Journal of Medicine and Medical Sciences Vol. 1(10) pp. 447-452 November 2010 Available online http://www.interesjournals.org/JMMS Copyright 2010 International Research Journals
Prevalence and treatment outcome of vulvovaginal candidiasis in pregnancy in a rural community in Enugu State, Nigeria P. A. Akah1, C. E. Nnamani1,2 and P.O. Nnamani3*
1Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Science
University of Nigeria, Nsukka 410001, Enugu State, Nigeria
2Nwa-Ossai Foundation Hospital, 20 Enugu Road Orba, P.O Box 932 Nsukka,
3Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria,
Vulvovaginal candidiasis (VVC) is a common condition, and an estimated 75 % of all women experience an infection with candida yeast during their lifetime. The study involved 901 pregnant women presenting to a rural hospital for ante-natal care within a period of ten months. Those with abnormal vaginal discharge or pruritus were screened for VVC. Those with symptomatic diagnosis of VVC were recruited for the cohort study after appropriate counseling and obtaining informed consent. Culture of high vaginal swab (HVS) and urinalysis were performed. Treatment of significant cases involved the use of nystatin and clotrimazole vaginal inserts. A total of four treatment groups (n = 157) were employed. Groups 1 and 2 received differently daily normal doses of the agents for 7 days respectively. Groups 3 and 4 received twice daily dosing of both agents for 7 days. In each case, the symptomatic response and re-culture of the HVS were repeated after treatment. Pharmacoeconomics of the two drugs was evaluated for the ten months period of the study and the prevalence of the VVC finally deduced. The result showed that the pregnant women had non-complicated VVC. Treatment outcome was generally the same with both nystatin and clotrimazole which invariably showed the same efficacy. In the first two groups, 72 % of those treated with once daily dosing of nystatin had their symptoms resolved within one week and 75 % achieved symptom resolution with clotrimazole during the same period. Some 96 % and 97 % of repeat culture of HVS for those that received twice daily dosing of the nystatin and clotrimazole had negative cultures respectively. The pharmacoeconomics of both agents reveal a remarkable difference in that a week treatment (once daily dosing) of nystatin costs ninety-one naira (N91. 00) which is less than $1 and clotrimazole for the same duration costs one hundred and sixty- eight naira (N168.00) which is $1.5. Going by cost minimization since both agents have similar outcomes, nystatin will naturally be selected. In the face of scarce resources, the costs and outcome analyses are valuable in therapeutic decisions. Keywords: Vulvovaginal candidiasis; Prevalence; Pregnant women; Ante-natal; Nigeria.
INTRODUCTION Vulvovaginal candidiasis (VVC) is a fungal infection of the
caused by Candida species (Sobel, 2007; Nyirjesy et al.,
female lower genital tract-the vulva and the vagina,
2003; Marrazzo, 2002). It is also known as candidosis or
moniliasis. VVC can be recurrent or relapsing (Ferris et al., 2002; Nyirjesy, 2001). When a woman presents with
four or more episodes per year, it is termed recurrent or
*Corresponding author E-mail: firstname.lastname@example.org;
relapsing VVC. Recurrent VVC is a condition that affects
email@example.com; Fax: +234-42-771709;
less than 5 % of healthy women (Rex et al., 2000).
Candida species are part of the lower genital tract flora in
potassium hydroxide (KOH) preparation of vaginal
20-50 % of healthy asymptomatic women (McClelland et
discharge (Geiger et al., 1995). Gram stain preparation
al., 2009). Carrier rates are higher in women treated with
may also be used since yeast is gram-positive. If
broad spectrum antibiotics (Singh, 2003), pregnant
microscopic studies are negative and the index of
women, diabetic women (Donders, 2002; de Leon et al.,
suspicion of VVC continues to be high, vaginal swab for
2002) and women with HIV/AIDS (Reed et al., 2003;
fungal culture is done (Sherrard, 2001; CEG, 2002; Sobel
Duerr et al., 2003). Candida albicans is both the most
et al., 1998). In all cases of pruritus vulvae, the urine
frequent colonizer and responsible for most cases of VVC
should be tested for glucose (urinalyisis). The
(Singh, 2003). Nevertheless, over the last decades there
commonest cause of vulva pruritus in pregnancy is VVC
have been reports demonstrating an increment in the
which may be associated with the lowered renal
frequency of cases caused by non-albicans species with
threshold for sugar which occurs in pregnant women (Ten
Candida glabrata consistently being the leading species
Teachers, 1997). The aim of the study was to assess the
(Ray et al., 2007; Ringdahl, 2000). The only well proven
prevalence of VVC in a rural community in Enugu State
predisposing factors are pregnancy, diabetes mellitus
and also to determine the pharmacoeconomics of the
(CDC, 2002), and the use of broad spectrum antibiotics
(Mardh et al.,2002) as well as oral contraceptive with
high oestogen content (Odds, 1988). Poorly supported
risk factors include use of sponge, intrauterine devices
MATERIALS AND METHODS
(IUDS), diaphragms, condoms, orogenital sex, douching
and intercourse (Mardh et al., 2002, Reed et al., 2002)
and diet with high glucose content (de Leon et al., 2002).
