were at the highest risk of dying from measles, a 6-month dose was added to the ... and fatal cases were reported in infants as young as 4 months (Mgone et al.
Tropical Medicine and International Health
doi:10.1111/j.1365-3156.2008.02214.x
volume 14 no 2 pp 167–173 february 2009
Immune response to measles vaccine in 6 month old infants in Papua New Guinea Jonah Kurubi1, John Vince1, Paulus Ripa1, Nakapi Tefuarani1, Michaela Riddell2 and Trevor Duke1,3 1 School of Medicine, University of Papua New Guinea, Boroko, Port Moresby, Papua New Guinea 2 Victoria Infectious Disease Reference Laboratory, Melbourne, Vic., Australia 3 Centre for International Child Health, University of Melbourne, MCRI, Melbourne, Vic., Australia
Summary
objective To assess the efficacy of the current measles immunization schedule in Papua New Guinea, which is to give the first dose at 6 months of age and the second at 9 months. methods Humoral immune response study of 140 Papua New Guinean infants at 6 months of age, measuring measles IgG antibodies by enzyme immunoassay before and 85 days after the 6-month dose of measles vaccine. results After vaccination at 6 months, 35.7% of infants developed a level of measles antibodies consistent with protection (IgG >330 IU ⁄ ml); 17.7% had an antibody response (150–330 IU ⁄ ml) that is likely to afford some protection; 46.8% had no detectable antibody response (IgG 99% after the second dose. PNG has a different epidemiology of measles to industrialized countries, where measles affects children older than 1 year and the disease is generally mild. In PNG measles has a high attack rate and high mortality in infants (Mgone et al. 2000). Although the 6 month dose of measles vaccine in PNG was introduced to protect infants younger than 9 months, there has been uncertainty about the efficacy and effectiveness of such an approach. A small study in the late 1980s using standard titre measles vaccine in infants aged 6–7 months in the Southern Highlands of PNG 167
Tropical Medicine and International Health
volume 14 no 2 pp 167–173 february 2009
J. Kurubi et al. Immune response to measles vaccine PNG
showed that none of 12 had residual maternal antibodies and all 12 infants (100%, 95% CI 77–100%) achieved titers of measles specific IgG consistent with protection (Rogers et al. 1991). Data from other countries are variable. A study from Guinea in Africa found that 91% of 71 infants vaccinated against measles at 6 months had seroconverted 1 year later (Kourouma et al. 1992) and a study from Ghana showed 92% seroconversion in infants vaccinated at 7 months (Sakatoku et al. 1994) However other studies from USA (Johnson et al. 1994; Gans et al. 2001), Latin America (Anonymous 2005), India (Vidvashankar 2002), Haiti (Halsey et al. 1985) and South Africa (Dick et al. 1975) have found much lower rates of seroconversion in infants at 6–7 months. A large, recent study from Malawi showed serocoversion of 59–68% at 6 months, but that the 6 month dose had an important priming effect on the seroconversion rate when a second dose of measles vaccine was given at 9 months (Helfand et al. 2008). We aimed to determine the serological response of PNG infants at 6 months of age to measles vaccine, to provide evidence for a review of the current national schedule.
