Risk Factors for Mortality Among Children Younger Than Age 5 Years With Severe Diarrhea in Low- and Middle-income Countries: Findings From the World Health Organization-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children younger than 5 years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low- and middle-income countries. METHODS: Data from the World Health Organization (WHO)-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children <5 years of age who were hospitalized with diarrhea between 2008 and 2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis comprises 234 781 cases, including 1219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI], 2.81-4.50), female sex (OR = 1.18; 95% CI, 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01-3.25), no vomiting (OR = 1.13; 95% CI, .98-1.30), severe dehydration (OR = 3.79; 95% CI, 3.01-4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO regions (OR = 130.62 comparing the African Region with the European Region; 95% CI, 55.72-422.73), whereas cases from the European Region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections.

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.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children.

BACKGROUND: Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years. METHODS: There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012-December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE). RESULTS: Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6-21.8) for all pneumococci and 39.2% (95% CI 26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7-33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4-35.8) by 2018, with a decrease of 36.3% (95% CI 23.8-46.9) for VT IPD and an increase of 101.4% (95% CI 62.0-145.4) for non-VT IPD. CONCLUSIONS: Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.

Japanese Encephalitis Surveillance and Immunization - Asia and Western Pacific Regions, 2016.

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

Pneumococcal colonization and severity of pneumonia in hospitalized Cambodian children following introduction of the 13-valent pneumococcal conjugate vaccine.

Objectives: This study sought to characterize pneumococcal colonization and clinical/radiological features in Cambodian children admitted to hospital with an illness compatible with pneumonia following national introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: Children aged 0-59 months admitted to Angkor Hospital for Children who met the World Health Organization (WHO) case definition for clinical pneumonia were enrolled over a 3-year period. Clinical, radiological and vaccination data were collected at enrolment. A nasopharyngeal swab was collected for detection of pneumococcal colonization using the WHO standard culture method. Results: Between 1 September 2015 and 31August 2018, 2209 analysable illness episodes were enrolled. Pneumococci were detected in 943/2209 (42.7%) children. PCV13 serotypes were detected less frequently in children who had been vaccinated appropriately for their age compared with undervaccinated children: 309/567 (53.6%) vs 216/342 (63.2%) (P=0.006). Age-appropriate PCV13 vaccination was negatively associated with hypoxic presentation [adjusted odds ratio (aOR) 0.72, 95% confidence interval (CI) 0.60-0.87; P=0.0006] and primary endpoint pneumonia on chest x ray (aOR 0.69, 95% CI 0.54-0.90; P=0.006). Conclusions: The introduction of PCV13 in Cambodia was associated with a decline in vaccine serotype nasopharyngeal colonization, and clinical and radiological severity in children hospitalized with clinical pneumonia.

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.

Comprehensive Vaccine-Preventable Disease Surveillance in the Western Pacific Region: A Literature Review on Integration of Surveillance Functions, 2000-2021.

INTRODUCTION: A strategic framework for 2021-2030 developed by the World Health Organization (WHO) Regional Office for the Western Pacific emphasizes the need for high-quality and integrated vaccine-preventable disease (VPD) surveillance. We conducted a literature review to document the barriers, enabling factors, and innovations for integrating surveillance functions for VPDs and other communicable diseases in Western Pacific Region (WPR) countries. METHODS: We searched published and gray literature on integrated VPD surveillance from 2000 to 2021. Articles in English, Spanish, or French were screened to identify those relating to VPD surveillance in a WPR country and not meeting defined exclusion criteria. We categorized articles using the 8 WHO surveillance support functions and abstracted data on the country; type of surveillance; and reported barriers, enabling factors, and best practices for integration. RESULTS: Of the 3,137 references screened, 87 met the eligibility criteria. Of the 8 surveillance support functions, the proportion of references that reported integration related to the laboratory was 56%, followed by workforce capacity (54%), governance (51%), data management and use (47%), field logistics and communication (47%), coordination (15%), program management (13%), and supervision (9%). Several references noted fragmented systems and a lack of coordination between units as barriers to integration, highlighting the importance of engagement across public health units and between the public and private sectors. The literature also indicated a need for interoperable information systems and revealed the use of promising new technologies for data reporting and laboratory testing. In some WPR countries, workforce capacity was strengthened at all administrative levels by the implementation of integrated trainings on data monitoring and use and on laboratory techniques applicable to multiple VPDs. CONCLUSION: This literature review supports integrating VPDs into broader communicable disease surveillance systems in WPR countries while ensuring that the minimal WHO-recommended standards for VPD surveillance are met.

