June 2019, Volume 69, Issue 6

Systematic Review

Cost-effectiveness of measles treatment: a systematic review

Authors: Nam Xuan Vo  ( Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam )
Anh Thi Van Nguyen  ( Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000 )
Ha Thi Mai Tran  ( Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000 )
Linh Thi Thuy Truong  ( Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000 )
Nghi Ngoc Bao Nguyen  ( Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000 )

Abstract


Objective: Measles is still common in many developing countries, and its outbreaks have been on the rise since 2009 even though the disease is almost entirely preventable through safe and effective vaccination. This paper aims to provide evidence about the systematic review of the cost-effectiveness of measles treatment in different regions worldwide.
Methods: The methodical search began on 10th January 2019 to look for all articles on the cost-effectiveness of measles treatment published from January 2019 to April 2019 in SCOPUS, Pubmed (www.ncbi.nlm.nih.gov) and Cochrane (www.cochrane.org).We summarised the articles by using a data table to extract all information using health economic evaluation methods.
Results: We identified 14 articles from the 69 total articles searched. These articles showed favourable costeffectiveness or cost-benefit ratios in high- and middle-income countries based on data organised by World Bank Income Level in 2018: the United States, Canada, Japan, India and Zambia. However, research is still limited in lowincome
countries and thus the effectiveness of vaccination programmes cannot be conclusively identified.
Conclusion: This review shows the overview of the research in health economic evaluations of measles in different places, years and using different methods of intervention. Overall, it evaluates the cost-effectiveness of measles treatment.
Keywords: Cost-effectiveness analysis, Measles, Systematic review, Literature review. (JPMA 69: S-148 (Suppl. 2); 2019)

Introduction

Measles, which is caused by morbillivirus, is one of the world's most infectious diseases. It affects mostly children, especially poorly nourished young children, those with insufficient vitamin A and those who have weak immune systems of any age, such as HIV/AIDS patients. In 2017, measles caused close to 110,000 deaths.1 Even in highincome countries, complications can result in hospitalisation in up to a quarter of the cases of measles infections, and could lead to lifelong disability from brain damage, blindness or hearing loss. 2 There is no specific antiviral treatment that exists for the measles virus, but measles is preventable and can be eliminated by two doses of a safe, effective and inexpensive vaccine which has been in use since the 1960s, when itwas immediately identified as highly costeffective. 3The World Health Organization (WHO) recommends immunisation for all susceptible children and adults for whom measles vaccination is notcontraindicated. Inoculating all children with two doses of the measles vaccine, either alone or in a measles-rubella (MR), measles-mumps-rubella (MMR) or measles-mumpsrubella-varicella (MMRV) combination should be the standard for all National Immunisation Programmes. 4 All six WHO regions have measles elimination goals before or by 2020, and the Global Vaccine Action Plan has a goal to eliminate measles in five of the six WHO regions by 2020. 2Achieving global measles-mortality reduction goals would require a further increase in measles vaccine coverage. Through a combination of innovation, resources and political action, we can work together to achieve and maintain the global elimination of measles. 1 However, measles is still common in many developing countries, particularly in parts of Africa and Asia. The overwhelming majority of measles deaths today occur in countries with low per capita income and weak health infrastructure. Outbreaks of measles have been on the rise since 2009, particularly in the African, South-East Asia and European Regions, and also in North America. 2 There is a clear trend that many countries are in the midst of sizeable measles outbreaks. As of 15th April 2019, 170 countries have reported 112,163 measles cases to the WHO. 5 In contrast, in April 2018 there were 28,124measles cases from 163 countries. Preliminary global data shows a 300% increase in reported cases in the first three months of 2019, compared to same period in 2018. 5 Due to the availability of an inexpensive and effective vaccine, measles immunisation is one of the most costeffective public health interventions in a wide range of developed regions. 1 The first health economic analysis of the measles vaccine was published in 19694 and over the past 50 years, many research articles explored a widerange of immunisation interventions for measles using cost-benefit analysis (CBA) and or cost-effectiveness analysis (CEA). The motivation for this paper is to provide a systematic review of the cost-effectiveness of measles treatments in different region worldwide.


Materials and Methods

The search for materials began on 10th January 2019 and continued through to 10th April 2019. We searchedfor all articles on the cost-effectiveness of measles treatments published from January 2019 to April 2019 in SCOPUS, Pubmed (www.ncbi.nlm.nih.gov) and Cochrane (www.cochrane.org). Our search strategy included the following terms: 'measles', 'treatment', 'regimen', 'cost-effectiveness' and 'economic evaluation'. After checking for duplication, the selected articles were reviewed one-by-one by reading their titles, abstracts and full text to identify the most appropriate articles. The details and results of our selection process are shown in Figure-1.



