Impact of an Intervention to Use a Measles, Rubella, and Polio Mass Vaccination Campaign to Strengthen Routine Immunization Services in Nepal.

Background: The potential to strengthen routine immunization (RI) services through supplementary immunization activities (SIAs) is an important benefit of global measles and rubella elimination and polio eradication strategies. However, little evidence exists on how best to use SIAs to strengthen RI. As part the 2012 Nepal measles-rubella and polio SIA, we developed an intervention package designed to improve RI processes and evaluated its effect on specific RI process measures. Methods: The intervention package was incorporated into existing SIA activities and materials to improve healthcare providers' RI knowledge and practices throughout Nepal. In 1 region (Central Region) we surveyed the same 100 randomly selected health facilities before and after the SIA and evaluated the following RI process measures: vaccine safety, RI planning, RI service delivery, vaccine supply chain, and RI data recording practices. Data collection included observations of vaccination sessions, interviews with the primary healthcare provider who administered vaccines at each facility, and administrative record reviews. Pair-matched analytical methods were used to determine whether statistically significant changes in the selected RI process measures occurred over time. Results: After the SIA, significant positive changes were measured in healthcare provider knowledge of adverse events following immunization (11% increase), availability of RI microplans (+17%) and maps (+12%), and awareness of how long a reconstituted measles vial can be used before it must be discarded (+14%). For the SIA, 42% of providers created an SIA high-risk villages list, and >50% incorporated this information into RI outreach session site planning. Significant negative changes occurred in correct knowledge of measles vaccination contraindications (-11%), correct definition for a measles outbreak (-21%), and how to treat a child with a severe adverse event following immunization (-10%). Twenty percent of providers reported cancelling ≥1 RI sessions during the SIA. Many RI process measures were at high proportions (>90%) before the SIA and remained high afterward, including proper vaccine administration techniques, proper vaccine waste management, and availability of vaccine carriers and vaccine registers. Conclusions: Focusing on activities that are easily linked between SIAs and RI services, such as using SIA high-risk village list to strengthen RI microplanning and examining ways to minimize the impact of an SIA on RI session scheduling, should be prioritized when implementing SIAs.

Predictors of micronutrient powder intake adherence in a pilot programme in Nepal.

OBJECTIVE: Poor adherence to recommended intake protocols is common and a top challenge for micronutrient powder (MNP) programmes globally. Identifying modifiable predictors of intake adherence could inform the design and implementation of MNP projects. DESIGN: We assessed high MNP intake adherence among children who had received MNP ≥2 months ago and consumed ≥1 sachet (n 771). High MNP intake adherence was defined as maternal report of child intake ≥45 sachets. We used logistic regression to assess demographic, intervention components and perception-of-use factors associated with high MNP intake. SETTING: Four districts of Nepal piloting an integrated infant and young child feeding and MNP project. SUBJECTS: Children aged 6-23 months were eligible to receive sixty MNP sachets every 6 months with suggested intake of one sachet daily for 60 d. Cross-sectional surveys representative of children aged 6-23 months were conducted. RESULTS: Receiving a reminder card was associated with increased odds for high intake (OR=2·18, 95 % CI 1·14, 4·18); exposure to other programme components was not associated with high intake. Mothers perceiving ≥1 positive effects in their child after MNP use was also associated with high intake (OR=6·55, 95 % CI 4·29, 10·01). Perceiving negative affects was not associated; however, the child not liking the food with MNP was associated with lower odds of high intake (OR=0·12, 95 % CI 0·08, 0·20). CONCLUSIONS: Behaviour change intervention strategies tailored to address these modifiable predictors could potentially increase MNP intake adherence.

Predictors of micronutrient powder sachet coverage in Nepal.

