The recent spread of monkeypox virus (MPXV) outside its known endemic regions has led to a recent global public health crisis. Indeed, on July 23, 2022, the World Health Organization (WHO) declared the current MPXV outbreak a Public Health Emergency of International Concern (PHEIC).
Study: Monkey Pox Outbreak: Wastewater and Environmental Monitoring Perspective. Image Credit: APIWAN BORRIKONRATCHATA / Shutterstock.com
The current outbreak of MPXV
MPXD cases have increased rapidly beyond endemic regions since May 2022. As of October 9, 2022, more than 70,000 MPXD cases have been reported in 106 countries, more than 98% of which have no records previous to MPXV. The United States has reported the largest number of MPXV cases in the current outbreak, followed by Brazil and Spain.
A new study in Science of the Total Environment reviews the current advantages and challenges associated with wastewater-based monitoring (WBS) of MPXV.
What is MPXV?
MPXV is a double-stranded, enveloped DNA virus that belongs to the Orthopoxvirus genus of the Poxviridae family. MPXV comprises two genetic clades, including Clade I and II. Formerly known as the Central African or Congo Basin clade, Clade I is associated with more severe and contagious diseases. In comparison, Clade II, formerly known as the West African clade, causes a less severe and contagious form of MPXD.
Poxviruses are capable of causing widespread infections in animals and mammals. Zoonotic transmission to humans can occur through direct contact with body fluids, blood, as well as mucous or skin lesions of infected animals or contaminated materials. Eating undercooked meat and other animal products from infected animals can also increase the risk of transmission.
Animal hosts for MPXV include various rodents and non-human primates, including chipmunks, Gambian rats, chipmunks, dormouses, and different monkey species. Rodents are currently believed to be the natural reservoir of MPXV.
Symptoms, characteristics and treatment of MPXV
The first case of monkeypox disease (MPXD) in humans was identified in the Democratic Republic of the Congo in 1970. Subsequently, several cases emerged in the rainforest regions of the Democratic Republic of the Congo, as as in other Central and West African countries.
The first outbreak of MPXD outside its endemic region occurred in the USA in 2003. This was linked to captive prairie dogs exposed to rodents imported from Ghana.
MPXV infections are mostly self-limiting, and the infection lasts two to four weeks. However, some cases can be fatal.
Common symptoms of MPXV infection include fever, swollen lymph nodes, and skin rashes. Immunocompromised people and children are more vulnerable to serious infections. The incubation period for MPXV infection can range from five to 21 days.
Many cases of MPXV reported during the current outbreak have atypical features including the absence of skin lesions in some cases, the presence of a few or even a single lesion, anal pain and bleeding, onset of lesions before onset of fever, lesions in different stages of development, and lesions in the genital or perineal/perianal area that do not extend beyond these localized areas.
The US Centers for Disease Control and Prevention (CDC) recommends that clinical confirmation of MPXV cases should include monitoring of both lesional and nonlesional materials. Clinical laboratories collect oral and throat swabs, skin lesions, blood, urine, and oral fluid samples to confirm MPXV quantitative polymerase chain reaction (qPCR) and digital PCR (dPCR).
Recently, the ACAM2000 vaccine based on the vaccinia virus that was used against smallpox has been licensed by the WHO to prevent MPXD in at-risk populations. Some antiviral drugs such as brincidofovir and tecovirimate (TPOXX) can also be used to treat immunocompromised and critically ill patients infected with MPXV in clinical settings.
WBS to control MPXV
WBS is an important technique used to detect and monitor the spread of notable pathogens within a community. This approach can help estimate the temporal and spatial distribution, genetic diversity, and prevalence of various pathogens.
WBS has previously been used for polio eradication and to control coronavirus disease 2019 (COVID-19). WBS has also been used for several other pathogens, including hepatitis E, hepatitis A, adenovirus, influenza A virus, norovirus, dengue virus, and circulating antimicrobial-resistant pathogens at the population level.
Wastewater is suitable for controlling communicable diseases at the community level because it includes biological materials such as wounds, body fluids and skin rashes from infected people in a community. WBS is capable of providing real-time evidence of the genetic components of infectious agents and/or their clearance in the sewer system days before symptoms appear or infected individuals seek care.
The global emergence of MPXD highlights the importance of epidemiological and laboratory surveillance systems that can help prevent and control infections in high-risk areas and populations. Clinical surveillance is associated with certain challenges, such as social stigma, cost and availability of clinical tests, as well as providing an accurate representation of disease prevalence. WBS can overcome these limitations and, as a result, serve as a better approach for monitoring communicable diseases such as MPXD.
Several studies have reported the presence of MPXV markers in saliva, semen, urine, nasopharyngeal, rectal and stool samples. MPXV DNA has also been identified in the upper respiratory tract and urine of clinical patients in the United Kingdom.
Defoliation of skin, epithelial tissues, and skin lesions during bathing is an important route of MXPV removal in wastewater systems. Therefore, WBS can be instrumental in controlling and containing critical cases of MPXD.
Current WBS methods for controlling MPXV
Currently, several laboratories around the world have started monitoring MPXV DNA in wastewater to evaluate the role of WBS as a management tool. For this purpose, two different assays have mainly been used. The G2R_G assay, for example, targets the OPG002 gene for all MPXV strains, while the G2R_WA assay only targets the Clade II OPG002 gene.
Several studies have reported the detection of MPXV DNA in wastewater samples with 103-fold higher virus concentrations in solid fractions compared to the liquid fraction of wastewater.
The results of these studies indicate that monitoring MPXV with WBS may be possible; however, many of these studies remain at the proof-of-concept level. Notably, levels of MPXV were found to be lower than levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected elsewhere.
challenges
There are several challenges associated with using WBS to monitor MPXV in communities. In addition to the lack of standard methodologies and procedures, detection assays must be 100% inclusive and not cross-react with other Orthopoxviruses or non-target species.
Information on viral DNA loads in asymptomatic and symptomatic individuals is unknown. In addition, the lack of data on MPXV infections makes it difficult to establish a relationship or prediction model between WBS data and clinical cases.
An additional challenge is that the detection of MPXV signals in wastewater can be affected by many factors, including the complexity of the wastewater matrix, the analytical detection process and limits, virus removal by of infected individuals and infection rates. Viral release from animal reservoirs may also interfere with data on human cases.
Transmission of MPXV from water matrices is unknown and there is a lack of sewage in low- and middle-income countries. Monitoring a small population is also difficult as it can lead to ethical issues and stigmatize the population.
Conclusions
WBS can play an effective role in the surveillance of MPXV infections to ultimately mitigate the spread of MPXV.
Further research is needed to address the current challenges to allow MPXV DNA to be accurately detected in wastewater. This information will later help to identify infectiousness among populations before the onset of symptoms.