The following materials used were nutrient agar, nutrient broth
An estimated 75 % of women will experience at least
one episode of vulvovaginal candidiasis during their
Belgium), clotrimazole (Drugfield Pharmaceuticals, Nigeria), Combi
lifetime (Singh, 2003). In fact, 70 to 75 % of healthy adult
9 multistix (Bohringer, Germany), sterile swab stick (Evepon
women have at least one episode of VVC during their
reproductive life and half of college women will, by the
age of 25, have had one episode of VVC diagnosed by a
physician (Sobel, 1997). Retrospective data reported
during the early period of the AIDS pandemic suggested
Preparation of culture media
that the prevalence of VVC was increased in HIV-infected
women compared to non-infected women (CDC, 2002).
The culture media were prepared according to the manufacturers specifications. Briefly, this involved weighing the appropriate
VVC is not considered a sexually transmitted disease
quantity of each medium, dissolving in the stated solvent using heat
(Singh, 2003), because it does affect celibate women and
and distribution into bijou bottles (20 ml) for sterilization in the
children and also Candida species is seen as normal
autoclave at 121 °C for 90 min. The contents of the bottles were
vagina flora in healthy women. However, this does not
aseptically poured into the plates and allowed to set at room
mean that Candida cannot be sexually transmitted (de
temperature. The solidified agar plates were used for the culture.
Leon et al.,2002, CDC, 2002; Mardh et al., 2002).
Indeed, evidence in favour of sexual transmission exists.
Study Area and Population
For instance, penile colonization is four times more
frequent in male partners of women affected with VVC
This study was carried out in a rural hospital, Nwa-Ossai
(McMclelland et al., 2009; Rodin and Kolator, 1976) and
Foundation Hospital, Orba Nsukka, Udenu L. G. A. of Enugu State,
infected partners commonly carry identical strains
Nigeria. Orba is a commercial town that shares a common border with the University of Nigeria, Nsukka.
Pregnant women presenting to the hospital for ante-natal care
transmission has been documented (Markos et al., 1992).
between January-October 2007, with symptoms of vulvovaginal
Diagnosis of VVC based solely on patients history and
candidiasis (VVC) (abnormal vaginal discharge or pruritus) were
genital examination is not possible because of the low
screened for VVC. A total of 901 pregnant women attended the
specificity of symptoms and signs since other causes
ante-natal care within this study period. Those with symptomatic
mimic VVC like leucorrhoea and pruritus vulvae (Geiger
diagnosis of VVC were recruited for the cohort study after appropriate counseling and obtaining informed consent. By means
et al., 1995). Therefore, to have a positive (specific)
of personal interviews, their socio-demographic data were obtained.
diagnosis of VVC, a number of steps are recommended
Culture of high vaginal swab (HVS) and urinalysis by dip stix
viz, determination of vaginal pH (normal 4-4.5) which
method were used. Ab initio, they were instructed to be off all
means that a higher pH more than 5 is suggestive of
antibiotics three days prior to the day of collection of the HVS and
bacterial vaginitis or trichomoniasis (CDC, 2002);
preparation of a wet mount of the vagina discharge for
The study was in accordance with the ethical committee of the
Enugu State Ministry of Health while informed oral consent was
identification of the yeast cells and mycelia and to rule
out other diagnoses e.g. bacteria vaginosis and
trichomoniasis (Marrazzo, 2002; CEG, 2002); a 10 %
Collection and processing of samples
Exposing the posterior fornix with a sterile vaginal speculum
Screening for significant vulvovaginal candidiasis
(Coscos), a sterile swab stick was inserted to pick a high vaginal swab. The swab stick was immediately replaced in its casing and
Out of 901 pregnant women who attended antenatal
Urine specimen was collected using clean-catch midstream urine
clinic, 629 (70 ± 2.5 %) presented with symptoms of
collection method. “Sterilin” Universal container was used to collect
about 20 ml of urine sample per subject. Each specimen was
(leucorrhoea). A total of 560 (62.2 ± 7.5 %) of this
refrigerated at 4 °C as soon as it was collected.
