Antibiotics are a group of medicines used to treat and prevent infections and diseases caused by single cell microorganisms called bacteria. They act either by killing bacteria directly or by preventing them from dividing and reproducing. A limited number of antibiotics can also treat diseases caused by single-cell parasites called protozoa, but none of them are effective against viruses, the agents responsible for cold and flu.
There is evidence that antibiotics have been used for thousands of years to cure infections. Various plant extracts, herbs, honey and even animal faeces were used by earlier civilisations to treat bacterial infections. In ancient Egypt, for example, people used to apply moulded bread to treat infected wounds. Despite the fact that antibiotics have been used throughout history, was only in the 19th century, that scientists linked bacteria as the cause of some infections. Also, up until the 1930s, many people often died with minor bacterial infections and surgeries were very risky. The discovery of penicillin revolutionised medicine, when in 1928 Alexandre Fleming noticed that bacteria present in his culture plates have been killed by a type of mould that accidentally contaminated them. The specie of mould (fungus) that invaded Fleming’s plates was a Penicillium notatum, what subsequently led to the name of penicillin. Recognising the potential of this discovery, Fleming and his colleagues rapidly tried to commercialise it as a medicine, but it took over 10 years for the penicillin to be available in the market. The 1940s and 1950s was a great period for discovery of new antibiotics, but since then, not many new ones have been developed.
Despite the fact that antibiotics have changed the face of medicine in the 20th century, very soon after, scientists realised that bacteria could evolve and change overtime to become resistant to them, meaning that they were able to survive and grow in the presence of antibiotics that otherwise would kill them. Currently this is one of the biggest threats for global public health. As resistance occur worldwide, treatments are becoming less effective making it harder or even impossible to treat diseases such as pneumonia, gonorrhoea, blood poisoning, tuberculosis and others. According to the world health organisation, antibiotic resistance is responsible for 700.000 humans’ deaths around the world every year and these numbers are increasing, with some studies predicting that by 2050, it could reach 10 million yearly deaths, becoming the leading cause of mortality worldwide.
Bacteria can become resistant to antibiotics naturally, but this process is very often fastened by the incorrect or overuse of antibiotics. This is a big reason for concern particularly because many countries do not follow treatment guidelines, allowing antibiotics to be over-prescribed and permitting their retail without medical prescription. Similarly, lack of sanitation and hygiene conditions in some hospitals, as well as the shortage of quick and reliable laboratory tests to identify infections, can further contribute to the increasing number of antibiotic resistance happening worldwide.
This is particularly concerning in veterinary medicine. In recent years, the increased number of pets and the requirement for their welfare has enhanced treatments for sick animals, and with it, the administration of antibiotics. More importantly, the increased demand of meat production as a result of the population growth, means that farmers are more reliable on antibiotics to treat and prevent diseases in their livestock. Furthermore, some countries still allow the routinely use of antibiotics to promote animal’s growth, making it a further reason for concern. It is believed that the meat industry on its own accounts for 73% of the global use of antibiotics. Additionally, the fact that farm animals are constantly under stress and often confined to overpopulated spaces, highly compromises their immune system making them more vulnerable to infections and increasing the risk of transmission. As such, animals often become reservoir of the resistant microorganisms increasing the chances of transmission to humans, either directly by close contact; during consumption of contaminated meat or through spread of the animal’s waste into the environmental surroundings.
Despite the fact that is important to incentive research to discover and develop new antibiotics, it is crucial to learn how to use them more effectively. Countries around the world should follow international guidelines to change the way they prescribe and use the antibiotics and should create actions to reduce the spread of infections, particularly in an era of easy travel.
It is also critical to restrict the use of unnecessary human antibiotics to promote animal growth and to prevent disease in healthy animals. As alternatives, farmers should consider vaccinate the animals, create better and more hygienic housing conditions and improve husbandry procedures such as better ventilation as well as reduction of animal confinement and stress conditions. It is, therefore, vital to educate farmers and pet-owners to collaborate with the vets to understand how to use these drugs responsibly.
Urgent actions are needed to avoid history repeating itself and to see common and minor infections killing again. Yet gain, humans actions, and not animals themselves, are to blame for the antibiotic crisis. In your opinion, what do you think can be done to revert this process?
