Diphtheria in a Swiss Asylum Seeker Reception Centre: Outbreak Investigation and Evaluation of Testing and Vaccination Strategies.

Objectives: To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. Methods: We retrospectively analysed clinical, microbiology, and case management data of all asylum seekers tested for C. diphtheriae between 28th August and 31st December 2022 while residing at the centre. Results are reported descriptively. Results: Among 265 individuals tested, ten cases of cutaneous diphtheria, one simultaneous respiratory and cutaneous case, and nine respiratory carriers were identified. Mass throat screening, targeted throat testing and targeted wound testing yielded 4.8%, 4.3%, and 17.4% positive results, respectively. No respiratory carrier was identified among cutaneous cases undergoing a throat swab, and no symptomatic case was identified among individuals with unspecific throat symptoms. Rates of vaccination implementation of newly arriving asylum seekers before and after the outbreak were low (17.5% and 15.5%, respectively), as were rates of targeted vaccination among cases and close contacts. Conclusion: We provide evidence for transmission both prior to arrival and within the setting, suboptimal practices and timeliness of testing, and implementation gaps in vaccination.

Balto and Togo during the cold winter of Alaska (1925): the two canine heroes in the fight against diphtheria.

In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance.

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded, randomized, parallel-group study.

OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).

Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis.

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.

Quantitative analysis of pertussis, tetanus, and diphtheria antibodies in sera and breast milk from Tdap vaccinated women using a qualified multiplex assay.

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

Immunogenicity at delivery after Tdap vaccination in successive pregnancies.

Background: Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination. Methods: Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay. Results: In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy. Conclusion: This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.

A phase 4, open-label study to evaluate the safety and immunogenicity of DTaP5-HBV-IPV-Hib in children previously vaccinated with DTaP2-HBV-IPV-Hib or DTaP5-HBV-IPV-Hib (V419-016).

DTaP5-HBV-IPV-Hib (Vaxelis®) is a hexavalent combination vaccine (HV) indicated in infants and toddlers for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. Switching between HVs during the childhood vaccination series is sometimes necessary due to, for example, vaccine availability, health-care provider preference, and/or tender awards. The purpose of this study was to describe the safety, tolerability, and immunogenicity of a booster dose of Vaxelis® in participants who previously received a primary infant series of either DTaP2-HBV-IPV-Hib (Hexyon®) or Vaxelis®. Healthy participants approximately 11-13 months of age who previously received a two-dose primary series of Hexyon® (HHV group) or Vaxelis® (VVV group) all received a Vaxelis® booster dose. Immunogenicity was evaluated by measuring antibody levels to individual vaccine antigens approximately 30 days following booster vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). The proportions of participants with antibody-specific responses for antigens contained in both Vaxelis® and Hexyon® at 30 days post-toddler-booster vaccination with Vaxelis® were comparable between groups, and higher in the VVV group for Vaxelis® antigens PRN and FIM2/3. The overall proportions of participants with AEs were generally comparable between groups. Following a booster dose of Vaxelis®, immune responses were comparable between groups for all shared antigens, and higher in the VVV group for antigens found only in Vaxelis®. The booster was well tolerated in both groups. These data support the use of Vaxelis® as a booster in mixed HV regimens.

Cost-effectiveness analysis of pertussis booster vaccination for adolescents in Japan.

INTRODUCTION: In Japan, the introduction of a fifth diphtheria-tetanus-acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11-12 years old who are currently receiving the diphtheria-tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. METHOD: We used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020-2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. RESULTS: The ICER from the payers' perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. CONCLUSION: The cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends.

Antenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization and risk of serogroup 19 IPD in children: An indirect cohort study.

The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been indicated for pregnant women in Quebec, Canada since 2018. Recent literature suggests maternal Tdap interferes with the pneumococcal vaccine response in children exposed in utero because of maternally transferred anti-diphtheria antibodies, a phenomenon known as blunting. Using an indirect cohort study, we investigated whether maternal Tdap vaccination could alter the protection of PCV vaccines against serotype 19A/F IPD (conjugated to diphtheria toxoid in PCV10). Thirty-seven immunized IPD cases (serotype 19A/F) and 90 immunized IPD controls (non-vaccine serotypes) were analyzed using multivariate logistic regression. Our analyses did not identify antenatal Tdap exposure as a risk factor for IPD in vaccinated children, with and odds ratio close to the null (odds ratio = 0.82, 95%CI = 0.32-2.07). As this study is the first to assess the impact of maternal immunization on pneumococcal disease risk, future investigations involving a larger number of cases should be conducted to confirm or infirm our findings.

Influenza and Tetanus, Diphtheria, and Acellular Pertussis Vaccination Coverage During Pregnancy: Pregnancy Risk Assessment Monitoring System, 2020.

