1
COURSEWORK ASSESSMENT SPECIFICATION
(PG)
Details of Module and Team
What Learning Outcomes are assessed?
What are my Deadlines and how much does
this assessment contribute to my Module
Grade?
What am I required to do in the assessment?
What are my assessment criteria? (What do I
have to achieve for each grade?)
Can I get formative feedback before submitting ?
If so, how?
What extra support could I look for myself?
How and when do I submit this assessment?
How and when will I get summative
feedback?
What skills might this work evidence to
employers?
MODULE CODE
BIOL40472
MODULE TITLE
Medical Microbiology
COURSEWORK TITLE
Review article
2
LEARNING OUTCOMES
ASSESSED
Kl: Relate theory to the clinical
and laboratory aspects of Medical
Microbiology investigations;
K2:
Demonstrate
a
critical
understanding of the role of the
microbiology laboratory in the
diagnosis of disease; K3: Demonstrate a
thorough understanding of the causes
of infection and evaluate appropriate
methods of prevention, detection and
treatment. K4:
Demonstrate a thorough understanding
of the principles and methodologies of
the techniques used in medical
microbiology.
Sl:
Critically evaluate research
and development work;
S2: Present work in written form to a
standard appropriate at Masters level;
S3: Collect, collate and critically report
on scientific literature;
S4: Show evidence of continued
learning by independent study;
3
4
Work handed in up to five working days late will be given a maximum
Grade of Low Pass whilst work that arrives more than five working
days will be given a mark of Zero.
Work will only be accepted beyond the five working day deadline if
satisfactory evidence, for example, an NEC is provided. Any issues
requiring NEC https:/(ntu.ac.uk/current students/ resources/ student
handbook/ app eals/index.html
The University views plagiarism and collusion as serious academic
irregularities and there are a number of different penalties which may
be applied to such offences. The Student Handbook has a section on
Academic Irregularities, which outlines the penalties and states that
plagiarism includes:
'The incorporation of material (including text, graph, diagrams,
videos etc.) derived from the work (published or unpublished) of
another, by unacknowledged quotation, paraphrased imitation or
other device in any work submitted for progression towards or for
the completion of an award, which in any way suggests that it is the
student's own original work. Such work may include printed
material in textbooks, journals and material accessible electronically
for example from web pages.'
Whereas collusion includes:
"Unauthorised and unacknowledged copying or use of material
prepared by another person for use in submitted work. This may be
with or without their consent or agreement to the copying or use of
their work." If copied with the agreement of the other candidate both
parties are considered guilty of Academic Irregularity.
Penalties for Academic irregularities range from capped
marks and zero marks to dismissal from the course and
termination of studies.
To help you avoid plagiarism and collusion, you are permitted to
submit your work once to a separate drop box entitled "Draft report"
to view both the matching score and look at what areas are affected.
It is then down to you to make any changes needed.
5
6
Turnitin cannot say if something has been plagiarised or not. Instead it
highlights matches between your text and other Turnitin content.
There is no Good or Bad score , it depends on the piece of work
If you find your text matching there may be a problem, see the examples
below.
7
1) The reference section is highlighted. This may mean you
have referenced correctly and this has been matched with
other well referenced documents online.
2) A table containing class data is highlighted. This is acceptable
as long as any text accompanying the table is not similar
picked up as identical
3) Paragraphs of text in the introduction or conclusion sections
are highlighted. This may mean they have been copied exactly
from another source. Even if this source is referenced this is
bad practice, see advice below
4) A sentence, or part of a sentence is highlighted. Sometimes there
are few ways to write a sentence, especially straightforward
ones. As long as this does not occur throughout a paragraph this
may be acceptable. There will be occasions where a few words
within a sentence produce a match. This is acceptable but
ensure that this not a common occurrence or a patchwork of
copied statements from different sources.
Overall when you look at the work, put yourself in the place of the
marker. Is a lot of the work highlighted so it does not really look like
the author's work? If so, then you need to work on it some more
For help, do not contact the setter of the work, but use these links
(Plagiarism Support and Turnitin support) to book time with staff and
students to help with
I. Assessment Requirements
You should produce a review article of approximately 3000 words
(absolute maximum is 3300 words excluding references, abstract,
boxes and figures/tables) on the topic outlined below. The review
should give sufficient background and context, critically cover recent
advances in the field, be clear and easy to follow even for non-experts,
progress logically with clear signposting, and include a concluding
section. Your article should be appropriately referenced and formatted
in the style of a professional journal, Trends in Microbiology. You
should format your
8
review article as if it were a published paper in this journal (see pdf
versions of recent papers from this journal to view the style; examples
are available in the Resource List).
In your review, you should include a title and authors (in this case
just yourself), an abstract, the main body of the review and two
additional boxes, the 'Highlights' box and the 'Outstanding Questions'
box, which are given in all Trends in Microbiology papers. You may
add further optional boxes if you wish, following the guidelines
provided in the Trends in Microbiology Instructions to Authors Note
that the abstract, boxes and reference list do not count towards the
3000-word limit (however, in-text citations do).
You are encouraged to use Figures and Tables to help explain complex
ideas in your review article. Figures should have a title and a legend
allowing the figure to be understood independently from the main
text. However, all figures and tables should be called out in the main
text of the review. If using a figure from some other publication, the
source of the figure must be cited. Use high-quality images with
sufficient resolution, so the images do not appear pixelated or blurry
in the final paper. Most scientific journals allow downloading highresolution images and using them for educational purposes if the
source publication is cited. You can also prepare your own figures. A
particularly useful programme is
Biorender
(www.biorender.com),
which
allows
making
professionallooking figures quickly and easily. This programme is free
to use for educational purposes. Tables should have a title and possible
explanatory notes and should be formatted according to the journal
style. Tables and figure legends do not count towards the 3000-word
limit.
You should cover the topic as described below. However, you are free
to choose a title and focus on a particular aspect of the topic, so long as
all the points noted in the specifications below are covered. You should
base your work on the latest primary research literature. You can also
cite other review articles or reputable online sources (e.g. the websites
of Public Health England, the World Health Organization, the Centers
for Disease Control and Prevention etc.), but most of your references
should be recent original research articles. Avoid using online sources
such as Wikipedia as your only references. Wikipedia is a good starting
point to get an overview of a subject, but it should not be referenced in
a scientific context as the content can be edited in a non-controlled
way. The citation style should be as in Trends for Microbiology.
9
When preparing your review article, it is highly recommended that you
use a reference manager. offers RefWorks - see the for further
information.
Note that the article is limited, so you probably cannot include all the
information you have found. You will therefore have to select which
information to include to make a clear, balanced, engaging and up-todate review article.
Some examples of excellent coursework are provided in the learning
room on NOW.