By Ricardo Ribas, Veterinary Doctor, doctorate in veterinary sciences and researcher in the area of oncology in London
1. Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol. 2010;1:134. Published 2010 Dec 8. doi:10.3389/fmicb.2010.00134
2. Gould K. Antibiotics: from prehistory to the present day. J Antimicrob Chemother. 2016;71(3):572‐575. doi:10.1093/jac/dkv484
3. Ventola CL. The Antibiotic Resistance Crisis. P T. 2015 Apr; 40(4): 277–283. PMID: 25859123
The subjects and ideas discussed in this article are for informational purposes only. For more information consult a professional in the area. Whilst every effort is made to make sure the article is accurate at the time of publication, I take no liability for any new developments on the subject as well as any errors or omissions.
Viruses are microscopic agents that infect living organisms and cause diseases. They are considered the most abundant biological entity on the planet, existing for over 1.5 billion years. Viruses have both life and non-life properties. They do not have cells and cannot turn food into energy, but have genetic material (either DNA or RNA). Without a host cell, viruses are inert containers of chemicals so they need to infect cells in order to reproduce, evolve and survive. Hosts can be humans, animals, plants, fungi and bacteria. Some viruses are harmless whilst others cause diseases, some of which leading to the death of the host. To date there are no drugs capable of killing viruses so the host is dependent on its own immune system to fight the infection. Nowadays, there are some antiviral drugs capable of inhibiting them from reproducing and developing, as well as vaccines able to prevent infections and control the spread of the disease.
There are many types of viruses, each one adapted to its own host, but at times, viruses can jump and infect different hosts through a process called “spillover”. This can happen as a result of increased contact between different species or due to mutations that allows the viruses to evolve and gain the capacity to spread more efficiency in order to survive and to become more dangerous. In recent years, we have heard more and more about viral diseases able to jump from animals to humans. Here are some examples:
Influeza: The Flu Viruses
In the last century, there have been many examples of flu-like diseases caused by viruses that jumped from animals to humans. Some are caused by influenza viruses, a family responsible for attacking the respiratory system and causing flu like symptoms in humans.
In 1918, a deadly flu-like pandemic (Spanish Flu) appeared and rapidly spread around the world, infecting 500 million people and killing an estimated of 50 million. There is still some controversy about where the virus was originated from since Europe, America and Asia were affected simultaneously, but recent studies tend to agree that the outbreak may have originated in the North of China, either from pigs or from domestic and wild birds.
But there are other more recent examples of influenza viruses that jump species, such as the ones responsible for the outbreaks of swine-flu and bird-flu.
Although pig’s influenza viruses are rarely transmitted to humans and are hardly spread between people, they were responsible for the worldwide outbreak of swine-flu in 2009-2010. The disease was firstly identified in 2009 when many cases of human respiratory illness were reported in Mexico. We now know that this virus is the result of a merge between genetic material from pigs, birds and human viruses. In animals, the disease is responsible for fever, coughing, nose and eyes discharge, sneezing, breathing difficulties and lack of appetite, however, some animals show no signs of illness. Humans show flu like symptoms and can be infected either by close contact with pigs through farming and fairs or by person-to-person contact during sneezing, coughing and by contaminated surfaces. Fortunately, the 2009 outbreak was not as serious as previously anticipated and only a relatively small number of cases lead to serious illnesses and deaths. Swine flu is now considered a normal type of seasonal flu and is included in the vaccination program.
Bird-flu is another infectious type of influenza that spreads among wild and domestic birds. The most common form of the disease is caused by H5N1, a deadly virus for birds. H5N1 was firstly identified in humans in Hong-Kong in 1997. Human cases of the disease were linked with the handling of faeces, nasal and mouth secretions of infected poultry, particularly in farms and markets. Bird symptoms include: sudden death, lack of coordination, purple discoloration of the wattles, combs and legs, misshapen eggs, diarrhoea, nasal discharge, coughing and sneezing. Humans generally suffer from fever, cough, sore throat, muscle ache but the disease can lead to pneumonia. The disease has high mortality rate and is responsible for causing the death of about 60% of those infected. The good news is that H5N1 only rarely infect humans and is not capable to spread from person to person. In spite of this, it is a fast mutating virus and if it gains the capacity to be transmissible between humans while retaining its capacity to cause severe disease, the consequences can be very serious.
