Predictors of esophageal candidiasis among patients attending endoscopy unit in a tertiary hospital, Tanzania: a retrospective cross-sectional study

Background Esophageal candidiasis is a common disease among patients with impaired cell mediated immunity. In the current study, we report esophageal candidiasis among patients with various co-morbidities attending the endoscopic unit at the Bugando Medical Centre. Methods This retrospective study was conducted from June to September 2015. All data of the patients who attended the endoscopic unit between 2009 and 2014 were retrieved and analyzed. Results A total of 622 patients who underwent oesophagogastroduodenoscopy were analyzed. A slight majority 334/622(53.7%) of patients were female. Out of 622 patients; 35(5.6%) had esophageal candidiasis. Decrease in age (OR 1.1, 95%CI; 1.0–1.1), female sex (OR 3.8, 95%CI; 1.1–13.1), drinking alcohol (OR 17.1, 95%CI; 4.9–58.9), smoking (OR 8.3, 95%CI; 1.7–41.0), antibiotic use (OR 5.7, 95%CI; 2.0–16.4), positive HIV status (OR 10.3, 95%CI; 4.6–6.0) and presence of peptic ulcer disease (OR 13.2, 95%CI; 3.5–49.0) independently predicted esophageal candidiasis. Conclusion Patients with a history of drinking alcohol, smoking, use of antibiotics and those with chronic diseases such as peptic ulcers were at high risk of developing esophageal candidiasis. Further studies are needed to identify Candida spp. and their anti-fungal susceptibility for proper management of esophageal candidiasis in HIV and non-HIV individuals.

tunistic fungal infections that occur in over 90% of the HIV infected individuals during the course of their illness 1,2 . Esophageal candidiasis has also been reported to occur in 39.1% of patients receiving anti-cancer treatment 3 . In HIV negative population, co-morbidities have been found to increase the risk of developing EC [4][5][6][7] . Other factors that increase the risk of EC include intensive chemotherapy, chronic use of corticosteroids, antibiotic therapy and alcoholism 8,9 . In low-income countries, the diagnosis of EC mainly depends on the clinical presentations; EC commonly presents with dysphagia, retrosternal chest pain and a feeling African Health Sciences of obstruction in the esophagus upon swallowing. It is estimated that 68.6% of patients with EC present with dysphagia 10 . In high-income countries, brushing technique following oesophagogastroduodenoscopy (OGD) then culture and sensitivity is routinely performed for the diagnoses of EC while in low-income countries this practice is not routinely done 11 . Many studies in low-income countries have focused on esophageal candidiasis among HIV infected population. This study investigated the magnitude and factors associated with EC among patients attending the endoscopy unit. In addition, the cases of EC among non-HIV infected population are presented in detail.

Methodology Study design and period
This retrospective cross-sectional study was conducted at the endoscopy unit of the Bugando Medical Centre (BMC) a tertiary hospital in Mwanza, Tanzania. BMC endoscopic unit performs a minimum of 80 endoscopic procedures per month. It provides endoscopic services for approximately 13 million people from eight regions in the lake zone of the country. The study was conducted from June 2015 to September 2015. Data from all patients attending the endoscopy unit between 19 th August 2009 and 19 th September 2014 were extracted and analyzed.

Data collection and study variables
Checklist was used to collect patients' information from hospital files and the endoscopy unit log book. Independent variables such as socio-demographic characteristics (age, sex, marital status, cigarette smoking and alcohol use) and clinical data (corticosteroid use, antibiotic use, HIV sero-status, diabetic and history of peptic ulcer diseases) were extracted. In this study the diagnosis of esophageal candidiasis was made during oesophagogastroduodenoscopy and was defined by the presence of white or slightly yellowish plaque like lesions on the esophageal mucosa as described in a previous study 12 .

Ethical consideration
Ethical clearance to conduct this study was granted by the Joint CUHAS/BMC research ethics and review committee (CREC) with certificate number CREC/045/2014. Permission to conduct the study was sought from the endoscopy unit and all data was kept confidential.

Data analysis
Data were entered and cleaned using Microsoft Excel software and analyzed using STATA Version 11. Age was summarized using mean ± standard deviations. Sex, alcohol use, smoking, antibiotic use, HIV status and presence of peptic ulcer diseases (PUD) were summarized as proportions. Univariate and multivariate logistic regression analysis was done to determine factors associated with esophageal candidiasis among patients attending endoscopy unit. All factors from the literature known to predict EC were subjected to multivariate analysis. A p value of less than 0.05 was considered as statistically significant at 95% confidence interval.

Demographic characteristics
Of the 625 patients who attended the endoscopy unit, 622 patients were enrolled in this study. Three patients were excluded because they had no data on clinical presentations or indication for the endoscopy. The mean age of enrolled patients was 41.59 +15.38 years. A slightmajority of patients were female 334(53.7%). A total of 396(63.7%) participants were unemployed and 121(19.5%) had a history of antibiotic use. Most of patients were HIV negative 554(89.07%) as shown in table 1. The co-morbidities among the studied population included peptic ulcer diseases 85(13.67), diabetics 14(2.25), cirrhosis 14(2.25), asthma 5(0.80) and cancer 4(0.64).   With improvement of the endoscopic services, EC has been reported in HIV negative patients 13,16 , as evidenced in the current study whereby 3.6% of HIV negative patients had EC. In HIV negative patients, the EC is normally associated with peptic ulcer diseases, diabetes and prolonged use of antibiotics 4 , these factors were confirmed in the current study.
In diabetic patients, EC is linked with depressed immune system and the stasis of the esophageal content 17 . Esophageal candidiasis among patients with PUD is linked to the chronic use of the proton pump inhibitors which lead to hypochlorhydria which in turn alters the stomach bacteria flora colonization and increases the risk of candida over growth 10,18 .
Use of broad spectrum antibiotics results in normal flora disturbances leading to over growth of Candida spp. which might progress to EC 4,10 . In the present study patients with a history of antibiotic use had 14 times odds of get-ting esophageal candidiasis than patients with no history of antibiotic use. As it was described in other studies 18,19 , alcohol drinking and smoking were confirmed in this study as predictors of getting EC. This can be explained by the fact that alcohol has the effect of elevating the gastric pH and augmenting the colonization of the esophagus by oral cavity bacteria and yeast 19 .
Despite the significance of the data presented in this study some limitations have been noted; firstly, the study was retrospective; hence the risk factors can be under estimated, secondly the sensitivity and specificity of the clinical diagnosis of EC by endoscopy might have affected the outcome.

Conclusion
Patients with history of drinking alcohol, smoking, use of antibiotics and those with chronic diseases such as peptic ulcers are at high odds of developing esophageal candidiasis. Further studies to identify Candida spp. and their anti-fungal susceptibility are recommended for proper management of esophageal candidiasis in HIV and non-HIV individuals.

Conflict of interest
Authors declare no conflict of interest in publishing this manuscript.