The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV.

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.

OBJECTIFS: L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD. CONCLUSIONS: Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.

Towards new business models for R&D for novel antibiotics.

In the face of a growing global burden of resistance to existing antibiotics, a combination of scientific and economic challenges has posed significant barriers to the development of novel antibacterials over the past few decades. Yet the bottlenecks at each stage of the pharmaceutical value chain-from discovery to post-marketing-present opportunities to reengineer an innovation pipeline that has fallen short. The upstream hurdles to lead identification and optimization may be eased with greater multi-sectoral collaboration, a growing array of alternatives to high-throughput screening, and the application of open source approaches. Product development partnerships and South-South innovation platforms have shown promise in bolstering the R&D efforts to tackle neglected diseases. Strategies that delink product sales from the firms' return on investment can help ensure that the twin goals of innovation and access are met. To effect these changes, both public and private sector stakeholders must show greater commitment to an R&D agenda that will address this problem, not only for industrialized countries but also globally.

Rapid diagnostic tests for determining dengue serostatus: a systematic review and key informant interviews.

OBJECTIVES: Vaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection. METHODS: PubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers. RESULTS: The performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection. CONCLUSIONS: Although current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach.

Spousal sexual violence and poverty are risk factors for sexually transmitted infections in women: a longitudinal study of women in Goa, India.

OBJECTIVES: To describe factors associated with incident sexually transmitted infections (STI) in a population-based sample of women in Goa, India. METHODS: A random sample of women aged 18-45 years was enrolled in Goa from November 2001 to May 2003. All subjects who consented to participate and completed the recruitment procedure were interviewed six and 12 months after recruitment. Incident chlamydia, gonorrhoea or trichomoniasis from vaginal and/or urine specimens were detected using a commercial polymerase chain reaction and the InPouch TV Culture Kit. RESULTS: Of the 2180 women followed up, 64 had an incident STI (incidence of 1.8% in the first six months, and 1.4% in the second six months). Incident STI was associated with low socioeconomic status, marital status, and with concurrent bacterial vaginosis. Incidence was highest among women who were married and exposed to sexual violence (10.9%), were concerned about their husbands' affairs (10.5%), or were separated, divorced or widowed women (11.0%). CONCLUSIONS: Socially disadvantaged women are at increased risk of STI in this population. Sexual intercourse outside marriage was rarely reported in this population, and women are at risk of becoming infected within marriage, especially those with sexual violence. This highlights the vulnerabilities of socially disadvantaged married women in India, and the need for healthcare professionals to screen STI patients for violence, and provide the necessary support. The results also stress the importance of effectively diagnosing and treating married men with STI and promoting safer sex within marriage.

Field evaluation of the performance and testing costs of a rapid point-of-care test for syphilis in a red-light district of Manaus, Brazil.

OBJECTIVES: To assess the performance, usefulness and cost of a rapid treponemal antibody assay (VisiTect Syphilis) to detect syphilis in high risk populations. METHODS: People who attended STI clinics in Manaus, Brazil, were screened for syphilis using the fluorescent treponemal antibody absorption (FTA-Abs) test and a non-treponemal test (Venereal Diseases Research Laboratory (VDRL)), and for HIV. Finger prick blood samples were tested with VisiTect Syphilis. The rapid test was evaluated against the reference FTA-Abs and for its usefulness in detecting active syphilis (FTA-Abs and VDRL positive). Operational performance was assessed through providers' and patients' interviews. An economic evaluation was conducted from the provider's perspective. RESULTS: 510 patients (60% men) were enrolled, of whom 13 (2.5%) were HIV-1 seropositive. Syphilis prevalence (FTA-Abs) was 18% and active syphilis prevalence was 7.5%. 11% (57/506) of samples were positive by VisiTect. The sensitivity, specificity, positive and negative predictive values of VisiTect Syphilis were 57% (95% CI 45.8 to 66.7), 99% (95% CI 97.0 to 99.6), 91% (95% CI 80.0 to 96.7) and 91% (95% CI 88.0 to 93.5), respectively. VisiTect Syphilis identified 79% (30/38) of active syphilis cases. The cost per case of syphilis was $16.8 for VDRL, $33.2 for low cost and $56.3 for high cost VisiTect Syphilis; the cost per case of active syphilis was $21.3, $57.5 and $97.6, respectively. Patients identified finger prick pain and preference for venous blood collection as minor barriers to test use. CONCLUSION: VisiTect Syphilis had low sensitivity in field use and was less cost effective than conventional VDRL. However, rapid and correct identification of a high proportion of active syphilis cases combined with operational characteristics suggest a role in high risk populations.

Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent.

Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics.

A novel approach to the laboratory diagnosis of Chlamydia trachomatis infections using monoclonal anti-idiotypic antibodies.

We have developed a novel enzyme immunoassay (EIA) for the specific detection of Chlamydia trachomatis utilizing a monoclonal anti-idiotypic antibody to an antibody directed against a chlamydia specific epitope on 60 kDa heat-shock protein (HSP60). The basis of the assay is the inhibition of the binding of idiotype to anti-idiotype by antigen present in test samples. Two configurations of the assay were developed: a blocking EIA and a competition EIA. Greater sensitivity was observed using the competition EIA, with the assay detecting purified recombinant HSP60 and purified chlamydia in a concentration-dependent manner from 0.01 to 10 micrograms protein and from 0.5 to 12 micrograms total protein, respectively. The assay is highly specific and offers several potential advantages over currently available EIAs for the detection of this pathogen.

Ambulatory patients with community-acquired pneumonia: the frequency of atypical agents and clinical course.

OBJECTIVES: To determine the etiology of community-acquired pneumonia in patients treated in an ambulatory setting, using serological methods, and to compare presenting symptoms, radiographic manifestations, and clinical outcomes of patients with pneumonia of "atypical" and undetermined etiology. PATIENTS AND METHODS: This prospective cohort study was conducted in emergency room and outpatient facilities of Victoria General Hospital, Halifax, Nova Scotia, and in offices of participating family doctors based in Halifax. One hundred forty-nine adults with acute onset of one or more symptoms or signs suggestive of pneumonia and radiographic evidence of pneumonia who provided informed consent were enrolled. Patients known to be HIV positive or who had been discharged from a hospital within the previous 10 days were ineligible for enrollment. Demographic features and clinical data were collected by direct patient interview and chart review by trained research nurses. Outcome measures included quantitative evaluation of pneumonia-specific symptoms, and responses to the Short Form 36 Health Survey at presentation and at 30 days after presentation. Information was also collected on each patient's health prior to pneumonia, as well as the time until each patient's self-reported return to work and to usual activities. The etiology of pneumonia was determined by testing acute and convalescent serum samples for antibodies to Legionella pneumophila serogroup 1, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, adenovirus, respiratory syncytia virus, influenza viruses A and B, and parainfluenza viruses 1, 2, 3. RESULTS: The study population consisted of 149 patients, 54 (36%) of whom were men, with a mean age (+/- SD) of 41 +/- 15 years. An etiological diagnosis was made in 74 (49.7%) patients using serological methods. Etiological agents included M pneumoniae 34 (22.8%); C pneumoniae 16 (10.7%); M pneumoniae and C pneumoniae 5 (3.4%); C burnetii 4 (2.7%); influenza A virus 4 (2.7%); and other agents 6% (7.4%). Three patients (2%) had a conventional bacterial etiology, and 72 patients (48.3%) had pneumonia of undetermined etiology. Patients with pneumonia of known (atypical) and undetermined etiology were similar in terms of age, gender, race, education, employment, and comorbidity. Despite a higher proportion of patients with pneumonia of known etiology reporting sweats, chills, and headache at presentation, the two groups were similar for symptom severity and bother. The patients with pneumonia of undetermined etiology were more likely to have multilobar pneumonia (P < 0.02). Both patients with atypical pneumonia and those with pneumonia of undetermined etiology suffered severe deterioration of physical functioning with a marked but incomplete recovery at 30 days. Those with atypical pneumonia had higher physical functioning and general mental health scores at 30 days. CONCLUSIONS: Nearly half the cases of ambulatory community-acquired pneumonia are due to "atypical" agents. It is not possible to reliably distinguish patients with atypical pneumonia from those with pneumonia of undetermined etiology by clinical features at baseline. The outcomes in terms of resolution of symptoms, functional status, return to work, and return to usual activities are essentially similar in the two groups.

Acceptability and usefulness of vaginal washes in premenarcheal girls as a diagnostic procedure for sexually transmitted diseases. The Child Protection Centre at the Winnipeg Children's Hospital.