Human Immunodeficiency Virus (HIV): one century with humans
Another example of a virus that crossed species is the one responsible for human immunodeficiency. Once infected, the virus attacks the immune system of the host, opening the door for other opportunistic diseases. This disease was first observed in 1981 in the USA, but scientists believe that humans got infected in the 1920’s in West-Central Africa, possibly in what is now the Democratic Republic of Congo. Scientists believe this happened when hunters consumed meat from non-human primates carrying a virus closely related to the HIV (Simian Immunodeficiency Virus or SIV), a virus that also attacks the immune system of these animals. It is suspected that the infection has reached the Caribbean islands in 1960s, New York City in the 1970’s and San Francisco a decade later, when it was finally discovered.
Ebola, the terrifying virus
The Ebola virus was first discovered in 1976 near the Ebola River in the Democratic Republic of Congo. Since then, the virus has been responsible for occasional outbreaks in human and primates in many African countries. Between 1976 and 2013, the world health organisation reported 24 human outbreaks of the disease with 1.600 deaths in total, but the largest outbreak occurred between 2013 and 2016 and was responsible for over 11.000 deaths. The disease is rare but very severe, often causing fever, sore throat, body aches, vomit, diarrhoea and sometimes bleeding inside and outside the body, with death occurring in 50% of the human infected. Scientist think that the Ebola virus may be carried by bats, because these animals don’t die of the disease. It is believed that humans get infected by contact with the infected animal’s body fluids, either directly from bats or during consumption of nonhuman primates. The virus spreads through human-to-human contact and it is also possible via blood or the body fluids of the infected person.
Coronaviruses repeated stories
Recent history also showed us how coronaviruses can jump from animals to cause a large number of human deaths. Coronaviruses are a large family of viruses known to exist for over 10.000 years. Its name derives from the latin word “corona”, that means crown due to the presence of crown-like spikes in their surface.
Coronaviruses are responsible for respiratory and intestinal diseases in mammals and birds, but the symptoms vary according to the host animal and the type of virus. For instance, in chickens, coronavirus attacks the respiratory and urogenital tracts, whilst in dogs, cats, ferret, rabbits, turkeys, pigs and cows the virus tends to affect the animal’s intestine leading to diarrhoea.
Humans, can only be infected by seven types of coronaviruses. Four of these are very common and responsible for mild respiratory infections with symptoms similar to the ones observed with a cold, but the remaining three viruses can lead to serious and sometimes lethal respiratory infections, such as pneumonia. These include the viruses responsible for the Severe Acute Respiratory Syndrome (SARS), the Middle East Respiratory Syndrome (MERS) and the most recent outbreak in China in 2019-2020 (Covid-19).
SARS was first identified in Southern China during the outbreak of the disease in 2003. Scientists believe that bats are the reservoir of the virus and that the disease was transmitted to humans through consumption of civet cats meat infected by the bats. Once in humans, the disease can spread from person to person. By the end of the outbreak, over 8000 people have been infected and approximately 10% of those died (774 people). Fortunately, no cases of SARS have been reported since 2004.
MERS was reported for the first time in 2012 in Saudi Arabia. It is known that the virus was firstly transmitted to humans by dromedary camels in the earlier 2010s, possibly during consumption of camel meat. This virus has also been found in bats and is believed that it may have infected camels in Africa in the 1990s. Even though the possibility of human to human transmission is very low, the mortality of the disease is quite high standing above 35%. So far, MERS killed 858 out of the 2494 reported cases since it appeared in 2012.
Very recently a new outbreak of coronavirus has emerged in Wuhan, China (Covid-19). Similarly to SARS and MERS, this infection is also responsible for severe acute respiratory infection that can lead to either mild or severe symptoms such as pneumonia, kidney failure and death. Since this is a very recent virus, not much is known about it yet. To date scientists haven’t yet identified which animal the reservoir for the virus is, however, it appears that the contamination to humans may have occurred in a wildlife market, possible during consumption of wild animals. Despite the fact that the rate of transmission between humans is high, the mortality rate seems low. So far, the disease has spread within China and other countries around the world and an international effort is being made to control the spread of the disease.
When human viruses infect animals?
