EUROPEAN JOURNAL OF MICROBIOLOGY AND INFECTIOUS DISEASES

2024; 1(1): 25-29.

10.5455/EJMID.20240411022823

REVIEW ARTICLE Open Access

Disease X, re-emerging viral and bacterial pathogens: another deadly pandemic

looming ahead—a mini review
Kannan Subbaram1* , Zeba Un Naher1 , Razana Faiz1 , Aminath Huda1 , Punya Laxmi Manandhar1 ,
Sheeza Ali1 , Sina Salajegheh Tazerji2 , Phelipe Magalhães Duarte3
1
School of Medicine, The Maldives National University, Male’, Maldives
2
Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
3
Postgraduate Program in Animal Bioscience, Federal Rural University of Pernambuco (UFRPE), Recife, Brazil

ARTICLE HISTORY
ABSTRACT Received April 11, 2024
The World Health Organization stated that there is a strong possibility for another pan- Accepted May 12, 2024
demic caused by a novel disease. This disease can be caused by an unidentified and new Published May 17, 2024
etiology. The World Health Organization named this disease as disease X. Scientists have
commented that the disease X maybe 20 times more fatal than COVID-19. Apart from KEYWORDS
disease X, there are diverse groups of viruses and bacteria that can contribute to emerg- Disease X; re-emerging
ing and re-emerging pandemic diseases. In this commentary, we evaluate all probable viruses; emerging viruses;
microorganisms and diseases that have the full potential to bring out another pandemic re-emerging bacteria; World
Health Organization
disease. There are several bacterial, viral, and other etiologic agents that are emerging as
virulent pathogens. Due to change in climate, overuse of antibiotics, deforestation, and
changes in lifestyle have resulted in the emergence of many pathogens. These diseases
may not be controlled using existing antibiotics/antiviral agents. Since many of these dis-
eases currently do not have vaccines, prophylaxis becomes difficult. All healthcare orga-
nizations and their staff should be prepared in the control of these emerging diseases.
We focus on Ebola hemorrhagic fever, Marburg hemorrhagic fever, Middle East respira-
tory syndrome Coronavirus, Measles, Herpes zoster, Influenza virus type A, Hepatitis C
virus, Monkeypox, Zika virus, other viral diseases, and Plague (Black Death).

The World Health Organization (WHO) recently (fig. 2). The Ebola virus can be transmitted through
declared that there is a high probability of another a patient’s aerosol, respiratory droplets, body fluids,
pandemic soon, caused by an unidentified disease urine, feces, and contact. Ebola hemorrhagic fever
[1]. This disease can be caused by an unknown eti-
is already endemic in many West African countries
ology or involving already existing pathogens. WHO
named this anticipated disease as X—disease [2]. such as the Democratic Republic of Congo, Sierra
According to WHO, there is more chance for another Leone, Ivory Coast, Nigeria, Guinea, and Liberia.
pandemic similar to COVID-19 [3]. This anticipated Several hundred deaths have been documented due
outbreak may involve any pathogen such as bacteria/ to Ebola hemorrhagic fever. The incubation period
virus/other microorganisms [4] (fig. 1). We propose for this disease is short and the outcome is usually
that emerging and re-emerging microorganisms may
fatal. Currently, there is no treatment or vaccine
play a crucial role in contributing to disease X.
available for this fatal disease. The primary symp-
Ebola hemorrhagic fever toms of this disease include fever, myalgia, pharyn-
Ebola hemorrhagic fever is a highly infectious and gitis, gastroenteritis, vomiting, severe unexplained
lethal disease caused by a virus called Ebola virus [5] hemorrhage/bleeding, and shock.

Contact Kannan Subbaram [email protected] School of Medicine, The Maldives National University, Male’,
Maldives.
© The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License (CC BY).
http://creativecommons.org/licenses/by/4.0/.
 K. Subbaram et al.

Figure 1. Disease X can be caused by any new pathogen (Image courtesy: jagranjosh.com
and Kate Bingham).

Marburg hemorrhagic fever

Marburg hemorrhagic fever is a very serious disease
caused by Marburg virus. The fatality rate of this
disease ranges from 24% to 88%. The natural host
for Marburg virus is fruit bats (Rousettus aegypti)
and may be transmitted from fruit bats to humans
[6]. The virus spreads within humans via human-
to-human transmission. There is no antiviral agent
or vaccine available for Marburg hemorrhagic fever.
Marburg hemorrhagic fever was originally identi-
fied in 1967 in Marburg, Germany. Marburg virus
is an RNA virus belonging to Filoviridae family. The
incubation period for Marburg hemorrhagic fever
may be 2 days followed by the development of sud-
den symptoms. The signs and symptoms include Figure 2. Electron micrograph of Ebola virus (Image
fever, myalgia, gastroenteritis, internal and external Credit: Wikimedia Commons).
hemorrhage and severe shock.
Middle East respiratory syndrome Coronavirus Measles
(MERS-CoV) Measles is caused by an RNA virus called Measles
virus. Measles usually affects children, but adults
Middle East respiratory syndrome (MERS) was orig-
can be infected. Measles can be a very serious dis-
inally detected in Saudi Arabia. It is a severe viral
ease with a fatality rate up to 15%. The severe com-
disease transmitted from camels to humans. There plications of Measles can be blindness, pneumonia,
were many cases of human-to-human transmis- and encephalitis. Nowadays there are few variants
sion were observed during the outbreak [7]. This of the Measles virus have been reported. These
disease was noted in other parts of the world, like variants have escaped the immunogenicity of the
the entire Gulf, and some countries in Europe and widely used MMR vaccine [8].
America. MERS was caused by an RNA virus belong-
Herpes zoster
ing to Coronaviridae, called MERS-CoV. The fatality
rate of MERS may go up to 34% and the symptoms Herpes zoster is caused by an RNA virus known
of MERS are similar to COVID-19. as Varicella-Zoster virus belonging to the family

