Estimating the number of unvaccinated Chinese workers against yellow fever in Angola.

BACKGROUND: A yellow fever epidemic occurred in Angola in 2016 with 884 laboratory confirmed cases and 373 deaths. Eleven unvaccinated Chinese nationals working in Angola were also infected and imported the disease to China, thereby presenting the first importation of yellow fever into Asia. In Angola, there are about 259,000 Chinese foreign workers. The fact that 11 unvaccinated Chinese workers acquired yellow fever suggests that many more Chinese workers in Angola were not vaccinated. METHODS: We applied a previously developed model to back-calculate the number of unvaccinated Chinese workers in Angola in order to determine the extent of lack of vaccine coverage. RESULTS: Our models suggest that none of the 259,000 Chinese had been vaccinated, although yellow fever vaccination is mandated by the International Health Regulations. CONCLUSION: Governments around the world including China need to ensure that their citizens obtain YF vaccination when traveling to countries where such vaccines are required in order to prevent the international spread of yellow fever.

On the origin and timing of Zika virus introduction in Brazil.

The timing and origin of Zika virus (ZIKV) introduction in Brazil has been the subject of controversy. Initially, it was assumed that the virus was introduced during the FIFA World Cup in June-July 2014. Then, it was speculated that ZIKV may have been introduced by athletes from French Polynesia (FP) who competed in a canoe race in Rio de Janeiro in August 2014. We attempted to apply mathematical models to determine the most likely time window of ZIKV introduction in Brazil. Given that the timing and origin of ZIKV introduction in Brazil may be a politically sensitive issue, its determination (or the provision of a plausible hypothesis) may help to prevent undeserved blame. We used a simple mathematical model to estimate the force of infection and the corresponding individual probability of being infected with ZIKV in FP. Taking into account the air travel volume from FP to Brazil between October 2013 and March 2014, we estimated the expected number of infected travellers arriving at Brazilian airports during that period. During the period between December 2013 and February 2014, 51 individuals travelled from FP airports to 11 Brazilian cities. Basing on the calculated force of ZIKV infection (the per capita rate of new infections per time unit) and risk of infection (probability of at least one new infection), we estimated that 18 (95% CI 12-22) individuals who arrived in seven of the evaluated cities were infected. When basic ZIKV reproduction numbers greater than one were assumed in the seven evaluated cities, ZIKV could have been introduced in any one of the cities. Based on the force of infection in FP, basic reproduction ZIKV number in selected Brazilian cities, and estimated travel volume, we concluded that ZIKV was most likely introduced and established in Brazil by infected travellers arriving from FP in the period between October 2013 and March 2014, which was prior to the two aforementioned sporting events.

Magnitude and frequency variations of vector-borne infection outbreaks using the Ross-Macdonald model: explaining and predicting outbreaks of dengue fever.

The classical Ross-Macdonald model is often utilized to model vector-borne infections; however, this model fails on several fronts. First, using measured (or estimated) parameters, which values are accepted from the literature, the model predicts a much greater number of cases than what is usually observed. Second, the model predicts a single large outbreak that is followed by decades of much smaller outbreaks, which is not consistent with what is observed. Usually towns or cities report a number of recurrences for many years, even when environmental changes cannot explain the disappearance of the infection between the peaks. In this paper, we continue to examine the pitfalls in modelling this class of infections, and explain that, if properly used, the Ross-Macdonald model works and can be used to understand the patterns of epidemics and even, to some extent, be used to make predictions. We model several outbreaks of dengue fever and show that the variable pattern of yearly recurrence (or its absence) can be understood and explained by a simple Ross-Macdonald model modified to take into account human movement across a range of neighbourhoods within a city. In addition, we analyse the effect of seasonal variations in the parameters that determine the number, longevity and biting behaviour of mosquitoes. Based on the size of the first outbreak, we show that it is possible to estimate the proportion of the remaining susceptible individuals and to predict the likelihood and magnitude of the eventual subsequent outbreaks. This approach is described based on actual dengue outbreaks with different recurrence patterns from some Brazilian regions.

Interpretations and pitfalls in modelling vector-transmitted infections.

