A new delay-SIR model for pulse vaccination

This paper introduces a new model for disease outbreaks. This model describes the disease evolution through a system of nonlinear differential equations with distributed-delay. The main difference between classical SIR-model resides in the fact that the recovery rate of the population is expressed as a distributed-delay term modeling the time spent being sick by infected people. This model is identified to fit realistic measurements which shows the effectiveness of the model. Finally, we develop an optimal campaign vaccination strategy based on recent results on the impulsive control of time-delay systems.     

Optimal Vaccination Policies for an SIR Model with Limited Resources

The purpose of the paper is to use analytical method and optimization tool to suggest a vaccination program intensity for a basic SIR epidemic model with limited resources for vaccination. We show that there are two different scenarios for optimal vaccination strategies, and obtain analytical solutions for the optimal control problem that minimizes the total cost of disease under the assumption of daily vaccine supply being limited. These solutions and their corresponding optimal control policies are derived explicitly in terms of initial conditions, model parameters and resources for vaccination. With sufficient resources, the optimal control strategy is the normal Bang–Bang control. However, with limited resources, the optimal control strategy requires to switch to time-variant vaccination.     

Cost-effectiveness of the national dog rabies prevention and control program in Mexico, 1990–2015

BackgroundRabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990–2015.MethodologyCombining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results.Principal findingsResults suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns.ConclusionsAnnual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective.     

Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology

Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.     

Costs of Illness Due to Cholera, Costs of Immunization and Cost-Effectiveness of an Oral Cholera Mass Vaccination Campaign in Zanzibar

Background

The World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective.

Methodology/Principal Findings

Public and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3).

Conclusions/Significance

Based on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3.     

Modelling cost effectiveness of meningococcal serogroup C conjugate vaccination campaign in England and Wales

ObjectivesTo assess the cost effectiveness of a meningococcal serogroup C conjugate vaccination campaign in 0-17 year olds.DesignCost effectiveness analysis from the perspective of the healthcare provider.SettingEngland and Wales.ResultsIn 1998-9, immediately before the introduction of meningococcal C vaccination, the burden of serogroup C disease was considerable, with an estimated 1137 cases in people aged 0-17 years and at least 72 deaths. The vaccination campaign is estimated to have cost between £126m ($180m, €207m) and £241m ($343m, €395m), depending on the price of the vaccine. Under base case assumptions the cost per life year saved from the vaccination campaign is estimated to be £6259. School based vaccination was more cost effective than general practice based vaccination because of lower delivery costs. Immunisation of infants aged under 1 year was the least cost effective component of the campaign because, although this maximises the life years gained, the three dose schedule required is more expensive than other methods of delivery. Estimates of the cost per life year saved were sensitive to assumptions on the future incidence of disease and the case fatality ratio.ConclusionsMeningococcal C vaccination is likely to be more cost effective in all age groups when the incidence of disease is high. It is also more cost effective when given to children aged 1-4 (by general practitioners) and to children and young people aged 5-17 years at school than when administered to infants under 12 months of age or young people aged 16-17 years who are not at school.

What is already known on this topic

The burden of group C meningococcal disease in England and Wales in the late 1990s was considerableIn November 1999 the United Kingdom was the first country to introduce mass vaccination against group C meningococcal diseaseThere are no published economic evaluations of the vaccination campaign

What this study adds

This economic evaluation supports the introduction of the meningococcal C vaccineSchool based vaccination is more cost effective than routine vaccination of infants because delivery costs are lower and fewer doses are required     

Using Mobile Health (mHealth) and Geospatial Mapping Technology in a Mass Campaign for Reactive Oral Cholera Vaccination in Rural Haiti

Background

In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities.

Methods

Data were collected using 7-inch tablets. Teams pre-registered and distributed vaccine cards with unique barcodes to vaccine-eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-fi to a web-hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-loaded on tablets to autopopulate the electronic form. Nightly analysis of the day''s community coverage informed the following day''s vaccination strategy. We generated case-finding reports allowing us to identify those who had not yet been vaccinated.

Results

During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-educated staff.

Conclusion

The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives.     

