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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: [email protected]; relapsing VVC. Recurrent VVC is a condition that affects [email protected]; 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) Materials

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 Stastical analysis
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 et al., 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 DISCUSSION
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 Czeizel AE, (1999). The role of pharmacol-epidermiology in were more effective than nystatin when treating vaginal Pharmacoepidermiol Drug Saf. Suppl. 1: S55-61. Czeizel AE, Toth M, Rockenbaner M (1999). No teratogenic effect after The result showed that repeat cultures of high vaginal clotrimazole therapy during pregnancy. Epidermiology ; 10: 437-40. swabs (HVS) after one week of treatment with once daily de Leon EM, Jacober SJ, Sobel JD, Foxman B (2002). Prevalence and dosing of nystatin and clotrimazole yielded some growth risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes. BMC Infect Dis. 2(1): doi:10.1186/1471-2334-2- of Candida in 41 % and 32 % cases respectively. On twice daily dosing for both nystatin and clotrimazole, Donders GG, (2002). Lower Genital Tract Infections in Diabetic Women. there was symptom resolution within one week of therapy in all the patients and cultures yielded only scanty growth Duerr A, Heilig CM, Meikle SF, Cu-Uvin S, Klein RS, Rompalo A, Sobel JD, (2003). Incident and persistent vulvovaginal candidiasis among in 4 % for nystatin and 3 % for clotrimazole. human immunodeficiency virus-infected women: Risk factors and Young and Jewel, (2001) reported that single dose severity. Obstet Gynecol 101(3): 548-56. treatment was less effective than three or four days Ferris DG, Nyirjesy P, Sobel JD, Soper D, Pavletic A, Litaker MS (2002) treatment when assessed by culture and by symptoms in Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet. Gynecol. 99(3): 419-425. three different trials, and treatment lasting for four days Garcia PJ, Chavez S, Feringa B, Chiappe M, Li W, Jansen KU, was less effective than treatment for seven days. They Carcamo C, Holmes KK (2004). Reproductive tract infections in rural concluded that topical imidazole appears to be more women from the highlands, jungle, and coastal regions of Peru. Bull effective than nystatin for treating symptomatic vaginal Geiger AM, Foxman B, Sobel JD (1995). Chronic vulvovaginal candidiasis in pregnancy with treatment lasting up to candidiasis: characteristics of women with Candida albicans, C. glabrata and no candida. Genitourin. Med. 71: 304-307. Cost analysis of both agents (nystatin and clotrimazole) Hainsworth T (2002). Diagnosis and management of candidiasis showed a remarkable difference. A week treatment (once Klufio CA, Amoa AB, Delamare O, Hombhanje M, Kariwiga G, Igo J daily dosing) of nystatin costs ninety-one naira (N91.00; (1995). Prevalence of vaginal infections with bacterial vaginosis, less than $1) and clotrimazole for the same duration Trichomonas vaginalis and Candida albicans among pregnant costing one hundred and sixty-eight naira (N168.00; women at the Port Moresby General Hospital Antenatal Clinic, Papua $1.5). Generally, the azole antifungals are more Mardh PA, Rodrigues AG, Genc M, et al. (2002). Facts and myths on expensive than nystatin. In the face of scarce resources, recurrent vulvovaginal candidosis: a review on epidemiology, clinical the costs and outcome analyses are valuable in manifestations, diagnosis, pathogenesis and therapy. Int. J. STD. Markos AR, Wads AA, Walzman M (1992). Oral sex and recurrent vulvovaginal candidiasis [letter]. Genitourin Med. 68: 61-62 Marrazzo J (2002). Vulvovaginal candidiasis. British Medical Journal CONCLUSIONS
McClelland RS, Richardson BA, Hassan WM, Graham SM, Kiarie J, The pregnant women in this study had non-complicated Baeten JM, Mandaliya K, Jaoko W, Ndinya-Achola JO, Holmes KK (2009). Prospective Study of Vaginal Bacterial Flora and Other Risk VVC. The study revealed that VVC among pregnant Factors for Vulvovaginal Candidiasis. J. Infect. Dis. 15; 199(12): women in this locality was not uncommon so that continuous ante-natal screening should be an on-going Nikolov A, Shopora E, Museva A, Dinitrov A (2006). Vaginal candida exercise for all pregnant women with history of itching infections in the third trimester of pregnancy, Akush Ginekol (Sofia); 45(6): 1-6. and vaginal discomfort. This will prevent further Nyirjesy P, (2001) Chronic vulvovaginal candidiasis. Am. Fam. Phys. complications and even transmission to partners. Nystatin has a long-standing efficacy and is cheap but Nyirjesy P, Sobel JD (2003) Vulvovaginal candidiasis. Obstetrics & clotrimazole is equally effective but far more expensive. Gynecology Clinics of North America 30(4): 671-684. O’Connor MI, Sobel JD (1986). Epidermiology of recurrent vulvovaginal; The study recommends that in the face of scarce identification and strain differential of Candida albicans. J. Infect. Dis. resources, the old traditional cheap values should not be abandoned for more expensive new ones when both Odds FC (1988). Candida and candidiasis, 2nd ed. Bailliere Tindall, Patel DA, Gillespie B, Sobel JD, Leaman D, Nyirjesy P, Weitz MV, Foxman B, (2004). Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a REFERENCES
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