What's going on with measles?

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute.

Detection of viral RNA and DNA and immune response following administration of live attenuated measles and varicella vaccines in children with chronic liver disease.

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all by 14 days postvaccination, but VZV DNA, which can be managed with antivirals, was detected in 1 child in the CLD group at 21 days and 1 control at 28 days postvaccination. Humoral or cell-mediated vaccine response was 100% to measles virus and 94% to VZV in the CLD group postvaccination, whereas it was 100% to both vaccines in controls. Our pilot study suggests that both live vaccines can be safely and effectively administered up to 14 days prior to transplantation in children with CLD. We anticipate this will improve vaccination rates and thus decrease rates of vaccine-preventable infections in vulnerable children with CLD.

Severe Adverse Reaction to Measles Vaccine Due to Homozygous Mutation in the IFNAR2 Gene: A Case Report and Literature Review.

Receiving the measles vaccination is crucial for controlling the disease and preventing severe complications. However, adverse reactions can occur in individuals with inborn errors of immunity. This case report details a severe reaction to the measles vaccine in a ten-month-old female with a homozygous mutation in the IFNAR2 gene, leading to immunodeficiency-45. Following vaccination, she developed viremia, meningoencephalitis, and multi-organ failure. Genetic analysis identified a Variant of Uncertain Significance (VUS) in the IFNAR2 gene, which is essential for type I interferon (IFN-I) signaling. This case highlights the importance of incorporating genetic screening into vaccination programs for individuals at risk. It demonstrates the complex relationship between genetic mutations and the immune responses to the vaccines.

Health system barriers to the first dose of measles immunization in Ethiopia: a qualitative study.

BACKGROUND: Ethiopia has made considerable progress toward measles elimination. Despite ongoing efforts, the country remains among those with the highest number of children missing their initial dose of measles vaccine, and the disease continues to be a public health emergency. The barriers within the health system that hinder the first dose of measles immunization have not been thoroughly investigated. This study aims to identify these barriers within the Ethiopian context. METHODS: Qualitative research, using purposive expert sampling to select key informants from health organizations in Addis Ababa, Ethiopia was employed. We conducted in-depth face-to-face interviews using a semi-structured interview guide. A thematic analysis based on the World Health Organization's health systems building blocks framework was conducted. RESULTS: The study uncovered substantial health system barriers to the uptake of the first dose of the measles vaccine in Ethiopia. These barriers include; restricted availability of immunization services, vaccine stockouts, shortage of cold chain technologies, data inaccuracy resulting from deliberate data falsification or accidental manipulation of data, as well as data incompleteness. CONCLUSION: Our research highlighted significant health system barriers to MCV1 immunization, contributing to unmet EPI targets in Ethiopia. Our results suggest that to accelerate the country towards measles elimination, there is an urgent need to improve the health systems components such as service delivery, information systems, as well as access to vaccine and cold chain technologies.

'I was terrified for my child': understanding the link between the Dengvaxia® controversy and the measles vaccine hesitancy in Pasay City, Philippines.

BACKGROUND: The Dengvaxia® (dengue vaccine) controversy has been identified as one of the main reasons for the measles vaccine hesitancy in the Philippines. Our study aimed to identify various issues related to the Dengvaxia® controversy and to link these issues with the social perspective of measles vaccine refusal. METHODS: Semi-structured interviews and a focus group discussion using ethnography research were conducted with 41 parents and healthcare workers in Pasay City. Using Victor Turner's Social Drama Theory, our study identified existing social issues relating to the different angles of the Dengvaxia® controversy and the measles vaccine hesitancy. RESULTS: Misinformation on the failed Dengvaxia® rollout implementation has challenged the fundamental understanding of the importance of immunization programs. Our findings on vaccine hesitancy in the community showed a complex problem with compounded factors, including medical populism, moral panics and other social views. We described how Pasay City's clinic waiting room became a significantly important scenario where individuals often discuss information, concerns and experiences on vaccines and vaccine hesitancy. CONCLUSION: Our study suggests that the Dengvaxia® controversy may reduce the measles vaccination confidence in the Philippines. Lack of transparency played a crucial role in this dilemma, producing a cascading effect on the other vaccines' safety.

Evaluating effective measles vaccine coverage in the Malaysian population accounting for between-dose correlation and vaccine efficacy.

BACKGROUND: Malaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population. METHODS: We define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia's routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia's measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters. RESULTS: This study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia. CONCLUSION: The persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.

A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine.

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.

Vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake among adults in Greece.

