Vaccination strategies for measles control and elimination: time to strengthen local initiatives.

BACKGROUND: Through a combination of strong routine immunization (RI), strategic supplemental immunization activities (SIA) and robust surveillance, numerous countries have been able to approach or achieve measles elimination. The fragility of these achievements has been shown, however, by the resurgence of measles since 2016. We describe trends in routine measles vaccine coverage at national and district level, SIA performance and demographic changes in the three regions with the highest measles burden. FINDINGS: WHO-UNICEF estimates of immunization coverage show that global coverage of the first dose of measles vaccine has stabilized at 85% from 2015 to 19. In 2000, 17 countries in the WHO African and Eastern Mediterranean regions had measles vaccine coverage below 50%, and although all increased coverage by 2019, at a median of 60%, it remained far below levels needed for elimination. Geospatial estimates show many low coverage districts across Africa and much of the Eastern Mediterranean and southeast Asian regions. A large proportion of children unvaccinated for MCV live in conflict-affected areas with remote rural areas and some urban areas also at risk. Countries with low RI coverage use SIAs frequently, yet the ideal timing and target age range for SIAs vary within countries, and the impact of SIAs has often been mitigated by delays or disruptions. SIAs have not been sufficient to achieve or sustain measles elimination in the countries with weakest routine systems. Demographic changes also affect measles transmission, and their variation between and within countries should be incorporated into strategic planning. CONCLUSIONS: Rebuilding services after the COVID-19 pandemic provides a need and an opportunity to increase community engagement in planning and monitoring services. A broader suite of interventions is needed beyond SIAs. Improved methods for tracking coverage at the individual and community level are needed together with enhanced surveillance. Decision-making needs to be decentralized to develop locally-driven, sustainable strategies for measles control and elimination.

The effect of distance on observed mortality, childhood pneumonia and vaccine efficacy in rural Gambia.

We investigated whether straight-line distance from residential compounds to healthcare facilities influenced mortality, the incidence of pneumonia and vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for pneumonia was conducted on 6938 children living in the catchment areas of the two largest healthcare facilities. Deaths were monitored by three-monthly home visits. Children living >5 km from the two largest healthcare facilities had a 2·78 [95% confidence interval (CI) 1·74-4·43] times higher risk of all-cause mortality compared to children living within 2 km of these facilities. The observed rate of clinical and radiological pneumonia was lower in children living >5 km from these facilities compared to those living within 2 km [rate ratios 0·65 (95% CI 0·57-0·73) and 0·74 (95% CI 0·55-0·98), respectively]. There was no association between distance and estimated pneumococcal vaccine efficacy. Geographical access to healthcare services is an important determinant of survival and pneumonia in children in rural Gambia.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Using models to shape measles control and elimination strategies in low- and middle-income countries: A review of recent applications.

After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct regular situation analyses and to leverage models to adapt interventions to local needs. Here, we review applications of models to develop locally tailored interventions to support control and elimination efforts. In general, statistical and semi-mechanistic transmission models can be used to synthesize information from vaccination coverage, measles incidence, demographic, and/or serological data, offering a means to estimate the spatial and age-specific distribution of measles susceptibility. These estimates complete the picture provided by vaccination coverage alone, by accounting for natural immunity. Dynamic transmission models can then be used to evaluate the relative impact of candidate interventions for measles control and elimination and the expected future epidemiology. In most countries, models predict substantial numbers of susceptible individuals outside the age range of routine vaccination, which affects outbreak risk and necessitates additional intervention to achieve elimination. More effective use of models to inform both vaccination program planning and evaluation requires the development of training to enhance broader understanding of models and where feasible, building capacity for modelling in-country, pipelines for rapid evaluation of model predictions using surveillance data, and clear protocols for incorporating model results into decision-making.

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. FINDINGS: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. INTERPRETATION: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

The epidemiology of measles: thirty years of vaccination.