OBJECTIVE: To assess the suitability of vaginal washes as specimens for sexually transmitted disease diagnosis and determine the usefulness of PCR technology for Chlamydia trachomatis diagnosis in prepubertal girls. STUDY DESIGN: Paired sets of vaginal secretions were collected with swabs and by vaginal wash from 138 prepubertal girls for evaluation because of alleged sexual abuse. Detection by culture of Neisseria gonorrhoeae and C. trachomatis was compared between the two sampling techniques. PCR techniques were also used to test 29 vaginal wash specimens for C. trachomatis. RESULTS: In the prepubertal girls N. gonorrhoeae was detected in two wash specimens but in only one swab specimen; C. trachomatis was detected by culture in both paired specimens from two children and by PCR in vaginal washes from both of the two children positive by culture; PCR identified two other infected children. CONCLUSIONS: A vaginal wash technique coupled with newer molecular amplification technology may be useful in the assessment of sexually abused children.

The presence of serum antibody to the chlamydial heat shock protein (CHSP60) as a diagnostic test for tubal factor infertility.

OBJECTIVE: To study the utility of testing for heat shock protein 60 (CHSP60) antibodies in the diagnosis of tubal factor infertility. DESIGN: Prospective case control. SETTING: Canadian university hospital infertility clinic. PATIENT(S): Women presenting for infertility investigation. INTERVENTION(S): Sera were collected from 77 patients. MAIN OUTCOME MEASURE(S): The relationship between tubal factor infertility and the presence of antibodies to Chlamydia trachomatis and CHSP60 was assessed. RESULT(S): There were no significant differences between antibodies to C. trachomatis in women with tubal factor infertility (63%) and other causes of infertility (46%). However, more women with tubal factor infertility (44%) had anti-CHSP60 antibodies compared with other causes of infertility (8%). Antibody testing for C. trachomatis has only a 63% sensitivity and a 54% specificity for detecting tubal factor infertility. In contrast, the CHSP60 antibody test has a 44% sensitivity and a 92% specificity for detecting tubal factor infertility. There is a good positive likelihood ratio of 5.5 for CHSP60 antibody testing detecting the presence of tubal factor infertility. Combining CHSP60 antibody with antibody testing for C. trachomatis has an excellent positive likelihood ratio of 10 for the detection of C. trachomatis-associated tubal factor infertility. CONCLUSION(S): CHSP60 antibody testing is a more accurate test than antibody testing for C. trachomatis for predicting chlamydia-associated tubal factor infertility. These tests, when used in combination at initial infertility evaluation, would provide a rapid noninterventive means of diagnosing tubal factor infertility.

Does serologic evidence of remote Chlamydia trachomatis infection and its heat shock protein (CHSP 60) affect in vitro fertilization-embryo transfer outcome?

OBJECTIVE: To examine IVF-ET outcome in patients with and without serologic evidence of Chlamydia trachomatis infection and chlamydia heat shock protein 60 (CHSP 60) antibodies. DESIGN: Retrospective case control. SETTING: University-affiliated IVF-ET program. MAIN OUTCOME MEASURES: A total of 195 IVF-ET patients with tubal factor infertility underwent oocyte pick-up, 166 of these women had ET resulting in a total of 37 pregnancies. Serum antibody testing for evidence of remote C. trachomatis and CHSP 60, as well as pregnancy outcome, were determined for all patients. RESULTS: There were no differences in pregnancy rates or outcomes between C. trachomatis seropositive versus seronegative groups: 27/118 (23%) C. trachomatis seropositive versus 10/77 (13%) C. trachomatis seronegative patients achieved pregnancy per oocyte pick-up. Pregnancy rates per ET were 27/105 (26%) in C. trachomatis seropositive versus 10/61 (16%) C. trachomatis seronegative patients. In the C. trachomatis positive subgroup, significantly higher pregnancy rates were found in the CHSP 60 antibody positive patients: 24/67 (36%) CHSP 60 positive versus 3/51 (6.0%) CHSP 60 negative patients were pregnant after oocyte pick-up (OR = 8.9, 95% CI = 2.3 to 27.5). Pregnancy rates per ET were 24/57 (42%) in CHSP 60 positive versus 3/48 (7%) CHSP 60 negative patients (OR = 10.9, 95% CI = 2.8 to 33.6). There were no significant differences in any group when examining the following pregnancy outcomes: spontaneous abortion, ectopic pregnancy, preterm and multiple pregnancy rates. CONCLUSIONS: [1] There are no differences in pregnancy rates or outcomes in patients with and without serologic evidence of previous C. trachomatis infections. [2] In women seropositive for C. trachomatis, significantly higher pregnancy rates are found in women who are CHSP 60 antibody positive versus negative. [3] Pregnancy outcomes do not appear to be different between these groups.

