The current monkeypox outbreak: Knowledge gaps and research priorities

Since May 2022, the world has witnessed the resurgence of the largest outbreak of monkeypox (MPX) after its initial diagnosis among a group of children from the Democratic Republic of the Congo (DRC) in 1970 [1]. This continuous surge could be explained by several factors. First, the cessation of smallpox vaccination after eradication in 1980 has been associated with an increased population lacking orthopoxvirus cross-immunological defense. Second, advances in civilization and rapid global travel facilitate previous sporadic cases and localized clusters to quickly shift as global epidemics. Finally, the possibility of mutations in the viral genome and their implication in MPX transmission and pathogenesis would not be ignored [2]. To secure everyone's health, the necessity for health equity and global connectedness has been highlighted. The current situation imposes taking a broader perspective on monkeypox in relation to emerging infectious diseases and pandemic preparedness. Highlighting current research priorities support the worldwide interdisciplinary collaborations to control MPX.

Infection control perspective. Lessons from previous global epidemics of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and recently Coronavirus disease 19 (COVID 19) showed that a comprehensive preventive plan should be urgently considered by clinicians, laboratorians, epidemiologists, and health decision-makers in all countries. Besides, the complex epidemiological profile of the current MPX outbreak in non-endemic countries [1] warrants effective preventive strategies to include both healthcare and community settings. In healthcare facilities, accurate and rapid diagnosis of active cases seems paramount. This task needs well-trained staff supported with all clinical and laboratory diagnostic tools to avoid missing confirmed, possible, or probable cases. In parallel, the protection of healthcare workers should be emphasized through strict adherence to infection control procedures including standard, contact, and droplet precautions for both inpatient wards and outpatient clinics [3], [4]. It is worth noting that hand hygiene and personal protective equipment (PPE) remain the cornerstone for control of MPX transmission and preventing cross-infection. In community settings, the role is to stop MPX transmission by breaking the infection chain. Intense surveillance activities with active notification measures would help improve the quality of patient care and detect and manage household contacts to prevent further virus transmission [4]. The role of animal reservoirs and how to prevent spillover is questionable. Education in a one-health context can protect against many pathogens [5]. Social science considerations can play a critical role in messaging and in interrupting transmission, reducing stigmatization and misinformation, and improving access to care [6].

Although the smallpox vaccine yields immunologic protection against MPX, its utility in the current 2022 outbreak is unlikely. This could be explained by the cessation of smallpox vaccination programs in the past 50 years, and the lack of vaccine supply in limited-resource countries. Smallpox and MPX vaccines can be used as pre- and post-exposure measures. Pre-exposure vaccination is best administered with second or third-generation vaccines such as ACAM2000, LC16m18, and JYNNEOS vaccines to protect contacts and susceptible individuals at high risk. Post-exposure vaccination can be administered within 4 – 14 days after exposure to ameliorate the infection and decrease the severity of the disease [7], [8]. Earlier experience with COVID 19 shows that heterologous vaccine programs utilizing vaccines from different platforms to augment vaccine-induced immunity are highly warranted to stimulate robust immunity which could eventually prevent viral infection and its transmission [9]. However, public confidence in vaccines should be reinforced [10]. The following research questions need to be addressed: How vaccines can and should be used, safety data, Cost, vaccine delivery strategies, and duration of vaccine effect. Could vaccines be used to generate herd immunity? Could asymptomatic vaccinated people transmit it? [5]. Following and upon availability, a multidimensional approach to increase the vaccine acceptability rate will be required [11].

Diagnosis and management perspective: Equity in the accessibility of laboratory diagnoses encounter the currently exerted efforts. The need for a biosafety level 3 for sample processing and laboratory work is a challenge, especially in limited-resource settings. The best testing techniques for finding cases are still not adequately addressed. Data on antivirals is evolving, and their effectiveness is still being investigated [12], [13]. The Food and Drug Administration (FDA) and European Medicines Agency (EMA) highly support randomized trials. It is crucial to specify who needs to be treated [5].

In conclusion, there is still much to know about monkeypox research priorities that should be promoted on both national and international levels. Sharing best practices is essential. Global research coordination is required to promote equity, generalizability, timeliness, and local competency. Interdisciplinary research teams could be of help.