Knowledge, awareness, and worry about human monkeypox and attitude toward its vaccination in non endemic countries: a concise critical review

Background: In May 2022, the world has seen the emergence of human monkeypox, a new zoonotic viral disease in multiple non endemic countries. This health threat has been associated with high worry especially after the COVID-19 catastrophe. Also, the population is exposed to a huge amounts of information making them exposed to false information which could lead to embracing conspiracy theories. Thus evaluating the level of knowledge and the attitude toward vaccination are of great importance to raise them for the categories with low levels of knowledge and acceptance. This scoping review was conducted using PRISMA guidelines with the aim to evaluate the level of knowledge and awareness about monkeypox and the attitude toward its vaccination by selecting studies. Results: The selection process allowed to include 16 studies in this review. These studies were conducted in 10 countries in Europe and Asia. 9 studies were exclusively related to monkeypox knowledge and awareness, 2 studies were exclusively related to monkeypox vaccines while 5 studies treated the two subjects. These studies were mainly conducted among healthcare workers or among the general population. Results showed an unsatisfactory level of knowledge and awareness with some categories including physicians and aged individuals as the most informed. Regarding vaccination, Results showed that vaccine hesitancy is still common for both healthcare workers except among Chinese healthcare workers where the rate of vaccine acceptance was estimated at 90.1%. Conclusions: This review could be helpful in the understanding of the knowledge and awareness and vaccines hesitancy in the �rst months of the emergence of the HMPX by comparing their evolution in the future studies.


Background
The humanity is in a continuous battle against infectious diseases since long times.After the pandemic of COVID-19 and its drastic health and economic consequences, the world is again witnessing a new health threat that consists on the re-emergence of a zoonotic disease in different non endemic countries: the monkeypox disease [1].This disease is caused by a Monkeypox virus.A double-stranded DNA virus which belongs to the Orthopoxvirus genus, the Chordopoxvirinae subfamily of the Poxviridae family responsible for multiple diseases in human and animals.Monkeypox virus is one of the four Orthopoxvirus species pathogenic for humans with variola virus, cowpox virus, and vaccinia virus [2,3].
Despite the name of monkeypox, the natural reservoir of this disease is still unknown.Non-human primates (like monkeys) are one of the main suspected reservoirs in association with other African rodents and mammals [3,4].Further studies are however necessitated to identify the virus' reservoir(s) and its main route of its circulation and its conservation in nature.A possible risk factor is eating inadequately cooked meat and other animal products of infected animals [5].
Historically, this viral zoonotic disease was rst reported on 1958 from lesions of an imported macaque in a Danish laboratory hence, the name of monkeypox.Later, the rst human case was detected in a 9years child in 1970 in RDC [6].Since then, thousands of con rmed and misdiagnosed cases in multiple outbreaks were reported in Africa, especially in the Central and Western African countries (Benin, Cameroon, Central African Republic, Cote d'Ivoire, Democratic Republic of the Congo, Gabon, Ghana, Liberia, Nigeria, Republic of the Congo, South Sudan and Sierra Leone) considered currently as an endemic region (Most of cases were reported in the Republic Democratic of Congo).Consequently, two genetic strains of Monkeypox virus have been characterized including the West African and the Central African clade geographically separated with epidemiological and clinical differences.The number of cases and outbreaks is increasing continually in these countries especially since the cessation of the smallpox vaccination in the years 1980s [2,5,6].
Out of Africa, the rst cases were reported in 2003 in the USA following importation of infected animals from Ghana.Later cases from different countries were also reported including United Kingdom (2018-2019 and 2021) and Singapore (2019) and also in the USA in 2021 [6].
Since May 06, 2022 the world has known the re-emergence of multiple cases in different non-endemic countries with no history of travel to endemic countries.As of November 10, 2022, the number of cases has reached 79,151 con rmed cases [7].
The West African clade was identi ed as the cause for the rst cases reported in non endemic countries.
Later, Genome sequencing of strains from con rmed case in Portugal, has shown a close similarity with the strains isolated from exported cases from Nigeria to the United Kingdom and Singapore in 2018 and 2019 [5,8].
The virus is mainly transmitted from person to person close contact with lesions, body uids, respiratory droplets and contaminated materials such as bedding [8].
Clinically, the disease is generally self-limiting with of the formation of lesions, skin nodules or disseminated rash but could be severe in some individuals, like children, pregnant women or immunede cient persons.The incubation period of Monkeypox is usually from 6 to 13 days but can range from 5 to 21 days.Even, the case fatality rate varied from 3.6-10.6% in the endemic countries, no deaths were reported in the recent outbreaks in the non endemic countries [6,9].
In response to this public health threat, the World Health Organization has released a range of recommendations to limit its spread.These recommendations are related to surveillance, case investigation and reporting, contact tracing, risk communication and community engagement, clinical management and infection prevention and control in health care settings [1,5].Later, the WHO declared the human monkeypox outbreak as a public health emergency of international concern since July 2022 [13,14].The rapid spread of this disease has engendered a signi cant worry among the public [15] which is due mainly to the lack of knowledge and the embracing of conspiracy beliefs towards emerging viral infections [16].Additionally, the health authorities are again asked to communicate and convince the population to agree with preventive measures and a probable future vaccination especially after the COVID-19 hard experience.
The present review was conducted to evaluate the level of knowledge and awareness and the attitude toward monkeypox vaccines and the associated factors which will be a start point about human monkeypox knowledge and vaccine acceptance.

