Identification of a novel HLA-A allele, A*29:28, in an East African population.

The new allele is identical to A*29:01:01:01 in exons 2 and 3, except for a single-nucleotide substitution (TTG to TGG) at codon 156.

Evidence that human Chlamydia pneumoniae was zoonotically acquired.

Zoonotic infections are a growing threat to global health. Chlamydia pneumoniae is a major human pathogen that is widespread in human populations, causing acute respiratory disease, and has been associated with chronic disease. C. pneumoniae was first identified solely in human populations; however, its host range now includes other mammals, marsupials, amphibians, and reptiles. Australian koalas (Phascolarctos cinereus) are widely infected with two species of Chlamydia, C. pecorum and C. pneumoniae. Transmission of C. pneumoniae between animals and humans has not been reported; however, two other chlamydial species, C. psittaci and C. abortus, are known zoonotic pathogens. We have sequenced the 1,241,024-bp chromosome and a 7.5-kb cryptic chlamydial plasmid of the koala strain of C. pneumoniae (LPCoLN) using the whole-genome shotgun method. Comparative genomic analysis, including pseudogene and single-nucleotide polymorphism (SNP) distribution, and phylogenetic analysis of conserved genes and SNPs against the human isolates of C. pneumoniae show that the LPCoLN isolate is basal to human isolates. Thus, we propose based on compelling genomic and phylogenetic evidence that humans were originally infected zoonotically by an animal isolate(s) of C. pneumoniae which adapted to humans primarily through the processes of gene decay and plasmid loss, to the point where the animal reservoir is no longer required for transmission.

Epidemiology of chlamydial infection: are we losing ground?

Are we losing ground in our efforts to control sexually transmitted Chlamydia trachomatis infection? Before we can answer this question, we must first consider recent trends in Chlamydia from around the world to establish a baseline for understanding the possible explanations underlying these data.

Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts.

BACKGROUND: Recent approval of interferon-gamma release assays that are more specific for Mycobacterium tuberculosis has given new options for the diagnosis of latent tuberculosis infection (LTBI). OBJECTIVE: To assess the cost-effectiveness of Quanti-FERON-TB Gold (QFT-G) vs. the tuberculin skin test (TST) in diagnosing LTBI in contacts of active TB cases using a decision analytic Markov model. METHODS: Three screening strategies--TST alone, QFT-G alone and sequential screening of TST then QFT-G--were evaluated. The model was further stratified according to ethnicity and bacille Calmette-Guérin (BCG) vaccination status. Data sources included published studies and empirical data. Results were reported in terms of the incremental net monetary benefit (INMB) of each strategy compared with the baseline strategy of TST-based screening in all contacts. RESULTS: The most economically attractive strategy was to administer QFT-G in BCG-vaccinated contacts, and to reserve TST for all others (INMB CA$3.70/contact). The least cost-effective strategy was QFT-G for all contacts, which resulted in an INMB of CA$-11.50 per contact. Assuming a higher prevalence of recent infection, faster conversion of QFT-G, a higher rate of TB reactivation, reduction in utility or greater adherence to preventive treatment resulted in QFT-G becoming cost-effective in more subgroups. CONCLUSIONS: Selected use of QFT-G appears to be cost-effective if used in a targeted fashion.

Acquisition and synthesis of folates by obligate intracellular bacteria of the genus Chlamydia.

We undertook studies focused on folate acquisition by Chlamydia trachomatis L2, Chlamydia psittaci 6BC, and C. psittaci francis. Results from in situ studies, using wild-type host cells, confirmed that C. trachomatis L2 and C. psittaci 6BC are sensitive to sulfonamides whereas C. psittaci francis is resistant. In addition C. trachomatis L2 and C. psittaci francis were inhibited by methotrexate in situ whereas C. psittaci 6BC was not. In contrast to C. trachomatis, neither C. psittaci strain was affected by trimethoprim. Surprisingly our results indicate that all three strains are capable of efficient growth in folate-depleted host cells. When growing in folate-depleted cells C. psittaci francis becomes sensitive to sulfonamide. The ability of all three strains to carry out de novo folate synthesis was demonstrated by following the incorporation of exogenous [3H]pABA into intracellular folates and by detecting dihydropteroate synthase activity in reticulate body crude extract. Dihydrofolate reductase activity was also detected in reticulate body extract. In aggregate the results indicate that C. trachomatis L2, C. psittaci francis, and C. psittaci 6BC can all synthesize folates de novo, however, strains differ in their ability to transport preformed folates directly from the host cell.

Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection.

The severe adverse effects of gonococcal infection on human fertility suggests that Neisseria gonorrhoeae would exert powerful selection for the development of a protective immune response in humans. N. gonorrhoeae is an obligate human pathogen and must persist in humans to survive. Since it is an ecologically successful organism, it must have evolved strategies to evade any human immune response it elicits. In a longitudinal study among 243 women working as prostitutes and experiencing frequent gonococcal infection, younger women, women with HIV infection, and women with antibody to the gonococcal outer membrane protein 3 (Rmp) were at increased risk of infection (adjusted odds ratio 3.4, CI95% 1.1-10.4, P < 0.05). Rmp is highly conserved in N. gonorrhoeae and the blocking of mucosal defences may be one of its functions. As similar proteins occur in many gram negative mucosal pathogens, the enhancing effect of such proteins may be a general strategy whereby bacteria evade human immune responses.

PIP: Between March 1985 and July 1986 researchers enrolled 243 female prostitutes in Pumwani community of Nairobi, Kenya, in a longitudinal study to examine the relationship between the antibody to the gonococcal outer membrane protein 3 (Rmp Ab) and gonococcal mucosal infection. Few women used condoms. 69% were HIV-1 seropositive. Just 9.5% (23) of the women had not had any gonococcal infections, despite probable exposure to them, indicating the possibility of some acquired protective immunity to Neisseria gonorrhoea. 90.5% had had at least 1 gonococcal infection. Women with Rmp Ab faced a greater risk of gonococcal infection than those who were Rmp Ab negative (OR = 3.4;l p .05), denoting that Rmp Ab increases susceptibility to gonococcal mucosal infections. Women older than 29 years were at lower risk of gonococcal infection than those younger than 29 years (odds ratio [OR] = 0.3; p .03). Women who used oral contraceptives (OCs) were also likely to be infected with N. gonorrhoea (OR = 3; p = .062). Further, 31% of OC users had cervical ectopy compared to just 14% of nonusers (OR = 2.8; p .005), suggesting that the effect of OCs on the cervix make it more susceptible to gonococcal infection. Rmp Ab also exists in many other gram-negative mucosal pathogens, often playing the same role as it does in N. gonorrhoea infection. Thus, Rmp Ab may be a common scheme bacteria used to elude human immune responses. These findings provide more understanding as to why N. gonorrhoea is an ecologically successful human pathogen.

Depression of the lymphocyte transformation response to microbial antigens and to phytohemagglutinin during pregnancy.

Lymphocyte transformation (LT) responses to Chlamydia trachomatis, to four other microbial antigens, and to phytohemagglutinin (PHA) were studied in 201 women during pregnancy and/or 3-18 wk postpartum. The LT responses to all stimulants tested were significantly depressed during pregnancy when compared with postpartum LT responses. This difference occurred whether LT assays were performed in autologous or pooled heterologous plasma collected from nonpregnant donors. Among women studied in the third trimester and again postpartum, the autologous LT stimulation index (LTSI) rose from 1.7 to 3.4 (P less than 0.001) with C. trachomatis elementary body antigen, from 3.7 to 7.9 (P less than 0.001) with Candida albicans cell wall extract, from 4.5 to 7.8 (P = 0.008) with streptokinase-streptodornase, from 1.7 to 3.0 (P = 0.007) with fluid tetanus toxoid, from 1.7 to 2.8 (P = 0.046) with mumps virus skin test antigen, from 35.5 to 87.0 (P less than 0.001) with PHA (2 micrograms/ml), and from 107.2 to 181.9 (P = 0.007) with PHA (10 micrograms/ml). LT responses to C. trachomatis were compared in 52 pregnant women and 58 nonpregnant women; all the women had C. trachomatis isolated at the time of LT assay. Using either plasma supplement, the mean LTSI with C. trachomatis antigen was significantly higher in nonpregnant women than in pregnant women, regardless of trimester (P less than 0.001). Among 12 women who were serially tested and remained culture positive for C. trachomatis throughout pregnancy and the postpartum period, the mean autologous LTSI rose from 1.9 in the third trimester to 7.8 postpartum (P = 0.0004). These data are the first to show that the immune response to an ongoing bacterial infection is depressed during pregnancy and to definitively document the depressed LT responses during human pregnancy.

