[Show abstract][Hide abstract] ABSTRACT: Globally, hookworms infect 440 million people in developing countries. Especially children and women of childbearing age are at risk of developing anaemia as a result of infection. To control hookworm infection and disease (i.e. reduce the prevalence of medium and heavy infection to <1 %), the World Health Organization has set the target to provide annual or semi-annual preventive chemotherapy (PC) with albendazole (ALB) or mebendazole (MEB) to at least 75 % of all children and women of childbearing age in endemic areas by 2020. Here, we predict the feasibility of achieving <1 % prevalence of medium and heavy infection, based on simulations with an individual-based model.
We developed WORMSIM, a new generalized individual-based modelling framework for transmission and control of helminths, and quantified it for hookworm transmission based on published data. We simulated the impact of standard and more intense PC strategies on trends in hookworm infection, and explored the potential additional impact of interventions that improve access to water, sanitation, and hygiene (WASH). The individual-based framework allowed us to take account of inter-individual heterogeneities in exposure and contribution to transmission of infection, as well as in participation in successive PC rounds.
We predict that in low and medium endemic areas, current PC strategies (including targeting of WCBA) will achieve control of hookworm infection (i.e. the parasitological target) within 2 years. In highly endemic areas, control can be achieved with semi-annual PC with ALB at 90 % coverage, combined with interventions that reduce host contributions to the environmental reservoir of infection by 50 %. More intense PC strategies (high frequency and coverage) can help speed up control of hookworm infection, and may be necessary in some extremely highly endemic settings, but are not a panacea against systematic non-participation to PC.
Control of hookworm infection by 2020 is feasible with current PC strategies (including targeting of WCBA). In highly endemic areas, PC should be combined with health education and/or WASH interventions.
[Show abstract][Hide abstract] ABSTRACT: Every year more than 200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. WHO has set a target to interrupt the transmission of leprosy globally by 2020. The aim of this study is to investigate whether this target, interpreted as global elimination, is feasible given the current control strategy. We focus on the three most important endemic countries, India, Brazil and Indonesia, which together account for more than 80 % of all newly registered leprosy cases.
We used the existing individual-based model SIMCOLEP to predict future trends of leprosy incidence given the current control strategy in each country. SIMCOLEP simulates the spread of M. leprae in a population that is structured in households. Current control consists of passive and active case detection, and multidrug therapy (MDT). Predictions of leprosy incidence were made for each country as well as for one high-endemic region within each country: Chhattisgarh (India), Pará State (Brazil) and Madura (Indonesia). Data for model quantification came from: National Leprosy Elimination Program (India), SINAN database (Brazil), and Netherlands Leprosy Relief (Indonesia).
Our projections of future leprosy incidence all show a downward trend. In 2020, the country-level leprosy incidence has decreased to 6.2, 6.1 and 3.3 per 100,000 in India, Brazil and Indonesia, respectively, meeting the elimination target of less than 10 per 100,000. However, elimination may not be achieved in time for the high-endemic regions. The leprosy incidence in 2020 is predicted to be 16.2, 21.1 and 19.3 per 100,000 in Chhattisgarh, Pará and Madura, respectively, and the target may only be achieved in another 5 to 10 years.
Our predictions show that although country-level elimination is reached by 2020, leprosy is likely to remain a problem in the high-endemic regions (i.e. states, districts and provinces with multimillion populations), which account for most of the cases in a country.
