 2019-2020 season. CONCLUSIONS: With rapid vaccine production, revising current timelines for vaccine selection could result in substantial epidemiological benefits, particularly when additional data could help improve the antigenic match between vaccine and circulating viruses.

Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine.

BACKGROUND: The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya. METHODS: In total, 1500 children aged 5-17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32). RESULTS: At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%-49%) to 53% (R012-14-26; 95% CI: 42%-62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32). CONCLUSIONS: Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply. CLINICAL TRIALS REGISTRATION: NCT03276962 (ClinicalTrials.gov).

Estimated population-level impact of pneumococcal conjugate vaccines against all-cause pneumonia mortality among unvaccinated age groups in five Latin American countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multi-country study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. METHODS: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000-2019, with 1,795,789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the post-vaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. RESULTS: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among ≥65 years in Chile. DISCUSSION: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Effectiveness of self-financed rotavirus vaccines on acute gastroenteritis primary care episodes using real-world data in Spain: a propensity score-matched analysis of cohort study.

The objective of this study was to estimate, by a novel spatiotemporal approach in an environment of non-funded rotavirus (RV) vaccines, the RV vaccine effectiveness (VE) to prevent acute gastroenteritis primary care (AGE-PC)-attended episodes, demonstrating how indirect protection leads to underestimation of direct VE under high vaccine coverage (VC). This population-based retrospective cohort study used electronic healthcare registries including all children 2 months-5 years old, born from 2009 to 2018 in the Valencia Region (Spain). Direct RV VE preventing AGE-PC episodes was estimated using propensity score matching and Poisson regressions stratified by VC, adjusted by age and calendar season. Indirect VE was estimated by Poisson regression comparing AGE-PC rates in unvaccinated children among the different VC levels. A total of 563,442 children were included for the RV VC estimation; of them, 360,576 were included in the birth-cohort for VE analysis. RV VC showed strong variability among districts and seasons, rising on average from 21% in 2009/2010 to 55% in 2017/2018. The highest direct VE was found in vaccinated children from districts with 0-30% RV VC (16.4%) and the lowest in those from districts with ≥ 70% RV VC (9.7%). The indirect protection in unvaccinated children raised from 6 to 16.6% for those living with 20-30% and ≥ 70% VC, respectively. CONCLUSION: Considering that RV is the causative agent in 20% of AGE cases, a direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with VC over 70% because of indirect protection. WHAT IS KNOWN: • The effectiveness of RV vaccines preventing hospitalizations due to RV-acute gastroenteritis (RV-AGE) has been extensively studied. However, RV also burdens the primary care (PC) setting, and data on vaccine effectiveness (VE) in preventing AGE-PC visits are scarce. • The RV vaccine distribution in Spain (non-funded), with large differences in vaccine coverage (VC) among healthcare districts, provides an ideal scenario to assess the actual VE in preventing AGE-PC consultations, including the direct and indirect protection. WHAT IS NEW: • A direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with high VC because of indirect protection. • These findings, together with existing data on the impact on hospitalizations due to RV-AGE, offer valuable insights for implementing vaccination initiatives in countries that have not yet commenced such programs.

The potential benefits of delaying seasonal influenza vaccine selections for the Northern Hemisphere: a retrospective modeling study in the United States.

BACKGROUNDS: Antigenic similarity between vaccine viruses and circulating viruses is crucial for achieving high vaccine effectiveness against seasonal influenza. New non-egg-based vaccine production technologies could revise current vaccine formulation schedules. We aim to assess the potential benefit of delaying seasonal influenza vaccine virus selection decisions. METHODS: We identified seasons where season-dominant viruses presented increasing prevalence after vaccine formulation had been decided in February for the Northern Hemisphere, contributing to their antigenic discrepancy with vaccine viruses. Using a SEIR model of seasonal influenza in the United States, we evaluated the impact of updating vaccine decisions with more antigenically-similar vaccine viruses on the influenza burden in the United States. RESULTS: In 2014/15 and 2019/20, the season-dominant A(H3N2) subclade and B/Victoria clade respectively presented increasing prevalence after vaccine decisions were already made for the Northern Hemisphere. Our model showed that the updated A(H3N2) vaccine could have averted 5,000-65,000 influenza hospitalizations in the United States in 2014/15, whereas updating the B/Victoria vaccine component did not substantially change influenza burden in 2019/20 season. CONCLUSIONS: With rapid vaccine production, revising current timelines for vaccine selection could result in substantial epidemiological benefits, particularly when additional data could help improve the antigenic match between vaccine and circulating viruses.

