Cost-Effectiveness of the Pneumococcal Conjugate Vaccine (10- or 13-Valent) Versus No Vaccination for a National Immunization Program in Tunisia or Algeria

Streptococcus pneumoniae (S. pneumoniae) is a common gram-positive bacterium with more than 95 serotypes, often colonizing the nasopharynx of healthy infants. S. pneumoniae can spread across the mucosa to cause non-invasive diseases, and occasionally the bacteria cross the mucosal barrier to cause invasive disease. Non-invasive disease is represented mainly by pneumonia (lung infection) and otitis media (OM, middle ear infection). Invasive pneumococcal disease (IPD) occurs if the bacteria enter the bloodstream (bacteremia/septicemia) or travel via the bloodstream to seed other sterile sites (meningitis, septic arthritis, and osteomyelitis). Both invasive and non-invasive pneumococcal diseases present a substantial health and economic burden worldwide.

A seven-valent pneumococcal polysaccharide-protein conjugate vaccine (Prevenar^®, PCV7) was licensed in February 2000 in the USA and subsequently recommended for routine immunization of all infants beginning at 2 months of age, with additional recommendations provided for the immunization of older infants and children at an increased risk of pneumococcal disease [1]. PCV7 offered protection against the seven serotypes responsible for a high proportion of disease worldwide (4, 6B, 9 V, 14, 18C, 19F, and 23F). Four years after PCV7 implementation in the USA, surveillance results indicated a 20% decrease in all-cause OM visit rates [2], a 52.4% decrease in all-cause pneumonia hospitalizations [3], and a 39% decrease in cases of all-cause pneumonia [4] in children < 2 years. Subsequently, the next generation of PCVs, the 10- (PCV10) and 13-valent (PCV13) vaccines, was introduced (Supplementary Table 1) and offered greater serotype coverage against disease caused by an additional three (1, 5, and 7F) and six (1, 3, 5, 6A, 7F, and 19A) serotypes, respectively, that were not covered in PCV7 [5, 6]. Now, 7 years since their introductions, real-word effectiveness studies indicate further effects for PCV10 [7, 8] and PCV13 [9‐12] on invasive and non-invasive disease, in proportion to the enhanced serotype coverage beyond PCV7.

Numerous countries around the world have adopted PCVs into a national immunization program (NIP) in response to the substantial prevalence of pneumococcal diseases [13, 14], morbidity, and mortality [15]. Vaccine serotypes of S. pneumoniae have been identified as the predominant cause of IPD [16] in North Africa, causing 76.9% [18], 86.8% [16], and up to 90% [17] in Algeria and 68% [19], 78% [20], and up to 78.7% [21] in Tunisia. Some countries now have adopted PCV NIPs [13, 14], beginning with PCV13 in Morocco in October 2010 followed by PCV10 in July 2012 [22, 23] and then PCV13 in Algeria in April 2016. Likewise, PCV10 and PCV13 are registered and available within the private markets of Morocco and Tunisia. The introduction and maintenance of childhood pneumococcal vaccination programs in Morocco and Algeria, and the introduction in Tunisia, are expected to result in reduced mortality, disease burden, and direct medical costs.

Cost-effectiveness analyses are an effective tool to inform decision-makers about the value of introducing a vaccination program and the clinical and economic impact of each available PCV program [24]. Lower-middle income countries often perceive the cost of PCVs as high relative to other vaccines, but evidence suggests that PCV immunization programs can be a cost-saving and/or highly cost-effective health intervention to reduce their substantial disease burden [25, 26]. The objective of this study was to assess the public health impact and value of vaccination as assessed by the cost-effectiveness of a PCV13 or PCV10 NIP compared with no vaccination. These outcomes are presented for Algeria as the expected impact of the ongoing NIP and in Tunisia as the potential impact should an NIP begin.

Tables 2 and 3 depict the health outcomes and costs of implementing a universal PCV vaccination program in Algeria and Tunisia under the base case scenario and under the varying sensitivity scenarios.

In Algeria, compared with no vaccination, implementing a PCV13 vaccination program would avoid 7608 cases of IPD, 57,800 cases of pneumonia, and 283,588 cases of AOM and save 2177 lives from pneumococcal diseases per year (Table 2). Each year, PCV13 is expected to offset $25.7 M of medical costs in Algeria and $2.24 M in Tunisia, respectively. Under the assumption of a 2 + 1 vaccination schedule, PCV13 would be highly cost effective at (USD) an incremental cost-effectiveness ratio (ICER) of $308 per QALY (< 1 × per capita GDP) from the payer perspective. Running a similar analysis for PCV10 versus no vaccination, 1224 deaths and 270,483 total cases of IPD, pneumonia, and acute otitis media would be avoided, and PCV10 would be highly cost-effective at $731/QALY (< 1 × per capita GDP) from the payer perspective. Each year, PCV10 is expected to offset $17.6 M of medical costs in Algeria and $1.8 M in Tunisia, respectively In scenarios assuming a price of 14.13 and 12.56 for PCV10, the cost per QALY was $616/QALY and $500/QALY, respectively.