The library also offers support with referencing and various other
aspects of writing; see
The Language Centre offers support with academic English:
https://www.ntu.ac.uk/studyandcourses/courses/ourschools/hum/english- classes
You should submit your article as a single pdf to the dropbox on NOW
by Friday 4th December (Week 19). You may also submit the original
Word document file in addition to the pdf.
Topic for coursework: Lung infections in cystic fibrosis
patients Introduce the condition of cystic fibrosis, the pathogens
associated with the condition,
discuss
disease
symptoms
and
progression
of the
disease, epidemiology, diagnosis, and treatment and control
options. You are free to give the review a title of your choice and focus
on a specific aspect of the topic, as long as the review covers all the
points noted above.
幫
岳 늠c
℃
그
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흐픈셛
Exceptionally well-
fully orofessional
standard.
Article is fully
in the suggested
journals.
papers and reputable
data sources. Cited
sources are highly
relevant to the topic
and of high quality.
10
Ill. Feedback
Opportunities
Formative (Whilst you're working on the coursework)
You will have an opportunity for peer feedback on a draft of your work
during Week 17. You can also join the online tutorials during Weeks 15
and 17 for support. Queries can be posted on the discussion forums in
the NOW learning room.
Summative (After you've submitted the coursework)
You will receive specific feedback regarding your coursework
submission together with your awarded grade when it is returned to
you. Clearly, feedback provided with your coursework is only for
developmental purposes so that you can improve for the next
assessment or subjectrelated module.
IV. Resources that may be useful
Referencing styles: please use the journal-specific style as detailed here.
Guide to planning your time here and an automated planner here. Further
guidance on avoiding cheating is here.
Remember to use Outlook or physical calendars to block out time between
lectures and labs to work on this coursework.
V.
Moderation
The Moderation Process
All assessments are subject to a two-stage moderation process. Firstly, any
details related to the assessment (e.g., clarity of information and the
assessment criteria) are considered by an independent person (usually a
member of the module team). Secondly, the grades awarded are considered
by the module team to check for consistency and fairness across the cohort
for the piece of work submitted.
VI. Aspects for Professional Development
The report itself covers examples
of: Writing a scientific-style
report Researching existing
literature Referencing
appropriately
Construction and proper labelling of figures
Many of these are useful transferable skills for employment applications or
your Skills Portfolio. Similarly, the practical class protocols provide several
examples appropriate for use in the Skills Portfolio as bioscience (i.e. subjectspecific) skills.
Candida infections
Zoe Taylor
The Candida genus has over 200 species in it, however only few of these species are
pathogenic. The main 5 clinically important are discussed in this review: Candida
tropicalis, Candida krusei, Candida glabrata, Candida parapsilosis and Candida
albicans. Superficial and invasive Infections are most commonly found in the
immunocompromised. Cases of superficial infection usually influence the mucosal
membranes, whereas invasive infections are seen all over the body’s organs. In this
review, we cover the main and emerging pathogens, epidemiology, symptoms,
diagnosis and treatment of these significant Candida species, while introducing the
worrying challenges antifungal resistance poses to the at-risk populations.
Pathogenic Candida species cause problems for immunocompromised
The genus Candida boasts over 150-200 recognised species; this review will focus on
distinct pathogenic species, adapted to survive in the human host as commensal
bacteria and behave opportunistically when the hosts immune and antimicrobial
defences are compensated. Candida albicans is most common species of the Candida
genus and where most research is focused [1]. Candida bacteria are the cause of most
fungal infections and around 90% of these are due to five species, Candida tropicalis,
Candida krusei, Candida glabrata, Candida parapsilosis and the most common, Candida
albicans. Candida fungus can cause mucosal and cutaneous infections as well as
systemic [2]. They pose a serious health risk to the immunocompromised and
hospitalised, with the source of around 8% of nosocomial bloodstream infections being
Candida species [3]. The incidence of Candida infections is rising, and many factors
contribute to the risk of catching opportunistic fungi infections, including the increase
in immunocompromised patients with mucosal or cutaneous barrier disruption and
neutrophil defects, an aging population and the escalated use of broad-spectrum
antibiotics, transplants and chemotherapeutics [2].
Main and emerging human pathogens
Candida albicans
Candida albicans colonizes a multitude of locations in the body, including the
gastrointestinal and genitourinary tracts of healthy people. It is the most common
fungal species found in human microbiota. Adjustments in host immunity, resident
microbiota, stress and other circumstances provokes C. albicans to overgrow, causing
two main types of infections in humans: superficial candidiasis in the vaginal and oral
regions, and life-threatening disseminated candidiasis [4]. To successfully infect the
host, C. albicans depends on an array of virulence factors (Figure 1); the ability to
morphologically convert between yeast and hyphal forms, the compilation of biofilms,
thigmotropism, phenotypic switching and then expression of adhesins and invasins on
the cell surface are a few pathogenicity mechanisms [5].
Highlights
Candida species such as C.
albicans transition from
commensal
to
opportunistic
pathogens
frequently
in
immunocompromised
hosts.
Mucosal
and
invasive
infections
are
the
consequence
of
this
transition and are a major
cause of mortality.
Optimal diagnosis and
treatment options are
needed to improve these
mortality rates, as well as
tacking growing antifungal
resistance.
Key Figure
Pathogenicity mechanisms in Candida species.
Figure 1. An outline of the different mechanisms of pathogenicity used by Candida species. (A) Expression
of adhesins allows yeast cells to adhere to cell surface membranes. (B-C) When the yeast cells come into
contact with the cell surface membrane, it triggers the yeast cell to transform into hyphae and directed
growth by thigmotropism. (D) Switching (phenotypic plasticity) is thought to influence antigenicity and
biofilm formation. (E) In medical devices (specifically catheters), biofilms can form, usually with yeast cells
on device and hyphae cells on top of the biofilm. (F) Fitness traits can influence fungal pathogenicity as well
as virulence factors. These include heat shock proteins (Hsps) in the response to stress, the uptake of amino
acids, excretion of NH₃ can cause yeast cells to turn into hyphae, the uptake of compounds such as carbon
and nitrogen and fundamental metals iron, zinc, copper and magnesium [5].
With the increase of opportunistic fungal infections and the rise in use of antifungals for
prophylaxis in patients, CNA species colonization has become more prevalent in the
immunocompromised populations. C. tropicalis has emerged as the second most
virulent Candida species to C. albicans. It is known for its ability to form true hyphae like
C.albicans, to produce strong biofilms and have properties which make it highly
adherent to epithelial and endothelial cells [6]. C. tropicalis is frequently found in
neutropenic hosts, specifically those with cancers such as leukaemia. It poses a great
threat to these patients due to the ability of it to move through the bloodstream to
peripheral organs [7].