Using LASSO Regression to Estimate the Population-Level Impact of Pneumococcal Conjugate Vaccines.

Pneumococcal conjugate vaccines (PCVs) protect against diseases caused by Streptococcus pneumoniae, such as meningitis, bacteremia, and pneumonia. It is challenging to estimate their population-level impact due to the lack of a perfect control population and the subtleness of signals when the endpoint-such as all-cause pneumonia-is nonspecific. Here we present a new approach for estimating the impact of PCVs: using least absolute shrinkage and selection operator (LASSO) regression to select variables in a synthetic control model to predict the counterfactual outcome for vaccine impact inference. We first used a simulation study based on hospitalization data from Mexico (2000-2013) to test the performance of LASSO and established methods, including the synthetic control model with Bayesian variable selection (SC). We found that LASSO achieved accurate and precise estimation, even in complex simulation scenarios where the association between the outcome and all control variables was noncausal. We then applied LASSO to real-world hospitalization data from Chile (2001-2012), Ecuador (2001-2012), Mexico (2000-2013), and the United States (1996-2005), and found that it yielded estimates of vaccine impact similar to SC. The LASSO method is accurate and easily implementable and can be applied to study the impact of PCVs and other vaccines.

Vaccine Impact and Effectiveness of Meningococcal Serogroup ACWY Conjugate Vaccine Implementation in the Netherlands: A Nationwide Surveillance Study.

BACKGROUND: In response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for children aged 14 months was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting individuals aged 14-18 years was executed. We investigated the impact of MenACWY vaccination implementation in 2018-2020 on incidence rates and estimated vaccine effectiveness (VE). METHODS: We extracted IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group-specific incidence rate ratios by comparing incidence rates before (July 2017-March 2018) and after (July 2019-March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method. RESULTS: Overall, the IMD-W incidence rate declined by 61% (95% confidence interval [CI], 40 to 74). It declined by 82% (95% CI, 18 to 96) in the vaccine-eligible age group (individuals aged 15-36 months and 14-18 years) and by 57% (95% CI, 34 to 72) in vaccine-noneligible age groups. VE was 92% (95% CI, -20 to 99.5) in vaccine-eligible toddlers (aged 15-36 months). No IMD-W cases were reported in vaccine-eligible teenagers after the campaign. CONCLUSIONS: The MenACWY vaccination program was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine-noneligible age groups may be caused by indirect effects of the vaccination program. However, disentangling natural fluctuation from vaccine effect was not possible. Our findings encourage the use of toddler and teenager MenACWY vaccination in national immunization programs.

Evaluating the Impact of Meningococcal Vaccines With Synthetic Controls.

Invasive meningococcal disease (IMD) has a low and unpredictable incidence, presenting challenges for real-world evaluations of meningococcal vaccines. Traditionally, meningococcal vaccine impact is evaluated by predicting counterfactuals from pre-immunization IMD incidences, possibly controlling for IMD in unvaccinated age groups, but the selection of controls can influence results. We retrospectively applied a synthetic control (SC) method, previously used for pneumococcal disease, to data from 2 programs for immunization of infants against serogroups B and C IMD in England and Brazil. Time series of infectious/noninfectious diseases in infants and IMD cases in older unvaccinated age groups were used as candidate controls, automatically combined in a SC through Bayesian variable selection. SC closely predicted IMD in absence of vaccination, adjusting for nontrivial changes in IMD incidence. Vaccine impact estimates were in line with previous assessments. IMD cases in unvaccinated age groups were the most frequent SC-selected controls. Similar results were obtained when excluding IMD from control sets and using other diseases only, particularly respiratory diseases and measles. Using non-IMD controls may be important where there are herd immunity effects. SC is a robust and flexible method that addresses uncertainty introduced when equally plausible controls exhibit different post-immunization behaviors, allowing objective comparisons of IMD programs between countries.

HPV prevalence among young adult women living with and without HIV in Botswana for future HPV vaccine impact monitoring.

