Rotavirus infections are the most common cause of diarrhoeal-related death in children under five. These infections can be deadly but, importantly, they are preventable.
Rotavirus vaccination has been proven to be effective in reducing deaths across the globe in settings spanning from industrialised nations to low-income countries. The vaccines have been added to the routine immunisation schedules of many countries, many with the aid of non-governmental organisations such as Gavi.
Eligibility for Gavi assistance in funding vaccine delivery is based on a country’s financial situation, with a number of low-middle income countries (LMICs) registering high vaccination coverage following funding allocation.
A recent study published in The Lancet has noted that while rotavirus vaccine uptake has been high in those countries assisted by Gavi — as well as in high income nations — uptake has been slow in middle-income countries (MICs) that do not qualify for Gavi assistance. The analysis of the report documents the cost-effectiveness of either adding rotavirus vaccination to the routine immunisation schedule of these nations, or increasing the coverage rates in countries that already provide the vaccine.
Middle income countries and the lack of uptake
The study assesses the cost-effectiveness and benefit–risk of rotavirus vaccination in 63 MICs not eligible to receive Gavi funding. The study notes that, as of July 2020, of the 63 MICs that are not currently eligible for financial support from Gavi, only thirty have included rotavirus vaccines in their national immunisation programmes, with most using Rotarix (manufactured by GlaxoSmithKline).
Among the barriers suggested for the lower vaccination coverage for rotavirus — compared to high income countries and those receiving Gavi support — the most commonly suggested issue is the associated cost.
This, as the paper suggests, is where their work may offer guidance to MICs. A clear issue in previous studies is the lack of data available in the context of MICs. While studies have taken place covering the use of rotavirus vaccines in LMICs, as well as their cost effectiveness in the setting, there is little documented evidence for their cost effectiveness in MICs.
Given the fact that the majority of rotavirus-associated deaths occur in low-income countries (LICs), MICs occupy a middle ground in which routine immunisation with the vaccine is not supported by international funding to the extent of LICs. This, coupled with the lower prevalence, has been a contributing factor to hesitancy by some countries to incorporate the vaccine into routine immunisation programmes given the absence of data on potential cost recuperation.
Viewing mortality reductions in isolation is, however, a simplistic view that ignores the non-fatal rotavirus cases that result in hospitalisation and serious illness. In a financial context, vaccines are an investment. While there is an upfront cost to MICs, there is the potential for savings in both money and vital resources such as hospital beds and the time of the doctors themselves, by preventing infection in the first place.
Secondary to the affordability of vaccination was the hesitancy of vaccination due to the perception of the possible risk of intussusception. This is a rare but serious bowel disorder that can lead to gut perforation due to necrosis resulting from bowel blockages. Especially in settings where access to healthcare is limited, this bowel disorder can be fatal.
Initial data from the very first rotavirus vaccine, Rotashield, indicated an almost thirty-fold risk of intussusception. This led to its temporary suspension from use and further investigations were conducted. Follow-up studies of newer generation rotavirus vaccines, RotaTeq and Rotarix, have provided more evidence on the relative risk of intussusception. Studies across a number of settings still show an increased risk of intussusception with both vaccines; however, this increase is marginal, with about one to six excess cases per 100,000 vaccinated infants. Given access to healthcare is adequate, these cases rarely result in mortality, though can be fatal in LICs if treatment is not provided in a timely manner.
Given the relatively low risk, assessments by the World Health Organization (WHO) and the other public health bodies have determined that the potential for disease cases averted and as such, lives saved, from the implementation of the rotavirus vaccine far outweighs the potential for illness created through the marginal increased risk of intussusception.
The risk that rotavirus represents
While rotavirus is more prevalent in LICs, it is not a risk that can be ignored in any country, as there still remains a risk of mortality in infants as well as the potential for hospitalisation resulting from the severe side effects of the resultant dehydration. In 2019, rotavirus was estimated to be responsible for 151,514 deaths in children younger than five, along with millions of cases and hospitalisations.
Vaccination against rotavirus is recommended by the WHO to be integrated into routine immunisation schedules. While it has been acknowledged that efficacy was lower in LICs, the WHO states that “even with this lower efficacy, a greater reduction in absolute numbers of severe gastroenteritis and death was seen, due to the higher background rotavirus disease incidence.”
Data gathered from Mexico — an upper middle income country — is highly positive regarding the use of rotavirus vaccines. After incorporating rotavirus vaccination into their routine immunisation schedule, a decline of up to fifty percent in diarrhoeal deaths in children under five years of age was recorded. This decline was attributed directly to the use of the vaccine.
The study notes that from their analysis, over the 2020–29 period, rotavirus vaccines could avert 77 million cases of rotavirus gastroenteritis; 21 million clinic visits; three million hospitalisations; and 37,900 deaths due to rotavirus gastroenteritis in the 63 MICs not eligible for Gavi support.
Economic benefits of the vaccine: is it worth the cost?
From an economic perspective, the paper assesses an incremental cost-effectiveness ratio (ICER) for each nation, expressed in US dollars per disability-adjusted life-year (DALY) averted. The costs and calculations were all performed on the calculation of 0.5 times the current gross domestic product (GDP) value of each nation, as had been set out in numerous other previous papers. Discounted costs averted from clinic visits and hospitalisations would be US$826 million from a government perspective and $1182 million from a societal perspective (including out-of-pocket payments, private medical care and private health insurance).
The study used three vaccines — Rotarix, Rotavac and Rotasiil — to analyse different situations for pricing and availability for each country, then assessing whether the ICER for each country is calculated to be cost-effective for at least one vaccine.
The study’s results indicated that “from the government perspective, 48 (77 percent) of 62 MICs (excluding Syria, as no GDP data was available at the time of the study) had a deterministic ICER lower than 0.5 times their GDP per capita with at least one of the rotavirus products under consideration.” This indicates that from government funding alone, a majority of the countries would see costs returned from the implementation, or expansion of rotavirus vaccination. From a societal perspective, 54 (87 percent) of 62 countries were noted as cost-effective with at least one vaccine.
The results of the study are encouraging. They indicate that even without outside funding sources, in the majority of MICs a vaccination programme for rotavirus will pay for itself through reductions in mortality and hospitalisations. Unique circumstances in some countries may explain the lack of a return on investment. In instances where supply chain issues drive up the cost of vaccines and the associated programmes, this may tip the balance of cost effectiveness. In others, there may simply be a far lower burden of rotavirus, naturally then reducing the costs recovered through reductions in hospitalisation.
Dissemination of data such as this could be a key component in driving vaccine uptake and the creation of vaccination programmes across MICs, even in the absence of international funding. The study suggests that not only would routine immunisation for rotavirus be cost effective, it is also undeniable that data exists that underlines the public health benefit of such campaigns.