Another emerging Candida pathogen is Candida krusei, especially among patients
suffering from acute leukaemia and other haematological malignancies. Naturally it is
resistant to fluconazole, a standard antifungal agent. It is therefore found most
commonly in patients who have previously been treated with fluconazole. The mortality
rate for Candida krusei infections is higher than C.albicans and other Candida species
[8].
The widespread use of immunosuppressive therapy and antimycotic therapy has led
to Candida glabrata infections to rise significantly. It was previously a nonpathogenic commensal fungus, but now is the third most common cause of
candidiasis. Like C.albicans it can cause systemic and mucosal infections in
immunocompromised hosts. Despite these similarities, C.glabrata is not dimorphic
and is found as blastoconidia in both pathogenic and non-pathogenic form. Like C.
krusei, C.glabrata infections are difficult to treat and have a high mortality rate [9].
The frequency of Candida parapsilosis infections has drastically increased over the
past decade and is a leading cause of invasive Candida disease. High risk patients
include neonates and those in intensive care. The fungus is strongly associated with
hyperalimentation solution, indwelling catheters and prosthetic devices. It is able to
form biofilms on catheters and other implanted devices, as well as adhere to
prosthetics and secrete hydrolytic enzymes, allowing them to persist in the hospital
environment [10].
Epidemiology
Candida species have become the most common cause of significant fungal
infections. C.albicans has historically accounted for 70-80% of Candida infection
isolates while CNA species, C.tropicalis and C.glabrata accounted for around 5-8% of
isolates. Epidemiological studies from recent years have highlighted a mycological
shift where Candida species such as C.glabrata, C.tropicalis, C. krusei and
C.parapsilosis are becoming more common [11]. Table 1 shows the global estimates
of Candida infections; however, these figures are now 3 years out of date, therefore
population distribution may have changed.
Table 1. Annual incidence of the different types of Candida infections in 2016 [Taken from
12,13].
Risk factors of invasive candidiasis
IC infections have been rising since the 1980s, specifically in immunocompromised
populations and in patients who have been hospitalized with underlying conditions
[14]. It is a leading cause of mortality, with candidemia being the most frequent
clinical presentation of IC. Factors contributing to the increased incidence include
the expanded use of broad spectrum anti-fungal agents, the number of
immunocompromised patients using intravenous catheters, a rise in the number of
invasive procedures, use of therapeutic drugs and transplantation [15].
Glossary
Invasive candidiasis: A
critical Candida infection
that can affect many
organs in the body,
including the blood, eyes
and brain.
Candida
non-albicans
species: Candida species
that does not include the
most
common
type,
Candida albicans
Candidemia:
The
existence of Candida in the
blood stream.
Vulvovaginal candidiasis:
A condition affecting over
75% of women in their
lifetime. Caused by an
overgrowth of Candida
yeast in the vagina and
vulva.
Oral candidiasis: The
overgrowth of Candida in
the mucosal membranes
of the mouth.
Species distribution
Candida is now the fourth most common organism found in blood cultures in
patients who have been hospitalized. In patients with AIDS, the most common fungal
infection is Candida [14]. The difference in distribution of Candida species in patients
can be related to varying factors. Candida parapsilosis is commonly identified in
neonates with candidemia and usually originates exogenously, contaminating
medical devices and subsequently leading to central venous catheter-associated
candidemia’s [15]. Other NAC species like Candida glabrata, Candida tropicalis and
Candida krusei are found in blood cultures from patients who are 65 and over. These
patients present with risk factors including solid tumours, abdominal surgery,
haematological malignancies, transplants and corticoid steroid treatments [16].
Geographically, C. albicans accounts for over half of the incidences of candidaemia
in Europe. Incidence rates for NAC infections showed C.glabrata and C.parapsilosis
at 14%, C.tropicalis at 7% and C.krusei at 2% [17]. In North America, despite
C.albicans being the most prevalent species, C. glabrata and other NAC species are
emerging [18]. C. parapsilosis is prevalent in Latin America, Australia and the
Mediterranean. In Chile, there is progressive expansion of NAC infections, with
C.parapsilosis overtaking C.albicans as the most abundant species, followed by C.
tropicalis and C.glabrata[19]. In Brazil, 20.9% of cases were C. tropicalis, 40.9%
C.albicans, 20.5% C.parapsilosis and 4.9% C.glabrata [20].
Symptoms
Oral
Oral candidiasis (OC) has a variety of clinical manifestations. Classically, it presents
as acute pseudomembranous, acute and chronic erythematous (atrophic) and
chronic hyperplastic variants [21]. Other Candida-associated lesions include median
rhomboid glossitis, angular cheilitis and linear gingival erythema, although the
latter’s microbial aetiology is poorly understood. Oral pseudomembranous
candidiasis (thrush) is distinguished by white pseudomembranes, formed of
desquamated epithelial cells, fungal hyphae and fibrin. The white patches can be
found on the hard and soft pallet, surface of the labial and buccal mucosa, tongue,
oropharynx and periodontal tissues. Other conditions can also present with these
symptoms, such as lichen panus and squamous cell carcinoma, therefore it is
imperative that clinicians look at patient history and identify any underlying diseases.
However, pseudomembranous candidiasis accounts for one third of oropharyngeal
candidiasis cases, and because it is so common it is straightforward to diagnose [22].
Vulvovaginal
Vulvovaginal candidiasis (VVC) can be categorized as either sporadic or recurrent,
depending on how frequent episodes of infection are. Clinically it is vital to
distinguish between these two categories in order to manage them effectively.
Symptoms include irritation, vulvovaginal pruritus, dyspareunia, white ‘cheesy’
discharge and burning when urinating. Unfortunately, both individually and
collectively, none of these symptoms are pathognomonic [23].
Invasive
Invasive candidiasis (IC) incorporates a myriad of different clinical conditions, the
most common being candidaemia. This is associated with a high mortality rate and
long stays in hospital. Another, deep-seated candidiasis causes various syndromes
which involve the liver, heart, eyes, spleen , kidney, mengies, bone, peritoneum
and lungs. This can be with or without concomitant candidaemia [24]. Invasive
candidiasis has non-specific symptoms and is usually a nosocomial infection, with
many risk factors contributing to the different symptoms exhibited by patients
(Table 2) [25].
As there are no disease specific symptoms or clinical signs of IC, research presents
a variety of different manifestations seen by patients. Most have found that
patients presenting with persistent fever which is unresponsive to broad spectrum
antibiotics is indicative of IC. It is also reported that some patients (19% of cases)
developed septic shock, found in a point prevalence study [26]. Another study has
shown a higher incidence of renal and hepatic failure and lower lactate
dehydrogenase levels in patients with septic shock caused by Candida species than
the bacterial septic shock [27].
