An Outbreak of the Monkeypox Virus: An Alert to Mankind
Ramavath Muralidhar Naik1*, Hindustan Abdul Ahad2, Haranath Chinthaginjala1,
Bogavalli Varalakshmi1, Siriguppa Dheeraj1, Pathakumari Jaya Sree1
1Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research (RIPER) -Autonomous, Ananthapuramu - 515001, AP, India.
2Department of Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER) - Autonomous, Ananthapuramu - 515001, AP, India.
*Corresponding Author E-mail: muralismc7@gmail.com
ABSTRACT:
A zoonotic condition known as monkeypox (MPX) is brought on by the monkeypox virus (MPXV), a species of the orthopoxvirus family. It was found in 1958 following an epidemic at a Copenhagen, Denmark, livestock facility. MPX has a clinical appearance that is comparable to smallpox (SPX). Laterit’sfinding, MPXV has shown a tendency to infect and cause disease in a significant number of mammalian animals from all over the world. Traveller’s MPX was exported from African countries (Nigeria) to other regions of the world in 2018 and 2019, respectively, raising concerns that MPXV may have emerged to occupy the ecological and immunological niche left by the smallpox virus (SPXV). MPXV first appeared again in 2017 in Bayelsa state after 39 years with no reported cases in Nigeria. This review's goal is to locate all documented cases of human MPXepidemics and pertinent epidemiological data. We made an effort to gather and discuss in this review all articles that have been written about MPXV infections that have been found experimentally or naturally. We also go through the comparative illness courses and the state of our understanding of the biology of infection, epidemiology, diagnosis, spread, and prevention of MPXV globally, particularly concerning humans. The MPXV is regarded as a high-danger pathogen that roots a disease that is significant for public health. To plan effective preventative, preparedness, and response actions, it is vital to concentrate on developing surveillance capacities that will yield meaningful information.
KEYWORDS: Infection, Disease, Monkeypox, Smallpox, Virus.
INTRODUCTION:
Monkeypox (MPX) is a developing zoonotic condition brought on by the monkeypox virus (MPXV) a double-stranded DNA virus belonging to the Orthopoxvirus (OPXV) genus in the Poxviridae family that replicates in theinfected cells (cytoplasm)1. When observed under an electron microscope, the poxviruses are displayed as brick-shapedstructures that range in size from 200 to 400 nm2. Along with the variola virus, which is the cause of smallpox (SPX), MPXV is one of the four OPXV species that are harmful to humans3,4.
A taxonomically diverse spectrum of mammalian species can contract MPX, although the actual natural host is unknown. Only two wild animals, a sooty mangabey in the Ivory Coast and a rope squirrel in the Democratic Republic of the Congo (DRC) have been used to isolate the MPXV5. It transmits thought that saliva, respiratory excretions, and contact with lesion exudate or crust material. Another exposure source may be the shedding of MPXV through faeces6. The clinical presentation of MPX is quite similar toSPX, but the lymph node widening that starts early, frequently at the onset of fever, distinguishes MPX from SPX7. Lesions begin to form concurrently and grow at a similar rate to a rash, which normally appears 1-3 days after fever and lymphadenopathy start. Although they mostly affect the periphery, they may cover the entire body in a serious illness. Up to 4 weeks may pass before the lesion desquamates due to infection6. Patients may develop a variety of side effects, including secondary bacterial infections, respiratory distress, bronchopneumonia, gastrointestinal involvement, dehydration, sepsis, encephalitis, and corneal infection with vision loss8. Supportive treatment and symptomatic therapy are increasingly used in the management of patients with an MPXV infection9.
The disease was initially identified in experimental monkeys in 1958, but the first human case was identified in a 9-month-old boy in the Democratic Republic of the Congo in 1970. (DRC)10. However, compared to SPX, human MPX has substantially lower morbidity and mortality rates11. Three occurrences of human MPX were recorded in Nigeria between 1970 and 2017 (one in 1970 and twoin 1978). The greatest epidemic of the West African Clade of Human MPX in Nigeria returned in September 2017, with 228 suspected cases and 60 confirmed cases recorded in 24 of the country's 36 states7. The Niger Delta University Teaching Hospital in Bayelsa state is where the majority of suspected and confirmed cases were reported and are being treated.
