Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism: A Substudy of the TRAVERSE Randomized Clinical Trial.

Importance: The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown. Objective: To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes. Design, Setting, and Participants: This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US. Participants included men aged 45 to 80 years with hypogonadism and prediabetes or diabetes who were enrolled in TRAVERSE between May 23, 2018, and February 1, 2022. Intervention: Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel until study completion. Main Outcomes and Measures: The primary end point was the risk of progression from prediabetes to diabetes, analyzed using repeated-measures log-binomial regression. The secondary end point was the risk of glycemic remission (hemoglobin A1c level <6.5% [to convert to proportion of total hemoglobin, multiply by 0.01] or 2 fasting glucose measurements <126 mg/dL [to convert to mmol/L, multiply by 0.0555] without diabetes medication) in men who had diabetes. Results: Of 5204 randomized participants, 1175 with prediabetes (mean [SD] age, 63.8 [8.1] years) and 3880 with diabetes (mean [SD] age, 63.2 [7.8] years) were included in this study. Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%). Risk of progression to diabetes did not differ significantly between testosterone and placebo groups: 4 of 598 (0.7%) vs 8 of 562 (1.4%) at 6 months, 45 of 575 (7.8%) vs 57 of 533 (10.7%) at 12 months, 50 of 494 (10.1%) vs 67 of 460 (14.6%) at 24 months, 46 of 359 (12.8%) vs 52 of 330 (15.8%) at 36 months, and 22 of 164 (13.4%) vs 19 of 121 (15.7%) at 48 months (omnibus test P = .49). The proportions of participants with diabetes who experienced glycemic remission and the changes in glucose and hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes. Conclusions and Relevance: In men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone- and placebo-treated men. Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism. Trial Registration: ClinicalTrials.gov Identifier: NCT03518034.

Depressive Syndromes in Men with Hypogonadism in the TRAVERSE Trial: Response to Testosterone Replacement Therapy.

CONTEXT: The effect of testosterone on depressive symptoms in men with hypogonadism remains incompletely understood. OBJECTIVE: We assessed the effects of testosterone replacement therapy (TRT) in improving depressive symptoms in hypogonadal men with and without depressive symptoms enrolled in the TRAVERSE cardiovascular safety trial. DESIGN: Randomized, placebo-controlled, double-blind. SETTING: 316 trial sites. PARTICIPANTS: Men, 45 to 80 years, with two fasting testosterone levels <300 ng/dL, one or more hypogonadal symptoms, cardiovascular disease (CVD), or increased risk of CVD. We evaluated three subgroups of participants: 1) men with rigorously defined late-life-onset, low-grade persistent depressive disorder (LG-PDD, previously "dysthymia"); 2) all men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and 3) all randomized men. INTERVENTION: 1.62% transdermal testosterone or placebo gel. OUTCOME MEASURES: Proportions of participants 1) meeting criteria for LG-PDD or 2) with significant depressive symptoms; changes in depressive symptoms, energy, sleep quality, and cognition in testosterone- vs. placebo-treated men in the three subgroups. RESULTS: Of 5,204 randomized participants, 2,643 (50.8%) had significant depressive symptoms, but only 49 (1.5%) met rigorous criteria for LG-PDD. Among those with LG-PDD, there was no significant difference in any outcome measure between the TRT and placebo groups, possibly reflecting low statistical power. In men with significant depressive symptoms n=2643) and in all randomized participants (n=5204), TRT was associated with modest but significantly greater improvements in mood and energy but not cognition or sleep quality. CONCLUSIONS: Depressive symptoms are common in middle-aged and older men with hypogonadism, but LG-PDD is uncommon. TRT is associated with small improvements in mood and energy in hypogonadal men with and without significant depressive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03518034.

Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism.

CONTEXT: Few long-term randomized trials have evaluated the efficacy of testosterone replacement therapy (TRT) in improving sexual function and hypogonadal symptoms in men with hypogonadism and whether effects are sustained beyond 12 months. OBJECTIVE: The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. The Sexual Function Study, nested within the parent trial, determined testosterone's efficacy in improving sexual activity, hypogonadal symptoms, libido, and erectile function among men reporting low libido. METHODS: Among 5204 men, 45-80 years, with 2 testosterone concentrations <300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk enrolled in the TRAVERSE trial, 1161 with low libido were enrolled in the Sexual Function Study (587 randomized to receive 1.62% testosterone gel and 574 to placebo gel for the duration of their participation in the study). Primary outcome was change from baseline in sexual activity score. Secondary outcomes included hypogonadal symptoms, erectile function, and sexual desire. RESULTS: TRT was associated with significantly greater improvement in sexual activity than placebo (estimated mean [95% CI] between-group difference 0.49 [0.19,0.79] and 0.47 [0.11, 0.83] acts per day at 6 and 12 months, respectively; omnibus test P = .011); treatment effect was maintained at 24 months. TRT improved hypogonadal symptoms and sexual desire, but not erectile function, compared with placebo. CONCLUSION: In middle-aged and older men with hypogonadism and low libido, TRT for 2 years improved sexual activity, hypogonadal symptoms, and sexual desire, but not erectile function.

Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism: A Randomized Clinical Trial.

Importance: Testosterone deficiency causes mild anemia. Whether testosterone replacement therapy (TRT) can correct anemia or prevent the development of anemia in men with hypogonadism remains incompletely understood. Objective: To assess the efficacy of TRT in correcting anemia in men with hypogonadism and anemia, and reducing the risk of developing anemia in those without anemia. Design, Setting, and Participants: This randomized, placebo-controlled trial included men with hypogonadism at 316 US sites enrolled between May 2018 and February 2022. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study, which evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. Eligible participants were aged 45 to 80 years, with 2 testosterone concentration results below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. The last study visit took place in January 2023. Data were analyzed between March and August 2023. Intervention: Participants were randomized with stratification for preexisting CVD to 1.62% testosterone gel or placebo gel daily for the study duration. Main Outcomes and Measures: Proportion of participants with anemia (hemoglobin below 12.7 g/dL) whose anemia remitted (hemoglobin 12.7 g/dL or above) over the study duration. Secondary end points included incidence of anemia among men who were not anemic. Binary end points were analyzed using repeated-measures log-binomial regression. Results: A total of 5204 men were included, 815 with anemia (mean [SD] age, 64.8 [7.7] years; 247 Black [30.3%], 544 White [66.7%], 24 other [2.9%]) and 4379 without anemia (mean [SD] age, 63.0 [7.9] years; 629 Black [14.4%], 3603 White [82.3%], 147 other [3.4%]). Anemia corrected in a significantly greater proportion of testosterone-treated than placebo-treated men at 6 months (143 of 349 [41.0%] vs 103 of 375 [27.5%]), 12 months (152 of 338 [45.0%] vs 122 of 360 [33.9%]), 24 months (124 of 290 [42.8%] vs 95 of 307 [30.9%]), 36 months (94 of 216 [43.5%] vs 76 of 229 [33.2%]), and 48 months (41 of 92 [44.6%] vs 38 of 97 [39.2%]) (P = .002). Among participants without anemia, a significantly smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Changes in hemoglobin were associated with changes in energy level. Conclusions and Relevance: In middle-aged and older men with hypogonadism and anemia, TRT was more efficacious than placebo in correcting anemia. Among men who were not anemic, a smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Trial Registration: ClinicalTrials.gov Identifier: NCT03518034.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Use of catch-up vaccinations in the second year of life (2YL) platform to close immunity gaps: A secondary DHS analysis in Pakistan, Philippines, and South Africa.

BACKGROUND: Immunity gaps caused by COVID-19-related disruptions highlight the importance of catch-up vaccination. Number of countries offering vaccines in second year of life (2YL) has increased, but use of 2YL for catch-up vaccination has been variable. We assessed pre-pandemic use of 2YL for catch-up vaccination in three countries (Pakistan, the Philippines, and South Africa), based on existence of a 2YL platform (demonstrated by offering second dose of measles-containing vaccine (MCV2) in 2YL), proportion of card availability, and geographical variety. METHODS: We conducted a secondary data analysis of immunization data from Demographic and Health Surveys (DHS) in Pakistan (2017-2018), the Philippines (2017), and South Africa (2016). We conducted time-to-event analyses for pentavalent vaccine (diphtheria-tetanus-pertussis-Hepatitis B-Haemophilus influenzae type b [Hib]) and MCV and calculated use of 2YL and MCV visits for catch-up vaccination. RESULTS: Among 24-35-month-olds with documented dates, coverage of third dose of pentavalent vaccine increased in 2YL by 2%, 3%, and 1% in Pakistan, Philippines, and South Africa, respectively. MCV1 coverage increased in 2YL by 5% in Pakistan, 10% in the Philippines, and 3% in South Africa. In Pakistan, among 124 children eligible for catch-up vaccination of pentavalent vaccine at time of a documented MCV visit, 45% received a catch-up dose. In the Philippines, among 381 eligible children, 38% received a pentavalent dose during an MCV visit. In South Africa, 50 children were eligible for a pentavalent vaccine dose before their MCV1 visit, but only 20% received it; none with MCV2. CONCLUSION: Small to modest vaccine coverage improvements occurred in all three countries through catch-up vaccination in 2YL but many missed opportunities for vaccination continue to occur. Using the 2YL platform can increase coverage and close immunity gaps, but immunization programmes need to change policies, practices, and monitor catch-up vaccination to maximize the potential.