Table 2. The risk factors involved in invasive Candidiasis and the subsequent range of
symptoms observed [Taken from 25].
Diagnosis
Oral
Diagnosis of OC is usually started by taking patient history and a thorough
examination of the mouth. This involves examining the hard and soft pallet and
buccal mucosa (for those with dentures) [28]. Correct diagnosis for acute
pseudomembranous and chronic atrophic candidiasis is made by identifying a
characteristic lesion and its response to antifungal therapy. There diagnosis can be
made clinically, however if anti-fungal treatment fails, subsequent culture and
sensitivity testing should be carried out. This includes imprint cultures using
Sabouraud’s broth. Sterile foam pads are dipped in the broth and then placed on
the lesion for 30 seconds. They are then cultured in Sabouraud’s agar with
chloramphenicol for an hour and then incubated. A biopsy is recommended for
acute atrophic and chronic hyperplastic forms on top of this, as these presentations
may mimic other diseases such as squamous cell carcinoma [22].
Vulvovaginal
As VVC is not pathognomonic, an accurate diagnosis cannot be made from a
patient’s history and physical examination alone. Laboratory tests are needed to
reliably diagnose patients due to the wide range of other causes for these nonspecific symptoms. Despite this, VVC is commonly diagnosed from only a physical
examination and self-diagnosis, leading to over-the-counter purchase of antifungal medication [29].
Methods used in the laboratory are summarised in figure 2. These include
microscopy using saline solution to detect yeast blastospores or pseudohyphae or
using 10% potassium hydroxide. The potassium hydroxide test has a higher
sensitivity out of the two, however one third of cases produce a negative result
[30]. Microscopy with saline solution poses difficulty in recognising blastospores
which don’t form hyphae or pseudohyphae from nonalbicans strains. Still, these
two tests in amalgamation with a normal vaginal pH reading is usually indicative of
vulvovaginal candidiasis and excludes other sources [31].
Key Figure
Diagnosis of vulvovaginal candidiasis
Figure 2. Investigation and laboratory diagnosis of vulvovaginal candidiasis in patients showing
signs and symptoms[23].
Invasive
IC is hard to diagnose due to the most common manifestation being candidaemia
which is largely asymptomatic. There is also a lack of disease specific symptoms,
like vulvovaginal candidiasis [32]. Therefore, there are a variety of diagnostic
methods used. IC can be diagnosed using direct, such as blood cultures and indirect
detection, using PCR assays and surrogate markers. A number of diagnostic tests
must be used as no laboratory test is 100% accurate in diagnosis of IC.
Blood cultures
Blood cultures are used to detect Candida which resides in the bloodstream.
Despite only having 50-70% sensitivity (reported in autopsy studies), they are the
gold standard technique when diagnosing candidaemia [33]. The sensitivity of
modern blood culture techniques is reduced by intermittent shedding of organisms
from the blood stream, non-viable organisms and also through blood volumes
having low pathogen numbers therefore it is recommended to sample frequently
[34]. Deep-seated candidiasis is diagnosed by the growth of positive cultures from
collected sterile tissue samples, however these are hard to obtain [33]. Other
drawbacks of blood cultures include slow turnaround times and that positive
results may only be seen in late stages of the disease. If a blood culture returns
positive, immediate treatment should be given [35].
Molecular techniques
Molecular tests for diagnosis of IC include the β-D-glucan assay and Candida
mannan antigens and antimannan antibodies (table 2). β-D-glucan is component of
the cell wall of different important fungi [36]. It can detect candidaemia and intraabdominal candidiasis, however it has low sensitivity and specificity, which is
sometimes overestimated due to studies using healthy and mildly ill patients.
Other limitations include false positive results in patients with high risk of IC due to
a high rate of contamination. Nonetheless, β-D-glucan has a negative predictive
value for invasive candidiasis in places where IC has a low to moderate prevalence.
For these reasons, these tests are not commonly used in many European
laboratories [37,38].
PCR assays also exists to diagnose IC. A Nguyen et al. study found an 89% sensitivity
for deep-seated candidiasis that wasn’t detected on blood cultures. Two
commercial PCR methods have been marketed in recent years; SeptiFast in 2015
and T2Candida Panel which has been recently tested one clinical trial, showing
encouraging results (table 2) [39]. Another commercial whole-blood multiplex PCR
assay that detects 5 of the most medically significant Candida species has reported
a 94% sensitivity [40]. An automated PCR based method named a T2 magnetic
resonance assay has found to be encouraging in rapid diagnosis of IC [41]. These
detection methods do have disadvantages, they have restricted validation and
standardization, which has halted their implementation and progression into
laboratories [42].
Other ways for diagnosing IC include MALDI-TOF, which has been promising in
accelerating the right identification of Candida spp. [43]. In diagnosis of
endophthalmitis, patients with visual disturbance are recommended to receive a
dilated fundoscopy [44]. When Candida species are found in urine or respiratory
isolates, the fungi have colonized, although if neutropenic patients have
symptomatic candiduria this can indicate to the presence of Candida cystitis and
needs treatment [45].
Table 3. The different types of laboratory-based tests used to diagnose IC. CSF denotes
cerebrospinal fluid, CNS central nervous system, IQR interquartile range. A spiked sample
is a negative sample where Candida has been added [Taken from 24].
Treatment
Treatment is given on suspicion of Candida infection, even in absence of clinical
symptoms. There are four main classes of anti-fungal drugs with treat mucosal and
invasive Candida infections. These are as follows; azoles, echinocandins, polyenes
and nucleoside analogues (figure 3) [46].
Key Figure
Antifungal treatments for Candida
Figure 3. The different classes of treatment for Candida infections and their mode of action [Taken from 76].
Azoles
As seen in figure 3, azoles are the largest group of antifungal drugs. They work by
inhibiting lanosterol 14-α-demethylase, causing disturbance in the cell membrane
[47]. Lanosterol 14-α-demethylase is an enzyme which is required for the
biosynthesis of ergosterol, the biggest sterol element of the cell membrane in
funguses. There is no cross reactivity with host cells as ergosterol differs
structurally to cholesterol found in human cell membranes. Azoles can be used
both topically and for therapy in IC. Drugs in this category include imidazole’s,
triazoles and posaconazoles [47,49].
An example of when azoles are used is in vulvovaginal candidiasis. Fluconazole,
ketoconazole and itraconazole are highly effective when treating uncomplicated
versions of the disease [50]. Fluconazole has particular advantages in singledosages as it is still secreted from vaginal tissue in therapeutic concentrations
after 72 hours. Studies have shown that all three drugs are clinically and
mycologically equivalent (single-dose fluconazole, single-day itraconazole) [51].
