Appropriate strategy for immunisation of children in India 3. Community-based annual pulse (cluster) immunisation

A strategy of annual pulse vaccination is proposed as the most appropriate technique for achieving high immunisation rates in our country. Because vaccine is taken to children in their communities on announced dates, acceptance will be much higher than with conventional clinic vaccination. A simplified immunisation schedule and a family-retained record are used to reduce complexity. Vaccines and other materials are managed at a district level; the local arrangements for vaccination are made by the PHC staff and village level workers. The advantages of this technique include higher coverage, shortened and strengthened cold chain, reduced red tape for recipients of vaccine, the involvement of private health institutions in a national campaign, and a strengthening of the PHC system

Comparison of different culture media and storage temperatures for the long-term preservation of Streptococcus pneumoniae in the tropics

Objective: The preservation of Streptococcus pneumoniae by standard freezing methods for subsequent tests- such as serotyping and antibiotic susceptibility-is not possible or is difficult in many developing countries because of the high cost of equipment, inadequate equipment maintenance, and irregular power supply. We evaluated alternative low-cost methods, by comparing different culture media and storage temperatures. Methods: Clinical isolates of five capsular types (1, 5, 7, 19, and 23) of S. pneumoniae were preserved in rabbit blood, sheep blood, skimmed milk, or glycerol-chocolate broth, and stored at -20 °C or -70 °C. The cultures were also preserved by lyophilization or sand desiccation, followed by storage at room temperature and 4 °C. The viability of the preserved cultures was determined by making serial colony counts on day 0 and after 1 week, 4 weeks, 4 months and 16 months. The viability of cultures preserved by sand desiccation and storage at 4 °C was also determined every 6 months for up to 68 months. Findings: Irrespective of the media used, cultures maintained at -20 °C became nonviable by the fourth month, while those maintained at -70 °C were still viable at 16 months. Cultures preserved by lyophilization or sand desiccation lost their viability by the fourth month when maintained at local room temperature (30-42 °C), but remained viable when stored at 4 °C for up to 68 months. Conclusions: Our results confirm that freezing at -70 °C, or lyophilization and storage at 4 °C are the ideal methods for the preservation of S. pneumoniae. In laboratories where lyophilization is not feasible, sand desiccation and storage at 4 °C offers an alternative low-cost method for the long-term preservation of S. pneumoniae

Maternal Influenza Immunization and Reduced Likelihood of Prematurity and Small for Gestational Age Births: A Retrospective Cohort Study

In an analysis of surveillance data from the state of Georgia (US), Saad Omer and colleagues show an association between receipt of influenza vaccination among pregnant women and reduced risk of premature births

Designs of two randomized, community-based trials to assess the impact of influenza immunization during pregnancy on respiratory illness among pregnant women and their infants and reproductive outcomes in rural Nepal

Background: Among the most important causes of illness and death in both pregnant women and their newborn infants are respiratory infections including influenza. Pregnant women in North America have a 4 to 5 fold excess rate of hospitalization compared to non-pregnant women. Rates of infant hospitalization associated with influenza are much higher than in their mothers. Fully half of children hospitalized for influenza in the US are in the age group 0–5 months, a group where no vaccine is licensed. Data on influenza are much fewer in low income countries where the risks of serious morbidity and mortality are much higher. A recent trial in Bangladesh suggested that influenza immunization in pregnant women could have important protective effects against influenza in both mothers and their infants. These trials were designed to provide additional evidence about the effect of influenza vaccination in pregnancy in settings where influenza may circulate for up to ten months/year. Methods/Design: We conducted a consecutive pair of community-based, placebo-controlled, randomized trials of influenza vaccination of pregnant women in a rural district in southern Nepal. Two trials were conducted to insure, as much as possible, the match of circulating strains with those included in the vaccine. Eligible women included all who were or became pregnant over a one year period. Each trial included a one year cohort of pregnant women who were individually randomized to the influenza vaccine available at the time of their enrollment or placebo. Exclusions included a history of allergy to vaccine components, prior influenza vaccine receipt, and for the second trial, participation in the first trial. Morbidity was assessed on a weekly basis for women throughout pregnancy and through 180 days post-partum. Infants were followed weekly through 180 days. Primary outcomes included: 1) incidence of influenza like illness in women, 2) incidence of laboratory confirmed influenza illness in infants, and 3) birthweight among newborn infants. Discussion: We have presented the design and methods of two randomized trials of influenza immunization of pregnant women

