Measles control in Sub-Saharan Africa: South Africa as a case study

Background

Due to intensified measles immunization efforts, measles mortality has decreased substantially worldwide, particularly in Sub-Saharan Africa (SSA). The World Health Organization (WHO) estimated a 92% decrease in measles-related deaths in the WHO AFRO region for the period 2000–2008. Recently, the AFRO region established a measles pre-elimination goal and experts have suggested engaging in a measles eradication campaign at the global level. However, recent large-scale outbreaks in many Sub-Saharan African countries present a challenge to measles control efforts. This paper examines measles immunization and the impact of measles supplemental immunization activities (SIAs) on routine immunization coverage in South Africa (SA).

Methods

We reported on immunization coverage trends in SA for the period 2001–2010 at the province and district levels. The data included routine immunization for 1st and 2nd doses of measles vaccine (MCV1, MCV2), SIAs, 1st dose of Bacille Calmette-Guérin vaccine, 1st and 3rd doses of oral polio vaccine (OPV1, OPV3), 3rd dose of Diphtheria–Tetanus–Pertussis–Haemophilus-influenzae-B vaccine (DTP-Hib3), and the number of under-one-year-olds having completed a primary course of immunization (Imm1). A regression model looked at the SIA impact on routine coverage.

Results

Over the past decade, MCV1 and MCV2 coverage have increased nationally from 68% and 57% in 2001 to 95% and 83% in 2010, respectively. SIA coverage has remained at high levels, around 90%, over the same period. Substantial heterogeneity in MCV1 and MCV2 coverage is present across SA districts, with differences in coverage of 56% (MCV1) and 51% (MCV2) in 2010. In any given year, occurrence of SIAs was associated with a decrease in routine immunization coverage of MCV1, MCV2, OPV1, OPV3, DTP-Hib3, and Imm1, at the district level.

Conclusions

The heterogeneity in measles vaccination coverage across SA districts challenges the goal of measles elimination in SA and SSA. The reduction in routine immunization coverage associated with the occurrence of SIAs raises the legitimate concern that SIAs may negatively impact health systems’ functioning.     

Following in the footsteps of smallpox: can we achieve the global eradication of measles?

Background  

Although an effective measles vaccine has been available for almost 40 years, in 2000 there were about 30 million measles infections worldwide and 777,000 measles-related deaths. The history of smallpox suggests that achieving measles eradication depends on several factors; the biological characteristics of the organism; vaccine technology; surveillance and laboratory identification; effective delivery of vaccination programmes and international commitment to eradication.     

The average cost of measles cases and adverse events following vaccination in industrialised countries

Background  

Even though the annual incidence rate of measles has dramatically decreased in industrialised countries since the implementation of universal immunisation programmes, cases continue to occur in countries where endemic measles transmission has been interrupted and in countries where adequate levels of immunisation coverage have not been maintained. The objective of this study is to develop a model to estimate the average cost per measles case and per adverse event following measles immunisation using the Netherlands (NL), the United Kingdom (UK) and Canada as examples.     

Measles in 2010. Knowledge and vaccination status of medical students

Objectives

In 2002, the WHO Regional Office for Europe developed a strategic plan for measles in the WHO European Region. WHO recommends that at least 95% of children receive two doses of measles vaccine. This plan targeted the elimination of measles for the year 2010 and is supported by the Federal Republic of Germany.

Methods

Questionnaire survey, serological tests and check-up of the certificates of vaccination were offered to second year medical students of Goethe University Frankfurt/Main, Germany.

Results

Only 62.3% of medical students had received two doses of measles vaccine. Serological data showed that 23.1% were not immune against measles. Important gaps of knowledge were identified in the knowledge test of the survey; less than one third of the students (n=95/324) were able to answer more than 50% of the questions correctly.

Discussion

The suboptimum measles-vaccination coverage shows that the goal of eliminating measles will not be met across Europe by the target year 2010. Both occupational and public health measures need to make sure that vaccination programs should achieve a minimum of 95% coverage with two doses. In addition, the obligation to notify the authorities even of suspected cases serve the same purpose and measures to improve the knowledge of medical students are required. Consequent surveillance systems are necessary to investigate chains of measles infections. Healthcare workers play a decisive role in this issue.     

