Tackling the resurgence of monkeypox in Africa: challenges and strategies for eradication

Monkeypox is a zoonotic viral disease previously limited to isolated regions of Central Africa. The reasons for resurgence of the disease in Africa are multifaceted, including waning herd immunity acquired from smallpox vaccination, the evolution of the virus, disruption of health systems by the COVID-19 pandemic, and lack of adequate global funding for monkeypox research and intervention commodities in African countries. Policymakers should regulate the distribution of African rodents, and healthcare workers must be trained in monkeypox surveillance and case definition. The adoption of the mobile digital Surveillance Outbreak Response Management and Analysis System (SORMAS) is recommended to improve disease surveillance and outbreak management. African governments must collaborate with global leaders and pharmaceutical industries to develop and distribute monkeypox vaccines and specific therapeutics. These measures are crucial in preventing and managing monkeypox outbreaks.


Introduction
Following the eradication of the smallpox virus, the monkeypox virus is the most dangerous virus in the orthopoxvirus genus [1] .Monkeypox is no longer a rare viral zoonotic disease limited to isolated regions of Central and West Africa; rather, it is a disease with great risk for global transmission and bioterrorism.The virus was first isolated in experimental monkeys in 1958, and the first human case was documented in the Democratic Republic of the Congo in 1970 [2] .Many cases have since been reported in neighboring African countries.Previously, confirmed human cases outside of Africa were only documented in the United States (47 cases) in 2003, the United Kingdom (4 cases), and Israel (1 case) in 2018, as well as in Singapore (1 case) in 2019 [2] .
Monkeypox is endemic in African countries, where it caused large outbreaks between 2017 and 2019 [1] .Since then, the disease has been under control thanks to appropriate public health measures implemented by Africa's Centres for Disease Control and Prevention, such as active surveillance, contact tracing, and public awareness campaigns [2] .However, the re-emergence is clearly the result of a breakdown in those interventions.
Monkeypox is a potentially fatal viral disease with a 10% case fatality rate if not controlled and treated promptly [3] .This article aims to highlight the challenges that have led to the disease's resurgence in Africa and to recommend practical and long-term solutions with global implications.

Epidemiology, transmission, and risk factors of monkeypox in Africa
The virus was first identified in monkeys in a Danish laboratory in 1958, hence the term monkeypox [4] .In Zaire (now the Democratic Republic of the Congo, DRC), a 9-month-old boy was found to have the first human case in 1970 [3] [5] .Since then, monkeypox has spread to other African nations, primarily in Central and West Africa, and has become endemic.In DRC, there were 6257 suspected instances of human monkeypox recorded in 2020 alone [6] and 1238 new cases were reported in the first four months of 2022 [7] .The Central African clade is responsible for the majority of human monkeypox cases (Fig. 1) [8] .
Humans can contract the monkeypox virus by coming into contact with an infected person or animal or by coming into contact with contaminated objects [7,9] .A total of 54 recorded occurrences of human monkeypox between 1970 and 1979 suggested that the monkeypox virus still exists in animals and that humans are merely incidental hosts [10] .Animals can transmit diseases to humans through open wounds, mucosal membranes, or respiratory tract droplets [2] .Consuming undercooked meat and other animal products that come from diseased animals is a potential risk factor.
The routes of transmission for human-to-human monkeypox are believed to be direct contact with the skin lesions or bodily fluids of an infected person, inhalation of respiratory droplets (during prolonged and close face-to-face contact), or contact with recently contaminated surfaces, objects, or fabrics (such as bedding, clothing, or towels) [2,7] .Hugs, massages, kisses, extended face-to-face contact, touching fabrics, and items during sex with a person infected with monkeypox, and intimate contact (sex that is oral, anal, and vaginal, or touching the genitals or anus of an infected person) are all examples of direct contact.
In general, endemic monkeypox is self-limited, with case fatality rates ranging from 1 to 10% depending on the lineage [8] .Fever is frequently the first sign of illness, which is then followed by the appearance of numerous papular, vesiculopustular, and ulcerative lesions on the face and body as well as a noticeable lymphadenopathy [11] .Pneumonitis, encephalitis, keratitis, and subsequent bacterial infections are complications [11] .However, it is unknown if effective antiretroviral therapy (ART) for HIV infection affects this risk.It has been documented that young children and immunocompromised individuals, including those living with HIV infection, are at increased risk for severe consequences [12] .