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 European Journal of Microbiology and Infectious Diseases.2024; 1(1): 25-29.

Figure 3. Patients admitted during the influenza pandemic (image credit: Otis Historical
Archives, National Museum of Health and Medicine—Emergency hospital during
influenza epidemic—NCP 1603).

Herpesviridae. Herpes Zoster is the painful reacti- Hepatitis C virus

vation of chicken pox (Varicella) [9]. After primary
Hepatitis C virus (HCV) is an RNA virus classified
infection (chicken pox) the virus (Varicella) goes to
under Flaviviridae and associated with hepatitis.
latency in the dorsal root ganglion. Later, the virus
HCV is usually transmitted through blood trans-
breaks the latency and emerges out, and causes a
fusion. There is no vaccine or therapeutic options
secondary infection called Zoster (Shingles). The available for HCV. HCV causes severe fatal liver
complications of Herpes zoster can be fatal pneu- damage/cirrhosis and hepatocellular carcinoma
monia, encephalitis, cranial nerve palsy, cerebelli- [11]. HCV can be transmitted through sexual, other
tis, giant cell arteritis, zoster paresis, and multiple parenteral, and vertical means. HCV after exposure
ocular disorders. can lead to a persistent, chronic infection and a car-
Influenza virus type A rier state. Mortality due to HCV is very high and is
above 31%.
Influenza virus type A belongs to the RNA virus
classified under Orthomyxoviridae family. This virus Mpox
possesses a segmented genome and can undergo Mpox is caused by a DNA virus classified under the
antigenic drift and antigenic shift [10]. Due to the family Poxviridae. Mpox can be transmitted through
properties of antigenic shift, the virus may undergo direct contact, sexual route, respiratory droplets,
genetic reassortment leading to the development of and in-utero ways. The symptoms of infection
new variants (subtypes). There are several notori- include papules, vesicles, or crusts that may occur
ous known subtypes of Influenza virus type A were in any part of the body. Complications of Mpox
observed. It includes (H1N1) swine flu and (H5N1 include pneumonia, blindness, and encephalitis.
(bird flu). This virus has caused several pandemics Mpox can spread rapidly involving many people,
involving millions of deaths in all parts of the world leading to often epidemic disease. Pregnant moth-
(fig. 3). Due to its mutagenicity, this virus is difficult ers if infected with Mpox, it can lead to develop-
to control by vaccination. mental anomalies in the fetus [12].

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 K. Subbaram et al.

Figure 4. Pandemic due to “black death” due to plague (image credit: Bettmann archive/Getty images).

Zika virus human population in the future. Plague is caused

by a Gram-negative bacterium called, Yersinia pes-
Zika virus is an arthropod virus disease (Arbovirus)
tis classified under the family Enterobacteriaceae.
transmitted through Aedes spp. Mosquitoes [13].
This virus belongs to the RNA group and is clas- It can be transmitted through rodents and human-
sified under Flavivirus. If a pregnant mother is to-human transmission is commonly observed.
infected by Zika virus it can infect the fetus trans- There are several fatal types of plague that include,
placental way leading to congenital abnormalities. bubonic plague, pneumonic plague, and septicemic
Other pregnancy-related adverse effects include plague. Out of these, untreated pneumonic plague
preterm birth, fetal loss, and stillbirth. Zika virus cases have a very high mortality rate (nearly 100%).
can be transmitted through sexual routes, affecting Other bacterial diseases
the sexual partners. Zika virus infection can lead to
neuropathy, meningoencephalitis, pneumonia, and Other potential diseases that can reach pan-
Guillain-Barré syndrome in adults. Since Zika virus demic proportions include tuberculosis, caused
has a wide transmission scope the infection can by MDR/XDR Mycobacterium tuberculosis, infec-
spread rapidly involving a huge population. tions due to MDR—Pseudomonas aeruginosa, MDR
Other viral diseases Acinetobacter baumanni, MDR Enterococcus, and
methicillin/vancomycin resistant Staphylococcus
Crimean-Congo hemorrhagic fever, Lassa fever, aureus (MRSA/VRSA) [15].
severe acute respiratory syndrome (SARS), Nipah
virus infection, Henipaviral disease, and Rift Valley Conclusion
fever are highly infectious diseases. These viral dis-
eases often result in hemorrhagic manifestations Overuse/misuse of antibiotics, lifestyle changes,
and death. These viruses are highly virulent and deforestation, and environmental changes have a
exhibit extremely high fatality rates. huge impact on bringing out emerging and remerg-
ing diseases. These diseases may not be controlled
Plague (Black Death) using existing antibiotics/antiviral agents. Since
Plague which was called “black death” was held many of these diseases currently do not have vac-
responsible for several millions of deaths around cines, prophylaxis becomes difficult. All healthcare
the globe in the past [14] (fig. 4). Plague disease organizations and their staff should be prepared in
has the potential to re-emerge and threaten the the control of these emerging diseases.

