An Expert Perspective from Algeria on Hexavalent Vaccine Adoption

An Exclusive Authored by L.Smati, N.Benhalla, A.Zertal, N.Sai, R.Boukari

An operational model developed in Algeria may show a way that countries can make childhood vaccines more effective, more acceptable and more economical. It is a model that may provide a framework for middle-income countries across the globe, including many across the rest of Africa.

Six-in-one (or hexavalent) vaccines are cutting the number of clinic visits needed to prevent multiple life‑threatening infections and easing pressure on already stretched health systems. Growing economic evidence from Algeria and several Latin American countries suggests that while these vaccines may cost more upfront, the investment may be largely or entirely recovered through fewer appointments, streamlined logistics, and a reduction in cases of vaccine-preventable diseases and potential adverse events from vaccination. Yet the children who could benefit most – those living in low‑ and middle‑income countries are still the least likely to receive them, widening an avoidable gap between what modern vaccines can do and the protection children actually receive.

Most hexavalent vaccines save money in another way: they reduce the number of adverse events – side effects – that require treatment in a hospital or clinic. Acellular hexavalent vaccines include a type of protection against pertussis, or whooping cough, which is the gold standard for immunization in higher-income countries but has not yet been widely adopted beyond them.

With more than a decade of historical data supporting safety and efficacy, these acellular pertussis vaccines have a notable track record of improving vaccination coverage rates (VCR) and parents’ willingness to have their children protected, as they cause fewer painful adverse events [1].

Acellular pertussis (aP) vaccines are formulated using isolated antigens, which are purified and detoxified, thereby removing most of the components of the bacterium that cause undesirable reactions [2].

Most low- to middle-income countries still use whole-cell pertussis vaccines, which include a suspension of the entire inactivated Bordetella pertussis organism – some 3,000 antigens. Although the inclusion of far more antigens can result in a marginally higher immune response, the complexity of the vaccine leads to varying amounts of reaction-causing components between batches of vaccine and varying levels of protection [2].

The combination of more adverse events and variable efficacy means that developing countries bear a disproportionate share of the burden incurred through side effects. The side effects in children lead to an increased reluctance among parents to agree to future vaccines for their children and higher costs for the healthcare system. These problems often arise in healthcare systems that are inadequately equipped to deal with them.

Expert opinion from Algeria indicates that acellular hexavalent vaccination has improved vaccination coverage levels and simplified the vaccination schedule by reducing the number of appointments. It reduces the required number of immunization visits from ten to six. This eases pressure on overstretched health services, simplifies logistics and cold-chain management, and reduces indirect societal costs, including the time parents spend away from work.

Algeria is the third WHO African region country to adopt the acellular hexavalent vaccine into its national immunization schedule. Economic data from those countries and several in Latin America demonstrate that a rollout of the vaccine across African countries is not only possible but also economically advantageous [3,4,5,6].

Algeria’s vaccination metrics: an operational model for success

Vaccines have transformed child health in Algeria, as they have across the world. Since the initial introduction of vaccination in Algeria, followed by sustained efforts to expand the vaccination schedule, infant mortality rates have dropped dramatically from 163 per 1,000 live births in 1966 to 20 per 1,000 in 2023, a reduction of around 87% [7].

The percentage of children protected in Algeria has exceeded the targets set by the World Health Organization (WHO) for decades, with diphtheria, tetanus toxoid and pertussis (DTP) coverage consistently above 90% [8]. As in many countries, the COVID-19 pandemic disrupted healthcare systems, leading to a decline in vaccination rates, with DTP-3 coverage, a key measure of childhood vaccination, reduced to 77% in 2022 [9]. This situation was quickly improved, with coverage increasing to 92% by 2024 [9].

In 2022, three cases of polio caused by circulating vaccine-derived poliovirus type 2 were reported [10]. Rarely, the circulating vaccine-derived virus causes polio, highlighting the necessity of timely vaccination with IPV, with which these vaccine-derived cases do not occur [11].

The shift to hexavalent vaccination

Algeria’s shift from its former schedule to hexavalent vaccination was not a straightforward process. Initially, the five-in-one (or pentavalent) vaccine was replaced by a combination of the tetravalent vaccine (DTP-Hib) and the monovalent Hepatitis B vaccine (HBV), administered across 10 separate healthcare visits, necessitating additional appointments [12].

The change in the vaccination schedule resulted in delays in dose administration and a decrease in vaccination coverage. This issue was resolved with the introduction of the new schedule, which integrated an acellular hexavalent vaccine in 2023, reducing the number of required healthcare visits to six [13].

While polio vaccination was present in the previous schedule (with one IPV dose at 3 months and 3 OPV doses at 2, 4, and 12 months), inclusion as part of a hexavalent vaccine simplified the schedule (giving three doses of IPV at 2, 4, and 12 months associated with three OPV doses), helping to maintain the global strategy for polio eradication. The WHO recommends that all countries using OPV adopt a vaccination schedule with at least two doses of inactivated vaccine, which gives individual protection without the risk of vaccine-related polio [14].

The financial metrics of the switch

A recent whitepaper conducted a pharmacoeconomic analysis of the budgetary impact of transitioning from a whole-cell tetravalent vaccination schedule to an acellular hexavalent schedule. While the switch was associated with an increase in annual program expenditure of approximately 26 million Euros (around a 58% rise in upfront costs), this was substantially offset by nearly 19 million Euros in annual savings generated through the management of adverse events, improved logistics and transportation, and increased parental productivity [13]. Overall, roughly 73% of the upfront cost was offset by these savings.