Supporting Global Health at the Pediatric Department Level: Why and How

Over the past 20 years, involvement in pediatric global health (GH), the study and practice of improving the health of children worldwide, has evolved from an extracurricular activity to a robust academic pursuit that enhances the clinical, educational, and research missions of academic health centers (Fig 1). As evidenced by the paradigm shift laid out in the United Nations Sustainable Development Goals, which focus on the health of all people worldwide, GH is no longer a field constrained by arbitrary borders.1 Likewise, pediatric departments seeking to expand knowledge, train pediatricians, or improve care for children through research and innovation must be concerned with the health of all children and addressing health equity, which by definition, implies GH work.2 This article aims to provide pediatric department leadership with the background and action steps necessary to respond to the call that support for GH should not be a luxury limited to a few elite institutions but a core part of pediatric education and research across the country.

Infant vaccination timing: Beyond traditional coverage metrics for maximizing impact of vaccine programs, an example from southern Nepal.

Background Immunization programs currently measure coverage by assessing the proportion of children 12–24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited. Objective To estimate the time to Bacillus Calmette–Guérin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants \u3c6 months of age in a district in southern Nepal where traditional coverage metrics are high. Design/methods Infants enrolled in a randomized controlled trial of maternal influenza vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan–Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine. Results The median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months. Conclusion A significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health

Pertussis Seroepidemiology in Women and Their Infants in Sarlahi District, Nepal.

Background Infants are at greatest risk for pertussis morbidity and mortality. Maternal vaccination during pregnancy has been shown to prevent pertussis in young infants in high- and middle-income countries. However, data on the levels of maternal pertussis antibodies and the efficiency of transplacental transfer in low-income South Asian settings are limited. Objective To estimate the prevalence of maternal pertussis antibodies and the efficiency of transplacental transfer in rural southern Nepal. Design/methods Paired maternal-infant blood samples were collected from a subsample of participants in a randomized, controlled trial of maternal influenza immunization (n = 291 pairs). Sera were tested by enzyme-linked immunosorbent assays for pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae. Maternal and infant pertussis antibody levels and transplacental transfer efficiency were determined and potential factors associated with both were assessed. Results Elevated maternal antibodies to pertussis toxin, suggesting recent pertussis infection, were rarely detected (4%, tested n = 305). However, paired maternal-cord sera were highly correlated across all antibodies; transplacental antibody transfer ratios for pertussis toxin were 1.14 (n = 291, 95% CI 1.07–1.20); filamentous hemagglutinin 1.10 (n = 120, 95% CI: 1.01–1.20); fimbriae 2/3 1.05 (n = 120, 95% CI: 0.96–1.15) and pertactin 0.96 (n = 289, 95% CI: 0.91–1.00). Older gestational age was associated with increased pertussis toxin and decreased fimbriae 2/3 antibody transport. Conclusions A low prevalence of maternal antibody to all four pertussis antigens was noted in Nepal, but transplacental antibody transfer was efficient. No consistent demographic factors were associated with elevated maternal antibody levels or efficiency of transplacental transfer. If an increase in infant pertussis disease burden was detected in this population, maternal immunization could be an effective intervention to prevent disease in early infancy

Impact of Maternal Vaccination Timing and Influenza Virus Circulation on Birth Outcomes in Rural Nepal.