Measles is a highly infectious disease which has a major impact on child survival, particularly in developing countries. The importance of understanding the epidemiology of this disease is underlined by its ability to change rapidly in the face of increasing immunization coverage. Much is still to be learned about measles epidemiology and the best strategies for administering measles vaccines, as well as about the biological mechanisms of action of measles vaccines. However, it is clear that tremendous progress can be made in preventing death and disease from measles with existing knowledge about the disease, and by using the presently available vaccines and applying well tried methods of treating cases. Research in the coming decade may provide improved strategies and more effective vaccines for use in immunization programmes.

Age- and sex-specific HIV-1 prevalence in the urban community setting of Addis Ababa, Ethiopia.

OBJECTIVE: To estimate the age and sex-specific prevalence of HIV infection in the population of Addis Ababa, Ethiopia. DESIGN: Two-stage cluster sampling of the population aged 0-49 years of Addis Ababa, using kebeles (urban dwelling associations) as clusters. METHODS: The sera used for this study were collected in an earlier study (1994) on the rate of acquisition of antibodies against measles, rubella, and hepatitis B. After separate approvals were obtained from the institutional ethics committees, sera were tested by enzyme-linked immunosorbent assay confirmed by Western blot. Age- and sex-specific HIV prevalence rates were estimated. The prevalence of HIV in men and women over 15 years of age was compared by calculating age-standardized HIV prevalence, using the age distribution of the census population as the standard. A time-dependent catalytic model was used to obtain crude estimates of HIV incidence from age-prevalence data. RESULTS: A total of 3853 sera were available for analysis. The prevalence of HIV in adults was 6.0% [95% confidence interval (CI), 4.5-7.4%] for men and 6.9% (95% CI, 5.3-8.5%) for women, with peak prevalence in the 25-29 year age group of 16.3 and 11.8%, respectively. After standardization for age using the direct method, the HIV prevalence ratio comparing adult men with women was 0.97:1 (95% CI, 0.70:1 - 1.35:1). Three children aged less than 5 years were HIV-positive. The prevalence of HIV among adults ranged from 0-21.3% in different clusters, indicating the heterogeneity of the spread of HIV in the city. HIV prevalence estimates among the antenatal clinic patients of Addis Ababa in 1996 far exceeded the estimates obtained during the community survey, particularly in the youngest age group (15-24 years). Estimates of HIV incidence (per susceptible person per annum) for the age group 16-22 years ranged from 1.3-2.25% for men and from 2.1-2.4% for women. CONCLUSION: By 1994, a substantial proportion of the adult population of Addis Ababa was infected with HIV. Promotion of behavioural changes and the control of sexually transmitted diseases should be strongly supported to limit the spread of the HIV epidemic in Ethiopia.

Successes and failures in vaccine delivery: evaluation of the immunization delivery system in Puerto Rico.

The objective of this study was to evaluate immunization delivery and determine reasons for low coverage among preschool-age public clinic attendees in Puerto Rico. In 25 randomly selected clinics, coverage and missed immunization opportunities were assessed in 273 children aged 2 to 59 months, exist interviews were conducted with parents, and providers were interviewed. Two neighborhoods close to the clinics were surveyed to determine parental knowledge about immunizations, and the vaccination status of children in these neighborhoods was assessed. Two hundred seventy-three clinic attendees were interviewed. Among 229 (84%) with vaccination cards, only 126 (55%) had received all indicated vaccines by completion of the clinic visit. Forty-five percent of children with cards in the household survey were not up-to-date. Of 171 (75%) clinic attendees eligible for vaccination at the visit, 118 (69%) missed one or more immunizations at the visit. In addition, half of all children had previously missed one or more immunizations when they had received another vaccine. Missed opportunities occurred because of nonavailability of vaccines, lack of integration of services, provider misconceptions about contraindications, and failure to administer vaccines simultaneously. Other problems included barriers to immunization services and lack of information and education activities. It is concluded that deficiencies in immunization delivery substantially delay immunization and reduce coverage.

Modelling the incidence of congenital rubella syndrome in developing countries.