Assessment of measles immunity among infants in Maputo City,Mozambique

Background  

The optimum age for measles vaccination varies from country to country and thus a standardized vaccination schedule is controversial. While the increase in measles vaccination coverage has produced significant changes in the epidemiology of infection, vaccination schedules have not been adjusted. Instead, measures to cut wild-type virus transmission through mass vaccination campaigns have been instituted. This study estimates the presence of measles antibodies among six- and nine-month-old children and assesses the current vaccination seroconversion by using a non invasive method in Maputo City, Mozambique.     

Knowledge synthesis of benefits and adverse effects of measles vaccination: the Lasbela balance sheet

Background

In preparation for a cluster-randomized controlled trial of a community intervention to increase the demand for measles vaccination in Lasbela district of Pakistan, a balance sheet summarized published evidence on benefits and possible adverse effects of measles vaccination.

Methods

The balance sheet listed: 1) major health conditions associated with measles; 2) the risk among the unvaccinated who contract measles; 3) the risk among the vaccinated; 4) the risk difference between vaccinated and unvaccinated; and 5) the likely net gain from vaccination for each condition.

Results

Two models revealed very different projections of net gain from measles vaccine. A Lasbela-specific combination of low period prevalence of measles among the unvaccinated, medium vaccination coverage and low vaccine efficacy rate, as revealed by the baseline survey, resulted in less-than-expected gains attributable to vaccination. Modelled on estimates where the vaccine had greater efficacy, the gains from vaccination would be more substantial.

Conclusion

Specific local conditions probably explain the low rates among the unvaccinated while the high vaccine failure rate is likely due to weaknesses in the vaccination delivery system. Community perception of these realities may have had some role in household decisions about whether to vaccinate, although the major discouraging factor was inadequate access. The balance sheet may be useful as a communication tool in other circumstances, applied to up-to-date local evidence.

     

Distinguishing vaccine efficacy and effectiveness

Background

Mathematical models of disease transmission and vaccination typically assume that protective vaccine efficacy (i.e. the relative reduction in the transmission rate among vaccinated individuals) is equivalent to direct effectiveness of vaccine. This assumption has not been evaluated.

Methods

We used dynamic epidemiological models of influenza and measles vaccines to evaluate the common measures of vaccine effectiveness in terms of both the protection of individuals and disease control within populations. We determined how vaccine-mediated reductions in attack rates translate into vaccine efficacy as well as into the common population measures of ‘direct’, ‘indirect’, ‘total’, and ‘overall’ effects of vaccination with examples of compartmental models of influenza and measles vaccination.

Results

We found that the typical parameterization of vaccine efficacy using direct effectiveness of vaccine can lead to the underestimation of the impact of vaccine. Such underestimation occurs when the vaccine is assumed to offer partial protection to every vaccinated person, and becomes worse when the level of vaccine coverage is low. Nevertheless, estimates of ‘total’, ‘indirect’ and ‘overall’ effectiveness increase with vaccination coverage in the population. Furthermore, we show how the measures of vaccine efficacy and vaccine effectiveness can be correctly calculated.

Conclusions

Typical parameterization of vaccine efficacy in mathematical models may underestimate the actual protective effect of the vaccine, resulting in discordance between the actual effects of vaccination at the population level and predictions made by models. This work shows how models can be correctly parameterized from clinical trial data.     

Identifying high-risk areas for sporadic measles outbreaks: lessons from South Africa

Objective

To develop a model for identifying areas at high risk for sporadic measles outbreaks based on an analysis of factors associated with a national outbreak in South Africa between 2009 and 2011.

Methods

Data on cases occurring before and during the national outbreak were obtained from the South African measles surveillance programme, and data on measles immunization and population size, from the District Health Information System. A Bayesian hierarchical Poisson model was used to investigate the association between the risk of measles in infants in a district and first-dose vaccination coverage, population density, background prevalence of human immunodeficiency virus (HIV) infection and expected failure of seroconversion. Model projections were used to identify emerging high-risk areas in 2012.

