The optimal age of vaccination against dengue with an age-dependent biting rate with application to Brazil

In this paper we introduce a single-serotype transmission model, including an age-dependent mosquito biting rate, to nd the optimal vaccination age against dengue in Brazil with Dengvaxia. The optimal vaccination age and minimal lifetime expected risk of hospitalisation are found by adapting a method due to Hethcote [1]. Any number and combination of the four dengue serotypes DENv1-4 is considered. Successful vaccination against a serotype corresponds to a silent infection. The effects of antibody dependent enhancement (ADE) and permanent cross-immunity after two heterologous infections are studied. ADE is assumed to imply risk-free primary infections, while permanent cross-immunity implies risk-free tertiary and quaternary infections. Data from trials of Dengvaxia indicate vaccine efficacy to be age- and serostatus-dependent, and vaccination of seronegative individuals to induce an increased risk of hospitalisation. Some of the scenarios are therefore reconsidered taking these findings into account. The optimal vaccination age is compared to that achievable under the current age-restriction of the vaccine. If vaccination is not considered to induce risk optimal vaccination ages are very low. The assumption of ADE generally leads to a higher optimal vaccination age in this case. For a single stereotype vaccination is not recommended in the case of ADE. Permanent cross-immunity results in a slightly lower optimal vaccination age. If vaccination induces a risk the optimal vaccination ages are much higher, particularly for permanent cross-immunity. ADE has no effect on the optimal vaccination age when permanent cross-immunity is considered, otherwise it leads to a slight increase in optimal vaccination age

A mathematical model for optimizing the indications of liver transplantation in patients with hepatocellular carcinoma

Abstract Background The criteria for organ sharing has developed a system that prioritizes liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) who have the highest risk of wait-list mortality. In some countries this model allows patients only within the Milan Criteria (MC, defined by the presence of a single nodule up to 5 cm, up to three nodules none larger than 3 cm, with no evidence of extrahepatic spread or macrovascular invasion) to be evaluated for liver transplantation. This police implies that some patients with HCC slightly more advanced than those allowed by the current strict selection criteria will be excluded, even though LT for these patients might be associated with acceptable long-term outcomes. Methods We propose a mathematical approach to study the consequences of relaxing the MC for patients with HCC that do not comply with the current rules for inclusion in the transplantation candidate list. We consider overall 5-years survival rates compatible with the ones reported in the literature. We calculate the best strategy that would minimize the total mortality of the affected population, that is, the total number of people in both groups of HCC patients that die after 5 years of the implementation of the strategy, either by post-transplantation death or by death due to the basic HCC. We illustrate the above analysis with a simulation of a theoretical population of 1,500 HCC patients with tumor size exponentially. The parameter λ obtained from the literature was equal to 0.3. As the total number of patients in these real samples was 327 patients, this implied in an average size of 3.3 cm and a 95% confidence interval of [2.9; 3.7]. The total number of available livers to be grafted was assumed to be 500. Results With 1500 patients in the waiting list and 500 grafts available we simulated the total number of deaths in both transplanted and non-transplanted HCC patients after 5 years as a function of the tumor size of transplanted patients. The total number of deaths drops down monotonically with tumor size, reaching a minimum at size equals to 7 cm, increasing from thereafter. With tumor size equals to 10 cm the total mortality is equal to the 5 cm threshold of the Milan criteria. Conclusion We concluded that it is possible to include patients with tumor size up to 10 cm without increasing the total mortality of this population

Age and regional differences in clinical presentation and risk of hospitalization for dengue in Brazil, 2000-2014

