{'fraction_non_alphanumeric': 0.030000804311107538, 'fraction_numerical': 0.0164883777044961, 'mean_word_length': 5.27979797979798, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Prospect of acute hepatitis E virus outbreak in the context of the COVID-19 Pandemic in Africa: A contingency plan

Hepatitis E virus (HEV) is the primary cause of acute viral hepatitis in Sub-Saharan Africa (SSA). It is transmitted by oral-faecal route via contaminated water or animal products, which is more pronounced in SSA, where inadequate hygiene measures, low socioeconomic situation, and frail healthcare system increase HEV susceptibility. During the coronavirus disease-19 (COVID-19), numerous initiatives concerning viral hepatitis relief in SSA are implemented. However, national programs do not support most services and are neglected when national and local attention rests on the COVID-19 pandemic. Furthermore, during the COVID-19 pandemic, hepatitis E prevention and control programs were affected in low-income countries due to economic losses. Therefore, an interdisciplinary approach should be adopted to mitigate HEV infections during COVID-19.


Introduction
Sub-Saharan Africa (SSA) has the most reported infectious disease worldwide, leaving the area with a consequential burden in healthcare [1]. Among these infections, hepatitis E Virus (HEV) is of particular concern with approximately 15% of HEV cases worldwide and 29% of stillbirths in HEV-infected women, per SSA's report [2]. HEV, a primary cause of acute viral hepatitis in SSA [3], facilitates oral-faecal transmission by contaminated water or animal products [4]; this phenomenon is more pronounced in SSA, where inadequate hygiene measures, low socioeconomic status, and frail healthcare systems increase HEV susceptibility [1].
Although most HEV infections go unnoticed or present with mild symptoms, the mortality rate is between one to two percent in the general population. Infection is more dangerous among the immunocompromised sector, and pregnant women, where the risk of death may reach 25% [4] and foetuses may develop severe pathology [5]. HEV poses an enormous burden on its young population. This sector is most severely impacted by infection [2] due to SSA's high incidence of immunodeficient HIV patients [6], poor maternity and childcare [7], a high percentage of HEV outbreaks [8], and lack of infection control strategies [9].
The COVID-19 pandemic has negatively affected the surveillance and control of the hepatitis virus worldwide [31]. The lockdown resulted in reduced patient follow-up and evaluation, transfer of healthcare workers, and travel constraints that slowed down the diagnosis, resulting in late intervention and as a consequence, more complications and expense. Due to the coronavirus situation, only a few kids are receiving the hepatitis virus vaccination, this will disrupt the ongoing viral hepatitis eradication program and a high chance of achieving a hepatitis-free world may be lost [32].
On the other hand, despite the low number of Coronavirus disease-19 (COVID-19) cases in SSA relative to other world regions, the COVID-19 pandemic established an additional burden on the fragile healthcare system SSA [10]. At the same time, HEV outbreaks continued to be reported in various SSA countries [11] . In addition to hepatitis E, some African countries have faced other infectious diseases and viral outbreaks such as Lassa fever, HIV/AIDS, cholera, Dengue fever, Rift Valley fever, pneumonia and African Swine fever [12][13][14][15][16][17][18][19]. This article aims to determine the current situation, burden, and challenges facing HEV in Africa to limit future outbreaks.

The situation of fighting hepatitis E virus before COVID-19 Pandemic in Africa
Hepatitis E is a leading cause of acute viral hepatitis worldwide, with an estimated 3.4 million symptomatic infections, over 44,000 deaths, and 3000 stillbirths every year [2]. Hepatitis E serves as an endemic in Africa with frequent outbreaks [9] and protracted outbreaks in East Africa in areas of civil conflicts and humanitarian emergencies [21]. Sanitation and access to potable water during endemics further exacerbate the fight against the infection and prevent adequate relief for populations already battling civil conflicts and humanitarian emergencies [21].
Moreover, HEV remains neglected with regard to public health awareness and funding [17]. As a result, the World Health Organization (WHO) launched a campaign in 2015 to eliminate viral hepatitis globally by 2030 [18]. In addition, in October 2016, Médecins Sans Frontières (MSF) organized a meeting to increase awareness around the burden of hepatitis E to propose a roadmap for encouraging broader interest in the disease and facilitating the use of an available efficacious vaccine [23].
Controlling hepatitis E is an evident challenge due to the limited supplies and the absence of an effective treatment 1. In fact, SSA has a shortage of data in about 50% of countries; outbreaks are more prone in refugees and displaced people; governments face difficulties finding the source of contamination, and inadequate awareness is limited to the general population and healthcare professionals [21].