number had positive culture of Candida spp. (significant
VVC). Some 71 women who were symptomatic (pruritus
Inoculation, isolation and purification of the culture
and leucorrhoea) had negative cultures. This constituted
about 7.7 ± 2.1 % of the studied population.
Using a sterile platinum loop, each agar plate was aseptically
The remaining 270 (27.7 ± 5.0 %) were asymptomatic
inoculated with the HVS specimen. The plates were incubated at 37
and were not subjected to laboratory diagnosis. The
°C for 24 h and thereafter observed for obvious microbial growth
mean age of the study population was 29.8 years (S.D.
(colonies) on the surface of the culture plate. Standard procedures (Sobel et al., 1998) were employed to
8.2 years). The results are summarized in Table 1.
identify and isolate the microbes there in. Subsequent sub-culturing
in selected media was carried out to further purify the isolates.
Urinalysis Antibiotic sensitivity test for mixed growth
Of the 629 pregnant women screened, none had
For each mixed isolate, sensitivity was determined using antibiotic
glucosuria. However, urinalysis was just a screening test
discs after due subculturing. Briefly, the mixed isolates were
for diabetes mellitus in pregnancy which is a predisposing
seeded in agar plates, rotated in different directions and allowed to
set at room temperature. Antibiotic discs were then placed on the
Treatment outcome of the patients (560) with positive
set agar plates, allowed to equilibrate at room temperature for 15
culture was the same with both nystatin and clotrimazole
min and finally incubated at 37 oC for 48 h. Thereafter, the plates were observed for obvious microbial growth (colonies) on the
showing that efficacy is invariably the same (Table 2).
surface of the culture plate. Using Combi 9 multi stix, each urine
Out of 140 that received once daily dosing of nystatin 102
sample was checked for proteinuria and sugar.
(72 %) had their symptoms resolved within the one week
of treatment. Also, 106 (75 %) of those who received
once daily dosing of clotrimazole had their symptoms
Treatment of significant cases
resolved. Repeat cultures of HVS after one week of
All significant cases of vulvovaginal candidiasis were subjected to
treatment with once daily dosing of nystatin and
chemotherapy. The subjects were divided into four groups (n = 157
clotrimazole yielded some growth of Candida in 46 (33
per group). Two groups A and B received differently daily normal
dosings of nystatin and clotrimazole vaginal inserts for 7 days
The 142 pregnant women that received twice daily
respectively. Groups C and D received twice daily dosings of
dosing of nystatin, had complaints (symptoms) at the end
nystatin and clotrimazole for seven days respectively. In each case, the symptomatic response and re-culture of the HVS were repeated
of the one week treatment and only 6 (4 %) yielded
scanty growth of Candida on repeat culture. For
Pharmacoeconomics of the two drugs were also evaluated for
clotrimazole, 5 (3 %) out of 138 that received twice daily
the ten months period of study. The prevalence of the VVC was
dosing yielded scanty growth and all of them had their
finally deduced from the record of all the ante-natal clients.
symptoms resolved within the one week of treatment.
Follow-up procedure Pharmacoeconomics of the therapeutic agents
At the end of the one week of chemotherapy, HVS and urinalysis
were repeated and evaluated as earlier described. This was to
Cost minimization analysis was used for the economic
perhaps determine the exact response (of the treated groups to the
evaluation. Nystatin insertable tablets used for the study
antimicrobial agents) as well as recurrence (relapse or re-infection)
cost N13.00 per tablet X 7 nights i.e. N91.00 (less than
of the infection. Treated patients were seen weekly until delivery.
$1) for once nocte course of treatment for one week. The
cost of clotrimazole vaginal tablets was N24.00 per tablet
i.e. N168.00 ($1.5) for once nocte course of treatment for
one week. Deduction from the above shows that
Differences between the treatment groups A-D were analyzed by
clotrimazole costs almost double that of nystatin.
