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.

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.

Modelling the cost effectiveness of rapid point of care diagnostic tests for the control of HIV and other sexually transmitted infections among female sex workers.

BACKGROUND: In sub-Saharan Africa, gonococcal and chlamydial infections are usually managed using the syndromic approach. However, many infections are asymptomatic in women, and the syndromic algorithm has poor sensitivity and specificity for infections caused by Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct). Because of this, rapid point of care (POC) tests for Ct/Ng could improve sexually transmitted infection (STI) management in women. This study uses mathematical modelling to estimate the incremental cost effectiveness of using POC tests to diagnose Ng/Ct instead of the current syndromic approach used by the SIDA2 HIV/STI prevention project for female sex workers in Cotonou, Benin. METHODS: A dynamic mathematical model was used with data from Cotonou to estimate the HIV impact of the existing SIDA2 project (1995-8), and to project how impact would change if POC tests had been used. As observed in test evaluations, the POC tests were assumed to have high specificity, but a range of sensitivities. The incremental economic cost effectiveness of using POC tests was modelled using data on intervention costs and an evaluation of an Ng POC test in Cotonou in 2004. All costs were in 2004 US dollars. RESULTS: The model estimated the STI treatment aspect of the intervention averted 18 553 Ng/Ct and 359 HIV infections over 4 years when the syndromic approach was used. In contrast, if Ng/Ct had been diagnosed with a 70-80% sensitive and 95% specific POC test then 24-31% fewer clinic attenders would have been treated, 40-60% more Ng/Ct and HIV infections would have been averted, and the incremental cost effectiveness of using them would have been 107-151 dollars per HIV infection averted if the POC tests cost 2 dollars and 58-81 dollars if they cost 1 dollar. CONCLUSIONS: POC tests can be a cost effective strategy for substantially increasing the impact on HIV transmission, and decreasing the degree of inappropriate treatment of STI treatment interventions that use syndromic management to diagnose Ng/Ct.

Modelling the cost-effectiveness of introducing rapid syphilis tests into an antenatal syphilis screening programme in Mwanza, Tanzania.

OBJECTIVES: A study found screening (with rapid plasma reagin (RPR)) pregnant women for maternal syphilis was cost-effective in Mwanza, Tanzania. Recently, four rapid point-of-care (POC) syphilis tests were evaluated in Mwanza, and found to have reasonable sensitivity/specificity. This analysis estimates the relative cost-effectiveness of using these POC tests in the Mwanza syphilis screening intervention. METHODS: Empirical cost and epidemiological data were used to model the potential benefit of using POC tests instead of RPR. Reductions in costs relating to training, supplies, and equipment were estimated, and any changes in impact due to test sensitivity were included. Additional modelling explored how the results vary with prevalence of past infection, misclassified RPR results, and if not all women return for treatment. RESULTS: The cost-effectiveness of using POC tests is mainly dependent on their cost and sensitivity for high titre active syphilis (HTAS). Savings due to reductions in training and equipment are small. Current POC tests may save more disability-adjusted life years (DALYs) than the RPR test in Mwanza, but the test cost needs to be <0.63 US dollars to be as cost-effective as RPR. However, the cost-effectiveness of the RPR test worsens by 15% if its HTAS sensitivity had been 75% instead of 86%, and by 25-65% if 20-40% of women had not returned for treatment. In such settings, POC tests could improve cost-effectiveness. Lastly, the cost-effectiveness of POC tests is affected little by the prevalence of syphilis, false RPR-positives, and past infections. DISCUSSION: Although the price of most POC tests needs to be reduced to make them as cost-effective as RPR, their simplicity and limited requirements for electricity/equipment suggest their use could improve the coverage of antenatal syphilis screening in developing countries.

A prospective study of Chlamydia pneumoniae infection and risk of MS in two US cohorts.

BACKGROUND: Chlamydia pneumoniae (Cpn) has been proposed as a possible etiologic agent in multiple sclerosis (MS). However, previous studies were cross-sectional and could not assess whether Cpn infection preceded the onset of MS. METHODS: The authors conducted a prospective nested case-control study among 3 million US Army personnel and 121,466 members of the Kaiser Permanente Medical Care Program (KPMCP) cohort. Serum samples collected prior to onset of MS symptoms were available for 83 MS cases in the Army and 46 in the KPMCP cohort. Two controls were matched to each case on age, sex, and date of blood collection. Microimmunofluorescence was used to measure serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody titers to Cpn; IgG titers > or 1:16 were considered positive for past Cpn infection. RESULTS: Seropositivity for Cpn was not significantly associated with risk of MS in either cohort (Army: OR = 1.0; 95% CI 0.6, 1.8; KPMCP: OR = 1.5; 95% CI 0.7, 3.1) or in the pooled analysis (OR = 1.2; 95% CI 0.8, 1.9). Serum levels of anti-Cpn IgG antibody were also not associated with an increased risk of MS in the Army (OR for a fourfold difference in antibody titers = 0.9; 95% CI 0.7, 1.2) or in the pooled analysis (OR = 1.2; 95% CI 0.9, 1.4), but a significant increase in risk was seen in the KPMCP cohort (OR = 1.7; 95% CI 1.2, 2.5). The difference between these results in the Army and the KPMCP cohort was significant (p = 0.01). CONCLUSIONS: Neither Cpn seropositivity nor serum anti-Cpn IgG antibody titers predicted risk of developing MS. However, due to the heterogeneity of results between cohorts, we cannot exclude the possibility that infection with Cpn may modify the risk of MS.