In this paper we propose a debate on the role of mathematical models in evaluating control strategies for vector-borne infections. Mathematical models must have their complexity adjusted to their goals, and we have basically two classes of models. At one extreme we have models that are intended to check if our intuition about why a certain phenomenon occurs is correct. At the other extreme, we have models whose goals are to predict future outcomes. These models are necessarily very complex. There are models in between these classes. Here we examine two models, one of each class and study the possible pitfalls that may be incurred. We begin by showing how to simplify the description of a complicated model for a vector-borne infection. Next, we examine one example found in a recent paper that illustrates the dangers of basing control strategies on models without considering their limitations. The model in this paper is of the second class. Following this, we review an interesting paper (a model of the first class) that contains some biological assumptions that are inappropriate for dengue but may apply to other vector-borne infections. In conclusion, we list some misgivings about modelling presented in this paper for debate.

Will people change their vector-control practices in the presence of an imperfect dengue vaccine?

Human behaviours, which are influenced by social, cultural, economic and political factors, can increase or decrease the risk of dengue infection, depending on the relationship with the insect vector. Because no vaccine is currently available, the spread of dengue can only be curtailed by controlling vector populations (Aedes aegypti and others) and by protecting individuals. This study tested the hypothesis that dengue-affected populations are likely to relax their vector-control habits if a potentially protective vaccine becomes available. The hypothesis was tested using two approaches: a mathematical model designed to describe dengue transmission and an empirical field test in which the local population of an endemic area was interviewed about their vector-control habits given the presence of a theoretical vaccine. The model demonstrated that depending on the level of vector-control reduction, there is a threshold in vaccine efficacy below which it is better not to introduce the vaccine. The interview showed that people who were informed that a very effective vaccine is available would reduce their vector-control habits significantly compared to a group that was informed that the vaccine is not very effective.

Dengue infections in non-immune travellers to Thailand.

Dengue is the most frequent arboviral disease and is expanding geographically. Dengue is also increasingly being reported in travellers, in particular in travellers to Thailand. However, data to quantify the risk of travellers acquiring dengue when travelling to Thailand are lacking. Using mathematical modelling, we set out to estimate the risk of non-immune persons acquiring dengue when travelling to Thailand. The model is deterministic with stochastic parameters and assumes a Poisson distribution for the mosquitoes' biting rate and a Gamma distribution for the probability of acquiring dengue from an infected mosquito. From the force of infection we calculated the risk of dengue acquisition for travellers to Thailand arriving in a typical year (averaged over a 17-year period) in the high season of transmission. A traveller arriving in the high season of transmission and remaining for 7 days has a risk of acquiring dengue of 0·2% (95% CI 0·16-0·23), whereas the risk for travel of 15 and 30 days' duration is 0·46% (95% CI 0·41-0·50) and 0·81% (95% CI 0·76-0·87), respectively. Our data highlight that the risk of non-immune travellers acquiring dengue in Thailand is substantial. The incidence of 0·81% after a 1-month stay is similar to that reported in prospective seroconversion studies in Israeli travellers to Thailand, highlighting that our models are consistent with actual data. Risk estimates based on mathematical modelling offer more detailed information depending on various travel scenarios, and will help the travel medicine provider give better evidence-based advice for travellers to dengue-endemic countries.

Does anti-hepatitis B virus vaccine make any difference in long-term number of liver transplantation?

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B infection is associated with an increased risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Our aim is to analyze, through a mathematical model, the potential impact of anti-HBV vaccine in the long-term (that is, decades after vaccination) number of LT. METHODS: The model simulated that the prevalence of HBV infection was 0.5% and that approximately 20% of all the liver transplantation carried out in the state of São Paulo are due to HBV infection. RESULTS: The theoretical model suggests that a vaccination program that would cover 80% of the target population would reach a maximum of about 14% reduction in the LT program. CONCLUSION: Increasing the vaccination coverage against HBV in the state of São Paulo would have a relatively low impact on the number of liver transplantation. In addition, this impact would take several decades to materialize due to the long incubation period of liver failure due to HBV.

Nowcasting and forecasting COVID-19 waves: the recursive and stochastic nature of transmission.