OBJECTIVES: Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. STUDY DESIGN: This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. METHODS: A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. RESULTS: Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52-8.14], pneumococcal disease: 15.73 [10.98-22.52], HZ: 17.01 [9.05-31.96], tetanus: 23.93 [16.20-35.35], measles: 33.47 [16.85-66.47], and hepatitis B: 73.92 [17.47-312.74]). Being well-informed about each vaccine was also a predictor of its uptake. CONCLUSIONS: Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage.

The Effect of a Second Dose of Measles Vaccine at 18 Months of Age on Nonaccidental Deaths and Hospital Admissions in Guinea-Bissau: Interim Analysis of a Randomized Controlled Trial.

BACKGROUND: The world is set on the eradication of measles. Continuation of the measles vaccine (MV) after eradication could still reduce morbidity because the MV has so-called beneficial nonspecific effects. We evaluated the effect of a "booster" dose of the MV on overall severe morbidity. METHODS: We conducted a randomized controlled trial among children aged 17.5 to 48 months in Guinea-Bissau, where the MV is recommended only at 9 months of age. At the time of this interim analysis, 3164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or to no vaccine. Severe morbidity (a composite outcome of nonaccidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns. RESULTS: There were no measles cases during the trial period. There were 43 nonaccidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR, 0.72; 95% confidence interval [CI], .38-1.38). At 12 months of follow-up, the number needed to treat to prevent 1 severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR, 0.91; 95% CI, .46-1.81). CONCLUSIONS: MV2 may reduce nonmeasles severe morbidity by 28% (-38% to 62%), although this did not achieve statistical significance in this study. If significant in higher powered studies, this has major implications for child health, even after measles eradication. CLINICAL TRIALS REGISTRATION: NCT02943681.

Determinants of measles vaccination dropout among 12 - 23 months aged children in pastoralist community of Afar, Ethiopia.

BACKGROUND: Measles is a viral disease and a leading vaccine-preventable childhood killer. More than 95% of measles deaths occur in countries with low incomes and weak health infrastructures. In response to this, Ethiopia prepared a measles elimination strategic plan to achieve by 2020. However, based on the Mini-Ethiopian demographic health survey 2019 the full coverage of immunization is 43% at the country level and it is lowest (20%) in the Afar region where this study was conducted. Therefore, this study aimed to identify the determinants of the measles vaccine dropout rate in Afar regional state which is one of the pastoralist communities in Ethiopia. METHODS: Community based unmatched case-control study design was used. The study was conducted in Awash district of Afar regional state, Ethiopia from June 1st -30th 2018. Data were collected from a study unit of 12-23 months old children. For this study, a sample of 166 cases and 331controls were selected by simple random sampling methods and the total sample size was 497. Data were collected using a pretested structured questionnaire by health workers using the local language. Data were entered into Epi-info - 7 and analyzed by SPSS version 20 software and logistic regression was used to assess the determinants measles dropout rate. RESULTS: A total of 487 children participated in this study with a response rate of 97.9%. More than half of the children were female (53.3%) and 113 (35.2%) children mothers' were not attended formal education. Mother who had antenatal care ≤ 2 visits [AOR:=5.7(3.2-10.14)], being in the birth order of 1 - 3 [AOR = 4.47(1.63-12.29)], long waiting time > 60 min at nearby health facility for vaccine [AOR = 2.37(1.36-4.15)], households visit by health extension workers [AOR = 2.03(1.12-3.66)], pregnant women not participating with women development army [AOR = 3.5(1.94-6.18)], and poor maternal knowledge on vaccination [AOR = 3.30(1.9-5.73)] were significant determinants with measles vaccination dropout rate. CONCLUSIONS: Health facility and mother characteristics were the determinants of the measles vaccine dropout rate. Therefore, tracing and strict follow up by the health extension works using home visits and women development army at the pastoralist community is necessary to reach them.

Out-of-Sequence Vaccinations With Measles Vaccine and Diphtheria-Tetanus-Pertussis Vaccine: A Reanalysis of Demographic Surveillance Data From Rural Bangladesh.

