Since COVID-19 reared its head and exploded around the globe, several previously fairly dormant diseases and viruses have also emerged, creating increasing awareness of the ease at which these can spread, and the importance of being alert to the unexpected, particularly zoonotic, diseases, reports MedicalBrief.
Apart from COVID-19 leading the pack, health authorities are also concerned about the resurgence of monkeypox, now spreading rapidly worldwide, with four reported cases in South Africa.
Last month there was an outbreak of the deadly Marburg virus in Ghana (linked to infected animals, including bats), and now, Finnish health experts are warning of a possible Sindbis virus epidemic (spread by mosquitoes, and which also reared its head in South Africa last year, as as well as in Russia and Sweden).
In China, cases are rising of the novel Langya henipavirus (LayV), creating ripples of anxiety: this zoonotic virus is being attributed to shrews, but has also been linked, in the past, to bats and pigs.
In February, researchers from the Zoonotic Arbo and Respiratory Virus Programme, Department of Medical Virology, Centre for Viral Zoonoses, University of Pretoria, published a study in Frontiers journal entitled Incidence of Sindbis Virus in Hospitalised Patients With Acute Fevers of Unknown Cause in South Africa, 2019-2020.
They said little was known about the febrile and neurological disease burden of Sindbis virus (SINV) in South Africa, but that it was initially identified as a human pathogen in 1961 when it was first isolated in patients with fever in Uganda. It has since been demonstrated to be the causative agent of a febrile illness associated with maculopapular rash, fatigue and joint pain in humans in Africa, Europe, Australia and Asia, and also in Finland, Sweden and Russia.
They concluded that “SINV contributed significantly to AFDUC cases in hospitalised patients during the late summer and autumn months in SA”.
The authors said: “Despite the historical SINV outbreaks and annual sporadic cases reported in SA, limited epidemiological data on hospitalisations in SA or other African countries existed before this study. The association with neurological signs reported here suggest the severity of the disease may be underestimated and needs further investigation. It is, therefore, important for medical health practitioners to be aware and familiar with zoonotic infections, how they present themselves as well as the potential for outbreaks. Because there is no known treatment, cure or vaccine for most of the arboviruses, such as SINV, preventative measures, such as vector control, can be introduced.”
More recently, and further afield (Finland), in a recent Eurosurveillance study, researchers warned of a potentially impending epidemic of the Sindbis virus, due to its high incidence throughout that country in 2021.
Although ribonucleic acid (RNA) viruses are not typically found in humans, they are responsible for many zoonotic diseases that eventually reach humans.
Different types of birds, especially migratory and game birds, act as amplifying hosts for the SINV, which is primarily transmitted by mosquitoes.
Among these RNA viruses are alphaviruses like SINV, which originated near Sindbis, Egypt. Pogosta disease, caused by infection with SINV, manifests as a rash, myalgia, arthralgia and fever. Arthralgia and myalgia from this disease may persist for up to several months or years, which can have a detrimental impact on the patient’s quality of life.
Enzyme-linked immunoassay (ELISA) is typically used to diagnose the Pogosta disease, with positive results reflecting the presence of either SINV immunoglobulin M (IgM) and IgG antibodies in a single serum sample or when seroconversion has occurred between two serum samples.
Since 1995, laboratory-confirmed cases of Pogosta disease have been reported to the National Infectious Diseases Register (NIDR).
The Finland SINV outbreak
Although SINV has been detected in mosquitoes and birds throughout the globe, symptomatic human infections are primarily reported in Finland, Russia, Sweden and South Africa. Notably, in 2021, the transmission of SINV in Finland led to a major outbreak involving 566 laboratory-confirmed human cases that were distributed countrywide.
Late-winter heavy snowfall in that country this year has rendered surplus melting water, encouraging early breeding of mosquitos.
Furthermore, there has been an increase in bird populations in Finland, also providing more amplifying hosts for SINV. Taken together, these elements rendered favourable conditions for increased SINV transmission in 2022.
Pogosta disease is possibly under-recognised in Finland, particularly where the condition is scarce. The definitive diagnosis of SINV patients is crucial due to the potential burden of long-lasting joint discomfort. In Finland and Sweden, 24.5% and 39% of diagnosed patients, respectively, have experienced these symptoms.
Considering this looming threat, surveillance is currently being conducted to raise awareness of an impending SINV outbreak in 2022.
About the Finnish study
The current study involved the use of laboratory-confirmed data from the National Infectious Diseases Register (NIDR) between 2002 and 2021. The period of sample collection, as well as the location of residence of the patients at the time of diagnosis, were analysed.