After reviewing the selected studies, we categorised them by year and by different methods of health economic evaluations, and then were compared the results together to assess the cost-effectiveness of measles treatments. We summarised them by using a data table to extract all article information using methods of health economic evaluations like CBA and CEA, as well as costutility analysis (CUA) and cost-minimisation analysis (CMA), to make a comparison of these studies together.


Results

Figure-1 shows our results from searching the syntax mentioned in the methods section. We found 1 article on Cochrane, 27 articles on SCOPUS and 54 articles on Pubmed. Because 13 of these were duplications, a total of 69 articles were identified. From these, 58 articleswere eliminated because of our exclusion criteria: 4articles were trial articles, 8 articles were not written in English (2 in German, 2 in Spanish, 2 in French, 1 in Russian and 1 in Slovak) and 46 articles were irrelevant to the cost-effectiveness measles treatments. Therefore, 11 articles from our initial search were included. After consulting the reference list of these 11 articles, three more articles were added referring to the searching topic. In total, the number of reviewed articles was 14. The types of economic evaluation used with the articles identified are summarised in Table-1.



There were seven cost-benefit analyses, five cost-effectiveness analyses, one extended cost-effectiveness analysis and one article used both cost-benefit analysis and cost-effectiveness analysis. In the cost-benefit analyses, the measles immunisation, 2- dose MMR vaccine, 2-dose measles immunisation and measles vaccine catch-up schedule were all proven to be cost- effective.3,6-11 The cost-effectiveness analyses indicated that the measles immunisation, measles eradication, measles-containing-vaccine first-dose (MCV1) combined with supplemental immunisation activities (SIAs), catch-up schedule and follow-up measles campaign appear to be cost-effective.5,12-15 The article which used both the cost-effectiveness analysis and the cost-benefit analysis showed that the 2-dose measles vaccination at 95% coverage is cost-effective in a hypothetical Western Europe country. 16 The article with the extended costeffectiveness analysis showed that the measles vaccination averted the most deaths per dollar spent in Ethiopia. 17









 

Tables-2, 3, 4 and 5 summarise the interventions and results of selected articles by cost-benefit analysis, costeffectiveness analysis, extended cost-effectivenessanalysis and the article that used both cost-benefit analysis and cost-effectiveness analysis. Measles immunisation appears to be more cost-effective compared to no measles immunisation, with the benefitcost ratio at 2.48 in Japan.6 Measles vaccination is also cost-saving in other regions: the cost per case averted was US$71.75 and the cost per death averted was US$15,000 in Latin America and the Caribbean;18 meanwhile the net savings per measles case averted were US$40 in Mpumalanga and US$7 in Western Cape.8 In the Afr-E region and Sear-D region, the costs per disability-adjusted life year (DALY) averted for measles immunisation were, respectively, US$82-$164 and US$240.14 Another article, which studied 73 low- and middle-income countries supported by Gavi, the Vaccine Alliance, also proved that measles vaccination is highly cost-effective and saved US$142 billion in the cost of illness from 2001 to 2020 and US$27,000 in the cost of illness per death averted.19 Sear- D includes the following countries: Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Maldives, Myanmar, Nepal, Timor Leste. Afr-E includes the following countries: Botswana, Burundi, Central African Republic, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Eritrea, Ethiopia, Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Uganda, United Republic of Tanzania Zambia, Zimbabwe When compared to other interventions, such as the  rotavirus vaccination, pneumococcal conjugate vaccination, diarrhoea treatment, caesarean section surgery, hypertension treatment and tuberculosis treatment, measles vaccination is the intervention that averted the most deaths: 367 deaths per US$100,000 spent by the Ethiopian Government.17 Measles eradication is cost-effective,5,20-22 and eliminating measles by 2020 is cost-effective in Uganda. The incremental cost-effectiveness ratio (ICER) per DALY averted was US$556 for a 2030 time horizon and US$284per DALY averted for a 2050 time horizon.20 Eradication by 2020 would save US$800 million compared to measles control in high income countries,21 while the incremental cost-effectiveness of control is similar to eradication in low- and middle- income countries.21 Measles eradication by 2020 is predicted to cost an additional discounted US$7.8 billion and avert 346 million DALYs,5 indicating that the ICER per DALY averted was US$22.5. In 72 of the world's poorest countries, increasing the measles vaccine coverage to 90% is cost-effective. The total cost averted was US$ 9.65 million and the number of deaths averted was 360,000,23 indicating that the incremental cost per death averted is approximately US$26.82. However, raising measles immunisation rates would not appear to be cost-effective, except during measles outbreaks in very low immunisation rate areas.24 The use of a 2-dose measles vaccination is more costeffective than a single-dose vaccination in Canada, with the benefit-cost ratios ranging from 2.61:1 to 4.31:1,  depending on the target population and the strategy used.7 Another study in a Western European country shows that a 2-dose measles vaccination at 95% coverage is cost-effective, with the benefit-cost ratio ranging from 2.47 in the base case of single-dose vaccination at 90% coverage to 3.96 in the base case of single-dose vaccination at 70% coverage. The ICER per life-year gained was €1209 compared to the base case of 90% vaccination coverage. The use of the first dose through routine immunization and the second dose through supplemental immunisation activities is cost-effective in Uganda, Zambia and India, with the ICER per DALY averted being US (2010) $1.50 in Uganda,12 the ICER per death averted being $US155.84 in Zambia25 and the cost per DALY averted being 30 in India.13 SIAs are also cost-effective in Bangladesh and Ethiopia, with the estimated costeffectiveness ratios per DALY averted being US$19.20 in Bangladesh and US$2.50 in Ethiopia.22 The catch-up vaccine schedule is also cost-effective.8,15 The benefit-cost ratios for a catch-up campaign in Mpumalanga and Western Cape were 2.27 and 0.89, respectively,8 and the cost per death averted was US$23.60 in Afghanistan.15 In India, West Bank and Gaza, continuing measles immunisation at 15 months plus a routine second measles immunisation at early school age is costbeneficial, with cost-benefit ratios of 4.53:1 in Israel, 5.74:1 in West Bank and 9.59:1 in Gaza.10 The measles and rubella vaccination is cost-beneficial, with a benefit-cost ratio of 14:1. The use of the MMR vaccine is cost-effective, with a benefit-cost ratio of 14.4:1 in the United States.11 One study, which also took place in the United States, shows that two doses of the combined MMR vaccine is more cost-beneficial compared to the absence of the MMR vaccine, with benefit-cost ratios of 0.31 and 0.49 from direct cost and societal perspectives, respectively.3 Another study shows that routine second dose immunisation with MMR vaccine is cost-effective, with net gains of US$6.34 per dollar spent from the ministry of health perspective and US$3.25 from the societal perspective.9 However, when the 2-dose MMR vaccine is compared with either the single-dose or 2-dose MR vaccine, the MR vaccine appears to be more costsaving than the 2-dose MMR vaccine, with savings of a single MR vaccine being US$4.1 billion at a 3% discount rate or US$2.1 billion at a 5% discount rate. 26