We propose a parsimonious, yet effective, susceptible-exposed-infected-removed-type model that incorporates the time change in the transmission and death rates. The model is calibrated by Tikhonov-type regularization from official reports from New York City (NYC), Chicago, the State of São Paulo, in Brazil and British Columbia, in Canada. To forecast, we propose different ways to extend the transmission parameter, considering its estimated values. The forecast accuracy is then evaluated using real data from the above referred places. All the techniques accurately provided forecast scenarios for periods 15 days long. One of the models effectively predicted the magnitude of the four waves of infections in NYC, including the one caused by the Omicron variant for periods of 45 days using out-of-sample data.

Estimation of R0 from the initial phase of an outbreak of a vector-borne infection.

The magnitude of the basic reproduction ratio R(0) of an epidemic can be estimated in several ways, namely, from the final size of the epidemic, from the average age at first infection, or from the initial growth phase of the outbreak. In this paper, we discuss this last method for estimating R(0) for vector-borne infections. Implicit in these models is the assumption that there is an exponential phase of the outbreaks, which implies that in all cases R(0)>1. We demonstrate that an outbreak is possible, even in cases where R(0) is less than one, provided that the vector-to-human component of R(0) is greater than one and that a certain number of infected vectors are introduced into the affected population. This theory is applied to two real epidemiological dengue situations in the southeastern part of Brazil, one where R(0) is less than one, and other one where R(0) is greater than one. In both cases, the model mirrors the real situations with reasonable accuracy.

A hypothesis for the 2007 dengue outbreak in Singapore.

A previous mathematical model explaining dengue in Singapore predicted a reasonable outbreak of about 6500 cases for 2006 and a very mild outbreak with about 2000 cases for 2007. However, only 3051 cases were reported in 2006 while more than 7800 were reported in the first 44 weeks of 2007. We hypothesized that the combination of haze with other local sources of particulate matter had a significant impact on mosquito life expectancy, significantly increasing their mortality rate. To test the hypothesis a mathematical model based on the reproduction number of dengue fever and aimed at comparing the impact of several possible alternative control strategies was proposed. This model also aimed at contributing to the understanding of the causes of dengue resurgence in Singapore in the last decade. The model's simulation demonstrated that an increase in mosquito mortality in 2006 and either a reduction in mortality or an increase in the carrying capacity of mosquitoes in 2007 explained the patterned observed in Singapore. Based on the model's simulation we concluded that the fewer than expected number of dengue cases in Singapore in 2006 was caused by an increase in mosquito mortality due to the disproportionate haze affecting the country that year and that particularly favourable environmental conditions in 2007 propitiated mosquitoes with a lower mortality rate, which explains the greater than expected number of dengue cases in 2007. Whether our hypothesis is plausible or not should be debated further.

Seroepidemiology of Toxoplasma infection in a metropolitan region of Brazil.

Seroprevalence data from a representative population were used to estimate the annual incidence of congenital toxoplasmosis in São Paulo Metropolitan Region (SPMR). Retrospective anti-toxoplasma IgG serological analysis was conducted to determine age-dependent seroprevalence, force of infection, average age of acquisition of infection and curve of decay of maternally derived antibodies. Seroprevalence was used to calculate the number of new infections. Toxoplasmosis in pregnant women was estimated by total number of deliveries in a given year as a proxy for the number of pregnancies per year. Toxoplasma seroprevalence was 64.9% in women of childbearing age. Average age of acquisition of toxoplasmosis was 10.74 years. The estimated annual incidence of congenital toxoplasmosis varied from 9.5 to 10.6/1000 births in the studied period. The toxoplasmosis seroprevalence model allowed a good incidence estimation of congenital disease in SPMR compared to other published data, indicating that this mathematical approach is useful in calculating the potential demand of congenital disease due to Toxoplasma gondii in a given community.

Vaccinating the vampire bat Desmodus rotundus against rabies.