SOURCE OF MPX IN THE UNITED STATES:
Investigations from the youngster and other patients traced the spread of MPX from Wisconsin to an Illinois distributor who had received a consignment of exotic animals that had been brought into the US via Texas from Ghana, West Africa (Figure 1)12,13. This shipment of animals contained about 800 tiny mammalsthat entered Texas on April 9. This was the likely source of the introduction. Six genera of African rodents, including rope squirrels (Funiscuirusspp.), tree squirrels (Heliosciurus spp.), Gambian giant rats (Cricetomys spp.), brush-tailed porcupines (Atherurus spp.), dormice (Graphiurus spp.), and striped mice, were included in the shipment of nine different species (Hybomys spp.)14. One Gambian giant rat, three dormice, and two rope squirrels were found to be infected with the MPXV by CDC laboratory testing using PCR and MPXV isolation of some of the animals. Upon the shipment'sentry into the United States, some of the animals that had been removed from the rest of the shipment were also found to have signs of infection. The prairie dogs blamed for the epidemic in Wisconsin andsome other states were kept nearby when the Gambian rats arrived in Illinois15.
Figure1: This diagram showing that how the infected species entered the USA and the numbers of confirmed and suspected cases of the MPX Virus. Dates indicatethe onset of illness.
HISTORY OF THE DISEASE:
MPX isa member of the orthopoxviral family of viruses, the MPXV is responsible for the uncommon viral disease known as MPX. It is only found in the nations of central and west Africa's rain forests16. First identified in laboratory monkeys held at a research facility in Copenhagen, Denmark, in 1958, MPX was later identified in various African rodents by testing of animal blood. On September 1, 1970, a nine-month-old baby was admitted to the Democratic Republic of the Congo Hospital, marking the first MPXV case in a human17. A virus-like to MPXV was discovered from the boy's sickness, which resembled SPX. Between October 1970 and May 1971, six human MPXV cases were reported in Liberia, Nigeria, and Sierra Leone. Ten MPXV cases were reported in Nigeria between 1971 and 1978, with the first index MPXV case being discovered there in 1971. In the DRC, 37 confirmed cases of MPX between 1981 and 1986 were reported18.
In the period between February 1996-1997, the same region was the site of the greatest MPX outbreak. Six deaths and 71 medical cases of MPX were recorded in 13 villages of Zaire between February and August 1996. At the peak of the outbreak, in August, there were the most secondary cases of the 11 specimens that were obtained, all tested positive for MPX and had only slight genetic differences from earlier strains that had been collected between 1970 and 197919.
Although there was some worry that MPX was evolving and becoming more contagious or virulent, such possibilities were ruled out when scientists examined a portion of one isolate from a patient who contracted it in 1996 and discovered no differences between it and strains discovered in Zaire between 1970 and 197920.
Since then, thousands of human cases of MPX have been documented in 15, with 11 of those locations being in Africa. Singapore, Israel, the USA, and the UK all received MPX imports21.
MORPHOLOGY, GENOMEORGANIZATION:
MPXV’s morphology reveals that virions are brick or ovoid-shaped particles that are encased by lipoprotein outer membrane, sharing similar physical traits with other Orth poxviruses (OPVs). The known MPXV size ranges are 200 by 250nm. A brick-shaped virion is created by a membrane bond and a tightly packed core that houses enzymes, a double-stranded DNA genome (about 197 kb), and is enclosed in a core that is slightly pleomorphic and has a dumbbell form18,22. Transcription factors are also protected by the outer membrane. The core has lateral bodies on both sides and is described as being biconcave due to an artefact of fixation in electron microscopy23.
Despite being a DNA virus, MPXV finishes its whole life cycle in the cytoplasm of diseased cells. The MPXV genome encodes every protein necessary for viral DNA replication, transcription, virion assembly, and egress24. While the genes that code for the interactions between the virus and the host are less conserved and are found in the terminal region, the genes that code for housekeeping functions are highly well-preserved among OPVs. Intracellular mature virus (IMV) and extracellular-enveloped virus (EEV) are two infectious virions produced in cells infected with poxvirus in Vaccinia viruses (VACV)25.