Molecular Techniques for HIV and STDs : Implications for Research and Disease Control in the New Millennium.

Molecular techniques have gradually shifted the paradigm in the laboratory diagnosis of sexually transmitted infections from biological to molecular amplification. It is now possible to combine the sensitivity and specificity of culture with all the convenience of nonculture tests, such as ambient specimen transport, automation, and fast turnaround time. Pathogens that cannot be cultivated in vitro, such as the human papillomavirus (HPV), can now be detected and typed to determine if they have oncogenic potential. These powerful tools have improved and will continue to have a significant impact on our ability to design strategies and programs for the control and prevention of sexually transmitted infections worldwide.

Reliability of cytology to detect chlamydial infection in asymptomatic women.

Chlamydia trachomatis is a frequent sexually transmitted disease. The diagnosis of C. trachomatis infection by cytology is controversial. We compared the ability of Papanicolaou (Pap) smears to detect C. trachomatis infection with antigen detection (enzyme immunoassay; EIA) and polymerase chain reaction (PCR). One hundred sixty-seven women attending a therapeutic abortion clinic were enrolled in the study. Endocervical samples were first collected for EIA and PCR, and then Pap smears were prepared for cytologic evaluation. Eight patients were excluded from the study due to the lack of an endocervical component. The criteria established by Gupta and associates (Diagn Cytopathol 1988;4:224-229; Acta Cytol 1979;23:315-320) were used in this study to assess the specificity and sensitivity of the Pap smear in recognizing C. trachomatis infection. After EIA testing, the remaining sample was subjected to phenol-chloroform extraction to purify the DNA and then tested by PCR. Positive PCR samples were subjected to repeat phenol-chloroform and retested to confirm the positive result. Using a confirmed PCR or a blocked EIA as the extended gold standard, the incidence of C. trachomatis infection was 9.4%. Fifteen of the 159 cases reviewed were positive by extended gold standard. Thirteen (86.7%) of those 15 cases were interpreted as negative by cytology (false-negatives), and two (13.3%) cases were positive. Of the remaining 144 cases, 14 cases (9.7%) were interpreted as positive by cytology (false-positives) but were not confirmed by the extended gold standard. Ten (66.7%) of the 15 cases confirmed by the extended gold standard were interpreted as negative by EIA (false-negatives), and five (33.3%) were positive. There were no false-positives by EIA. In this study, the sensitivity and the specificity for cytology were 13.3% and 90.3%, respectively. The positive predictive value was 12.5%, and the negative predictive value for cytology was 90.9%. The sensitivity and the specificity for EIA were 33.3% and 100%, respectively. The positive predictive value was 100%, and the negative predictive value for EIA was 93.5%. Both EIA and cytology are insensitive methods compared with PCR. Based on these data, cytology should not be used to diagnose C. trachomatis infection in an asymptomatic female population with a moderate risk of C. trachomatis infection.

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.

Laboratory diagnosis of Chlamydia pneumoniae infections.

Chlamydia pneumoniae is an important cause of respiratory illness. There is a need for accurate and rapid laboratory diagnostic methods that will lead to improved patient care, appropriate use of antimicrobial therapy and a better understanding of the epidemiology of this emerging pathogen. Culture is highly specific but is technically demanding, expensive, has a long turnaround time and its sensitivity is highly dependent on transport conditions. Antigen detection tests such as enzyme immunoassay and direct fluorescent antibody assay, and molecular detection methods such as the polymerase chain reaction assay, may provide a rapid diagnosis without the requirement for stringent transport conditions. The results of these tests should be interpreted with caution until more thorough evaluation is available. Serology remains the method of choice. The limitations of different serological methods for the laboratory diagnosis of C pneumoniae are discussed.

Chlamydia pneumoniae pneumonia: An evolving clinical spectrum.

Chlamydia pneumoniae is a recently recognized respiratory tract pathogen. It accounts for 6 to 10% of all cases of community acquired pneumonia requiring admission to hospital. Two patients hospitalized with C pneumoniae pneumonia are presented to illustrate its range of severity and the extrapulmonary manifestations.

Noninvasive screening for genital chlamydial infections in asymptomatic men: Strategies and costs using a urine PCR assay.