Sometimes viruses can jump the opposite way. There are also examples of human viruses that alter and adapt to infect animals. This is the case of the human respiratory syncytial virus (HRSV) and the human metapneumovirus (HMPV) that have jumped from humans to chimpanzees. It is believed that this has occurred between 1999 and 2006 in West Africa possibly through tourists visiting the area. Whilst these viruses rarely cause severe disease in healthy adult humans, they are responsible for outbreaks of respiratory diseases among African chimpanzees leading to the death of entire populations.
Why are animal-derived outbreaks getting more frequent?
The fast-growing world population and the development of large metropolis are incentives to the expansion of wildlife trade, which favoured diseases to spill over from animals to humans. Additionally, environment and climate changes are shifting animal habitats, altering their life-styles, their geographic locations and their eating habits (who eat whom). Finally, in an era of international travel means that diseases can spread very quickly.
But a question remains. In a world more vulnerable than ever to new animal-borne diseases, what do you think can be done to prevent future outbreaks?
By Ricardo Ribas, Veterinary Doctor, doctorate in veterinary sciences and researcher in the area of oncology in London
1.Taubenberger JK & Morens, DM. 1918 Influenza: the Mother of All Pandemics. Emerg Infect Dis. 2006 Jan; 12(1): 15–22. doi: 10.3201/
2.Mena I, Nelson MI, Quezada-Monroy F, et al. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico. Elife. 2016;5:e16777. Published 2016 Jun 28. doi:10.7554/eLife.16777
3. Chan PKS. Outbreak of Avian Influenza A(H5N1) Virus Infection in Hong Kong in 1997. Clinical Infectious Diseases, Vol 34, Suppl. 2, 2002, https://doi.org/10.1086/338820
4. Sharp PM & Hahn BH. Origins of HIV and the AIDS Pandemic. Cold Spring Harb Perspect Med. 2011 Sep; 1(1): a006841. doi: 10.1101/cshperspect.a006841
5. Wertheim JO; Chu, DKW et al. A Case for the Ancient Origin of Coronaviruses. J Virol. 2013 Jun; 87(12): 7039–7045. doi: 10.1128/JVI.03273-12
6. Wang LF & Eaton BT. Bats, Civets and the Emergence of SARS. Curr Top Microbiol Immunol. 2007;315:325-44. doi: 10.1007/978-3-540-70962-6_13.
7. Haagmans, BL; Dhahiry SHSA et al., Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014 Feb; 14(2): 140–145. doi: 10.1016/S1473-3099(13)70690-X
8. Kondgen S; Kuhl H et al., Pandemic Human Viruses Cause Decline of Endangered Great Apes. Current Biology 18, 260–264, 2008 Feb. DOI 10.1016/j.cub.2008.01.012
The subjects and ideas discussed on this article are for informational purposes only. For more information consult a vet or a professional in the area. Whilst every effort is made to make sure the article is accurate at the time of publication, I take no liability for any new developments on the subject as well as any errors or omissions.
Dogs have long been man’s best friends but this was not always the case. Dogs are descendants from wolves and up until domestication, they were considered wild animals. It is believed that humans, as solitary hunters, needed help hunting and herding, as well as companionship and protection, so they would have captured wolf pups, kept them as pets and gradually domesticated them. Alternatively, dogs benefited from this process by obtaining protection, love, food and shelter from humans.
Recent studies comparing genomes from several breeds of dogs and wolves showed that the genetic divergence between both species has occurred around 20.000-40.000 years ago, which is the same time that the domestication process is believed to have happened. Besides that, archaeological reports have found remains of domestic dogs buried besides humans, the oldest of which dating back 14.000 years ago in Germany.
The geographic location where domestication has occurred is still controversial. Some studies suggest East Asia, whilst others the Middle East and Europe. More recent data indicates that dog’s domestication may actually have occurred twice in both Europe and Asia.
And what about other species?
After dogs, other species have also gone through the process of domestication. Cats, for instance, became domesticated around 8.000 years ago in the Middle East to control mice and rats that use to attack crops and farms. Other animals were domesticated for food, such as goats around 10.000 years ago in Iran and pigs/cattle approximately 8.500 years ago in Western Asia. But many other animals have become domesticated around the world. Examples include horses, camels, donkeys, llamas, sheep, guinea pigs and many birds used either for work, food, wool, transportation or for company.