BACKGROUND: As of 1997, less than one-third of developing countries included rubella vaccine in their national immunization programme. In countries that have achieved high coverage of measles vaccine, an ideal opportunity exists to include control of rubella and congenital rubella syndrome (CRS) in enhanced measles control activities. Data on the burden of congenital rubella syndrome are important to guide rubella vaccination policies. METHODS: We reviewed the literature to identify studies of rubella antibody prevalence in developing countries that were conducted on populations with no major selection bias, prior to wide-scale rubella vaccination in the country. We used a simple catalytic model to describe the age-specific prevalence of susceptibility to rubella virus infection in given populations. Estimates of the incidence of infection among pregnant women were calculated using expressions for the average prevalence of susceptibility to infection and the incidence of infection during gestation. To estimate the number of cases of CRS, we assumed an overall risk of 65% after infection in the first 16 weeks of pregnancy and zero risk thereafter. These estimates were derived for each country for which data were available, then for each World Health Organization region, excluding Europe. RESULTS: The estimated mean incidence of CRS per 100,000 live births was lowest in the Eastern Mediterranean region (77.4, range 0-212) and highest in the Americas (175, range 0-598). The mean of the estimates of the total number of cases of CRS in developing countries in 1996 was approximately 110,000. The range was, however, very wide, from as few as 14,000 to as many as 308,000 cases. CONCLUSIONS: Congenital rubella syndrome is an under-recognized public health problem in many developing countries. There is an urgent need for collection of appropriate data to estimate the cost-effectiveness of a potential global rubella control programme.

PIP: Inclusion of rubella vaccine in the national immunization program was found to be implemented in less than one-third of the developing countries in a review conducted by WHO. This paper examines the incidence of congenital rubella syndrome (CRS) cases in developing countries using published rubella infection prevalence. Documented literature of previous studies and medical data on women attending antenatal clinics were gathered and rubella antibody prevalence was identified before the wide-scale rubella vaccination. A catalytic model was used in describing age-specific prevalence of rubella virus infection in given populations, while expressions for the average prevalence of susceptibility to infection and incidence of infection during gestation was used to estimate the incidence of infection among pregnant women. Using the data gathered from each country and WHO regions, an overall risk of 65% after infection in the first 16 weeks and zero risk of defect later in pregnancy was assumed to estimate the incidence of CRS. Results revealed that the estimated mean incidence of CRS per 100,000 live births was significantly lower in the eastern Mediterranean region (77.4, range 0-212) and higher in the Americas (175, range 0-598). On the other hand, the 1996 CRS mean estimate for developing countries was approximately 110,000, ranging from 14,000 to 308,000 cases. This study concludes with the stated need for an improved CRS program in developing countries as well as adequate data collection necessary for cost-effectiveness evaluation of potential global rubella control programs.

Determinants of vaccination in an urban population in Conakry, Guinea.

A community survey was conducted in 1989 in Conakry, Guinea to determine reasons for low vaccination coverage. Some 377 children aged 12-23 months and their guardians were studied, of whom 204 (54%) had vaccination records. According to their records 19% of children were fully and correctly vaccinated. Thirty-nine incompletely vaccinated children (19% of those with records) had sufficient documented contacts with health services to be fully vaccinated, but at least one immunization opportunity was missed. Multivariate analyses were conducted to identify factors associated with receipt of first dose diphtheria/pertussis/tetanus/oral polio vaccine (DPT/OPV) and with completion of the DPT/OPV series. Factors determining initiation of the series included maternal education (assessed by ability to speak French), household possession of a television, maternal age less than 35 years, child's birth in hospital, and, for non-French speakers, the mother considering vaccination to be affordable. Factors determining completion of the DPT/OPV series, among children who began vaccination, included maternal education, employment, and past positive experience with vaccination services (short waiting times, not having been turned away from vaccination, and not knowing a child with a post-vaccine 'abscess'). Vaccination coverage can be substantially increased in Conakry by improving health services to avoid missed opportunities, following the vaccination schedule correctly, reducing waiting times and avoiding abscesses.

Evaluation of factors influencing vaccine uptake in Mozambique.