Algeria is the latest in a series of examples where this is the case. The nominal, upfront cost of acellular hexavalent vaccines is typically higher than that of whole-cell vaccines; this has, in many cases, deterred countries from adopting them. However, there are many benefits at both the economic and systemic levels that recoup much of the costs of acellular hexavalent vaccines. In many instances, these costs are hidden and not factored into initial value calculations.

Similar experiences have been seen in other countries. In Argentina, Peru, and South Africa, the switch to hexavalent vaccines led to higher initial costs, but these were substantially offset by savings from fewer adverse events, lower programmatic expenses, and improved logistics. For example, in data from Argentina, roughly 90% of the initial investment into acellular hexavalent vaccines was recovered through fewer adverse event-associated costs and lower programmatic costs [15]. Peru reported a reduction in logistical costs by nearly 60%, with roughly 44% of the initial increase in costs recovered [16]. South Africa achieved overall savings of about 10 USD per child [3].

These calculations overlook benefits that are more difficult to quantify. For example, what costs are generated because of vaccines missed and infections caused by increased vaccine hesitancy on the part of parents. Across these settings, the higher upfront investment in hexavalent vaccines has proven to be economically viable, with much of the cost recouped through broader system efficiencies.

Programmatic benefits of hexavalent vaccination

Hexavalent vaccination offers the potential for simpler systems and higher levels of acceptance among patients. For the child, integrating six antigens into a single injection drastically reduces the number of needle sticks, alleviating injection-related anxiety and the prevalence of local reactions. This increases parental acceptance and helps to improve vaccination coverage.

Parents are relieved of the burden of coordinating multiple medical appointments, covering travel costs, and dealing with lost workdays. By reducing parental anxiety and the strain of repeated visits, combined vaccines help mitigate vaccine hesitancy within communities. This has been demonstrated in multiple studies across Africa, with investigations in Gambia and South Africa documenting concerns among parents about a child receiving more than two injections in a single visit [17,18]. Limiting the number of healthcare visits is also a crucial factor in increasing vaccine coverage in areas with limited healthcare infrastructure, such as those in rural southern Algeria.

For healthcare professionals, particularly in resource-limited settings such as rural areas in Africa, the adoption of combined vaccines helps to ease the administrative burden of multiple appointments. These formulations optimize consultation efficiency by drastically reducing the required administration time and simplifying inventory management [19].

The use of ready-to-use liquid vaccines, such as the hexavalents, has been shown to simplify and enhance the safety of the vaccination procedure when compared to vaccines that come as a powder that has to be reconstituted [20]. The preference for this approach among frontline workers is overwhelming: one study indicated that 97.6% of healthcare providers favored these liquid, combined formulations in their daily work [21]. Evidence supports this preference, demonstrating that the switch led to a dramatic reduction in administration errors (from 42.8% to 4%) and needlestick injuries (from 42.3% to 9.5%), while also yielding an average time savings of 1.1 minutes per dose [22].

The case for Hexavalent vaccination across Africa

Across the WHO Africa region, VCR has improved significantly over the last few decades; however, unfortunately, this improvement has stalled. The level of coverage for the third dose of DTP-containing vaccines, a standard benchmark for immunization system performance, has sat in the mid-70s for over a decade, with a current coverage of 76% [23].

This stagnation of the VCR is reflective of the ongoing issue of inequality. The gap in vaccine access runs not only between Africa and higher‑income regions, but also within the continent itself, where some countries consistently outperform others. Diseases, however, do not recognize borders; any outbreak that affects one country is likely to increase the risk to surrounding countries. Air travel enables a disease case to be spread to virtually any country in the world within just two days [24].

The COVID-19 pandemic was a clear example of the rapid spread in today’s world. Within a period of weeks, the virus spread from its origin in China to the entire globe, despite public health measures and lockdowns. With this in mind, any country that is falling behind on vaccination coverage becomes a weak link in a global chain where diseases can flourish and form reservoirs of cases that can allow diseases such as polio to spread unchecked.

Bringing vaccine equity to lower- and middle-income countries is therefore vital to addressing global health concerns. Hexavalent vaccination has demonstrated its ability to increase vaccine coverage in these countries. Among the WHO Africa region, Mauritius, which adopted hexavalent vaccination in 2017 [4] currently stands notably above the average for the region, with 96% coverage for the first dose of inactivated polio vaccine, and 93% for the benchmark based on DTP-containing vaccines [25].

Vaccine coverage translates into increased prosperity. Vaccination cannot be viewed as an inconvenient expense but as an investment. The WHO estimates that for every dollar spent, vaccination can yield a return on investment of around 54 USD – provided, of course, that the vaccines actually find their way into the arms of children [26].

As the Algerian case study demonstrates, higher upfront costs for acellular hexavalent      vaccines are often paid back by improvements in logistical efficiency, reduced healthcare burdens, and improved parental compliance. By bridging the gap between high- and low-income immunization standards through this investment, the life-saving benefits of gold standard vaccinations can become more than a privilege of geography, but a universal foundation for human health.

[This consensus paper is based on the findings of a white paper discussing the findings of a group of vaccination experts focusing on paediatric immunisation, supported by Sanofi. Intended for professional use.]

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