Epidemiology of measles and mumps in Lebanon:
The literature is scant regarding the epidemiology of measles and mumps in Lebanon. The above data clearly portray that Lebanon has experienced several measles outbreaks in the past two decades. Given the <90% MCV1 coverage rate and the lower MCV2 coverage, Lebanon is still far from achieving the goal of measles elimination and is at risk of experiencing new outbreaks, especially with the decline in the proportion of seropositive young adults over the past 15 years. In 2011, Chamat et al. assessed the measles and mumps antibody titers of 502 medical and paramedical students in Lebanon showing a decline in seropositivity which equaled 86% for measles and 76% for mumps; this was attributed to the decreased incidence of both diseases [16]. In 2016, Ozaras et al. described the impact of the neighboring Syrian crisis on the Lebanese public health scene; the influx of more than 1 million Syrian refugees living in poor sanitory conditions into Lebanon had created a favorable medium for the circulation of multiple infectious diseases [11]. This might explain increases in the number of measles and mumps cases in 2013 and 2014 respectively, as seen in Figure 3. Fortunately, the LMPH reacted and initiated a national immunization campaign in 2014 [11]. In 2019, Kmeid et al evaluated the vaccination status of 571 Syrian and Lebanese children, showing low compliance with the measles vaccine (55-70%) and a higher compliance with the MMR vaccine (96-100%). Socioeconomic factors seemed to play a major role in vaccination compliance [17], while contracting measles has been itself associated with a significant economic burden [18].
As for morbidity, previous measles outbreaks in Lebanon were associated with a case fatality rate of 2 per 1000 reported cases [6]. It has been revealed that new strains like the B3 strain, which is a more transmissible genotype, are becoming increasingly widespread leading to new epidemics worldwide [19]. Data in Lebanon showed that the measles strains in 2013 were B3, D8, and H1 while mumps strains are yet to be identified [6].
Age distribution of measles & mumps and current vaccine protocol:
In Figure 1, it is clear that children aged between 1 and 4 years are the most susceptible individuals to contracting measles. Early in life, children usually acquire passively transferred maternal antibodies providing them with immunity against the virus. These antibodies are usually cleared within 6 months from the newborn’s serum, and as a result, children become more susceptible to infection. There is no data in Lebanon that would help assess the seropositivity of women of childbearing age against measles or mumps. However, children from immunized mothers may still be susceptible to infection despite maternal immunization since maternal antibody levels can be affected by certain factors like prematurity and declining maternal immunity due to decreased exposure to wild-type viruses. [20, 21]
The Center for Disease Control (CDC) recommends routine vaccination of children with the measles-mumps-rubella (MMR) vaccine in a 2-dose series scheduled at 12-15 months and 4-6 years with the possibility of giving the 2nd dose as early as 4 weeks after the 1st one. [22] The WHO recommends that the first dose be given at 9 months when attack rates are high and risk of serious disease among infants exists. In low risk areas, the first dose can be administered at 12-15 months. Although the second dose is generally administered at school age (4-6 years), it may be given as early as one month following the 1st dose, depending on the measles status in the country. [23] In Lebanon, the LMPH adopted a vaccination strategy where children will receive a zero dose (MCV0) at 9 months followed by a first dose of MMR (MCV1) at 12 months and a second dose of MMR (MCV2) at 18 months [24]. This appears to be well warranted given the significant number of measles cases in the younger ages as seen in Figure 1.
It is clear that measles is a disease of the pediatric population in low vaccination areas, but adult cases must not be overlooked (Figure 1). A recent study by the WHO revealed that almost 77% of the potentially preventable cases of measles were among children aging less than 15 years. Although the average number of measles cases in individuals older than 14 years in Lebanon (Figure 1) is much less than the 45% reported by the European CDC database in 2017 for the same age group, it remains a significant percentage that should not be ignored [25]. A study implemented in China revealed that the seropositivity rate of measles antibodies was significantly lower in subjects aged 15-19 years than those aged 5-9 years. This result was attributed to the waning antibody titers especially that there are no circulating wild-type viruses to confer natural immunity. It is rather challenging to implement a vaccination campaign to target adults. It would be more feasible to conduct an immunization program that involves high school students when they are still in mandatory education. This will protect those teenagers from future measles infections and will contribute to the protection of their children via increasing the measles maternal antibody levels.
