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Fungi is widely distributed in nature, there are around 100,000 named species, but about 500 kind have been recognized to cause disease (mycosis) in human (Warnock, 2007).
Fungal infections have recently become sources of growing risk to human health, particularly in persons with a compromised immune system. Normally, fungi are connected with complex disease entities in complicated medical patients (e.g. Cryptococcosis in AIDS (Acquired Immune Deficiency Syndrome) patients or Aspergillosis in bone marrow or organ transplant patients).
Moreover, the use of a high amount of antifungal drugs can lead to drug resistance by fungi microbes, especially in hospitals, which increase the spreading of hospital-acquired infections. The recent studies have documented resistance of Candida's species to fluconazole and other azole and Triazole drugs, that are used widely in systemic fungal diseases (NIAID, 2006).
1.1.1 Hospital-acquired infections
A hospital-acquired infection is describedd as one that develops at least 48 hours after the patient is admitted to the hospital, or up to 48 hours after being discharged. Outside this period, infections are considered to be community-acquired (Jamieson, 2008).
According to the Infectious Diseases Society of America (IDSA); an infection was described as "the attacking of the body's natural barriers by microscopic organism, bacterial, fungal, viral, or parasitic, which multiplies to create symptoms" (IDSA, 2003).
1.1.2(b) Pathogenesis of infection disease
There are many stages involved in the disease caused by microorganisms (Inglis, 2003). The most common of these stages are: acquisition, colonization, penetration, spread and, damage and resolution.
In this case, the indigenous flora is already present on the body surface, the major routes of transmission are:
Direct contact like sexual which can cause gonorrhea.
Inhalation or droplet infection which can cause common cold, pneumonia.
Ingestion such as gastroenteritis.
Transplacentally such as congenital toxoplasmosis.
In this stage, the microbe's needs to establish itself in its new habitat, also at this stage it needs to survive and multiply under the local conditions like temperature and PH.
In order to attack living in human tissues in this stage microorganism must breach the relevant surface barrier
Here the attack of microorganisms happens by different routes like direct extension through surrounding tissues, veinus lymphatic vessel. Furthermore, In this stage organism plays an active part in spreading by destroying cells.
v. Damage and resolution
Microorganism use many ways to damage the body tissues like bulk effect, toxin mediated, altered function of host system and host response to infection.
1.1.2(c) Classification of microorganisms that causes the infections
Usually in human, the infectious diseases are caused by pathogenic microorganisms; the diseases can spread, directly or indirectly, from one person to another. In addition, there are some infectious diseases of animals like Zoonotic diseases considered as infectious diseases because they are caused by being transmitted to humans (WHO, 2009)
The microorganisms are usually classifiedd into five groups;
Bacteria are among the oldest living organisms on Earth and are very small. They can only be seen through a microscopic diagnosis. Bacteria are a single cell organisms (prokaryotes) contain both DNA and RNA, have a cell wall, it lives in different places such as ground, water and in other living organisms. Some types of bacteria can cause diseases and become harmful to the environment, particularly animals and humans. Other types of bacteria can attack plants and cause diseases like leaf spot and fire blight. In human hosts, certain types of bacteria can cause infections such as tetanus, pneumonia, syphilis, tuberculosis and other illnesses.
Viruses are a microscopic organism that lives in a cell of another living thing. Although they are extremely small and simple capsules with genetic material inside, they are much smaller than bacteria. Viruses cause familiar infectious diseases such as the common cold, influenza and measles. In adition to other severe illnesses such as AIDS and smallpox; they produce disease in an organism by damaging some of its cells (Anonymous, 2008).
Fungi possess DNA, RNA, and defined nucleus, they also have a cell wall, binomial name, however because all fungi can reproduce asexually (anamorphic state), sexually as well (teliomorphic state), some fungi have different names for each state (Inglis, 2003).
1.1.3(a) Significances of fungi
Fungi are not always harming or transporting diseases only, but there are beneficial sides. However, fungi are quite useful to human and play an essential role because they are eukaryotes and heterotrophy that absorb their food. They secrete digestive chemicals into an environment, where the food is digested, and after absorb the nutrients. In addition, we have taken out several kinds to make antibiotics to fight bacterial infections. Basing on natural compounds that fungi produce; fungi is competing with bacteria for nutrients and space..
In addition, some Fungi yeast like Saccharomyces cerevisiae are known as baker's yeast because they are used in making bread rise, and they are also used to ferment beer and wine. We do benefit from Fungi, they break down dead plants and animals and breakingg down organic matter and returning essential mineral to the soil (Talaro, 2008)
1.1.3(b) Classification of fungal
There are three major types of fungi:
They are small oval or round in shape, predominantly unicellular, e.g. Candida spp.
Grow as branching filments (hyphae), that are connected to form a Knotted mass (mycelium), e.g. mucor sp, trichophyton sp.
iii. Dimorphic fungi
This type is capable to changing and existing in both mould and yeast forms. The yeast form in the body while the filamentous one forms in the environment, e.g. histoplasma sp, sporothrix sp (Warnock, 2007)
1.1.3(c) Fungi structure
Fungi have defined nucleus with both DNA and RNA. They have a complex cell wall that contains sterols. Yeast is single cell organisms that reproduce by budding, whereas moulds grow by developing filamentous (Inglis, 2003).