BACKGROUND: Due to delays in vaccinations, diphtheria-tetanus-whole-cell-pertussis (DTP) is often given with or after measles vaccine (MV)-out of sequence. We reanalyzed data from Matlab, Bangladesh, to examine how administration of MV and DTP out-of-sequence was associated with child survival. METHODS: In sum, 36 650 children born between 1986 and 1999 were followed with registration of vaccinations and survival. Controlling for background factors using Cox proportional hazards models, survival was analyzed between 9 and 24 months of age. We measured the mortality rate ratio (MRR) to compare vaccination groups. Oral polio vaccine (OPV) campaigns, which started in 1995, reduced the mortality rate and reduced the difference between vaccination groups. In the main analysis, we therefore censored for OPV campaigns; there were 151 nonaccident deaths before the OPV campaigns. RESULTS: Compared with MV administered alone (MV-only), DTP administered with or after MV had MRR 2.20 (1.31-3.70), and DTP-only had MRR 1.78 (1.01-3.11). Compared with MV-only, DTP administered with MV had a female-male MRR 0.56 (0.13-2.38), significantly different to DTP administered after MV, which had MRR 14.83 (1.88-117.1), test of interaction P = .011. Compared with having DTP (no MV) as most recent vaccination, MV-only had a nonaccident MRR of 0.56 (0.32-0.99). CONCLUSION: The negative effects of non-live DTP with or after live MV are not explained merely by selection bias. These observations support a live-vaccine-last policy where DTP should not be given with or after MV.

Emergence of Attenuated Measles Illness Among IgG-positive/IgM-negative Measles Cases: Victoria, Australia, 2008-2017.

BACKGROUND: Waning measles immunity among vaccinated individuals may result in an attenuated illness. This study compares the epidemiological, clinical, and laboratory profile of measles cases with waning immunity with other measles cases. METHODS: Polymerase chain reaction-positive (+) measles cases notified to Victoria's Department of Health and Human Services from 2008 to 2017 with immunoglobulin (Ig) M and IgG tested at diagnosis were classified according to serology at diagnosis: IgG negative (-) (nonimmune), IgM+/IgG+ (indeterminate), or IgM-/IgG+ (waning immunity). RESULTS: Between 2008 and 2017, 297 measles cases were notified, of whom 190 (64%) were included; 151 of 190 (79%) were nonimmune at diagnosis, 26 (14%) were indeterminate, and 13 (7%) had waning immunity. Between 2008-2013 and 2014-2017, the proportion of cases with waning immunity increased from 0 of 87 (0%) to 13 of 103 (13%) (P < .001) and the diagnostic sensitivity of initial IgM fell from 93% to 81% (P = .012), respectively. Seven (54%) waning immunity cases reported receiving measles-containing vaccines; 1 case had 2 documented doses. Compared with nonimmune and indeterminate cases, waning immunity cases were more likely to be male; less likely to report fever, coryza, and cough; and had lower burden of virus (higher cycle threshold values). Waning immunity cases had higher IgG titers than indeterminate cases (mean optical density values, 1.96 vs 0.71; P = .004). Onward transmission from 1 waning immunity case was documented. CONCLUSIONS: Waning immunity among measles cases, associated with secondary vaccine failure and modified clinical illness, is emerging in Victoria with transmission potential.

Transverse myelitis following measles vaccination in a rhesus macaque (Macaca mulatta).

A 16-year-old rhesus macaque presented with progressive, ascending quadriparesis following measles vaccination. He was diagnosed with transverse myelitis following MRI, gross necropsy, and histopathology. This is the first report of transverse myelitis in a rhesus macaque following measles vaccination.

Effect of age at vaccination on the measles vaccine effectiveness and immunogenicity: systematic review and meta-analysis.

BACKGROUND: The objectives of this review were to evaluate the effect of age at administration of the first dose of a measles-containing vaccine (MCV1) on protection against measles and on antibody response after one- and two-dose measles vaccinations. METHODS: We conducted a systematic review of the PubMed/MEDLINE, Embase, Web of Science and Cochrane databases (1964-2017) to identify observational studies estimating vaccine effectiveness and/or measles attack rates by age at first vaccination as well as experimental studies comparing seroconversion by age at first vaccination. Random effect models were used to pool measles risk ratios (RR), measles odds ratios (OR) and seroconversion RR of MCV1 administered at < 9, 9-11 or ≥ 15 months compared with 12 or 12-14 months of age. RESULTS: We included 41 and 67 studies in the measles protection and immunogenicity analyses. Older age at MCV1, from 6 to ≥15 months, improved antibody response and measles protection among one-dose recipients. Pooled measles RR ranged from 3.56 (95%CI: 1.28, 9.88) for MCV1 at < 9 months to 0.48 (95%CI: 0.36, 0.63) for MCV1 at ≥15 months, both compared to 12-14 months. Pooled seroconversion RR ranged from 0.93 (95%CI: 0.90, 0.96) for MCV1 at 9-11 months to 1.03 (95%CI: 1.00, 1.06) for MCV1 at ≥15 months, both compared to 12 months. After a second dose, serological studies reported high seropositivity regardless of age at administration of MCV1 while epidemiological data based on few studies suggested lower protection with earlier age at MCV1. CONCLUSIONS: Earlier age at MCV1 decreases measles protection and immunogenicity after one dose and might still have an impact on vaccine failures after two doses of measles vaccine. While two-dose vaccination coverage is most critical to interrupt measles transmission, older age at first vaccination may be necessary to keep the high level of population immunity needed to maintain it.