But would dogs be able to survive in a world free of humans???
The domestication process made the dogs very dependent upon humans for food, love and protection, so how would our best friends behave and learn to survive without humans?
There are many examples of free-range dogs being able to live in the absence of humans as well as several reports of family dogs that survived after disappearing from home for several months. As a matter of fact, it is believed that around 80% of the dogs in the world are already living without humans. Certainly, family dogs would struggle in an initial phase, but with the time they would learn to go back to their natural instincts, to adjust and become independent. To do that, dogs would need to learn survival skills such as forming packs in a similar manner to the wolves, create new relationships with other species, become independent and more willing to take risks, adapt quickly to the changing conditions and find shelter to protect themselves from predators. With time, they probably would also need to breed with other species such as wolves and coyotes to be able to produce fertile offspring to propagate survival genes to future generations.
But not all breeds would survive in the same way. Some believe that small animals would be more vulnerable whilst others think they would be at an advantage as they required less food and would easily hide from predators. On the contrary, large animals would be more visible to predators, but would be stronger at fighting them back. Hunting dogs, such as Foxhound, Pointer, Retrievers and Irish Setter would have the advantage to run quicker and easily catch preys, but some breeds such as Pugs, Pekingeses and Bulldogs would struggle to survive due to their breathing issues. Weather conditions would also influence dog’s survival capacities. Huskies, for instance, would have a better chance of survival in cold climates, whilst dogs with short hair would be more resistant to hot conditions.
But not only the animal’s size, gender and breed would influence its survival. Individual characteristics such a personality and social skills would also be of extreme importance. Street dogs, which are more independent and risk-taking, would likely be at more of an advantage compared with house-dogs who are less adventurous and not used to co-habit with other animals.
It is difficult to predict which breeds of dogs would be more likely to survive in a world without humans or indeed ‘how’ they might survive, but one thing is for sure, our best friends will be here to stay for a long time to come yet.
What’s your opinion?
By Ricardo Ribas
Veterinary doctor, doctorate in veterinary sciences and Researcher in the field of oncology
1. Thalmann, O. & Perri, AR Paleogenomic Inferences of Dog Domestication. In: Lindqvist C., Rajora O. (eds) Paleogenomics. 2018 Population Genomics. Springer, Cham. https://doi.org/10.007/13836_2018_27.
2. Thalmann, O. “Complete mitochondrial genomes of ancient canids suggest a European origin of domestic dogs”. 2013 Science. 342: 871–4. Doi: 10.1126/science.1243650
3. Driscoll, CA; Menotti-Raymond, M et al The Near Eastern Origin of Cat Domestication 2007 Science. 317 (5837): 519–523. doi:10.1126/science.1139518.
The subjects and opinions discussed on this article are for informational purposes only. For more information consult a vet or a professional in the area. Whilst every effort is made to make sure the article is accurate at the time of publication, I take no liability for any new developments on the subject as well as any errors or omissions.
Rabies is a rare but very serious viral infection affecting the nervous system. It is generally present in the saliva of the infected animals and transmitted to humans through their bite. Whilst currently eradicated from the United Kingdom and Western Europe, rabies still exists in over 150 countries around the world, particularly in Asia, Africa as well as Central and South America and is responsible for thousands of human deaths each year, half of which involving children under the age of 15.
Get to know a little more about one of the oldest diseases of mankind.
By Ricardo Ribas
Rabies is a serious and almost always fatal zoonosis that affect mammals. The term “rabies” was originated during Roman times, meaning rage/madness down to the disease’s frightening symptoms. As a matter of fact, humans have always been terrorised from catching this disease, and it was already the subjected of myths in the Mesopotamian civilization over 4,500 years ago.
THE WORLD OVERVIEW?
Rabies is a disease that is currently spread all over the world. However, some countries have achieved disease eradication, such as Australia, New Zealand and many Scandinavian and Western European countries.
By the early twentieth century, rabies was eradicated from all Europe, however, in 1940s, it was re-entered from the east, and since the virus is transported through wildlife, its progression was difficult to control and the disease spread to Western countries. Nowadays and thanks to efficient preventive measures, rabies is currently eradicated from most Western and Scandinavian European countries. The United Kingdom has been free of rabies for 100 years with the exception of a rabies-like virus that is still existent in a small number of wild bats.