Findings

A clear spatial pattern of high-risk areas was noted, with many interconnected (i.e. neighbouring) areas. An increased risk of measles outbreak was significantly associated with both the preceding build-up of a susceptible population and population density. The risk was also elevated when more than 20% of infants in a populous area had missed a first vaccine dose. The model was able to identify areas at high risk of experiencing a measles outbreak in 2012 and where additional preventive measures could be undertaken.

Conclusion

The South African measles outbreak was associated with the build-up of a susceptible population (owing to poor vaccine coverage), high prevalence of HIV infection and high population density. The predictive model developed could be applied to other settings susceptible to sporadic outbreaks of measles and other vaccine-preventable diseases.     

The potential for measles transmission in England

Background  

Since the schools vaccination campaign in 1994, measles has been eliminated from England. Maintaining elimination requires low susceptibility levels to keep the effective reproduction number R below 1. Since 1995, however, MMR coverage in two year old children has decreased by more than 10%.     

Timeliness and completeness of measles vaccination among children in rural areas of Guangxi,China: A stratified three-stage cluster survey

Background

Large-scale outbreaks of measles occurred in 2013 and 2014 in rural Guangxi, a region in Southwest China with high coverage for measles-containing vaccine (MCV). This study aimed to estimate the timely vaccination coverage, the timely-and-complete vaccination coverage, and the median delay period for MCV among children aged 18–54 months in rural Guangxi.

Description of a large measles epidemic in Democratic Republic of Congo, 2010–2013

Background

Although measles mortality has declined dramatically in Sub-Saharan Africa, measles remains a major public health problem in countries like the Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic that occurred in the Democratic Republic of Congo between 2010 and 2013 using data from the national surveillance system as well as vaccine coverage surveys to provide a snapshot of the epidemiology of measles in DRC.

Methods

Standardized national surveillance data were used to describe measles cases from 2010 to 2013. Attack rates and case fatality ratios were calculated and the temporal and spatial evolution of the epidemic described. Data on laboratory confirmation and vaccination coverage surveys as a part of routine program monitoring are also presented.

Findings

Between week 1 of 2010 and week 45 of 2013, a total of 294,455 cases and 5,045 deaths were reported. The cumulative attack rate (AR) was 0.4%. The Case Fatality Ratio (CFR) was 1.7% among cases reported in health structures through national surveillance. A total of 186,178 cases (63%) were under 5 years old, representing an estimated AR of 1.4% in this age group. Following the first mass vaccination campaigns, weekly reported cases decreased by 21.5%. Results of post-vaccination campaign coverage surveys indicated sub-optimal (under 95%) vaccination coverage among children surveyed.

Conclusions

The data reported here highlight the need to seek additional means to reinforce routine immunization as well as ensure the timely implementation of Supplementary Immunization Activities to prevent large and repeated measles epidemics in DRC. Although reactive campaigns were conducted in response to the epidemic, strategies to ensure that children are vaccinated in the routine system remains the foundation of measles control.

     

Rubella control in Papua New Guinea: Age-specific immunity informs strategies for introduction of rubella vaccine

Aim

To determine the age specific immunity profile for rubella from three discrete study populations in Papua New Guinea, and to inform policy regarding the possible introduction of rubella vaccine.

Background

In 2005, the Western Pacific Region (WPR), of which Papua New Guinea (PNG) is a member state, declared the goal of regional measles elimination by 2012. Recently, WPR has incorporated an accelerated control goal for rubella and congenital rubella syndrome (CRS). PNG currently recommends two doses of measles vaccination at 6 and 9 months of age with a monovalent measles vaccine, which does not include rubella vaccine.

Methods

Convenience samples were collected from 1326 eligible participants in PNG and assessed for rubella immunity using the Dade Behring Enzygnost™ Anti-Rubella-Virus enzyme immunoassay. Nearly 34% were collected during an age stratified prospective survey of febrile patients in Madang Province; approximately 49% were collected from women of childbearing age in East Sepik and Milne Bay Provinces. Remaining specimens were collected from 6 to 7-month-old infants in Port Moresby prior to receiving the first dose of measles vaccine.

