CYP3A5*3 Genetic Polymorphism and Tacrolimus Concentration in Myanmar Renal Transplant Patients.

BACKGROUND: Genetic polymorphism is an important factor that influences tacrolimus concentrations and has the potential to predict the optimal dosage of tacrolimus in personalized medicine. Tacrolimus, a drug of narrow therapeutic index, is used in renal transplant recipients as an immunosuppressant agent. It is a substrate of cytochrome P450 3A (CYP3A) and has highly variable pharmacokinetic parameters. OBJECTIVE: The aim of this study was to identify the proportion of CYP3A5 gene polymorphism in Myanmar kidney transplant recipients and to determine the impact of CYP3A5 gene polymorphisms on tacrolimus level in CYP3A5 expressors and nonexpressors. METHODS: This study included 41 adult Myanmar post-renal transplant patients. Tacrolimus trough blood levels were determined and CYP3A5 genotype analysis was conducted by using polymerase chain reaction amplification of target followed by detection by restriction fragment length polymorphism analysis. RESULTS: The CYP3A5 nonexpressors and expressors were detected in 25 (60.97%) and 16 (39.02%) of the 41 renal transplant recipients, respectively. The tacrolimus concentration/dose ratio in the CYP3A5 expressor group was lower than in the CYP3A5 nonexpressor group (1.49 ± 0.69 vs 3.49 ± 3.08 [P = .003] at 1 month; and 1.54 ± 0.9 vs 7.88 ± 8.25 [P = .0001] at 3 months). CONCLUSIONS: The findings of the present study revealed that more than one half of the study population were carrying the mutant allele CYP3A5*3(A6986G). CYP3A5 genetic polymorphism is one of the important factors in determining daily requirements for tacrolimus and in adjusting tacrolimus trough concentrations.

Comparison of a TaqMan-based real-time polymerase chain reaction with conventional tests for the detection of Trichomonas vaginalis.

OBJECTIVE: To compare a TaqMan-based real-time polymerase chain reaction (PCR) with conventional PCR, culture, and wet-mount microscopy for the diagnosis of trichomoniasis in women. METHODS: Vaginal swabs from 119 women were tested for Trichomonas vaginalis by wet mount and culture. Paired vaginal lavage and urine specimens were tested by conventional and real-time PCR. RESULTS: Using an expanded "gold standard", defined as a positive culture result using vaginal swabs and/or a positive PCR test using TVK3/7 primers, the overall prevalence of T vaginalis in the study population was 65.5% (78/119). The detection rate of T vaginalis was 65.5% (78/119) and 36.9% (44/119) by conventional PCR using vaginal washings and urine specimens, respectively; 68.9% (82/119) by real-time PCR using vaginal washings and 61.3% (73/119) by real-time PCR using urine specimens. The sensitivities of conventional PCR using vaginal washings and urine and real-time PCR using vaginal washings and urine, compared with the gold standard were 100%, 56.4%, 100% and 76.7%, and the specificities of these tests were 100%, 97.6%, 82.9% and 97%, respectively. CONCLUSIONS: The real-time PCR test proved to be significantly more sensitive than culture and wet-mount microscopy, although its specificity was slightly lower than these tests. In addition, it was more sensitive, rapid and less time consuming than conventional PCR for the detection of T vaginalis.

Coexistence of urethritis with genital ulcer disease in South Africa: influence on provision of syndromic management.

OBJECTIVE: To assess whether syndromic management of genital ulcer disease was sound, if based on the premise that men with genital ulcers rarely have a concomitant urethral infection. METHODS: Specimens were taken in 1998 from 186 mine workers in Carletonville, South Africa, who were seen consecutively with genital ulcers. The specimens comprised a swab from the ulcer, a urethral swab for a Gram stained smear, and 10-15 ml of a first catch urine sample. The latter was tested by ligase chain reaction assays for Neisseria gonorrhoeae and Chlamydia trachomatis specific DNA sequences and by a polymerase chain reaction (PCR) assay for Mycoplasma genitalium. Ulcer inducing micro-organisms were detected either by a multiplex PCR assay, or in the case of lymphogranuloma venereum (LGV) serologically, and human immunodeficiency virus (HIV) infection was detected by an enzyme linked immunosorbent assay (ELISA) test. RESULTS: Most (54%) of the ulcers were chancroidal, 18% were herpetic (HSV type 2), 6.5% primary syphilitic, and 3.2% due to LGV. More than one micro-organism was detected in 9.1% of the ulcers and less than 10% were undiagnosed. Microscopic examination of the urethral smears showed that 99 (53%) of the men had urethritis, of whom 45 (45%) were infected with N gonorrhoeae. Of the 54 men (55%) who had non-gonococcal urethritis (NGU), 11 (19.6%) harboured C trachomatis or M genitalium. Almost two thirds (64.5%) of the men had HIV infection, but this did not seem to have influenced the aetiology of the ulcers. Nor was a particular ulcer associated with one type of urethritis more than the other. Neither C trachomatis nor M genitalium was associated significantly with non-gonococcal urethritis (NGU) in either HIV positive or HIV negative men. CONCLUSION: The combination of antibiotics used for the management of genital ulcer disease in men in this South African mining population needs to be widened to encompass frequently occurring concomitant gonococcal urethritis and NGU infections. This means treatment with long acting penicillin, combined with ciprofloxacin and azithromycin or erythromycin. A similar situation may exist in other geographical locations with a need to provide appropriate antimicrobial combinations depending on the patterns of infection detected.

Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection.

BACKGROUND AND OBJECTIVES: While genital ulcers are a risk factor in HIV infection, the association of specific agents of genital ulcer disease (GUD) with HIV infection may vary. GOAL: To determine the etiology of GUD in HIV-infected and HIV-uninfected men attending sexually transmitted disease (STD) clinics in Durban, Johannesburg, and Cape Town, South Africa, and the association of previous and current sexually transmitted infections with HIV infection in men with ulcerative and nonulcerative STDs. STUDY DESIGN: A cross-sectional study of 558 men with genital ulcers and 602 men with urethritis. RESULTS: Patients with GUD were more likely to be infected with HIV than patients with urethritis (39.4% versus 21.4%, P< or =0.001). Herpes simplex virus 2 (HSV-2) was the most common agent identified in ulcer specimens (35.9%), and was detected in a significantly higher proportion of ulcer specimens from HIV-infected patients than in specimens from HIV-uninfected patients (47.4% versus 28.2%, P< or =0.001). Patients infected with HIV-1 were significantly more likely to have HSV-2 infection, as measured by the presence of the antibody to glycoprotein G-2, than patients not infected with HIV (63.1% versus 38.5%, P< or =0.001). Patients infected with HIV-1 were also significantly more likely to have initial HSV-2 infection than HIV-uninfected patients with GUD (50.0% versus 31.6%, P = 0.007). Haemophilus ducreyi was detected in 31.7% of ulcer specimens; prevalence did not vary by HIV-infection status. Treponema pallidum DNA was detected significantly less frequently in ulcer specimens from patients infected with HIV than in specimens from patients not infected with HIV (10.2% versus 26%, P< or =0.001); no association was found between HIV-infection status and fluorescent treponemal antibody absorption test seroreactivity, even when men with M-PCR-positive syphilis lesions were excluded from the analyses. CONCLUSION: The authors found that HSV-2 is a more common etiology of GUD than has been suggested by previous studies conducted in South Africa; serologic evidence of HSV-2 infection and current cases of genital herpes are strongly associated with HIV infection among men who present to STD clinics with GUD or urethritis.

Evaluation of the use of calendar blister packaging on patient compliance with STD syndromic treatment regimens.

BACKGROUND: Good compliance with antibiotic therapy is critical for successful management of sexually transmitted diseases (STDs). GOAL OF THIS STUDY: To evaluate the use of user-friendly drug packaging as a means of improving patient compliance with STD therapy and the acceptability of the packaging. STUDY DESIGN: Compliance of patients with STDs with treatment regimens for three different STD syndromes, using antibiotics packed in standard medicine packaging (SP), was compared to that of patients using calendar blister packaged drugs. Compliance was measured by counting the remaining pills at two return visits. Questionnaires were used to evaluate acceptability of the packs. RESULTS: Compliance was significantly better among patients using the calendar blister packs than among those using standard packs, irrespective of dosing frequency. The degree of poor compliance increased with increasing dosing frequency. There was a high level of satisfaction with the blister pack among patients and health care workers. CONCLUSION: Compliance can be improved by the introduction of user-friendly drug packaging, especially for more complex dosing regimens.

Human otoacariasis.

Accidental entry of insects and other arthropods is a common aetiology of aural foreign bodies (FB) presenting to accident and emergency departments. A retrospective study revealed that the FB in almost half (148) of 348 cases of aural FB investigated at the Universiti Sains Malaysia Hospital was an arthropod. The most common arthropod encountered was the cockroach, followed by a cattle tick. The high prevalence of tick infestation of the human ear canal (i.e. human otoacariasis) currently appears to be unique to the Malaysian state of Kelantan. The presentation of patients with intra-aural ticks, the methods used to remove the ticks, the complications encountered, and recommendations for an appropriate course of action in such cases are discussed.

Comparison of clinically directed, disease specific, and syndromic protocols for the management of genital ulcer disease in Lesotho.