Progress towards the elimination of hepatitis B in children in Colombia: A novel two-phase study approach.

The World Health Organization (WHO) has established a target to eliminate mother-to-child-transmission (EMTCT) of hepatitis B virus (HBV), defined as a prevalence of hepatitis B surface antigen (HBsAg) of ≤0.1% among children, by 2030. Using nationally representative serosurveys to verify achievement of this target requires large sample sizes and significant resources. We assessed the feasibility of a potentially more efficient two-phase method to verify EMTCT of HBV in Colombia. In the first phase, we conducted a risk assessment to identify municipalities at the highest risk of ongoing HBV transmission. We ranked the 1122 municipalities of Colombia based on the reports of HBV infection in pregnant women per 1000 population. Municipalities with ≥0.3 reports per 1000 persons (equating to the top quartile) were further assessed based on health facility birth rates, coverage with three doses of hepatitis B vaccine (HepB3) and seroprevalence data. Hepatitis B risk was considered to be further increased for municipalities with HepB3 coverage or health facility birth rate <90%. In the second phase, we conducted a multistage household serosurvey of children aged 5-10 years in 36 municipalities with the highest assessed HBV risk. HBsAg was not detected in any of 3203 children tested, yielding a 90% upper confidence bound of <0.1% prevalence. Coverage with HepB3 and hepatitis B birth dose was high at 97.5% and 95.6%, respectively. These results support the conclusion that Colombia has likely achieved EMTCT of HBV.

Measles susceptibility in maternal-infant dyads-Bamako, Mali.

Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity. We investigated the relationship between maternal age and measles susceptibility in mother-infant pairs in Mali through six months of infancy. We measured serum measles antibodies in 340 mother-infant pairs by plaque reduction neutralization test (PRNT) and calculated the proportion of mothers with protective titers (>120 mIU/mL) at delivery and the proportion of infants with protective titers at birth, and at three and six months of age. We explored associations between maternal age and measles antibodies in mothers and infants at the timepoints noted. Ten percent of Malian newborns were susceptible to measles; by six months nearly all were. Maternal and infant antibody titers were highly correlated. At delivery, 11% of mothers and 10% of newborns were susceptible to measles. By three and six months, infant susceptibility increased to 72% and 98%, respectively. Infants born to younger mothers were most susceptible at birth and three months. Time to susceptibility was 6.6 weeks in infants born to mothers with measles titer >120-<430 mIU/mL versus 15.4 weeks when mothers had titers ≥430 mIU/mL. Maternal and newborn seroprotective status were positively correlated. Improved strategies are needed to protect susceptible infants from measles infection and death. Increasing measles immunization coverage in vaccine eligible populations, including nonimmune reproductive-aged women and older children should be considered.

Decision Making and Implementation of the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

BACKGROUND: Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings. METHODS: We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel-based tool to estimate the financial and economic vaccination campaign costs. RESULTS: The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July-August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively. CONCLUSION: The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns.

Estimating population immunity to poliovirus in Lebanon: Results from a seroprevalence survey, 2016.

INTRODUCTION: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. METHODS: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Progamme on Immunization (EPI) methodology. Sera from selected children aged 12-59 months were tested for poliovirus neutralizing antibodies. RESULTS: Of 2,164 children recruited in this study, 1,893 provided sufficient quantity of serum samples for laboratory testing. Seroprevalence for all three poliovirus serotypes was greater than 90% in all six governorates. Poliovirus vaccine coverage with three or more doses, based on vaccination cards or parental recall, ranged between 54.1% for children aged 36-47 months in the North and 83.5% for children aged 48-59 months in Beirut. CONCLUSION: Immunity to polioviruses was high in Lebanon in 2016 following a series of supplementary immunization activities. It is essential to continue strategies that increase vaccination coverage in order to sustain the considerably high immunity levels and prevent reintroduction and transmission of poliovirus. Educating caregivers and training health care workers on the standardized usage of home-based vaccination records is needed to guarantee the accuracy of records on children's vaccination status.

