Diphtheria in the WHO European Region, 2010 to 2019.

BackgroundDiphtheria is uncommon in the World Health Organization (WHO) European Region. Nevertheless, sporadic cases, sometimes fatal, continue to be reported.AimTo report on diphtheria cases and coverage with first and third doses of diphtheria, tetanus and pertussis vaccines (DTP1 and DTP3, respectively) for 2010-19 in the Region with a focus on 2019.MethodsData on diphtheria cases were obtained from WHO/United Nations International Children's Emergency Fund (UNICEF) Joint Reporting Forms submitted annually by the Region's Member States. WHO/UNICEF Estimates of National Immunization Coverage for DTP1 and DTP3 were summarised for 2010-19. For 2019, we analysed data on age, and vaccination status and present data by country on DTP1 and DTP3 coverage and the percentage of districts with ≥ 90% and < 80% DTP3 coverage.ResultsFor 2010-19, 451 diphtheria cases were reported in the Region. DTP1 and DTP3 coverage was 92-96% and 95-97%, respectively. For 2019, 52 cases were reported by 11 of 48 countries that submitted reports (including zero reporting). Thirty-nine countries submitted data on percentage of their districts with ≥ 90% and < 80% DTP3 coverage; 26 had ≥ 90% districts with ≥ 90% coverage while 11 had 1-40% districts with < 80% coverage.ConclusionLong-standing high DTP3 coverage at Regional level probably explains the relatively few diphtheria cases reported in the Region. Suboptimal surveillance systems and inadequate laboratory diagnostic capacity may also be contributing factors. Still, the observed cases are of concern. Attaining high DTP3 coverage in all districts and implementing recommended booster doses are necessary to control diphtheria and prevent outbreaks.

The Global Landscape of Pediatric Bacterial Meningitis Data Reported to the World Health Organization-Coordinated Invasive Bacterial Vaccine-Preventable Disease Surveillance Network, 2014-2019.

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

The Use of Adaptive Sampling to Reach Disadvantaged Populations for Immunization Programs and Assessments: A Systematic Review.

Vaccines prevent 4-5 million deaths every year, but inequities in vaccine coverage persist among key disadvantaged subpopulations. Under-immunized subpopulations (e.g., migrants, slum residents) may be consistently missed with conventional methods for estimating immunization coverage and assessing vaccination barriers. Adaptive sampling, such as respondent-driven sampling, may offer useful strategies for identifying and collecting data from these subpopulations that are often "hidden" or hard-to-reach. However, use of these adaptive sampling approaches in the field of global immunization has not been systematically documented. We searched PubMed, Scopus, and Embase databases to identify eligible studies published through November 2020 that used an adaptive sampling method to collect immunization-related data. From the eligible studies, we extracted relevant data on their objectives, setting and target population, and sampling methods. We categorized sampling methods and assessed their frequencies. Twenty-three studies met the inclusion criteria out of the 3069 articles screened for eligibility. Peer-driven sampling was the most frequently used adaptive sampling method (57%), followed by geospatial sampling (30%), venue-based sampling (17%), ethnographic mapping (9%), and compact segment sampling (9%). Sixty-one percent of studies were conducted in upper-middle-income or high-income countries. Data on immunization uptake were collected in 65% of studies, and data on knowledge and attitudes about immunizations were collected in 57% of studies. We found limited use of adaptive sampling methods in measuring immunization coverage and understanding determinants of vaccination uptake. The current under-utilization of adaptive sampling approaches leaves much room for improvement in how immunization programs calibrate their strategies to reach "hidden" subpopulations.

Rotavirus genotypes in children under five years hospitalized with diarrhea in low and middle-income countries: Results from the WHO-coordinated Global Rotavirus Surveillance Network.

Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network. Data from a convenience sample of children under five years of age hospitalized with acute watery diarrhea who tested positive for rotavirus were included. Country results were weighted by their estimated rotavirus disease burden to estimate regional genotype distributions. Globally, the most frequent genotypes identified after weighting were G1P[8] (31%), G1P[6] (8%) and G3P[8] (8%). Genotypes varied across WHO Regions and between countries that had and had not introduced rotavirus vaccine. G1P[8] was less frequent among African (36 vs 20%) and European (33 vs 8%) countries that had introduced rotavirus vaccines as compared to countries that had not introduced. Our results describe differences in the distribution of the most common rotavirus genotypes in children with diarrhea in low- and middle-income countries. G1P[8] was less frequent in countries that had introduced the rotavirus vaccine while different strains are emerging or re-emerging in different regions.

