In the 2007 campaign, we followed 5567 (92%) of the 6026 children aged 6–35 months registered in the study area. Reasons for losses to follow-up are given in . For 7% (367/5567), we obtained no information on campaign status since the family was travelling at all visits. Among the remaining 5200 children, 3009 (58%) had received VAS and 2191 (42%) had not. In the 2008 campaign, we followed 5799 (93%) of 6210 children. For 10% (596/5799), we were unable to obtain information on campaign status. Among the remaining 5203 children, 3520 (68%) had received VAS and 1683 (32%) had not (). Median length of follow-up and IQR was 6.2 (4.4–6.4) months for supplemented, 4.2 (3.2–5.1) months for non-supplemented and 2.9 (1.8–3.4) months for children for whom we did not obtain information.
The distribution of background factors is shown in . Children for whom we had no information on campaign status had lower socioeconomic status, were more likely to be from the Muslim ethnic groups (Fula and Mandinga) and were younger. These children also tended to have higher mortality, crude mortality rate ratio (MRR)=2.17 (0.96; 4.94) (). In contrast, there were only few differences in background factors between supplemented and non-supplemented children. Non-supplemented children were more likely to have mothers with no formal education (p<0.001), to belong to the Muslim ethnic groups (p<0.001) and were less likely to have their vaccination card inspected (p<0.001). Furthermore, more supplemented children were enrolled in trials and as a result more supplemented children had received OPV as the most recent vaccine in 2007 (p=0.05). In 2008, the distribution of different vaccines did not differ between supplemented and non-supplemented children (p=0.23) ().
Distribution of background factors between children followed in the two campaigns*
The effect on mortality of receiving VAS in a campaign, overall and by sex, campaign and age group
Effect of VAS
There was no significant difference in mortality between supplemented and non-supplemented children, the crude MRR being 0.93 (0.55; 1.58). When the estimate was adjusted for sex, campaign, maternal education, ethnicity and inspected vaccination card, the difference in mortality between supplemented and non-supplemented children was 0.78 (0.46; 1.34) (). The effect did not differ significantly for children aged 6–11 months who received 100 000 IU vitamin A (adjusted MRR=1.14 (0.41; 3.19)) and children above 12 months who received 200 000 IU vitamin A and 250 mg mebendazole (adjusted MRR=0.69 (0.36; 1.29)) (p=0.41, test of interaction) (). The effect did not differ for boys and girls (p=0.72).
Mortality was much higher in the rainy season after the 2008 campaign (57 deaths/2208 person-years) than in the dry season after the 2007 campaign (15 deaths/2154 person-years); the adjusted MRR was 3.79 (2.13; 6.74) comparing 2008 versus 2007. The difference between supplemented and non-supplemented tended to differ between the two campaigns; the adjusted MRR was 0.38 (0.13; 1.10) after the 2007 campaign and 1.02 (0.53; 1.96) after the 2008 campaign (p=0.12, test of interaction). This difference may have been strongest for girls; the adjusted MRR was 0.16 (0.02; 1.59) after the 2007 campaign and 1.32 (0.44; 3.94) after the 2008 campaign (p=0.11, test of interaction), whereas there was no evidence of a difference in boys (p=0.50) (). Further adjusting for last vaccine at the time of the campaign did not change the conclusions.
The difference between supplemented and non-supplemented children varied with maternal education. Supplementation was associated with lower mortality in children of educated mothers (adjusted MRR=0.41 (0.21; 0.80)) but not in children of mothers with no schooling (adjusted MRR=1.78 (0.60; 5.31)) (p=0.02, test of interaction). The effect did not vary with the other socioeconomic indicators presented in (data not shown).
Effect of VAS by vaccination status
Vaccination cards were seen for 86% of the children in 2007 and 84% in 2008, with more cards seen for supplemented compared with non-supplemented children (2007: 90% vs 81%, p<0.001; 2008: 88% vs 75%, p<0.001, ); 9% (6/64) of the deaths in the study were excluded due to no information on vaccination status.
The difference in mortality between supplemented and non-supplemented children varied with vaccination status. In the 2814 children who had received MV as the most recent vaccine prior to the campaign, the adjusted MRR was 0.34 (0.14; 0.85). In the 3680 children who had received DTP as the most recent vaccine, the adjusted MRR was 1.29 (0.52; 3.22) (p=0.04 for different effect in MV and DTP recipients). The pattern was similar in boys and girls (). The small group of non-supplemented children with OPV as the most recent vaccine had lower mortality than all other groups ().
The effect on mortality of receiving VAS in a campaign, overall and by sex and vaccine status prior to the campaign*
Effect of supplementation in the 2007 campaign on survival after the 2008 campaign
Supplementation in the 2007 campaign was associated with improved survival after the 2008 campaign. Among 3520 children supplemented in 2008, 69% (2441) had been eligible for supplementation in 2007; 1435 (59%) had received VAS, 917 (38%) had not and 89 (4%) had no information on participation. After the 2008 campaign, children supplemented in both campaigns had lower mortality (8 deaths/623 person-years) than children who had not received VAS in 2007 but received VAS in 2008 (15 deaths/394 person-years), the adjusted MRR being 0.34 (0.14; 0.80). This beneficial effect of prior VAS was more pronounced for girls (MRR=0.14 (0.03; 0.68)) than for boys (MRR=0.59 (0.20; 1.77)) (test of interaction between sex and VAS, p=0.14).
Cause of death
We aimed to examine the effect of VAS on all-cause mortality. However, from May 2008 to January 2009 a cholera epidemic occurred.22
This epidemic could potentially explain the higher mortality after the 2008 campaign. Verbal autopsies were conducted for 66 of the 72 deaths, for the remaining six the family had moved prior to the interview. One death which occurred after receiving VAS in 2008 was classified as due to cholera. Further 10 deaths (15%) were due to diarrhoeal disease, one after the 2007 campaign (no VAS) and nine after the 2008 campaign (eight VAS and one no VAS). The peak of the epidemic occurred in September 200822
; five diarrhoeal deaths in 2008 occurred in August and September (all VAS) and four deaths (three VAS and one no VAS) occurred in the late epidemic in November and December where few cholera cases were detected. Campaign participation had no significant effect on the risk of death due to diarrhoea, the MRR being 1.87 (0.40; 8.71). The other causes of death were prolonged disease with failure to thrive and anaemia, 18 (27%, 14 VAS, three no VAS and one no information); respiratory infection, 17 (26%, nine VAS, six no VAS and two no information); malaria, 14 (21%, five VAS, seven no VAS and two no information); fever of unknown origin, three (5%, two VAS and one no VAS); cerebral palsy, two (3%, one VAS and one no VAS) and accident, one (2%, VAS). There were significantly more malaria deaths among the non-supplemented and the children with no information, the MRRs being 3.26 (1.03; 10.3) and 5.43 (1.05; 28.2), respectively, presumably reflecting that they were less likely to seek early treatment or to be absent in the rural areas where the incidence of severe and untreated malaria would be higher.