The objective of this study was to extend the previous work of indirect oral rabies immunization of vampire bats (Desmodus rotundus) maintained in captivity, which demonstrated the immunogenicity of the V-RG vaccine (Vaccinia-Rabies Glycoprotein) and indicated that although the results had been encouraging, a new method for concentrating the vaccine should be tested in order to avoid vaccine loss and increase the survival proportion of bats after rabies challenge. In this study, three groups of seven bats each were tested with vaccine concentrated by ultrafiltration through a cellulose membrane. The vaccine was homogenized in Vaseline paste and applied to the back of one vector bat, which was then reintroduced into its group. A dose of 10(5.0) MICLD(50) rabies virus was used by intramuscular route to challenge the bats postvaccination. The survival proportion in the three groups after the challenge was 71.4%, 71.4% and 100%.

Time variation of some selected topics in bioethical publications.

OBJECTIVE: To analyse the time variation of topics in bioethical publications as a proxy of the relative importance. METHODS: We searched the Medline database for bioethics publications using the words "ethics or bioethics", and for 360 specific topics publications, associating Medical Subject Heading topic descriptors to those words. We calculated the ratio of bioethics publications to the total publications of Medline, and the ratio of each topic publications to the total bioethics publications, for five-year intervals, from 1970 to 2004. We calculated the time variation of ratios, dividing the difference between the highest and lowest ratio of each topic by its highest ratio. Four topics were described, selected to illustrate different patterns of variation: "Induced Abortion", "Conflict of Interest", "Acquired Immunodeficiency Syndrome", "Medical Education." RESULTS: The ratio of bioethics publications to total Medline publications increased from 0.003 to 0.012. The variation of the topic's ratios was higher than 0.7 for 68% of the topics. The Induced Abortion ratios decreased from 0.12 to 0.02. Conflict of Interest ratios increased from zero to 0.07. The Acquired Immunodeficiency Syndrome ratios were nearly zero in the first three intervals, had a peak of 0.06 during 1985-9, followed by a decrease to 0.01. Medical Education ratios varied few, from 0.04 to 0.03. CONCLUSIONS: There was an increase of bioethical publications in the Medline database. The topics in bioethics literature have an important time variation. Some factors were suggested to explain this variation: current legal cases, resolution of the issue, saturation of a discussion and epidemiologic importance.

Seroprevalence of human parvovirus B19 in a suburban population in São Paulo, Brazil.

OBJECTIVE: To analyze the prevalence of IgG antibodies to human parvovirus B19. METHODS: Cross-sectional study in a suburban community in São Paulo, Southeastern Brazil, between November 1990 and January 1991. Randomly selected (N=435) representative samples of sera were collected from healthy children older than 15 days old and adults up to 40 years old. IgG antibodies were detected using ELISA. RESULTS: High prevalence of IgG antibodies to B19 parvovirus was found in 87% of newborns. The prevalence of maternally derived IgG antibodies exponentially plunged up to the 19th month of age. Low prevalence of antibodies was found in the first 4 years of life, increasing up to 72% in those aged 31-40 years. It was estimated that the average age of first infection in this population is 21 +/- 7 years old and the optimal age for vaccination with a hypothetical vaccine would be 1 year of age. CONCLUSIONS: Parvovirus B19 IgG antibody prevalence was high in newborns and those aged 31-40 years. The analysis by age groups showed a pattern similar to that found in previous studies, i.e., low prevalence of infection in children that increases with age.

ZikaPLAN: Zika Preparedness Latin American Network.

The ongoing Zika virus (ZIKV) outbreak in Latin America, the Caribbean, and the Pacific Islands has underlined the need for a coordinated research network across the whole region that can respond rapidly to address the current knowledge gaps in Zika and enhance research preparedness beyond Zika. The European Union under its Horizon 2020 Research and Innovation Programme awarded three research consortia to respond to this need. Here we present the ZikaPLAN (Zika Preparedness Latin American Network) consortium. ZikaPLAN combines the strengths of 25 partners in Latin America, North America, Africa, Asia, and various centers in Europe. We will conduct clinical studies to estimate the risk and further define the full spectrum and risk factors of congenital Zika virus syndrome (including neurodevelopmental milestones in the first 3 years of life), delineate neurological complications associated with ZIKV due to direct neuroinvasion and immune-mediated responses in older children and adults, and strengthen surveillance for birth defects and Guillain-Barré Syndrome. Laboratory-based research to unravel neurotropism and investigate the role of sexual transmission, determinants of severe disease, and viral fitness will underpin the clinical studies. Social messaging and engagement with affected communities, as well as development of wearable repellent technologies against Aedes mosquitoes will enhance the impact. Burden of disease studies, data-driven vector control, and vaccine modeling as well as risk assessments on geographic spread of ZIKV will form the foundation for evidence-informed policies. While addressing the research gaps around ZIKV, we will engage in capacity building in laboratory and clinical research, collaborate with existing and new networks to share knowledge, and work with international organizations to tackle regulatory and other bottlenecks and refine research priorities. In this way, we can leverage the ZIKV response toward building a long-term emerging infectious diseases response capacity in the region to address future challenges.