Findings

Of all samples tested, 65.2% (95% confidence interval (CI): 62.6–67.8) had evidence of immunity to rubella infection. Of women more than 15 years of age, 91.6% (95% CI: 89.4–93.5) were immune. The force of infection was highest between 5 and 19 years of age.

Conclusions

Although a population-based sample was not used, our multi-centre study of the population immunity profile suggests that immunity against rubella is extremely high in most women of childbearing age, but women who become pregnant at an early age may be at high risk of rubella infection during pregnancy and potential delivery of an infant with CRS. Routine measles vaccine coverage, a proxy for measles-rubella vaccine coverage, as measured in recently published studies, is well below the WHO target of 80% coverage. Introduction of a child or infant dose of rubella vaccine requires caution and further study.     

Mass Measles Rubella Immunization Campaign: Bhutan Experience

Background:

Bhutan has attained universal child immunization since 1991. Since then, immunization coverage is maintained at high level through routine immunization, periodic National Immunization Days, and mop up campaigns. Despite high immunization coverage, every year, significant numbers of clinically suspected measles cases were reported.

Objective:

To assess the cause of continuing high “suspected measles cases” and take appropriate public health measures.

Materials and Methods:

Febrile rash outbreaks occurred in several districts in 2003. These episodes were investigated. Simultaneously, a retrospective data search revealed evidence of congenital rubella syndrome (CRS) in the country.

Results:

Thirty five percent of the tested samples were positive for rubella but none for measles. There were evidences of the presence of CRS. This was discussed in the annual health conference 2004, amongst health policy makers and district heads who recommended that a possibility of inclusion of rubella as an antigen be looked into. A nationwide measles and rubella immunization campaign was conducted in 2006 followed by introduction of rubella vaccine in the immunization schedule.

Conclusion:

Febrile rash can be caused by a host of viral infections. Following universal measles immunization, it is pertinent that febrile rash be looked in the light of rubella infections. Following the introduction of rubella vaccination in the national immunization schedule, there has been significant reduction of febrile rash episodes, cases of rubella, and congenital rubella syndrome.     

Safety and immunogenicity of live-attenuated Japanese encephalitis SA 14-14-2 vaccine co-administered with measles vaccine in 9-month-old infants in Sri Lanka

Introduction

To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine at 9 months of age. Serum immune responses were evaluated post-vaccination on days 28, 180, and 365 using JE neutralization test and anti-measles IgG ELISA.

Results

278 infants received one dose of LJEV and measles vaccine. Of these, 257 were eligible for the per-protocol analysis. On Day 0, 14 infants (5.5%) were seropositive for JE, but none were seropositive for measles. At Day 28, seropositivity rates were 90.7% (95% CI, 86.4–93.9%) for JE and 84.8% (95% CI, 79.8–89.0%) for measles. The geometric mean titer for JE neutralizing antibodies was 111 (95% CI, 90–135), and the geometric mean concentration (GMC) for anti-measles IgG was 375 mIU/mL (95% CI, 351–400 mIU/mL). Over the next year, JE neutralizing antibody responses declined only slightly, with seropositivity at 87.4% (95% CI, 82.6–91.2%) at Day 365. In contrast, measles antibody levels continued to increase over time. Seropositivity for anti-measles IgG reached 97.2% (95% CI, 94.4–98.9%) at Day 365, and the GMC rose to 1202 mIU/mL (95% CI, 1077–1341 mIU/mL). Co-administration of LJEV and measles vaccine was also safe. Most adverse reactions were mild, and no serious adverse events were related to study vaccinations.

Conclusion

The safety and immunogenicity of LJEV co-administered with measles vaccine in Sri Lankan infants is similar to that seen in other populations, and our results support use of LJEV at 9 months of age. Live SA 14-14-2 vaccine is now prequalified by the WHO for use in infants in Asia, and other countries may wish to introduce LJEV to combat this devastating disease.     