doubt whether they could return for the 9 month dose received their first measles vaccine and were advised to return in 3 months, or to visit the nearest functioning health facility for the second dose. At follow-up we recorded weight, clinical signs of malnutrition and clinical history of measles during the intervening period. A second blood sample was taken, after which the second dose of measles vaccine was given. Sample size calculation We calculated that if 70% of 140 6–7 month old infants seroconverted, the 95% CI for probability of seroconversion would be 62–77%. We considered even the lower limit of 62% would probably be sufficient to recommend a continuation of the 6 month dose, as well as a dose in later infancy. With coverage of measles vaccine in PNG being 60–70% we assumed many mothers would not return for second vaccination and follow-up serological testing, so we aimed to reach a sample of 200 enrolled infants to ensure that 140 infants had paired serological results. Sample collection and specimen handling
Materials and methods We assessed the humoral immune response to measles vaccine among infants presenting for their first measles vaccine at 6 months of age. The infants were recruited at Port Moresby General Hospital’s Well Baby Clinic between May and December 2006. Infants were eligible for inclusion if they were presenting for their 6 month vaccines and were younger than 7 months, lived close to the health facility and had a health book to document the vaccines administered and other health events. Infants born prematurely were only recruited if the corrected age was 6 months. Infants were not recruited if they had previously had an illness requiring hospital admission; if the parents were in doubt whether they would return at 9 months; and if parents declined to participate. The demographic data recorded during the first contact included the following from the infant: date of birth, history of clinical measles and other infections, weight and clinical signs of malnutrition. The following information was recorded from the mothers: weight, height, highest level of education, the family’s source of income and the type of housing the family was living in. Initially, parents were asked to bring their child for the second blood sample 1 month after the 6 month measles vaccine. As this involved an additional visit, the time interval was changed to 3 months, when the child was brought for the second measles vaccine. Infants of parents who declined to be enrolled in the study or who were in 168
Two blood samples were collected from each child; one prior to the 6-month measles vaccine and one either at around 1 month later or just prior to the 9 month vaccine. The measles vaccine used was the Edmonston-Zagreb strain. Mothers were requested to breastfeed their infants 2–3 min before 2 ml of venous blood were drawn from a vein in the hand or the foot. A sterile technique was followed to obtain all blood specimens. The blood specimens were taken to the Port Moresby Central Public Hospital Laboratory (CPHL) and centrifuged for 20 min. The serum was then pipetted into a sterile tube, which was then labelled with a unique identifying number. The specimens were stored at )20C. On the day of transportation, serum specimens were packed in three layers into the three carriers that had jelly ice frozen at )20C. An express freight courier transported the serum specimens from CPHL to Victoria Infectious Disease Reference Laboratory in Melbourne for immunoassays. Serum samples were evaluated for the presence of measles IgG antibodies by commercial indirect enzyme immunoassay (Enzygost, Dade Behring, Marburg, Germany) in accordance with the manufacturers’ instructions. We defined protective immunity as a measles IgG level of >330 mIU ⁄ ml [equivalent to >0.2 optical density (OD) value]; and an equivocal antibody response as 150– 330 mIU ⁄ ml (0.1–0.2 OD value). Specimens which tested equivocal initially (OD value 0.1–0.2) were retested and
ª 2009 Blackwell Publishing Ltd
Tropical Medicine and International Health
volume 14 no 2 pp 167–173 february 2009
J. Kurubi et al. Immune response to measles vaccine PNG
the second test result recorded, according to standard procedures in the reference laboratory. A negative response to vaccination was defined as IgG level 0 but 330 mIU ⁄ ml. An additional 25 (17.7%) infants had a measles IgG level between 150 and 330 mIU ⁄ ml; 66 (46.8%) had no detectable antibody response (IgG 150 IU ⁄ ml) after vaccination were the absence of pre-existing antibodies in serum at 6 months (odds ratio for seroconversion if maternal antibodies present: 0.41, 95% CI 0.19–0.87, P = 0.021), and a shorter time interval between vaccination and the second serum IgG estimation (odds ratio for seroconversion if sample taken within 60 days of measles vaccine being given: 4.1, 95% CI 1.04–15.00, P = 0.043) (Figure 2). Mothers of participating infants came from each of the 20 provinces in PNG. The probability of seroconversion varied markedly between the province of origin (from 14% to 80%, although the numbers of mothers from some provinces were small), but this was not significant (Kruskall–Wallis Chi-square P = 0.169). No other factors recorded, including infants anthropomorphic characteristics, age or maternal physical or
Table 1 Relationship between presence of any maternal antibodies and lack of antibody response
Antibodies present in infants serum prior to first vaccination No antibodies present prior to first vaccination Trace (OD >0,
