Coccidioida is a type of two fungi, including two species, namely Coccidioidae and Coccidioidae. It is mainly caused by inhalation of human lungs and infection, and in severe cases, it can spread infection and cause death.

Epidemiology shows that coccidioidosis is mainly prevalent in southwestern United States and some parts of Central and South America. It is generally believed that coccidioidosis is an extraterrestrial fungus, and infections found outside epidemic areas are mainly considered imported. There are few reports of coccidioidosis in China, and clinical workers generally have a low level of awareness of the disease, and the rate of misdiagnosis and misdiagnosis is high.

1. Ecological characteristics of coccidioids

Coccidioids include C.

immitis and C.

posadasii two types. It was originally believed that C.

immitis exists only in California, and C.

The distribution area of ​​posadasii is more extensive. Latest research shows that these two species overlap in geographical distribution and have the same clinical pathogenic characteristics.

Coccidioids live in arid or semi-arid areas, especially in desert or Gobi environments, and are typical bipolar fungi. In the soil, the fungus is a branched mycelium with a septum. When the soil is dry, the mycelium can develop gangliopores, and then split into single arthrospores to spread in the air.

Fisher studied the effects of soil quality, climate, precipitation, temperature, soil pH value and soil electrolyte on the growth of coccidioids, and showed that temperature and precipitation were the most critical factors. Its suitable growth environment was alkaline sandy soil with an average annual temperature of 0.5 to 24.4℃, an average annual precipitation of 5 to 50cm and a depth of 10 to 30cm from the surface.

Coccidioids can spread with the wind to non-epidemic areas hundreds of kilometers away, while physical movements such as sandstorms can promote the spread of the bacteria.

Nina found that coccidioids can survive in seawater for more than 6 weeks, and there are also reports of bottlenose dolphins and sea lion infections, indicating that seawater can be a natural storage for the bacteria.

It is worth noting that Del believes that Coccidioids can parasitize in non-rodent animals such as bats, beavers, armadillos, or they can also be separated in the soil around the caves of rodents such as groundhogs, grasshoppers, cyst rats, ground squirrels and deer rats, or infected with otters, kangaroos, chickens, horses, etc., which all suggest that animals may be potential transmission vectors of Coccidioids.

2. World Epidemiology of Coccidioidosis

Coccidioid inhalation infection is the most common, and its rare infection method is to receive transplanted organs of infected people, skin inoculation, and contact with contaminated items or soil.

Previous reports have been reported that dust contact and dust environments can increase the probability of coccidioid infection. It has experienced outbreaks and epidemics in soldiers, archaeologists, farm personnel, earthquake areas and sandstorm areas.

Coccidioidosis mainly exists in the southwestern United States, especially California and Arizona, followed by Nevada, New Mexico and Utah, and Texas and Washington states.

Data from the US Centers for Disease Control and Prevention shows that about 10,000 people are infected every year. The average annual death to coccidioidosis from 1990 to 2016 was about 200. The highest number of reported cases in 2011 was more than 22,600, and more than 14,300 cases were reported in 2017.

Coccidioidosis is also prevalent in northern Mexico, Panama, Brazil, Venezuela and Argentina. There are scattered imported cases in non-endemic areas of Europe, Asia and Africa, and animal infections are also reported.

Indigenous Coccidioid infection cases were discovered in Washington State, USA after 2010. The systemic evolutionary analysis was a new evolutionary branch, suggesting that the strain can survive in non-traditional epidemic areas, suggesting that the coccidioids have strong environmental adaptability and possible geographical migration.

Based on the study of epidemiological dynamic analysis and geographical environment correlation, Fisher's research believes that there is biological migration of coccidioids, that is, North America gradually spread to Central and South America, etc.

The migration of Coccidioids can be affected by wind, sand, atmosphere, animal and human activities, and its epidemiological influencing factors are numerous and complex, and it is not yet clear. It suggests that Coccidioids may migrate to a wider geospatial area.

In addition, as time accumulates, whether coccidioids can migrate to regions in the eastern hemisphere with suitable natural conditions at the same latitude is worthy of continuous attention and exploration.

3. Review of cases of coccidioidosis in China and epidemiological reviews analyzed reports of coccidioidosis in China and identified diagnostic evidence.