Seroprevalence of chronic hepatitis B virus infection and immunity to measles, rubella, tetanus and diphtheria among schoolchildren aged 6-7 years old in the Solomon Islands, 2016.

The Western Pacific Region (WPR) established a goal to decrease chronic hepatitis B virus (HBV) infection among children to <1% and to achieve ≥95% hepatitis B vaccine birth dose (HepB-BD) and ≥95% three-dose (HepB3) coverage by 2017. In 2016, we conducted a national serosurvey in the Solomon Islands among 6-7-year-old school children to assess progress towards the control goal and immunity to measles, rubella, tetanus and diphtheria. Eighty schools were selected systematically proportional to their 6-7-year-old population; all 6-7-year-olds were enrolled. We collected basic demographic information and vaccination history. Children were tested for HBV surface antigen (HBsAg) using a rapid test, and for immunity to measles, rubella, tetanus, and diphtheria using a multiplex bead assay. In total, 1,249 out of 1,492 children (84%) were enrolled, among whom 1,169 (94%) underwent HBsAg testing and 1,156 (93%) provided dried blood spots. Almost 80% (n = 982) of enrolled children had vaccination cards, among whom 59% (n = 584) received a timely HepB-BD (within 24 hours of birth), 95% (n = 932) received HepB3, and >90% received vaccines for diphtheria, tetanus, and measles (rubella vaccine was not available at the time). HBsAg prevalence was 3.1% (95% confidence interval (CI): 2.0%-4.9%), with 55% of identified cases from one province. Among 982 children with vaccination cards, HBsAg prevalence was higher among children who had not received a timely HepB-BD and at least two HepB doses compared to those who had (4% vs. 2%). Of 1,156 tested children, immunoprotection estimates were 99% (95% CI: 98%-99%) for measles, 99% (95% CI: 97%-100%) for rubella, 85% (95% CI: 83%-87%) for tetanus, and 51% (95% CI: 47%-55%) for diphtheria. Improving timely HepB-BD coverage and maintaining high HepB3 coverage could help Solomon Islands reach the regional HBV control goal. Low immunity to tetanus and diphtheria suggests the need to introduce booster doses to ensure long-term protection.

Measles and rubella IgG seroprevalence in persons 6 month-35 years of age, Mongolia, 2016.

BACKGROUND: In 2015-2016, Mongolia experienced an unexpected large measles outbreak affecting mostly young children and adults. After two nationwide vaccination campaigns, measles transmission declined. To determine if there were any remaining immunity gaps to measles or rubella in the population, a nationally representative serosurvey for measles and rubella antibodies was conducted after the outbreak was over. METHODS: A nationwide, cross-sectional, stratified, three-stage cluster serosurvey was conducted in November-December 2016. A priori, four regional strata (Ulaanbaatar, Western, Central, and Gobi-Eastern) and five age strata (6 months-23 months, 2-7 years, 8-17 years, 18-30 years, and 31-35 years) were created. Households were visited, members interviewed, and blood specimens were collected from age-appropriate members. Blood specimens were tested for measles immunoglobulin G (IgG) and rubella IgG (Enzygnost® Anti-measles Virus/IgG and Anti-rubella Virus/IgG, Siemens, Healthcare Diagnostics Products, GmbH Marburg, Germany). Factors associated with seropositivity were evaluated. RESULTS: Among 4598 persons aged 6 months to 35 years participating in the serosurvey, 94% were measles IgG positive and 95% were rubella IgG positive. Measles IgG seropositivity was associated with increasing age and higher education. Rubella IgG seropositivity was associated with increasing age, higher education, smaller household size, receipt of MMR in routine immunization, residence outside the Western Region, non-Muslim religious affiliation, and non-Kazakh ethnicity. Muslim Kazakhs living in Western Region had the lowest rubella seroprevalence of all survey participants. CONCLUSIONS: Nationally, high immunity to both measles and rubella has been achieved among persons 1-35 years of age, which should be sufficient to eliminate both measles and rubella if future birth cohorts have ≥ 95% two dose vaccination coverage. Catch-up vaccination is needed to close immunity gaps found among some subpopulations, particularly Muslim Kazakhs living in Western Region.