OBJECTIVE: To evaluate two protocols for the syndromic management of genital ulcer disease (GUD) in Lesotho, southern Africa and to compare the performance of these protocols with that of a conventional disease specific approach. METHODS: A cross sectional study was conducted among consecutive patients with GUD attending an STD clinic in Maseru, Lesotho. The clinical diagnoses were made by using predefined criteria at the initial visit before the performance of laboratory tests. Attempts were made to detect the specific aetiology of the genital ulcers using PCR assays and syphilis serology. The results of PCR assays and syphilis serology were used as the gold standard against which the performance of the management approaches were applied. RESULTS: Of 100 patients initially recruited into the study, Haemophilus ducreyi infection was detected in 56%, herpes simplex virus in 26%, Treponema pallidum in 23%, and lymphogranuloma venereum in 7%. No pathogens were detected in 6% of patients. 17% of patients had mixed infections. Sensitivity, specificity, positive and negative predictive values of the three management protocols for GUD were compared after applying each to the study population. Theoretically, the lowest correct treatment rate would have been obtained by using the disease specific protocol (62%) compared with more than 90% in both syndromic management protocols. Considerable overtreatment for primary syphilis would occur following application of both syndromic protocols. This would be the result of the overdiagnosis of chancroid, in particular the misdiagnosis of genital herpes as chancroid, which would receive treatment for syphilis unnecessarily. The HIV seroprevalence among these patients was 36%. A significantly higher rate of HIV seropositivity was detected among the patients with herpes simplex virus infection when compared with those patients having other causes of genital ulcer disease (58% v 27%; odds ratio 3.73; 95% CI 1.26-11.26; p = 0.01). CONCLUSIONS: Poor sensitivity, specificity, and predictive values were recorded when the disease specific protocol was applied to the study population. In contrast, the syndromic management protocols provided adequate treatment for more than 90% of patients with GUD. Protocol C, which identified a minority of cases of genital herpes, was found to have an advantage when compared with protocol B (all patients with genital ulcer disease treated for both syphilis and chancroid) in that 29% of genital herpes cases would receive appropriate counselling.

Comparison of clinical diagnosis and standard laboratory and molecular methods for the diagnosis of genital ulcer disease in Lesotho: association with human immunodeficiency virus infection.

A multiplex polymerase chain reaction (M-PCR) assay for Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) was compared with clinical and standard laboratory methods for the diagnosis of genital ulcer disease (GUD) in 105 patients; 36% were human immunodeficiency virus (HIV)-seropositive. Chancroid (80%), syphilis (8%), and genital herpes (8%) were the most frequent diagnoses. H. ducreyi and HSV were isolated from ulcers of 43% and 18% of patients, respectively; in 35%, all cultures were negative and the laboratory diagnosis indeterminate. M-PCR detected H. ducreyi, T. pallidum, and HSV in 56%, 23%, and 26% of patients, respectively; (no definitive diagnosis, 6%). The proportion of patients with more than one agent was 4% by culture and 17% by M-PCR (P = .002). Resolved sensitivities of M-PCR for H. ducreyi and HSV cultures were 95% and 93%, respectively. The sensitivities of H. ducreyi and HSV cultures were 75% and 60%, respectively. HSV, detected in 47% of specimens from HIV-infected versus 16% from HIV-uninfected patients (P < .001), may be emerging as a more frequent cause of GUD.

Fourth branchial pouch cyst: an unusual cause of neonatal stridor.

Fourth branchial pouch anomalies are extremely rare and only a few such cases showing sinuses and cystic masses have been reported in the literature. We describe a patient who presented on the third day of life with cystic neck swelling of fourth branchial pouch origin giving rise to respiratory obstruction and stridor. Despite repeated aspiration of the cystic mass to relieve respiratory obstruction, rapid recurrence of the mass continued to cause stridor and ultimately required surgical excision. The clinical, radiological, and histopathological findings of this unusual condition are discussed with a review of the literature.

Aetiology of stridor in Malaysian children.

Eighty-five children who presented with stridor were reviewed in order to determine the aetiology of stridor in these cases. Congenital causes accounted for 57.6% of cases. Laryngomalacia was the commonest congenital abnormality (77.5%). Other common causes of stridor were a foreign body in the airway (acquired) and laryngotracheobronchitis (33.3%) (infective). Tracheostomized children are a problem in developing countries, requiring prolonged hospitalization. We overcome this problem by teaching parents how to maintain the tracheostomy tube at home.

Additional conductive hearing loss in children from a school for the deaf in Malaysia.

A total of 165 children from a school for the deaf in Malaysia were screened to find out the prevalence of additional conductive hearing loss. Otological examination, tympanometry and pure tone audiometry were performed in all these children. Fifty-one children (30.9%) had additional conductive hearing loss. Middle ear disorders were present in 15 children (9.09%). The deaf children seldom complain about the change in their hearing sensitivity, so there is a need for regular otological examination in deaf children to detect the additional conductive hearing loss.