Antibodies to opacity proteins (Opa) correlate with a reduced risk of gonococcal salpingitis.

Acute salpingitis complicating cervical gonococcal infection is a significant cause of infertility. Relatively little data are available concerning the pathophysiologic mechanisms of this disease. A cohort of 243 prostitutes residing in Nairobi were followed between March 1985 and April 1988. Gonococcal cultures were performed at each visit, and acute salpingitis was diagnosed clinically. Serum at enrollment was tested by immunoblot for antibody to gonococcal outer membrane proteins. 8.6% (146/1689) of gonococcal infections were complicated by salpingitis. Increased risk of salpingitis was associated with younger age, shorter duration of prostitution, HIV infection, number of gonococcal infections, and episodes of nongonococcal salpingitis. Rmp antibody increased the risk of salpingitis. Antibody to Opa decreased the risk of salpingitis. By logistic regression analysis, antibody to Opa was independently associated with decreased risk of gonococcal salpingitis (adjusted odds ratio [OR], 0.35; 95% confidence interval [95%CI], 0.17-0.76); HIV infection (adjusted OR, 3.5; 95% CI, 0.96-12.8) and episodes of nongonococcal salpingitis (adjusted OR, 3.4; 95% CI, 1.8-6.4) were independently associated with an increased risk of salpingitis. Antibody to Opa appears to protect against ascending gonococcal infection, perhaps by interfering with Opa mediated adherence and endocytosis. The demonstration of natural immunity that protects against upper genital tract infection in women suggests that a vaccine to prevent gonococcal salpingitis is possible.

Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): examining the role of niche-specific genes in the evolution of the Chlamydiaceae.

The genome of Chlamydophila caviae (formerly Chlamydia psittaci, GPIC isolate) (1 173 390 nt with a plasmid of 7966 nt) was determined, representing the fourth species with a complete genome sequence from the Chlamydiaceae family of obligate intracellular bacterial pathogens. Of 1009 annotated genes, 798 were conserved in all three other completed Chlamydiaceae genomes. The C.caviae genome contains 68 genes that lack orthologs in any other completed chlamydial genomes, including tryptophan and thiamine biosynthesis determinants and a ribose-phosphate pyrophosphokinase, the product of the prsA gene. Notable amongst these was a novel member of the virulence-associated invasin/intimin family (IIF) of Gram-negative bacteria. Intriguingly, two authentic frameshift mutations in the ORF indicate that this gene is not functional. Many of the unique genes are found in the replication termination region (RTR or plasticity zone), an area of frequent symmetrical inversion events around the replication terminus shown to be a hotspot for genome variation in previous genome sequencing studies. In C.caviae, the RTR includes several loci of particular interest including a large toxin gene and evidence of ancestral insertion(s) of a bacteriophage. This toxin gene, not present in Chlamydia pneumoniae, is a member of the YopT effector family of type III-secreted cysteine proteases. One gene cluster (guaBA-add) in the RTR is much more similar to orthologs in Chlamydia muridarum than those in the phylogenetically closest species C.pneumoniae, suggesting the possibility of horizontal transfer of genes between the rodent-associated Chlamydiae. With most genes observed in the other chlamydial genomes represented, C.caviae provides a good model for the Chlamydiaceae and a point of comparison against the human atherosclerosis-associated C.pneumoniae. This crucial addition to the set of completed Chlamydiaceae genome sequences is enabling dissection of the roles played by niche-specific genes in these important bacterial pathogens.

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

Increased interleukin-10 in the the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission?