As can be seen in Figure 2, it is evident that mumps cases are most commonly observed in children and adolescents. In a recent study by Cardemil et al, there was a call for a third shot of MMR to control mumps outbreaks in university students in the face of waning immunity [14]. It is reasonable to assume that the resurgences of the mumps outbreaks in Lebanon for those who are 10-19 years old could be attributable to waning immunity [14]. Given this common theme of waning immunity, revaccination with MMR should be encouraged in an attempt to adopt a strategy that will aid in measles and mumps elimination and prevention of the Congenital Rubella Syndrome. In one study, revaccination of secondary school students regardless of previous measles vaccination or disease status resulted in complete protection, raising seropositivity from 91% to 100% making it a very promising initiative. [26]
Measles and Mumps relationship:
It appears from Figure 3 that there is a close relationship between the number of incident measles and mumps cases in Lebanon, and a clear pattern can be noticed when examining the outbreaks of each of these diseases. Over the past 20 years, after every increase in measles cases among the Lebanese population, a parallel increase – although less intense – in mumps cases can be observed one or two years later. This trend has not been established elsewhere in the literature, yet it might be expected as the two diseases share a common vaccine. Should the rise in measles cases reflect a shortfall in the vaccination strategy, it would be logical to expect a deficiency in the immunity against mumps as well, and thus mumps outbreaks paralleling the measles outbreaks. Taking into consideration that the mumps vaccine is less immunogenic than that of measles [27], this might be of immense importance for public health strategies, as it might help anticipate any mumps epidemic before it occurs. For example, Israel witnessed an outbreak of 262 mumps cases between January and August 2017 although vaccination levels reached ≥ 96% [28]. This was concomitant with a measles outbreak during the summer of the same year. [29].
It is important to note that measles outbreaks will have long-lasting impacts that could be explained by measles-induced immune damage. Epidemiological studies from the USA, Denmark and England back in 1940, found that rates of non-measles infectious disease mortality were tightly coupled to measles incidence—with a greater mortality rate when the incidence of measles was higher. Using computer models, measles infection was found to predispose children to all other infectious diseases for up to a few years, due to reduction in host resistance following measles infection that may extend over a period of more than 2 years [30]. In vitro and in vivo studies attributed this to the immunosuppression effects of measles that caused depletion of B and T lymphocytes. The effect is more on the memory than naïve cells in the case of T cells [31, 32] but it is equal on both memory and naïve B cells [31, 33]. Thus, after fighting off measles, the immune system makes a comeback but has ‘forgotten’ what it had once learned. The child’s immune system has to start afresh, rebuilding immune protection against viruses and bacteria it had previously fought off.
While we are still far from defeating measles, we can use the measles epidemics to review our vaccination strategies, reassess the level of herd immunity, and prepare our healthcare systems for an imminent mumps epidemic as per the established pattern. In light of the rising number of measles cases in 2018, the LMPH has established an outbreak control strategy via increasing training sessions for health centers, hospitals, and ESU teams, spreading public awareness through publishing a weekly bulletin on measles surveillance, sending out posters and other advocacy materials, and initiating a massive media campaign. Immunization activities with the MMR vaccine in vulnerable areas were conducted to help curb the ongoing measles outbreak and help prevent possibly incoming mumps outbreaks [34].
Measles cases distribution according to vaccination status:
Figure 4 shows that most of the measles cases were unvaccinated. Multiple factors might affect the accuracy of these figures and numbers. One factor that must be taken into consideration is the number of vaccine doses administered; many of those who claimed they contracted measles despite vaccination might have received an insufficient dose of the vaccine. This misunderstanding might thus skew the percentages and falsely elevate the numbers of those contracting measles despite vaccination. Only 61.92% of the cases had a documented vaccination status, which still lags behind the target set by the WHO at a minimum of 80%, indicating a far-from-sufficient immunization system [15]. The possibility that non-vaccinated persons are clustered together should be considered, implying that the estimated vaccination coverage rates do not reflect the status of the general population but rather represent that of a higher risk subpopulation [35].
Referring to Figure 4, 52.26% of people who contracted measles were unvaccinated. A recent study by Mansour et al, found several factors that hinder vaccination, and these include socio-demographics, as well as knowledge, beliefs and practices associated with age-appropriate vaccination [36]. Mothers may perceive that the vulnerability to disease lessens with older age considering the first dose as the main source of protection whereas boosters are regarded as add-ons. Subsequent non-compliance will result and their children will be lost to follow up [37].
The current used vaccine in Lebanon is an-attenuated live measles vaccine that belongs to the Schwartz strain according to the WHO [6]. As mentioned earlier, individuals in Lebanon get a total of 3 doses of vaccine against measles. National catch-up campaigns against measles are conducted in case of any outbreaks as was the case in 2001, 2008 and 2013 in an attempt to enhance vaccination coverage and reduce the number of susceptible individuals. In an American study that discussed one of the largest measles outbreaks among highly vaccinated students, whose source case had coincidentally contracted the virus from Lebanon, it was revealed that students who had received both doses of the vaccine outside the United States were more susceptible to the infection than those who received both doses in the United States [38]. This was partly attributed to the quality of storage of the vaccine (the cold chain). Measles vaccine should be stored at 2-8°C as improperly stored vaccines may fail to provide protection against the disease. The quality of vaccine storage should be reviewed in Lebanon in lights of our results. Besides, immunological and genetic research is recommended to evaluate vaccine effectiveness against the aforementioned strains and identify any new ones that might not be covered by the available vaccines [19].
