Is the rare "multiple infection" really that scary? ​

"Multiple infections" are rare, and many times the test results are due to contaminated samples; even if multiple infections do occur, the situation may not be as bad as the public imagines.

Written by Li Changqing (Doctor of Medicine, practicing physician in the United States)

This fall and winter, along with respiratory diseases, the concept of "multiple infections" is also prevalent.

There is a case that has been widely circulated in the media and self-media. A hospital took blood samples from a patient with fever and cough and tested 9 respiratory pathogen serum antibodies. 7 of them were found to be positive. The hospital then believed that the patient was infected with 7 viruses and bacteria at the same time, and then attributed the patient's recovery to the effectiveness of their own treatment.

Similar situations are not uncommon: just open a search engine and type in "multiple infections" to find a large amount of recent news and online Q&A related to this. The content is nothing more than describing the severity of the current multiple infection situation, the difficulty of treatment, and recommending various medication regimens.

This has caused panic among patients and their families, especially parents of sick children, to a certain extent. In fact, this panic is unnecessary.

Do multiple infections exist? Of course they do. A person can be infected with multiple pathogens at the same time, including multiple viruses. For example, someone can be infected with hepatitis B and hepatitis C at the same time, and an AIDS patient can be infected with herpes virus, influenza, multiple bacteria, fungi, etc. However, some of these situations are chronic viral infections, while others are special manifestations of patients with low immunity.

When it comes to common acute infections targeting a specific part of the body, the meaning of "multiple infections" is different.

There are many different types of infections, which can be simply divided into bacterial infections that may require antibiotics, and viral infections that do not. If it is a bacterial infection, it is important to determine whether it is a multi-bacterial infection, because different bacteria may require different antibiotics to treat. Antibiotics that are effective against one bacteria may not be effective against another.

So, are multiple bacterial infections common? In clinical practice, except for surgical infections caused by surface trauma, most common visceral infections such as the digestive tract and respiratory tract and relatively rare nervous system infections are mostly single bacterial infections.

This is verified by many bacterial culture results for diagnosis and guidance of antibiotic treatment. Valuable bacterial culture specimens are basically single bacteria. If multiple bacteria are cultured, especially those containing common normal colonies, it is often considered that the specimen is contaminated.

Why are most bacterial infections caused by a single bacterium? This is related to the source of infection, the route of infection, the body's defense mechanism, and competition between bacteria.

Let's talk about the source of infection first. Some bacteria can survive in special environments, including natural environments and medical environments. In the natural environment, for example, the well-known tetani bacillus can survive in oxygen-deficient soil, and it is easy to be infected if it is stabbed by a sharp weapon contaminated by the soil. Pseudomonas aeruginosa is particularly suitable for survival in bathtubs. The rash caused by infection with this bacteria has a special common name, called "bathtub rash." Because of the screening of antibiotics and disinfection measures in medical environments, Clostridium difficile, which is resistant to many antibiotics and can evade conventional disinfection methods, can infect the human body. These survival advantages give them priority in infecting humans in specific environments.

Then there are the infection routes of fungi. Many bacteria have their own unique channels for infecting the human body, such as pneumococcus, which mainly infects the lower respiratory tract, and salmonella, which mainly infects the lower digestive tract. Some bacteria have evolved special proteins in the process of co-evolution with humans, which can bind to special receptors of human cells and cause specific infections. Some bacteria can also colonize in parts of the human body where other bacteria cannot survive. These abilities come from special receptors and special biochemical mechanisms, such as Helicobacter pylori, which can colonize in the stomach in the strong acid environment of the human body.

Next, let's talk about the human body's defense mechanism. The human body has an immune recognition system, collectively known as PRR (pattern recognition receptor). PRR is divided into two major categories. One is Toll-like receptors, which are expressed by more than a dozen different genes, denoted as TLRs, and recognize different exogenous substances, such as TLR2 recognizes Gram-positive bacteria and TLR4 recognizes Gram-negative bacteria. The other is cGAS/STING receptors, which can recognize viral nucleic acids.