Discussion

This review shows a variety of evidence accumulated in a 35-year period from 1982 to 2017 that demonstrates the cost-effectiveness and economic benefits of different kinds of measles vaccines, such as the 2-dose measles vaccination, supplemental immunisation and MMR. In addition, this review also shows the effectiveness achieved on benefit-cost ratios and the incremental costeffectiveness ratio per quality-adjusted life year (QALY) or DALY in a data source. Moreover, this assessment compares the costs of vaccination to the cost of treatment after being infected with measles in some countries. The vaccination cost was assessed to be US$165 million, while the whole nationwide cost for measles treatment was US$404 million in Japan.6 Other research shows that a vaccination policy averts a single case of measles at the cost of US$71.75 and prevents a death due to measles at the cost of US$15,000.18 A vaccination strategy saves a total of US$208 million in treatment costs due to reduced incidences of measles.18 Therefore, the benefit of vaccination not only minimises costs, but also provides high efficiency in preventing measles in infants. Our analysis has a number of limitations. Some research we used was from the 1980s and 1990s, when researchers did not use optimal economic evaluation methods such as cost-minimisation, cost-benefit, cost-effectiveness or cost-utility analyses. Therefore, the cost-effectiveness has not been specifically assessed on life years gained, DALYs or QALYs. Another limitation mentioned is that all research was studied in different regions of the world, so it is impossible to compare the results between developed and developing countries. The cost-effectiveness of most health interventions of measles not only depends on how well the health systems function in different countries,27 but also on a mother's knowledge of measles epidemics during and after pregnancy. We hope that this review provides useful background about the cost-effectiveness of the treatment of measles and the differences in costs, as well as the benefits of vaccination immunisation compared to measles treatment. Therefore, the economic analyses likely play a vital role in measles eradication.


Conclusion

This review shows the overview of the research in health economic evaluations of measles in different places, years and using different intervention methods. Measles prevention by vaccination programmes is the most effective intervention. It shows favourable costeffectiveness or cost-benefit ratios in high- and middleincome countries based on data organised by World Bank Income Level in 2018: The United States, Canada, Japan, India and Zambia. However, research is still limited in lowincome countries, and thus the effectiveness of these vaccination programmes cannot be conclusively identified. Therefore, it is necessary to advance the scope of research in low-income countries to evaluate the effectiveness of vaccination programmes in these countries.


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