Reproductive-tract infections in women in low-income, low-prevalence situations: assessment of syndromic management in Matlab, Bangladesh.

BACKGROUND: In the control of reproductive-tract infections, including sexually transmitted infections (STIs), in low-income and middle-income countries, WHO recommends syndromic management for individuals with symptoms. This intervention was initially developed in areas where prevalence of such infections is high. We investigated the clinical effectiveness and cost of this approach among a group of women with a low prevalence of infection. METHODS: During a 5-month period, we investigated all women complaining of abnormal vaginal discharge and seeking care at maternal and child health/family-planning centres in Matlab, Bangladesh, for the presence of laboratory-diagnosed reproductive-tract infections and STIs. Syndromic diagnoses made by trained health-care workers were compared with laboratory diagnosis of infection. We then calculated the costs of treating women by means of the recommended WHO algorithm and an adapted algorithm incorporating use of a speculum and simple diagnostic tests. FINDINGS: The prevalence of endogenous infections among 320 women seen was 30%. Cervical infections (Neisseria gonorrhoeae and Chlamydia trachomatis) were found in only three women. The WHO algorithm had a high sensitivity (100%) but a low specificity (zero for bacterial vaginosis, candida, and Trichomonas vaginalis). The speculum-based algorithm had a low sensitivity (between zero and 59%) but a higher specificity (79-97%). Between 36% and 87% of costs would have been spent on uninfected women. INTERPRETATION: The high rate of overtreatment in the population studied carries both financial and social costs--the latter in potentially exposing women misdiagnosed as having an STI to threats of domestic disruption or even violence. We make recommendations for management programmes in areas of low STI prevalence and low income.

PIP: This paper presents a study on the syndromic management of reproductive tract infections among women in low-income and low-prevalence situations. Women complaining of abnormal vaginal discharge and seeking care at health centers in Matlab, Bangladesh, were examined for the presence of laboratory-diagnosed reproductive tract infections and sexually transmitted infections. In the results, 30% of 320 women were diagnosed as having endogenous infections. Overall result of the study revealed a low prevalence of sexually transmitted infections among these women. The WHO algorithm had 100% sensitivity but a low specificity, while the speculum-based algorithm had a low sensitivity (0-59%) but a higher specificity (79-97%). Cost analysis indicated that 87% of expenditure was wasted on overtreatment under the WHO algorithm, while only 36% of expenditure was wasted on overtreatment using the speculum-based algorithm. In conclusion, the development of simple, affordable and effective diagnostic tests should be prioritized by policymakers and public health specialists to ensure the provision of adequate services among the higher risk groups in society.

Pooling of urine specimens for PCR testing: a cost saving strategy for Chlamydia trachomatis control programmes.

OBJECTIVES: To evaluate pooling of first catch urine (FCU) specimens as a cost effective strategy for chlamydia testing. METHODS: Mock specimens were pooled with and without dilution to determine optimal pool size and ease of work flow. The performance of the Amplicor Chlamydia trachomatis PCR assay on pooled specimens was compared with individual testing using 370 FCU specimens from asymptomatic men presenting to an STD clinic. Cost savings associated with pooling were estimated. RESULTS: Using mock specimens, the sensitivity and specificity of the Amplicor PCR assay were not affected by pool sizes of two and five, but at a pool size of 10 decreased sensitivity due to inhibition was observed in one of five mock pools when the pooling method which involved no dilution was used. Archived FCU specimens from a study of 370 asymptomatic men were combined consecutively into 74 pools of five and tested by PCR. Of the 18 pools that contained positive specimens, 17 were PCR positive. Compared with testing FCU specimens individually, pooling resulted in a sensitivity of 95%, specificity of 100%, and a cost savings of 57% based on reduced number of tests required. CONCLUSION: Depending on the prevalence of infection, pooling of FCU specimens for PCR testing may result in cost savings compared with testing specimens individually. Further evaluations to validate this strategy using fresh FCU specimens are needed.

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.