Is the new 'super fungus' here?

At the end of June this year, a study in the journal "Emerging Infectious Diseases" published by the Centers for Disease Control and Prevention in the United States showed that between January 2019 and October 2022, a hospital in northern China discovered 19 patients infected with a fungus called Candida Southeast Asia. The study was led by the Huang Guanghua team from Fudan University

At the end of June this year, a study in the journal "Emerging Infectious Diseases" published by the Centers for Disease Control and Prevention in the United States showed that between January 2019 and October 2022, a hospital in northern China discovered 19 patients infected with a fungus called Candida Southeast Asia. The study was led by the Huang Guanghua team from Fudan University.

Huang Guanghua, a distinguished professor of the School of Life Sciences of Fudan University and a part-time professor of the Infection Department of Huashan Hospital, told China Newsweek that the drug resistance and transmission of Candida in Southeast Asia found in the existing research is much stronger than that of Candida auris, which is more widely known, and may become another serious threat to hospital infection in the future. We believe this is a new type of 'super fungus', "Huang Guanghua said.

Candida in Southeast Asia is not the first to be discovered. As early as 2016, two scientists from Malaysia and Hungary first isolated this new species from plants and flowers on Mindanao Island in the Philippines. Afterwards, multiple countries isolated Candida from clinical specimens such as blood and wounds in Southeast Asia, but all came from sporadic cases.

Liao Wanqing, an academician of the CAE Member and director of the Institute of Dermatology, Venereal and Fungal infection of Shanghai Long March Hospital, said in an interview with China News Weekly that the number of 19 cases of infection in three years was not small. At present, he has not been exposed to Candida from Southeast Asia in clinical practice. The strains that caused the infection this time have been fully preserved, which has great clinical significance and value. Unfortunately, due to issues such as patient transfer, the research team has not continuously tracked the complete treatment status of the cases. It is not yet clear what kind of symptoms these fungi can cause, "Liao Wanqing said

"Cousin" of Candida auris

The study by Huang Guanghua's team involved 19 patients with outbreaks of infection, most of whom were blood infection cases, including 17 males and 2 females. The hospital where the infection occurred has one intensive care unit (ICU). Among the 19 infected cases, 11 were from the ICU, 4 were from the neurology ward, and 4 were from other departments within the hospital. The patient's age range is 13-83 years old, with a median age of 63 years.

Huang Guanghua said that at first, the hospital tested the pathological samples of patients with fever and patients with obvious infection symptoms, observed abnormal blood routine and serological tests of many patients, and predicted that they might be fungal infection. Subsequently, through further testing and identification, the hospital discovered that multiple patients had similar symptoms.

"Cousin" of Candida auris

Electron microscopy of Southeast Asian Candida cells isolated by Huang Guanghua's team. Image/provided by respondents

Candida auris strains in Petri dish of CDC laboratory. Image/Visual China

Since the first case of Candida auris infection occurred in Japan in 2009, Candida auris has spread rapidly around the world. According to Huang Guanghua, about 50 countries have reported tens of thousands of related infection cases, and a total of 60 cases have been reported in China, including Beijing, Liaoning, Fujian, Hong Kong, and Taiwan.

In April this year, the monitoring data published in the well-known medical journal Internal medicine Yearbook published by the American Medical Doctor Association showed that as of December 31, 2021, the United States had reported 3270 clinical cases of Candida auris and more than 7400 screening cases. The study points out that the percentage of clinical case growth is increasing every year, from 44% in 2019 to 95% in 2021. In 2021, the screening volume and screening cases of this strain increased by over 80% and over 200% respectively.

Liao Wanqing stated that since the first discovery of Candida in Southeast Asia in 2016, the related infection cases have been sporadic worldwide and there have been no outbreaks of infection in hospitals. This time, there is an outbreak of infection in domestic hospitals, and we should be alert to the possibility of such a large outbreak as Candida auris. Huang Guanghua said that according to the genome sequence of Candida isolated from Southeast Asia, these 19 cases are most likely from the same source of infection, but the Pathogen transmission is still unclear.

Huang Guanghua said that more than half of the 19 patients used peripherally inserted central catheters (PICC). Among these patients, some were severely injured due to car accidents, while others were injured after brain or tumor surgery and used PICC for several months or even longer. The use of PICC catheters may be the main risk factor for Candida infection in Southeast Asia, "the study wrote. All 19 patients used PICC delivery drugs, and the strain was isolated from the tip of the PICC catheter in 7 patients. PICC can directly deliver various drugs to the central vein near the heart, avoiding damage to blood vessels caused by irritating drugs. It is usually used for patients who require long-term infusion or intravenous use of irritating drugs.