For people with normal immune function, once a pathogen invades and binds to the corresponding receptor, the body will respond by secreting interferon. This is part of the cell's inherent immunity, not specific immunity. It not only fights against the pathogens that have already invaded and infected, but also inhibits other pathogens, making it difficult for other types of pathogens to invade.

Competition means that many bacteria produce special substances to inhibit the growth of other bacteria. The combined effect of the above factors leads to the fact that most bacterial infections are caused by a single pathogen.

Although most bacterial infectious diseases are mainly caused by a single bacteria, clinical treatment often chooses to use multiple antibiotics in combination. This is because before bacterial culture, it is difficult to determine which type of bacteria it is through clinical manifestations, imaging and laboratory tests, and bacterial culture takes several days to produce results. In order to be safe, it is often necessary to consider the possibility of multiple common bacterial infections, and try to cover these common bacteria when choosing antibiotics. For example, the common combination for the treatment of community-acquired pneumonia, ceftriaxone combined with azithromycin, takes into account the multiple possibilities of infection by Gram-positive bacteria, Gram-negative bacteria and atypical pathogens; the combination of ceftriaxone and doxycycline for the treatment of sexually transmitted diseases is also to cover gonococci and chlamydia, two common sexually transmitted bacteria. Even if it is clear that it is a certain bacteria, combined medication can cover possible drug-resistant bacteria and reduce the occurrence of drug resistance. Common ones include combined medication for tuberculosis infection. In-hospital Pseudomonas aeruginosa infection also requires more than two anti-Pseudomonas aeruginosa antibiotics.

If multiple infections are confirmed, additional antibiotics may be needed.

So do we need the same strategy for viral infections? The answer is no.

Currently, the main infections that plague hospitals are respiratory viral infections. We mainly discuss acute respiratory viral infections. Like bacterial infections, most people are infected with a single virus during a single illness. This can be verified by viral nucleic acid tests of most respiratory specimens - few people's nasal swab specimens will be positive for more than two viruses.

The reason why single virus infection is common is similar to the mechanism of bacterial infection: first, the source of infection. Most patients with respiratory infectious diseases are infected from other patients. People who excrete toxins only excrete one virus, and people who are infected are also infected with only one virus. Secondly, the human immune mechanism and the competition mechanism between viruses. After the virus infects the human body, it will induce human cells to produce interferon, which prevents other viruses from infecting the human body. During the respiratory virus epidemic, the trend of many viruses is opposite. There is always one virus that is dominant and other viruses are at a disadvantage.

However, some researchers believe that multiple viral infections may be more common than expected, with reports showing that dual infection can reach 30%. However, in terms of disease outcomes, different observations have drawn different conclusions. Some studies believe that multiple infections will aggravate the disease, some believe that it has no effect on the disease, but will prolong the duration of symptoms, and some studies believe that it has no effect on the duration of symptoms.

Considering that there is still a lack of specific drugs for most viral infections, and most viral infections develop in a benign manner (self-limiting), the presence or absence of multiple viral infections has little effect on diagnosis and treatment. Since testing or not has no obvious effect on treatment, excessive testing will not bring any benefits, but only harm. If the detection method is inappropriate, such as using serum antibodies to detect respiratory viral infections (high false positive rate), it will inevitably lead to unnecessary panic and excessive treatment.

Existing signs show that in the current season of high incidence of respiratory virus infections, a considerable part of the so-called "multiple infections" should come from sample contamination. Excessive promotion of this concept will increase panic and confusion, not only will it not help improve the efficiency of diagnosis and treatment, but it may increase the burden on the medical system.

Reference Links

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047693/

[2] https://www.bbc.com/future/article/20230210-can-you-get-two-viruses-at-the-same-time

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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