Feasibility of oral rabies vaccination campaigns of young foxes (<Emphasis Type="Italic">Vulpes vulpes</Emphasis>) against rabies in summer

Oral vaccination of foxes (Vulpes vulpes) against rabies has been shown to be highly effective. Several baiting strategies to increase vaccination coverage of the target population have been developed. For example, to increase the vaccination coverage of the young fox population before dispersal an additional summer vaccination campaign has been suggested. The effectiveness of such a campaign was evaluated using field data on home range size and shape of young foxes and a simulation model for aerial bait distribution. The results indicated that the limited ranging behaviour of the young fox population during the summer months severely reduced bait accessibility and consequently such an additional vaccination campaign would be very cost-ineffective.     

Determination of optimal vaccination strategies using an orbital stability threshold from periodically driven systems

We analyse a periodically driven SIR epidemic model for childhood related diseases, where the contact rate and vaccination rate parameters are considered periodic. The aim is to define optimal vaccination strategies for control of childhood related infections. Stability analysis of the uninfected solution is the tool for setting up the control function. The optimal solutions are sought within a set of susceptible population profiles. Our analysis reveals that periodic vaccination strategy hardly contributes to the stability of the uninfected solution if the human residence time (life span) is much larger than the contact rate period. However, if the human residence time and the contact rate periods match, we observe some positive effect of periodic vaccination. Such a vaccination strategy would be useful in the developing world, where human life spans are shorter, or basically in the case of vaccination of livestock or small animals whose life-spans are relatively shorter.     

Immunological effect of Moringa Oleifera leaf extract on vaccinated and non-vaccinated Hubbard chickens experimentally infected with Newcastle virus

In veterinary medicine plant based medicine is achieving a huge importance worldwide. This research was subjected to rectify the hydrophilic Moringa Oleifera alcoholic leaves extract could improve the immune system in vaccinated and non-vaccinated broiler Hubbard chickens experimentally exposed to Newcastle disease (ND) virus. Seventy five chicks with age one day old were splitted randomly into five groups equally in distribution with fifteen chick in each group. Group I was untreated unvaccinated (control negative group) while group IV was infected group with NDV (control positive group). The experimental Groups II and V were given daily oral treatment of hydrophilic alcoholic leaves extract of M. oleifera at 200 mg/kg body weight until day 21 of age while groups III and V were ND vaccinated with La Sota strain of ND vaccines. The four groups (II, III, IV, V) were infected with ND virus velogenic strain (VNDV) on day 21. Following to infection, Monitoring of birds were done daily for clinical signs, postmortem examination, morbidity and mortality. Cellular, humeral immune response and phagocytic activity were evaluated and the data were statistically analyzed using (SPSS). Total and differential cell numbers as well as Haemagglutination inhibition (HI) titre increased in the extract treated and vaccinated group which give total protection against NDV much more than treated and unvaccinated group. As a result it could be recommended to use M. Olifera extract from the first day of rearing in Hubbard chicken with ND vaccination program as a prophylactic treatment in protection of birds against ND infection.     

Application of the GARC Data Logger—a custom-developed data collection device—to capture and monitor mass dog vaccination campaigns in Namibia

Domestic dogs are responsible for 99% of all cases of human rabies and thus, mass dog vaccination has been demonstrated to be the most effective approach towards the elimination of dog-mediated human rabies. Namibia demonstrated the feasibility of this approach by applying government-led strategic rabies vaccination campaigns to reduce both human and dog rabies incidences in the Northern Communal Areas of Namibia since 2016. The lessons learnt using paper-based form for data capturing and management of mass dog vaccination campaign during the pilot and roll out phase of the project (2016–2018) led to the implementation of a simple and accurate data collection tool in the second phase (2019–2022) of the rabies elimination program. In this paper, we describe the implementation of such custom-developed vaccination tracking device, i.e. the Global Alliance for Rabies Control (GARC) Data Logger (GDL), and the integration of the collected data into a website-based rabies surveillance system (Rabies Epidemiological Bulletin—REB) during 2019 and 2020 campaigns. A total of 10,037 dogs and 520 cats were vaccinated during the 2019 campaign and 13,219 dogs and 1,044 cats during the 2020 campaign. The vaccination data were recorded with the GDL and visualized via REB. Subsequent GIS-analysis using gridded population data revealed a suboptimal vaccination coverage in the great majority of grid cells (82%) with a vaccination coverage below 50%. Spatial regression analysis identified the number of schools, estimated human density, and adult dog population were associated with the vaccination performance. However, there was an inverse correlation to human densities. Nonetheless, the use of the GDL improved data capturing and monitoring capacity of the campaign, enabling the Namibian government to improve strategies for the vaccination of at-risk areas towards achieving adequate vaccination coverage which would effectively break the transmission of rabies.     