A pulse immunization project was started in Mozambique to compensate for the decrease in routine immunization caused by destabilization. A study was conducted to evaluate the project and identify determinants of vaccination in urban and rural areas of Mozambique. Vaccine coverage based on a documented record, the 'Road to Health' card, was 53% in urban and 60% in rural project areas, and 12% higher if a verbal history of vaccination was considered. A further 17% of children would have received effective vaccination if the correct schedule had been followed for all vaccines given and all preventive health services contacts had been used for vaccination. Factors relating to the individual mother and child and factors relating to the clusters were investigated for their association with vaccine uptake. Those which showed a strong negative association included vaccination on offer at the nearest vaccination post for only a small number of days per week; cancellation of an outreach session; knowing a child with a post-vaccination abscess; child born at home; at least five children in the family; mother's inability to speak Portuguese and her inability to name at least two target diseases. Improving the supervision of health services and immunizing at least three days per week at permanent immunization clinic sites may be the most important measures to improve coverage further.

Child and maternal mortality during a period of conflict in Beira City, Mozambique.

BACKGROUND: Child mortality rates have been declining in most developing countries. We studied child and maternal mortality risk factors for child mortality in Beira city in July 1993, after a decade of conflict in Mozambique. METHODS: A community-based cluster sample survey of 4609 women of childbearing age was conducted. Indirect techniques were used to estimate child mortality ('children ever born' method and Preceding Birth Techniques (PBT) and maternal mortality (sisterhood method). Deaths among the most recent born child, born since July 1990, were classified as cases (n = 106), and two controls, matched by age and cluster, were selected per case. RESULTS: Indirect estimates of the probability of dying from birth to age 5 (deaths before age 5 years, (5)q(0) per 1000) decreased from 246 in 1977/8 to 212 in 1988/9. The PBT estimate of 1990/91 was 154 (95 percent confidence interval [CI]: 124-184), but recent deaths may have been underreported. Lack of beds in the household (odds ratio [OR] = 2.0, 95 percent CI: 1.1-3.8), absence of the father (OR = 2.4, 95 percent CI : 1.2-4.8), low paternal educational level (OR = 2.1, 95 percent CI: 0.8-5.4), young maternal age (OR = 2.0, 95 percent CI: 1.0-3.7), self-reported maternal illness (OR = 2.4, 95 percent CI : 1.2-4.9), and home delivery of the child (OR = 2.3, 95 percent CI : 1.2-4.5) were associated with increased mortality, but the sensitivity of risk factors was low. Estimated maternal mortality was 410/100 000 live births with a reference date of 1982. CONCLUSIONS: Child mortality decreased slowly over the 1980s in Beira despite poor living conditions caused by the indirect effects of the war. Coverage of health services increased over this period. The appropriateness of a risk approach to maternal-child-health care needs further evaluation.

PIP: In July 1993, public health specialists conducted a cluster sample survey of 4609 women aged 15-49 living in 3190 houses in Beira city to determine child and maternal mortality after 10 years of internal conflict in Mozambique and a nested case control study of risk factors for child mortality. The indirect estimate techniques were child ever born and preceding birth techniques for child mortality and the sisterhood method for maternal mortality. The case control study compared 106 deaths among the most recent born child born since July 1990 with two age- and cluster-matched controls. The proportion of dead sisters who died of pregnancy-related causes was only 10.3% compared to 25-33% in developing countries. In 1982, the estimated maternal mortality ratio was 410/100,000 live births. The lifetime risk of maternal mortality was 263/1000. The preceding birth technique obtained a much lower child mortality estimate than the child ever born technique (154 vs. 212/1000). The child ever born technique analyzed data from 1977-1978 to 1988-1989 and found that the probability of dying from birth to age 5 fell 14% (246-212). During this period, coverage of health services improved. Even though the preceding birth technique is usually more reliable for recent estimates, underreporting of recent child deaths likely contributed to the lower child mortality estimate. Risk factors for child mortality included no beds in the household (odds ratio [OR] = 2.02), absence of the father (OR = 2.43), low paternal educational level (OR = 2.08), young maternal age (OR = 1.96), self-reported maternal illness since birth of child (OR = 2.43), and home delivery (OR = 2.31). Yet the sensitivity of these risk factors was rather low (15-57%). These findings show that child mortality fell slowly during the 1980s despite the poor living conditions brought about by the indirect effects of the civil war. They point to the need to further evaluate the appropriateness of a risk approach to maternal and child health care needs.