Risk factors for measles virus infection and susceptibility in persons aged 15 years and older in China: A multi-site case-control study, 2012-2013.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. METHODS: Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. RESULTS: 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1-3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6-38.8%). CONCLUSIONS: Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.

Estimating population immunity to poliovirus in Jordan's high-risk areas.

A community-based serosurvey was conducted among children ages 6-59 to assess population immunity in Jordan's high-risk areas following the Middle East polio outbreak response. The survey was a two-stage cluster-quota sample with high risk areas as the primary sampling units. High-risk areas included border and hard-to-reach areas, and areas with a high proportion of refugees, mobile communities and/or low coverage during previous immunization campaigns. Population immunity to poliovirus was high overall. In high-risk areas, Type 1 seroprevalence = 98% (95% CI = 96, 99), Type 2 = 98% (95% CI = 96, 99) and Type 3 = 96% (95% CI = 94, 98). Seroprevalence was higher in the refugee camps: Type 1 seroprevalence = 99.6% (95% CI = 97.9, 100); Type 2: 99.6% (95% CI = 97.9, 99.9), and Type 3: 100% (95% CI = 100,100). The vigilance that the Jordan Ministry of Health has placed on locating and vaccinating high-risk populations has been successful in maintaining high population immunity and averting polio outbreaks despite the influx of refugees from Syria.

Evaluation of the Impact of Meningococcal Serogroup A Conjugate Vaccine Introduction on Second-Year-of-Life Vaccination Coverage in Burkina Faso.

BACKGROUND: After successful meningococcal serogroup A conjugate vaccine (MACV) campaigns since 2010, Burkina Faso introduced MACV in March 2017 into the routine Expanded Programme for Immunization schedule at age 15-18 months, concomitantly with second-dose measles-containing vaccine (MCV2). We examined MCV2 coverage in pre- and post-MACV introduction cohorts to describe observed changes regionally and nationally. METHODS: A nationwide household cluster survey of children 18-41 months of age was conducted 1 year after MACV introduction. Coverage was assessed by verification of vaccination cards or recall. Two age groups were included to compare MCV2 coverage pre-MACV introduction (30-41 months) versus post-MACV introduction (18-26 months). RESULTS: In total, 15 925 households were surveyed; 7796 children were enrolled, including 3684 30-41 months of age and 3091 18-26 months of age. Vaccination documentation was observed for 86% of children. The MACV routine coverage was 58% (95% confidence interval [CI], 56%-61%) with variation by region (41%-76%). The MCV2 coverage was 62% (95% CI, 59%-65%) pre-MACV introduction and 67% (95% CI, 64%-69%) post-MACV introduction, an increase of 4.5% (95% CI, 1.3%-7.7%). Among children who received routine MACV and MCV2, 93% (95% CI, 91%-94%) received both at the same visit. Lack of caregiver awareness about the 15- to 18-month visit and vaccine unavailability were common reported barriers to vaccination. CONCLUSIONS: A small yet significant increase in national MCV2 coverage was observed 1 year post-MACV introduction. The MACV/MCV2 coadministration was common. Findings will help inform strategies to strengthen second-year-of-life immunization coverage, including to address the communication and vaccine availability barriers identified.

Home-based records and vaccination appointment stickers as parental reminders to reduce vaccination dropout in Indonesia: A cluster-randomized controlled trial.

INTRODUCTION: Limited evidence is available about the effectiveness of strategies to remind caregivers when to bring children back for future vaccinations in low- and middle-income country settings. We evaluated the effectiveness of two reminder strategies based on home-based vaccination records (HBR) in Indonesia. METHODS: In this cluster-randomized controlled trial involving 3616 children <1 year of age, 90 health facilities were randomly assigned to either a control group or one of two intervention groups: (1) HBR-only group, where healthcare workers provided an HBR to any child without an HBR during a vaccination visit and instructed the caregiver to keep it at home between visits, or (2) HBR + sticker group, where, in addition to HBR provision, healthcare workers placed vaccination appointment reminder stickers on the HBR. The primary outcome was receipt of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) within 7 months and the secondary outcome was receipt of a timely DTPcv3 dose. RESULTS: Control group DTPcv3 coverage was 81%. In intention-to-treat analysis, neither intervention group had significantly different DTPcv3 coverage compared with the control group (RR = 0.94, 95% confidence interval [CI] 0.87; 1.02 for HBR-only group; RR = 0.97, 95% CI 0.90; 1.04 for HBR + sticker group) by study end. However, children in the HBR + sticker group were 50% more likely to have received a DTPcv3 vaccination (RR = 1.46, 95% CI 1.02, 2.09) within 60 days of DTPcv1 vaccination, compared with children in the control group; children in the HBR-only group were not more likely to have done so (RR = 1.05, 95% CI 0.71, 1.55). DISCUSSION: Reminder stickers had an immediate effect on coverage by improving the proportion of children who received a timely DTPcv3 dose but no effect on the proportion who received DTPcv3 after 7 months. Coupling reminder stickers with strategies to address other reasons why children do not return for vaccination visits should be further explored.