OBJECTIVES: Estimates of vaccination coverage during pregnancy and identification of disparities in vaccination coverage can inform vaccination campaigns and programs. We reported the prevalence of being offered or told to get the influenza vaccine by a health care provider (hereinafter, provider); influenza vaccination coverage during the 12 months before delivery; and tetanus, diphtheria, and acellular pertussis (Tdap) vaccination coverage during pregnancy among women with a recent live birth in the United States. METHODS: We analyzed 2020 data from the Pregnancy Risk Assessment Monitoring System from 42 US jurisdictions (n = 41 673). We estimated the overall prevalence of being offered or told to get the influenza vaccine by a provider and influenza vaccination coverage during the 12 months before delivery. We estimated Tdap vaccination coverage during pregnancy from 21 jurisdictions with available data (n = 22 020) by jurisdiction and select characteristics. RESULTS: In 2020, 84.9% of women reported being offered or told to get the influenza vaccine, and 60.9% received it, ranging from 35.0% in Puerto Rico to 79.7% in Massachusetts. Influenza vaccination coverage was lower among women who were not offered or told to get the influenza vaccine (21.4%) than among women who were offered or told to get the vaccine (68.1%). Overall, 72.7% of women received the Tdap vaccine, ranging from 52.8% in Mississippi to 86.7% in New Hampshire. Influenza and Tdap vaccination coverage varied by all characteristics examined. CONCLUSIONS: These results can inform vaccination programs and strategies to address disparities in vaccination coverage during pregnancy and may inform vaccination efforts for other infectious diseases among pregnant women.

Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines.

At present, quality control of diphtheria vaccines by both manufacturers and national control laboratories relies heavily on in vivo assays to confirm potency. As part of the VAC2VAC project we have developed a monoclonal antibody (mAb) enzyme-linked immunosorbent assay (ELISA) to measure the relative amount and quality of diphtheria toxoid (DTxd) in diphtheria-tetanus based vaccines and believe this test has the potential to play a key role in a control strategy no longer including an in vivo potency test. The mAb ELISA is highly specific, has good dilutional linearity, and is suitable for detecting DTxd in a range of different human vaccine products. We demonstrate the ability of the assay to discriminate between batches of different content and quality using vaccine batches that were prepared to contain differing amounts of DTxd or were altered by exposure to heat or oxidative stress. We also demonstrate successful transfer of the method to other laboratories and show that different diphtheria antigen materials may be able to serve as a reference antigen for local standardization of the method. The assay is ideally suited for incorporation into a consistency approach for routine diphtheria vaccine quality control testing and may be suitable to serve as the stability indicating test in replacement of the current in vivo potency test.

Diphtheria vaccines help to protect against diphtheria infection. Currently, animal tests are used to ensure the potency of such vaccines. Since these tests were first introduced, there have been improvements in non-animal technologies that can be used to ensure consistent production of potent vaccine batches. To demonstrate that a new batch of diphtheria vaccine is consistent with a previous batch of known potency, the quality and amount of the component that stimulates the immune response upon vaccination must be assessed in comparison. We have developed an assay that can measure the quality of a range of different diphtheria vaccine product types. The assay is very specific and reliable, and different laboratories obtained comparable results, showing that the assay is suited for routine use. Once validated by manufacturers and recognized by regulators, this assay will greatly reduce the number of animals needed for batch release of diphtheria vaccines.

Vaccine Immunity in Children After Hematologic Cancer Treatment: A Retrospective Single-center Study.

BACKGROUND: Children lose their vaccine-induced protection and are particularly vulnerable to vaccine-preventable diseases after chemotherapy. However, revaccination guidelines are heterogeneous, and there is often a lack of revaccination post-treatment. AIMS: We conducted a retrospective study of children with hematologic cancer to evaluate vaccine immunity before and after the end of treatment and to determine whether the current institutional revaccination program based on vaccine serology results was followed and effective. MATERIALS AND METHODS: Data of all children treated by chemotherapy between April 2015 and July 2021 were extracted from hospital medical records for analysis. Serum antibody levels and time of vaccination were evaluated for diphtheria, tetanus, Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), measles, varicella, and hepatitis B. RESULTS: We included 31 patients (median age, 9 years). At cancer diagnosis, 90% of children were protected against tetanus, diphtheria, and measles; 65% to 67% were protected against pneumococcus and varicella; and 25% against hepatitis B. At the end of chemotherapy, 67% to 71% of patients were protected against tetanus, varicella, and measles; 40% remained protected against hepatitis B; and 27% to 33% against pneumococcus and diphtheria. Patients were revaccinated at various times after the end of treatment but not systematically. During the first-year post-treatment, 20% to 25% of children remained unprotected against pneumococcus, measles, and hepatitis B, one third against diphtheria, but all were protected against tetanus and varicella. CONCLUSIONS: An effective individualized vaccination program post-cancer based on serology results should be accompanied by an appropriate serology tracking method and follow-up to assess if booster doses are necessary. Our study supports vaccinating all children with a dose of the 13-valent pneumococcal conjugate at cancer diagnosis and at 3 months post-treatment with the combined diphtheria-tetanus-acellular pertussis/poliomyelitis vaccine/hepatitis B virus plus or minus Hib and 13-valent pneumococcal conjugate and meningococcal vaccine, including measles/mumps/rubella-varicella zoster virus vaccine if good immune reconstitution is present.