Reasons for the resurgence of monkeypox in Africa
Of the several possible reasons for the re-emergence of monkeypox in Africa, the most cited is waning herd immunity acquired from smallpox infection and vaccination.The vaccine is reported to be about 85% protective against monkeypox.Immune responses to one orthopoxvirus can identify other orthopoxviruses, resulting in varying levels of protection depending on the degree of similarity between the orthopoxviruses.This cross-reactivity is caused primarily by two factors.One is a high degree of sequence similarity among orthopoxviruses, particularly among immunologically relevant proteins, resulting in a large number of shared immune epitopes.Second, the response's breadth, with antibodies targeting at least 24 membrane and structural proteins [13] .Therefore, the increase in monkeypox incidence since the end of smallpox vaccination has been attributed to an increasingly immunologically naive population particularly in the endemic African region [13][14][15] .Another plausible explanation is that the monkeypox virus has evolved its infectivity and its ability to transmit from human to human.The variant of the virus identified in the recent outbreaks belongs to the West African clade.The virus is known to be a brick-shaped double-stranded DNA virus, which means it is less likely to mutate into more lethal or transmissible variants.However, recent genetic analysis showed that the virus has acquired several genetic mutations over the years that have improved its ability to infect and spread between human hosts, as well as escape some of our immune defenses.This may also explain the disease's rapid transborder and transregional spread, as well as the sudden increase in infection among homosexuals [14,16,17] .It is still unclear whether monkeypox is transmitted sexually or the high incidence among homosexuals is just a mere coincidence; hence, further research is needed to unravel this mystery.
Furthermore, monkeypox has been found in a number of African countries, with no clear link between many of the clusters, suggesting the possibility of undetected local transmission of the virus.The disruption of Africa's already fragile health system by the COVID-19 pandemic has a significant impact on active surveillance of several diseases, including monkeypox.This, combined with lower utilization of healthcare facilities caused by the COVID-19 pandemic and a low index of suspicion of monkeypox among health-care workers, resulted in under-reporting and misdiagnosis of monkeypox, promoting widespread community transmission [18] .
Finally, there is a lack of adequate global funding for monkeypox research and intervention commodities (diagnostic and treatment tools) in African countries.This has severely hampered the generation of high-quality scientific evidence, which is critical for understanding the disease and developing policies, laws, regulations, frameworks, and effective strategies to eradicate the disease, as seen with smallpox, as well as limiting early diagnosis and treatment.

Challenges impeding monkeypox eradication from Africa
Several factors have been reported to be responsible for impeding the eradication of monkeypox in Africa.Rural-urban migration, international travel and trade, pastoral farming, high cost of treatments, and stigmatization of patients with monkeypox have been implicated to impede the public health management measures put in place by these countries [2,19] .The challenges impeding the eradication of monkeypox in Africa are shown in Figure 2.

Surveillance and medical laboratories
Poor disease surveillance systems and medical laboratories have been documented to contribute significantly to the increased impedance against monkeypox eradication in African countries especially the West and Central region (Fig. 2) [20] .The disease surveillance system put in place by African nations during COVID-19 pandemic is enough to build upon to eradicate monkeypox, but lack of medical personnel and reagents required for monkeypox diagnosis in most African countries is a great challenge [21] .African nations witnessed many suspected cases in the recent monkeypox outbreak with Democratic Republic of Congo (DRC) and Nigeria topping the list.Although, the number of reported cases in Africa was low compared to that from European countries and the USA, it is not gainsaying that there are much more suspected cases undetected in Africa in the recent outbreak [20] .Statistically, 92% of the total cases from African continents was generated from these two countries with DRC contributing about 80%, which is an indication for the need of a n enhanced and rapid diagnostic facilities [21] .DRC recorded a total of 90% mortality of the total 65 cases from monkeypox; however, just 10 laboratory confirmed cases were documented in the recent outbreak [22] .