Optimal control of epidemics with limited resources

We extend the existing work on the time-optimal control of the basic SIR epidemic model with mass action contact rate. Previous results have focused on minimizing an objective function that is a linear combination of the cost associated with using control and either the outbreak size or the infectious burden. We instead, provide analytic solutions for the control that minimizes the outbreak size (or infectious burden) under the assumption that there are limited control resources. We provide optimal control policies for an isolation only model, a vaccination only model and a combined isolation–vaccination model (or mixed model). The optimal policies described here contain many interesting features especially when compared to previous analyses. For example, under certain circumstances the optimal isolation only policy is not unique. Furthermore the optimal mixed policy is not simply a combination of the optimal isolation only policy and the optimal vaccination only policy. The results presented here also highlight a number of areas that warrant further study and emphasize that time-optimal control of the basic SIR model is still not fully understood.     

Domestic dog demographics and estimates of canine vaccination coverage in a rural area of Zambia for the elimination of rabies

BackgroundAn estimated 75% or more of the human rabies cases in Africa occur in rural settings, which underscores the importance of rabies control in these areas. Understanding dog demographics can help design strategies for rabies control and plan and conduct canine mass vaccination campaigns effectively in African countries.Methodology/Principal findingsA cross-sectional survey was conducted to investigate domestic dog demographics in Kalambabakali, in the rural Mazabuka District of Zambia. The population of ownerless dogs and the total achievable vaccination coverage among the total dog population was estimated using the capture-recapture-based Bayesian model by conducting a canine mass vaccination campaign. This study revealed that 29% of the domestic dog population was under one year old, and 57.7% of those were under three months old and thus were not eligible for the canine rabies vaccination in Zambia. The population growth was estimated at 15% per annum based on the cross-sectional household survey. The population of ownerless dogs was estimated to be small, with an ownerless-to-owned-dog ratio of 0.01–0.06 in the target zones. The achieved overall vaccination coverage from the first mass vaccination was estimated 19.8–51.6%. This low coverage was principally attributed to the owners’ lack of information, unavailability, and dog-handling difficulties. The follow-up mass vaccination campaign achieved an overall coverage of 54.8–76.2%.Conclusions/SignificanceThis paper indicates the potential for controlling canine rabies through mass vaccination in rural Zambia. Rabies education and responsible dog ownership are required to achieve high and sustainable vaccination coverage. Our findings also propose including puppies below three months old in the target population for rabies vaccination and emphasize that securing an annual enforcement of canine mass vaccination that reaches 70% coverage in the dog population is necessary to maintain protective herd immunity.     

Risk-Sensitive Optimal Feedback Control Accounts for Sensorimotor Behavior under Uncertainty

Many aspects of human motor behavior can be understood using optimality principles such as optimal feedback control. However, these proposed optimal control models are risk-neutral; that is, they are indifferent to the variability of the movement cost. Here, we propose the use of a risk-sensitive optimal controller that incorporates movement cost variance either as an added cost (risk-averse controller) or as an added value (risk-seeking controller) to model human motor behavior in the face of uncertainty. We use a sensorimotor task to test the hypothesis that subjects are risk-sensitive. Subjects controlled a virtual ball undergoing Brownian motion towards a target. Subjects were required to minimize an explicit cost, in points, that was a combination of the final positional error of the ball and the integrated control cost. By testing subjects on different levels of Brownian motion noise and relative weighting of the position and control cost, we could distinguish between risk-sensitive and risk-neutral control. We show that subjects change their movement strategy pessimistically in the face of increased uncertainty in accord with the predictions of a risk-averse optimal controller. Our results suggest that risk-sensitivity is a fundamental attribute that needs to be incorporated into optimal feedback control models.     

