A general framework to support cost-efficient survey design choices for the control of soil-transmitted helminths when deploying Kato-Katz thick smear

Background To monitor and evaluate soil-transmitted helminth (STH) control programs, the World Health Organization (WHO) recommends screening stools from 250 children, deploying Kato-Katz thick smear (KK). However, it remains unclear whether these recommendations are suffi-cient to make adequate decisions about stopping preventive chemotherapy (PC) (preva-lence of infection &lt;2%) or declaring elimination of STHs as a public health problem (prevalence of moderate-to-heavy intensity (MHI) infections &lt;2%). Methodology We developed a simulation framework to determine the effectiveness and cost of survey designs for decision-making in STH control programs, capturing the operational resources to perform surveys, the variation in egg counts across STH species, across schools, between and within individuals, and between repeated smears. Using this framework and a lot quality assurance sampling approach, we determined the most cost-efficient survey designs (number of schools, subjects, stool samples per subject, and smears per stool sam-ple) for decision-making. Principal findings For all species, employing duplicate KK (sampling 4 to 6 schools and 64 to 70 subjects per school) was the most cost-efficient survey design to assess whether prevalence of any infection intensity was above or under 2%. For prevalence of MHI infections, single KK was the most cost-efficient (sampling 11 to 25 schools and 52 to 84 children per school). Conclusions/Significance KK is valuable for monitoring and evaluation of STH control programs, though we recom-mend deploying a duplicate KK on a single stool sample to stop PC, and a single KK to declare the elimination of STHs as a public health problem.</p

Appropriateness of strategy comparisons in cost-effectiveness analyses of infant pneumococcal vaccination: a systematic review

Objectives: Cost-effectiveness analysis (CEA) is the standard framework for informing the efficient allocation of scarce healthcare resources. The importance of considering all relevant intervention strategies and appropriate incremental comparisons have both long been recognized in CEA. Failure to apply methods correctly can lead to suboptimal policies. Our objective is to assess if CEAs of infant pneumococcal vaccination apply appropriate methods with respect to the completeness of strategies assessed and incremental comparisons between them. Methods: We conducted a systematic search of the PubMed, Scopus, Embase, and Web of Science databases and performed a comparative analysis of the retrieved pneumococcal vaccination CEAs. We checked the appropriateness of the incremental analyses by attempting to replicate the published incremental cost-effectiveness (CE) ratios from the reported costs and health effects. Results: Our search returned twenty-nine eligible articles. Most studies failed to recognize one or more intervention strategies (n = 21). Incremental comparisons were questionable in four CEAs and insufficient reporting of cost and health effect estimates was identified in three studies. Overall, we only found four studies that made appropriate comparisons between all strategies. Lastly, study findings appear to be strongly associated with manufacturer sponsorship. Conclusions: We found considerable scope for improvement regarding strategy comparison in the infant pneumococcal vaccination literature. To prevent overestimation of the CE of new vaccines, we urge greater adherence to existing guidelines recommending that all available strategies are evaluated to capture relevant comparators for CE evaluation. Closer adherence to existing guidelines will generate better evidence, leading to more effective vaccination policies

Assessment of the required performance and the development of corresponding program decision rules for neglected tropical diseases diagnostic tests: Monitoring and evaluation of soil-transmitted helminthiasis control programs as a case study.

Recently, the World Health Organization established the Diagnostic Technical Advisory Group to identify and prioritize diagnostic needs for neglected tropical diseases, and to ultimately describe the minimal and ideal characteristics for new diagnostic tests (the so-called target product profiles (TPPs)). We developed two generic frameworks: one to explore and determine the required sensitivity (probability to correctly detect diseased persons) and specificity (probability to correctly detect persons free of disease), and another one to determine the corresponding samples sizes and the decision rules based on a multi-category lot quality assurance sampling (MC-LQAS) approach that accounts for imperfect tests. We applied both frameworks for monitoring and evaluation of soil-transmitted helminthiasis control programs. Our study indicates that specificity rather than sensitivity will become more important when the program approaches the endgame of elimination and that the requirements for both parameters are inversely correlated, resulting in multiple combinations of sensitivity and specificity that allow for reliable decision making. The MC-LQAS framework highlighted that improving diagnostic performance results in a smaller sample size for the same level of program decision making. In other words, the additional costs per diagnostic tests with improved diagnostic performance may be compensated by lower operational costs in the field. Based on our results we proposed the required minimal and ideal diagnostic sensitivity and specificity for diagnostic tests applied in monitoring and evaluating of soil-transmitted helminthiasis control programs

Impact of Changes in Detection Effort on Control of Visceral Leishmaniasis in the Indian Subcontinent.