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 European Journal of Microbiology and Infectious Diseases.2024; 1(1): 25-29.

References 8. Afrin S, Taib Mamun K, Mahboob N, Iqbal H, Jannat

1. What Is Disease X? How scientists are prepar- H. Elimination of measles by 2024: achievements
ing for the next pandemic | The transmission | and challenges. J Med Sci 2020; 14:7.
University of Nebraska Medical Center. Available 9. Steinmann M, Lampe D, Grosser J, Schmidt J, Hohoff
via https://www.unmc.edu/healthsecurity/trans- ML, Fischer A, et al. Risk factors for herpes zoster
mission/2023/09/27/what-is-disease-x-how-sci- infections: a systematic review and meta-analysis
entists-are-preparing-for-the-next-pandemic/ unveiling common trends and heterogeneity pat-
terns. Infection 2024 Jan 18.
2. ‘Disease X’ could cause the next pandemic, accord-
10. Curran SJ, Griffin EF, Ferreri LM, Kyriakis CS,
ing to the WHO—or Ebola, SARS, or Nipah. 9 patho-
Howerth EW, Perez DR, et al. Swine influenza A
gens researchers are keeping a watchful eye on |
virus isolates containing the pandemic H1N1 ori-
Fortune Well. Available via https://fortune.com/ gin matrix gene elicit greater disease in the murine
well/2024/01/12/what-is-disease-x-world-eco- model. Microbiol Spectr 2024; 12(3):e03386–23.
nomic-forum-pandemic-planning/ 11. McArthur DB. Emerging infectious diseases. Nurs
3. What Is Disease X? How scientists are prepar- Clin North Am 2019; 54:297–311.
ing for the next pandemic—the washington post. 12. Mohanto S, Faiyazuddin M, Dilip Gholap A, Jc
Available via https://www.washingtonpost.com/ D, Bhunia A, Subbaram K, et al. Addressing the
business/2023/09/27/what-is-disease-x-how- resurgence of global monkeypox (Mpox) through
scientists-are-preparing-for-the-next-pandemic/ advanced drug delivery platforms. Travel Med
a557100a-5d05-11ee-b961-94e18b27be28_story. Infect Dis 2023;56:102636.
html 13. de Sales-Neto JM, Madruga Carvalho DC, Arruda
4. What is Disease X and how will pandemic prepa- Magalhães DW, Araujo Medeiros AB, Soares MM,
rations help the world? | Health News | Al Jazeera. Rodrigues-Mascarenhas S. Zika virus: antiviral
Available via https://www.aljazeera.com/ immune response, inflammation, and cardiotonic
news/2024/1/18/what-is-disease-x-and-how- steroids as antiviral agents. Int Immunopharmacol
will-pandemic-preparations-help-the-world 2024; 127:111368.
5. Ntoumi F, Veas F. Preparedness for future outbreaks: 14. Andrianaivoarimanana V, Savin C, Birdsell DN,
Vogler AJ, Le Guern AS, Rahajandraibe S, et al.
strengthening surveillance of survivors of Ebola
Multiple introductions of Yersinia pestis during
virus disease. Lancet Infect Dis 2024; 24:221–3.
Urban pneumonic plague epidemic, Madagascar,
6. Mujahid U, Ahmad M, Mujahid A, Narayan E,
2017. Emerg Infect Dis 2024; 30:289–98.
Rehman SU, Iqbal HMN, et al. Recent outbreak of
15. Ismail A, Saahath A, Ismail Y, Ismail MF, Zubair Z,
Marburg virus; a global health concern and future Subbaram K. ‘Tomato flu’ a new epidemic in India:
perspective. Eur J Clin Microbiol Infect Dis 2024; virology, epidemiology, and clinical features. New
43:209–11. Microbes New Infect 2022; 51:101070.
7. Kannan S, Subbaram K, Ali S, Kannan H. Molecular
characterization and amino acid homology of Author Query
nucleocapsid (N) protein in SARS-CoV-1, SARS-
CoV-2, MERS-CoV, and Bat Coronavirus. J Pure Appl Please provide volume and page number for the ref-
Microbiol 2020; 14:757–63. erence “9.”

https://wisdomgale.com/ejmid/ 29