Malaria intervention scale-up in Africa : effectiveness predictions for health programme planning tools, based on dynamic transmission modelling

Scale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. Statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the Spectrum health programme planning tool.; The dynamic Plasmodium falciparum transmission model OpenMalaria was used to simulate health effects of scale-up of insecticide-treated net (ITN) usage, indoor residual spraying (IRS), management of uncomplicated malaria cases (CM) and seasonal malaria chemoprophylaxis (SMC) over a 10-year horizon, over a range of settings with stable endemic malaria. Generalized linear regression models (GLMs) were used to summarize determinants of impact across a range of sub-Sahara African settings.; Selected (best) GLMs explained 94-97 % of variation in simulated post-intervention parasite infection prevalence, 86-97 % of variation in case incidence (three age groups, three 3-year horizons), and 74-95 % of variation in malaria mortality. For any given effective population coverage, CM and ITNs were predicted to avert most prevalent infections, cases and deaths, with lower impacts for IRS, and impacts of SMC limited to young children reached. Proportional impacts were larger at lower endemicity, and (except for SMC) largest in low-endemic settings with little seasonality. Incremental health impacts for a given coverage increase started to diminish noticeably at above ~40 % coverage, while in high-endemic settings, CM and ITNs acted in synergy by lowering endemicity. Vector control and CM, by reducing endemicity and acquired immunity, entail a partial rebound in malaria mortality among people above 5 years of age from around 5-7 years following scale-up. SMC does not reduce endemicity, but slightly shifts malaria to older ages by reducing immunity in child cohorts reached.; Health improvements following malaria intervention scale-up vary with endemicity, seasonality, age and time. Statistical models can emulate epidemiological dynamics and inform strategic planning and target setting for malaria control

A critical evaluation of the Beckman Coulter Access hsTnI: analytical performance, reference interval and concordance

We investigated the analytical performance, outlier rate, carryover and reference interval of the Beckman Coulter Access hsTnI in detail and compared it with historical and other commercial assays.We compared the imprecision, detection capability, analytical sensitivity, outlier rate and carryover against two previous Access AccuTnI assay versions. We established the reference interval with stored samples from a previous study and compared the concordances and variances with the Access AccuTnI+3 as well as with two commercial assays.The Access hsTnI had excellent analytical sensitivity with the calibration slope 5.6 times steeper than the Access AccuTnI+3. The detection capability was markedly improved with the SD of the blank 0.18-0.20 ng/L, LoB 0.29-0.33 ng/L and LoD 0.58-0.69 ng/L. All the reference interval samples had a result above the LoB value. At a mean concentration of 2.83 ng/L the SD was 0.28 ng/L (CV 9.8%). Carryover (0.005%) and outlier (0.046%) rates were similar to the Access AccuTnI+3. The combined male and female 99th percentile reference interval was 18.2 ng/L (90% CI 13.2-21.1 ng/L). Concordance amongst the assays was poor with only 16.7%, 19.6% and 15.2% of samples identified by all 4 assays as above the 99th, 97.5th and 95th percentiles. Analytical imprecision was a minor contributor to the observed variances between assays.The Beckman Coulter Access hsTnI assay has excellent analytical sensitivity and precision characteristics close to zero. This allows cTnI measurement in all healthy individuals and the capability to identify numerically small differences between serial samples as statistically significant. Concordance in healthy individuals remains poor amongst assays

Syphilis prevalence trends in adult women in 132 countries - estimations using the Spectrum Sexually Transmitted Infections model.

We estimated national-level trends in the prevalence of probable active syphilis in adult women using the Spectrum Sexually Transmitted Infections (STI) model to inform program planning, target-setting, and progress evaluation in STI control. The model fitted smoothed-splines polynomial regressions to data from antenatal clinic surveys and screening and representative household surveys, adjusted for diagnostic test performance and weighted by national coverage. Eligible countries had ≥1 data point from 2010 or later and ≥3 from 2000 or later from adult populations considered representative of the general female population (pregnant women or community-based studies). Between 2012 and 2016, the prevalence of probable active syphilis in women decreased in 54 (41%) of 132 eligible countries; this decrease was substantive (≥10% proportionally, ≥0.10% percentage-point absolute difference and non-overlapping 95% confidence intervals in 2012 and 2016) in 5 countries. Restricting eligible data to prevalence measurements of dual treponemal and non-treponemal testing limited estimates to 85 countries; of these, 45 countries (53%) showed a decrease. These standardized trend estimates highlight the need for increased investment in national syphilis surveillance and control efforts if the World Health Organization target of a 90% reduction in the incidence of syphilis between 2018 and 2030 is to be met

Rapid amino acid quantitation with pre-column derivatization; ultra-performance reverse phase liquid chromatography and single quadrupole mass spectrometry

Background: We optimized a quantitative amino acid method with pre-column derivatization, norvaline (nva) internal standard and reverse phase ultra-performance liquid chromatography by replacing the ultraviolet detector with a single quadrupole mass spectrometer (MSnva)

