Options for change in the Australian cervical cancer screening program in context of HPV detection and vaccination

Introduction:
Cervical cancer screening has been implemented for over a decade in Australia and has significantly reduced the mortality and morbidity of the disease. The emergence of new technologies for cervical cancer, such as the Human Papillomavirus (HPV) vaccine and DNA testing has encouraged debate regarding the effective use of resources in cervical cancer prevention. The present study evaluates the cost-effectiveness, from a health sector perspective, of various screening strategies in the era of these new technologies.

Methods:
A stochastic epidemiological model using a discrete event and continuous algorithm was developed to describe the natural history of cervical cancer. By allowing one member of the cohort into the model at a time, this micro-simulation model encompasses the characteristics of heterogeneity and can track individual life histories. To evaluate the cost-effectiveness of the HPV vaccine a Markov model was built to simulate the effect on the incidence of HPV and subsequent cervical cancer. A number of proposed screening strategies were evaluated with the stochastic model for the application of HPV DNA testing, with changes in the screening interval and target population. Health outcomes were measured by Disability-Adjusted Life-Years (DALYs), adjusted for application within an evaluation setting (i.e. the mortality component of the DALY was adjusted by a disability weight when early mortality due to cervical cancer is avoided). Costs in complying with the Australian updated guidelines were assessed by pathway analysis to estimate the resources associated with cervical cancer and its pre-cancerous lesion treatment. Sensitivity analyses were performed to investigate the key parameters that influenced the cost-effectiveness results.

Results:
Current practice has already brought huge health gain by preventing more than 4,000 deaths and saving more than 86,000 life-years in a cohort of a million women. Any of the alternative screening strategies alter the total amount of health gain by a small margin compared to current practice. The results of incremental analyses of the alternative screening strategies compared to current practice suggest the adoption of the HPV DNA test as a primary screening tool every 3 years commencing at age 18, or the combined pap smear/HPV test every 3 years commencing at age 25, are more costly than current practice but with reasonable ICERs (AUD$1,810 per DALY and AUD$18,600 per DALY respectively). Delaying commencement of Pap test screening to age 25 is less costly than current practice, but involves considerable health loss. The sensitivity analysis shows, however, that the screening test accuracy has a significant impact on these conclusions. Threshold analysis indicates that a sensitivity ranging from 0.80 to 0.86 for the combined test in women younger than 30 is required to produce an acceptable incremental cost-effectiveness ratio.

Conclusions:
The adoption of HPV and combined test with an extended screening interval is more costly but affordable, resulting in reasonable ICERs. They appear good value for money for the Australian health care system, but need more information on test accuracy to make an informed decision. Potential screening policy change under current Australian HPV Vaccination Program is current work in progress. A Markov model is built to simulate the effect on the incidence of HPV and subsequent cervical cancer. Adoption of HPV DNA test as a primary screening tool in the context of HPV vaccination is under evaluation.

Handover of patient information from the crisis assessment and treatment team to the inpatient psychiatric unit.

Handover, or the communication of patient information between clinicians, is a fundamental component of health care. Psychiatric settings are dynamic environments relying on timely and accurate communication to plan care and manage risk. Crisis assessment and treatment teams are the primary interface between community and mental health services in many Australian and international health services, facilitating access to assessment, treatment, and admission to hospital. No previous research has investigated the handover between crisis assessment and treatment teams and inpatient psychiatric units, despite the importance of handover to care planning. The aim of the present study was to identify the nature and types of information transferred during these handovers, and to explore how these guides initial care planning. An observational, exploratory study design was used. A 20-item handover observation tool was used to observe 19 occasions of handover. A prospective audit was undertaken on clinical documentation arising from the admission. Clinical information, including psychiatric history and mental state, were handed over consistently; however, information about consumer preferences was reported less consistently. The present study identified a lack of attention to consumer preferences at handover, despite the current focus on recovery-oriented models for mental health care, and the centrality of respecting consumer preferences within the recovery paradigm.

Testing for error correction in panel data

This paper proposes new error correction-based cointegration tests for panel data. The limiting distributions of the tests are derived and critical values provided. Our simulation results suggest that the tests have good small-sample properties with small size distortions and high power relative to other popular residual-based panel cointegration tests. In our empirical application, we present evidence suggesting that international healthcare expenditures and GDP are cointegrated once the possibility of an invalid common factor restriction has been accounted for. © 2007 Blackwell Publishing Ltd.