Methods
This review was conducted following the PRISMA guidelines [17].Published papers in PubMed/Medline that aimed at evaluating monkeypox knowledge, attitude, awareness and vaccine hesitancy/vaccine acceptance using a survey/questionnaire were included in this review.
Included article in this review (inclusion criteria) contains: (i) English published articles indexed in PubMed; (ii) cross sectional studies among the general population, healthcare workers and students; and (iii) studies aiming to evaluate monkeypox awareness, knowledge, worry and attitude toward monkeypox vaccine.
Articles with the following criteria were excluded (exclusion criteria): (i) Preprints (non peer-reviewed manuscripts); (i) articles that did not deal with monkeypox knowledge awareness and vaccine intention; and (i) articles published with another language than English.At the end of the screening of titles and abstracts, data extraction was done and articles were classi ed according to the following criteria: name of the authors, country/countries in which the survey was conducted, date of survey, target population, sample size, level of knowledge, awareness and worry, used tool of evaluation of knowledge, associated factors, vaccines acceptance and its associated factors.

Results
The research procedure found a total of 135 published papers in the current year.At the end of the screening and selection process, 16 studies were included in this review.All the selected studies were conducted in Asia (11) or in Europe (4).They were from 9 different countries including Saudi Arabia (5 studies), Jordan (2), Kuwait (1), UAE(1), China (1), India (1), Italy (2), France and Belgium (1) and Romania (1).
These studies focused mainly on the awareness, knowledge and attitude toward HMPX vaccine.Some of them were however exclusively related to knowledge and awareness (9) while 2 studies were exclusively related to vaccination and 5 studies studied the two subjects (knowledge and vaccination).Among these studies: 7 studies were related to healthcare workers, 3 studies were conducted among the general population while others were conducted among certain categories including students (1), medical students (2) and adults (1).The studies were conducted between May and August, 2022 using in general an online questionnaire with a sample size varying between 314 to 1546 individuals (Table 1).The level of knowledge was estimated in the different studies using different scales.These scores or the level of knowledge were conducted by estimating the level of correct responses to a number of items related to HMPX ranging from 9 to 27 items.(Table 1).These items are related to the etiology, the epidemiology and transmission, the clinical signs and the treatment and preventive measures.The authors qualify generally a high level of knowledge as a level higher than the median level of knowledge of the studied sample.
Overall, a poor to medium level of knowledge was obtained in almost all studies.The percentage of the population with a high score varied from 22.8% [22] to 56% [15].The lower score was obtained among university students while the highest score was obtained the general population.
Multiple factors were associated with high levels of knowledge.Age and educational level were the most cited factor [16,18,20,[22][23][24][25].Other factors were also cited and were mainly related to the professional position and pro le, the source of information and conspiracy beliefs [25].
Regarding the sex, results of two studies are opposed.Sallam et al [16] reported that male are more informed while Jairoun et al [24] showed that females had the highest level of knowledge.The last category (females) in association with individuals who were not infected with COVID-19 and medical students are more worried about human monkeypox as reported by Aljamaan et al. [21] In this way, the level of worry varied from the different studies.This level varied from 26.37% of the total population [26] and 28.5% among Frensh and Belgian healthcare workers [27] to 60.4% among the general population in Saudi Arabia [15].Moreover, 37.5% of the studied Saudi healthcare worker were more concerned about HMPX than COVID-19 [21].
Vaccination Acceptance: results obtained from the different studies showed that the lowest vaccination acceptance rate was obtained in the general population in Romania 29% [26] while the highest rate was obtained among healthcare workers in China (90.1%) [28] (Table 3).The rate of acceptance/willingness in the general population varied from 29% [26] to 50.6% [15] while it varied from 55.4% [27] to 90.1% [28].additionally, if 55.4% among French and Belgian healthcare workers agree to be vaccinated this rate of acceptance reaches 79.1% in the case of the spread of HMPX within the general population [27].