Inclusion criteria meet at least one of the following four evidences: 1. Histopathological diagnosis requires typical balloons and endospores; 2. Fungal culture requires typical cotton-like colonies and microscopic joint mycelium characteristics; 3. Immunological examination, strong positive coccidioxin test; 4. Molecular identification: polymerase chain reverse PCR, ITS, etc. sequencing analysis or matrix-assisted laser analysis ionization time-of-flight mass spectrometer.

In view of this, those with insufficient diagnostic evidence were not included.

The search literature shows that from 1958 to August 2019, a total of 43 cases of coccidioidosis were reported, and 36 cases were included in this article.

3.1, imported cases

There are 15 imported cases with sufficient diagnostic evidence, of which 10 have been reported in the past 10 years.

In 1958, Ganty reported the first confirmed case of coccidioidosis in China. The researchers conducted fungal culture, histopathological examinations and animal experiments fully confirmed that it was coccidioid infection.

The patient is a Chinese American and has traveled to Arizona and California in the United States. It can be considered to be imported infection.

Since then, the number of imported cases has increased and has been reported one after another. In 2017, 1 case was diagnosed with molecular identification for the first time in China.

Pneumococcycosis caused by posadasii.

The geographical distribution of imported cases indicates that it is mainly concentrated in relatively economically developed areas, and there may be more opportunities to go to epidemic areas such as the United States and increase the risk of infection.

3.2. Some suspected local infection cases reported without a clear history of travel in the epidemic area. A total of 16 cases of coccidioids have been preliminarily identified as suspicious cases of domestic infection.

In 1963, Murraywu reported a case of coccidioid infection. The investigator confirmed that it was coccidioid through histopathology, fungal culture and animal experiments. The patient was a semi-agricultural and semi-businessman with no history of travel to the epidemic area. The patient started in Lanzhou, Gansu, and this was the first most suspicious locally infected patient.

In 2010, Lian Ningfang reported 8 cases of coccidioidosis diagnosed between 2004 and 2008, all of which were pathologically confirmed. The patients were mainly young men, and there were no records of traveling abroad or epidemic areas. The site of the disease was in Fujian.

Lan reported in 2007 that a 14-year-old boy choked water while diving in Hainan and suffered symptoms such as cough and fever, and later diagnosed pulmonary coccycosis. The remaining reported cases may have risk factors for fungal infection, such as the use of immunosuppressants, xidu and AIDS.

The geographical distribution of suspicious local cases suggests that compared with the geographical distribution of imported cases, there are many reported cases in economically underdeveloped areas.

The author has focused on analyzing the geographical environment, ecological and meteorological factors of the diseased regions such as gansu and fujian in my country, suggesting that some areas may have the living conditions of coccidioids.

3.3. The travel history information was missing in the 5 confirmed cases that were not clearly classified. The reporter's consultation or records of the patient's information were incomplete and failed to accurately classify it.

Three of the reports are worth paying attention to: Liang Cuihua reported a patient with coccidioid meningitis in 2009. This patient is a construction worker in Zhangjiagang area. The patient is less likely to go to an epidemic area abroad, and he has more opportunities to get in contact with soil, sand, etc.

Ouyang Wenxian reported a case of disseminated coccidioids in 2008. The child fell ill at 4 months old and died one month later. Histopathological diagnosis was the disease after autopsy.

This case also lacks travel history information. Based on common sense of life, the child's travel history in the epidemic area is also less likely.

Tang reported that a container loading and unloading worker developed fever, cough and rash after cleaning containers from the United States with a broom. Later, he was diagnosed with coccidioidosis, which had a large possibility of imported infection.

3.4. The cases to be discussed, Tong Jingya and Wu Xuancheng reported Coccidioidae and Coccidioidae around 1985 respectively. Later, in 1991, the bacteria was re-identified as Imonella by Wu Shaoxi and Shadomy, and the disease caused was determined to be infertile mesophilia. Therefore, the reports of these two cases should be corrected here.

In 2016, Wang Chunbao and others reported cases of coccidioidosis, with pathological pictures and descriptions as hollow stains in the balloon, spores are 4 to 60 μm in size, thick walls and 2 to 7 μm in surroundings, etc. According to this pathological characteristics, it cannot be diagnosed as coccidioids, and they are more likely to be infertile mesophilic diseases caused by Imonella.

Fu Xinxiang reported a case of systemic coccidioidosis in 1988. The patient was a textile worker. He had repeated and intermittent fever for 3 years and had no history of travel in the epidemic area. Histopathology was found in "spherical fungal sporophytes", but no details such as endospores were mentioned. The patient recovered from ketoconazole for 3 months and could not confirm that this was a coccidioid infection.

