Mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in Kenya (M-SIMU): a cluster randomised controlled trial

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with logbinomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%

Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania

OBJECTIVE To investigate the relationship between a panel of angiogenic and inflammatory biomarkers measured in mid-pregnancy and small-for-gestational age (SGA) outcomes in sub-Saharan Africa. STUDY DESIGN Concentrations of 18 angiogenic and inflammatory biomarkers were determined in 432 pregnant women in Dar es Salaam, Tanzania who participated in a trial examining the effect of multivitamins on pregnancy outcomes. Infants falling below the 10th percentile of birth weight for gestational age relative to the applied growth standards were considered SGA. Multivariate binomial regression models with the log link function were used to determine the relative risk of SGA associated with increasing quartiles of each biomarker. Stepwise cubic restricted splines were used to test for non-linearity of these associations. Receiver operating curves obtained from multivariate logistic regression models were used to assess the discriminatory capability of selected biomarkers. RESULTS A total of 60 participants (13.9%) gave birth to SGA infants. Compared to those in the first quartile, the risk of SGA was reduced among those in the fourth quartiles of VEGF-A (adjusted risk ratio (RR) 0.38, 95% Confidence Interval (CI), 0.19-0.74), PGF (adjusted RR 0.28, 95% CI, 0.12-0.61), sFlt-1 (adjusted RR 0.48, 95% CI, 0.23-1.01), MCP-1 (adjusted RR 0.48, 95% CI, 0.25-0.92), and Leptin (adjusted RR 0.46, 95% CI, 0.22-0.96) CONCLUSION Our findings provide evidence of altered angiogenic and inflammatory mediators, at mid-pregnancy, in women who went on to deliver small for gestational age infants

Plasma concentrations of leptin at mid-pregnancy are associated with gestational weight gain among pregnant women in Tanzania: a prospective cohort study

Background: Gestational weight gain (GWG) has critical implications for maternal and child health. Inflammation and angiogenesis are implicated in various aspects of maternal metabolism that may play a role in gestational weight gain. The associations of inflammatory, angiogenic, and metabolic pathways with GWG are yet to be elucidated. This study evaluated associations between a panel of inflammatory, angiogenic, and metabolic proteins measured in mid-pregnancy and gestational weight gain. Methods: Pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. The participants were enrolled at mid-pregnancy (12 to 27 weeks of gestation) and followed up until delivery. This analysis focused on a cohort of 1002 women who were primigravid, had singleton live births, had longitudinal measures of gestational weight, and whose mid-pregnancy plasma samples underwent analysis for 18 proteins. Results: Higher plasma concentrations of leptin (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 10.24; 95% CI 3.31, 17.16; p-trend = 0.003) and chitinase-3-like protein-1 (CH3L1) (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 7.02; 95% CI 0.31, 13.72; p-trend = 0.007) were associated with greater GWG in a dose-response pattern. Higher leptin concentrations were associated with a lower risk of inadequate GWG (risk ratio comparing highest with lowest quartiles: 0.77; 95% CI 0.65, 0.91; p-trend = 0.001) and a higher risk of excessive GWG (risk ratio comparing highest with lowest quartiles: 1.57; 95% CI 1.03, 2.39; p-trend = 0.03). Higher CH3L1 concentrations were associated with a higher risk of excessive GWG (p-trend = 0.007). The associations of leptin and CH3L1 with inadequate GWG were stronger during the second than the third trimester. The other 16 proteins examined were not significantly associated with GWG. Conclusions: Mid-pregnancy plasma leptin concentrations may be associated with GWG and have clinical predictive utility in identifying women at a higher risk of inadequate or excessive gestational weight gain

Optimization and Stability Testing of Four Commercially Available Dried Blood Spot Devices for Estimating Measles and Rubella IgG Antibodies.

Blood collection using dried blood spots (DBS) provides an easier alternative to venipuncture for sample collection, transport, and storage but requires additional processing that can cause variability in results. Whole-blood samples spotted on four DBS devices and respective paired serum samples were tested for antimeasles and antirubella IgG antibody concentrations by enzyme immunoassay. Elution protocols for DBS devices were optimized for comparability relative to serum samples using 12 adult volunteers. Stability of DBS collected on HemaSpot HF was assessed under various temperature conditions (+4, 22 to 25, and 45°C) at six time points (0, 7, 15, 30, 60, and 90 days) in a controlled laboratory setting using six adult volunteers. Devices were shipped and stored for 30 days at four settings with variable temperature and humidity conditions to assess the impact on antibody concentrations. Three DBS devices demonstrated comparable antibody concentrations with paired sera following optimization. Antibodies recovered from DBS were stable for at least 90 days at 4°C and for 30 days at ambient temperature (22 to 25°C) using the HemaSpot HF device. A drastic decline in antibody concentrations was observed at 45°C, resulting in quantitative and qualitative discrepancies by day 7. HemaSpot HF devices shipped to field sites and stored at ambient temperature and humidity resulted in quantitative, but not qualitative, variability. Measurement of antimeasles and antirubella IgG antibodies with DBS devices is an accurate alternative to testing serum, provided elution protocols are optimized. Stability of HemaSpot HF devices at ambient temperature enables broader use in surveys when serum processing and cold storage are not feasible. IMPORTANCE Dried blood spot (DBS) collection offers various advantages over conventional methods of blood collection, especially when collecting and transporting samples for a serosurvey. Yet use of DBS requires additional processing steps in the laboratory that can add to variability in results. We optimized a protocol to elute IgG antibodies against measles and rubella viruses in four DBS devices, demonstrating high concordance with paired venous sera for most devices. Extensive stability studies with various temperature and storage conditions in the laboratory and in the field were conducted using HemaSpot HF DBS devices prior to its use in one of the largest community-based measles and rubella serological surveys in the world

Experiences of sharing results of community based serosurvey with participants in a district of Maharashtra, India.