Oral cholera vaccination coverage after the first global stockpile deployment in Haiti, 2014.

INTRODUCTION: In 2014, an oral cholera vaccine (OCV) campaign targeting 185,314 persons aged ≥1 years was conducted in 3 departments via fixed post and door-to-door strategies. This was the first use of the global OCV stockpile in Haiti. METHODS: We conducted a multi-stage cluster survey to assess departmental OCV coverage. Target population estimates were projected from the 2003 Haiti population census with adjustments for population growth and estimated proportion of pregnant women. In the three departments, we sampled 30/106 enumeration areas (EAs) in Artibonite, 30/244 EAs in Centre, and 20/29 EAs in Ouest; 20 households were systematically sampled in each EA. Household and individual interviews using a standard questionnaire were conducted in each selected household; data on OCV receipt were obtained from vaccination card or verbal report. We calculated OCV campaign coverage estimates and 95% confidence intervals (CIs) accounting for survey design. RESULTS: Overall two-dose OCV coverage was 70% (95% CI: 60, 79), 63% (95% CI: 55, 71), and 44% (95% CI: 35, 53) in Artibonite, Centre, and Ouest, respectively. Two-dose coverage was higher in the 1-4 years age group than among those ≥ 15 years in Artibonite (difference: 11%; 95% CI: 5%, 17%) and Ouest (difference: 12%; 95% CI: 3, 20). A higher percentage of children aged 5-14 years received both recommended doses than did those ≥ 15 years (Artibonite: 14% (95% CI: 8%, 19%) difference; Centre: 11% difference (95% CI: 5%, 17%); Ouest: 10% difference (95% CI: 2%, 17%). The most common reason for not receiving any OCV dose was being absent during the campaign or not having heard about vaccination activities. CONCLUSIONS: While coverage estimates in Artibonite and Centre were comparable with other OCV campaigns in Haiti and elsewhere, inadequate social mobilization and outdated population estimates might have contributed to lower coverage in Ouest.

Measles and rubella immunity in the population of Bhutan, 2017.

BACKGROUND: In 2017, measles elimination was verified in Bhutan, and the country appears to have sufficiently high vaccination coverage to achieve rubella elimination. However, a measles and rubella serosurvey was conducted to find if any hidden immunity gaps existed that could threaten Bhutan's elimination status. METHODS: A nationwide, three-stage, cluster seroprevalence survey was conducted among individuals aged 1-4, 5-17, and >20 years in 2017. Demographic information and children's vaccination history were collected, and a blood specimen was drawn. Serum was tested for measles and rubella immunoglobulin G (IgG). Frequencies, weighted proportions, and prevalence ratios for measles and rubella seropositivity were calculated by demographic and vaccination history, taking into account the study design. RESULTS: Of the 1325 individuals tested, 1045 (81%, 95% CI 78%-85%) were measles IgG seropositive, and 1290 (97%, 95% CI 95%-99%) were rubella IgG seropositive. Rubella IgG seropositivity was high in all three age strata, but only 47% of those aged 5-17 years were measles IgG seropositive. Additionally, only 41% of those aged 5-17 years who had documented receipt of two doses of measles- or measles-rubella-containing vaccine were seropositive for measles IgG, but almost all these children were rubella IgG seropositive. CONCLUSIONS: An unexpected measles immunity gap was identified among children 5-17 years of age. It is unclear why this immunity gap exists; however, it could have led to a large outbreak and threatened sustaining of measles elimination in Bhutan. Based on this finding, a mass vaccination campaign was conducted to close the immunity gap.

Immunogenicity of full and fractional dose of inactivated poliovirus vaccine for use in routine immunisation and outbreak response: an open-label, randomised controlled trial.

BACKGROUND: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response. METHODS: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026. FINDINGS: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV. INTERPRETATION: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses. FUNDING: US Centers for Disease Control and Prevention.