Huang Guanghua explained that PICC is generally made of polyurethane or silicone, and bacteria and fungi prefer to adhere to such materials. After adhering to PICC, bacteria and fungi gradually form biofilms on the surface of PICC, enhancing drug resistance. Antibiotics and antifungal drugs, as well as patients' autoimmune cells, are difficult to remove them. Some sporadic cases of Candida infection in Southeast Asia abroad are also related to the use of PICC catheters. He speculates that at least some of the Southeast Asian Candida strains isolated by foreign hospitals, like the strains they isolated this time, have strong adhesive characteristics. Huang Guanghua analyzed that this adhesiveness not only facilitates the spread of the pathogen between the environment and humans, but also easily leads to persistent infections.

Not all fungi have the strong adhesion of Southeast Asian Candida. Huang Guanghua said that the adhesion of the Candida isolated from Southeast Asia was stronger than other fungi such as Candida albicans and Candida auris, and the survival time after adhesion to PICC was longer. Under electron microscopy, thousands or even tens of thousands of cells of Candida albicans from Southeast Asia gather together, while the cells of the other two fungi under electron microscopy are dispersed.

Fungi with strong adhesion will mobilize all cells to "fight as a team". From this perspective, pathogens with stronger adhesion have a higher risk of infecting patients. In Huang Guanghua's view, for bacterial strains, the change from single cell "combat" to multi cell "group warfare" may be due to genetic mutations occurring during the evolution process of the strains themselves. Huang Guanghua said that the strong adhesion of Candida auris is caused by specific gene mutations.

Huang Guanghua said that candida in Southeast Asia can be spread through medical devices, door handles, thermometers, Sphygmomanometer and other media. In addition to PICC, trauma, hypertension, cancer, and blood and lung infections are also risk factors.

He analyzed that for patients with immune deficiencies, especially those infected with HIV or transplant recipients, once infected with such fungi, the risk of death is higher. At that time, in these 19 cases, they may have been infected due to physical trauma, or they may have been contaminated with Candida from Southeast Asia on their food, or the patients themselves had low immunity, with fungi invading the body through channels such as the eyes, nose, or ducts.

Candida was first isolated from plants and flowers in Southeast Asia and has now become a pathogen that can infect humans. In Huang Guanghua's view, the source of Southeast Asian Candida causing hospital infection this time is unclear, and it cannot be confirmed whether it belongs to environmental fungi or human symbiotic bacteria. Generally speaking, to understand these, one can track each patient's travel history, lifestyle, living environment, etc. Their team plans to go to the local area for sampling in the future, but due to the subsequent transfer of many patients, tracing the source is more difficult.

Liao Wanqing stated that further analysis can be conducted in this study, such as conducting animal experiments on the isolated Southeast Asian Candida to observe the symptoms, treatment effects, and mortality rate after infection.

Image/Visual China

How to prevent and respond?

There have been reports of cases of Candida in Southeast Asia abroad. In June 2022, an 83 year old man with acquired cystic kidney disease, primary hypertension and Dyslipidemia was admitted to the hospital due to repeated infection and received long-term antibiotic treatment in a study conducted by the University of Malaysia School of Medicine. On the 33rd day of hospitalization, Candida Southeast Asia was isolated from samples collected from its peripheral veins and PICC.

To our knowledge, this is the first reported case of human Candida infection in Southeast Asia. The infection of this strain in this case is related to PICC, long-term use of broad-spectrum antibiotics, and the patient's weakened immune system. "The study wrote that Southeast Asia Candida is a rare species of Candida, but it is worth noting as it is considered a multidrug-resistant fungus.

In July 2023, a research conducted by a South Korean team published in the Yearbook of Medical laboratory showed that the team isolated candida in Southeast Asia from an infant about 4 months old. The baby was born in the Philippines and was hospitalized 4 times on the 25th day after birth due to recurrent fever, bloody diarrhea, abdominal distension, and other reasons. During his repeated hospitalization in the Philippines, he received treatment with antibiotics, blood transfusions, and rectal lavage fluid. Afterwards, he was transferred to the pediatric intensive care unit of the National Health University of Korea for further treatment, and ultimately the patient's condition improved.

Guo Jian is the deputy chief technician of the Laboratory Department of the South Hospital of Shanghai East Hospital. He told China News Weekly that his hospital is the responsible unit of the Shanghai Bacterial Fungal Resistance Monitoring Network and the East China Invasive Fungal Monitoring Cooperation Group, and has been monitoring fungal resistance for 10 years. Every quarter, they will collect strains from each monitoring network hospital in East China to recheck and confirm, and so far no candida from Southeast Asia has been found.

Candida in Southeast Asia is not common in healthy individuals. Due to the lack of detailed clinical data reported, the pathogenesis and clinical symptoms of Candida infection in Southeast Asia are still largely unknown. Huang Guanghua analyzed that over time, the toxic factors, invasion ability, adhesion, and drug resistance of these fungi are all evolving.