Burden and current status of hepatitis E Virus in Africa during COVID-19 pandemic
During the spread of COVID-19, HEV served as a burden in countries with poor hygiene, where contaminated water is consumed. Hepatitis E outbreaks have been recorded in Asia, the Middle East, Africa, and Central America, affecting significant populations [24].
SSA faced three outbreaks of Hepatitis E amidst COVID-19 [20]. One of these outbreaks took place in Burkina Faso. According to the WHO, 442 cases of febrile jaundice were recorded between September 8 and November 24, 2020 [21]. The outbreak left 16 deaths, 15 of which were reported in pregnant and postpartum women [25].
The contrast in signs and symptoms between HEV and COVID-19 is evident, with HEV having several distinct symptoms that assist clinicians in distinguishing between a COVID-19 and HEV infection. The geographical distribution of HEV is also critical in determining the likelihood of infections (Table 1).
Although liver-related deaths in Covid-19 patients have been reported caused by elevated liver function tests attributed to the coronavirus disease and/or use of hepatotoxic drugs that may adversely affect patients, particularly those with underlying liver diseases [35], there are no direct reports on this aggravated onset of HEV in Covid19 patients, despite numerous studies for HAV, HBV, and HCV. Covid-19 co-infections are quite prevalent. COVID19 coinfections are relatively rare. Because the symptoms of COVID19 can be similar to those of many other infectious illnesses, misdiagnosis or delayed diagnosis is unavoidable, and can have serious repercussions in certain situations [36]. As a result, it becomes crucial to mention any concurrent infectious illnesses linked with COVID19 infection in order to educate practitioners about the risks.

Current efforts and challenges Facing Responses to hepatitis E Virus in Africa during COVID-19 pandemic
The COVID-19 pandemic increases mortality, especially in lowincome countries with limited resources [27,28]. The number of patients at hepatitis clinics dropped significantly during the pandemic in African countries, and a shortage of critical diagnostic tests was simultaneously at stake [29]. Numerous initiatives concerning viral hepatitis relief in SSA are implemented. Yet, national programs do not support most services and are neglected when national and local attention rests on the COVID-19 pandemic. However, some research has been conducted concerning Hepatitis E. The WHO has announced additional efforts to eliminate hepatitis by 2030 as the infection takes a heavy toll on lives and is considered a major public health burden. Access to safe food and water is a challenge but essential for the prevention and control of the hepatitis E epidemic [9]. The economic burden of the COVID-19 pandemic is a fresh challenge for countries, namely those in Africa, with limited resources.

Recommendations
Beyond the direct mortality and morbidity associated with COVID-19, the ongoing pandemic has taken a substantial toll on worldwide healthcare. The strain on combatting HEV has been disproportionately placed on resource-constrained regions [29,30].
Rigorous efforts are required to develop a sustainable program to mitigate the spread of HEV in SSA, where a significant proportion of hepatitis cases are found [21].
As primary healthcare centers have been in shortage or avoided by the public, there is a need to increase awareness among community members about the importance of approaching PHC centers for more focused community-based management. Moreover, the importance of prevention measures has been brought to the fore. There is a demand for awareness campaigns on the importance of good personal hygiene and general measures for food safety until an effective vaccine becomes widely accessible. Authorities are further recommended to ensure the availability of clean water supplies and proper disposal of faecal waste. Lessons can be learned from the benefits of large-scale COVID-19 surveillance, mass testing, and contact tracing, as similar strategies can be implemented with HEV. Although blood screening for HEV is costly, high-risk individuals (pregnant women and immunosuppressed persons) should be prioritized for such procedures [37,38].
The adoption of interdisciplinary initiatives is of utmost importance in mitigating the spread of HEV facilitated through the collaboration of healthcare experts and policymakers in the region. Irrespective of the negative impact of the Covid-19 pandemic on the eradication of the Hepatitis E virus, it is imperative that innovative and targeted strategies are integrated to preserve and develop low-income nations' health systems which will, in turn, lead to the elimination of the virus. This begins at the rural level, with the implementation of fundamental preventive care measures and the participation of international organizations and governments, as well as community support. The present epidemic paints a clear image of the healthcare system's issues and successes, allowing the world to improve and develop a comprehensive strategy. One of the most prevalent causes and high-risk factors for the development of liver cirrhosis, which is also a complication of viral hepatitis, is excessive alcohol abuse. The practice should be phased out, and public campaigns and education should be conducted. Psychological services and therapies should be disseminated to the general public in order to successfully reduce alcohol and drug consumption. It is impossible to overemphasize the importance of promoting a healthy lifestyle and Table 1 Comparison between COVID-19 and hepatitis E virus.

Similar symptoms
Fever, Nausea and vomiting, Fatigue [4,22] Unique symptoms keeping a healthy body weight to prevent obesity and preserve liver health, which includes avoiding the aforementioned causal risk. Antiviral therapy distribution to afflicted patients, as well as accessible and affordable access, with a focus on regimen compliance, is critical [34,37,38].

Conclusions
Because of the COVID-19 pandemic, there is likely to be a lack of attention to preventing viral hepatitis. However, eradicating viral hepatitis in Africa would necessitate an innovative and targeted strategy to adopt novel ways to preserve and develop low-income nations' health  systems; this begins at the grassroots level, with the implementation of fundamental preventive care measures and the participation of international organizations and governments, as well as community support. In addition, the present pandemic paints a clear image of the healthcare system's issues and successes, allowing the country to improve and formulate a strategic plan.

Ethical approval
Not Applicable.

Please state any sources of funding for your research
None.

Please state any conflicts of interest
No conflicts of interest declared.

Registration of research studies
1. Name of the registry: Not Applicable 2. Unique Identifying number or registration ID: Not Applicable 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): Not Applicable

Guarantor
Not Applicable.

Consent
Not Applicable.

Provenance and peer review
Not commissioned, externally peer reviewed.

Individual's personal data
Not applicable.

Financial support
None.

Data availability statement
Not Applicable.