Health workers' perceptions and challenges in implementing meningococcal serogroup a conjugate vaccine in the routine childhood immunization schedule in Burkina Faso.

BACKGROUND: Meningococcal serogroup A conjugate vaccine (MACV) was introduced in 2017 into the routine childhood immunization schedule (at 15-18 months of age) in Burkina Faso to help reduce meningococcal meningitis burden. MACV was scheduled to be co-administered with the second dose of measles-containing vaccine (MCV2), a vaccine already in the national schedule. One year following the introduction of MACV, an assessment was conducted to qualitatively examine health workers' perceptions of MACV introduction, identify barriers to uptake, and explore opportunities to improve coverage. METHODS: Twelve in-depth interviews were conducted with different cadres of health workers in four purposively selected districts in Burkina Faso. Districts were selected to include urban and rural areas as well as high and low MCV2 coverage areas. Respondents included health workers at the following levels: regional health managers (n = 4), district health managers (n = 4), and frontline healthcare providers (n = 4). All interviews were recorded, transcribed, and thematically analyzed using qualitative content analysis. RESULTS: Four themes emerged around supply and health systems barriers, demand-related barriers, specific challenges related to MACV and MCV2 co-administration, and motivations and efforts to improve vaccination coverage. Supply and health systems barriers included aging cold chain equipment, staff shortages, overworked and poorly trained staff, insufficient supplies and financial resources, and challenges with implementing community outreach activities. Health workers largely viewed MACV introduction as a source of motivation for caregivers to bring their children for the 15- to 18-month visit. However, they also pointed to demand barriers, including cultural practices that sometimes discourage vaccination, misconceptions about vaccines, and religious beliefs. Challenges in co-administering MACV and MCV2 were mainly related to reluctance among health workers to open multi-dose vials unless enough children were present to avoid wastage. CONCLUSIONS: To improve effective administration of vaccines in the second-year of life, adequate operational and programmatic planning, training, communication, and monitoring are necessary. Moreover, clear policy communication is needed to help ensure that health workers do not refrain from opening multi-dose vials for small numbers of children.

Factors associated with childhood vaccine hesitancy and measles vaccine hesitancy among healthcare students.

This study aims to determine the prevalence and causes of childhood vaccine and measles vaccine hesitancy and refusal among healthcare students in Turkey. The pool of this cross-sectional study, which included 718 students, was made up of healthcare students from the Faculty of Health Sciences at Balikesir University (N = 960). It was determined that 10% of students surveyed were hesitant regarding childhood vaccines, while 11.8% were hesitant with regard to the measles vaccine, specifically. Many of the participants held the belief that chronic idiopathic diseases such as multiple sclerosis and autism are related to vaccines; they also believed that vaccines should not be mandatory. More alarming than this, however, was that in response to a question regarding the measles vaccine, many of the students responded that "I would not have my child vaccinated with the vaccines administered by the Ministry of Health if I had a child." The findings revealed, overall, that the rates of childhood vaccine hesitancy and measles vaccine hesitancy are high among the healthcare students who were surveyed and that a high number of healthcare students hold negative attitudes that are related to rates of vaccine hesitancy.

Immunogenicity and Safety of an Early Measles Vaccination Schedule at 6 and 12 Months of Age in Human Immunodeficiency Virus (HIV)-Unexposed and HIV-Exposed, Uninfected South African Children.