BIOLOGY OF POXVIRUSES: TAXONOMY AND HISTORICAL BACKGROUND:
Poxviruses are a distinct, intricate, and varied class of big DNA viruses that produce both their RNA and DNA in the infected cell's cytoplasm. Several clinically significant viruses exist in the Poxviridae family, separated into two sizable subfamilies and 16 genera. Based on their range of hosts, the two subfamilies are Chordopoxvirinae, which affects vertebrates, and Entomopoxvirinae, which affects insects26. In the first category, some viruses, including cowpox, MPX, and tanapox, infect birds and other animals, including cows and monkeys, and on occasion, they spread to humans and cause illness. In 1978, MPXV officially joined the Poxviridae family. Since the SPXV was eradicated, the Chordopoxvirinae subfamily and genus Orthopoxviral have continued to be the most pathogenic species. MPXV is an enclosed double-stranded DNA virus with about 190 kb genome that is encased in a core that is slightly pleomorphic and has a diameter of 140–260 nm, giving the virion a brick-like appearance27,28. The genome features many open reading frames (ORF) that span more than 180 nucleotides in size as well as tight hairpins on both ends29. A 56–120 kb highly conserved central coding region is surrounded by variable sections and terminal repeats, which contain four additional ORFs that are mostly used for immunomodulation for host range determination and pathogenicity.
EPIDEMIOLOGY:
Eleven nations in the Central African Republic and the Congo now have an endemic MPXV outbreak. Preben Christian Alexander von Magnus discovered MPX in 1958 in Denmark while looking into two pox-like disease epidemics that took place in monk colonies. The first recorded human case of MPX happened on September 1, 1970, in a nine-month-old child admitted to the Hospital in the Republic of the Congo. The second case was the mother of a four-year-old girl, and it was assumed that the mother contracted the disease from her child. In a similar vein, a 35-year-old man from Omi unfun in Nigeria became infected with MPXV for the third time in 1978. (Oyo state). Between 1971 and 1978, there were 10 reported cases, but only three were confirmed, and no deaths were noted. There were other outbreaks in Sudan in 2005 (19 cases), in the DRC in 2009, and elsewhere (2 cases)30,31.
In Nigeria, there haven't been any MPXV cases reported for so long that in September 2017, MPX returned23,32. A possible MPXV case in an 11-year-old boy with anextensive rash, fever, headache, malaise, and sore throat was reported by the Niger Delta University Teaching Hospital (NDUTH) to NCDC. Since the MPXV outbreak began in September and continued until December 2017, 177 suspected cases in 23 states of Nigeria were recorded33. With 40, 29, 21, 22, and 15 instances, respectively, Bayelsa, Rivers, Lagos, Cross River, and Akwa Ibom had the greatest numbers of suspected cases (Figure 2). 2017 saw a total of 68 confirmed cases, and two deaths were reported from two different states. Out of the 23 states that had suspected instances, only nine had no confirmed cases, while 14 states had one to twenty confirmed cases34,35.
Figure 2. Total MPXV Cases in Nigeria states, in 2017
Figure 3. Human MPXV cases across Nigeria state, in 2019
72 confirmed or suspected cases of febrile sickness with vesiculopuster eruptions were recorded in the USA in 2003, which illustrates the propensity for MPXV transmission to naive populations as well as its capacity to appear outside of its typical ecological region36,37. In a similar vein, there is verified evidence that the MPXV exists in wild animals in Zambia, Uganda, and East Africa. In contrast to females, males are preferred by human MPX. Young children have a significant mortality rate, with case fatalities ranging from 10% to 11%, depending on the age of presentation and SPX immunization status38,39.
Since November 13th, 2018, the NCDC had identified 104 suspected cases across 19 states, 38 confirmed cases across 12 states, and one fatality in Imo state. 68% of suspected cases are in the states of Rivers, Cross River, Bayelsa, and Akwa Ibom, while 66% of confirmed cases are in the states of Rivers, Bayelsa, Delta, and Oyo. With 35, 20, and 15 suspected cases and 14, 10, and 8 confirmed cases, respectively, Lagos, Rivers, and Delta states led 2019 MPXV cases18,40.
Nigeria generally has 424 MPXV suspected cases and 155 confirmed cases, with the 2017 outbreak having the most confirmed cases (Figure 3). The number of confirmed and suspected cases decreased in 2018, which would indicate that Nigeria's attempts to battle MPXV were successful, but the 2019 data revealed otherwise (Figure4)41. Between 2017 and 2019, MPXV cases were documented in people aged 21 to 40 (median age = 30), with a 3:1 male-to-female ratio of confirmed cases. Although there have been no MPXV cases reported or recorded in 2020, this may be due to several circumstances, including the shifting of manpower and resources from MPXV surveillance and response to more serious viral illnesses, like covid-19and Lassa fever42,43.
Figure 4.All Human MPXV cases in Nigeria over the years
After more than three decades, MPX has returned to Nigeria. This could be because a weighty portion of the population there did not receive the SPX vaccination, which also protects MPX36.