OBJECTIVE: To evaluate cost saving strategies to screen for genital chlamydial infection in men using polymerase chain reaction (PCR) technology. METHODS: Men with no urethral symptoms presenting to a sexually transmitted disease (STD) clinic were recruited. Study participants underwent a questionnaire interview. Urethral swabs were taken to perform a smear for polymorphonuclear leucocytes (PMN) and for the detection of Chlamydia trachomatis by culture and PCR. First-catch urine was collected for a leukocyte esterase test (LET) and PCR. RESULTS: C trachomatis infection was detected in 36 of 463 (7.8%) men. LET and PMN were positive in 10 (28%) and 12 (33%) infected men, respectively. Risk factors for chlamydial infection were younger than age 25 years, LET-positive, PMN-positive and STD contact (P<0.001). The direct cost of genital chlamydial infection in men in Canada has been previously estimated at $381/case. Based on a sensitivity of 90% for urine PCR, the estimated direct cost of testing all participants to detect 32 cases was $453/case. Using risk factors recommended in the Canadian STD Guidelines (age younger than 25 years, new partner, STD contact or unprotected sex), the same number of cases would have been detected by testing only 384 men at $376/case. Using age younger than 25 years or STD contact as the screening criterion, 78% of those infected would have been detected at $259/case, and no new cases would have been detected by adding LET-positive or PMN-positive as risk factors. CONCLUSION: Targeted screening for chlamydial infection using urine PCR assay and risk factors recommended in the Canadian guidelines could substantially reduce the cost of screening at a STD clinic setting. LET and PMN smear did not appear to be useful indicators of chlamydial infection in this population.

Field performance of a rapid point-of-care diagnostic test for antenatal syphilis screening in the Amazon region, Brazil.

We evaluated an immunochromatographic point-of-care (POC) syphilis test in 712 pregnant women under field conditions in remote communities of the Amazon region (Brazil), and identified risk factors for syphilis. Women were screened by POC test using whole blood obtained by fingerprick, the fluorescent treponemal antibody absorption (FTA-Abs) test as the gold standard and the Venereal Diseases Research Laboratory (VDRL) test to determine test performance in active syphilis. Multivariate analysis was conducted to identify factors associated with syphilis infection. Among women, 2.2% had syphilis (positive FTA-Abs) and 0.8% active syphilis (FTA-Abs and VDRL positive). In all, 2.2% of samples were positive by the POC test. The sensitivity, specificity, positive and negative predictive values were 62.5% (95% confidence interval [CI]: 38.6-81.5), 99.1% (95% CI: 98.1-99.6), 62.5% (95% CI: 38.6-81.5) and 99.1% (95% CI: 98.1-99.6), respectively. The POC test identified 62.5% (10/16) of syphilis cases, 66.7% (4/6) of active syphilis cases and all high-titre syphilis cases (VDRL > 1:8). Older age was associated with syphilis infection. The rapid test performed moderately well as a screening tool for low-risk populations. This combined with on-site testing and same day treatment could expand antenatal syphilis screening programmes in distant communities characterized by difficult access to antenatal services and infrequent clinical follow-up visits.

Point-of-care tests for diagnosing infections in the developing world.

Infectious diseases continue to cause an enormous burden of death and disability in developing countries. Increasing access to appropriate treatment for infectious diseases could have a major impact on disease burden. Some common infections can be managed syndromically without the need for diagnostic tests, but this is not appropriate for many infectious diseases, in which a positive diagnostic test is needed before treatment can be given. Since many people in developing countries do not have access to laboratory services, diagnosis depends on the availability of point of care (POC) tests. Historically there has been little investment in POC tests for diseases that are common in developing countries, but that is now changing. Lack of regulation of diagnostic tests in many countries has resulted in the widespread use of sub-standard POC tests, especially for malaria, making it difficult for manufacturers of reliable POC tests to compete. In recent years increased investment, technological advances, and greater awareness about the importance of reliable diagnostic tests has resulted in rapid progress. Rapid, reliable and affordable POC tests, requiring no equipment and minimal training, are now available for HIV infection, syphilis and malaria, but POC tests for other infections are urgently needed. Many countries do not have established criteria for licensing and introducing new diagnostic tests, and many clinicians in developing countries have become disillusioned with diagnostic tests and prefer to rely on clinical judgment. Continuing advocacy and training in the use of POC tests are needed, and systems for quality control of POC tests need to be developed if they are to achieve their maximum potential.