Objective To describe the effect of maternal vaccination on birth outcomes in rural Nepal, modified by timing of vaccination in pregnancy and influenza virus activity. Methods A secondary analysis was conducted using data from two annual cohorts of a randomized controlled trial. A total of 3693 pregnant women from Sarlahi District were enrolled between April 25, 2011, and September 9, 2013. All participants were aged 15–40 years and received a trivalent inactivated influenza vaccine or placebo. The outcome measures included birth weight, pregnancy length, low birth weight (\u3c2500 g), preterm birth, and small‐for‐gestational‐age birth. Results Data were available on birth weight for 2741 births and on pregnancy length for 3623 births. Maternal vaccination increased mean birthweight by 42 g (95% confidence interval [CI] 8–76). The magnitude of this increase varied by season but was greatest among pregnancies with high influenza virus circulation during the third trimester. Birth weight increased by 111 g (95% CI −51 to 273) when 75%–100% of a pregnancy\u27s third trimester had high influenza virus circulation versus 38 g (95% CI −6 to 81) when 0%–25% of a pregnancy\u27s third trimester had high influenza virus circulation. However, these results were nonsignificant. Conclusion Seasonal maternal influenza vaccination in rural Nepal increased birth weight; the magnitude appeared larger during periods of high influenza virus circulation. ClinicalTrials.gov NCT01034254

Nutritional Status of Infants at Six Months of Age Following Maternal Influenza Immunization: A Randomized Placebo-controlled Trial in Rural Nepal.

Background Maternal influenza vaccination has increased birth weight in two randomized trials in South Asia but the impact on infant growth is unknown. Methods A randomized placebo-controlled trial of year round maternal influenza immunization was conducted in two annual cohorts in Sarlahi District, southern plains of Nepal, from April 2011 through April 2014. Infants born to women enrolled in the trial had weight, length, and head circumference measured at birth and 6 months of age. The study was powered for the 3 primary trial outcomes but not for stunting and wasting at 6 months of age. Results 3693 women received placebo or influenza vaccine between 17 and 34 weeks gestation, resulting in 3646 live births. About 72% of infants who survived had weight and length measurements between 150 and 210 days of age. Prevalence of stunting (\u3c−2 Z scores length-for-age) was 14.8% in the placebo and 13.6% in the vaccine groups, respectively. Stunting \u3c −3 Z scores was 3.2% versus 2.0% in placebo versus vaccine groups (RR: 0.64 (95% CI: 0.39, 1.04)). Wasting (\u3c −2 Z scores weight for length) was 10.3% versus 11.0% for placebo versus vaccine groups. Severe wasting (\u3c −3 Z scores weight for length) was 3.8% for placebo versus 2.6% for vaccine (RR: 0.69 (95% CI: 0.44, 1.07)). The impact of flu vaccine on wasting was greater in cohort 2 than in cohort 1, (RR: 0.66 (0.44, 0.99) for any wasting), and RR: 0.45 (0.19, 1.09) for severe wasting. This corresponded to a larger impact on birth weight and a better vaccine match with circulating viruses in cohort 2. Conclusions Although maternal immunization reduced low birth weight by 15%, only wasting at 6 months in the 2nd cohort was statistically significantly difference. However, the study was underpowered to detect reductions of public health importance. Trial Registration: Clinicaltrials.gov (NCT01034254)

Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal.

Background. Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal. Methods. Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, infants were visited weekly from birth through 6 months to assess respiratory illness in the prior week. If any respiratory symptoms had occurred, a nasal swab was collected and tested with a multitarget pertussis polymerase chain reaction (PCR) assay. The prospective cohort study includes infants observed between May 2011 and August 2014. Results. The incidence of PCR-confirmed Bordetella pertussis was 13.3 cases per 1000 infant-years (95% confidence interval, 7.7–21.3) in a cohort of 3483 infants with at least 1 day of follow-up. Conclusions. In a population-based active home surveillance for respiratory illness, a low risk for pertussis was estimated among infants in rural Nepal. Nepal’s immunization program, which includes a childhood whole cell pertussis vaccine, may be effective in controlling pertussis in infants