As of June 16, 2022, there have been more than 2,100 occurrences of MPX recorded, 2,066 of which have been confirmed, 100 of which are suspected, and a total of 2,166 cases, dating from the end of April to the beginning of May 2022. In the Americas, Europe, Oceania, and the Middle East and North Africa (MENA) region, just fewer than 60 countries and territories are affected.
DIAGNOSIS:
Since SPX was eradicated, MPXV is the orthopoxviral that has caused the greatest attention in humans. The incubation period for the human MPX has been estimated at 5 to 21 days, and the length of symptoms and signs is believed to be 2 to 5 weeks. The aetiology and clinical presentation substantially mimic that of common SPX. Before rashes form, the sickness starts with non-specific symptoms and indications such as fever, chills, headaches, lethargy, asthenia, lymph node swellings, back pain, and myalgia (muscle aching). Rashes of all sizes start after 1 to 5 days of fever starts, first on the face, then spread to the body, hands, legs, and feet. The rash progresses through multiple stages, beginning with macules, papules, vesicles (fluid-filled blisters), and pustules, before clearing up over time with crusts and scabs that fall off when the patient is well. The rash could be in several stages at the same time. Around distinct lesions, areas of erythema and/or skin hyperpigmentation are frequently visible. Pharynx, eyes, and genitalia’s Mucosal inflammation may alsooccur44,45.
MPX has milder clinical symptoms than SPX, yet it can still be lethal, with mortality rates between 1% and 10%. Children and young adults have a greater mortality rate, while immunocompromised people have a more severe course. The clinical picture is changed toward a milder disease and some cross-protection against MPX is conferred by prior SPXimmunization46.
For the clinical distinction between the rashes, a complete clinical history, including travel, occupation, and contact, along with a laboratory diagnosis, are necessary. A conclusive diagnosis must be made utilizing viral isolation and culture, immunohistochemistry for the detection of viral antigens, ELISA for the detection of antibodies (IgG and IgM), and specific viral DNA detection using PCR47. Additionally, only containment laboratories with a Biosafety level 3 rating should handle any suspected infectious sample processing. GeneXpert recently underwent an evaluation of its accuracy and validity, indicating its usefulness as a diagnostic platform that might enhance and speed up present MPXV detection capacities in endemic areas48.
TRANSMISSION:
It is yet unclear how MPXV is transmitted to people. Although the precise mechanism(s) is/are still unknown, it is considered that the primary animal-to-human infection happens when handling MPX-infected animals, whether through direct (touch, bite, or scratch) or indirect contact. The respiratory tract, mucous membranes, or broken skin are supposed to be the main entry points for the virus into the body (eyes, nose, or mouth). In addition, sera taken from 55 monkeys in Nigeria of unknown species were reported to be negative. Secondary human-to-human transmission, which is thought to occur often, is most likely to occur by large respiratory droplets, direct or indirect contact with bodily fluids, lesion material, contaminated surfaces, or other materials like garments or linens49. Hospital employees and relatives are more susceptible to infection from prolonged patient interaction. There have been descriptions of nosocomial transmission50. There is currently no proof that MPX infections in the human population can be sustained by human-to-human transmission alone51.
SEXUALLY TRANSMITTED?
This multi-nation pandemic is spreading through sustained human-to-human contact, primarily between males who have intercourse with other men and non-travelers (MSM). The prospect that MPX has been sexually transmitted has also caused alarm. One recent instance of syphilis coinfection has been reported in the Czech Republic. Someof those cases involve MSM who are HIV-positive52. Additionally, the 2022 outbreak was recently linked to virus identification in seminal fluid, vaginal and rectal lesions, and faeces of four MSM in Italy. The theory that MPX can be sexually transmitted is supported by recent research. Even though these results cannot prove infectivity with certainty53.
COMPLICATIONS:
Among the known risks include bronchopneumonia, shock brought on by diarrhoea, vomiting, corneal scarring that results in lifelong blindness, encephalitis, particularly in individuals with subsequent bacterial infection, and septicemia54. The long-term effect is pitted skin scarring55.
THERAPY AND CONTROL:
Meanwhile, there are no clinically approved and licensed antiviral medicines for the particular treatment of MPX, treating the condition is currently syndromic56. The CDC advises placing patients who arrive at the ER or an outpatient clinic with a fever and vesiculopustular in a private examination room as soon as possible and have them thoroughly examined while keeping in mind a differential diagnosis of chickenpox, vaccinia in a patient who has recently received anSPX vaccination, and even the unlikely possibility of SPX57. The CDC has also recommended several general preventative measures that must be followed. To prevent MPX, the CDC currently advises SPX vaccination.
