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Japanese Bats Found Carrying High Levels Of Novel Viruses, Raising Concerns About Zoonotic Outbreaks
Researchers discover a startling diversity of viruses in Japanese bats, with over 60% infected, including novel strains, highlighting the urgent need for viral surveillance to prevent future pandemics.
Study: Detection of various DNA and RNA viruses in bats in Yamaguchi Prefecture, Japan. Image Credit: Agami Photo Agency / Shutterstock
In a recent study published in the journal Microbes and Infection, researchers conducted an intensive survey of bat-derived DNA and RNA viruses from the Yamaguchi prefecture, Japan. They sequenced tissue from more than 130 bats (4 species) from four sampling locations and found that more than 60% (n = 80) of them were infected with at least one strain of potentially zoonotic viruses.
Alarmingly, the study revealed significant genetic divergence in some viral strains, particularly adenoviruses, and astroviruses, indicating that these viruses may be evolving rapidly. Notably, the study identified ten novel herpesvirus strains, reported the first occurrence of astrovirus in Japanese bats, and revealed numerous representatives of adenovirus and coronavirus families.
These findings highlight the hitherto unknown diversity of viral pathogens in Japanese bats and their surprisingly high prevalence across sampled bat species. The detection of viral sequences that were genetically identical to strains found in China and Korea underscores a potential connection between Japanese and mainland Asian bats despite the general belief that these populations do not intermingle.
The study found viral sequences identical to those of Chinese and Korean origins, suggesting limited chiropteran migration between these landmasses. However, the possibility of occasional bat migration or viral exchange through other mechanisms, such as human or animal movement, cannot be ruled out.
Additional research to characterize these viruses' life histories and pathophysiologies is imperative before action plans against zoonotic transmission can be formulated, thereby preventing future bat-transmitted disease outbreaks.
BackgroundBats are speciose (>1470 species) and highly successful members of the order Chiroptera, representing at least 20% of all known mammalian species. Unlike other mammals, bats are capable of true flight, with some species known to embark on seasonal migrations of hundreds of miles. These fascinating animals are almost ubiquitous in their distribution, found on every major landmass except the Arctic and Antarctic zones.
Unfortunately, bats are also known reservoirs (natural hosts) for more than 20,000 viral species (33 families), some of which cause zoonotic diseases, including rabies, Nipah, Hendra, Ebola, and coronavirus.
Recent research suggests that the coronavirus disease 2019 (COVID-19) outbreak, arguably the worst pandemic in human history, originated in Chinese bats. Therefore, monitoring bats and their viral parasites is imperative to prepare for future zoonotic outbreaks.
While bats in China and the Western world have been the subject of extensive research, Japanese bats have been comparatively ignored. Hitherto, the limited number of bat-derived virus investigations have only revealed 109 strains (9 families) from the country, a probable severe underestimate of these viral carriers' true pathogenic potential and diversity.
This limited research also leaves gaps in understanding how virus strains in Japanese bats genetically differ from those found in other regions, particularly Southeast Asia. Unraveling the viral populations in Japanese bats would allow the island nation and (given bats' long-range dispersal ability) the rest of the SE Asian and Australasian region to better prepare for future zoonotic events.
About the studyThe present study comprised a year-long (2021-22) intensive investigation of DNA and RNA viruses inhabiting Japanese bats (n = 132, 4 species) from four locations within the Yamaguchi prefecture, Japan. Bats were captured in nets, and morphological examinations were conducted to classify individuals as Miniopterus fuliginosus, Myotis macrodactylus, Rhinolophus ferrumequinum, or Rhinolophus cornutus.
Of the 132 individuals captured, 85 were euthanized and harvested for lung (n = 40), brain (n = 40), and rectal swab samples (n = 85). Additionally, oral swab samples were collected from all 132 captured individuals. DNA extracted from samples was amplified using nested polymerase chain reaction (PCR) to identify and characterize DNA viruses.
Similarly, RNA was extracted and amplified using reverse transcription (RT) -PCR followed by nested or semi-nested PCR to identify RNA viruses. While 178 samples were screened for the presence of calicivirus, paramyxovirus, flavivirus, and rotavirus, all were negative for these pathogens.
Finally, the Molecular Evolutionary Genetics Analysis (MEGA) software package was used for sequence cleaning and alignment (ClustalW). Cleaned sequences were compared with preexisting genetic data from the GenBank database. Neighbor-joining (NJ) trees were constructed for phylogenetic analysis using MEGA, with visualization done in R Software.
Study findingsOf the 297 samples collected, 124 (~42%) were positive for viral nuclear material. Notably, more than 60% of screened bats (80 of 132) were found to be infected with one or more virus strains (36% of infected bats presented multiple viral strains). Herpesvirus was the most prevalent viral family, infecting all sampled bat species and present in 42.4% (56/132) of screened oral swabs.