Candida from Southeast Asia is resistant to azoles and other antifungal drugs. Multiple studies have shown that infections caused by fungi belonging to the genus Candida in Southeast Asia are becoming increasingly frequent in clinical settings. According to the previous study in the Internal medicine Yearbook, from 2019 to 2021, Candida auris cases were found in 17 states of the United States. In 2021, the number of Candida auris cases resistant to echinocandin will be about three times that of the previous two years. Echinocandin is a first-line antifungal drug for the treatment of invasive candida infection.

In October 2022, WHO listed 19 fungi that pose the greatest public health risk, and divided them into three categories according to the priority of fungal pathogens: the highest priority, high priority and medium priority. Among them, Candida auris and Candida albicans were listed as the highest priority fungal pathogens.

Fungi with drug resistance 'directly cause 1.27 million deaths annually and indirectly cause about 4.95 million deaths', which is enough to reflect the potential threat of fungal infection on a large scale, "the World Health Organization pointed out. According to WHO, it is worrisome that most fungal pathogens cannot be diagnosed quickly and sensitively at present, and most people cannot access or afford existing antifungal drugs globally.

There are not many drugs available for fungal treatment. Compared to bacteria or viruses, fungi are more complex organisms, therefore antibiotics and other antibacterial drugs are usually ineffective against fungi. WHO pointed out in October 2022 that currently there are only four categories of antifungal drugs available to humans. "Few pharmaceutical enterprises are willing to invest in the research and development of Antifungal. Compared with the basic research of bacteria and viruses, the volume of basic research of fungi and the market size of antifungal drugs are much smaller." Huang Guanghua said.

In the research conducted by Huang Guanghua's team, the Southeast Asian Candida strains isolated have very high tolerance to various clinical first-line drugs. In addition, due to limited testing conditions and doctor experience, the early diagnosis rate of fungal infections is not high, and misdiagnosis may also occur.

Guo Jian told China News Weekly that after being infected with bacteria, inflammation indicators such as white blood cells in the human body can be clearly detected, making it easy for symptomatic drug treatment. Relatively speaking, the effectiveness of early diagnosis of fungal infections is currently low, which also affects the subsequent precise medication. In addition, the limited variety of antifungal drugs brings great challenges to the diagnosis and treatment of fungal infections. Guo Jian's laboratory has attempted to use new molecular diagnostic methods and drug sensitivity tests to improve the sensitivity and specificity of fungal infection diagnosis.

In Liao Wanqing's view, the Southeast Asian Candida infection discovered by Huang Guanghua's team may also exist in other hospitals, but due to testing conditions or hospital attention, there may be missed detections. Patients with a fever lasting for more than 5 days and ineffective use of various antibacterial drugs are likely to be infected with fungi and should be screened as soon as possible, "he suggested.

In the previous study by Huang Guanghua's team, the majority of cases were found in 2019, with only 2 cases of infection occurring from January 2020 to January 2022. In 2019 alone, 12 cases of infection were detected, "Huang Guanghua said. At that time, their team communicated with relevant personnel in the hospital and learned that due to the epidemic, the hospital has attached great importance to infection prevention and control since 2020. Everyone entering the hospital needs to wear masks and disinfect their hands, and disinfection in the hospital is frequent. Huang Guanghua said that during the COVID-19 pandemic, the hospital implemented comprehensive and strengthened health measures, significantly reducing the overall infection rate. The research results indicate that strengthening disinfection and other methods can prevent the spread of this strain.

Liao Wanqing stated that all fungal infections can be prevented and treated, and the key lies in precise treatment. For example, infection can be detected in a timely manner in the early stages, and when the infection has not yet spread to the whole body, the treatment effect is relatively good. Different strains also have different coping strategies. For example, for candida in Southeast Asia or Candida auris, in addition to Antifungal, other supportive treatments should also be used. Fungal infection patients are often not a single fungal infection, and most patients with other underlying diseases or severe diseases themselves need to keep up with nutritional support and ventilator support for critically ill patients.

Huang Guanghua suggested that once candida infection in Southeast Asia is found, the infected patients should be transferred to the Isolation ward in time, reported to the hospital infection and Fungal infection monitoring department, actively screened all patients and medical staff in the ward, and relevant departments should develop monitoring and prevention plans. At the same time, timely environmental monitoring should be carried out, and the ward, medical equipment, and other facilities in the ward should be disinfected as required to prevent clustered infections. In addition, patients should undergo terminal disinfection before discharge.

Published in the 1100th issue of China Newsweek magazine on July 17, 2023

Magazine Title: New "Superfungal" Infections in China

Reporter: Niuhe

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