Whilst dog vaccination is not necessary in the UK, some European countries still require a compulsory annual vaccination for all dogs to avoid serious public health problems in the event of an outbreak. If you’re planning on taking your pet abroad to another European country, remember that your animal will need to be at least 12 weeks-old and already microchipped to have the rabies jab.
According to the world health organisation, there are currently 3 billion people in the world at risk of contracting this disease and an estimate of 59,000 deaths every year. This means that rabies kills one person every 9 minutes. Unfortunately, when the signs and symptoms start to manifest, the disease is almost always lethal.
WHO IS TO BLAME?
The rabies agent is a bullet-shaped virus belonging to the family of the Rhabdoviridae. Carnivores such as foxes, wolves, bats, monkeys, racoons and coyotes are wildlife hosts of the virus. Domestic animals are usually contaminated by other domestic or wild animals, whilst humans are mainly contaminated through the bites of domestic animals (dogs and cats). Dogs contribute to 99% of all rabies transmissions to humans.
The virus lives in the saliva of the diseased animals and is usually transmittable through a bite, however, in rare cases, contamination is also possible via sneezing, coughing or through superficial wounds.
WHAT ARE THE SYMPTONS?
Upon entering the host wound, the virus multiplies in their local muscle cells for several weeks or months before migrating to their central nervous system (brain and spinal cord), causing inflammation (encephalomyelitis) and leading to changes in the host behaviour. In animals, the incubation period (period from the entry in the body to the appearance of the first symptoms) is on average one to two months. In humans, the incubation period can range from four days to as long as 19 years, but in the majority of the cases it takes around 20 to 90 days for the first symptoms to appear.
IN THE PETS …
At the early stages of the disease, the animal exhibits increased nervousness and activity, difficulties breathing, fever and changes in vocalisation and sexual behaviour. Subsequently, two forms of the disease are possible: the furious and the silent forms. In the furious form, the animal becomes very alert and aggressive with dilated pupils, loss of appetite and changing in barking. Contrary, in the silent form, the animal becomes lethargic, paralysed, with muscle tremors and cries persistently. Cats present similar symptomatology with lack of mobility particularly in the chewing and swallowing muscles.
…AND IN THE HUMAN.
Humans affected by the disease show slightly different symptoms from the animals. Infected individuals, initially have flu-like symptoms, such as general weakness, headache and fever but with time those progress to neurological/behaviour symptoms. These include confusion, hallucinations, muscle spasms, bizarre beating and biting behaviours, fear of water (hydrophobia) and general deterioration of mental state, often culminating in death by cardiac or respiratory arrest.
PREVENTION AND CONTROL OF THE DISEASE
In order to keep control of rabies and to provide prompt actions to eradicate the disease in the event of the outbreak, several countries are implementing measures such as:
– Compulsory annual vaccination for all dogs aged four months old and older.
– Registration and compulsory licensing of dogs.
– Slaughter of all animals that are angry or have been bitten by animals infected with rabies.
– Veterinary examination and compulsory quarantine for all pets coming from countries with rabies.
– Wildlife vaccination by releasing oral vaccines into the ground to prevent the spread of the disease.
HUMAN PREVENTION AND TREATMENT
It is recommended that people travelling to rabies endemic areas are vaccinated and avoid contact with domestic and/or wild animals, particularly dogs and cats.
Unfortunately, no treatment is available. Infected animals are usually slaughtered and humans rarely survive from the disease. For humans exposed to rabies, post-exposure treatments such as a course of rabies vaccine or a specific immunoglobulin can be effective in preventing the disease from developing particularly if given before the start of the symptoms. Washing the bite sites and scratches with soaped water or detergent may also reduce the number of virus entering the skin and may be somewhat effective at preventing transmission.
As of 2016, only fourteen people had survived rabies infection after starting of the symptoms.
By Ricardo Ribas, Veterinary Doctor, doctorate in veterinary sciences and researcher in the area of oncology in London
The subjects, ideas, control and prevention measures discussed in this article are for informational purposes only. For more information consult a vet or a professional in the area. Whilst every effort is made to make sure the article is accurate at the time of publication, I take no liability for any new developments on the subject as well as any errors or omissions.