INTRODUCTION: In 2015, Botswana introduced quadrivalent human papillomavirus (HPV) vaccine for girls aged 9-13 years. To establish a baseline HPV prevalence for future HPV vaccine impact monitoring, we evaluated HPV prevalences among the youngest unvaccinated women in Botswana and compared HPV prevalences among women living with HIV (WLHIV) and without HIV. METHODS: Women aged 18-22 years were recruited from the University of Botswana and HIV clinics in Gaborone from October 2019-January 2021. Demographic and behavioral characteristics were self-reported during structured interviews; HIV clinical characteristics were abstracted from medical charts. Self-collected vaginal swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared prevalence of any HPV, high risk (HR)-HPV, and quadrivalent HPV vaccine types (HPV6/11/16/18) among WLHIV and women without HIV and evaluated risk factors for prevalence of HR-HPV. RESULTS: A total of 306 WLHIV and 500 women without HIV were recruited. Compared to women without HIV, WLHIV were more likely to be sexually experienced (86.6% versus 74.4%) and have ≥ 3 lifetime sex partners (55.3% versus 27.8%). All HPV type prevalences were significantly higher among WLHIV compared to women without HIV, including prevalence of any HPV (82.7% versus 63.0%), HR-HPV (72.9% versus 53.8%), and quadrivalent vaccine HPV types (34.3% versus 21.0%). Among WLHIV, there were no differences between those perinatally and non-perinatally infected for HPV prevalences, number of HPV types detected, CD4 count, or viral load. CONCLUSIONS: Over one-third of WLHIV and nearly a quarter of those without HIV had vaccine-type HPV detected. This study supports need for the national HPV vaccination program in Botswana and provides important baseline data for future evaluation of impact of the program.

Impact of Meningococcal B Vaccine on Invasive Meningococcal Disease in Adolescents.

BACKGROUND: From 2017, a statewide cluster randomized trial was conducted in South Australia to assess the impact of the meningococcal B vaccine 4CMenB on pharyngeal Neisseria meningitidis carriage in adolescents. Senior schools were randomized to receive the vaccine in 2017 (intervention) or 2018 (control). In this study we report the vaccine impact of 4CMenB on serogroup B invasive meningococcal disease (IMD) in 16- to 19-year-old adolescents in South Australia. METHODS: This observational time series analysis of serogroup B IMD cases compares the 14 years prior to the commencement of the trial (2003-2016) with the 2 years following 4CMenB vaccination of the 2017 adolescent cohort. RESULTS: Approximately 62% of year 10 and 11 students (15-16 years old) in South Australia enrolled in the trial. A total of 30 522 year 10-12 students received at least 1 dose of 4CMenB. The number of serogroup B IMD cases in 16- to 19-year old adolescents in South Australia increased on average by 10% per year from 2003 to 2016 (95% confidence interval [CI], 6%-15%, P < .001), peaking with 10 cases in 2015. Serogroup B IMD cases reduced to 5 in 2017-2018 and 1 in 2018-2019, below the expected numbers of 9.9 (95% prediction interval [PI], 3.9-17.5) and 10.9 (95% PI, 4.4-19.1), respectively. This translated to an overall reduction in the number of serogroup B IMD cases of 71% (95% CI, 15%-90%, P = .02). There were no serogroup B IMD cases in vaccinated adolescents. CONCLUSIONS: Vaccinating adolescents with 4CMenB was associated with a reduction in group B meningococcal disease in South Australia. CLINICAL TRIALS REGISTRATION: NCT03089086.

Effectiveness of Meningococcal Vaccines at Reducing Invasive Meningococcal Disease and Pharyngeal Neisseria meningitidis Carriage: A Systematic Review and Meta-analysis.