Detection of IgG in cerebrospinal fluid for diagnosis of neurocysticercosis: evaluation of saline and SDS extracts from Taenia solium and Taenia crassiceps metacestodes by ELISA and immunoblot assay

We compared saline (S) and sodium dodecyl sulphate (SDS) extracts from Taenia solium (homologous species - HO) and Taenia crassiceps (heterologous species - HE) metacestodes in order to detect Ige by ELISA and immunoblot assay (IBA) in cerebrospinal fluid (CSF) for the diagnosis of human neurocysticercosis (NC). CSF samples were obtained from 93 patients. of these, 40 had NC, five had a diagnosis of probable NC, nine had central nervous system schistosomiasis or strongyloidiasis and 39 had other neurological alterations. Samples were analysed by ELISA and the results were compared with IBA in all samples with confirmed and probable NC diagnosis, in all samples with other central nervous system parasitic infection, and in 10 of those with another neurological alterations. ELISA sensitivity was 100%, 85%, 95% and 87.5% for the S-HO, S-HE, SDS-HO and SDS-HE extracts, respectively, and ELISA specificity was 100% for S-HO, S-HE, SDS-HO extracts and 97.9% for SDS-HE antigen. Immunodominant peptides detected by IBA were, by decreasing percentage of recognition: 64-68 and 45 kDa for S-HO; 108-114, 92-95, 64-68, 83 and 88 kDa for S-HE; 64-68, 108-114, 77 and 86 kDa for SDS-HO; and 108-114, 88 and 92-95 kDa for SDS-HE. Overall the homologous antigenic extracts showed higher sensitivity than the heterologous extracts in the diagnosis of NC in CSF samples. The heterologous extracts contained most of the immunodominant peptides presented in the homologous extracts, which are recognized by Ige antibodies in CSF samples.

Application of synthetic peptides to the diagnosis of neurocysticercosis

We tested the possible diagnostic utility of five Taenia saginata oncosphere-derived synthetic peptides in T. solium neurocysticercosis (NC). The five peptides correspond to protein sequences with high antigenic indexes that were cloned from a T. saginata oncosphere cDNA library. The test samples consisted of cerebrospinal fluid (CSF) samples randomly collected from patients referred from Mexican and Brazilian neurological institutes. Indirect enzyme-linked immunosorbent assays (ELISA) were carried out with the peptides either unconjugated or coupled to carrier proteins, and were compared with results obtained using T. solium cyst fluid as a positive control. For active inflammatory NC, the higher sensibility (93%) and specificity (85%) was obtained with peptides HP6-2 and Ts45W-1, respectively, coupled to ovalbumin, in both Mexican and Brazilian patients. Examining the results of the individual peptide assays in combination, in some instances, improved the sensitivity to 100%.

Plasmodium vivax Duffy binding protein: baseline antibody responses and parasite polymorphisms in a well-consolidated settlement of the Amazon Region

Objective To investigate risk factors associated with the acquisition of antibodies against Plasmodium vivax Duffy binding protein (PvDBP) a leading malaria vaccine candidate in a well-consolidated agricultural settlement of the Brazilian Amazon Region and to determine the sequence diversity of the PvDBP ligand domain (DBPII) within the local malaria parasite population. Methods Demographic, epidemiological and clinical data were collected from 541 volunteers using a structured questionnaire. Malaria parasites were detected by conventional microscopy and PCR, and blood collection was used for antibody assays and molecular characterisation of DBPII. Results The frequency of malaria infection was 7% (6% for P. vivax and 1% for P. falciparum), with malaria cases clustered near mosquito breeding sites. Nearly 50% of settlers had anti-PvDBP IgG antibodies, as detected by enzyme-linked immunosorbent assay (ELISA) with subjects age being the only strong predictor of seropositivity to PvDBP. Unexpectedly, low levels of DBPII diversity were found within the local malaria parasites, suggesting the existence of low gene flow between P. vivax populations, probably due to the relative isolation of the studied settlement. Conclusion The recognition of PvDBP by a significant proportion of the community, associated with low levels of DBPII diversity among local P. vivax, reinforces the variety of malaria transmission patterns in communities from frontier settlements. Such studies should provide baseline information for antimalarial vaccines now in development.