Recommendations for measles prevention:
The presented data should serve as a guide for the strategies that must be followed in the current fight against measles. The WHO has published a global strategy which can serve as the base upon which we build our own national strategy [2]. Active surveillance of measles contacts should be implemented in case national vaccination campaigns are not possible, regardless of the vaccination status; in fact, secondary measles contraction in vaccinated individuals can present itself with symptoms dissimilar to those typical of the disease, allowing viral circulation in the absence of active monitoring [29]. This has been the case during the Israeli outbreak where the primary case presented with only fever and rash which made it quite challenging to suspect measles [29]. More to the point, the surveillance system must also improve in tracking vaccination through encouraging families to hold onto home-based records [15]. This is to be bolstered by routine re-vaccination of high-risk individuals including health-care workers and contacts of measles cases in a strategy similar to the ring vaccination adopted in eradicating other viruses like the Pox virus; this would help limit the dissemination of the virus and lead to eventual elimination [19].
Several infectious disease outbreaks were noted in Lebanon in correlation with the huge influx of Syrian refugees into the country [11, 39]. Data from Syria have shown subpar levels of first dose coverage of the measles vaccine ranging between 50-79% among their population [8]. The Italian experience showed that the migrant communities are not necessarily representative of their source population when it comes to measles vaccine coverage rates [40]. The discrepancy between migrants and their source population reflects the need for special screening and vaccination campaigns in migrants and refugees in Lebanon.
One of the cornerstones in the strategy to eliminate measles will be building public trust in the measles vaccine. Ever since the spread of the later-falsified MMR-Autism theory, measles vaccination rates witnessed a hefty drop in some regions in the Western world. The UK was declared endemic for measles in 2008, with some areas of London and Ireland reaching a vaccination level of only 60%. The United States also witnessed several outbreaks in the current decade with vaccination levels as low as 50% - far from the 95% herd immunity threshold [41]. Although the advocates of this theory are decreasing, some parents are still exhibiting a general anti-immunization approach [42]. Effective communication teams should be created and invested in to target different audiences and inform them on the importance of vaccination and the dangers of unvaccination [2]. This is highlighted in a recent study by Hoffman et al, which warned that social media outlets may facilitate anti-vaccination by enabling the diffusion of century old arguments and techniques and facilitating anti-vaccination behaviour [43].
Last but not least, investing in local capacity building and research projects to understand the epidemiology and behaviour of the measles virus in relation to the population dynamics in Lebanon is of immense importance to establish national strategy and guidelines [6].
Recommendations for mumps prevention:
It is essential that clinicians and individuals are made aware of any ongoing mumps outbreaks to increase suspicion and reporting of the disease. The LMPH must arrange awareness campaigns in national high schools and universities to educate adolescents on the clinical presentations and complications of mumps. High school and college students should be encouraged to maintain adequate hygiene by washing hands before meals and after toilet use and minimizing contact with their peers [44]. In the face of outbreaks, the effectiveness and feasibility of booster vaccination campaigns must be considered. Cardemil et al. suggest that a booster MMR dose helps prevent mumps cases among adolescents [14]. This was later backed up with evidence of the possible contribution of a third dose of MMR in preventing mumps infection in military recruits with waning antibody titers [45], especially that a study by Lewnard et al. showed that protection from the mumps vaccine lasts for 27 years on average [46]. Principi et al. acknowledge the effectiveness of booster doses in controlling outbreaks but argue that it is not clear whether these boosters can actually prevent them as the protection they provide wanes over time [47]. Another hurdle to be considered is the emergence of new mumps strains that are resistant to already established vaccines; it is thus recommended to maintain an active surveillance of circulating strains so that new vaccines including newer mumps strains are developed [47].
Limitations:
Our study is a retrospective descriptive analysis based on data gathered by LMPH-ESU about reported cases of measles and mumps. It lacks key information regarding the seroprevalence of measles and mumps in the whole population and in specific groups: mainly women of child-bearing age. Unfortunately, data showing measles cases with only one dose of the measles vaccine is also lacking, and the presence of a high percenetage of measles cases with unknown vaccination status remains a major issue that may have affected and skewed our analysis. As for mumps, no information was available about the circulating strains and vaccination status of those affected.