In Tunisia, a PCV13 vaccination program would reduce the impact of pneumococcal disease by 1305 cases of IPD, 4833 cases of pneumonia, and 54,957 cases of AOM, and PCV13 would save 308 lives compared with the absence of a program at a highly cost-effective ICER of $848/QALY (< 1 × per capita GDP) (Table 2). In Tunisia, a PCV10 program would prevent 172 deaths and over 56,610 total cases of IPD, pneumonia, and acute otitis media, and it would be highly cost-effective at $1366/QALY (< 1 × per capita GDP). In scenarios assuming prices for PCV10 of 14.13 or 12.56, the cost per QALY was $1405/QALY and $1205/QALY, respectively.

Table 3 indicates the cost-effectiveness of PCV10 and PCV13 under varying assumptions for the impact of indirect effects. A PCV13 vaccination program remained highly cost-effective, even under the most restrictive assumption that there were no indirect effects, in Algeria at $475 per QALY (< 1 × per capita GDP) and Tunisia at $1239/QALY (< 1 × per capita GDP). For PCV10, the cost under the assumption that PCV10 conferred no indirect protection was $731/QALY in Algeria and $1366/QALY in Tunisia compared with no vaccination. By assuming that there was indirect protection for IPD and pneumonia, the cost per QALY decreased from the base case scenario to $198/QALY in Algeria and to $650/QALY in Tunisia. PCV13 versus no vaccination is expected to be more cost-effective compared with PCV10 versus no vaccination in all scenarios. All results remained cost-effective (< 1 × GDP per capita GDP) after varying mortality and utility rates and under a 0% discount rate.

We used a well-established decision-analytic model to assess the cost-effectiveness in Algeria and Tunisia of a PCV13 pediatric immunization program compared with no vaccination and ran a similar analysis for PCV10. Compared with no vaccination, both PCV10 and PCV13 are cost-effective strategies in both Algeria and Tunisia. PCV13 prevents 348,997 total cases of disease in Algeria and 61,095 in Tunisia, and PCV10 prevents 270,483 and 56,610 total cases, respectively. A PCV13 program is expected to generate $25.79 M and $2.24 M in direct medical cost-savings in Algeria and Tunisia, respectively, offsetting a significant portion of the cost of vaccination. PCV10 can generate $17.6 M and $1.8 M in direct medical savings in Algeria and Tunisia, respectively.

Pharmacoeconomic analyses provide decision-makers with a holistic assessment of cost and benefits of vaccination programs and can be used as a tool to inform for future NIPs. This decision-analytic model has been applied in many settings [27‐30] and provides a robust estimate of cost-effectiveness for the current situations in both Algeria and in Tunisia under varying scenarios that represent potential uncertainties. Epidemiologic inputs used in the model were informed by country-level estimates from the literature.

Our findings are supported by economic evidence of the continued cost-effectiveness of pneumococcal vaccination with PCV13 around the world. For instance, a cost-effectiveness study in Tunisia reported PCV13 to be a highly cost-effective strategy compared with no vaccination [26]. In addition, a study on the cost-effectiveness of PCVs across 35 pooled lower-middle-income countries, inclusive of both Tunisia and Algeria, reported both PCV10 and PCV13 as cost-effective compared with no vaccine, though a PCV13 program would reduce the most disease and associated costs [25]. In Spain, PCV13 implemented as a 2 + 1 schedule was found to be a cost-effective intervention from the payer perspective, compared with no vaccination [46]. Similar results were reported for Portugal when comparing PCV13 to no vaccination [47]. Our results suggest both PCV10 and PCV13 are cost-effective. Due to the broader serotype coverage of PCV13, numerous European countries have implemented a PCV13 program to prevent the most morbidity and mortality due to S. pneumoniae [27, 28, 30, 48]. In part due to the cost-effectiveness of PCVs, Algeria implemented a PCV13 NIP in April 2016, and our findings suggest Tunisia would benefit from a similar program.

Several limitations must be acknowledged in interpreting these results. First, due to a lack of publicly available cost data, all direct costs were derived from local experts, utilizing a conservative view, potentially biasing our results to underestimate the value of an NIP [26]. Yet, because costs were equally applied to both PCV10 and PCV13 vaccination, the bias would likely be non-differential between the two vaccines. Second, the model extrapolated the indirect protection that has been observed for PCV7 to PCV13 (as a base case). Numerous real-world studies have demonstrated a reduction in IPD among adults after implementing a national PCV13 infant immunization program, supporting the relevant impact of indirect effects [9, 49‐51]. In a scenario analysis, indirect protection was assumed for PCV10. Nonetheless, even in a no indirect protection scenario analysis, each vaccine remained cost-effective in both Algeria and Tunisia. In the absence of country-specific epidemiologic data, global or regional disease estimates are an accepted method to inform gaps. However, future studies should aim to address these limitations by obtaining country-specific estimates for all disease states, as opposed to applying global or regional data, which may under- or overestimate the true disease incidence. In addition, the validity of these findings may be confirmed in future studies by assessing the impact of the implemented PCV program in Algeria.

A national program of pneumococcal vaccination can have a tremendous public health impact by preventing pneumococcal disease morbidity and mortality in Algeria and Tunisia. PCV13 has the highest coverage of local disease-causing pneumococcal serotypes and can offer significant prevention of disease through indirect protection, resulting in a highly cost-effective prevention program. This can lead to substantial health benefits and cost savings in North African societies.