Discussion
The ongoing monkeypox outbreak is the nth zoonotic disease threatening the public health through the world.While the world has not yet recovered from the COVID-19 pandemic, the current monkey pox disease has since May 2022 in some non endemic countries provoked a real concern.In fact, known as an endemic disease in central-western African countries since the years 1970s, the disease has been reported out of Africa since the year 2003 in multiple countries with a link of travel to endemic countries.
However, the reemergence of disease in non endemic countries in the current years has gained more concerns for multiple reasons: rst, multiple sporadic cases were reported simultaneously in different countries with no travel link to travel to endemic countries, second he rapid spreading of this disease, the zoonotic character and the lessons learned from the COVID-19.
Thus the current review aimed to report the level of knowledge and awareness in non endemic countries and the attitude toward HMPX vaccination.
The ndings of this review showed a moderate level of awareness about HMPX.In fact, if 24.8% and 27% of dental professionals [18] and healthcare workers [19] respectively never heard about monkeypox disease before the current outbreak is explicable due to the disease was typically reported in endemic countries, the low level of awareness about the current outbreak reported among healthcare workers and medical students is surprising.These results could be related to the fact, that this studies were conducted during the rst months of the emergence of the diseases and no cases were reported in the countries where they were conducted [16,18,25].The level of awareness could be as 26.7% among adults [20].
Regarding the knowledge about HMPX in the different studies, and even multiple scale were used to assess the level of knowledge, results showed generally a poor to moderate level even among healthcare workers and university students [23,25].This low level of knowledge could be explained by the fact that the population in the non endemic countries are in the discovering stage of HMPX.
The low level of knowledge obtained among healthcare workers in some studies is however alarming.In fact, this category is considered as a key group in the ghting and the prevention against the spread of health threats and especially following the emergence of new infectious diseases [16,29].They represent also the main source of information about health threat for the general population and thus play an important role in raising knowledge and are the main partner in any awareness campaigns.Of notes the same observation was reported in Indonesia in some studies conducted in 2020 [30,31].Some of the selected studies of this review have however shown that being a healthcare workers is associated with high level of knowledge the general population [23] and physicians are more informed [32].
In addition, other factors were associated with high level of knowledge.Even the categories were not standardized in the different studies, older individuals and those with higher educational level were shown to be more informed about HMPX than their counterparts [16,18,20,22,24,25,32].Other factors were also cited including the source of information and conspiracy beliefs.In fact, the conspiracy theories beliefs are the main source acquiring misinformation and thus reducing the level of knowledge and awareness [16].
For the effect of sex on the level of knowledge, most of studies failed to nd a statistical relationship between sex and HMPX knowledge while the results of Sallam et al [16] were in favor of males and those of Jairoun et al [24] were in favor of females.In the same way females were more worried about HMPX than females.These may be due to the fact that females were reported to believe more in rumors and conspiracy theories than males [25].Medical students and individuals who were not infected with COVID-19 were also more worried about human monkeypox [21].
Regarding attitude toward vaccination, apparent is a high level of acceptance among healthcare workers in China (90.1%).These results may be due to the experience of China with the emerging disease especially after he tow experience of SARS and COVID-19.