Many countries implement micronutrient powder (MNP) programmes to improve the nutritional status of young children. Little is known about the predictors of MNP coverage for different delivery models. We describe MNP coverage of an infant and young child feeding and MNP intervention for children aged 6-23 months comparing two delivery models piloted in rural Nepal: distributing MNPs either by female community health volunteers (FCHVs) or at health facilities (HFs). Cross-sectional household cluster surveys were conducted in four pilot districts among mothers of children 6-23 months after starting MNP distribution. FCHVs in each cluster were also surveyed. We used logistic regression to describe predictors of initial coverage (obtaining a batch of 60 MNP sachets) at 3 months and repeat coverage (≥2 times coverage among eligible children) at 15 months after project launch. At 15 months, initial and repeat coverage were higher in the FCHV model, although no differences were observed at 3 months. Attending an FCHV-led mothers' group meeting where MNP was discussed increased odds of any coverage in both models at 3 months and of repeat coverage in the HF model at 15 months. Perceiving ≥1 positive effects in the child increased odds of repeat coverage in both delivery models. A greater portion of FCHV volunteers from the FCHV model vs. the HF model reported increased burden at 3 and 15 months (not statistically significant). Designing MNP programmes that maximise coverage without overburdening the system can be challenging and more than one delivery model may be needed.

Comparison of Methods to Assess Consumption of Micronutrient Powders Among Young Children in Nepal.

BACKGROUND: Assessing micronutrient powder (MNP) consumption is the key for monitoring program performance; no gold standard exists for assessing consumption in nutrition programs. OBJECTIVE: To compare estimates of MNP consumption assessed by maternal report versus observed unopened MNP sachets in the household. METHODS: Cross-sectional household surveys of children aged 6 to 23 months were conducted to assess an MNP project in Nepal; eligible children received 60 sachets per distribution. Mothers reported the number of sachets consumed and showed unused sachets. Directly observed difference (DOD) of MNP consumption was calculated by subtracting the number of observed unopened sachets from 60. Spearman correlation coefficient, categories of MNP consumption, and end digit preference were assessed. RESULTS: A total of 205 mothers did not show remaining unopened sachets despite reporting that all were not consumed. For the remaining 605 children, median consumption was 60.0 sachets by DOD and maternal report; the correlation coefficient was 0.91. With consumption grouped into categories of 0 to 14, 15 to 29, 30 to 44, and 45 to 60 sachets, the percent categorized into the same groupings by DOD and maternal report was 100%, 80.6%, 80.7%, and 91.2%, respectively. Excluding those who consumed 60 sachets, 16.9% and 8.0% by report and 14.2% and 6.1% DOD, ended with 0 and 5, respectively. CONCLUSION: Had the observation of unused sachets been used alone to assess MNP consumption, 205 children would not have been assessed. Estimates of MNP consumption by DOD and maternal report were similar in this population with high intake adherence.

High Prevalence of Vitamin B12 Deficiency and No Folate Deficiency in Young Children in Nepal.

Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 < 150 pmol/L) and folate deficiencies (red blood cell (RBC) folate < 226.5 nmol/L) were assessed. We used logistic regression to identify predictors of vitamin B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a) age six to 11 months (adjusted odds ratio (aOR) 1.51; 95% confidence interval (CI): 1.18, 1.92) or 12-17 months (aOR 1.38; 95% CI: 1.10, 1.72) compared to 18-23 months; (b) being stunted (aOR 1.24; 95% CI: 1.03, 1.50) compared to not being stunted; (c) and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41) compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

Micronutrient powder use and infant and young child feeding practices in an integrated program.

Integrated infant and young child feeding (IYCF)/micronutrient powder (MNP) programs are increasingly used to address poor IYCF practices and micronutrient deficiencies in low-income settings; however, little is known about how MNP use may affect IYCF practices. We describe how MNP use was associated with IYCF practices in a pilot program in select districts of Nepal where free MNP for children 6-23 months were added to an existing IYCF platform. Representative cross-sectional surveys were conducted in pilot districts with mothers of eligible children at 3 months (plains ecozone, n=1054) or 15 months (hill ecozone, rural only, n=654) after implementation of an integrated MNP/IYCF program. We used logistic regression to assess how IYCF practices varied by MNP use (none, 1-30, 30-60 sachets). At both time points, consuming 30-60 MNP sachets vs. none was associated with achieving minimum dietary diversity and minimum acceptable diet. In the 3 month survey consuming 30- 60 MNP sachets vs none was also associated with achieving minimum meal frequency and continued breastfeeding at 2 years. In this setting, addition of MNP to an existing platform of IYCF messaging did not appear detrimental to IYCF practices.