[Show abstract][Hide abstract] ABSTRACT: Background: The World Health Organization (WHO) has set ambitious targets for the elimination of onchocerciasis by 2020-2025 through mass ivermectin treatment. Two different mathematical models have assessed the feasibility of reaching this goal for different settings and treatment scenarios, namely the individual-based microsimulation model ONCHOSIM and the population-based deterministic model EPIONCHO. In this study, we harmonize some crucial assumptions and compare model predictions on common outputs. Methods: Using a range of initial endemicity levels and treatment scenarios, we compared the models with respect to the following outcomes: 1) model-predicted trends in microfilarial (mf) prevalence and mean mf intensity during 25 years of (annual or biannual) mass ivermectin treatment; 2) treatment duration needed to bring mf prevalence below a provisional operational threshold for treatment interruption (pOTTIS, i.e. 1.4 %), and 3) treatment duration needed to drive the parasite population to local elimination, even in the absence of further interventions. Local elimination was judged by stochastic fade-out in ONCHOSIM and by reaching transmission breakpoints in EPIONCHO. Results: ONCHOSIM and EPIONCHO both predicted that in mesoendemic areas the pOTTIS can be reached with annual treatment, but that this strategy may be insufficient in very highly hyperendemic areas or would require prolonged continuation of treatment. For the lower endemicity levels explored, ONCHOSIM predicted that the time needed to reach the pOTTIS is longer than that needed to drive the parasite population to elimination, whereas for the higher endemicity levels the opposite was true. In EPIONCHO, the pOTTIS was reached consistently sooner than the breakpoint. Conclusions: The operational thresholds proposed by APOC may have to be adjusted to adequately reflect differences in pre-control endemicities. Further comparative modelling work will be conducted to better understand the main causes of differences in model-predicted trends. This is a pre-requisite for guiding elimination programmes in Africa and refining operational criteria for stopping mass treatment.
[Show abstract][Hide abstract] ABSTRACT: Background: HIV and tuberculosis (TB) services are provided free of charge in many sub-Saharan African countries, but patients still incur costs. Methods: Patient-exit interviews were conducted in primary health care clinics in rural South Africa with representative samples of 200 HIV-infected patients enrolled in a pre-antiretroviral treatment (pre- ART) program, 300 patients receiving antiretroviral treatment (ART), and 300 patients receiving TB treatment. For each group, we calculated health expenditures across different spending categories, time spent traveling to and using services, and how patients financed their spending. Associations between patient group and costs were assessed in multivariate regression models. Results: Total monthly health expenditures [1 USD = 7.3 South African Rand (ZAR)] were ZAR 171 [95% confidence interval (CI): 134 to 207] for pre-ART, ZAR 164 (95% CI: 141 to 187) for ART, and ZAR 122 (95% CI: 105 to 140) for TB patients (P = 0.01). Total monthly time costs (in hours) were 3.4 (95% CI: 3.3 to 3.5) for pre-ART, 5.0 (95% CI: 4.7 to 5.3) for ART, and 3.2 (95% CI: 2.9 to 3.4) for TB patients (P < 0.01). Although overall patient costs were similar across groups, pre-ART patients spent on average ZAR 29.2 more on traditional healers and ZAR 25.9 more on chemists and private doctors than ART patients, whereas ART patients spent ZAR 34.0 more than pre-ART patients on transport to clinics (P < 0.05 for all results). Thirty-one percent of pre-ART, 39% of ART, and 41% of TB patients borrowed money or sold assets to finance health care. Conclusions: Patients receiving nominally free care for HIV/TB face large private costs, commonly leading to financial distress. Subsidized transport, fewer clinic visits, and drug pick-up points closer to home could reduce costs for ART patients, potentially improving retention and adherence. Large expenditure on alternative care among pre-ART patients suggests that transitioning patients to ART earlier, as under HIV treatmentas- prevention policies, may not substantially increase patients' financial burden.
[Show abstract][Hide abstract] ABSTRACT: Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasitic infections. In this study, we roughly assessed the additional impact of APOC activities on the burden of the most important off-target infections: soil-transmitted helminthiases (STH; ascariasis, trichuriasis, hookworm, and strongyloidiasis), lymphatic filariasis (LF), and scabies. Based on a literature review, we formulated assumptions about the impact of ivermectin treatment on the disease burden of these off-target infections. Using data on the number of ivermectin treatments in APOC regions and the latest estimates of the burden of disease, we then calculated the impact of APOC activities on off-target infections in terms of disability-adjusted life years (DALYs) averted. We conservatively estimated that between 1995 and 2010, annual ivermectin mass treatment has cumulatively averted about 500 thousand DALYs from co-endemic STH infections, LF, and scabies. This impact comprised approximately an additional 5.5% relative to the total burden averted from onchocerciasis (8.9 million DALYs) and indicates that the overall cost-effectiveness of APOC is even higher than previously reported.