BACKGROUND: Measles morbidity and mortality rates are greatest in children <12 months old, with increased susceptibility in human immunodeficiency virus (HIV)-exposed children. We evaluated the immunogenicity and safety of an early 2-dose measles vaccine regimen administered at 6 and 12 months of age in South Africa. METHODS: HIV-unexposed (HU) (n = 212) and HIV-exposed, uninfected (HEU) (n = 71) children received measles vaccination (CAM-70) at 6 and 12 months of age. Measles immunoglobulin G titers were measured by means of enzyme-linked immunosorbent assay before and 1 month after each vaccine dose. RESULTS: The majority of children (88.2% HU and 95.8% HEU; P = .04) were seronegative (<150 mIU/mL) to measles at 4.2 months of age. This was particularly evident among infants of mothers born from 1992 onwards (year of public nationwide measles vaccine availability). One month after the first measles vaccine, 42.3% of HU and 46.4% of HEU children were seropositive (≥330 mIU/mL). After the second dose, the proportion seropositive increased to 99.0% in HU and 95.3% in HEU children. Safety profiles were similar between HU and HEU children. CONCLUSIONS: Early 2-dose measles vaccination at 6 and 12 months of age was safe and induced antibody responses in HU and HEU children, which could partly offset the early loss of maternally derived antibodies in infants born to predominantly measles-vaccinated mothers. CLINICAL TRIALS REGISTRATION: NCT03330171.

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.

Measles Seroprevalence and Vaccine Responses in Human Immunodeficiency Virus-infected Adolescents and Adults: A Systematic Review.

BACKGROUND: The World Health Organization (WHO) recommends an additional dose of measles-containing vaccine (MCV) for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy following immune reconstitution. We conducted a systematic review to synthesize available evidence regarding measles seroprevalence and measles vaccine immunogenicity, efficacy, and safety in HIV-infected adolescents and adults to provide the evidence base for recommendations on the need for measles vaccination. METHODS: We conducted searches of 8 databases through 26 September 2017. Identified studies were screened independently by 2 reviewers. RESULTS: The search identified 30 studies meeting inclusion criteria. Across studies, measles seroprevalence among HIV-infected adolescents and adults was high (median, 92%; 27 studies), with no significant difference compared to HIV-uninfected participants (10 studies). In 6 studies that evaluated the immunogenicity of MCVs among seronegative HIV-infected adults, measles seropositivity at end of follow-up ranged from 0% to 56% (median, 39%). No severe adverse events were reported following measles vaccination in HIV-infected patients. CONCLUSIONS: Based on similar measles seroprevalence between HIV-infected and HIV-uninfected adolescents and adults, and the low response to vaccination, these studies do not support the need for an additional dose of MCV in HIV-infected adolescents and adults. These findings support WHO guidelines that measles vaccine be administered to potentially susceptible, asymptomatic HIV-infected adults, and may be considered for those with symptomatic HIV infection if not severely immunosuppressed. Measles-susceptible adolescents and adults, regardless of HIV status, may require targeted vaccination efforts to reach critical vaccination thresholds and achieve regional elimination goals.

Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children.

BACKGROUND: Human immunodeficiency virus (HIV)-infected and HIV-exposed-uninfected (HEU) children may be at increased risk of measles infection due to waning of immunity following vaccination. We evaluated persistence of antibodies to measles vaccination at 4.5 years of age in HIV-unexposed, HEU, and HIV-infected children with CD4+ ≥25% previously randomized to immediate antiretroviral therapy (ART) interrupted at 12 months (HIV/Immed-ART-12), 24 months (HIV/Immed-ART-24), or when clinically/immunologically indicated (HIV/Def-ART). The HIV/Def-ART group initiated ART by median 5.8 (interquartile range, 4.4-10.3) months of age. METHODS: In this study, HIV-unexposed (n = 95), HEU (n = 84), HIV/Immed-ART-12 (n = 70), HIV/Immed-ART-24 (n = 70), and HIV/Def-ART (n = 62) children were scheduled to receive measles vaccination at age 9 and 15-18 months. Antimeasles serum immunoglobulin G titers were quantified using enzyme-linked immunosorbent assay at 4.5 years. RESULTS: Compared with HIV-unexposed children (2860 mIU/mL), measles antibody geometric mean titers (GMTs) were significantly lower in both HIV/Immed-ART-12 (571; P < .001) and HIV/Immed-ART-24 (1136; P < .001) but similar in the HIV/Def-ART (2777) and HEU (3242) groups. Furthermore, compared with HIV-unexposed, antibody titers ≥330 mIU/mL (ie, presumed serocorrelate for protection; 99%) were also significantly lower in HIV/Immed-ART-12 (70%; P < .001) and HIV/Immed-ART-24 (83%; P < .001) but similar in the HIV/Def-ART (90%) and HEU (98%) groups. CONCLUSIONS: HIV-infected children in whom ART was interrupted at either 12 or 24 months had lower GMTs and lower proportions with seroprotective titers than HIV-unexposed children, indicating a potential downside of ART treatment interruption. CLINICAL TRIALS REGISTRATION: NCT00099658 and NCT00102960.