1.1.3(d) Fungal infections diseases
Fungal infection has become one of the most dangerous diseases that cause morbidity and mortality among the patients, advances in medical technology and the development of new diagnostic and treatment have described fungi as the main reasons which have increased the life expectancy of critically ill patients. On the other hand, Candidiasis remains as the most common fungal infection in immunosupressed patients. Aspergillosis, zygomycosis and others invasive filamentous fungal infections are major problem for certain groups of patients (Anonymous, 1998).
i. Morphology of pathogenic fungi
The pathogenic fungi that infect humans are none motile eukaryotes, which are reproduced by sporulation. Moreover, pathogenic fungi are alive in two forms: filamentous molds and unicellular yeasts. These forms are not mutually excusive and depending on the growth conditions (Kimble et al., 2005).
ii. Types of fungal infections
The major type of fungal which causes infections to human is called mycoses. Mycoses live in association with humans as commensals. Fungal might present in the environment, but until recently, serious superficial infections were relatively uncommon as well as systemic infections which were very uncommon indeed, at least in cool and temperate climaticzones. In such zones, a fungal infection usually means athlete's foot, oral and vaginal thrush, which all of them cause discomfort.
During the recent 30 years there has been a steady increase in the incidence of serious secondary systemic fungal infections. One factor was the widespread use of broad-spectrum antibiotics, which eliminate or decrease the non pathogenic bacterial population that normally competes with fungi. Another factor was the increase in the number of individuals with reduced immune responses due to Acquired Immunodeficiency Syndrome (AIDS), the action of immunosuppressant drugs, or cancer chemotherapy agents. This has lead to an increased prevalence of opportunistic infections (Rang et al., 1999).
Fungi (mycoses) which cause infections disease to the human can be classified into a number of broad groups according to the initial site of infection. This classification shows the different groups of fungi and the way in which the site effected is related to the route by which the fungus enters to the body (Kimble et al., 2005).
A. Superficial mycoses
These types of fungal infections involve only the outer layers of the skin and hair. These infections are often harmless that patients do not realize their condition. The most famous example for these mycoses is Malasseziasis (tenea versicolor).
B. Cutaneous mycoses
In the case of cutaneous mycoses the fungal extend deeper into the epidermis and also may infect the nails as well. The most common example for these mycoses is (dermatophytosis)
C. Subcutaneous mycoses
These kinds of fungal microorganisms are chronic. It leads to localized infections of the skin and subcutaneous tissue following the traumatic implantation of the etiologic agent. The example for these mycoses is Sporotrich.
D. Systemic mycoses
These are dangerous microbes that infect the human body. They usually cause diseases in the internal organs by dimorphic fungal pathogens. They often overcome the physiological and cellular defenses of the normal human host by changing their morphological form. In addition, they infect the lung, and gastrointestinal tract, after the inhalation of conidia.
E. Opportunistic mycoses
These types of mycoses cause fungal infections for the human body in the immunocompromised patients when the normal defense mechanisms are weak, an example of that is AIDS patients, more aggressive cancer and post-transplantation chemotherapy and the use of antibiotics, cytotoxins, immunosuppressive, corticosteroids and other macro disruptive procedures that result in lowered resistance of the host.
Â The organisms involved in these infections are cosmopolitan fungi, which have a very low inherent virulence. The increased incidence of these infections and the diversity of fungi causing them; have paralleled the emergence of AIDS, more aggressive cancer and post-transplantation chemotherapy and the use of antibiotics, cytotoxins, immunosuppressive, corticosteroids and other macro disruptive procedures that result in lowered resistance of the host. The examples for these mycoses are Cryptococcus, Aspergillosis and mucomycosis.
F. Non opportunistic fungi (primary pathogens)
Usually the primary pathogens cause diseases in the immunologically normal host. The most common examples for these mycoses are histoplasmosis, blastomycosis, and coccidioidomycosis (Kimble et al., 2005).
iii. Pathogenic of fungal infections
Many people think that the word "Fungi" indicates an organism that causes only mildew and old shoes, moldy bread, or skin infection with graphic names like athlete's athlete's foot or jock itch. However, actually fungi have major effect on the health and people life all around the world. Fungi causes a wide range of clinical diseases, from simple superficial problems to serious and harms systemic infections (Schaechter et al., 1999).