OBJECTIVES: Dengue cases range from asymptomatic to severe, eventually leading to hospitalization and death. Timely and appropriate management is critical to reduce morbidity. Since 1980, dengue has spread throughout Brazil, affecting an increasing number of individuals. This paper describes age and regional differences in dengue’s clinical presentation and associated risk of hospitalization based on more than 5 million cases reported to the Brazilian Ministry of Health from 2000-2014. METHODS: We performed a retrospective analysis of ∼5,450,000 dengue cases, relating clinical manifestations and the risk of hospitalization to age, gender, previous infection by dengue, dengue virus serotype, years of formal education, delay to first attendance and the occurrence of dengue during outbreaks and in different Brazilian regions. RESULTS: Complicated forms of dengue occurred more frequently among those younger than 10 years (3.12% vs 1.92%) and those with dengue virus 2 infection (7.65% vs 2.42%), with a delay to first attendance >;2 days (3.18% vs 0.82%) and with ≤4 years of formal education (2.02% vs 1.46%). The risk of hospitalization was higher among those aged 6-10 years old (OR 4.57; 95% CI 1.43-29.96) and those who were infected by dengue virus 2 (OR 6.36; 95% CI 2.52-16.06), who lived in the Northeast region (OR 1.38; 95% CI 1.11-2.10) and who delayed first attendance by >;5 days (composite OR 3.15; 95% CI 1.33-8.9). CONCLUSIONS: In Brazil, the occurrence of severe dengue and related hospitalization is associated with being younger than 10 years old, being infected by dengue virus 2 or 3, living in the Northeast region (the poorest and the second most populated) and delaying first attendance for more than 2 days

Analysis of the optimal vaccination age for dengue in Brazil with a tetravalent dengue vaccine.

In this paper we study a mathematical model to analyse the optimal vaccination age against Dengue in Brazil. Data from Brazil are used to estimate the basic reproduction numbers for each of the four Dengue serotypes and then the optimal vaccination age is calculated using a method due to Hethcote [1]. The vaccine has different efficacies against each serotype. Vaccination that is too early is ineffective as individuals are protected by maternal antibodies but leaving vaccination until later may allow the disease to spread. First of all the optimal vaccination ages are calculated where there is just one serotype in circulation and then when there are multiple serotypes. The calculations are done using data both assuming constant vaccine efficacy and age-dependent vaccine efficacy against a given serotype. The multiple serotype calculations are repeated assuming that the first infection is a risky infection and that it is not (to model Dengue Antibody Enhancement). The calculations are then repeated when any third or fourth Dengue infections are asymptomatic, so that two Dengue infections with different serotypes provide effective permanent immunity. The calculations are also repeated when the age-dependent risk function (fitted to Brazilian data) is hospitalisation from Dengue and when it is mortality due to Dengue. We find a wide variety of optimal vaccination ages depending on both the serotypes in circulation and the assumptions of the model

Modeling the risk of malaria for travelers to areas with stable malaria transmission

BACKGROUND: Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. MATERIALS AND METHODS: A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. RESULTS: The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. CONCLUSIONS: Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions

HPV type infection in different anogenital sites among HIV-positive Brazilian women

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Forecasting versus projection models in epidemiology: the case of the SARS epidemics.

In this work we propose a simple mathematical model for the analysis of the impact of control measures against an emerging infection, namely, the severe acute respiratory syndrome (SARS). The model provides a testable hypothesis by considering a dynamical equation for the contact parameter, which drops exponentially with time, simulating control measures. We discuss the role of modelling in public health and we analyse the distinction between forecasting and projection models as assessing tools for the estimation of the impact of intervention strategies. The model is applied to the communities of Hong Kong and Toronto (Canada) and it mimics those epidemics with fairly good accuracy. The estimated values for the basic reproduction number, R0, were 1.2 for Hong Kong and 1.32 for Toronto (Canada). The model projects that, in the absence of control, the final number of cases would be 320,000 in Hong Kong and 36,900 in Toronto (Canada). In contrast, with control measures, which reduce the contact rate to about 25% of its initial value, the expected final number of cases is reduced to 1778 in Hong Kong and 226 in Toronto (Canada). Although SARS can be a devastating infection, early recognition, prompt isolation, and appropriate precaution measures, can be very effective to limit its spread

Dengue outlook for the World Cup in Brazil

Univ São Paulo, Fac Med, São Paulo, BrazilLondon Sch Hyg & Trop Med, London WC1, EnglandUniv São Paulo, Fac Vet Med, São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, São Paulo, BrazilUmea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, SwedenNanyang Univ, Lee Kong Chian Sch Med, Singapore, SingaporeUniversidade Federal de São Paulo, Paulista Sch Med, São Paulo, BrazilWeb of Scienc