An integral equation model for the control of a smallpox outbreak

An integral equation model of a smallpox epidemic is proposed. The model structures the incidence of infection among the household, the workplace, the wider community and a health-care facility; and incorporates a finite incubation period and plausible infectivity functions. Linearisation of the model is appropriate for small epidemics, and enables analytic expressions to be derived for the basic reproduction number and the size of the epidemic. The effects of control interventions (vaccination, isolation, quarantine and public education) are explored for a smallpox epidemic following an imported case. It is found that the rapid identification and isolation of cases, the quarantine of affected households and a public education campaign to reduce contact would be capable of bringing an epidemic under control. This could be used in conjunction with the vaccination of healthcare workers and contacts. Our results suggest that prior mass vaccination would be an inefficient method of containing an outbreak.     

猪脾转移因子对La Sota株鸡新城疫弱毒疫苗的免疫增强作用

【目的】本文旨在研究猪脾转移因子（TF）对新城疫（ND）病毒弱毒疫苗La Sota株的免疫增强作用及机理,为兽医临床防控提供理论依据。【方法】以4种不同剂量La Sota疫苗株分别单独、与TF联合免疫SPF鸡,14 d后以ND病毒（NDV）参考强毒F₄₈E₉株(10^4.7 ELD₅₀)进行攻毒,采用蛋白质芯片技术测定鸡外周血IL-6、IL-10、IL-16和IL-21浓度,并以血凝抑制（HI）试验和荧光定量RT-PCR方法分别检测鸡ND HI抗体效价和F₄₈E₉株的病毒血症水平。【结果】攻毒保护试验表明,单独免疫10^5.17、10^4.17、10^3.17和10^2.17 EID₅₀剂量时疫苗攻毒保护率分别为100%、55%、0%和0%,半数保护量(PD₅₀)为12 023 EID₅₀;对应剂量联合免疫时疫苗攻...     

A model of bovine tuberculosis control in domesticated cattle herds.

A typical strategy for disease control in domesticated animals involves regular field tests and quarantine of infected herds. This prevents disease spread beyond the herd, while slaughter of diseased animals removes the infection from within the herd. A model of bovine tuberculosis (Tb) control in cattle is examined, which includes ''test and slaughter'' combined with herd isolation and vaccination. Herd status is represented by an integral equation expressing the duration of herd isolation. The current Tb situation in New Zealand is used as an example, and vaccination strategy discussed. Extrapolation of existing management strategies indicate that a vaccine of efficacy greater than 96% would be required, reaching 95% of target Tb levels within six years. These results suggest that a complementary strategy of vaccination and vector control may be more promising than vaccination alone.     

Mass Vaccination with a New,Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

Introduction

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.

Methods

All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.

Results

The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.

Discussion

This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.     

Modeling control of rabies outbreaks in red fox populations to evaluate culling,vaccination, and vaccination combined with fertility control

A predictive model of spread and control of rabies in red fox (Vulpes vulpes) populations was used to evaluate efficacy of culling, oral vaccination, and oral vaccination and fertility control (V + FC) as rabies control strategies. In addition, effects of season, fox population density, and a delay in starting control were modeled. At fox densities of 0.5 fox families/km2 or greater, a single oral vaccination campaign with bait uptake rates of less than 50% resulted in ineffective rabies control. An uptake rate of at least 80% was required to give a better than 80% chance of eliminating rabies. Vaccination was least effective at controlling rabies if applied 1 or 2 mo before the foxes gave birth. Seasonal timing of poison or V + FC had little effect on efficacy, which was always more successful than the oral vaccination alone. The longer the delay between the simulated start of the rabies infection and the application of a single vaccination campaign, the less successful was the control, particularly at the higher fox densities tested. At a fox density of 0.25 families/km2, all the strategies were equally successful at eliminating rabies. At higher fox densities V + FC was slightly less successful than culling, whereas vaccination-only was considerably less successful. The sole use of vaccination is not considered a viable control method for areas with high fox densities. The model suggests that an area of culling centered on the disease focus, plus an outer ring of vaccine or V + FC, could be the best strategy to control a point-source wildlife rabies outbreak.     

Model‐free feedback design for a mixed cancer therapy

In this article, a model‐free feedback control design is proposed for the drug administration in mixed cancer therapy. This strategy is very attractive because of the important issue of parameter uncertainties unavoidable when dealing with biological models. The proposed feedback scheme use past measurements to update an on‐line simplified model. The control design is then based on model predictive control in which a suitable switching is performed between two different cost functions. The effectiveness of the proposed model‐free control strategy is validated using a recently developed model (unknown to the controller) governing the cancer growth on a cells population level under combined immune and chemotherapy and using real human data. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009