OBJECTIVE: Although non-ulcerative sexually transmitted diseases (STD) and bacterial vaginosis are implicated as cofactors in heterosexual HIV-1 transmission, the mechanisms have not been defined. Recent in vitro data suggest that interleukin (IL)-10 may increase susceptibility of macrophages to HIV-1 infection. Therefore, we performed this study to assess whether non-ulcerative STD are associated with detection of IL-10 in the female genital tract. METHODS: Women with clinical pelvic inflammatory disease with or without cervicovaginal discharge were recruited from an STD clinic in Nairobi, Kenya. Endocervical and endometrial specimens were obtained for Neisseria gonorrhoeae and Chlamydia trachomatis DNA detection, Trichonomas vaginalis culture, and CD4 and CD8 T-cell enumeration. Bacterial vaginosis was diagnosed by Gram stain. IL-10 was detected in endocervical specimens using enzyme-linked immunosorbent assay. Blood was obtained for HIV-1 serology. RESULTS: One hundred and seventy-two women were studied. N. gonorrhoeae, C. trachomatis, bacterial vaginosis, and T. vaginalis were detected in 38 (21%), 17 (9%), 71 (43%), and 22 (12%) women, respectively. Cervical IL-10 was detected more often in women with N. gonorrhoeae [adjusted odds ratio (AOR), 3.4; 95% confidence interval (CI), 1.4-8.4], C. trachomatis (AOR, 4.4; 95% CI, 1.2-15.6), and bacterial vaginosis (AOR, 3.1; 95% CI, 1.4-6.9) than in women without these infections. CONCLUSIONS: The association of non-ulcerative STD and bacterial vaginosis with increased frequency of IL-10 detection in endocervical secretions suggests a potential mechanism through which these infections may alter susceptibility to HIV-1 infection in women.

Infection with HIV as a risk factor for adverse obstetrical outcome.

We carried out a case-control study to investigate the role of sexually transmitted diseases (STDs), including infection with HIV, as risk factors for adverse outcome of pregnancy. Overall, 1507 women were enrolled within 24 h of delivery. Cases (n = 796) were mothers of low-birthweight infants (less than 2500 g) or of stillborns. Low-birthweight infants were divided into preterms (n = 373) and neonates small for gestational age (n = 234). Stillborns were separated into intrauterine fetal deaths (n = 120), and intrapartum fetal deaths (n = 69). Controls were selected from mothers delivering a live baby of greater than or equal to 2500 g (n = 711). The maternal HIV seroprevalence in the control group was 3.1%. Prematurity was associated with maternal HIV antibody [8.6% seropositive; adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.1-4.0], as was being born small for gestational age (7.7% seropositive; adjusted OR 2.3; 95% CI 1.2-4.2). In mothers who delivered a stillborn baby, both intrauterine fetal death (11.7% seropositive; adjusted OR 2.7; 95% CI 1.3-5.5) and intrapartum fetal death (11.6% seropositive; adjusted OR 2.9; 95% CI 1.3-6.5) were independently associated with HIV seropositivity in the mother. Maternal syphilis was confirmed as an important risk factor for intrauterine fetal death (14.3% positive; adjusted OR 4.8; 95% CI 2.4-9.5). No significant association was found between other STDs, including gonococcal and chlamydial infection, and adverse obstetrical outcome. These results suggest an association between maternal HIV infection and adverse obstetrical outcome, defined as low birthweight and stillbirth.

Magic bullets need accurate guns--syphilis eradication, elimination, and control.

When cases of early syphilis are treated promptly, the spread of the bacteria within a population is interrupted. However, if complacency is induced by successful control, then upsurges in syphilis incidence can occur. The methods and aims of syphilis control in industrialised countries are reviewed in the light of the potential for regional elimination and global eradication programmes. While the medical means to eliminate syphilis are at hand, acceptable means for finding and treating cases that transmit infection need to be developed, particularly in the marginalized communities with limited access to care.

Gonococcal infection and human fertility in sub-Saharan Africa.

An analysis is presented of the influence of Neisseria gonorrhoeae on human population growth in regions of sub-Saharan Africa where gonococcal infections are prevalent in sexually active adults. Combining epidemiological and demographic data within the framework of a mathematical model, we show that gonorrhoea has a major impact on fertility and, concomitantly, on net population growth in areas with a high prevalence of untreated infections. Specifically, a 20% prevalence in sexually active adults is predicted to induce a 50% reduction in net population growth. Model predictions are in good agreement with observed data from Uganda, and the sensitivity of the prediction to various complications, such as heterogeneity in sexual behaviour, is assessed. The analysis suggests that the predicted increase in fertility arising from expanded sexually transmitted disease (STD) control programmes in Africa to help combat the spread of human immunodeficiency viruses (HIV-1 and HIV-2) will help to offset the predicted demographic impact of AIDS in the worst afflicted areas. In other areas the rise in fertility associated with effective STD control will need to be countered by the linkage of STD control programmes with family planning initiatives.