Measles control in Kinshasa, Zaire improved with high coverage and use of medium titre Edmonston Zagreb vaccine at age 6 months.

BACKGROUND: To improve measles control in Kinshasa, Zaire, a project to increase vaccine coverage was begun in 1988, and in 1989, the city vaccination programme changed measles vaccination policy from Schwartz vaccine at age 9 months to medium titre Edmonston Zagreb (EZ) vaccine at age 6 months. We report the impact of the programme on measles incidence and mortality. METHODS: Data on vaccine coverage were obtained from cluster sample surveys conducted every 1-2 years and from routine reports of vaccine doses administered. Data on measles incidence and mortality were obtained from sentinel surveillance sites. The serological response to EZ measles vaccine was evaluated at a health centre in 1989 and in a community survey in 1990. RESULTS: Measles vaccine coverage estimated in cluster surveys increased from 50% of the 1984 birth cohort to 89% of the 1989 birth cohort, accepting either a home-based record or a verbal history of vaccination. Reported measles incidence per 10,000 [corrected] population decreased by over 90%, from 37.5 in 1980 (early vaccination years) to 1.6 in 1991. There was a relative decrease in the proportion of cases aged < 9 months (32% of cases in 1986-1987 and 23% of cases in 1990-1991) and an increase in the proportion aged > 23 months (29% of cases in 1986-1987 and 43% in 1990-1991). According to ELISA assays, 74-76% of children seroresponded to EZ vaccine administered at age 6-7 months under routine programme conditions. CONCLUSIONS: Measles can be controlled in urban areas, although it is difficult to determine how great a contribution vaccination at age 6 months makes over and above the achievement of high coverage.

Vaccines for neonatal viral infections: hepatitis B vaccine.

In many parts of the world, intervention in the neonatal period is required for prevention of hepatitis B virus infection and its consequences.

Detection of measles specific IgG in oral fluid using an FITC/anti-FITC IgG capture enzyme linked immunosorbent assay (GACELISA).

An IgG antibody capture enzyme linked immunosorbent assay (GACELISA) for the detection of measles specific IgG in oral fluid was developed using an FITC/anti-FITC amplification system. The GACELISA was evaluated by testing paired oral fluid and serum samples from 787 subjects in an epidemiological study of measles in rural Ethiopia. Oral fluids were tested by GACELISA and corresponding serum samples by a sensitive indirect ELISA for measles IgG (Behring Enzygnost). By comparison with the serum measles IgG assay, the oral fluid GACELISA had a sensitivity of 97.4% (95% confidence intervals: 95.9, 98.2) and a specificity of 90.0% (81.9, 94.3), with no significant differences observed by age group. Total IgG concentrations were measured on a subset of 160 oral fluids by an in-house ELISA. This showed that false negative GACELISA results tended to occur in samples with low concentrations of total IgG, although the trend was not statistically significant. It is concluded that the overall performance of the GACELISA was satisfactory, showing close agreement to the serum ELISA, and has potential to serve as an easily transferable tool for large scale epidemiological studies as required for the World Health Organisation's programme for the global control of measles.

Maternal rubella-specific antibody prevalence in Ethiopian infants.

In countries with a high transmission rate of rubella the optimal age for universal rubella vaccination of infants is critically dependent upon the rate of loss of maternal antibodies. Few studies have investigated the decay characteristics of such antibodies. Mother:infant pairs were recruited at the Ethio-Swedish Children's Hospital, Addis Ababa, in 1994/95. Rubella antibody levels, determined by radial haemolysis, were available for analysis from 1542 infants aged 0-12 months, with 942 repeat measures, and from 846 mothers. Decay in seropositivity was well described by a delayed exponential function. The proportion seropositive at age 6, 9, or 12 months was 6-13%, 1-4%, or 0-1%, respectively, dependent upon assay cutoff level. Only infant age and mother's antibody level were important predictors of seropositivity. Results suggest that the success of vaccination at age 9 months or above would be little affected by residual maternal antibodies.

An evaluation of oral-fluid collection devices for the determination of rubella antibody status in a rural Ethiopian community.