In particular, the herpesvirus strains identified in this study displayed phylogenetic similarities to previously identified strains from China and Spain, suggesting a more complex evolutionary history of these viruses than previously thought. Astroviruses (15.2%) and coronaviruses (9.4%) were represented in all sampled species except R. Cornutus. Adenovirus was the rarest viral family observed in only five R. Ferrumequinum and My. Macrodactylus individuals.
Herpesviruses isolated in this study were found to belong to subfamilies Betaherpesvirinae and Gammaherpesvirinae, 10 of which were novel to science. Bats infected with herpesviruses often presented multiple strains (a 'superinfection').
"In the present study, we also observed some mixed peaks in the Sanger sequencing chromatograms, precluding the accurate determination of nucleotide sequences in these samples (data not shown). Considered together, these lines of evidence strongly suggest that bats may be superinfected with multiple herpesviruses, meaning that the detection of bat herpesviruses by sequencing may be complicated by the presence of mixed sequences derived from distinct viruses."
Surprisingly, each of the five animals depicting adenovirus infections presented a unique viral strain, all aligned with sequences from the genus Mastadenovirus. These adenoviruses showed significant genetic divergence from previously sequenced Japanese bat-derived viruses, suggesting a rapid evolutionary process, possibly driven by host-specific factors. This study is also the first report of astroviruses from Japanese bats.
Since adenoviruses and astroviruses are often implicated in mammalian interspecies transmission (including humans), additional research on these strains' pathogenicities, transmission routes, and transmission cycles is required to help prepare policymakers and clinicians for future viral outbreaks.
"To date, many coronaviruses belonging to the genus Betacoronavirus, including merbecoviruses isolated from Vespertilio sinensis and Eptesicus japonensis and sarbecoviruses isolated from R. Cornutus, have been detected in eastern Japan. In the present study, only alphacoronaviruses were detected in R. Cornutus, although this correlation may reflect the small sample size employed in our study. Further investigation will be needed to identify possible infection of bats by betacoronaviruses, especially sarbecovirus and merbecovirus in the western part of Japan."
ConclusionsThe present study reveals an unexpectedly high prevalence (>60%) of zoonotic viral infections among Japanese bats from the Yamaguchi prefecture. At least 10 novel species of herpesvirus and five novel strains of adenovirus were obtained from genetic analysis, some of which displayed genetic sequences identical to those found in mainland Asia, raising questions about bat migration patterns or alternative routes of viral transmission. The rapid evolution of these viruses highlights the need for routine monitoring and screening of bat populations and parallel epidemiological research on identified strains to help prevent or address future epi- or pandemic viral outbreaks in bats, mammals, and humans.
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Tackling Antimicrobial Resistance Needs A Tailored Approach — Four Specialists Weigh In
This month, world leaders are gathering at the 79th session of the United Nations General Assembly in New York to discuss the problem of bacteria, fungi and protozoans increasingly evolving resistance to antimicrobial drugs. Historically, solutions have focused on high-income countries, even though 4.3 million of the estimated 5 million deaths associated with infections of drug-resistant bacteria occur in low- and middle-income countries. Ahead of the UN meeting, four specialists — from Bangladesh, Brazil, Nigeria and the Middle East — told Nature which changes will be most crucial where they live.
SENJUTI Saha: Bangladesh
Senjuti Saha sees the need for a global commitment to support data collection on resistance.Credit: Vivan Mehra
For more than a decade, I have seen the impact of antimicrobial resistance (AMR) on people, particularly newborns, at first hand. Bangladesh Shishu Hospital and Institute in Dhaka — one of the collaborating organizations of the Child Health Research Foundation, where I work — is the country's largest children's hospital. Here, six out of every ten babies with infections caused by multidrug-resistant Klebsiella pneumoniae bacteria die, often just a few days after being infected.
In Bangladesh, a major difficulty in the fight against AMR is the lack of data on which bacteria are infecting whom, on how the various strains respond (or not) to which antibiotics and on how decisions are made about which drugs to use.
Stop delaying action on antimicrobial resistance — it is achievable and affordable
Bangladesh's health-care system is unusual in that most people receive treatment in community clinics, diagnostic centres and pharmacies rather than in hospitals. People tend to go to hospitals only when treatment obtained from these other places fails. But because most of the country's AMR data come from hospitals, government officials, clinicians and microbiologists have a skewed understanding of the problem.
Thanks to biases in the available data, many people think, for instance, that resistance is ubiquitous. Physicians often give patients late-generation or last-resort antibiotics even though early-generation drugs could still work. This in itself might be worsening resistance.