Seroprevalence of measles,mumps and rubella among children in American Samoa, 2011, and progress towards West Pacific Region goals of elimination

Introduction

In line with the global goals for measles elimination, countries in the West Pacific Region (WPR) have set a goal to eliminate measles by 2012. Due to its contagiousness, high population immunity is needed for achieving and documenting measles elimination. We assessed population immunity to measles, mumps and rubella among first grade children in American Samoa (AS) through a seroprevalance study.

Methods

Using commercial indirect enzyme-linked immunosorbant IgG assays (Wampole Laboratories, Cranbury, NJ) we determined IgG antibodies against the measles, mumps, and rubella (MMR) viruses in sera collected from first grade students in AS in April–May 2011. Vaccination status was retrieved from the immunization cards. Factors associated with seropositivity of measles, mumps, and rubella were analyzed separately.

Result

Among 509 first grade students, measles, mumps, and rubella seroprevalence were 92%, 90%, and 93%, respectively. The proportions of first grade students with documented one or two doses of MMR vaccine were 93% and 84%, respectively. The vaccination status of 6% of the first graders was unknown and 1% was unvaccinated. Receiving two-doses of MMR vaccines was associated with high measles and mumps seropositivity (p < 0.01).

Conclusion

The high measles seroprevalence among children shows the progress by American Samoa towards measles elimination. Achieving and maintaining high two-dose MMR vaccine coverage in all age groups will aid in attaining the measles elimination status and prevent transmission of measles from potential imported measles cases from other countries.     

Seasonal gaps in measles vaccination coverage in Madagascar

Introduction

Measles elimination depends on the successful deployment of measles containing vaccine. Vaccination programs often depend on a combination of routine and non-routine services, including supplementary immunization activities (SIAs) and vaccination weeks (VWs), that both aim to vaccinate all eligible children regardless of vaccination history or natural infection. Madagascar has used a combination of these activities to improve measles coverage. However, ongoing massive measles outbreak suggests that the country was in a “honeymoon” period and that coverage achieved needs to be re-evaluated. Although healthcare access is expected to vary seasonally in low resources settings, little evidence exists to quantify temporal fluctuations in routine vaccination, and interactions with other immunization activities.

Prevalence and factors associated with incomplete immunization of children (12–23 months) in Kwabre East District,Ashanti Region,Ghana

Background

Childhood immunization is one of the most cost effective health interventions but its rate has been declining recently in Ghana. Information on immunization coverage and determinants is needed to improve immunization programmes. The objective of this study was to determine the prevalence and factors associated with incomplete immunization of children (12–23 months) in Kwabre East District, Ghana.

Methods

A cross-sectional, community-based survey involving 322 children and their mothers was carried out. Data were collected on socio-demographic characteristics of mothers, childhood immunization history and mothers’ knowledge and practices of immunization using a structured questionnaire. Children were classified as incompletely immunized if they failed to receive at least one of 8 vaccine doses: - one dose of Bacillus Calmette–Guérin (BCG), 3 doses each of pentavalent, 3 doses of polio and one dose of measles per WHO/UNICEF definition. Chi-square and logistic regression analyses were used to identify the factors associated with incomplete immunisation.

Results

The prevalence of incomplete immunization was low (15.5%) suggesting high immunisation coverage but the coverage of the second measles dose, taken at 18 months of age, was the lowest (23.9%). Most of the mothers knew the importance of immunisation (95.7%) and at least one vaccine-preventable disease or symptom (84.9%). Two factors associated with incomplete immunisation in bivariate analyses (community of residence, and mother’s knowledge of number of oral polio vaccines given to children) were no longer significant in a logistic regression model. Compared to children in Aboaso, children in Gyamfi Wonoo (AOR?=?1.81, 95% CI?=?0.80–4.08), Mamponteng (Bonwunu) (AOR?=?0.59, 95% CI?=?0.24–1.48) and Mamponteng (Town) (AOR?=?0.63, 95% CI?=?0.26–1.55) had similar odds of incomplete immunisation. Similarly, mother’s lack of knowledge of the number of doses of polio vaccine given to children had no effect on the odds of incomplete immunisation (AOR?=?0.53, 95% CI?=?0.22–1.26).