BACKGROUND: Control of visceral leishmaniasis (VL) on the Indian subcontinent relies on prompt detection and treatment of symptomatic cases. Detection efforts influence the observed VL incidence and how well it reflects the underlying true incidence. As control targets are defined in terms of observed cases, there is an urgent need to understand how changes in detection delay and population coverage of improved detection affect VL control. METHODS: Using a mathematical model for transmission and control of VL, we predict the impact of reduced detection delays and/or increased population coverage of the detection programs on observed and true VL incidence and mortality. RESULTS: Improved case detection, either by higher coverage or reduced detection delay, causes an initial rise in observed VL incidence before a reduction. Relaxation of improved detection may lead to an apparent temporary (1 year) reduction in VL incidence, but comes with a high risk of resurging infection levels. Duration of symptoms in detected cases shows an unequivocal association with detection effort. CONCLUSIONS: VL incidence on its own is not a reliable indicator of the performance of case detection programs. Duration of symptoms in detected cases can be used as an additional marker of the performance of case detection programs

Antibody and antigen prevalence as indicators of ongoing transmission or elimination of visceral leishmaniasis: a modelling study

Background: Control of visceral leishmaniasis (VL) on the Indian subcontinent has been highly successful. Hopefully, control efforts such as indoor residual spraying and active case detection can be scaled down or even halted over the coming years. We explore how after scale-down, potential recurrence of VL cases may be predicted based on population-based surveys of antibody or antigenaemia prevalence. Methods: Using a stochastic age-structured transmission model of VL, we predicted trends in case incidence and biomarker prevalence over time after scaling down control efforts when the target of three successive years without VL cases has been achieved. Next, we correlated biomarker prevalence with the occurrence of new VL cases within 10 years of scale-down. Results: Occurrence of at least one new VL case was highly correlated with the seroprevalence and antigenaemia prevalence at the moment of scale-down, or one or two years afterwards. Receiver operating characteristic curves indicated that biomarker prevalence in adults provided the most predictive information, and seroprevalence was a more informative predictor of new VL cases than antigenaemia prevalence. Thresholds for biomarker prevalence to predict occurrence of new VL cases with high certainty were robust to variation in pre-control endemicity. Discussion: The risk of recrudescence of VL after scaling down control efforts can be monitored and mitigated by means of population-based surveys. Our findings highlight that rapid point-of-care diagnostic tools to assess (preferably) seroprevalence or (otherwise) antigenaemia in the general population could be a key ingredient of sustainable VL control

Feasibility of eliminating visceral leishmaniasis from the Indian subcontinent: explorations with a set of deterministic age-structured transmission models

textabstractBackground: Visceral leishmaniasis (VL) is a neglected tropical disease transmitted by sandflies. On the Indian subcontinent (ISC), VL is targeted for elimination as a public health problem by 2017. In the context of VL, the elimination target is defined as an annual VL incidence of <1 per 10,000 capita at (sub-)district level. Interventions focus on vector control, surveillance and on diagnosing and treating VL cases. Many endemic areas have not yet achieved optimal control due to logistical, biological as well as technical challenges. We used mathematical modelling to quantify VL transmission dynamics and predict the feasibility of achieving the VL elimination target with current control strategies under varying assumptions about the reservoir of infection in humans. Methods: We developed three deterministic age-structured transmission models with different main reservoirs of infection in humans: asymptomatic infections (model 1), reactivation of infection after initial infection (model 2), and post kala-azar dermal leishmaniasis (PKDL; model 3). For each model, we defined four sub-variants based on different assumptions about the duration of immunity and age-patterns in exposure to sandflies. All 12 model sub-variants were fitted to data from the KalaNet study in Bihar (India) and Nepal, and the best sub-variant was selected per model. Predictions were made for optimal and sub-optimal indoor residual spraying (IRS) effectiveness for three different levels of VL endemicity. Results: Structurally different models explained the KalaNet data equally well. However, the predicted impact of IRS varied substantially between models, such that a conclusion about reaching the VL elimination targets for the ISC heavily depends on assumptions about the main reservoir of infection in humans: asymptomatic cases, recovered (immune) individuals that reactivate, or PKDL cases. Conclusions: Available data on the impact of IRS so far suggest one model is probably closest to reality (model 1). According to this model, elimination of VL (incidence of <1 per 10,000) by 2017 is only feasible in low and medium endemic settings with optimal IRS. In highly endemic settings and settings with sub-optimal IRS, additional interventions will be required

Global Skin Disease Morbidity and Mortality: An Update From the Global Burden of Disease Study 2013.