An outbreak of wild poliovirus in the Republic of Congo, 2010-2011.

BACKGROUND: The Republic of Congo has had no cases of wild poliovirus type 1 (WPV1) since 2000. In October 2010, a neurologist noted an abnormal number of cases of acute flaccid paralysis (AFP) among adults, which were later confirmed to be caused by WPV1. METHODS: Those presenting with AFP underwent clinical history, physical examination, and clinical specimen collection to determine if they had polio. AFP cases were classified as laboratory-confirmed, clinical, or nonpolio AFP. Epidemiologic features of the outbreak were analyzed. RESULTS: From 19 September 2010 to 22 January 2011, 445 cases of WPV1 were reported in the Republic of Congo; 390 cases were from Pointe Noire. Overall, 331 cases were among adults; 378 cases were clinically confirmed, and 64 cases were laboratory confirmed. The case-fatality ratio (CFR) was 43%. Epidemiologic characteristics differed among polio cases reported in Pointe Noire and cases reported in the rest of the Republic of Congo, including age distribution and CFR. The outbreak stopped after multiple vaccination rounds with oral poliovirus vaccine, which targeted the entire population. CONCLUSIONS: This outbreak underscores the need to maintain high vaccination coverage to prevent outbreaks, the need to maintain timely high-quality surveillance to rapidly identify and respond to any potential cases before an outbreak escalates, and the need to perform ongoing risk assessments of immunity gaps in polio-free countries.

Impact and effectiveness of monovalent rotavirus vaccine in Tajik children.

BACKGROUND: In 2015, Tajikistan became the second country in Central Asia to introduce rotavirus vaccine into its national immunization program. Before vaccine introduction, rotavirus was estimated to cause > 40% of pediatric diarrhea hospitalizations in Tajikistan. We aimed to assess the impact of rotavirus vaccine introduction on rotavirus disease burden and estimate rotavirus vaccine effectiveness (VE). METHODS: Using surveillance data from 2013 through 2019, we examined trends in monthly hospital admissions among children < 5 years old, before and after rotavirus vaccine introduction. Poisson regression was used to quantify decreases. VE was estimated using a test-negative case control design, with data from admissions during 2017 - 2019. Immunization records were obtained from clinics. RESULTS: Among enrolled children, rotavirus positivity declined from 42% to 25% in the post-vaccine introduction period, a decrease of 41% (95% Confidence Interval [CI]: 36 - 45%). Declines were greatest in children < 12 months of age. Estimated VE of a complete course of rotavirus vaccine was 55% (95% CI: 21 - 73%) among children 5 - 59 months of age and 64% (95% CI: 36 - 80%) among children 5 - 23 months of age. VE point estimates were higher among children receiving both doses of rotavirus vaccine non-concurrently with OPV and among children receiving their first dose of rotavirus vaccine at 4 - 11 months of age, but CIs were wide and overlapping. CONCLUSIONS: Our data demonstrate that rotavirus vaccine introduction was associated with a substantial reduction in pediatric rotavirus hospitalization burden in Tajikistan, and that rotavirus vaccination is effective in Tajik children.

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

Evaluating a Mobile Phone-Delivered Text Message Reminder Intervention to Reduce Infant Vaccination Dropout in Arua, Uganda: Protocol for a Randomized Controlled Trial.