Rural and urban Vietnamese mothers utilization of healthcare resources for children under 6 years with pneumonia and associated symptoms.

Worldwide, pneumonia causes 14% of deaths among children and infants (ages 4 weeks to 5 years). UNICEF and WHO have established treatment guidelines to reduce risk of death from pneumonia including caregiver symptom recognition, appropriate care, and use of antibiotics. In June 2008, cross-sectional survey data were collected in Khanh Hoa Province Viet Nam with 329 mothers of children under 6 years. In relation to pneumonia and associated symptoms (fever >38 °C, strong cough, "fast or difficult" breathing), data were collected on perceptions of symptom severity and child vulnerability, reported healthcare utilization including use of antibiotics, sources of health information, and barriers to care. Pearson's chi square, independent t tests, and multinomial analysis were conducted to assess different patterns of reported healthcare utilization in relation to residency (rural/urban), mother's education, and household income. Outcomes include rural and urban residency-based patterns related to perceptions of child's vulnerability and symptom severity, health facility utilization and barriers to care, and reported use of antibiotics during previous episodes of pneumonia. Implications include the need to target different healthcare facilities in urban and rural Viet Nam in relation to education about symptoms of childhood pneumonia and associated treatments.

Timeliness of childhood vaccinations in the Philippines.

Timeliness of vaccinations is rarely part of monitoring in a routine immunization program. We reviewed infant immunization and conducted caregiver interviews in three regions in the Philippines from January to October 2016. We randomly selected thirty public health centers, one for each region. We defined timeliness of the receipt of antigen as within 4 weeks after the recommended age at vaccination. We assessed a total of 986 infants for timeliness of vaccination. The median age of receipt of vaccine was at 2.7 weeks (BCG), 10.1 weeks (Penta 1), and 21.7 weeks (Penta 3) compared to the recommended 0, 6, and 14 weeks of age, respectively. We found timely receipt only in 74.4% for BCG, 70.3% for Penta 1, and 39.1% for Penta 3 recipients. Thus, alongside declining immunization coverage, the infants in the Philippines had substantial delays in vaccine receipt.

Evidence-informed vaccination decision-making in countries: Progress, challenges and opportunities.

Countries face an increasingly complex vaccination landscape. As well as ever-changing infectious disease epidemiology, the number and diversity of vaccine-preventable diseases, vaccine products, and vaccine technologies continue to increase. To ensure that vaccination decision-making is transparent, country-owned and informed by sound scientific evidence, many countries have established national immunization technical advisory groups (NITAGs) to provide independent expert advice. The past decade has seen substantial growth in NITAG numbers and functionality, and there is now a need to consolidate this progress, by further capacity building, to ensure that NITAGs are responsive to the changing face of immunization over the next decade.

Impact of rotavirus vaccine on diarrheal hospitalization and outpatient consultations in the Philippines: First evidence from a middle-income Asian country.

BACKGROUND: Monovalent rotavirus (RV) vaccine was introduced in the Philippines in a phased manner beginning in 2012. To assess the impact of RV vaccine, we conducted a retrospective review of diarrheal admissions in two hospitals. METHODS: Records of physician-diagnosed diarrheal admissions were reviewed in D.O. Plaza Hospital (DOPH) from 2009 to 2016 in Agusan del Sur where RV vaccine was introduced in the immunization program; and in Cotabato Regional Medical Center (CRMC) from 2011 to 2016 in a region where the vaccine was not introduced. Reports from consultations in public health clinics in Agusan Del Sur and RV vaccine coverage were obtained. RESULTS: All-cause diarrheal admissions among children <5 years old in DOPH declined from 2013 to 2016 following RV vaccine introduction in 2012. Using the 2009-2011 mean number of hospitalizations as baseline (X‾ = 1,141), the reductions were 28% (n = 821), 56% (n = 507), 63% (n = 417) and 59% (n = 466) in 2013, 2014, 2015 and 2016, respectively. In comparison, no substantial declines in diarrheal hospitalizations were seen in CRMC from 2011 to 2016. A declining trend was also seen in outpatient consultations in Agusan del Sur following RV vaccine introduction with declines of 27% (n = 2,333), 33% (n = 2,143), 45% (n = 1,764) and 67% (n = 1,059) in 2013, 2014, 2015 and 2016. From September 2012 to December 2016, the 1 and 2-dose RV vaccine coverage gradually increased from 5% and 4% in 2012 to 92% and 88% in 2015, but decreased in 2016 to 53% and 52%, respectively. DISCUSSION: RV vaccine introduction was associated with a substantial decline in diarrheal hospitalizations and outpatient consultations for diarrhea in Agusan del Sur, Philippines.