We compared 3 different oral-fluid collection devices to assess their suitability for use in community studies of rubella antibody. Of 58 individuals enrolled from 13 households from a southern Ethiopian village, 38 provided a blood sample and oral fluids by the 3 devices: 2 proprietary, Omni-SAL and OraSure, and a third a polystyrene sponge swab (Sponge). The Sponge swab, used like a toothbrush, was most acceptable to survey staff and to participants of all ages, although it proved ill-adapted for fluid extraction. The other devices more often caused participant discomfort or anxiety, particularly in the young. Statistical comparison of rubella-specific immunoglobulin (Ig) G in oral fluid, measured by antibody-capture radioimmunoassay, and in serum, by indirect enzyme-linked immunosorbent assay, showed no clear differences between the devices in oral-fluid performance. Specificity range was 75-100% and sensitivity 73-85%, relative to serum. Specific-antibody levels declined with increasing age, with concomitant decreases in sensitivity, as previously documented. The relationship between specific IgG and total IgG in oral fluid differed by device. Specific IgG levels were highly correlated between paired samples using the Sponge device. We consider the Sponge device to be the most suitable for community survey work, although the extraction method requires improvement. Further work is needed to improve the sensitivity of antibody status determination in adults.

Prevalence of measles antibody among children under 15 years of age in Santa Cruz, Bolivia: implications for vaccination strategies.

We conducted a community-based survey in Santa Cruz city, Bolivia, to determine the age-specific prevalence of measles antibodies, determine factors associated with absence of detectable measles antibodies, and to compare results of salivary and serum measles immunoglobulin G (IgG) antibody assays. Serum samples from 1654 children were assayed for measles IgG antibody using the haemagglutination inhibition (HI) assay, and salivary samples were also obtained from 187 children and tested for measles IgG antibody using an antibody capture radioimmunoassay. Reported measles vaccine coverage in children aged 12-35 months was 77% (95% confidence interval [CI], 72-81%). Eighty-seven percent (95% CI 85-89%) had detectable HI antibody, but a high proportion had antibody levels below 200 miu (30-40% of 2-14 years old children). Measles seronegativity was associated with not being vaccinated against measles, a negative history of measles disease, living in the inner city, being a lifetime resident of Santa Cruz, and young age. Of 212 children without detectable measles antibody, 58% had a positive history of vaccination or measles disease, so that historical information was not sufficiently reliable to identify susceptibles. The salivary measles antibody assay was not sufficiently sensitive to be used for population screening; only 54% of 171 salivary samples from children who had detectable serum HI antibody were positive. A mass measles vaccination campaign of all children under 15 years of age is planned in Bolivia in 1994. Although only 7% of school-age children in Santa Cruz were seronegative, the effectiveness of a mass campaign in this age group depends in part on the response to revaccination of children with low, but detectable, antibody levels.

Response to measles revaccination among Bolivian school-aged children.

The response to measles revaccination was evaluated in 1994 among 202 Bolivian school-aged children whose antibody levels were below 200 miu (milli-international units) by haemagglutination inhibition (HI) in a large-scale serosurvey conducted in Santa Cruz one year earlier. Of the 202 revaccinated children, 164 (82%) had seroconverted between the 1993 serosurvey and the pre-revaccination blood sample. A measles outbreak occurred in Santa Cruz 6 months before the revaccination. Among the seroconvertors, only 6% gave a history of measles, and 15% a history of contact with a case of measles. All 20 children with undetectable HI antibody pre-revaccination, and all 6 children with levels below 100 miu, seroconverted after revaccination. The geometric mean titres by HI at 4 weeks after revaccination were 2018 miu (95% confidence limits [95% CL] 1143, 3564) and 398 miu (95% CL 254, 625) in the 2 groups, respectively. Six of 9 children with pre-revaccination antibody titres of 100-199 miu also seroconverted. No child demonstrated a measles-specific immunoglobulin M response. Among the 29 children who seroconverted and were followed up at one year after revaccination, 15(52%) showed a fourfold or greater decline in antibody levels, which in 8 fell to levels below 200 miu. This study confirmed the observation that revaccination is successful in producing an antibody response in children with low or undetectable pre-revaccination titres, but it also confirmed that vaccine-induced immunity wanes rapidly.