BACKGROUND: Globally, suboptimal vaccine coverage is a public health concern. According to Uganda's 2016 Demographic and Health Survey, only 49% of 12- to 23-month-old children received all recommended vaccinations by 12 months of age. Innovative ways are needed to increase coverage, reduce dropout, and increase awareness among caregivers to bring children for timely vaccination. OBJECTIVE: This study evaluates a personalized, automated caregiver mobile phone-delivered text message reminder intervention to reduce the proportion of children who start but do not complete the vaccination series for children aged 12 months and younger in select health facilities in Arua district. METHODS: A two-arm, multicenter, parallel group randomized controlled trial was conducted in four health facilities providing vaccination services in and around the town of Arua. Caregivers of children between 6 weeks and 6 months of age at the time of their first dose of pentavalent vaccine (Penta1; containing diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b antigens) were recruited and interviewed. All participants received the standard of care, defined as the health worker providing child vaccination home-based records to caregivers as available and providing verbal instruction of when to return for the next visit. At the end of each day, caregivers and their children were randomized by computer either to receive or not receive personalized, automated text message reminders for their subsequent vaccination visits according to the national schedule. Text message reminders for Penta2 were sent 2 days before, on the day of, and 2 days after the scheduled vaccination visit. Reminders for Penta3 and the measles-containing vaccine were sent on the scheduled day of vaccination and 5 and 7 days after the scheduled day. Study personnel conducted postintervention follow-up interviews with participants at the health facilities during the children's measles-containing vaccine visit. In addition, focus group discussions were conducted to assess caregiver acceptability of the intervention, economic data were collected to evaluate the incremental costs and cost-effectiveness of the intervention, and health facility record review forms were completed to capture service delivery process indicators. RESULTS: Of the 3485 screened participants, 1961 were enrolled from a sample size of 1962. Enrollment concluded in August 2016. Follow-up interviews of study participants, including data extraction from the children's vaccination cards, data extraction from the health facility immunization registers, completion of the health facility record review forms, and focus group discussions were completed by December 2017. The results are expected to be released in 2021. CONCLUSIONS: Prompting health-seeking behavior with reminders has been shown to improve health intervention uptake. Mobile phone ownership continues to grow in Uganda, so their use in vaccination interventions such as this study is logical and should be evaluated with scientifically rigorous study designs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04177485; https://clinicaltrials.gov/ct2/show/NCT04177485. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17262.

Rotavirus vaccine effectiveness and impact in Uzbekistan, the first country to introduce in central Asia.

Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005-2009. Children aged <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%-15% of infants and 10%-16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%-68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2-75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan.

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.

Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008-16: findings from the Global Rotavirus Surveillance Network.

BACKGROUND: Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN). METHODS: Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction. FINDINGS: 403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32·9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38·0% (95% CI 4·8-73·4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23·0% (0·7-57·7) of admissions for acute gastroenteritis, showing a 39·6% (35·4-43·8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26·4% (15·0-37·8) in the Eastern Mediterranean Region to 55·2% (43·0-67·4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6-10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction. INTERPRETATION: A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. FUNDING: The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.

Rotavirus gastroenteritis surveillance in Azerbaijan, 2011-2016.

INTRODUCTION: Rotavirus is a leading cause of acute gastroenteritis and mortality among children worldwide but data describing rotavirus disease in Azerbaijan are lacking. This analysis describes the rotavirus disease burden in Baku, the largest city in Azerbaijan. METHODS: We conducted active, prospective, sentinel hospital surveillance with laboratory confirmation for rotavirus among children under 5 years of age hospitalized at a large pediatric hospital in Baku during 2011-2016. Children with bloody diarrhea, or prior use of antibiotics or intravenous fluids were excluded. The guardians of enrolled children completed a questionnaire documenting clinical and demographic information. A stool specimen was collected from each enrolled child. We report the number and proportion of rotavirus positive hospitalizations during the surveillance period and a clinical description of rotavirus-positive and rotavirus-negative children. RESULTS: From July 2011 through June 2016, 3139 children <5 years of age were enrolled into the surveillance system. Of these, 523 (17%) were positive for rotavirus, varying from 13% to 21% by surveillance year, with a median of 16% over the surveillance period. Increase in rotavirus detections occurred during December-May. Most rotavirus infections (303/523; 58%) occurred in children aged 6-23 months. CONCLUSION: Rotavirus is responsible for approximately 16% of annual hospital admissions for acute gastroenteritis in children <5 years of age in Baku. This is lower than regional estimates. Exclusion of children with a history of antibiotic use or intravenous fluids may be accounting for this lower prevalence, and expansion of surveillance to include these groups could provide a more comprehensive picture of acute rotavirus gastroenteritis in Baku.

Rotavirus hospitalizations among children <5 years of age-Tajikistan, 2013-2014.

BACKGROUND: In January 2015, Tajikistan introduced the monovalent rotavirus vaccine into the national immunization program. Our objective was to estimate pre-vaccine burden of rotavirus-associated hospitalizations in children <5 years of age in Tajikistan. METHODS: During January 2013-December 2014, active surveillance for acute gastroenteritis (AGE)-associated hospitalizations in children <5 years of age was conducted by sentinel surveillance site staff. Patients' demographic and clinical data were summarized and a stool sample was collected. An Enzyme Linked Immunosorbent Assay was used for diagnosis of rotavirus infection and subset of the specimens was sent for polymerase chain reaction (PCR) genotyping. RESULTS: Of 2860 eligible children enrolled and tested, 1207 (42%) were positive for rotavirus. An increase in the number and proportion of rotavirus cases attributed to rotavirus season, with positivity rates >40%, was annually observed during June-September. The median age of rotavirus patients was 9 months and 939/1207 (78%) rotavirus patients were aged 6-23 months. Most (1097/1203; 91%) rotavirus patients were treated with intravenous fluids. G1P[8] was the predominant genotype during both years of surveillance, accounting for 133/222 (60%) of genotyped cases. CONCLUSION: Rotavirus is a major cause of hospitalization due to severe AGE in children <5 years of age in Tajikistan, accounting for >40% of cases. Continued, enhanced rotavirus surveillance may allow documentation of changes in rotavirus disease burden following vaccine introduction and assessment of vaccine effectiveness.