BACKGROUND: Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, leads to significant morbidity and mortality worldwide. This review aimed to establish the effectiveness of meningococcal vaccines at preventing IMD and N. meningitidis pharyngeal carriage. METHODS: A search within PubMed, Embase, Scopus, and unpublished studies up to 1 February 2020 was conducted. RESULTS: After removal of duplicates, 8565 studies were screened and 27 studies included. Protection was provided by meningococcal C vaccines for group C IMD (odds ratio [OR], 0.13 [95% confidence interval {CI}, .07-.23]), outer membrane vesicle (OMV) vaccines against group B IMD (OR, 0.35 [95% CI, .25-.48]), and meningococcal A, C, W, Y (MenACWY) vaccines against group ACWY IMD (OR, 0.31 [95% CI, .20-.49]). A single time series analysis found a reduction following an infant 4CMenB program (incidence rate ratio, 0.25 [95% CI, .19-.36]). Multivalent MenACWY vaccines did not reduce carriage (relative risk [RR], 0.88 [95% CI, .66-1.18]), unlike monovalent C vaccines (RR, 0.50 [95% CI, .26-.97]). 4CMenB vaccine had no effect on group B carriage (RR, 1.12 [95% CI, .90-1.40]). There was also no reduction in group B carriage following MenB-FHbp vaccination (RR, 0.98 [95% CI, .53-1.79]). CONCLUSIONS: Meningococcal conjugate C, ACWY, and OMV vaccines are effective at reducing IMD. A small number of studies demonstrate that monovalent C conjugate vaccines reduce pharyngeal N. meningitidis carriage. There is no evidence of carriage reduction for multivalent MenACWY, OMV, or recombinant MenB vaccines, which has implications for immunization strategies. CLINICAL TRIALS REGISTRATION: CRD42018082085 (PROSPERO).

Impact of Rotavirus Vaccines on Gastroenteritis Hospitalizations in Western Australia: A Time-series Analysis.

BACKGROUND: Rotavirus vaccination was introduced into the Australian National Immunisation Program in mid-2007. We aimed to assess the impact of the rotavirus vaccination program on the burden of hospitalizations associated with all-cause acute gastroenteritis (including rotavirus gastroenteritis and non-rotavirus gastroenteritis) in the Aboriginal and non-Aboriginal population in Western Australia. METHODS: We identified all hospital records, between July 2004 and June 2012, with a discharge diagnosis code for all-cause gastroenteritis. Age-specific hospitalization rates for rotavirus and non-rotavirus acute gastroenteritis before and after the introduction of the rotavirus vaccination program were compared. Interrupted time-series models were used to examine differences in the annual trends of all-cause gastroenteritis hospitalization between the two periods. RESULTS: Between July 2004 and June 2012, there were a total of 106,974 all-cause gastroenteritis-coded hospitalizations (1,381 rotavirus-coded [15% among Aboriginal] and 105,593 non-rotavirus gastroenteritis-coded [7% among Aboriginal]). Following rotavirus vaccination introduction, significant reductions in rotavirus-coded hospitalization rates were observed in all children aged <5 years (up to 79% among non-Aboriginal and up to 66% among Aboriginal). Among adults aged ≥65 years, rotavirus-coded hospitalizations were 89% (95% confidence interval, 16-187%) higher in the rotavirus vaccination program period. The time-series analysis suggested reductions in all-cause gastroenteritis hospitalizations in the post-vaccination period among both vaccinated and unvaccinated (age-ineligible) children, with increases observed in adults aged ≥45 years. CONCLUSIONS: Rotavirus vaccination has been associated with a significant decline in gastroenteritis hospitalizations among children. The increase in the elderly requires further evaluation, including assessment of the cost-benefits of rotavirus vaccination in this population.

Continued Evidence of the Impact of Rotavirus Vaccine in Children Less Than 3 Years of Age From the United States New Vaccine Surveillance Network: A Multisite Active Surveillance Program, 2006-2016.

BACKGROUND: Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. METHODS: Children < 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006-2007 defined as the prevaccine period and 2008-2016 as the postvaccine period. Rotavirus genotype trends were compared over time. RESULTS: Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (P < .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. CONCLUSIONS: The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children < 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes.

Impact of the Introduction of Rotavirus Vaccine on Hospital Admissions for Diarrhea Among Children in Kenya: A Controlled Interrupted Time-Series Analysis.