In 2021, August and September witnessed the greatest number of SINV cases at 175 and 309 cases, respectively. Significantly fewer cases were reported in June, July, October, November and December as compared to previous months.
In 2021, the incidence of Pogosta disease in various hospital districts ranged from 0 on land Islands to 40.6 in North Savo per 100 000 inhabitants. Most cases were reported in hospital districts in central, eastern and western Finland, and in Lapland.
While several hospital districts reported considerable numbers of cases during both outbreaks in 2002 and 2021, clear disparities were reported in the Western and Southern coastal hospital districts in 2021 compared with 2002, within the range of 26-64%.
Conclusions
Among mosquito-borne viruses in the EU in 2021, SINV was responsible for the largest outbreak, including a total of 566 confirmed cases in Finland alone.
It remains difficult to determine the factors that contribute to and facilitate SINV outbreaks. Thus, there is an urgent need to raise public awareness about the Pogosta disease and preventive measures capable of minimising mosquito bites, especially in areas with a high incidence and forecasted risk, like central, eastern and western Finland.
Cases tend to fluctuate from one region to another, symptom identification and diagnosis remain difficult. Thus, virus-specific diagnostic testing of febrile patients who present with disease-specific symptoms is warranted.
And nearly 6 000km away, scientists are investigating the discovery of the novel Langya henipavirus (LayV) in eastern China.
In their report published in The New England Journal of Medicine, they said so far 36 patients have been diagnosed with acute LayV infection in the Shandong and Henan provinces, noting that the Hendra virus and the Nipah virus, which belong to the genus henipavirus in the family Paramyxoviridae, are known to infect humans and cause fatal disease; however, other related henipaviruses have been detected in bats, rodents and shrews.
The current outbreak
While monitoring febrile patients who reported recent contact with animals in eastern China, LayV infection was first identified through metagenomic analysis of a patient’s throat swab sample. This revealed that the LayV genome consists of 18 402 nucleotides and is phylogenetically related to the Mojiang henipavirus previously discovered in southern China in 2014.
The researchers then identified another 35 patients with acute LayV infection: 26 of them were infected with LayV alone. Of these 26, 100% had fever, 54% had fatigue, 50% presented with anorexia and cough, 46% with myalgia, 38% with headache, and 35% with vomiting. Thrombocytopenia and leukopenia were reported in 35% of patients: liver and kidney function were reported in 35% and 8% of these patients, respectively.
The researchers who identified the first LayV virus also surveyed 25 species of wild small animals as potential hosts for this virus. LayV ribonucleic acid (RNA) was identified in 27% of the surveyed shrews, suggesting that this animal is the most likely reservoir for this virus. Other domestic animals that were seropositive for LayV included 2% and 5% of surveyed goats and dogs.
A review of other henipaviruses
Other notable viruses of the henipavirus genus include the Nipah virus (NiV) and Hendra virus (HeV). Both are naturally found in Pteropus spp bats; however, their spillover into mammals ultimately led to their ability to infect human beings.
During a 1994 HeV outbreak, the infection initially presented with influenza-like symptoms after a seven to 16-day incubation period. Of the seven infected individuals, two recovered, and one developed pneumonitis and died from organ failure. The remaining three patients experienced encephalitic manifestations, including confusion, and ataxia, with fatal seizures reported in two patients.
NiV was first discovered in 1999 after an outbreak reported among both pigs and people in Malaysia and Singapore. Since then, several NiV outbreaks have been identified in Bangladesh, India and Malaysia.
Whereas the Malaysia strain of NiV (NiV-M) is associated with a case fatality rate (CFR) of 40% and primarily causes neurological symptoms, the Bangladesh strain (NiV-B) typically causes severe respiratory distress and has a CFR of 90%.
Approaches to mitigate LayV outbreak
In previous NiV outbreaks, public health officials have urged the widespread use of sensitive rapid diagnostic tests (RDTs) to quickly identify and isolate potentially infected individuals. Several preventative and non-pharmaceutical measures can also be implemented to effectively reduce the R0 until medical countermeasures become available.
NiV and other henipaviruses are associated with high pathogenicity and are considered to be pathogens of notable epidemic potential. Although there are no therapies available to treat henipavirus encephalitis, several antiviral therapeutics targeting different RNA and DNA viruses could be used against henipavirus infection.
Several monoclonal antibodies (mAbs) are also under development against henipaviruses.