In addition, Yu Biyun reported primary coccidioidosis, thick capsular fungi were seen in lung histopathology, and no typical structure was seen from the pathological pictures;

Li Yongping and others reported that coccidioids infected the cornea, and corneal pathology showed the balloon structure and mycelium, but no endospores were seen. The mycelium of coccidioids was rarely seen in human tissues. These two cases cannot be excluded from infertile mesophilia.

The rest of the cases are not described here, and cases whose diagnosis information cannot be confirmed will be discussed.

4. Preliminary analysis of suspected local coccidioidosis in China

The author once summarized and analyzed domestic suspicious local coccidioidosis in 2016. Based on the current theoretical basis, the following analysis was made:

goods

Direct infection of people in non-epidemic areas caused by logistics media such as transportation. Coccidioids can exist in dust, etc. Contaminated goods or items can be transported to non-epidemic areas, and people in non-epidemic areas can be inhaled and caused by disease.

riben once reported that American cotton contaminated by coccidioids can cause disease in Japanese textile workers, and Tang reported that port workers inhaled dust after cleaning US transport ships and caused disease. These cases all support the possibility of infection in non-epidemic populations caused by pollutants.

However, some cases do not support infection after international freight transport brings pollutants into the country, especially those reported by Murray Wu in 1963. In 1963, my country was under a comprehensive blockade by the United States and others, and my country has a small possibility of international freight and personnel exchanges with North American epidemic areas.

Survival conditions.

my country and the United States are at the same latitude, and some basic geographical environments of the two countries are similar.

my country has a large land area span and there are arid and semi-arid areas. In some areas such as Fujian, especially Gansu, there may be suitable living conditions for Coccidioids, and the strong adaptability of Coccidioids makes it possible to exist in nature.

It can survive but cannot spread.

The growth cycle of Coccidioids in nature is mainly divided into two stages, namely the mycelium formation period and the articular spore formation period. When the rain is abundant and the soil is humid, Coccidioids can grow in mycelium, and when the soil gradually drys, the mycelium can stop growing and turn into articular spores, thus spreading with the wind and dust.

In nature, the growth cycle of the bacteria depends on multiple factors such as temperature, humidity and soil quality. Natural conditions that are fully in line with the epidemic area do not exist yet, especially the annual precipitation is larger than that of the epidemic area and the drought environment is relatively insufficient, resulting in the formation of the bacteria arthrospore stage, which may be a limiting factor for large-scale transmission.

Based on scientific exploration, we propose the hypothesis of "fungal migration-environmental adaptation-accidental pathogenic" of Coccidioids.

That is, coccidioids migrate into my country's natural environment through personnel, goods, animals, sand and dust, seawater and other media. Due to its strong adaptability, they can survive in some areas for a long time. However, due to the imperfect matching of precipitation, temperature and soil quality, a typical drought environment in the epidemic area cannot be formed, and a large number of arthrospores cannot be formed to spread. It can only be inhaled under certain accidental conditions and cause disease.

It must be further explained that this hypothesis is based on limited theoretical analysis and there is no direct evidence. It will be confirmed that bacterial species are isolated from nature in the future.

However, it is difficult to isolate coccidioids in nature, and the positive rate of isolating the bacteria in high-risk soils in the epidemic areas of the United States is still relatively low.

In view of this, whether coccidioids exist in the Chinese environment and whether this hypothesis is valid remains to be observed in the future and mycological evidence is directly obtained.

5. Summary

This article reviews and analyzes the reports of coccidioidosis cases in China over 60 years and draws the following conclusions:

Anti-collection, automatic loading fails, click to load manually, and the reading mode is not supported!

Transcoding is prohibited, reading mode is prohibited, the following content is hidden, please exit reading mode!

Some reported cases are to be discussed: Most domestic units unconditionally conduct coccidioid culture identification, PCR molecular diagnosis and immunologic diagnosis, mainly rely on histopathological diagnosis, and some reported cases do not provide typical histopathological evidence, which may be misdiagnosed.

In addition, some cases did not provide key information such as the travel history of coccidioidosis patients, indicating a lack of understanding of the epidemiology of the disease.

To sum up, the clinical diagnosis, case reports and journal review of coccidioidosis should be more rigorous, and misdiagnosis and false alarms and information loss should be avoided as much as possible. We should be vigilant against coccidioidosis and explore the possibility of locally derived infection with a more cautious attitude.
Chapter completed!