However, in complicated vulvovaginal candidiasis, studies have compared
single-dose fluconazole with multidose 7-day treatments of miconazole or
clotrimazole. Patients with a history of recurrent VVC showed a reduced
response to both therapies, highlighting the need for it to be treated longer with
anti-fungal therapy [52]. Studies are ongoing to find the correct oral treatment
regime. In severe infection, the 7-day multidose treatment worked better than
the single-dose of fluconazole [53].
Polyenes
Polyenes also bind to ergosterol (figure 3), disrupting the cell membrane and
leading to the production of aqueous pores. This causes the cells permeability
to alter, cytosolic components leak, and the cell to die. Drugs in this family
include nystatin and amphotericin B [54].
Polyenes are used in the treatment of IC, and amphotericin B has a low
minimum inhibitory concentration resistance patterns and broad activity
throughout most Candida species [55]. It has been the first line treatment for
severe Candida infections for 5 decades, however it has toxic adverse effects,
including infusion reactions and kidney damage. Other therapies have been
proposed for IC; a Duarte et al study compared caspofungin with amphotericin
B, reporting significantly less drug-related adverse effects in the caspofungin
group [56].
Echinocandins
Echinocandins are a relatively new antifungal agent. They inhibit the synthesis
of the fungal wall by blocking (1,3)-β-D-glucan synthase non-competitively
(figure 3)[57]. This causes the cell walls to have a damaged structure, leading to
osmotic lysis. Echinocandins include the drugs caspofungin, micafungin and
anidulafungin and the all have concentration-dependent anti-fungal activity
against most Candida species [58].
They are used in treatment of oesophageal candidiasis, IC and candidaemia.
They have a lower incidence of infusion related unpleasant effects and their
nephrotoxicity is lower than amphotericin B [59]. Despite this, they have an
adverse effect of hepatoxicity and therefore liver function needs to be
monitored. The drug is also more expensive than azole therapies and therefore
their use may be limited to cases where azole resistance is found [60].
Nucleoside Analogues
Nucleoside Analogues inhibit DNA and RNA synthesis (figure 3) by inhibiting
thymidylate synthase [61]. Therapies in this family include flucytosine, and it is
commonly used together with amphotericin B for treatment of CNS candidiasis.
Studies have shown that flucytosine is effective in small doses at frequent time
intervals. Bone marrow toxicity is a side effect linked to large concentrations
[62].
Antifungal resistance
The extensive use of some of the drugs mentioned in treatments has
encouraged selection pressure and subsequent antifungal resistance [63].
Resistant C.albicans strains have been seen frequently in people with HIV and
oropharyngeal candidiasis [64]. Despite this, NAC species are more frequently
showing resistance, most significantly in C.glabrata and C.parapsilosis [65].
Azole resistance
Around 7% of bloodstream Candida infections show resistance to fluconazole,
the most used drug for C.albicans infections [66]. The rise in infection from NAC
species is thought to be due to their intrinsic azole resistance. This ability for
Candida species to have high levels of azole resistance is well documented, with
research showing C. glabrata with the highest. Patients with oropharyngeal
candidiasis have shown higher levels of fluconazole resistance depending on
whether they have been previously treated with the drug [67]. Resistance arises
through a multitude of mechanisms; decreasing the concentration of azole
inside the cell via the upregulation of efflux pumps, decreasing the drugs target
affinity and counterbalancing the drugs effect [68].
Polyene resistance
It is rare for antifungal resistance to develop in polyenes such as amphotericin
B, even though it has been around for over 30 years. However, as there has
been an increase in infections caused by NAC species, resistance to
amphotericin B resistance has recently risen [69]. Studies have shown
C.glabrata and C.krusei have higher minimum inhibitory concentrations to
polyenes than C.albicans, meaning that larger doses of amphotericin B are
needed, and more antifungal resistance has been reported in these species
[70]. Resistance occurs because of a decrease in ergosterol in cell membranes.
Studies have shown that isolates of Candida species that are resistant to
polyenes have lower ergosterol levels than susceptible species [71].
Echinocandin resistance
Despite resistance in polyenes being rare, echinocandin resistance is a serious
problem due to their critical importance in the treatment of invasive
candidiasis. Resistance is most frequent in C.glabrata, with a 7.4% increase
from 2001-2010 [72]. In even more worrying statistics, species are emerging
with resistance to echinocandins and azoles [73]. Resistance arises due to point
mutations in genes which code for (1,3)-β-D-glucan synthase, causing reduced
target processivity for the drug [74].
Even with the treatments discussed in this review, therapy for Candida
infections is limited, and the evolvement of antifungal resistance, new
treatments are needed. Studies have shown that antifungal treatments that
intervene early are important in effective treatment of IC . Once an effective
approach has been defined, mortality rates should decline [24].
Conclusion and future perspectives
Pathogenic Candida species have been an emerging threat to at risk
populations for decades. Excluding fairly common infections such as
vulvovaginal and oral candidiasis, IC is now the most common fungal disease
found in hospital patients and it poses serious danger to those at most risk,
causing up to 40% mortality [75]. Fortunately, its management has improved
vastly in the past 10 years. Patients are able to receive intervention in the early
stages of disease thanks to new laboratory methods such as PCR assays and
antigen tests. However, more research is needed into non-culture-based tests
to fully validate their ability to strongly diagnose IC.
Even with the treatments discussed in this review, therapy for Candida
infections is limited, and the evolvement of antifungal resistance, new
treatments are needed. Studies have shown that antifungal treatments that
intervene early are important in effective treatment of IC . Once an effective
approach has been defined, mortality rates should decline [24].
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Candida: Epidemiology, Pathogenesis, Diagnosis, and
Treatment.
Highlights
Introduction
Candida species such as Candida albicans,
Candida infections are considered one of the most
Candida
glabrata,
Candida parapsilosis,
prevalent kinds of opportunistic yeast infection [1,2]. They
responsible for causing fungal infection in the
Candida krusei, and Candida tropicalis are
constitute a lethal form of infection that can affect the
human body.
organs but are commonly identified by yeast growth in
C. albicans is considered as one of the most
bloodstream samples. The number of Candida infections
has been increasing dramatically all over the world
because
of
the
increased
number
of
immunocompromised patients [3,4,5]. The
cases
of
Candida
species are responsible for causing fungal infection, with
Candida
albicans,
Candida
glabrata,
Candida
prevalent kinds of Candida species.
The pathogenic Candida species are capable
of causing local and superficial infections in
the vagina, intrauterine device, anal, and oral
cavity.
Candida infections are known to be a major
threat to global public health.
C. albicans is the most predominant and
parapsilosis, Candida krusei, and Candida tropicalis being
widespread species in UK and China.
identified
Diagnostic approaches that can be used for
as
the
most
prevalent
[6,7,8,33].
