Faculty Bibliography

OBJECTIVES: To update the WHO global and regional estimates of the prevalence and incidence of syphilis, gonorrhoea, chlamydia, and trichomoniasis. METHODS: Prevalence estimates for syphilis, gonorrhoea, chlamydia, and trichomoniasis were generated for each of the nine UN regions for males and females between the ages of 15 and 49 in 1995 based on an extensive review of the published and unpublished medical literature since 1985. Incidence estimates were based on the prevalence figures and adjusted to take into account the estimated average duration of infection for each disease in a particular region. The latter was assumed to depend upon a number of factors including the duration of infection in the absence of treatment, the proportion of individuals who develop symptoms, the proportion of individuals treated, and the appropriateness of treatment. RESULTS: In 1995 there were over 333 million cases of the four major curable STDs in adults between the ages of 15 and 49--12 million cases of syphilis, 62 million cases of gonorrhoea, 89 million cases of chlamydia, and 170 million cases of trichomoniasis. Geographically, the vast majority of these cases were in the developing world reflecting the global population distribution. CONCLUSIONS: STDs are among the most common causes of illness in the world. Estimates of the global prevalence and incidence of these infections are limited by quantity and quality of data available from the different regions of the world. Improving global STD estimates will require more well designed epidemiological studies on the prevalence and duration of infection.

SETTING: Five IS6110 chromosomal insertion sites were characterized in the multidrug resistant Mycobacterium tuberculosis 'W' strain. OBJECTIVE: To use insertion site probes to study the phylogenetic distribution of IS6110 in the M. tuberculosis genome. DESIGN: A total of 722 M. tuberculosis isolates, previously genotyped using the standard IS6110 Southern blot hybridization methodology, were re-hybridized with the Region A insertion site probe and representative strains were further hybridized with the Region B and C probes. Strains were grouped on the basis of having IS6110 insertions in these different regions and their relatedness was further compared by sequencing the IS6110 insertion sites. RESULTS: The insertion site probes revealed that the collection of Chinese isolates previously grouped as the Beijing strain family shared IS6110 insertions in common with the W and other genotypic group 1 strains. Unexpectedly, we found that IS6110 integrated at least 10 independent times between the dnaA and dnaN genes encoding deoxyribonucleic acid replication proteins. CONCLUSIONS: IS6110 insertion site mapping is able to identify genetic relatedness among a collection of M. tuberculosis clinical strains representing the breadth of species diversity. The mapping data indicate that IS6110 insertion sites are not always random

Background: Several molecular methods potentially useful in the detection of Mycobacterium tuberculosis mutations, specifically in rpoB and katG, were compared. Methods and Results: DNA from 24 M. tuberculosis clinical isolates, with mutations associated with resistance to rifampin and/or isoniazid, was analyzed. A 128 bp amplicon, spanning the 81 bp rpoB region containing most mutations leading to rifampin resistance, was analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and a recently introduced mutation scanning method, cleavase fragment length polymorphism (CFLP) analysis. Also, a 350 bp amplicon encompassing that region was analyzed by the CFLP method. CFLP analysis of the 350 bp amplicon (23 isolates) identified 14 of 17 mutants; however, CFLP analysis of the 128 bp amplicon accurately identified all mutants as did PCR-SSCP with interpretative difficulty for two codon 513 mutations. CFLP and PCR-restriction fragment length polymorphism (RFLP) analyses of a 623 bp amplicon encompassing katG codons 315 and 463 showed that the CFLP method identified single and dinucleotide codon 315 substitutions with or without codon 463 (CGG-->CTG) changes, whereas PCR-RFLP (MspI) missed one codon 315 polymorphism (AGC-->ACA) in three isolates. Conclusion: Both PCR-SSCP and CFLP analyses were sensitive in identifying all mutations on short sequences in the rpoB mutants. CFLP appears to be more efficient than SSCP and RFLP for the detection of mutations in large amplicons

BACKGROUND: Porphyria cutanea tarda is known to be associated with HIV infection and hepatitis C virus (HCV). OBJECTIVE: Our purpose was to evaluate whether early infection with HIV, with or without HCV infection, is associated with elevated serum porphyrin levels. METHODS: Serum porphyrin levels were measured in samples obtained from 103 patients with early HIV infection. The results were compared with those of 89 late-stage HIV-positive patients and 78 HIV-negative patients. RESULTS: The highest median porphyrin level was in early-stage HIV-positive/HCV-positive samples, followed in decreasing order by those in early-stage HIV-positive/HCV-negative, late-stage HIV-positive/HCV-positive, late-stage HIV-positive/HCV-negative, HIV-negative/HCV-positive, and HIV-negative/HCV-negative groups. Elevated porphyrin levels were independently associated with early-stage HIV infection (P < .0001) and HCV infection (P = .03). CONCLUSION: This finding suggests abnormal porphyrin metabolism is most noticeable in early-stage HIV infection; it becomes less severe with the progression of HIV disease