Importance: Disability secondary to skin conditions is substantial worldwide. The Global Burden of Disease Study 2013 includes estimates of global morbidity and mortality due to skin diseases. Objective: To measure the burden of skin diseases worldwide. Data Sources: For nonfatal estimates, data were found by literature search using PubMed and Google Scholar in English and Spanish for years 1980 through 2013 and by accessing administrative data on hospital inpatient and outpatient episodes. Data for fatal estimates were based on vital registration and verbal autopsy data. Study Selection: Skin disease data were extracted from more than 4000 sources including systematic reviews, surveys, population-based disease registries, hospital inpatient data, outpatient data, cohort studies, and autopsy data. Data metrics included incidence, prevalence, remission, duration, severity, deaths, and mortality risk. Data Extraction and Synthesis: Data were extracted by age, time period, case definitions, and other study characteristics. Data points were modeled with Bayesian meta-regression to generate estimates of morbidity and mortality metrics for skin diseases. All estimates were made with 95% uncertainty intervals. Main Outcomes and Measures: Disability-adjusted life years (DALYs), years lived with disability, and years of life lost from 15 skin conditions in 188 countries. Results: Skin conditions contributed 1.79% to the global burden of disease measured in DALYs from 306 diseases and injuries in 2013. Individual skin diseases varied in size from 0.38% of total burden for dermatitis (atopic, contact, and seborrheic dermatitis), 0.29% for acne vulgaris, 0.19% for psoriasis, 0.19% for urticaria, 0.16% for viral skin diseases, 0.15% for fungal skin diseases, 0.07% for scabies, 0.06% for malignant skin melanoma, 0.05% for pyoderma, 0.04% for cellulitis, 0.03% for keratinocyte carcinoma, 0.03% for decubitus ulcer, and 0.01% for alopecia areata. All other skin and subcutaneous diseases composed 0.12% of total DALYs. Conclusions and Relevance: Skin and subcutaneous diseases were the 18th leading cause of global DALYs in Global Burden of Disease 2013. Excluding mortality, skin diseases were the fourth leading cause of disability worldwide

Cost and cost-effectiveness analysis of mass drug administration compared to school-based targeted preventive chemotherapy for hookworm control in Dak Lak province, Vietnam

Background: School-based targeted preventive chemotherapy (PC), the main strategy for soil-transmitted helminths (STH) control, excludes other at-risk populations including adults and preschool children. Mass drug administration (MDA), covering all age groups, would bring additional health benefits but also requires greater investment. This cost survey and cost-effectiveness analysis compared MDA with school-based targeted PC for STH control in Dak Lak, Vietnam, where STH are endemic. Methods: A cost survey was conducted in 2020 to estimate the total and per person economic and financial cost of each strategy. Monte Carlo simulation accounted for uncertainty in cost estimates. The primary effectiveness measure was hookworm-related disability-adjusted life years (DALYs) averted, and secondary measures were hookworm infection-years averted and moderate-to-heavy intensity hookworm infection-years averted. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of MDA compared to school-based targeted PC using a government payer perspective and a ten-year time horizon. One-way and probabilistic sensitivity analyses (PSA) were performed. Costs are reported in 2020 USD ($). Findings: The economic cost per person was$0.27 for MDA and $0.43 for school-based targeted PC. MDA in Dak Lak will cost$472,000 per year, while school-based targeted PC will cost $117,000. Over 10 years, MDA is estimated to avert an additional 121,465 DALYs; 4,019,262 hookworm infection-years, and 765,844 moderate-to-heavy intensity hookworm infection-years compared to school-based targeted PC. The ICER was$28.55 per DALY averted; $0.87 per hookworm infection-years averted, and$4.54 per moderate-to-heavy intensity hookworm infection-years averted. MDA was cost-effective in all PSA iterations. Interpretation: In areas where hookworm predominates and adults suffer a significant burden of infection, MDA is cost effective compared to school based targeted PC and is the best strategy to achieve global targets. \</p