Dik Habbema

Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics

Objective: To understand the changing impact of herpes simplex 2 (HSV-2) and other sexually transmitted infections (STIs) on HIV incidence over time in four sub-Saharan African cities, using simulation models. Methods: An individual-based stochastic model was fitted to demographic, behavioural and epidemiological data from cross-sectional population-based surveys in four African cities (Kisumu, Kenya; Ndola, Zambia; Yaoundé, Cameroon; and Cotonou, Benin) in 1997. To estimate the proportion of new HIV infections attributable to HSV-2 and other STIs over time, HIV incidence in the fitted model was compared with that in model scenarios in which the cofactor effect of the STIs on HIV susceptibility and infectivity were removed 5, 10, 15, 20 and 25 years into the simulated HIV epidemics. Results: The proportion of incident HIV attributable to HSV-2 infection (the model estimated population attributable fraction (PAFM)) increased with maturity of the HIV epidemic. In the different cities, the PAFM was 8–31% 5 years into the epidemic, but rose to 35–48% 15 years after the introduction of HIV. In contrast, the proportion of incident HIV attributable to chancroid decreased over time with strongest effects five years after HIV introduction, falling to no effect 15 years after. Sensitivity analyses showed that, in the model, recurrent HSV-2 ulcers had more of an impact on HIV incidence than did primary HSV-2 ulcers, and that the effect of HSV-2 on HIV infectivity may be more important for HIV spread than the effect on HIV susceptibility, assuming that HSV-2 has similar cofactor effects on HIV susceptibility and infectivity. The overall impact of other curable STIs on HIV spread (syphilis, gonorrhoea and chlamydia) remained relatively constant over time. Conclusions: Although HSV-2 appears to have a limited impact on HIV incidence in the early stages of sub-Saharan African HIV epidemics when the epidemic is concentrated in core groups, it has an increasingly large impact as the epidemic progresses. In generalised HIV epidemics where control programmes for curable STIs are already in place, interventions against HSV-2 may have a key role in HIV prevention.

Monitoring a national cancer prevention program: Successful changes in cervical cancer screening in the netherlands

The success of screening, an important cancer prevention tool, depends on the quality and efficiency of protocols and guidelines for screening and follow‐up. However, even centrally organized screening programs such as the Dutch cervical screening program occasionally show problems in performance. To improve this program, the screening scheme, follow‐up, administration and financing protocols and guidelines were thoroughly changed in 1996. This study evaluates the consequences for the performance of the national program. Five‐year coverage rate, the proportion of screened women sent to follow‐up, follow‐up compliance and duration, and the yearly number of Pap smears before and after the changes in 1996 were compared. Five‐year coverage increased substantially in the added target age groups (30–34, and 54–60 years); in the old target age group (35–53 years) it remained around 80%. The percentage of screened women sent to follow‐up decreased from almost 19–3% per screening round, due to a more restrictive use of the Pap 2 classification, and an evidence‐based cessation of follow‐up of negative smears without endocervical cells. Follow‐up compliance has improved, and the average time until a woman is either referred or rejoins the regular screening schedule, has become shorter. The total number of smears, a strong determinant of screening costs, has decreased by 20% primarily due to the changed follow‐up recommendations. In conclusion, the 1996 changes in protocols and guidelines, and their implementation have increased coverage and efficiency, and decreased the screening‐induced negative side effects.

Predictors for biopsy outcome in the European Randomized Study of Screening for Prostate Cancer (Rotterdam region)

In the European Randomized Study of Screening for Prostate Cancer (ERSPC, Rotterdam region), men aged 55–74 years are screened for prostate cancer by prostate‐specific antigen (PSA) sampling, digital rectal examination (DRE), and transrectal ultrasound investigation (TRUS). All men with a PSA ≥4 ng/ml and/or a suspicious DRE and/or a suspicious TRUS are biopsied.

Model-based evaluation of single-round mass treatment of sexually transmitted diseases for HIV control in a rural African population.

