Virology & Mycology
Open Access

Oral Candidiasis in Leukemia Patients

Ouanassa Hamouda^{* *}Correspondence: Ouanassa Hamouda, Department of Parasitology and Mycology, UHC Benflis Touhami, Batna, Algeria, Email:

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Introduction

Oral candidiasis is extremely common. It is a yeast infection of the oral mucosa caused by a fungus of the genus Candida. Today there are more than 200 species belonging to the genus Candida, 23 of which are pathogenic for humans, Candida albicans is responsible for infection which, by their frequency and severity, rank first among fungal infections. Others Candida species are occasionally pathogenic for the oral cavity: Candida tropicalis, Candida pseudotropicalis, Candida glabrata, Candida guillermondii, Candida krusei, Candida parapsilosis [1]. These yeasts are part of the normal flora of most individuals and live as commensals in the oral mucosa, the digestive tract, the urogenital tract and the skin covering, becoming opportunistic when local conditions become favorable for its growth [1,2]. The transition to pathogenicity is linked to several factors including broad-spectrum, antibiotic therapy, immunosuppression, neutropenia, chemotherapy, hematologic malignancies, cancers, diabetes and acquired immunosuppression (HIV) [3].

Oral candidiasis is often encountered in immunocompromised patients, leukemia patients being an example. Diagnosis is generally easy, based on clinical and laboratory criteria [4]. The mycological diagnosis of candidiasis is part of the approach based on clinical and biological criteria and the classic identification of a microorganism. Direct examination of the surface sample is followed by cultivation to isolate the germs in question. The isolated yeast colonies can then be identified by carrying out various tests which are based on morphological, immunological, biochemical and even genotypic criteria [5,6].

Patients and Methods

This is a cross-sectional descriptive observational study, carried out over a period of four months from November 7, 2016 to March 2, 2017 in collaboration between the laboratory of Parasitology and Medical mycology and the hematology service at the Hospital Center University (HCU) and the Anti-Cancer Center (ACC) of Batna-Algeria.

All leukemia patients of both sexes were included in our study. Professional secrecy has been safeguarded and the patient's consent requested and obtained in advance. Patients recently diagnosed with leukemia and not yet treated with chemotherapy or corticosteroid therapy favoring the onset of oral candidiasis were excluded from our study. This study is based on an information sheet which contains information on the patients, specifying age, sex, reason for hospitalization and risk factors.

We performed a total of 56 oral swabs. These were carried out by swabbing the diaper using sterile cotton swabs on the internal face of the cheeks, the soft palate, or an acute lesion. They are sent to the parasitology and medical mycology laboratory for direct examination and cultivation on Sabouraud-Chloramphenicol and Sabouraud-Chloramphenicol.

Actidionne medium, incubated at 37 °C for 24 to 48 hours. The Candida colonies that have appeared measure a few millimeters in diameter. Rather whitish, their surface is smooth and shiny. The microscopic examination is carried out on a colony resulting from the culture, it is examined between slide and coverslip by adding a drop of KOH or cotton blue, it allows the detection of yeasts in spherical or ovoid form measure of 4-5 µm with or without bud.

The identification of the isolated yeast was done by the filamentation test, carbohydrate fermentation and assimilation.

Results

Distribution of cases of diagnosed oral candidiasis

Out of 56 patients included in our study, 27/56 (48,21%) had proven oral candidiasis (Figure 1).

Figure 1: Distribution of cases of diagnosed oral candidiasis.

The male sex was the most representative with 36/56 (64.28%), with a sex ratio of 1.8 (Figure 2).

Figure 2: Distribution of patients by sexs.

The average age was 35.86 years old. The most representative age groups are in the 15 to 30 year range (Figure 3). The mean age of the patients is 35.86 years; the median is 38 years with ranges of [6-75 years].

Figure 3: Distribution of patients by age groups.

Services

The hematology service of the University Hospital Center was the most representative of the positive results with a number of 17 cases (54.84%), followed by the hematology service of the Anti-Cancer Center with 7 cases (36.84%), which is also followed by the day hospital with 3 cases (50%) (Table 1).

Table 1: Breakdown of all results at the service level.

Mycological data

Of the 27 positive cultures, Candida albicans was isolated in 15 cases (Figure 4 and 5).

Figure 4: Distribution of patients by Candida species.

Figure 5:Distribution of patients by Candida species.

The main contributing factor found was parenteral nutrition 15/27 (55,55%), corticosteroid therapy 15/27 (55,55%), antibiotherapy 10/27 (37,03%), neutropenia 7/27 (25,92%) and diabetes 3/27 (11,11%).

Discussion

Oral candidiasis is a big problem for people with leukemia because of the possibility of a potentially fatal systemic infection. C. Albicans is the main causative agent, but there is significant involvement of other species. The Candida species existing in the mouth have a high probability of infecting the digestive tract and spreading through the circulation, developing a systemic infection which threatens the life of the sick.

Our objective in this study was to determine the prevalence of oral candidiasis in leukemia patients, to identify the Candida species involved and to assess the risk factors.

In our study, the prevalence of oral candidiasis was 48.21%, this result is far from that reported by Yahyaoui [7] in the MOHAMMED V RABAT military training hospital in 2013, which found a percentage of 81.8%. Another study by Gravina et al, in Maracaibo (Venezuela), reported a rate of 69.35% [8]. The 16-30 age group was the most representative with 39.29% of cases, a result close to that found by Dembel MA during an epidemiological clinical study on oral candidiasis at the National Center of Odonto Stomatology (CNOS) of Bamako in 2007 which showed that the age group of 20-29 is the most representative with a percentage of 27.4% [9].

