Candida - An Emerging Pathogen of Clinical Importance

April 2, 20120 comments

Candida albicans is a popularly known fungal organism that can cause several infections in humans. Candida colonizes the mucosal surfaces of all humans soon after birth and the risk of endogenous infection is ever-present. Carriage rate of candida spp. tends to increase with age C.albicans continues to be important commensal and a constituent of the normal gut flora comprising microorganisms that live in the human mouth and gastrointestinal tract. C. albicans lives in 80% of the human population without causing harmful effects, although overgrowth of the fungus results in candidiasis.  It can manifest in pathogenic state causing painful mucosal Infections presenting as oral thrush, and vaginal infections, among many other clinical manifestations. One of the primary causes of Candidiasis is the overuse and inappropriate use of antibiotics, steroids, birth control pills, anticancer drugs and several other drugs. To acknowledge Candidiasis as a disease is to acknowledge a problem often caused by drugs! On few occasions Candidiasis predisposes to life threatening systemic infections. The relation of humans to Candida is a dynamic process can change their status from commensals to an opportunistic state, Most of the time, Candida infections of the mouth, skin, or vagina occur for no defined reason. A common cause of infection may be the immunosuppressive conditions, use of antibiotics that destroy beneficial, as well as harmful, microorganisms in the body, permitting candida to multiply in their place. The resulting condition is known as candidiasis.

Candidiasis is emerging problem

                                              With the increase in the prevalence of immunosuppressed patients during the last few decades, as a result of chemotherapy or disease with AIDS which led to a parallel increase in the incidence of Candida infection in general and the less pathogenic non candida albicans spp. in particular. Candida spp. are the fifth most common cause of blood stream infections and fourth common cause of nosocomial infections.
                                        An interesting feature of C. albicans is its ability in growing two different ways; reproduction by budding, forming an ellipsoid bud, and in hyphal forms, which can periodically fragment and give rise to new mycelia, or yeast-like forms. Transitions between the two phenotypes can be induced in vitro in response to several environmental cues such as pH or temperature, or different media. Like other pathogenic fungi, C. albicans  exhibits a number of different morphological forms under different environmental conditions; such forms include budding yeast cells (blastospores, blastoconidia), pseudo hyphae (elongated cells which appear as filamentous cell chains), true hyphae, and clamydospores.

Microbiology of Candida spp

Candida albicans historically has been documented as the predominant cause of Candidiasis There are several species among the Candida, few have higher predisposition in causing Candidiasis. The genus Candida includes around 154 species. Among these, six are most frequently isolated in human infections. While Candida albicans is the most abundant and significant species, Candida tropicalis, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida lusitaniae are also isolated as causative agents of Candidal infections. Importantly, there has been a recent increase in infections due to non-albicans Candida spp., such as Candida glabrata and Candida krusei. Patients receiving fluconazole prophylaxis are particularly at risk of developing infections due to fluconazole-resistant Candida krusei and Candida glabrata strains. Nevertheless, the diversity of Candida spp. that are encountered in infections is expanding and the emergence of other species that were rarely in causing diseases  in the past is now likely which include,  C glabrata Candida parapsilosis, Candida krusei . However majority of isolates are still C.albicans and account for 85 – 95% of infections. Many studies prove C.glabrata can cause 10 -20 % of the infections. The importance of speciation is gaining importance as several anti-candida drugs are becoming drug resistant due to over the counter availability, failure to administer the optimal dosage and lead to recurrent infections. Future demands will rise for identification of species and antifungal sensitivity

Why Specific diagnosis of Candida Infection still difficult

                           Clinical manifestations of candidiasis are extremely varied, ranging from acute, sub-acute, chronic and episodic. Involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, toes shown to the left), nails, bronchi, lungs or gastrointestinal tract. It may also be systemic as in septicaemia (circulating in the blood and causing damage to blood vessels and sometimes blood cells), endocarditis and meningitis. Pathologic processes evoked are diverse and vary from irritation and inflammation to chronic and acute suppuration or granulomatous response

Invasive fungal disease occurs in at-risk patient population

·         Immunocompromised patients
·         Patients on immunomodulatory therapy
·         Patients with indwelling devices
·         Critically ill patients
·          Manifestations of infection may occur in one or more body sites

Candidiasis: Why the Elusive Diagnosis
The diagnosis of Candidiasis is often overlooked in conventional medicine.  Many doctors “give less importance to Candidiasis,” even though there is ample scientific evidence to document the condition. It is difficult to say exactly why this condition is ignored by conventional medicine in spite of the vast scientific evidence?  As the symptoms of Candidiasis are widespread and can mimic many other diseases. There is no definitive lab test that confirms the disease, this makes correct diagnosis difficult.

Clinical Diagnosis can be attempted with several specimens

1.      Clinical Material: Skin and nail scrapings; urine, sputum and bronchial washings; cerebrospinal fluid, pleural fluid and blood; tissue biopsies from various visceral organs and indwelling catheter tips.
2.      It is important to identify the species as less known Candida too are responsible for Candidiasis

         As PCR is expensive and not available at all places, speciation of candida can be done by using Chrome agars for candida species differentiation and Carbohydrate assimilation patterns with readily available diagnostic reagents.

     3 Testing isolates for Antifungal sensitivity patterns

                                It is now possible for the clinical microbiology laboratory to perform reliable in vitro antifungal susceptibility tests on a wide range of yeasts and moulds
Development of standardized antifungal susceptibility testing methods has been the focus of intensive research in the last 15 years. Antifungal sensitivity tests can be done with Disk diffusion with simple techniques or by E-test and by broth micro dilution method.  E-test is preferred as it gives better sensitivity results on Candida species than dermatophytes for all drugs expect Itraconazole.

Disk diffusion with standard protocols   
                               Can be done in laboratories with few facilities it recommends the use of Mueller-Hinton agar supplemented with 2% glucose and 0.5 ug/ml methylene blue dye medium. Mueller-Hinton agar is readily available and shows acceptable batch-to-batch reproducibility, the glucose provides a suitable growth for most yeasts and the addition of methylene blue enhances the zone edge definition. The pH of the medium needs to be adjusted between 7.2 and 7.4 at room temperature after gelling. The inoculum is standardized to 0.5 McFarland using a densitometer and plates should be incubated at 35 ͦ C for 24 hours. Some strains where insufficient growth has occurred after 24 hours may need to be read after 48 hours incubation. Commercially prepared paper disks for fluconazole (25 µg) and voriconazole (1 µg) are available from Oxoid and Becton Dickinson, and indigenously available from Hi-media in India. The laboratories should use Hi-comb (MIC) method available from Hi-media for doing determining the Minimum inhibitory concentration to commonly used antifungal drugs.
All the newly established laboratories are at a beginning stage in the development of in vitro antifungal susceptibility testing systems. However many issues remain. It goes without saying that you need a culture, which is not always possible. The identity of the culture is often predictive of its in vitro susceptibility, so which isolates should be tested? Only those clinically warranted or should the laboratory screen all isolates? However it needs more wisdom to do or not and too report an isolate a commensal or pathogen.                                                            
Needs just not knowledge but good wisdom.

Guest post by : T.V.Rao*. Deepa Babin
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