Moreover, healthcare workers wore more likely to accept HMPX than the general population.This results make sense knowing that healthcare workers are in the frontline in ghting any health threat and thus the risk of their contamination and thus they are prioritized in any vaccination strategy as it was the case of COVID-19.These results are in accordance with the results of previous studies conducted in Indonesia before the COVID-19 pandemic where the rate of acceptance could reach 96% [33,34] The second important results is the high rate of hesitancy among the general population especially in Romania were only 29% had a favorable attitude towards vaccination [26].These low rates of acceptance/willingness go in the same direction with the rates obtained for COVID-19 vaccines especially in the rst months of their approvals.National and international health authorities should make more efforts the sensitize about the bene ts of vaccines in the struggle of infectious disease and the last example is the COVID-19 pandemic.Of notes, the phenomenon of vaccine hesitancy is classi ed as one of the top 10 public health threats by the WHO [35].
The selected studies reported some factors that were in favor of vaccination which include COVID-19 infection and worry, professional place occupation, age, educational level, In uenza vaccination and some beliefs which could help in the strategy of ghting the phenomenon of vaccine hesitancy by raising awareness about the importance of vaccination targeting the hesitant categories.
This review presents some strengths and limitations.Regarding the strengths, to our knowledge, this is the rst review in its nature to deal with monkeypox knowledge and attitude toward its vaccination in non endemic countries.Also, the review was conducted using PRISMA guidelines.Thus the nding of this review could be used as a baseline in estimating knowledge and vaccines acceptance in the rst months of the HMPX outbreak.
For the limitations, They are mainly due to the study included only manuscript available in PubMed which could affect its nding.It is however conducted in one of the most important engine research about medical and biological studies allowing to include only indexed studies and make of this review a concise and succinct.In addition most of these studies were conducted in the initial stage of the MPX outbreak and thus the level of knowledge ad awareness could increase over time.Another limitation is related to the evaluation of the level of knowledge where different scales wee used making the comparison between the different reason inadequate.At last the rate of acceptance was evaluated in the absence of a speci c vaccine against HMPX which could change according the evolution of the situation and the probable approval and introduction of a new HMPX vaccine.

Table 1
General characteristics of the included studies [21]lts of the different studies showed that different levels of awareness were obtained (Table2).In fact, according of the studies of Kaur et al.[18]and Ricco et al[19], 24.8% of dental professionals and 27% of healthcare workers respectively never heard about monkeypox disease before this pandemic.Additionally, the level of awareness about the current pandemic could be low among healthcare workers (45.05%) [16], dental professionals (39.5%) and health students 50.24%[16].This level is lower among the general population where 26.7% of the Italian adults heard about the current outbreak of HMPX as reported by Gallé et al.[20].Another study was based however of a self reported awareness where the participants declared that they have a low (4.1%), a moderate(36.8%)orahigh (23.24%)level of awareness[21].

Table 3
Attitude toward vaccination in the different studies Participants were asked if healthcare workers are prioritized Regarding associated factors with HMPX vaccine acceptance, results showed that COVID-19 infection and worry, professional place occupation, age, educational level, In uenza vaccination and some beliefs are all a predictor factors of acceptance/willingness to vaccinate. *