Comparison of two-dose priming plus 9-month booster with a standard three-dose priming schedule for a ten-valent pneumococcal conjugate vaccine in Nepalese infants: a randomised, controlled, open-label, non-inferiority trial.

BACKGROUND: Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood. METHODS: We did an open-label, randomised, parallel group, controlled trial in healthy infants aged 40-60 days from Kathmandu, Nepal. Participants were randomly allocated (4:4:5 ratio) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost (2+1), three-dose prime (3+0), or two doses after completion of the initial study phase (0+2). We used a computer generated randomisation list with randomly varying block sizes. We followed up participants at age 2-4 years together with a group of unvaccinated controls. Sera were analysed for opsonophagocytic activity, protein D, and PCV10 serotype-specific IgG. Laboratory staff was masked to intervention group assignment. The primary outcome measure was to determine the proportion of participants in the 2+1 group at age 10 months with specific IgG for serotypes 1, 5, and 14 of at least 0·2 µg/mL in the per-protocol population. The secondary outcomes were non-inferiority (within 10% levels) at age 18 weeks for the proportion of participants in the 2+1 group compared with the 3+0 group with serotypes 1, 5, and 14 specific IgG of at least 0·2 µg/mL; the proportion of participants with PCV10 serotype-specific IgG of at least 0·2 µg/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study group. In the follow-up study, the primary outcome measure was the proportion of participants with IgG of at least 0·2 µg/mL for PCV10 serotypes at age 2-4 years in children previously immunised with a 3+0 schedule compared with a 2+1 schedule. The trial is registered with Current Controlled Trials, registration number ISRCTN56766232. FINDINGS: Between May 10, 2010, and Jan 7, 2011, 390 children were randomly assigned to each group: 119 to the 2+1 group, 120 to the 3+0 group, and 151 to the 0+2 group. At age 10 months, the proportions of 2+1 participants with IgG of at least 0·2 µg/mL were 99·0% (95% CI 94·2-100·0) for serotype 1, 100% (96·2-100·0) for serotype 5, and 97·9% (92·5-99·7) for serotype 14. At age 18 weeks, non-inferiority (within 10% levels) of the 2+1 group was shown compared with the 3+0 group, and there was no difference between the 2+1 and 3+0 groups for the proportion with IgG of at least 0·2 µg/mL for any of the PCV10 serotypes. At age 10 months, proportions with IgG of at least 0·2 µg/mL for serotypes 1, 5, 6B, and 23F, were higher in the 2+1 group than in the 3+0 group. At age 18 weeks, there were no differences in opsonophagocytic activity between the 2+1 and 3+0 groups for reciprocal titres of at least 8, but at age 10 months, proportions with an opsonophagocytic reciprocal titre of at least 8 for serotypes 1, 4, 5, 6B, 18C, 19F and 23F were higher in the 2+1 group than in the 3+0 group. At age 2-4 years, there were higher proportions in the 2+1 group versus the 3+0 group with IgG of at least 0·2 µg/mL for serotypes 1, 5, 6B, and 18C. INTERPRETATION: Use of a 2+1 PCV schedule with booster at age 9 months in a resource-poor setting improved antibody persistence through early childhood without compromising antibody responses in early infancy. This schedule is now recommended by WHO for progressive introduction across Nepal, with PCV10 introduction having commenced on Jan 18, 2015. Concurrent pre-implementation and post-implementation surveillance is being done by a GAVI Alliance funded study. FUNDING: This study was supported by funding from the National Institute for Public Health and the Environment, The Netherlands; Oxford Vaccine Group, University of Oxford, UK; and GlaxoSmithKline Biologicals, Belgium.