Four substances, NIOCH-14, Cidofovir, Brincidofovir, and ST-246 that are still in several stages of clinical testing could have beneficial therapeutic effects. The first antipox viral medication just received approval from the US Food and Drug Administration (FDA) to treat OPXV including SPX and MPX. Non-human primates exposed to the variola virus were well-protected by tecovirimat, a virion egress inhibitor (the causative agent of SPX). In compliance with Animal Efficacy Rule68 of theFood and Drug Administration. There are no serious side effects when placebo-controlled pharmacokinetic and safety trials are conducted with 449 healthy adult human volunteers. Therefore, Tecovirimat is the only currently available antipox viral therapeutic agent, and it is stockpiled as part of the US Strategic National Stockpile for use as a defense to treat SPXV infections in the event of a bioterrorist attack58.
PREVENTION:
To prevent the transmission of MPXV in locations where it is endemic, one must limit direct contact with blood and undercooked meat while avoiding all interaction with rodents and primates59. Massive health education efforts are required to raise public awareness, provide instructions on how to handle potential animal reservoir species (gloves, protective clothes, surgical masks), and warn people to stand back from tormented people49,60.
The prevention of human-to-human transmission in healthcare depends on infection control techniques. Improved isolation procedures and nursing techniques (gloves, protective clothes, surgical masks) call for training as well as sufficient resources in the form of staff and facilities.
Health professionals and individuals treating or exposed to patients with MPX or their samples should be immunized against SPX by national health authorities. According to estimates, receiving an SPX vaccination offers 85% cross-protection against MPX. SPX vaccination was advised by the Centers for Disease Control and Prevention (CDC) within two weeks, preferably before four days, of considerable unprotected exposure to an infected animal or a confirmed human case61.
The main focus should be on raising alertness and taking appropriate action (decisions, medical personnel, sampling, surveillance, and education), both by local and international authorities.
In hospitals in developed nations, patients should be put in a negative air pressure isolation room right away if such facilities are not available, or a private room if there is a suspicion of MPX (e.g., a patient with fever, skin lesions, and a history of visiting an endemic area or contact with patients). Precautions should be made for droplets, contacts, and general hazards. Personnel in charge of infection control should be called right away62,63.
CONCLUSION:
As indicated in, twelve African nations have reported monkeypox (MPX) cases since 1970, with Nigeria having had the disease's biggest known outbreak. With certain foci in West Africa, the monkeypox virus (MPXV) continues to be the most dangerous pox virus in circulation throughout Central Africa. The most serious MPXV outbreak in West Africa, Nigeria, the United States, and a few other nations highlights the need for immediate surveillance and a thorough investigation into the beginning of the virus's spread. Human MPX patients typically exhibit constitutional symptoms such as fever, headache, muscle aches, and backaches. These symptoms are then followed by lymphadenopathy and well-defined pustular rashes with the centrifugal distribution. Antiviral therapy has made progress with the recent development and licensing of tecovirimat as a treatment for the chickenpox virus. In September 2018, the UK received distinct reports of the two MPXV instances for the first time. The first was a Nigerian resident who was residing at a Cornwell naval installation, while the second was a local who had previously visited Nigeria. This was MPXV's second emergence outside of the African location and its first appearance as a human pathogen in Europe. In September 2018, the third case of a healthcare professional was identified as having MPXV after treating the second verified MPXV case in the UK. The United States saw 37 laboratory-confirmed cases and 10 possible cases of MPXV infection in humans in 2003, which were the only other documented occurrences outside of Africa. The majority of patients reportedly had direct contact with pet prairie dogs that were brought into Texas and other US states in a cargo of wild animals from Ghana, West Africa, and were infected by African rats. In general, the recent appearance of MPX across a large geographic area raises concerns about the possibility of further spread and necessitates better attention and action. Further coordinated global efforts are needed to contain disease due to the region's inadequate specialized experience, surveillance capability, laboratory capabilities, management, disease treatment, infection control, and awareness of the disease.
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Received on 08.11.2022 Modified on 13.07.2023
Accepted on 20.11.2023 ©Asian Pharma Press All Right Reserved
Asian J. Res. Pharm. Sci. 2024; 14(1):11-18.
DOI: 10.52711/2231-5659.2024.00003