Clusters of leprosy transmission and of late diagnosis in a highly endemic area in Brazil: focus on different spatial analysis approaches

Objective The Brazilian National Hansens Disease Control Program recently identified clusters with high disease transmission. Herein, we present different spatial analytical approaches to define highly vulnerable areas in one of these clusters. Method The study area included 373 municipalities in the four Brazilian states Maranha o, Para ', Tocantins and Piaui '. Spatial analysis was based on municipalities as the observation unit, considering the following disease indicators: (i) rate of new cases / 100 000 population, (ii) rate of cases < 15 years / 100 000 population, (iii) new cases with grade-2 disability / 100 000 population and (iv) proportion of new cases with grade-2 disabilities. We performed descriptive spatial analysis, local empirical Bayesian analysis and spatial scan statistic. Results A total of 254 (68.0%) municipalities were classified as hyperendemic (mean annual detection rates > 40 cases / 100 000 inhabitants). There was a concentration of municipalities with higher detection rates in Para ' and in the center of Maranha o. Spatial scan statistic identified 23 likely clusters of new leprosy case detection rates, most of them localized in these two states. These clusters included only 32% of the total population, but 55.4% of new leprosy cases. We also identified 16 significant clusters for the detection rate < 15 years and 11 likely clusters of new cases with grade-2. Several clusters of new cases with grade-2 / population overlap with those of new cases detection and detection of children < 15 years of age. The proportion of new cases with grade-2 did not reveal any significant clusters. Conclusions Several municipality clusters for high leprosy transmission and late diagnosis were identified in an endemic area using different statistical approaches. Spatial scan statistic is adequate to validate and confirm high-risk leprosy areas for transmission and late diagnosis, identified using descriptive spatial analysis and using local empirical Bayesian method. National and State leprosy control programs urgently need to intensify control actions in these highly vulnerable municipalities.

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe, North-east Brazil

Objectives To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. Methods Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. Results Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.48.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. Conclusions The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.

Antiparasitical chemotherapy in Chagas' disease cardiomyopathy: current evidence

Chronic chagasic cardiomyopathy affects 20% of Chagas disease patients. At present, Chagas disease chemotherapy uses nitrofurans, benznidazole (Rochagan (R), Rodanil (R), Roche) or nifurtimox (Lampit (R), Bayer). Treatment during acute and recent chronic phases in childhood effects 71.5% and 57.6%, respectively, of parasitological cure. However, in clinical trials during the late chronic phase, only 5.9% of parasitological cure were achieved. This review focuses on the benefit from aetiological treatment to avoid, stop or revert myocarditis. Divergent data gathered from clinical practice are not convincing to support prescription of aetiological treatment as routine for indeterminate and cardiac chronic patients.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

OBJECTIVES: Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. METHODS: A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2-4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). RESULTS: There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). CONCLUSIONS: If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.

Growth response to antiretroviral treatment in HIV-infected children: a cohort study from Lilongwe, Malawi

Objective  Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. Methods  All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. Results  A total of 497 children started ART and were followed for 972 person-years. Median age (interquartile range; IQR) was 8 years (4–11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from −2.1 (−2.7 to −1.3) and −2.6 (−3.6 to −1.8) to −1.4 (−2.1 to −0.8) and −1.8 (−2.4 to −1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions  Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.

Mortality after failure of antiretroviral therapy in sub-Saharan Africa

Objective  To assess the outcome of patients who experienced treatment failure with antiretrovirals in sub-Saharan Africa. Methods  Analysis of 11 antiretroviral therapy (ART) programmes in sub-Saharan Africa. World Health Organization (WHO) criteria were used to define treatment failure. All ART-naive patients aged ≥16 who started with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and had at least 6 months of follow-up were eligible. For each patient who switched to a second-line regimen, 10 matched patients who remained on a non-failing first-line regimen were selected. Time was measured from the time of switching, from the corresponding time in matched patients, or from the time of treatment failure in patients who remained on a failing regimen. Mortality was analysed using Kaplan–Meier curves and random-effects Cox models. Results  Of 16 591 adult patients starting ART, 382 patients (2.3%) switched to a second-line regimen. Another 323 patients (1.9%) did not switch despite developing immunological or virological failure. Cumulative mortality at 1 year was 4.2% (95% CI 2.2–7.8%) in patients who switched to a second-line regimen and 11.7% (7.3%–18.5%) in patients who remained on a failing first-line regimen, compared to 2.2% (1.6–3.0%) in patients on a non-failing first-line regimen (P < 0.0001). Differences in mortality were not explained by nadir CD4 cell count, age or differential loss to follow up. Conclusions  Many patients who meet criteria for treatment failure do not switch to a second-line regimen and die. There is an urgent need to clarify the reasons why in sub-Saharan Africa many patients remain on failing first-line ART.

Impact of a national HIV voluntary counselling and testing (VCT) campaign on VCT in a rural hospital in Tanzania

To evaluate the impact of a national HIV voluntary counselling and testing (VCT) campaign on presentation to HIV care in a rural population in Tanzania.

Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - The IeDEA Southern Africa Collaboration

Objectives  To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART). Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment. Results  Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008). Conclusion  Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.