[Show abstract][Hide abstract] ABSTRACT: Background:
Mathematical modelling is used to estimate the effectiveness of HPV vaccination. These estimates depend strongly on herd immunity and thus on naturally acquired immunity, a mechanism of which little is known. We estimated the impact of different vaccination strategies on HPV-16 and HPV-18 transmission and cervical cancer incidence in the Netherlands, considering different acquired immunity mechanisms.
We used the STDSIM microsimulation model, and considered two mechanisms for acquired immunity after infection: (I) full immunity with variable duration; (II) cumulatively decreasing susceptibility to reinfection. Girls aged 13-16 years received vaccination (94.7% efficacy for HPV-16 and 92.3% for HPV-18) during a once-off catch-up campaign with 50% coverage, followed by annual vaccination of 12-year-old girls (60% coverage). Alternative vaccination scenarios included increased coverage, including boys, and lower vaccine efficacy.
HPV-16 incidence reduced by 64% under mechanism I and 75% under mechanism II; HPV-18 incidence reduced by 58% and 73%, respectively, and these reductions lead to 48-56% fewer cervical cancer cases. Increasing coverage can lead to over 96% reduction in HPV incidence. Vaccinating boys reduced incidence by 79-89% for HPV-16 and 83-98% for HPV-18 in women.
Effectiveness estimates of HPV vaccination differ slightly between different acquired immunity mechanisms, yet these differences are unlikely to affect policy decisions. Offering vaccination to boys as well may be considered to further reduce cancer incidence.
[Show abstract][Hide abstract] ABSTRACT: HIV and TB services are provided free-of-charge in many sub-Saharan African countries, but patients still incur costs.
Patient-exit interviews were conducted with a representative sample of 200 HIV-infected patients not yet on ART (pre-ART), 300 ART patients, and 300 TB patients receiving public sector care in rural South Africa. For each group, we calculated health expenditures across different spending categories, time spent traveling to and utilizing services, and how patients financed their spending. Associations between patient group and costs were assessed in multivariate regression models.
Total monthly health expenditures (7.3 South African Rand: 1 USD) were: 171 (95%CI 134-207) for pre-ART, 164 (95%CI 141-187) for ART, and 122 (95%CI 105-140) for TB patients. Total monthly time costs (in hours) were: 3.4 (95%CI 3.3-3.5) for pre-ART, 5.0 (95%CI 4.7-5.3) for ART and 3.2 (95%CI 2.9-3.4) for TB patients. Though costs were similar across groups, pre-ART patients spent significantly more on traditional healers, chemists, and private doctors, while ART and TB patients spent more on transport to clinic visits. 31% of pre-ART, 39% of ART and 41% of TB patients borrowed money or sold assets to finance health costs.
Patients receiving nominally free care for HIV/TB face large private costs. Subsidized transport, fewer clinic visits, and drug pick-up points closer to home could reduce costs for ART patients, potentially improving adherence and retention. Large expenditure on alternative care among pre-ART patients suggests that transitioning patients to ART earlier, as under TASP, may not impose substantial costs on patients.
[Show abstract][Hide abstract] ABSTRACT: Highly pathogenic avian influenza (HPAI) H5N1 has posed a significant threat to both humans and birds, and it has spanned large geographic areas and various ecological systems throughout Asia, Europe and Africa, but especially in mainland China. Great efforts in control and prevention of the disease, including universal vaccination campaigns in poultry and active serological and virological surveillance, have been undertaken in mainland China since the beginning of 2006. In this study, we aim to characterize the spatial and temporal patterns of HPAI H5N1, and identify influencing factors favoring the occurrence of HPAI H5N1 outbreaks in poultry in mainland China. Our study shows that HPAI H5N1 outbreaks took place sporadically after vaccination campaigns in poultry, and mostly occurred in the cold season. The positive tests in routine virological surveillance of HPAI H5N1 virus in chicken, duck, goose as well as environmental samples were mapped to display the potential risk distribution of the virus. Southern China had a higher positive rate than northern China, and positive samples were mostly detected from chickens in the north, while the majority were from duck in the south, and a negative correlation with monthly vaccination rates in domestic poultry was found (R = −0.19, p value = 0.005). Multivariate panel logistic regression identified vaccination rate, interaction between distance to the nearest city and national highway, interaction between distance to the nearest lake and wetland, and density of human population, as well as the autoregressive term in space and time as independent risk factors in the occurrence of HPAI H5N1 outbreaks, based on which a predicted risk map of the disease was derived. Our findings could provide new understanding of the distribution and transmission of HPAI H5N1 in mainland China and could be used to inform targeted surveillance and control efforts in both human and poultry populations to reduce the risk of future infections.