Conclusions

Immunization coverage is high in the Kwabre East district but very few children received the second measles dose. None of the maternal and child factors assessed is associated with immunisation coverage. Further research is needed to identify the determinants of immunisation coverage and the reasons for the low uptake of second measles dose in the study area.

     

Economic analysis of measles elimination program in the Republic of Korea, 2001: A cost benefit analysis study

Background

In this study, we modeled the cost benefit analysis for three different measles vaccination strategies based upon three different measles-containing vaccines in Korea, 2001. We employed an economic analysis model using vaccination coverage data and population-based measles surveillance data, along with available estimates of the costs for the different strategies. In addition, we have included analysis on benefit of reduction of complication by mumps and rubella.

Methods

We evaluated four different strategies: strategy 1, keep-up program with a second dose measles-mumps-rubella (MMR) vaccine at 4–6 years without catch-up campaign; strategy 2, additional catch-up campaign with measles (M) vaccine; strategy 3, catch-up campaign with measles-rubella (MR) vaccine; and strategy 4, catch-up campaign with MMR vaccine. The cost of vaccination included cost for vaccines, vaccination practices and other administrative expenses. The direct benefit of estimated using data from National Health Insurance Company, a government-operated system that reimburses all medical costs spent on designated illness in Korea.

Results

With the routine one-dose MMR vaccination program, we estimated a baseline of 178,560 measles cases over the 20 years; when the catch-up campaign with M, MR or MMR vaccines was conducted, we estimated the measles cases would decrease to 5936 cases. Among all strategies, the two-dose MMR keep-up program with MR catch-up campaign showed the highest benefit-cost ratio of 1.27 with a net benefit of 51.6 billion KRW.

Conclusion

Across different vaccination strategies, our finding suggest that MR catch-up campaign in conjunction with two-dose MMR keep-up program was the most appropriate option in terms of economic costs and public health effects associated with measles elimination strategy in Korea.     

Measles outbreak in Burkina Faso, 2009: a case-control study to determine risk factors and estimate vaccine effectiveness

Objective

We investigated a large measles outbreak that occurred in 2009 in Burkina Faso in order to describe the epidemic, assess risk factors associated with measles, and estimate measles vaccine effectiveness.

Methods

We reviewed national surveillance and measles vaccine coverage data, and conducted a case–control study in three geographic areas. Case-patients were randomly selected from the national case-based measles surveillance database or, when a case-patient could not be traced, were persons in the same community who experienced an illness meeting the WHO measles clinical case definition. Controls were matched to the same age stratum (age 1–14 years or age 15–30 years) and community as case-patients. Risk factors were assessed using conditional logistic regression.

Results

Lack of measles vaccination was the main risk factor for measles in all three geographic areas for children aged 1–14 years (adjusted matched odds ratio [aMOR] [95% confidence interval (CI)], 19.4 [2.4–155.9], 5.9 [1.6–21.5], and 6.4 [1.8–23.0] in Bogodogo, Zorgho, and Sahel, respectively) and persons aged 15–30 years (aMOR [95% CI], 3.2 [1.1–9.7], 19.7 [3.3–infinity], 8.0 [1.8–34.8] in Bogodogo, Zorgho, and Sahel, respectively). Among children aged 1–14 years, VE of any measles vaccination prior to 2009 was 94% (95% CI, 45–99%) in Bogodogo, 87% (95% CI, 37–97%) in Zorgho, and 84% (95% CI, 41–96%) in Sahel. Main reasons for not receiving measles vaccination were lack of knowledge about vaccination campaigns or need for measles vaccination and absence during vaccination outreach or campaign activities.

Conclusion

These results emphasize the need for improved strategies to reduce missed opportunities for vaccination and achieve high vaccination coverage nationwide in order to prevent large measles outbreaks and to continue progress toward measles mortality reduction.