Leukemia is a malignant proliferation of hematopoietic tissue, there are four types of leukemia: Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), Acute Myelogenous Leukemia (AML), Chronic Myeloid Leukemia (CML), and Acute Lymphoblastic Leukemia (ALL) especially those aged 16 to 30 years (70%). Previous studies have shown that acute lymphoblastic leukemia mainly affects children but also adults to a lesser extent, it is favored by several risk factors: Genetic, toxic chemicals, physical, as well as anticancer treatments received previously [10].

In our studies, the male sex was the most represented (64.29%); the sex ratio was 1.8 this can be explained by the fact that leukemia affects men much more than women. Epidemiological data in France in 2012 indicate that the crude incidence rate of Acute Lymphoid Leukemia (ALL) is 1.6/100,000/year in men and 1/100,000/year in women and that of Acute Myeloid Leukemia (AML) is 2.8/100,000/year in men and 2.5/100,000/year in women [10].

We found 27 positive cultures, Candida albicans was demonstrated in 15 cultures (55.56%), a result similar to several studies [7,8]. These results can be explained by several parameters, related either to the host or to the species itself. Candida albicans is a saprophyte of the oral cavity, it becomes pathogenic under the influence of changing environmental conditions in its host [11]. The results obtained further prove the performance and superiority of Candida albicans caused infection over all other Candida species; this capacity is linked to the various virulence factors which characterize it. These factors include polymorphism, adhesion and biofilm formation [12]. Importantly, most epidemiological studies have pointed to the emergence of non-albicans species over the past two decades [13]. Oral candidiasis are serious opportunistic infections in immunocompromised patients. They represent a frequent complication in onco-hematology. The change to the pathogenicity of Candida is linked to several factors including cytotoxic treatment, neutropenia, broad-spectrum antibiotic therapy, immunosuppression secondary to corticosteroid therapy and diabetes [14]. According to our result 25.93% of the patients were neutropenic. This rate is close to that found by Stinnent et al 1992 (30.95%) [14].

Malignant disease also promotes oral candidiasis through the immunosuppression caused by chemotherapy. Most chemotherapy drugs can induce neutropenia 8 to 16 days after administration. Leukemia is accompanied by febrile neutropenia characterized by fever (≥ 38.3 °C) and a decrease in the number of circulating neutrophils. Polynuclear neutrophils constitute the first line of defense of the mucous membranes against Candida. They have a crucial role in the initiation of cellular and humoral immunity. They secrete soluble mediators such as IL-1, IL-6 or TNF- α. PNNs have many properties including:

*Limitation of tissue colonization.

*Protection against the dissemination of endogenous yeasts.

*Zn2+dependent fungistatic activity characteristic of PNNs by blocking Candida filamentation.

*Modification of the composition of the fungal cell during the Candida-PNN interaction.

*Release by dead PNNs of a protein inhibiting the growth of Candida.

The intensity and duration of neutropenia are risk factors for infection in leukemic patients [15].

Exposure to broad-spectrum antibiotics is another key risk factor for oral thrush, 37.04% of our patients were treated with broad-spectrum antibiotics. Likewise Pauld E (2005), found that 42.1% of patients with oral candidiasis were put on broad-spectrum antibiotic therapy [16]. Another study carried out at the level of the geriatric ward reported that 95% of patients with oral candidiasis had previously been exposed to antibiotics [17]. The use of antibiotics can contribute to the development of fungal infections by changing the ecology of the resident microflora, opportunistic microbes like Candida can take advantage and grow rapidly in the surfaces of the mucous membranes, when the integrity of these the latter is ruptured, a locally invasive infection develops and secondary hematogenous dissemination can then ensue, even with a decrease in immunity. The duration of treatment can also have an impact, the longer it is, the greater the risk [18].

Corticosteroid therapy: During our work we found that 55.56% of candidiasis patients were on corticosteroid therapy. The Stinnett E study in leukemic children for oral candidiasis research reported a rate of 21.1% of the population were on corticosteroids [14].

Inhaled or systemic corticosteroids have a major impact on the occurrence of oral candidiasis. They interfere with macrophage and neutrophilic functions. The risk of fungal infection increases with the dose and duration of corticosteroid therapy. In autoimmune diseases, the dysfunction of the T cell response necessary to stimulate granulocytes increases the risk of infection [19].

Diabetes is a very common disease which has become one of the greatest public health burdens due to its degenerative complications. Oral candidiasis in diabetic patients is also common. As part of our study, we evaluated the prevalence of oral candidiasis in this field where three cases were reported (11.11%). This prevalence is explained by the availability of the highest levels of sugar in the oral microenvironment, which promotes the adhesion of Candida to epithelial cells, which amplifies the development of Candida and activates the expression of virulence factors [20]. A prospective study of 150 type 2 diabetic patients has shown that 47% of patients have oral candidiasis [21].

Parenteral nutrition: In our study, 55.56% of patients were previously exposed to vascular access. Patients in the hematology department most often wore catheters to deliver their treatments. Colonization of these catheters can occur as early as the first twenty-four hours after placement, it is due to the formation of the biofilm in the internal lumen and on the external surface of the catheter, this microbial biofilm is a population of microorganisms fixed on an inert or living support and constituting a physical barrier to anti-infectives and to mediators of the immune response. Long-term use of catheters leads to complications, the most common and serious of which is infection. These infections can have deleterious consequences for the patient, leading to suspension or discontinuation of chemotherapy, blood transfusion and parenteral nutrition. They can even be life-threatening for patients [22]. Several studies have been carried out on the complications infect.

Competing Interest

The authors declare that they have no conflict of interest directly or indirectly related to this article.

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