Candida Colonization among Neonates with Low Birth Weight: There Is Much More to Explore

Background and Objectives: Candida colonization in neonates with low birth weight is reported to be the first step for invasive candidiasis. This study was designed to describe the patterns of Candida spp. colonizing neonates with low birth weight in Mwanza, Tanzania to provide baseline information for future studies in this field. Methodology: The hospital based cross sectional study was conducted between January 2019 and April 2019 among neonates with low birth weight. Clinical and social demographic data were collected using interview guide questionnaire. Oral and umbilical rectal swabs were collected on the first and seventh day of life to assess Candida spp. colonization status. Data were analyzed using STATA version 13 following the study objectives. Results: A total of 320 neonates with median body weight of 1600 [IQR 1000 - 2000] grams were enrolled. Prevalence of Candida spp. colonization on either oral, umbilical or rectum was 16.2% (52/320). A total of 34 (10.6%) and 41 (12.8%) neonates were colonized by Candida spp. on the first day and seventh day of life, respectively. Of 34 neonates colonized on the first day of life, 23 (67.7%) were still being colonized on the seventh day.


Introduction
Globally the leading cause of neonatal deaths is infection with 10% reported to be due to Candida spp. [1] [2]. The mortality due to neonatal-candidiasis is estimated to range between 30% and 73% [2] [3]. Candida colonization in neonates with low birth weight is reported to be the first step for invasive candidiasis [2] [4]. Studies have shown 7% -25% of low birth weight neonates are colonized by Candida spp. and are at high risk of developing invasive candidiasis [5] [6].
Among neonates with very low birth weight admitted in intensive care unit, Candida spp. is reported to be the third leading causative agent of sepsis [1] [7].
Neonatal Candida spp. colonization is reported to commonly occur in the first weeks of life whereby up to 10% -64% of neonates can be colonized [8]. The neonatal Candida spp. colonization was reported in a study conducted in India to be significantly more in neonates with low birth weight < 1500 gram with prevalence of 33.3% compared to the prevalence of 10% among neonates with birth weight > 1500 gram [9].
Risk factors for Candida spp. colonization include: use of broad spectrum antibiotics, resuscitation after birth and per vaginal deliver with colonized mother [9] [10]. Furthermore, Candida spp. colonization has been pronounced more in premature neonates regardless of their birth weight [11].  [14]. Despite having 40% -50% admissions of neonates with low birth weight at Bugando Medical Centre neonatal intensive care unit (BMC NICU), there is paucity of data on the magnitude and patterns of Candida spp. colonization in this and other centers in the developing countries. Here, we report the prevalence of Candida spp. and their distribution among recruited neonates from intensive care unit of the Bugando Medical Centre (BMC), Sekou Toure Regional Referral Hospital (SRRH) and Sengerema District Designated Hospital (SDDH).

Material and Methods
The descriptive cross sectional hospital based study was conducted from January 2019 to April 2019. The study recruited neonate with low birth weight below 2500 grams on their first day of life admitted in neonatal intensive care units and premature units of BMC, SRRH and SDDH. The neonatal admission per month at BMC ranges from 100 -200 with about 40% -50% having low birth weight. At SRRH and SDDH the admissions due to low birth weight range from 40 -50 and 150 -200, respectively. The study excluded all neonates with abdominal wall malformations such as gastroschisis, omphalocele and genital urinary tract like bladder exstrophy. The sample size was obtained by the use of Kish Leslie formula [15] using the prevalence of Candida spp. colonization obtained from a study conducted in Uganda [11].
Screening of the neonatal gestation age and maturity was done using Ballard score [16]. Parents with neonates fulfilling inclusion criteria were interviewed to obtain social demographic and clinical data like age, sex, residence mode of delivery, serological HIV status and history of premature rupture of membrane (PROM). Clinical examination to assess temperature, respiratory rate, presence or absence of cyanosis, jaundice, umbilical redness, convulsions, reduced movements and inability to feed was done by qualified pediatrician. Oral and umbilical-rectal swabs were taken on day 1 and day 7. All swabs were transported to microbiology laboratory in the Stuart transport media (HiMedia-Mumbai, India) within two hours of collection for processing. All swabs were cultured on Sabouraud's dextrose agar (SDA) supplemented with 50 µg/ml gentamicin and 50 µg/ml chloramphenicol (HiMedia-Mumbai, India) as previously described [17]. Colonial morphology, germ tube test and reaction on the

Discussion
Candida colonization in neonates has been documented as a major predisposing factor to invasive candidiasis [18] [19] [20]. In the current study the prevalence of neonatal candida colonization on either oral, umbilicus or rectum was found to be 16.3%. This prevalence is within the range of 12.  [22]. The prevalence reported in the current study is significantly lower (p = 0.022) than the prevalence reported from Uganda 23.3% [11]. The study in Uganda recruited much younger neonates with low birth weight than the current study, age and birth weight have been found to increase risk of Candida spp. colonization [11]. In the current study the median gestation age and birth weight was 33 [30 -35] weeks and 1600 [100 -200] grams, respectively. As in previous studies, [11] [19] [23] Candida albicans was the predominant specie detected. The ability of C. albicans to maintain synergistic relationship with other bacteria flora of the skin and buccal cavity can explain the findings [24] [25]. Non-albicans Candida spp. were detected to colonize 26.9% of colonized neonates with low birth weight. Candida colonization by non-albicans Candida spp. have also been observed in different population from our previous studies [17] [23]. This has also been reported in other studies worldwide in the past decade [26] [27] and is highly associated with increased rate of candida infections due to non-albicans Candida spp.
Candida glabrata has been noted as one of the leading non-albicans Candida spp. colonizing and causing infections in different population [17] [27]. This has also been observed in the current study whereby Candida glabrata was the most frequently non-albicans Candida spp. isolated. The isolation of Candida glabrata is of public health concern due to its variable susceptibility to fluconazole the most frequently used antifungal agents [28]. Candida glabrata has also been reported as emerging health threat causing neonatal sepsis [27].

Conclusion
The prevalence of candida colonization among neonates with low birth weight is within the reported range of other studies from Africa, and is mainly due to Candida albicans. Future studies are highly needed to explore the role of colonization and subsequent Candida spp. infections.

Limitation
The patterns of Candida spp. colonizing these neonates might not reflect the true picture due to low discriminatory index of the techniques used to speciate the isolated Candida spp. Open Journal of Pediatrics

Availability of Data and Materials
The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Conflicts of Interest
None declared.