Recurrent diphtheria outbreaks in Nigeria: A review of the underlying factors and remedies.

INTRODUCTION: The introduction of the diphtheria-tetanus-pertussis (DTP) vaccine into childhood immunization programs resulted in its widespread elimination in high-income countries. However, Nigeria is currently experiencing an outbreak. The primary cause of diphtheria outbreaks and its high mortality rates in Nigeria was waning herd immunity due to low DTP coverage and a lack of diphtheria antitoxin (DAT), respectively. However, the underlying causes of Nigeria's low DTP coverage and DAT supply remain unknown. METHOD: Relevant studies and reports included in our review were obtained by a search through Google Scholar, PubMed, and organization websites using the terms "Diphtheria-Pertussis-Tetanus vaccine OR Diphtheria antitoxin and Nigeria OR Diphtheria Outbreak." All articles considering diphtheria outbreaks, DTP vaccine, and DAT supply in Nigeria were considered without time restriction due to the paucity of data. We used the narrative synthesis approach to critically appraise, analyze, and draw inferences from the selected articles. RESULTS: The main causes of low DTP coverage are insufficient supply, an inefficient cold chain system, and low uptake due to poor health literacy and negative sociocultural and religious beliefs, whereas the key barriers to DAT availability are insufficient production by pharmaceutical industries because of low demand and priority. CONCLUSION: The underlying causes of Nigeria's low DTP coverage and DAT supply are multifactorial. Both short-term and long-term measures are needed to control this outbreak and prevent future occurrences.

A looming epidemic: combating the recurrent outbreaks of diphtheria in Nigeria.

Nigeria has endured several diphtheria outbreaks over the last few decades, mirroring a suboptimal population immunity across several demographics within the country. The country's northern region has been affected mainly by this infectious disease; it directly depicts the effect of poor DPT vaccine uptake amongst children in this region compared to other geopolitical zones in Nigeria. Whilst pharmaceutical intervention and surveillance activities have commenced as directed by the NCDC, to combat this public health menace, top leaders of the Nigerian healthcare system - public and private sectors, must understudy the predisposing factors gearing the recurrence of diphtheria in Nigeria and provide robust, research-based and scientific mechanisms to arrest the root causes of the incessant outbreaks. This article discusses the factors promoting the recurrent diphtheria outbreaks in Nigeria, the preexisting interventions with their existential deterrents, and new strategies recommended to curb the further resurgence of the disease.

Effect of immunization registry-based provider reminder to initiate HPV vaccination at age 9, Washington state.

Human papillomavirus (HPV) vaccination rates are lower than Tetanus-diphtheria-pertussis (Tdap) and Meningococcal conjugate (MenACWY) rates, although the Advisory Committee on Immunization Practices recommends all three vaccines be given routinely at age 11-12. Evidence is mounting that children who initiate HPV vaccination starting at age 9 are more likely to complete the series on time. Washington state implemented a provider reminder through its immunization information system (WAIIS) in January 2023 to increase HPV vaccine initiation at 9-years-old by updating the forecasted recommended age for HPV from age 11 to 9. The effectiveness of provider reminders when implemented via an immunization information system (IIS) is poorly understood. We evaluated the impact of this forecast update using a seasonally adjusted interrupted time series regression of weekly HPV initiations at 9-years-old before and after implementation. We also examined time series trends of vaccine administration between 2018 and 2023 for HPV initiation at age 9, as well as Tdap, MenACWY and HPV initiation at age 11. The WAIIS forecast update doubled the weekly rate of HPV initiation among 9-year-olds in Washington state, although the weekly count of initiation at 9 remains far lower than initiations at 11. Jurisdictions wanting to increase HPV vaccine initiation at earlier ages should consider updating their forecast algorithm and investing in complementary evidence-based strategies such as provider and parent education, and clinic-based quality improvement efforts. The reach of IIS forecaster updates may be enhanced by working with administrators of electronic medical record systems to ensure parity of provider prompts with IIS.