The
pathogenicity of the Candida species has been linked to
various virulence factors, including the ability to evade the
candidiasis
detection
include:
examination, c
direct
- -D-
Glucan method, and Polymerase Chain
defence systems of the host, biofilmformation, adherence,
Reaction (PCR) techniques.
and the production of hydrolytic enzymes that damage
The primary therapeutic agents for Candida
tissues [5,10]. Even though C. albicans are the key cause
alternative
of Candida infections in humans, they are known to form
infections
are
antifungal
treatments
can
drugs,
also
help
with
candidiasis management.
an important component of the commensal flora among a
large
percentage
of
the
healthy
population
[1,10,11,12,33]. Studies have shown that colonisation by C. albicans is beneficial to
individuals because it hinders the growth and multiplication of pathogenic fungi and
enhances the proper functioning of the immune system [1,2].
The opportunistic fungi within the Candida genus can become pathogenic when the
immune system is weakened. It has been observed that the pathogenic Candida
species cause high rates of morbidity and mortality globally, and thus represent a
significant threat to public health [6,13,14]. The Candida species are responsible for
1
causing various superficial and systemic infections [15]. It is recommended that
individuals with invasive candidiasis receive early and effective treatment because
delayed initiation of therapy is linked with increased mortality [16,17]. Another
significant challenge associated with some Candida species is the development of
resistance to the various systemic antifungals and their capacity to spread fast within
healthcare institutions [16,17,18]. The development of new drugs with novel targets
and efficient antifungal properties has contributed to improving the control of Candida
infections [20,21,22]. This review will discuss Candida infections by focusing on the
characteristics of the pathogenic organisms in the genus Candida, the symptoms of
the disease and epidemiology, diagnosis, and treatment.
Characteristics of Candida genus
The organisms that belong to the genus
Candida are mainly yeasts, and occur in the
unicellular form. They are small in size (46µm) and have a thin wall, as well as an ovoid
aspect referred to as blastospheres [29].
Most of the organisms under the genus
Candida are reproduced by budding. The
available evidence indicates that there are
over 200 species of Candida, but only a few
species have harmful effects on humans
[12,31]. The characteristics of the common
pathogenic Candida species are summarised
in Table 1.
The Candida genus forms part of the human
microbiota
and
resides
in
the
Candida
species
Characteristics
Candida albicans
The first most commonly found fungal
pathogen globally. It is responsible for various
infections, including oropharyngeal thrush,
esophagitis, genital candidiasis, cutaneous
candidiasis, and deep candidiasis [19,49,52].
Candida
Causes systemic candidiasis and candidemia
tropicalis
in immunosuppressed individuals.
Candidemia can be linked to severe myalgia
and myositis [19,61].
Candida glabrata
Second most common cause of candida
infections after C. albican. Causes systemic
candidiasis, urinary tract infections, and
candidaemia [19,29,49].
Candida
Linked with deep-seated infections related to
parapsilosis
implanted devices.
Infections also linked to contaminated solution
[19,49].
Candida krusei
Linked with candidaemia, diarrhoea in infants,
and endophthalmitis [19,61].
Candida
Associated with endocarditis in drug abusers,
guillermondii
as well as systemic candida [19].
Candida
Causes oropharyngeal infections in patients
dubliniensis
with HIV [19,49].
Table 1. Characteristics of the Candida species that are
frequently found in human disease.
human
mucosae as well as the skin [3,24]. The genus can also occur in fruits, vegetables, the
ground, animals, and in hospital environments. Despite occurring in hospitals, the
Candida genus is not considered a laboratory contaminant [29]. The Candida genus
is classified as an endogenous microbe because approximately 70% of individuals can
2
have it in the mucosal epithelium, particularly in the genital and gastrointestinal tracts
[26].
C. albicans, which constitute the common species in the gastrointestinal and
genitourinary tracts also cause vaginal infections in women, and are linked to
mucocutaneous and mouth infections [3,27,46]. They are characterised by
polymorphism, which is the capacity to occur in many forms, including blastospores,
pseudohyphae, true hyphae, germ tubes, and chlamydospores [25,27,46]. The ability
of C. albicans and other pathogenic species within the Candida genus to switch from
one form of growth to another depends on the environmental conditions, which
facilitate colonisation and invasion of the host organs [28,46]. C. albicans have a high
degree of flexibility and are able to grow under diverse environmental conditions with
regard to nutrient availability, pH, amount of oxygen available, temperature variation,
and osmolarity [6,23].
Candida Infections
The pathogenic Candida species have the capacity to cause local and superficial
infections. Various classes of Candida infections have been identified over the years
and they include:
Vaginal candidiasis
Vaginal infections, also known as vulvovaginal candidiasis (VVC), are very common.
It is estimated that approximately 70% of women develop VVC at a certain period in
their lifetime [32,34]. Further, over 80% of VVC is linked to C. albicans, with only 20%
being caused by other species, usually C. glabrata [34,35]. This infection occurs
mostly among pregnant women, especially during the final trimester of pregnancy
[1,32,35]. This can be attributed to the fact that diabetes causes immune dysfunction.
Other risk factors for VVC infection include antibiotic therapies, use of oral
contraceptives, engaging in sexual activities that involve oral-genital contact, and
having immunosuppressed immunity [1,32,35]. Although it is not a significant threat to
life, VVC is challenging and unpleasant, causing a variable degree of itching and
abnormal whitish discharge. Other common symptoms include development of rash
3
around the vagina, a burning feeling when urinating or having sex, and redness or
swelling around the vagina [1].
Intrauterine candidiasis
Despite the reported high incidence of VVC, intrauterine candidiasis is considered a
rare infection [37]. This forms if infection occurs during pregnancy. The occurrence of
this type of infection should be avoided, especially during the final few weeks of
pregnancy, because of its capacity to extend to the uterus and cause complications,
and even infect the child before birth [1,38]. The common symptoms of intrauterine
candidiasis include: the presence of a widespread rash and maculopapular or
pustular-vesicular.
Anal candidiasis
Anal candidiasis is characterised by pruritis or intense itching, accompanied by
localised erythmia or a burning sensation around the anus [1,39,40]. The skin usually
appears macerated with circumscribed lesions. Anal candidiasis occurs commonly
among children and women. Its occurrence in women is associated with the use of
hormonal contraceptives, practice of oral and anal sex, and use of intimate hygiene
products [1].
Oral candidiasis
This is the most common form of candida infection within the oral cavity, and is mainly
caused by the invasion of Candida species, especially C. albicans [41,43]. Other
species of Candida which cause oral candidiasis include C. tropicalis, C. glabrata, and
C. krusei [43]. Oral candidiasis commonly occurs in the extremes of age [41,44].
Approximately 7% of infants are at risk of developing oral candidiasis. The prevalence
of oral candidiasis is approximately 9-30% in AIDS patients and about 20% in those
with cancer. Further, oral candidiasis is known to affect individuals with immune
system disorders and those with dental prostheses. Healthy individuals also face the
risk of developing oral infection, with approximately 30-45% of the healthy adults being
carriers of candida organisms [44].