Other infectious outbreak
The emergence of monkeypox during the period in which the entire globe is faced with COVID-19 and Marburg virus increased the impossibilities of eradicating the reemerged monkeypox disease in African nations (Fig. 2).It is a great concern that regions faced with these existing outbreaks still must deal with monkeypox outbreak [20,23] .Consequently, the fragile health care system in the African region broke down due to excessive strain.The lack and implementation of an effective monitoring system, lack of enough isolation facilities, and health care personnel, insufficient disease testing and verification in designated medical laboratories and lack of aggressive awareness about the relevance of zoonosis to monkeypox transmission critically impede all efforts put in place by the affected African countries [18] .

Unavailability of vaccines
The scarce and limited distribution of monkeypox vaccines especially to rural areas with high numbers of cases has reduced to a greater extent all efforts geared towards the eradication of monkeypox in Africa (Fig. 2).Smallpox vaccine was reported to protect against monkeypox, however, the halt in the administration of the smallpox vaccine in the 1970s due to the global declaration of smallpox eradication is also a contributing factor [20] .This singular action resulted in a boom of individuals susceptible to monkeypox.

Origin of infection
The origin of infection has been documented to be the principal factor responsible for the increasing inability to eradicate monkeypox in the Africa continent [24] .The identification of the source of infection is critical in breaking the disease transmission cycle in a population.Smallpox eradication in Africa was achievable due to its singular host being humans [25] .However, the availability of animal reservoirs for monkeypox will certainly impede the eradication in the African region (Fig. 2).Of great concern is possibility of having more endemic regions from the recent outbreak due to animal reservoir that may transmit back to humans [25] .

Documentation of local transmission
Poor documentation of local transmission among individuals has been implicated as a challenge facing eradication of monkeypox in Africa (Fig. 2).Poor reporting of cases could result in a bloom of asymptomatic individuals who do not show any clinical signs or symptoms of monkeypox virus disease [24] .

Current intervention and their limitation
Parts of Central and West Africa have experienced outbreaks of Monkeypox for years.The WHO, in June 2022, noted that 28 members of states across the WHO, which include the Eastern Mediterranean, Western Pacific regions, the regions of Americas as well as European, where reports of Monkeypox are uncommon or have never been documented [26] .While epidemiological studies are still being conducted, more than 3000 confirmed cases of monkeypox have been recorded outside Central and West Africa this year, but no fatalities have been noted.However, in Africa, there has been a report from health officials that over 70 deaths were thought to be caused by monkeypox [27] .
Monkeypox is no longer a rare viral zoonotic disease restricted to isolated regions of Central and West Africa during the past 10 years and the current outbreaks in numerous countries.Recently, the World Health Emergency of International Concern [26] , this declaration makes the outbreak of Monkeypox the highest in order to gather resources to curb the global outbreak of the disease [28] .
Current intervention guidelines that apply to Africa, where there are cases of human-to-human transmission of Monkeypox virus, is evident, including implementing a co-ordinated response [26] .These strategies include case detection, supported isolation of cases and treatment, contact tracing, targeted immunization for those at high-risk of exposure to Monkeypox, and focused risk communication and community participation [26] .
Other intervention recommendations include clinical management and infection prevention and control for screening, triage, isolation, testing as well as clinical assessment of suspected cases in an individual having Monkeypox, provision of personal protective equipment for laboratory workers and health facility, harmonizing data collection report, use of therapeutics and antiviral agent as well as strengthening international travel measures [26] .
The prevention and management of a zoonotic disease like Monkeypox in Africa, particularly in those operating in a resource-constrained situation, remains a big challenge.Due to the absence of robust animal infection data in areas where the disease is endemic, it has limited monitoring and laboratory capacity, disease treatment, and management [20] , thereby resulting in difficulty for public health and medical professionals to offer an adequate standard of care for the patient due to unavailability of evidence-based treatment guidelines [20] .
Although the smallpox vaccination protects against Monkeypox, it is in poor supply.This vaccine was abandoned in the 1970s, just before smallpox was proclaimed extinct, leaving many people vulnerable to Monkeypox due to high-risk contact [20] .Even though Africa is the only continent to have documented deaths from the monkeypox virus, the Africa Centers for Disease Control and Prevention announced that there is still not a single dosage of the monkeypox vaccination in Africa [29] .