Molecular characterization of rotavirus diarrhea among children aged under five years in the Philippines, 2013-2015.

With the availability of new and existing rotavirus vaccines, credible and reliable data on burden of rotavirus-associated disease are needed to enable evidence-based decision making regarding the introduction of rotavirus vaccines. The national rotavirus surveillance program in the Philippines, a sentinel-based surveillance, was established in 2012 to determine the proportion of laboratory-confirmed rotavirus cases among children under five years with acute gastroenteritis and to describe the geographic distribution and molecular epidemiology of rotavirus in the country. During 2013 to 2015, rotavirus infection was the cause of acute gastroenteritis among children under five years admitted to hospitals or evaluated in emergency rooms, constituting more than one-third of gastroenteritis hospitalizations at the sentinel site hospitals. The predominant genotype observed was G1P[8]. Although a rotavirus surveillance network has been established, findings suggest the need to strengthen the network in the country and to continue monitoring prevalent rotavirus strains to help identify the possible emergence of new strains.

Epidemiology of acute diarrhea caused by rotavirus in sentinel surveillance sites of Vietnam, 2012-2015.

A prospective, multicentre study was conducted in four sentinel surveillance hospitals to assess the trend and epidemiology of acute diarrhea caused by Rotavirus in Vietnam. During the period 2012-2015, a total 8,889 children under 5 years of age were enrolled in the surveillance, and 8689 stool samples were collected. Of these cases, Rotavirus was most common pathogen 46.7% (4054 cases); in which 26.6% (1117) rotavirus-positive stool samples were evaluated to identify genotypes. The proportion of rotavirus positive specimens decreased annually from 54.7% in 2012 to 36.6% in 2015. Rotavirus was detected year-round, but most rotavirus gastroenteritis cases (77.1%) occurred between December and May, corresponding to the rotavirus seasonality. It is found that the peaks varied by regions. Rotavirus positivities varied between the youngest and oldest age, but children 6-11 months old (38.8%) and 12-23 months old (38.4%) counted for most cases. A significant higher number of diarrhea within 24 hours (8.3 times, 95%CI: 8.1-8.4 times) and higher proportion of severe dehydration (12.9%) in Rotavirus positive group than that in Rotavirus negative group (7.7 times, 95%CI: 7.6-7.9 times; and 9.7%, respectively). A downtrend of prevalence of G1P[8] was observed from 82% in 2013 to 15% in 2015. However, G2P[4] was found in 5% of samples in 2012, 9% in 2013, 36% in 2014, and 28% in 2015. Rotavirus infection is the most important cause of acute diarrhea among hospitalized children in Vietnam, and a rotavirus vaccination program for children may significantly reduce this disease.

Supporting countries in establishing and strengthening NITAGs: lessons learned from 5 years of the SIVAC initiative.

To empower governments to formulate rational policies without pressure from any group, and to increase the use of evidence-based decision-making to adapt global recommendations on immunization to their local context, the WHO has recommended on multiple occasions that countries should establish National Immunization Technical Advisory Groups (NITAGs). The World Health Assembly (WHA) reinforced those recommendations in 2012 when Member States endorsed the Decade of Vaccines Global Vaccine Action Plan (GVAP). NITAGs are multidisciplinary groups of national experts responsible for providing independent, evidence-informed advice to health authorities on all policy-related issues for all vaccines across all populations. In 2012, according to the WHO-UNICEF Joint Reporting Form, among 57 countries eligible for immunization program financial support from the GAVI Alliance, only 9 reported having a functional NITAG. Since 2008, the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative (at the Agence de Médecine Préventive or AMP) in close collaboration with the WHO and other partners has been working to accelerate and systematize the establishment of NITAGs in low- and middle-income countries. In addition to providing direct support to countries to establish advisory groups, the initiative also supports existing NITAGs to strengthen their capacity in the use of evidence-based processes for decision-making aligned with international standards. After 5 years of implementation and based on lessons learned, we recommend that future efforts should target both expanding new NITAGs and strengthening existing NITAGs in individual countries, along three strategic lines: (i) reinforce NITAG institutional integration to promote sustainability and credibility, (ii) build technical capacity within NITAG secretariats and evaluate NITAG performance, and (iii) increase networking and regional collaborations. These should be done through the development and dissemination of tools and guidelines, and information through a variety of adapted mechanisms.