Stine Byberg 2016

Summary

Besides conferring specific immunity against measles infection, measles vaccine (MV) is associated with major reductions in all-cause child mortality, so-called “non-specific effects”. 
In Guinea-Bissau, West Africa, the first dose of MV, recommended at 9 months of age, is delivered through the routine vaccination programme at public health centres. Due to increasingly lower vaccine wastage targets for MV in Guinea-Bissau, and because donor vaccine statistics only count children below 12 months of age, it has become increasingly difficult to obtain routine MV. In Guinea-Bissau, a 10-dose MV vial is only opened if six or more children aged 9-11 months are present at the same time (the restrictive MV policy). 
In addition to the routine MV, a second dose of MV is provided in national vaccination campaigns conducted every three years, targeting all children aged 9-59 months, irrespective of routine MV vaccination status. 

In the present thesis, we evaluated both the routine delivery and the campaign delivery of MV. We assessed 1) the household experience and costs of seeking routine MV in rural Guinea-Bissau; 2) the cost-effectiveness of the restrictive MV policy versus providing MV for all children (MV-for-all policy), in rural Guinea-Bissau; 3) the effect on survival and cost-effectiveness of the December 2012 MV campaign in Bissau city, Guinea-Bissau. 
The studies draw on the infrastructure of the Bandim Health Project (BHP). BHP is a health and demographic surveillance system (HDSS) which surveys 182 clusters of women and children in rural Guinea-Bissau as well as the total population living in six suburbs in the capital Bissau. Several vaccine trials are conducted within this setting.

In paper I, we interviewed 1308 mothers of children aged 9-21 months living in the rural clusters, about their experiences with seeking routine MV, and calculated the costs of- and time spent on seeking routine MV. We assessed the MV status of the children through the HDSS. 34% of children who were measles unvaccinated at time of interview had sought MV at least once and 19% of children already measles vaccinated had been taken for MV more than once. In total, 80% had gone for MV but the coverage was only 70%. Mothers on average took their child for MV 1.4 times, the cost of one time being USD 1.33.

In paper II, we calculated the incremental cost-effectiveness of abandoning the restrictive MV policy, and providing MV to all children regardless of age and number of children present. Since 2011, the BHP has conducted a cluster-randomized trial, assigning children to either receive MV according to the restrictive MV policy or to receive MV regardless of age and number of children present (MV-for-all policy), in rural Guinea-Bissau. We used MV coverage estimates from this study to calculate the effect of the MV-for-all policy. We estimated the costs of delivering MV using different MV wastage scenarios; 40% wastage under the restrictive MV policy and 90% wastage under the MV for all policy. In the villages followed by BHP, MV coverage was 84% under the restrictive MV policy and 97% under the MV-for-all policy. Among 54,573 children born in 2011 and alive at 9 months of age, the MV-for-all policy was cost-effective, assuming 90% wastage, at USD 10.7 per life year gained (LYG) and USD 282 per death averted. At 87% wastage, the MV-for-all policy was cost-saving.

In paper III, we assessed the effect of the December 2012 MV campaign on general mortality. The BHP registered all children seen during the 2012 MV campaign in Bissau city. Participation status was assessed among all children living in the BHP study area. We compared mortality differences between participants and non-participants one year after the campaign using Cox regression. 85% (5641/6654) of eligible children received MV during the campaign. Adjusted for background factors associated with campaign participation, the hazard ratio (HR) comparing mortality in participants versus non-participants was 0.28 (0.10-0.77). There was no circulating measles at the time, so this mortality reducing effect of MV was non-specific. The beneficial effect of campaign MV on overall survival was most pronounced among girls and among children who already received routine MV. We also conducted a cost-effectiveness analysis of the December 2012 campaign, using the effect estimate found in paper 3. The cost of one LYG was USD 1.33 and the cost of one death averted was USD 35.2.

Taking the marked benefits and the high cost-effectiveness of increasing MV coverage into account, barriers to obtaining MV should be minimized. The restrictive MV policy entails a lower MV coverage compared with not limiting MV according to age and number of children present. The restrictive MV policy also means that mothers have to take their child for routine MV several times before receiving MV. We demonstrated that it was cost-effective and in some scenarios even cost-saving to provide MV for all children.

Based on the results of this thesis, for routine MV delivery, we recommend that a 10-dose MV be reclassified as a “1+ dose vial”, which should be opened for a single child, but can be extended to vaccinate up to 10 children. With respect to measles vaccination campaigns, these may soon cease to be conducted with measles elimination approaching. However, our results indicate that MV campaigns should in fact be continued or maybe even intensified, even after measles has been eliminated. 

In conclusion, non-specific effects of vaccines should be taken into account when assessing the effect and cost-effectiveness of vaccines. Doing so may help define the optimal measles vaccination policies to improve overall survival, also after measles eradication.