Assessment of epidemic projections using recent HIV survey data in South Africa: a validation analysis of ten mathematical models of HIV epidemiology in the antiretroviral therapy era

Background Mathematical models are widely used to simulate the eff ects of interventions to control HIV and to project future epidemiological trends and resource needs. We aimed to validate past model projections against data from a large household survey done in South Africa in 2012. Methods We compared ten model projections of HIV prevalence, HIV incidence, and antiretroviral therapy (ART) coverage for South Africa with estimates from national household survey data from 2012. Model projections for 2012 were made before the publication of the 2012 household survey. We compared adult (age 15–49 years) HIV prevalence in 2012, the change in prevalence between 2008 and 2012, and prevalence, incidence, and ART coverage by sex and by age groups between model projections and the 2012 household survey. Findings All models projected lower prevalence estimates for 2012 than the survey estimate (18·8%), with eight models’ central projections being below the survey 95% CI (17·5–20·3). Eight models projected that HIV prevalence would remain unchanged (n=5) or decline (n=3) between 2008 and 2012, whereas prevalence estimates from the household surveys increased from 16·9% in 2008 to 18·8% in 2012 (diff erence 1·9, 95% CI –0·1 to 3·9). Model projections accurately predicted the 1·6 percentage point prevalence decline (95% CI –0·3 to 3·5) in young adults aged 15–24 years, and the 2·2 percentage point (0·5 to 3·9) increase in those aged 50 years and older. Models accurately represented the number of adults on ART in 2012; six of ten models were within the survey 95% CI of 1·54–2·12 million. However, the diff erential ART coverage between women and men was not fully captured; all model projections of the sex ratio of women to men on ART were lower than the survey estimate of 2·22 (95% CI 1·73–2·71). Interpretation Projections for overall declines in HIV epidemics during the ART era might have been optimistic. Future treatment and HIV prevention needs might be greater than previously forecasted. Additional data about service provision for HIV care could help inform more accurate projections

HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa

Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

BACKGROUND: New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS: We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the$/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia:$1425, India: $1489, Vietnam:$1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS: In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from$237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to$749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to$241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION: Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING: The Bill and Melinda Gates Foundation and World Health Organization

Assessment of epidemic projections using recent HIV survey data in South Africa: A validation analysis of ten mathematical models of HIV epidemiology in the antiretroviral therapy era

Background: Mathematical models are widely used to simulate the effects of interventions to control HIV and to project future epidemiological trends and resource needs. We aimed to validate past model projections against data from a large household survey done in South Africa in 2012. Methods: We compared ten model projections of HIV prevalence, HIV incidence, and antiretroviral therapy (ART) coverage for South Africa with estimates from national household survey data from 2012. Model projections for 2012 were made before the publication of the 2012 household survey. We compared adult (age 15-49 years) HIV prevalence in 2012, the change in prevalence between 2008 and 2012, and prevalence, incidence, and ART coverage by sex and by age groups between model projections and the 2012 household survey. Findings: All models projected lower prevalence estimates for 2012 than the survey estimate (18·8%), with eight models' central projections being below the survey 95% CI (17·5-20·3). Eight models projected that HIV prevalence would remain unchanged (n=5) or decline (n=3) between 2008 and 2012, whereas prevalence estimates from the household surveys increased from 16·9% in 2008 to 18·8% in 2012 (difference 1·9, 95% CI -0·1 to 3·9). Model projections accurately predicted the 1·6 percentage point prevalence decline (95% CI -0·3 to 3·5) in young adults aged 15-24 years, and the 2·2 percentage point (0·5 to 3·9) increase in those aged 50 years and older. Models accurately represented the number of adults on ART in 2012; six of ten models were within the survey 95% CI of 1·54-2·12 million. However, the differential ART coverage between women and men was not fully captured; all model projections of the sex ratio of women to men on ART were lower than the survey estimate of 2·22 (95% CI 1·73-2·71). Interpretation: Projections for overall declines in HIV epidemics during the ART era might have been optimistic. Future treatment and HIV prevention needs might be greater than previously forecasted. Additional data about service provision for HIV care could help inform more accurate projections. Funding: Bill & Melinda Gates Foundation

Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: point

The reliable detection of paraprotein in serum and urine is the primary purpose of electrophoretic procedures in clinical laboratories. Screening immunofixation electrophoresis (sIFE) employs a single application of antisera directed against heavy and light chains that facilitates the detection of paraproteins that migrate in the non-γ region or that are below the detection limit of protein electrophoresis. These paraproteins that are missed by routine electrophoresis occur in up to 27.3% of newly investigated and 13.6% of monitored patients. Small paraproteins missed by conventional electrophoretic techniques are clinically important in the diagnosis and monitoring of malignant plasma and B-cell disorders. The superior diagnostic performance of sIFE makes it suitable as the initial laboratory procedure to investigate paraproteins in complex serum and urine matrices