The common symptoms associated with this infection include the presence of whitish
papules or small spots on the tongue or in the inner region of the cheeks, a painful or
4
burning sensation in the mouth, difficulty eating or swallowing, and redness in the
mouth [1].
Mucocutaneous candidiasis
Mucocutaneous candidiasis can be classified into genitourinary disease and
nongenitourinary disease. Oropharyngeal manifestations are common among
individuals with nongenitourinary candidiasis, and are usually diagnosed in
immunocompromised patients [46]. Areas of the body that are moist, warm, or sweaty
serve as good environments for the growth of yeast. These areas include the skin
between toes and fingers, armpits, the region under the breasts, and the groin [1]. The
key risk factors associated with the development of mucocutaneous candidiasis
include: poor hygiene, wearing tight undergarments, having diabetes, antibiotic use,
and having a weakened immune system. The symptoms associated with Candida skin
infection include the development of a red rash in the affected part and the formation
of blister-like lesions [1].
Epidemiology of Candida Infections
The available evidence indicates that over 17 types of Candida species have been
identified as key causative agents of Candida infections [5,28,51]. The National
Nosocomial Infections Surveillance System (NNISS), and most recent studies, have
shown that Candida species is the fourth most commonly isolated pathogen in US
hospitals [9,12]. Candida infections are known to be a significant threat to public health
globally. C. albicans colonises approximately 90% of the total human population, but
in most cases does not cause infection or any health issues [5,12]. The incidence of
invasive candida is reported to be lower in Europe and the US compared to other
regions of the world. However, the incidence rates experienced an increase in the two
regions from the 1970s to the 1990s before the situation was stabilised [51,53]. In
Europe, the highest incidence has been reported in Denmark (10.4 cases per 100,000
individuals) [53]. The UK was reported to have an overall rate of 3.6 cases per 100,000
individuals in 2016 and 2017. During this period, the three Candida species frequently
identified from blood samples were C. albicans (42%), C. glabrata (23%), and C.
parapsilosis (11%) [72]. In the US, the average incidence of candidiasis between 2013
and 2017 was approximately 9 per 100,000 individuals [54]. In china, as illustrated in
5
the (Figure 1), C. albicans is the most predominant and widespread species (46.4%).
Other prevalent Candida species include C. parapsilosis at 19.5%, C. glabrata
(15.9%), C. tropicalis (14.6%), and C. dubliniensis, C. guillier-mondii, and Candia spp
each at 1.2% [55].
Figure 1. Illustration of the distribution of Candida species responsible for causing
Candida in China [55].
Diagnosis
Diagnosis is important not only for the confirmation of infection, but also for the
identification and initiation of the appropriate treatment. Diagnosis of candidiasis has
been reported to be difficult due to the non-specific nature of clinical presentation.
Some of the key diagnostic approaches that can be employed for diagnosis of
candidiasis include:
Direct examination
Direct microscopic examination is a rapid and cost-effective method that can be used
to diagnose candidiasis [27,28,48]. It is carried out using wet mount preparation. This
6
approach involves swabbing or scraping the infected area and placing the obtained
swab on a microscopic slide. 10% potassium hydroxide (KOH) solution is then added
so as to dissolve the skin cells without interfering with the integrity of the Candida cells.
The KOH solution aids in digesting the proteinaceous debris. This is important for
enabling complete visualisation of the pseudohyphae and the yeast cells of the various
Candida species [27,28,47]. The appearance in direct microscopy of mycelial forms of
Candida is a diagnostic marker of candidiasis; however, in the C. glabrata situation, a
major cause of VVC cannot be diagnosed with microscopic examination, only because
this species of Candida is haploid and does not develop hyphae or pseudohyphae
invitro [28,36].
Culture method
The media most widely employed for the isolation of Candida species is Sabouraud
dextrose agar (SDA), as shown in the (Figure 2) [27,28,30]. Its low pH value allows
Candida to grow while inhibiting the reproduction of other bacteria [27]. For the
isolation of Candida, a sterile swab is rubbed onto the area that is infected and the
swab is then stroked across the SDA medium [30]. Because SDA is not a differential
medium, it is difficult to distinguish the colonies of varying yeast species developed on
this agar. Chromogenic agars and Pagano-Levin agars are therefore sometimes
utilised. Yeast infections can thus be diagnosed much more quickly, as the
Candida species can be differentiated through the colour of their colonies, as shown
in the (Figures 3,4) [28,30]. Some species of Candida (such as C. krusei, C.
parapsilosis and C. tropicalis) are sensitive to cycloheximide; SDA with cycloheximide
should not be used as a single isolation of the Candida species [28,36]. Improvements
in blood culturing techniques have also contributed to improving sensitivity and
lowering the time required to detect a positive blood culture. One of the culture
methods that is commonly used is the comprehensive digestive stool analysis (CDSA).
This method aids in determining the existence of digestive disturbances as well as the
functional and clinical status of the gastrointestinal tract, which may be one of the
major causes of Candida's overgrowth [1].
7
Figure2. Colonies of Candida spp on SDA [28].
Figure 3. Different morphotypes of Candida albicans on Pagano-Levin agar [28].
Figure 4. Differentiation of Candida spp. on CHROM agar [28].
8
- -D-Glucan method
- -D-Glucan assay is a chromogenic, quantitative enzyme immunoassay (EIA)
[57]. The cell walls of all the Candida
- -D-glucan (BDG) as a
structural component [27,28,45,57]. Given that this polysaccharide does not occur in
other organisms such as viruses, bacteria, or mammals, its detection in the circulation
of patients can be used to indicate the presence of Candida infections [27]. BDG can
help to diagnose Candida infections in their early stages. The levels of BDG may also
be a valuable tool for monitoring how a patient is responding to therapy. [45].The
interpretation of the test results must take into account the possibility of false positivity
and false negativity. Researchers have reported a number of factors that can cause a
false positive BDG result, such as abdominal surgery, haemodialysis and being
treated with -lactam antibiotics [28,45]. False positive results can also be caused by
receiving blood products, albumin, immunoglobulin, coagulation factors, or plasma
protein that has been fraction filtered through BDG-containing filters. This is also true
for high triglycerides, haemoglobin (hemolysed samples) and bilirubin [45].