BACKGROUND: Monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs). METHODS: Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged <5 years in 2 health facilities in Kenya. A controlled interrupted time-series analysis was undertaken to compare RVH pre- and post-vaccine introduction using rotavirus-negative cases as a control series. The change in incidence post-vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality, and multiple health worker industrial actions (strikes). RESULTS: Between January 2010 and June 2017 there were 1513 and 1652 diarrhea hospitalizations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively. There was a 57% (95% confidence interval [CI], 8-80%) reduction in RVHs observed in the first year post-vaccine introduction in Kilifi and a 59% (95% CI, 20-79%) reduction in Siaya. In the second year, RVHs decreased further at both sites, 80% (95% CI, 46-93%) reduction in Kilifi and 82% reduction in Siaya (95% CI. 61-92%); this reduction was sustained at both sites into the third year. CONCLUSIONS: A substantial reduction in RVHs and all-cause diarrhea was observed in 2 demographic surveillance sites in Kenya within 3 years of vaccine introduction.

Spatio-temporal impact of self-financed rotavirus vaccination on rotavirus and acute gastroenteritis hospitalisations in the Valencia region, Spain.

BACKGROUND: Several studies have shown a substantial impact of Rotavirus (RV) vaccination on the burden of RV and all-cause acute gastroenteritis (AGE). However, the results of most impact studies could be confused by a dynamic and complex space-time process. Therefore, there is a need to analyse the impact of RV vaccination on RV and AGE hospitalisations in a space-time framework to detect geographical-time patterns while avoiding the potential confusion caused by population inequalities in the impact estimations. METHODS: A retrospective population-based study using real-world data from the Valencia Region was performed among children aged less than 3 years old in the period 2005-2016. A Bayesian spatio-temporal model was constructed to analyse RV and AGE hospitalisations and to estimate the vaccination impact measured in averted hospitalisations. RESULTS: We found important spatio-temporal patterns in RV and AGE hospitalisations, RV vaccination coverage and in their associated adverted hospitalisations. Overall, ~ 1866 hospital admissions for RV were averted by RV vaccination during 2007-2016. Despite the low-medium vaccine coverage (~ 50%) in 2015-2016, relevant 36 and 20% reductions were estimated in RV and AGE hospitalisations respectively. CONCLUSIONS: The introduction of the RV vaccines has substantially reduced the number of RV hospitalisations, averting ~ 1866 admissions during 2007-2016 which were space and time dependent. This study improves the methodologies commonly used to estimate the RV vaccine impact and their interpretation.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis, Burkina Faso, 2016-2017.

BACKGROUND: In 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program, to be administered to children at 8, 12, and 16 weeks of age. We evaluated the impact of PCV13 on pneumococcal meningitis. METHODS: Using nationwide surveillance, we gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We compared annual incidence (cases per 100 000) 4 years after PCV13's introduction (2017) to average pre-PCV13 incidence (2011-2013). We adjusted incidence for age and proportion of cases with CSF tested at national laboratories. RESULTS: In 2017, pneumococcal meningitis incidence was 2.7 overall and 10.5 (<1 year), 3.8 (1-4 years), 3.5 (5-14 years), and 1.4 (≥15 years) by age group. Compared to 2011-2013, PCV13-serotype incidence was significantly lower among all age groups, with the greatest decline among children aged <1 year (77%; 95% confidence interval [CI], 65%-84%). Among all ages, the drop in incidence was larger for PCV13 serotypes excluding serotype 1 (79%; 95% CI, 72%-84%) than for serotype 1 (52%; 95% CI, 44%-59%); incidence of non-PCV13 serotypes also declined (53%; 95% CI, 37%-65%). In 2017, 45% of serotyped cases among all ages were serotype 1 and 12% were other PCV13 serotypes. CONCLUSIONS: In Burkina Faso, meningitis caused by PCV13 serotypes continues to decrease, especially among young children. However, the concurrent decline in non-PCV13 serotypes and short pre-PCV13 observation period complicate evaluation of PCV13's impact. Efforts to improve control of serotype 1, such as switching from a 3 + 0 schedule to a 2 + 1 schedule, may improve overall control of pneumococcal meningitis in this setting.

Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo.

