IPD remain a global public health problem in both children and adults [1, 2]. Vaccination with PCVs recommended by the WHO since 2007 remains the best option to prevent IPD. Nowadays, the vaccination coverage throughout all the country is 100% since 2017 [17]. However, WHO recommends and encourages all the countries that have introduced pneumococcal vaccination in their NIPs to set up an IPD surveillance system to assess the impact of the vaccines. In response, the microbiology laboratory of the IR-UHC has carried out laboratory based surveillance of IPD for more than 25 years [7,8,9].
Based on obtained results, although the overall incidence rate of IPD in adult patients was < 1/100,000 populations, a significant reduction from 0.71 to 0.54/100,000 populations (P = 0.02) was observed during the early post-vaccine period and decreased to 0.47/100,000 populations in mature post-vaccine period (P = 0.0137) compared to the pre-vaccine period. The use of PCVs in vaccination programmes has also led to IPD incidence reduction among the unvaccinated population due to the herd effect in other countries. These results demonstrate the herd effect following the implementation of vaccination in the NIP in Morocco. However, given there are ~ 100 pneumococcal serotypes and PCVs only include a small number of these, subsequent serotype replacement by NVS may consequently start to cancel out any reduction (possibly substantial) in the overall disease burden initially achieved with the vaccine through both direct and indirect means. As it was the case in our study where the significance decrease in VS was accompanied by a dramatic increase in NVS in the mature post-vaccine period, as reported in many countries where they witnessed the emergence and increase of NVS during the PCV era [18, 19]. It is well established now that paediatric PCVs induce valuable herd protection that extends across the age range but also drive serotype replacement, and these have opposing effects on the overall disease burden [20].
Among the groups most affected by IPD, there is also the elderly population group. Our results showed a non-significant increase in the incidence of IPD during the early post-vaccine period. Contrariwise, there was a non-significance decrease of the incidence rate in the mature post-vaccine period compared to the pre-vaccine period (P = 0.11). This variation may be explained by a natural fluctuation of IPD incidence as already reported by Elmdagrhi et al. before vaccination in Casablanca [8]. Whilst Sweden reported no overall decrease in total IPD in those aged > 65 years old, vaccine type IPD in this age group did decrease [21]. Ireland similarly saw a decrease in cases of PCV7 vaccine serotype IPD in adults aged > 65 years in the post introduction of vaccine in the paediatric programme [22].
However, the absence of a herd effect in the older population has been reported in several countries [21,22,23]. In contrast, in Australia, a reduction of 71% (95% CI: 36%; 88%) was observed in the post-vaccination period in people over 60 years of age, reflecting the herd effect [24]. As the herd effect increases with the time since the introduction of vaccination in the NIP, we expect even greater indirect protection of that age group in the coming years. Furthermore, these data suggest an alternative solution to this age group. New higher valent PCVs could be considered for protecting Moroccan adults against pneumococcal diseases. Nowadays, adult PCV15 and PCV20 are now licensed (EU/US). Besides PCVs, The Pneumococcal Polysaccharide Vaccine (PPV), PPV-23, has been recommended in several countries around the world, but the Moroccan NIP does not include adult pneumococcal vaccination. Djennad et al. (2019) [25] supports limited/moderate short-term effectiveness of PPV23 against vaccine type IPD in those aged > 65 years which aligns with the consensus that PPV23 provides some protection against IPD in older adults, as is stated by Wang et al. [26]. However, evidence that PPV23 is effective against community acquired pneumococcal pneumonia in older adults continues to remain very inconsistent.
Furthermore, in some countries, especially in Europe, certain serotypes that are common in one age group, but rare in others, are increasing in incidence in groups where they were rare. This is the case in Finland with serotype 11A common in adults increasing in children, in France with serotypes 8 and 9 N common in adults increasing in children, serotypes 10A and 23B common in children increasing in adults and in Norway with serotype 24F common in children increasing in adults; serotypes 8 and 9 N commonly found in adults increasing in children [27]. In our study in Casablanca, Morocco, no serotype was particularly dominant in any age group.
In addition to the impact on IPD and serotype distribution, PCVs have been shown to be effective in reducing the prevalence of resistant strains in the countries where they have been introduced. In the present study, in contrast to the elderly population group, the prevalence of PNSP strains decreased from 23.94 to 8.77% during the early post-vaccine period (P = 0.02) and to 15.94% in mature post-vaccine period (P = 0.23) compared to the pre-vaccine period in adult population, while the strains with decreased susceptibility to co-trimoxazole decreased significantly both from 29.58 to 8.77% in early post-vaccine period and to 7.24% in mature post-vaccine period. As reported by Diawara et al., the rate of co-trimoxazole-resistant strains decreased following vaccination even in the children population [9]. Variable rates of PNSP strains have been reported in several regions. In Malaysia, the rate of PNSP strains was 22.4% between 2014 and 2017 [28], 27.5% in Iran between 2017 and 2019 and 75.3% in Tunisia between 2012 and 2016 [29]. Overall, the highest rates are reported in Africa (64.3%), the Middle East (46.4%) and North America (38.5%) [30].
It is important to note that this rate does not vary only by region and period of surveillance, it also depends on circulating serotypes. In Japan, antimicrobial susceptibility testing revealed that 88.9% and 89.4% of serotype 35B and 15A strains respectively were of PNSP [31]. In Tunisia, the two most frequent serotypes 19F and 14 represented higher rates of PNSP strains with 18% and 29.4% respectively [29]. In Casablanca, vaccination has significantly reduced the prevalence of multi-antibiotic resistant serotypes; PNSP strains were often associated with some pre-vaccine era serotypes covered by PCV including serotypes 9 V, 6B, 14, 19A, 19F and 23F [9]. As a result, the low rate observed in Casablanca during our study period would be linked to the persistence of 6B serotype and 19A in the early and mature post-vaccine period respectively. The study conducted in Taiwan showed that although the overall rate of β-lactam non-susceptible S. pneumoniae strains decreased in 2010 due to the decline of serotypes 19F and 23F, it has increased since 2012, partly due to the rise of serotypes 15A and 23A [32]. The rate of ceftriaxone non-susceptible S. pneumoniae strains remains very low but very concerning. Given that ceftriaxone remains a reference choice for the empirical treatment of IPD, selective pressure through overuse of this antibiotic could lead to increased rates of PNSP strains to this molecule as reported elsewhere [33]. However, regional study, maybe a national multisite scale study would be important for the future to highlight the country’s situation.
Limit of the study
Our study is a one site laboratory-based surveillance of invasive pneumococcal isolates. Regional study or a national multisite scale study would be important to highlight the serotype distribution and the antimicrobial susceptibility of invasive Streptococcus pneumoniae isolates in the whole country.