Objectives:To compare the impact of single-round mass treatment of sexually transmitted diseases (STD), sustained syndromic treatment and their combination on the incidence of HIV in rural Africa. Methods:We studied the effects of STD interventions by stochastic simulation using the model STDSIM. Parameters were fitted using data from a trial of improved STD treatment services in Mwanza, Tanzania. Effectiveness was assessed by comparing the prevalences of gonorrhoea, chlamydia, syphilis and chancroid, and the incidence of HIV, in the general adult population in simulations with and without intervention. Results:Single-round mass treatment was projected to achieve an immediate, substantial reduction in STD prevalences, which would return to baseline levels over 5–10 years. The effect on syphilis was somewhat larger if participants cured of latent syphilis were not immediately susceptible to re-infection. At 80% coverage, the model projected a reduction in cumulative HIV incidence over 2 years of 36%. A similar impact was achieved if treatment of syphilis was excluded from the intervention or confined to those in the infectious stages. In comparison with sustained syndromic treatment, single-round mass treatment had a greater short-term impact on HIV (36 versus 30% over 2 years), but a smaller long-term impact (24 versus 62% over 10 years). Mass treatment combined with improved treatment services led to a rapid and sustained fall in HIV incidence (57% over 2 years; 70% over 10 years). Conclusions:In populations in which STD control can reduce HIV incidence, mass treatment may, in the short run, have an impact comparable to sustained syndromic treatment. Mass treatment combined with sustained syndromic treatment may be particularly effective.

African Programme for Onchocerciasis Control 1995–2015: Model-Estimated Health Impact and Cost

Background Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. Methods and Findings With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US

Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening

257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US

Diagnostic Yield Improves With Collection of 2 Samples in Fecal Immunochemical Test Screening Without Affecting Attendance

221 million. Conclusions Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.

Heart transplantation in the Netherlands; costs, effects and scenarios☆

Objective Colorectal cancer screening by means of faecal immunochemical tests (FITs) requires successive screening rounds for an optimal preventive effect. However, data on the influence of the length of the screening interval on participation and diagnostic yield are lacking. Repeated FIT screening was therefore performed in a population-based trial comparing various repeat intervals. Design 7501 Dutch individuals aged 50–74 years were randomly selected and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration ≥50 ng/ml, corresponding to 10 μg Hb/g faeces) with intervals of 1 (group I), 2 (group II) or 3 years (group III). Results In group I, participation was 64.7% in the first screening round and 63.2% in the second. The corresponding percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%. Triennial screening resulted in a higher participation rate in the second screening round compared with annual screening (p=0.04). The overall positivity rate in the second screening round was significantly lower compared with the first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on interval length (p=0.23). Similarly, the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not depend on interval length (p=0.62). The positive predictive value of the FIT did not significantly change over time (41% vs 33%; p=0.07). Conclusion The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1–3 years. Furthermore, there is a stable and acceptably high participation in the second screening round. This implies that screening intervals can be tailored to local resources.

Fecal Occult Blood Testing When Colonoscopy Capacity is Limited

BACKGROUND & AIMS The fecal immunochemical test (FIT) is superior to the guaiac-based fecal occult blood test in detecting neoplasia. There are not much data on the optimal number of FITs to perform. We conducted a population-based trial to determine attendance and diagnostic yield of 1- and 2-sample FIT screening. METHODS The study included 2 randomly selected groups of subjects aged 50-74 years (1-sample FIT, n=5007; 2-sample FIT, n=3197). The 2-sample group was instructed to collect fecal samples on 2 consecutive days. Subjects were referred for colonoscopy when at least 1 sample tested positive (≥50 ng hemoglobin/mL). RESULTS Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95% confidence interval, 59.6%-63.0%; P=.84). In the 1-sample group 8.1% tested positive, and in the 2-sample group 12.8% had at least 1 positive test outcome and 5.0% had 2 positive test outcomes (P<.05). When the mean from both test results in the 2-sample group was used, 10.1% had a positive test outcome (P<.05). The detection rates for advanced neoplasia were 3.1% in the 1-sample group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5% when both test results were positive, and 3.7% among subjects with the mean from both test results being positive. CONCLUSIONS There is no difference in attendance for subjects offered 1- or 2-sample FIT screening. The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities, rather than varying the cut-off value in a 1-sample strategy.

No difference in HIV incidence and sexual behaviour between out-migrants and residents in rural Manicaland, Zimbabwe.

The Dutch heart transplantation programme was subjected to a prospective economic evaluation and costs and effects with or without such programme were estimated. The no-programme estimates were derived from pretransplant patient data. Future projections of both options were based on micro-stimulation using additional data on severe heart disease prevalence and on multi-organ donation. Costs per life year gained are estimated at NLG 57,650 (quality adjusted: NLG 71,900). Sensitivity analysis showed these results to depend highly on long term incidence of costs and on quality of life after transplantation.