Two-step high resolution sequence-based HLA-DRB typing of exon 2 DNA with taxonomy-based sequence analysis allele assignment.

A two-step high resolution sequence-based DRB typing method was developed. The system needs only one polymerase chain reaction (PCR) to type all functional DRB alleles of a given individual. It uses a pair of generic PCR primers to amplify exon 2 DNA of all functional DRB genes and a first-step taxonomy-based sequence analysis (FSTBSA) method to assign allele groups after sequencing the PCR products with a generic primer. In the second step, group-specific primers are used to sequence the same PCR products and a taxonomy-based sequence analysis (TBSA) is used to assign alleles. Thus, both low and high resolution DRB typing can be done with PCR amplified exon 2 DNA from a single PCR reaction. Correct allele group assignment by FSTBSA was confirmed by sequencing the PCR products with group-specific primers and correctly assigned all 158 DNA samples including 34 samples pre-typed by PCR-sequence-specific primer or PCR-sequence-specific oligonucleotide probe. FSTBSA correctly assigned 116 heterozygous combinations of 81 DRB1-DRB3/4/5 haplotypes. Sixty-seven DRB1, 6 DRB3, 1 DRB4, and 3 DRB5 alleles were identified in this study. TBSA successfully resolved all heterozygous allele combinations including 31 heterozygous combinations of 33 alleles of DRB1*03, 08, 11, 12, 13, and 14 allele groups, and six heterozygous combinations of six DRB3 alleles.

Chlamydia trachomatis infection in women with ectopic pregnancy.

Fifty women with ectopic pregnancy and 49 control women with intrauterine pregnancy were interviewed and evaluated for evidence of Chlamydia trachomatis infection. Among women with ectopic pregnancy, 14 women were wearing an intrauterine contraceptive device or had a tubal ligation (group A), and 36 women had no readily identifiable risk factors (group B). Group B women had greater total numbers of sexual partners than did control women with intrauterine pregnancy (P less than .005). Group B women more often had C trachomatis antibody than group A (P = .03) and control women (P = .002). Of 27 C trachomatis cultures from fallopian tube tissue from women with ectopic pregnancy, none were positive. Fallopian tube tissue distant from the site of ectopic implantation was available for histopathology of 41 cases. Nine (22%) had extensive subepithelial plasma cell infiltration. All nine were among group B women (P = .06) and all seven with plasma cell salpingitis who were tested for C trachomatis antibody were seropositive (P = .004). It is concluded that a subset of women with ectopic pregnancy were at increased risk for acquiring a sexually transmitted disease by virtue of their sexual behavior and that women in this subset frequently have serologic evidence of C trachomatis infection and histologic evidence of plasma cell salpingitis. Because few of these women recall having had pelvic infection, the authors speculate that subclinical C trachomatis tubal infection producing plasma cell salpingitis may commonly underly ectopic pregnancy.

Human leukocyte antigen class II DQ alleles associated with Chlamydia trachomatis tubal infertility.

OBJECTIVE: To investigate epidemiologic tubal infertility risk factors and the relationship between HLA class II alleles and Chlamydia trachomatis tubal infertility. METHODS: Forty-seven women with tubal infertility and 46 fertile controls were studied in Nairobi, Kenya. A questionnaire was administered and serum collected for measurement of C trachomatis antibodies. HLA class II molecular typing was done with DNA extracted from peripheral blood lymphocytes. The prevalence of C trachomatis microimmunofluorescence antibody, chlamydia heat shock protein 60 antibody, and HLA class II alleles was compared among cases of tubal infertility and fertile controls. RESULTS: Women with tubal infertility more often had histories of pelvic inflammatory disease (15% versus 0%; odds ratio [OR] 16; 95% confidence interval [CI] 5.5, 47) histories of spontaneous abortion (34% versus 7%; OR 6.7; 95% CI 2.8, 16), and antibodies to C trachomatis (53% versus 26%; OR 3.2; 95% CI 1.3, 7.7) than controls. Among infertile women, DQA*0101 and DQB*0501 alleles were positively associated with C trachomatis tubal infertility (OR 4.9; 95% CI 1.3, 18.6, and OR 6.8; 95% CI 1.6, 29.2, respectively). DQA*0102 was negatively associated with C trachomatis tubal infertility (OR 0.2; 95% CI 0.005, 0.6). CONCLUSION: Chlamydia trachomatis infection is an important cause of tubal infertility in Nairobi. The association of specific HLA class II alleles with C trachomatis microimmunofluorescence seropositivity among women with tubal infertility suggests that the DQ locus might modify susceptibility to and pathogenicity of C trachomatis infection.