Richard and Cihlar, (2002) mentioned that Pathogenic fungi cause a variety of infections, which lead to be life-threatening through many ways to the human body including skin contact, inhalation, and translocation across physical barriers pursuant to host defects, accidental or iatrogenic abridgement of epithelial integrity.
iv. Transmission of fungal
The majority of fungi live in the soil or on plants. They are transmitted to humans by contact with fungus or its spores. They are frequently inhaled (e.g. Aspergillus spores and Cryptococcus), but they can also enter to the body through the broken skin. Some other cataneous mycoses are transmitted by contact with infected skin area, or by direct contact with a lesion on the skin of an infected human or animal (e.g. ringworm on cats (Lee and Bishop, 2002).
v. Sign and symptoms of fungal infections
The signs and symptoms of fungal infection differ in accordance to the infected parts of the body. Often superficial fungal infections, such as jock itch, vaginal yeast, athlete's foot, and ringworm are typically annoying, but they are not very serious. Their symptoms generally include itchy, dry, red, scaly, or irritated skin. In addition, there are systemic fungal infections often begin in the lungs and take time to develop. Furthermore, severe infections occur in people, whose immune systems have been weakened, allowing the infection to spread beyond the lungs to other organs. Moreover, symptoms of systemic fungal infections depend on which organs become infected and may include respiratory problems, extreme tiredness, coughing, weight loss, fever, night sweats, and headache (Anonymous, 2007).
vi. Factors contributing to fungal infection
There are a number of factors contribute to patient susceptibility to infection; include many medical procedures, which lead to weakness of patient's patient's immune system. These factors are summarized by Lee and Bishop, (2002) as the following:
1. Transplant organ surgery with administration of immunosuppressive drugs.
2. Prolonged broad spectrum antibiotic therapy, which destroys the normal flora.
3. Other invasive therapies such as intravenous total parenteral nutrition (TPN). This involves the use of solutions of glucose, which inhibit bacterial growth but favor the growth of fungi such as Candida albicans. The use of fat emulsion in TPN also encourages the growth of Malassezia further, an otherwise harmless superficial fungus.
4. Continuous Ambulatory Peritoneal Dialysis (CAPD). This is used to haemodialysis for patients with renal failure (RF), the main problem is the risk of fungal infection as well as bacterial infection through the indwelling cannulae.
5. Fungal infection may also occur from contaminated equipment or material (Lee and Bishop, 2002).
1.1.3(e) Epidemiology of fungal infections
Fungal infections have become main factors that play an increasing important role in our life such as pathogens in nosocomial infections and nosocomial Candidemia which is associated with significant mortality, longer hospital stays and higher health care costs (Klein and Watanakunakron, 1979; Edmond et al., 1999).
Toscano and Jarvis, (1999) from the national foundation for infectious disease, reported that during the past few decades, advances in medical technology and the development of new diagnostic and treatment approaches lead to increase the life expectancy of critically ill patients. They added that the global Human Immunodeficiency Virus (HIV) epidemic has resulted in an increase in severely ill immunocompromised hospitalized patients, accompanied by more reports of fungal infections.
The data from the National Nosocomial Infections Surveillance (NNIS), (1994) showed that Candida now ranks as the fourth most common cause of nosocomial blood stream infections in United States, and the prevalence of systemic fungal infections has increased significantly during the past decade.
Walsh et al., (1996); Ng (1994) declared that the increase was due to great use of bread-spectrum antibiotics, immunosuppressive agent. also hyperalimentation products and central venous catheters, intensive care of low birth weight infections, besides the organ transplantation and the acquired immunodeficiency syndrome (AIDS) epidemic.
1.1.4 Fungal infections in Malaysia
Up to our knowledge, the prevalence and incidence of fungal infection in Malaysia have not been studied extensively, but there were little studies, which concentrated in specific types of fungal infections.
A study was conducted by Ng et al., (1999) at the medical microbiology department of Malaya University. One thousand and one hundred fourteen fungal yeasts were isolated from a virus clinical specimens. The study identified a species of Candida and the high frequency Candida albicans (44.2%), Candida parapsilosis (26.0%), Candida tropicalis (17.7%), Candida globrata (9.6%), Candida krusis(1.2%), Candida ruosa (0.6%), Candida guilliermondii (0.2%),Candida lustaniae (0.08%), and Candida keyr (0.8%). However, in this study a higher numbers of microorganisms were obtained. The most non-albicans was isolated from the blood, respiratory system, urine and skin. The higher number of Candida albicans was obtained from the vaginal swabs, then Candida globrata 82.2, and Candida kurodei was 64.2%.
There was a study conducted in the National university of Malaysia (UKM) by Bee-See et al., (2005) to determine the incident of allergic fungal sinusitis (AFS) by involved 30 patients of immunocompetent chronic rhino sinusitis (CRS) who were under surgery. After analysis the patient's specimen was found to be fungal positive in 5(16.7%), and 11(36.7%) of 30 patients from the nasal secretions and surgical specimen respectively. Allergic mucin was found in 8 surgical specimens (26.7%), hence prevalence of AFS was 26.7%. It was also observed that the most common causative agent was Aspergillus.Sp (54.5%), in 3(37.5%) of 8 patients, AFS found with asthma. 25% (2/8 patients), had Aspirin intolerance, and 62.5% (5/8 patient) had elevated total immunoglobulin E levels. All patients' results were positive in the test done for discovering the skin reactivity to the fungal allergen