Future recommendations
We recommend that policymakers in endemic countries prohibit or regulate the distribution of African rodents (reservoirs) in the region, as practiced by the US in 2003.This would significantly reduce animal to human transmission and transborder transmission of monkeypox [3] .
Furthermore, all endemic countries should adopt the mobile digital Surveillance Outbreak Response Management and Analysis System (SORMAS), which was deployed in Nigerian and shown to outperform the conventional surveillance system, which is paper-based and transferred manually [30] .SORMAS is an accessible mHealth (mobile health) system that structures and enables infectious disease control and outbreak management procedures, as well as disease surveillance and epidemiologic analysis at all levels of a public health system [31][32][33] .SORMAS includes 12 user interfaces (for example, laboratorian, epidemiologist, and contact tracing officer), disease-specific process modules for 12 epidemic-prone diseases, and a configurable process module for unexpected emerging diseases.It conforms to the Integrated Disease Surveillance and Response System.The majority of SORMAS users use mobile digital devices (e.g.smartphone and tablet), which are bi-directionally synchronized with a central server via mobile telecommunication networks.When SORMAS is used, it can speed up the visualization and analysis of case reports, as well as the production of daily situation reports and improve data completeness, timeliness, and a variety of other aspects of usefulness.The automated generation of transmission chains would allow response teams to assess overall transmissibility and contact tracing effectiveness, as well as aid in the allocation of field staff during an outbreak.
relevant stakeholders should support the training and retraining of healthcare workers in monkeypox surveillance, clinical features, and case definition, in addition to provision of monkeypox investigation kits that consist of surveillance manuals, monkeypox specific case investigation forms, personal protective equipment, and sample collection supplies to enhance laboratory-based surveillance [1] .This would promote a high index of suspicion among healthcare workers which in turn would lead to prompt identification and accurate diagnosis of the disease, as well as early institution of specific control measures (isolation and contact tracing).Healthcare and community extension workers should also be trained in data management and Geographic Information System (GIS) maps [34] .The GIS maps provide information about what is located in even the most difficult-to-reach areas, thereby managing logistical issues with active surveillance and infection control in hinterlands.
The under-reporting of monkeypox must also be addressed.It is highly desirable to use modern epidemiological tools to better understand how sociocultural factors interplay with the healthseeking behavior of Africans.This would allow for the conceptualization and development of simple and practical policies, regulations, and laws, as well as cost-effective multipronged and socioculturally sensitive frameworks that would change Africans' attitudes toward seeking orthodox healthcare.It is also critical to use appropriate health literacy advocacy tools to drive public health campaigns.
The unprecedented speed with which the COVID-19 vaccine was developed-from identifying the virus's genetic sequence to administering the first doses to the general public in less than 11 months [35] is a stark reflection of strong political and global organization will.We hereby urge African governments, in collaboration with global leaders, policymakers, global organizations, and pharmaceutical industries, to accelerate the development and widespread distribution of monkeypox vaccines and specific therapeutics, by removing all obstacles to production and distribution, including but not limited to patent waiver, technology, and information sharing, human capacity building, facilitating partnerships, promoting research, and providing funds, among other essential resources [34] .This will greatly aid in the control of the disease's spread and the reduction of case fatality rates.

Conclusion
The resurgence of monkeypox in Africa poses significant challenges to the continent's public health systems and global health security.Given the virus's high infectivity and mortality rates, it is imperative that African countries take proactive measures to control the spread of monkeypox.Several factors have contributed to the disease's resurgence, including the gradual loss of herd immunity following smallpox vaccination, viral evolution, the disruptions caused by the COVID-19 pandemic to healthcare systems, and inadequate funding for research and interventions.Strategies such as regulating African rodent distribution, adopting digital surveillance systems, training healthcare workers, utilizing geographic information systems, and addressing sociocultural factors contributing to under-reporting can help curb the disease's spread.African governments, public health agencies, and communities must work together to tackle the resurgence of monkeypox in Africa and ensure the eradication of this disease.

Figure 1 .
Figure 1.Choropleth map showing the confirmed Monkeypox cases in Africa between 1 January 2022 and 15 February 2023 as reported by US CDC.

Figure 2 .
Figure 2. Challenges impeding the eradication of Monkeypox in Africa.