A growing number of organisations, including medical associations, recommend that research subjects should be given the option of being informed about the general outcome and results of the study. We recently completed a study involving nine serosurveys from 2018 to 2020 in five districts of India among three age groups (children 9 months to < 5 years; 5 to < 15 years of age, and women 15 to < 50 years of age before and after the measles and rubella (MR) vaccination campaigns). In Palghar district of Maharashtra all individuals in 30 selected clusters were enumerated, and 13 individuals per age group were randomly sampled. We established the procedures to return the results to the respondents for each stage of the survey. Of the 1,166 individuals selected for the measles and rubella serosurvey, 971 (83%) agreed to participate and were enrolled. Participants were informed that they will only be contacted if they test seronegative for measles and/or rubella antibodies. Overall, 140 individuals enrolled in the survey tested seronegative for IgG antibodies to measles and/or rubella viruses; were provided the reports and informed to seek medical advice. Upon follow up by phone, 10% (14) of the 140 participants reported to have been vaccinated. In this paper we discuss the procedures, experiences and considerations in returning results to participants in a community-based measles and rubella serosurvey. Although the lessons learned are specific to post measles-rubella vaccine campaign serosurvey in India, they might be helpful to those contemplating sharing results to participants of large scale survey settings

Implementing Serosurveys in India: Experiences, Lessons Learned, and Recommendations.

Serological surveillance for vaccine-preventable diseases, such as measles and rubella, can provide direct measures of population immunity across age groups, identify gaps in immunity, and document changes in immunity over time. Rigorously conducted, representative household serosurveys provide high-quality estimates with minimal bias. However, they can be logistically challenging, expensive, and have higher refusal rates than vaccine coverage surveys. This article shares lessons learned through implementing nine measles and rubella household serosurveys in five districts in India-the challenges faced, the potential impact on results, and recommendations to facilitate the conduct of serosurveys. Specific lessons learned arose from challenges related to community mobilization owing to lack of cooperation in certain settings and populations, limitations of outdated census information, nonresponse due to refusal or unavailability during survey enumeration and enrollment, data collection issues, and specimen collection and handling issues. Although some experiences are specific to serosurveys in India, these lessons are generalizable to other household surveys, particularly vaccination coverage and serosurveys conducted in low- and middle-income settings

Diagnostic Accuracy of Dried Blood Spots Collected on HemaSpot HF Devices Compared to Venous Blood Specimens To Estimate Measles and Rubella Seroprevalence.

Fingerprick blood spotted onto filter paper offers an alternative to venous blood for use in population-based surveillance because it is comparatively inexpensive, acceptable, and easy to manage in the field. Prior studies have shown excellent agreement for immunoglobulin G (IgG) antibody detection from dried blood spots (DBS) and venous blood samples. However, much of this evidence is from high-income settings or laboratories where the samples were unlikely to be exposed to extreme temperatures and humidity, factors known to degrade DBS. We report the diagnostic accuracy of DBS collected using HemaSpot HF devices against venous sera in measuring measles- and rubella-specific IgG antibodies in a household serosurvey conducted in two districts in India. Paired serum and DBS samples collected by fingerprick were collected from women aged 15 to 50 years enrolled in a serosurvey in Palghar District of Maharashtra and Kanpur Nagar District of Uttar Pradesh in India. Specimen quality and volume were assessed in the laboratory. Samples were tested for antimeasles and antirubella IgG antibodies by an enzyme-linked immunosorbent assay (ELISA) (Euroimmun). Sensitivity of antibody detection by DBS was greater than 98%, and specificity was 90% and 98%, for measles and rubella IgG, respectively. Antibody concentrations were strongly correlated between paired specimens with adequate volume (measles R2 = 0.94; rubella R2 = 0.89). Although correlation was poor if DBS specimens had lower volumes, impact on qualitative results was minimal. This study showed DBS collected with HemaSpot HF devices can generate highly accurate results of measles- and rubella-specific IgG compared to sera in community-based surveys when protocols are optimized for DBS specimens. IMPORTANCE Dried blood spot (DBS) collection provides an easy, practical, and acceptable alternative to venous blood collection, especially for community-based studies, provided that results from DBS are accurate. We demonstrated high sensitivity and specificity for measles- and rubella-specific immunoglobulin G (IgG) with DBS collected via HemaSpot HF devices compared to serum samples. This is one of the largest community-based diagnostic accuracy studies of measles and rubella antibody testing with DBS and the first application we are aware of using HemaSpot HF device for measles and rubella serology. Results support the use of DBS in community-based serosurveillance