Another issue that affects Bangladesh in particular is the lack of protocols and basic interventions in and around health care that, if implemented, would greatly improve the situation.
For the babies at Shishu hospital, the most effective approach to saving lives is preventing infections from taking hold in the first place. Strategies that could substantially reduce AMR include investing in parental nutrition during gestation (which, in turn, would improve babies' birth weights and reduce their susceptibility to infection), ensuring that pregnant people receive antenatal and perinatal care and promoting delivery practices that minimize the risk of babies (and birthing parents) getting infections.
What's needed in Bangladesh — and in low- and middle-income countries more broadly — is a global commitment to support research and data collection on AMR, and investment in the basic interventions that will reduce it.
ANA CRISTINA GALES: Brazil
Ana Cristina Gales thinks that even small changes can be transformative for Brazil.Photo courtesy of Ana Cristina Gales
Five years ago, a 15-year-old boy was brought into the hospital where I work in São Paulo, Brazil, after developing an infection. He had cut his ankle while retrieving a kite from a stream. The boy developed a severe, systemic infection caused by methicillin-resistant Staphylococcus aureus and died around five weeks after being admitted.
That boy stuck in my mind, because he was around the age of my two daughters at the time. As a consultant in infectious diseases, I have seen too many people affected by AMR. One of the most frustrating aspects is that this devastating problem could be greatly reduced with relatively simple measures1.
Issues that affect hospitals in Brazil — and in many other countries — include staff members failing to keep surfaces and their hands clean, and failing to isolate people infected with bacteria that are resistant to antimicrobial drugs. Some people have to spend days waiting for beds on stretchers in hospital corridors, making it harder for health-care workers — who are often overworked — to implement basic measures to prevent and control infections. In fact, over the past two decades, investigators have described several cases in which identical antimicrobial-resistant bacteria (of the same clone) have been found in distinct hospitals2 — the implication being that resistant bacteria are being transferred between institutions, perhaps through the movement of patients.
But as illustrated by the case I described, AMR does not occur only in hospital settings. And in Brazil, one of the biggest challenges is people's failure to recognize AMR as a public-health problem. Most people who don't work in hospitals lack the knowledge needed to understand what AMR is and how it could affect their health. The country is battling endemic diseases, such as malaria, leishmaniasis and Chagas disease. And over the past 10 years, Brazil has experienced numerous epidemics caused by mosquito-borne viruses, including Zika, chikungunya, yellow fever, dengue and, most recently, Oropouche fever. Such diseases tend to receive more attention than does AMR, which is harder for people to pin to a particular cause.
Antibiotic resistance is a growing threat — is climate change making it worse?
As long as AMR is not seen as a significant health threat at a societal level, it will continue to be overlooked by policymakers and politicians. More positively, however, Brazil has enormous potential to reduce AMR, because it has a universal, decentralized health-care system in place for bringing medical interventions to everyone. It also has national programmes that provide people with vaccines and medications to treat HIV and hepatitis for free. Moreover, as one of the world's largest producers of animal protein, Brazil could help to lead the reduction of antimicrobial use in livestock rearing. In fact, over the past decade or so, Brazil has already made some key advances when it comes to tackling AMR.
Since a law was introduced in 2010, people have been able to buy antibiotics (for human use) only with a medical prescription. Over the past few years, the government has invested millions of US dollars in research on AMR — and in surveillance, both in state laboratories and in hospitals. Furthermore, Brazil has developed a national plan to reduce the problem using a multisectoral and transdisciplinary 'One Health' approach, which is currently under review.
Transforming this plan into a successful programme, similar to the country's vaccination, HIV and hepatitis schemes, will require more political buy-in and a lot more investment in efforts to raise public awareness. It will also require the integration of priorities across human, animal and environmental health. But clinicians, scientists, government officials and others don't need access to advanced technologies and new antimicrobials to make an enormous difference. A few, relatively simple changes could be transformative: more parents and other caregivers vaccinating children; more people avoiding the use of antimicrobials when they are unnecessary, such as those used to treat viral respiratory infections; and expanding the nation's basic sanitation programme, so that every Brazilian city treats its sewage before releasing it into the environment.
IRUKA N. OKEKE: Nigeria
Improved access to health care can help to reduce antimicrobial resistance, says Iruka Okeke.Credit: Science for Africa Foundation
Most Nigerian people have a severe bacterial infection or malaria at least once a year. So they have a real as well as a perceived need for antimicrobials. But people are often unable to obtain the ones they need, or they use antimicrobials without advice from health-care providers. (In 2019, only 41% of Nigeria's population could access health care easily.) Often, physicians don't have access to the diagnostic tools needed to inform their decisions about what antimicrobials people should take, or individuals can't afford those specific drugs. So, although in many settings the use of antimicrobials is excessive or inappropriate, in Nigeria, improving people's access to health care and medications must be part of any plan to address AMR.