Observations on the epidemiology of rotavirus infection among hospitalized children younger than 5 years in 2 Ukrainian hospitals, 2007-2015.

BACKGROUND: Acute gastroenteritis remains a burden among children under 5 years of age. Ukraine joined the World Health Organization's Global Rotavirus Surveillance Network in 2006, with a goal of providing accurate rotavirus burden data to aid policy makers in planning for rotavirus vaccine introduction. This analysis describes rotavirus epidemiology among Ukrainian children enrolled in Kyiv and Odesa, two large Ukrainian cities. METHODS: Children 0-59 months of age hospitalized for acute gastroenteritis at 2 sentinel sites in Kyiv and Odesa were enrolled into the active, prospective surveillance program. In Odesa, the surveillance period was during 2007-2015 and in Kyiv, it was during 2011-2015. Acute gastroenteritis was defined as 3 or more episodes of diarrhea per day during a 24 h period, with symptom duration before hospitalization not exceeding 7 days. Guardians of enrolled children completed a questionnaire including demographic, clinical and treatment information. Each child provided a stool specimen within 2 days of hospitalization. Stools were tested for rotavirus using ProSpecT™ Rotavirus Kit (Oxoid Ltd., Great Britain), and positive specimens were genotyped. Descriptive data are reported, as well as comparison of demographic, clinical and treatment data among rotavirus positive and negative children. RESULTS: During July 2007-June 2015, 12,350 children were enrolled in the surveillance programs and had stool specimens collected and tested for rotavirus. Overall, rotavirus infection was diagnosed in 5412/12350 (44%) of children, 929/1734 (54%) of those in Kyiv and 4483/10616 (42%) in Odesa. Rotavirus infections peaked during the winter months. Children with rotavirus acute gastroenteritis displayed more severe clinical symptoms than those without rotavirus. Predominant genotypes identified included G1P[8], G2P[4], G3 P[8], G4 P[8] and G9 P[8]. CONCLUSION: Active surveillance of acute gastroenteritis in hospitalized children younger 5 years in two large Ukrainian cities reveals a significant burden of rotavirus infection. These data provide scientific justification for incorporating rotavirus vaccines into the Ukrainian national immunization schedule.

Assessment of vaccine wastage rates, missed opportunities, and related knowledge, attitudes and practices during introduction of a second dose of measles-containing vaccine into Cambodia's national immunization program.

INTRODUCTION: Missed opportunities for vaccination (MOV) can result in inadequate protection against disease. Although healthcare provider reluctance to open multi-dose, lyophilized vaccine vials (particularly the measles-containing vaccine [MCV]) for every eligible child due to concerns about wasting vaccine is a known reason for MOV, little is known about providers' related attitudes and practices. METHODS: In 100 randomly selected health facilities and 24 districts of Cambodia, we surveyed healthcare providers and their district supervisors regarding routine vaccine administration and wastage knowledge and practices, and child caregivers (five per facility) regarding MOV. Vaccine stock management data covering six months were reviewed to calculate facility and district level wastage rates and vaccine usage patterns for six vaccines, including a recently introduced second dose of MCV (MCV2). RESULTS: Response rates were 100/100 (100%) among facility staff, 48/48 (100%) among district staff, and 436/500 (87%) among caregivers. Mean facility-level wastage rates varied from 4% for single-dose diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine to 60% for 10-dose MCV; district-level wastage rates for all vaccines were 0%. Some vaccines had lower wastage rates in large facilities compared to small facilities. The mean MCV wastage rate was the same before and immediately after MCV2 introduction. Providers reported waiting for a mean of two children prior to opening an MCV vial, and 71% of providers reported offering MCV vaccination less frequently during scheduled vaccination sessions than other vaccines. Less than 5% of caregivers reported that their child had been turned away for vaccination, most frequently (65%) for MCV. DISCUSSION: Although the MCV wastage rate in our study was in line with national targets, providers reported waiting for more than one child before opening an MCV vial, contrary to vaccine management guidelines. Future research should explore the causal links between provider practices related to vaccine wastage and their impact on vaccination coverage.

Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator knowledge, attitudes and practices.

INTRODUCTION: The introduction of new vaccines highlights concerns about high vaccine wastage, knowledge of wastage policies and quality of stock management. However, an emphasis on minimizing wastage rates may cause confusion when recommendations are also being made to reduce missed opportunities to routinely vaccinate children. This concern is most relevant for lyophilized vaccines without preservatives [e.g. measles-containing vaccine (MCV)], which can be used for a limited time once reconstituted. METHODS: We sampled 54 health facilities within 11 local government areas (LGAs) in Nigeria and surveyed health sector personnel regarding routine vaccine usage and wastage-related knowledge and practices, conducted facility exit interviews with caregivers of children about missed opportunities for routine vaccination, and abstracted vaccine stock records and vaccination session data over a 6-month period to calculate wastage rates and vaccine vial usage patterns. RESULTS: Nearly half of facilities had incomplete vaccine stock data for calculating wastage rates. Among facilities with sufficient data, mean monthly facility-level wastage rates were between 18 and 35% across all reviewed vaccines, with little difference between lyophilized and liquid vaccines. Most (98%) vaccinators believed high wastage led to recent vaccine stockouts, yet only 55% were familiar with the multi-dose vial policy for minimizing wastage. On average, vaccinators reported that a minimum of six children must be present prior to opening a 10-dose MCV vial. Third dose of diphtheria-tetanus-pertussis vaccine (DTP3) was administered in 84% of sessions and MCV in 63%; however, the number of MCV and DTP3 doses administered were similar indicating the number of children vaccinated with DTP3 and MCV were similar despite less frequent MCV vaccination opportunities. Among caregivers, 30% reported being turned away for vaccination at least once; 53% of these children had not yet received the missed dose. DISCUSSION: Our findings show inadequate implementation of vaccine management guidelines, missed opportunities to vaccinate, and lyophilized vaccine wastage rates below expected rates. Missed opportunities for vaccination may occur due to how the health system's contradicting policies may force health workers to prioritize reduced wastage rates over vaccine administration, particularly for multi-dose vials.

Assessing strategies for increasing urban routine immunization coverage of childhood vaccines in low and middle-income countries: A systematic review of peer-reviewed literature.

INTRODUCTION: Immunization programs in developing countries increasingly face challenges to ensure equitable delivery of services within cities where rapid urban growth can result in informal settlements, poor living conditions, and heterogeneous populations. A number of strategies have been utilized in developing countries to ensure high community demand and equitable availability of urban immunization services; however, a synthesis of the literature on these strategies has not previously been undertaken. METHODS: We reviewed articles published in English in peer-reviewed journals between 1990 and 2013 that assessed interventions for improving routine immunization coverage in urban areas in low- and middle-income countries. We categorized the intervention in each study into one of three groups: (1) interventions aiming to increase utilization of immunization services; (2) interventions aiming to improve availability of immunization services by healthcare providers, or (3) combined availability and utilization interventions. We summarized the main quantitative outcomes from each study and effective practices from each intervention category. RESULTS: Fifteen studies were identified; 87% from the African, Eastern Mediterranean and Southeast Asian regions of the World Health Organization (WHO). Six studies were randomized controlled trials, eight were pre- and post-intervention evaluations, and one was a cross-sectional study. Four described interventions designed to improve availability of routine immunization services, six studies described interventions that aimed to increase utilization, and five studies aiming to improve both availability and utilization of services. All studies reported positive change in their primary outcome indicator, although seven different primary outcomes indicators were used across studies. Studies varied considerably with respect to the type of intervention assessed, study design, and length of intervention assessment. CONCLUSION: Few studies have assessed interventions designed explicitly for the unique challenges facing immunization programs in urban areas. Further research on sustainability, scalability, and cost-effectiveness of interventions is needed to fill this gap.

Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection.