Conclusions
Since LayV was the only pathogen identified in a majority of the patients with acute LayV infection, the researchers are confident LayV was the primary cause of their febrile illness. Contact tracing of 15 people who interacted with nine LayV-infected patients did not reveal that human-to-human transmission occurred; however, the study’s small sample size does not eliminate the possibility that human-to-human transmission is possible.
Sentinel surveillance of similar febrile illnesses reported among people who recently interacted with shrews or other potential reservoirs of LayV is essential to better understand this human illness.
Study 1 details
Sindbis virus outbreak and evidence for geographical expansion in Finland, 2021
Suvanto, M. T., Uusitalo, R., Im Kampe, E. O., et al. (2022).
Published in Eurosurveillance on 4 August 2022
Sindbis virus (SINV) (Togaviridae family, Alphavirus genus) is the causative agent of Pogosta disease, a typically self-limited disease with common symptoms of rash, arthralgia, myalgia and fever. In some cases, arthralgia and myalgia can persist from months to years and negatively affect quality of life [2,3]. While circulation of SINV has been reported in mosquitoes and birds globally, symptomatic human infection has almost exclusively been reported in Finland, Sweden, Russia and South Africa. However, larger outbreaks and annual cases are reported only from Finland, where the SINV seroprevalence in the general population was 5.2% in the years 1999 to 2003 [5].
Laboratory diagnosis of Pogosta disease is done using ELISA, and paired samples are often needed because the antibody response against SINV develops slowly [6]. In Finland, SINV has been endemic since the 1960s, and the first epidemic occurred in 1974 [1,7]. A laboratory-confirmed case is defined as either detection of SINV IgM and IgG in a single serum specimen or seroconversion between paired specimens.
The laboratory-confirmed cases have been notified to the National Infectious Diseases Register (NIDR) since its implementation in 1995. A total of 566 laboratory-confirmed cases were notified in 2021, compared with an average of 158 annual cases between 1995 and 2021, making it a notable outbreak year. Similarly, high incidence had previously been reported in 2002 with 597 laboratory-confirmed cases.
The aim of this rapid communication is to increase awareness of an upcoming SINV epidemic in 2022. The high SINV incidence in 2021 may precede a larger epidemic.
South African Study details
Incidence of Sindbis Virus in Hospitalized Patients With Acute Fevers of Unknown Cause in South Africa, 2019–2020
Kgothatso Meno, Clarence Yah, Adriano Mendes and Marietjie Venter.
Published in Frontiers on 7 February 2022
Background
Sindbis virus (SINV) is a mosquito-borne alphavirus that is widely distributed worldwide. Little is known about the febrile and neurological disease burden due to SINV in South Africa.
Patients and Methods
Clinical samples of patients with acute febrile disease of unknown cause (AFDUC) were collected through the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents at three sentinel hospital surveillance sites in South Africa. In total, 639 patients were screened using a PCR-based macroarray that can simultaneously detect nucleic acids of 30 pathogens, including SINV, from January 2019 to December 2020. Serum samples were randomly selected from the arbovirus season (January–June) and also screened with a commercial indirect immunofluorescence assay for anti-SINV IgM. In addition, 31 paired cerebrospinal fluid (CSF) specimens from the same patients were screened for IgM. Micro-neutralization assays were performed on all IgM-positive samples.
Results
None of the specimens tested positive for SINV by molecular screening; however, 38/197 (19.0%) samples were positive for SINV-specific IgM. A total of 25/38 (65.8%) IgM-positive samples tested positive for SINV-neutralizing antibodies, giving an overall incidence of 12.7%. Furthermore, 2/31 (6.5%) CSF specimens tested positive for IgM but were negative for neutralizing antibodies. There was a higher incidence of SINV-positive cases in Mpumalanga (26.0%) than Gauteng province (15.0%). The most significant months for IgM-positive cases were April 2019 (OR = 2.9, p < 0.05), and May 2020 (OR = 7.7, p < 0.05).
Conclusion
SINV or a closely related virus contributed to 12.7% of AFDUC cases in hospitalised patients during the late summer and autumn months in South Africa and was significantly associated with arthralgia, meningitis, and headaches.
See more from MedicalBrief archives:
Scientists warn of more zoonotic diseases as third SA monkeypox case confirmed
HEV re-emerging as a zoonotic virus also afflicting the affluent
Zoonotic transfer study fuels call for ban of wildlife trade, markets and medicinal use
First cases of deadly Marburg virus reported in Ghana
Monkeypox possibly linked to decrease in smallpox vaccine – global experts