The impact of imperfect vaccines on the evolution of HIV virulence.

A theoretical framework is proposed on which some hypotheses related to the impact of imperfect vaccines on the evolution of HIV virulence can be tested. For this, a linear increase of risk behaviour with vaccine efficacy is assumed. This is based on the hypothesis that people are prone to relax preventive measures by knowing that they and their partners are vaccinated and that this effect is more intense the more effective the vaccine is known to be. An additional, and perhaps more important hypothesis is related to the theoretical possibility that increased risk behaviour of some vaccinated individuals in partially protected populations could act as a selective pressure toward more virulent HIV strains. Those hypotheses were tested by a mathematical model that considers three different HIV strains competing against each other in a population partially protected by imperfect vaccines of distinct efficacies. Simulations of the model demonstrated that, under the above hypotheses, there is a shift in HIV virulence towards more aggressive strains with increase in vaccine efficacy, associated with a marked reduction in the total amount of transmission and, consequently, in the prevalence of HIV. Potential ways for further testing the theory/model and the implications of the results are discussed.

Brain mappings of the arithmetic processing in children and adults.

Despite the increasing number of experimental mapping showing that human arithmetic cognition is supported by widely spread neural circuits; the theoretical reasoning about these data remains mostly metaphorical and guided by a connectionist approach. Although neurons at distinct areas in the brain are assumed to take charge of different duties in the solution of the experimental task, the results are always discussed by hypothesizing some association between the different areas without questioning any difference of behavior at the level of the neurons at each of these areas. Here, the brain is assumed as Distributed Intelligent Processing System (DIPS) formed by collections of loosely interacting specialized agents (neurons), each agent specializing, for example, in data collection (sensors), problem solving (associative neurons), data communication (interneuronal systems) and in acting upon the surrounding environment (motorneurons). A new technique for EEG brain mapping is proposed and used to study arithmetic cognition in elementary school aged children and adults. Factor analysis showed three distinct patterns of neuronal recruitment for arithmetic calculations in all experimental groups which varied according to the type of calculation, age and sex.

Liver transplantation: waiting list dynamics in the state of São Paulo, Brazil.

São Paulo is the first Brazilian state to perform liver transplantation in 1968. Since then the recipient waiting list has increased; now approximately 150 new cases per month are referred to the single list at the central organ procurement organization. Official data have shown 37.3 monthly deaths on the waiting list in the state of São Paulo. The number of liver transplants has increased after the creation of São Paulo transplant notification centers but are insufficient to deal with the increasing waiting list. The aim of this study was to demonstrate the performance of our state liver transplantation program and analyze when the number of liver transplantations will meet our waiting list demand.

Fuzzy logic and measles vaccination: designing a control strategy.

BACKGROUND: The State of São Paulo, the most populous in Brazil, was virtually free of measles from 1987 until the end of 1996 when the number of cases started to rise. It reached alarming numbers in the middle of 1997 and local health authorities decided to implement a mass vaccination campaign. METHODS: Fuzzy Decision Making techniques are applied to the design of the vaccination campaign. RESULTS: The mass vaccination strategy chosen changed the natural course of the epidemic. It had a significant impact on the epidemic in the metropolitan area of São Paulo city, but a second epidemic in the State's interior forced the public health authorities to implement a second mass vaccination campaign 2 months after the first. CONCLUSIONS: Fuzzy Logic techniques are a powerful tool for the design of control strategies against epidemics of infectious diseases.