The impact of HIV and other STDs on human populations. Are predictions possible?

This article presents an overview of the use of mathematical models to study the demographic impact of STDs. Written for the nonmathematician, the article introduces the basic concepts of mathematical epidemiology for infectious diseases, such as the mass-action principle, the threshold density concept, and the basic reproductive rate. Described are the main features that characterize the epidemiology of STDs and those features that differentiate them from other directly transmitted diseases, such as measles, rubella, and others. Also presented are major findings concerning the importance of sexual behavior on the dynamics of STD transmission, and the numerical analysis of the demographic impact on gonococcal and HIV infections using a mathematical model. The epidemiology of these two STDs is explored, as well as how the growth rate of the population can influence the epidemiology of these STDs. Finally, the authors demonstrate how, under some circumstances, early treatment of gonorrhea can reduce the demographic impact of HIV in regions most affected by both diseases.

A general model of sexually transmitted disease epidemiology and its implications for control.

Achieving control of STDs may be possible by integrating the activities discussed previously with further research to provide additional empiric data on sex behavior, to develop innovative strategies to access and communicate with those most at risk of STD (i.e., core-group members), and to foster biologic study of STD pathogens with the goal of vaccine development. New strategies to identify core-group members aside from the currently used STD-repeater status would be of immense help in targeting educational efforts, laboratory screening, and vaccines. Achieving more complete control of STDs may be possible if recent advances in our understanding of their epidemiology and transmission dynamics can be translated into effective new interventional strategies.

The role of the laboratory in a Chlamydia control programme in a developing country.

The laboratory components of a Chlamydia trachomatis disease control programme for a developing country are reviewed. Early diagnosis of chlamydial infections is the most cost effective means of preventing the long term sequelae of trachoma, pelvic inflammatory disease, ectopic pregnancy and infertility, which are now a major public health burden to the health care system in developing countries. Public health strategies are required to establish both a co-ordinated limited system of laboratory services, and to promote the diagnosis and treatment of disease syndromes in the absence of laboratory support. Laboratory tests for the specific diagnoses of chlamydial infections requiring different levels of expertise and equipment can be instituted within settings appropriate to the resources and technical expertise available. Emphasis is given to appropriate cost effective utilization of laboratory testing.

PIP: Current methods used for the laboratory diagnosis of a Chlamydia trachomatis disease control program for a developing country are reviewed to guide clinical microbiology laboratories to develop criteria for testing. Human chlamydia infections are a major public health problem in both developed and developing countries. Worldwide an estimated 360 million persons are infected by the ocular serovars of Chlamydia trachomatis and 6.4 million are blind from the scarring, sequelae. The genital strains of Chlamydia trachomatis cause cervical, endometrial or tubal infections in women, resulting in pelvic inflammatory disease (PID) or ectopic pregnancy, and infertility. Over 50% of chlamydia infections in women are asymptomatic and progress to silent PID and infertility. In industrialized countries chlamydia infections are the major cause of sexually transmitted disease-related infertility. Infants born to infected mothers are at risk for chlamydia pneumonia and ophthalmia neonatorum. More tentative associations of chlamydia infections exist with Reiter's Syndrome. Early diagnosis of chlamydia infections is the most cost effective means of preventing the longterm sequelae of trachoma, pelvic inflammatory disease, ectopic pregnancy and infertility, which are a major public health liability in developing countries. In many developed and developing countries, public health decision maker are not aware of the extent of chlamydia infections in the community. One of the priorities of the disease control program is to provide accurate epidemiologic data through seroprevalence studies. This includes estimates of persons infected, the severity of complications and sequelae. Public health strategies are required to establish laboratory services and to diagnose and treat the disease. The diagnostic methods for C. trachomatis include specimen collection, cytologic methods, serologic methods, cell culture method, antigen detection methods, and nucleic acid hybridization tests that should be available at the national reference laboratory.