International Journal of Environmental Research and Public Health 05/2015; 12(5-5):5026-5045. DOI:10.3390/ijerph120505026 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Female sex workers (FSWs) are highly vulnerable to HIV but make little use of HIV-related intervention services provided by the Chinese government. Determinants of the low uptake of HIV services by FSWs in Shenzhen, Guangdong province were investigated. Methods: FSWs were recruited by venue-based sampling; 1656 FSWs were interviewed about sociodemographics, behaviours and uptake of HIV-related intervention services. Determinants of no uptake of HIV testing, condom promotion, and peer education were determined through logistic regression. The association between uptake of HIV-related services, condom use and HIV-related knowledge was also assessed. Results: The overall uptake of HIV testing, condom promotion, and peer education by FSWs was 21.5%, 47.8% and 28.0%, respectively. Young age and shorter duration of working in Shenzhen were statistically significantly correlated with no uptake of all three interventions. Uptake of these services was positively associated with consistent condom use and good HIV-related knowledge. Conclusions: The uptake of HIV-related intervention services by FSWs is low in Shenzhen. As their uptake is positively associated with condom use and HIV-related knowledge, it is necessary to intensify promotion of these, focusing on young and recently started FSWs.
Sexual Health 02/2015; 12(3). DOI:10.1071/SH14189 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections.
We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence.
A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18.
Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer.
PLoS ONE 02/2015; 10(2). DOI:10.1371/journal.pone.0116618 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.
[Show abstract][Hide abstract] ABSTRACT: The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.
PLoS ONE 12/2014; 9(12):e115886. DOI:10.1371/journal.pone.0115886 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Men who have sex with men (MSM) are a key population for HIV control and prevention in China. It is difficult to acquire representative samples of this hidden population. Respondent-driven sampling (RDS), based on peer referral, and time-location sampling (TLS) based on random selection of venue-day-time periods, are among the most commonly used sampling methods. However, differences in HIV-related characteristics of MSM recruited by these two methods have not been fully evaluated. We compared sociodemographics, risk behaviors, utilization of HIV-related intervention services, and HIV/syphilis infection rates between samples of 621 RDS MSM and 533 TLS MSM in Shenzhen, China in 2010. We found that the HIV prevalence was comparable in RDS and TLS MSM. TLS recruited larger proportions of more marginalized MSM than RDS: MSM recruited by TLS were older, less educated and more likely to be migrants (without Shenzhen hukou registration), to be non-gay identified and to engage in risky sexual behaviors. On the other hand, MSM recruited by TLS were more likely to have been covered by HIV-related intervention services. To conclude, in Shenzhen, TLS is more effective to reach the marginalized population of MSM. But because TLS can only reach MSM who physically attend venues and HIV-related intervention services are already commonly available at gay venues in Shenzhen, RDS is more informative for allocating prevention efforts than TLS. Furthermore, researchers and public health authorities should take into account the different sample compositions of RDS and TLS and apply sampling methods consistently when evaluating trends over time.
Archives of Sexual Behavior 09/2014; 44(7). DOI:10.1007/s10508-014-0350-y · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage.
We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP.
In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective.
Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets.
The Lancet Global Health 08/2014; 2(1):e23. DOI:10.1016/S2214-109X(13)70172-4 · 10.04 Impact Factor