Polymerase Chain Reaction (PCR) techniques
Various PCR techniques have been developed to aid in the identification of Candida
species. The sensitivity of PCR-based techniques enhances the possibility of detecting
infections during the early stages, when it is relatively easy to treat or prevent their
clinical manifestation [58,59,60,63]. PCR is an amplification method that provides
rapid and objective identification of Candida species. Prior to amplification, primers
are selected according to the appropriate target sequences. Studies have shown that
the sensitivity of PCR assays depends mainly on various aspects including sample
preparation, DNA target selection, extraction of DNA, and efficiency of amplification
[64,65]. Before conducting PCR, it is recommended to obtain DNA from appropriate
samples. In most cases, serums or whole blood samples from individuals with Candida
infections are used [65,66,67]. Appropriate target nucleic acid is critical for the success
of PCR. As a result, species-specific sequences are often used so as to produce better
diagnostic results.
9
Treatment of Candida Infections
Treatments aimed at managing Candida infections are often based on the anatomic
status, the type of species responsible for the infection, and the susceptibility of the
Candida species to antifungal agents [27,44]. Antifungal drugs have been widely used
for the clinical treatment of Candida infections [44]. Even though there are numerous
types of antifungal drugs, only a few classes are available to treat systemic infections
associated with Candida species, as shown in (Figure 5).
Azoles
inhibit Lanestrol 14- -Demethylase
Azoles form the largest class of antifungal drugs. Azoles mainly disrupt the cell
membrane by binding and inhibiting the lanosterol 14- -demethylase enzyme [3,62]
which is involved in the generation of ergosterol, as shown in (Figure 5). Ergosterol
has been identified as the largest sterol component of fungal cell membranes. Most of
the azoles are effective when used topically or when used as prophylaxis of invasive
of Candida infections [3,16]. The common drugs found within the azole family include:
imidazoles, triazoles, and posaconazole [3].
Echinocandins
Inhibit glucan synthesis
Echinocandins are lipopeptidic antifungal drugs that function by inhibiting the synthesis
of the fungal wall. This is achieved by inhibiting the (1, 3)- -D-glucan synthase
enzyme, as illustrated in (Figure 5) [3,12]. The inhibition of the enzyme activity results
in the formation of fungal cell walls that have poor structural integrity, and this results
in the vulnerability of the cells to osmotic lysis [14]. The common echinocandins
include: micafungin, caspofungin, and anidulafungin. All these types of drugs exhibit
concentration-dependent activity against the various Candida species [3].
Polyenes
Bind ergosterol
Polyenes function by binding to ergosterol and consequently disrupt the lipidic
component of the fungal cell membrane [3,12]. This leads to the formation of aqueous
spores. Moreover, the permeability of the cells is altered, thus leading to the leakage
10
of cytosolic components and eventually the death of the invasive Candida species
[56]. Examples of polyenes include nystatin and amphotericin B [12].
Nucleoside analogues
Inhibit DNA/RNA synthesis
Nucleoside analogues such as flucytosine are transported into the cells of the invasive
Candida by cytosine permeases. The members of this group of drugs are then
deaminated to 5-fluorouracil and subsequently phosphorylated to 5-fluorodeoxyuridine
monophosphate. The fluorinated nucleotide functions by inhibiting thymidylate
synthase, and in the process interferes with the DNA formation. The 5fluorodeoxyuridine monophosphate can undergo further phosphorylation and be
integrated into RNA, thus affecting both RNA and protein synthesis [12,42].
Allylamines
Disrupt cell membrane
Allylamines inhibit squalene epoxidase and in the process disrupt the cell membrane.
Allylamines have been shown to be effective against various fungal agents such as
the azole-resistant Candida species [3,12]. Treatment with allylamines results in the
accumulation of squalene in cells while ergosterol is reduced. The subsequent steps
in the ergosterol biosynthetic pathway also become blocked. Allylamines cause the
death of fungal cells through accumulation of squalene, which in turn alters the plasma
membrane and interferes with membrane organisation [3,44,50]. This causes
increased permeability of the membrane and eventually cell death. Examples of
allylamines include terbinafine and naftifine.
11
Figure 5. The common antifungal classes and their modes of action [12].
Alternative treatment
Studies have shown that certain factors, such as high sugar diets, antibiotic therapies,
allergies and other factors, can interfere with the normal balance of the intestinal
environment, thus killing the beneficial bacteria and stimulating the overgrowth of
pathogenic microbes [1,68]. Complementary treatment mechanisms can therefore be
employed to reduce and control the levels of Candida. The key alternative treatment
approaches that can be taken into consideration include:
12
Nutrition and diet
Dietary factors can affect and enhance the overgrowth of the Candida species.
Therefore, adhering to a special diet as a form of treatment for candidiasis may be
beneficial. Given that C. albicans grow in environments rich in sugar, there is a need
to avoid refined sugars including sucrose, sweetened foods, and fruit juice. In addition,
it is necessary to avoid diets with high content of yeast or fungi, such as alcoholic
beverages, bread, and fermented food products [1,27]. Milk and other daily products
can also be avoided because they contain high levels of lactose that promote
overgrowth of Candida and are also considered the most common food allergens. The
presence of traces of antibiotics in milk and dairy products can disrupt the
gastrointestinal bacterial flora [44,96,70].
Enhancing the immune system
A weakened immune system allows rapid growth of C. albicans and other invasive
Candida species [1,52,71]. Therefore, restoring optimal functioning of the immune
system can aid in the management of candidiasis. Various strategies can be employed
to enhance the immune system, including: effective management of stress, nutritional
supplementation, diet restriction, use of plant-based medicines, exercise, and
glandular therapy [1].
Conclusion
Every individual is exposed to the various candidiasis predisposing factors, and as
such it is almost impossible to avoid the risk factors. Candida infections can affect
different parts of the body, including the gastrointestinal tract, vagina, and the skin.
Candida infections are considered a significant public health issue. The past few
decades have witnessed an increase in Candida infections globally due to the rising
population of immunocompromised patients. C. albicans constitute the most common
Candida species and are responsible for causing more than 60% of all the Candida
infections in humans. The common Candida infections which have been outlined
include genital candidiasis, intrauterine candidiasis, anal candidiasis, mucocutaneous
candidiasis, and oral candidiasis. Proper diagnosis is important for the identification
13
and confirmation of the infections and for facilitating the initiation of appropriate
treatment. The key diagnostic approaches that can be used with individuals suspected
- D-glucan method, and Polymerase Chain Reaction (PCR) techniques. Antifungal
drugs are the primary treatment agents for Candida infections. The antifungal drugs
have been placed into various classes depending on their mechanisms of action,
including: azoles, achinocandins, polyenes, nucleoside analogues, and allylamines. In
addition to the use of pharmaceutical agents, alternative treatments can aid in the
management of candidiasis, with the common approaches being: adherence to a
special diet and improving the immune system.
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