An article in the Lancet Series on Antimicrobial Resistance published in May1 proposes that authorities should aim to reduce the number of deaths caused by AMR by 10% and the inappropriate use of antibiotics in humans and other animals by 20% and 30%, respectively, by 2030. I am convinced that Nigeria could meet these targets using tools available today.
A patient receives dialysis in June at Al-Shifa hospital in Gaza City, which was damaged during the Israel–Hamas conflict.Credit: Dawoud Abu Alkas/Reuters
One-quarter of Nigeria's population defecates outside, such as in fields, gutters and forests, instead of using a toilet, some or all of the time. And data from a 2024 report3 I was involved in show that most city residents rely on household water from wells or boreholes that is contaminated by faeces. This is the case in Ibadan, where I live. Agents of disease — including typhoid, diarrhoea and cholera — can spread easily, as can non-harmful (commensal) organisms harbouring resistance genes that can be transmitted to pathogenic bacteria. One such commensal microorganism is Escherichia coli, which is typically found in the intestine. Providing people with safe water and better sanitation could reduce the impact of both enteric infections (stomach or intestinal illnesses caused by microbes, such as viruses, bacteria and parasites) and AMR simultaneously, yielding an estimated return of US$5 or more for every $1 spent4.
Modest investment could also improve infection prevention and control practices at health-care facilities — such as promoting handwashing or the isolation of people infected with antimicrobial-resistant bacteria. In 2020, the Nigeria Centre for Disease Control and Prevention released updated guidelines on infection control and prevention. A modelling study5, published in May as part of the Lancet series, indicates that by following such guidelines judiciously, health-care providers could prevent antimicrobial-resistant infections in health-care settings, which currently account for about 300,000 deaths worldwide.
The fight against antimicrobial resistance
Nigeria has been rolling out pneumococcal vaccines since 2014 and rotavirus vaccines since 2022. But coverage, currently at 60% and 49%, respectively (according to data from the United Nations' children's charity UNICEF), needs to be extended. Malaria and typhoid-conjugate vaccines are yet to be deployed. Moreover, a global shortage of cholera vaccines has hampered their use in recent outbreaks. All of these vaccines could reduce levels of AMR — by lowering the chance of complications arising that involve bacterial infections, and of people administering antibiotics inappropriately. According to the modelling study in the Lancet series, vaccines could prevent around 180,000 deaths associated with AMR annually5.
In 2017, Nigeria launched an AMR surveillance system. Once this system covers a greater geographical area and more comprehensive data are collected — from people, animals and the environment — investigators will be able to quantify the impacts of each of these tools and support the prioritization of interventions for national deployment.
NOUR SHAMAS: Middle East
Humanitarian relief efforts should prioritize infection surveillance, says Nour Shamas.Credit: Aziz Reguig
I am constantly worrying about whether my mother, who has a recurrent infection of the urinary tract (which is resistant to most antibiotics), will be able to keep accessing the health-care services and antibiotics she needs. She lives in Beirut, Lebanon, and I am always reminding her to keep her passport and antibiotics to hand in case she has to flee in the face of a military attack.
The impacts of political and economic instability and conflict are often overlooked when people consider the factors contributing to AMR. But it's much harder to implement and maintain the types of intervention often recommended to mitigate resistance, such as restrictions that limit over-the-counter dispensing of antimicrobials, in Lebanon and other eastern Mediterranean countries that are experiencing ongoing conflict. In fact, such an intervention could limit access to lifesaving antimicrobials for those who cannot otherwise obtain them.
The destruction of health-care facilities, schools and other infrastructure as well as people's livelihoods, and the displacement of both local people and refugees, provide an ideal environment for AMR to increase. In those places facing conflict or receiving refugees, living spaces are becoming increasingly crowded. Many people have lost access to clean water and sanitation, health care, medications and vaccinations. Most have lost wages and many are no longer able to obtain adequate nutrition, and people are more likely to use antimicrobials inappropriately — if they can get hold of them.
Although investment must be made globally in interventions to mitigate resistance, I urge all funders and aid organizations to factor AMR into humanitarian relief efforts. More research must be done on the impact of AMR on communities living in conflict-affected areas, and on context-specific solutions. Extra resources must be devoted to improving supply chains and access to antimicrobials and diagnostic tools, and to improving their use in these regions. And AMR surveillance, infection control and health systems as a whole must be strengthened in conflict-affected areas.
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