ANOVA and Students t-test using SPSS version. Correlational analysis was performed with the Spearman rank correlation test.
In terms of side effects and tolerability on both mother
Results with values of p<0.05 were considered significant.
and offspring, clotrimazole is preferred since there is no
Table 1. Prevalence of significant VVC in pregnant women Parameter No. of subjects Percentage VVC (% ± S.D.) Table 2. Treatment outcome Clinical outcome Laboratory outcome Drug doses & duration of treatment (days) Resolved Symptoms not Negative Positive Symptoms resolved culture culture
teratogenic effect after clotrimazole therapy during
etal., 2004). The result of this study which agreed with
pregnancy (Czeizel et al., 1999). Besides, nystatin lacks
an earlier observation (Sobel et al., 1996) is shown in
controlled human studies making it difficult to establish its
Table 2. Candidiasis is often diagnosed on the basis of
relative safety in pregnancy. However, the anxiety and
clinical features alone and as many as half of these
fear created by the notion that nearly all drugs cause
women may have other conditions e.g. allergic reactions
congenital abnormalities is more harmful than the effect
(Patel et al., 2003; Berg et al., 1984). Klufio et al., (1995)
of proven human teratogenic drugs themselves (Shehata
reported the prevalence of individual infections as
and Nelson-Piercy, 2000; Czeizel, 1999).
Trichomonas vaginalis 19 %, Candida albicans 23 % and
bacterial vaginosis 23 %. The rate which could be
misdiagnosed as vulvovaginal candidiasis on clinical
presentation alone is high and could be wrongly
subjected to treatment. This highlights the need for
The study showed high prevalence rates (62.2 %) of
laboratory diagnosis before commencing therapy.
vulvovaginal candidiasis among pregnant women
The results of urinalysis of the 629 pregnant women
attending antenatal clinic over the period of ten (10)
screened showed no glucosuria. This implied that none of
months in this rural community. About 70 % had clinical
the candidates with VVC had diabetes, a known
symptoms of VVC and as high as 62.2 % were
predisposing factor for increased rates of VVC (Vaquez
microbiologically confirmed. Nikolov et al., (2006)
and Sobel, 1995). Reduced renal threshold for sugar
reported 88.3 % prevalence by microscopy while Klufio et
occurs in many pregnant women with many having
al., (1995) reported 57 % infection microbiologically. The
glucosuria without being obviously diabetic (Ten
high rates are in conformity with the fact that Candida
Teachers, 1997). Increased glucose levels in the genital
albicans is both the most frequent colonizer and
tissue enhance yeast adhesion and growth, and vaginal
responsible for most cases of vulvovaginitis (Singh, 2003;
epithelial cells have a greater propensity to bind to C.
Hainsworth, 2002; Watson al., 2001).
albicans in women with diabetes than in those without
Some 7.7 % of the studied population had clinical
symptoms – pruritus vulvae and leucorrhoea – without
Treatment outcome was generally the same with both
Candida species being isolated. The symptoms are not
nystatin and clotrimazole which invariably showed the
specific for Candida vulvovaginitis. For example, vaginal
same efficacy. Seventy-two percent (72 %) of those who
pruritus predicted Candida vulvovaginitis only 38 % of the
received once daily dosing of nystatin had their
time (Bergman, 1994). About 90 % of patients with
symptoms resolved within one week and seventy-five (75
vaginal discharge (leucorrhoea) suffer from infection of
%) achieved symptom resolution during the same period
the vagina caused by Candida, Gardnerella or
with clotrimazole once daily dosing. This result was
Trichomonas (Ray et al., 2007; Ten Teachers, 1997).
comparable to that by Reef et al., (1995) which showed
In another study, the prevalence of vaginal candidiasis
that topical azoles and nystatin therapies gave 80 – 95 %
in pregnant women was only 28 % with Candida albicans
and 70 – 90 % clinical and mycological cure rate
being implicated in more than 90 % of the cases (Garcia
respectively in vulvovaginal candidiasis. However, Young
and Jewel, (2001) found in their five trials that imidazoles
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Compartmentation of Enzymes of Glucose, Glutamate, and Branched Chain Amino Acid Metabolism in the CNS. Susan M. Hutson , Ph.D. Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA Glutamate is the major excitatory neurotransmitter in mammalian brain. Detoxification and repletion of glutamate released by neurons is achieved by glutamate/glut
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