BACKGROUND: Hepatitis B vaccination is recommended for patients on hemodialysis, however, seroprotection after a primary vaccine series is suboptimum. Limited data are available on the effect of revaccination of non-responders and on persistence of immunity in this population. METHODS: Hepatitis B vaccine (40 µg/dose) was given to 77 susceptible patients on hemodialysis (0, 1, and 6 month schedule). Levels of hepatitis B surface antibody (anti-HBs) were tested ≥ 28 days after the third dose was administered, and non-responders revaccinated with an additional 3-dose series. Vaccine responders (anti-HBs ≥10 mIU/mL) were re-tested every 6 months and booster doses given as needed. Kaplan-Meier survival curve was used to estimate the probability of maintaining protective antibody level. Cox-proportional hazards models were used to assess the association between time to loss of protective antibody levels and certain explanatory variables. RESULTS: Overall primary vaccine-induced response was 79.2% (95% CI 68.2%, 87.3%), including 49/77 (63.6%; 95% CI 51.8%, 74.7%) patients who received the initial primary hepatitis B vaccine series and 12/21 (57.1%; 95% CI 34.4%, 77.4%) non-responders who were revaccinated with an additional series. Among weak responders (anti-HBs level 10.0-99.9 mIU/mL), protective antibody levels persisted in 44% for 12 months post-vaccination; whereas among strong responders (anti-HBs level ≥100 mIU/mL), protective antibody levels persisted in 92% for 12 months, and 68% for 24 months post-vaccination. A weak post-vaccination response increased the risk of losing protective antibody levels (adjusted hazard ratio, 9.7; 95% confidence interval, 3.5-28.5; p<0.0001). CONCLUSION: Revaccinating patients undergoing hemodialysis who do not respond to a primary vaccine series substantially increases the pool of protected patients. The threshold for defining hepatitis B vaccine-induced immunity should be revisited in this patient population to maximize the duration of protection.

Surveillance for acute viral hepatitis - United States, 2007.

PROBLEM: In the United States, acute viral hepatitis most frequently is caused by infection with any of three distinct viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV). These unrelated viruses are transmitted through different routes and have different epidemiologic profiles. Safe and effective vaccines have been available for hepatitis B since 1981 and for hepatitis A since 1995. No vaccine exists against hepatitis C. HBV and HCV can persist as chronic infections and represent a leading cause of chronic liver disease and hepatocellular carcinoma in the United States. REPORTING PERIOD COVERED: Cases in 2007, the most recent year for which data are available, are compared with those from previous years. DESCRIPTION OF SYSTEM: Cases of acute viral hepatitis are reported voluntarily to CDC by state and territorial health departments via CDC's National Notifiable Disease Surveillance System (NNDSS). Reports are received electronically via CDC's National Electronic Telecommunications System for Surveillance (NETSS). RESULTS: Acute hepatitis A incidence has declined 92%, from 12.0 cases per 100,000 population in 1995 to 1.0 case per 100,000 population in 2007, the lowest rate ever recorded. Declines were greatest among children and in those states where routine vaccination of children was recommended beginning in 1999. Acute hepatitis B incidence has declined 82%, from 8.5 cases per 100,000 population in 1990 to 1.5 cases per 100,000 population in 2007, the lowest rate ever recorded. Declines occurred among all age groups but were greatest among children aged <15 years. Following a peak in 1992, incidence of acute hepatitis C declined; however, since 2003, rates have plateaued. In 2007, as in previous years, the majority of these cases occurred among adults, and injection-drug use was the most common risk factor. INTERPRETATION: The results documented in this report suggest that implementation of the 1999 recommendations for routine childhood hepatitis A vaccination in areas of the United States with consistently elevated hepatitis A rates has reduced rates of infection. In addition, universal vaccination of children against hepatitis B beginning in 1991 has reduced disease incidence substantially among younger age groups. Higher rates of hepatitis B continue among adults, particularly among males aged 30-44 years, reflecting the need to vaccinate adults at risk for HBV infection. The decline in hepatitis C incidence after 1992 was attributable primarily to a decrease in incidence among injection-drug users. The reasons for this decrease were unknown but probably reflected changes in behavior and practices among injection-drug users. PUBLIC HEALTH ACTIONS: The expansion in 2006 of recommendations for routine hepatitis A vaccination to include all children in the United States aged 12-23 months is expected to reduce hepatitis A rates further. Ongoing hepatitis B vaccination programs ultimately will eliminate domestic HBV transmission, and increased vaccination of adults with risk factors will accelerate progress toward elimination. Further prevention of hepatitis B and hepatitis C relies on identifying and preventing transmission of HBV or HCV in hospital and nonhospital health-care associated settings. In addition, prevention of hepatitis C relies on identifying and counseling uninfected persons at risk for hepatitis C (e.g., injection-drug users) regarding ways they can protect themselves from infection. Public health management of persons with chronic HBV or HCV infection will help to interrupt the transmission to susceptible persons, and their medical management will help to reduce the development of the sequelae from chronic liver disease.