BACKGROUND: Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. METHODS: Cerebrospinal fluid was collected from children <5 years with suspected PBM admitted to the Sylvanus Olympio Teaching Hospital. Phenotypic detection of pneumococcus, meningococcus, and H. influenzae was confirmed through microbiological techniques. Samples were shipped to the Regional Reference Laboratory to corroborate results by species-specific polymerase chain reaction. RESULTS: Overall, 3644 suspected PBM cases were reported, and 98 cases (2.7%: 98/3644) were confirmed bacterial meningitis. Pneumococcus was responsible for most infections (67.3%: 66/98), followed by H. influenzae (23.5%: 23/98) and meningococcus (9.2%: 9/98). The number of pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction with 59 cases from July 2010 to June 2014 and 7 cases from July 2014 to June 2016. However, 5 cases caused by nonvaccine serotypes were observed. Fewer PBM cases caused by vaccine serotypes were observed in infants <1 year compared to children 2-5 years. CONCLUSIONS: Routine surveillance showed that PCV13 vaccination is effective in preventing pneumococcal meningitis among children <5 years of age in the Maritime region. This complements the MenAfriVac vaccination against meningococcal serogroup A to prevent meningitis outbreaks in the northern region of Togo. Continued surveillance is vital for estimating the prevalence of PBM, determining vaccine impact, and anticipating epidemics in Togo.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Meningitis and Pneumonia Hospitalizations in Children aged <5 Years in Senegal, 2010-2016.

BACKGROUND: Senegal introduced a 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, given at 6, 10, and 14 weeks of age. We document trends of meningitis and pneumonia after the PCV13 introduction. METHODS: From October 2010-October 2016, hospitalization data for clinical meningitis and pneumonia in children aged <5 years were collected from logbooks at a large, tertiary, pediatric hospital in Dakar. We used a set of predetermined keywords to define hospitalizations for extraction from hospital registers. We conducted a time-series analysis and compared hospitalizations before and after the PCV13 introduction, accounting for seasonality. The initial PCV13 uptake period (October 2013-September 2014) was considered to be transitional and was excluded. RESULTS: Over the 7-year period, 1836 and 889 hospitalizations with a discharge diagnosis of pneumonia and meningitis, respectively, occurred in children aged <5 years. In children aged <12 months, a small, significant reduction in pneumonia was observed post-PCV13 (-3.8%, 95% confidence interval [CI] -1.5 to -5.9%). No decline was observed among children aged 12-59 months (-0.7%, 95% CI -0.8 to 2.2%). Meningitis hospitalizations remained stable for children aged <12 months (1.8%, 95% CI -0.9 to 4.4%) and 12-59 months (-0.5%, 95% CI -3.6 to 2.6%). CONCLUSIONS: We used data from 1 hospital to detect a small, significant reduction in all-cause pneumonia hospitalizations 2 years post-PCV13 introduction in infants; the same trend was not measurable in children aged 12-59 months or in meningitis cases. There is a need for continued surveillance to assess the long-term impact of sustained PCV13 use and to monitor how pneumococcus is causing disease in the meningitis belt.

Trends in High-grade Cervical Lesions and Cervical Cancer Screening in 5 States, 2008-2015.

BACKGROUND: We describe changes in rates of cervical intraepithelial neoplasia grades 2, 3 and adenocarcinoma in situ (CIN2+) during a period of human papillomavirus (HPV) vaccine uptake and changing cervical cancer screening recommendations. METHODS: We conducted population-based laboratory surveillance for CIN2+ in catchment areas in 5 states, 2008-2015. We calculated age-specific CIN2+ rates per 100000 women by age groups. We estimated incidence rate ratios (IRR) of CIN2+ for 2-year periods among all women and among screened women to evaluate changes over time. RESULTS: A total of 16572 CIN2+ cases were reported. Among women aged 18-20 and 21-24 years, CIN2+ rates declined in all sites, whereas in women aged 25-29, 30-34, and 35-39 years, trends differed across sites. The percent of women screened annually declined in all sites and age groups. Compared to 2008-2009, rates among screened women were significantly lower for all 3 periods in women aged 18-20 years (2010-2011: IRR 0.82, 95% confidence interval [CI] 0.67-0.99; 2012-2013: IRR 0.63, 95% CI 0.47-0.85; 2014-2015: IRR 0.44, 95% CI 0.28-0.68) and lower for the latter 2 time periods in women aged 21-24 years (2012-2013: IRR 0.86, 95% CI 0.79-0.94; 2014-2015: IRR 0.61, 95% CI 0.55-0.67). CONCLUSIONS: From 2008-2015, both CIN2+ rates and cervical cancer screening declined in women aged 18-24 years. The significant decreases in CIN2+ rates among screened women aged 18-24 years are consistent with a population-level impact of HPV vaccination.

Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.