Repeating platinum/bevacizumab in recurrent or progressive cervical cancer yields marginal survival benefits

Our objective was to assess overall survival of cervical cancer patients following prior platinum/bevacizumab chemotherapy, comparing retreatment with platinum/bevacizumab with alternative therapies. A retrospective analysis was performed of women who received platinum/bevacizumab (PB) chemotherapy for cervical cancer at Washington University between July 1, 2005 and December 31, 2015. Wilcoxon rank-sum exact test and Fisher's exact test were used to compare the treatment groups, and Kaplan Meier curves were generated. Cox regression analyses were performed, with treatment free interval and prior therapy response included as covariates. Of 84 patients who received PB chemotherapy, 59 (70%) received no second line chemotherapy, as they did not recur, progressed without further chemotherapy, were lost to follow up, or expired. Of the remaining 25 patients, 9 were retreated with the combination of platinum/bevacizumab (PB), 6 were retreated with a platinum regimen without bevacizumab (P), and 10 were retreated with neither (not-P). The only long-term survivor was in the not-P group and was treated with an immunotherapy agent. Median overall survival of all patients was 7.1 months. There was a marginal difference in survival between women in the PB and not-PB groups (11.8 versus 5.7 months; HR 3.02, 95% CI, 0.98–9.28). There was no difference in survival based on platinum interval (HR 0.81; 95% CI, 0.27–2.45). Outcomes are grim for women retreated after platinum/bevacizumab therapy and are only marginally improved by retreatment with a platinum/bevacizumab regimen. Rather than additional PB therapy, women with cervical cancer who recur after platinum/bevacizumab should consider supportive care or clinical trials

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

An approximate threshold condition for a non-autonomous system: an application to a vector-borne infection

A non-autonomous system is proposed to model the seasonal pattern of dengue fever. We found that an approximate threshold condition for infection persistence describes all possible behavior of the system. As far as we know, the kind of analysis here proposed is entirely new. No precise mathematical theorems are demonstrated but we give enough numerical evidence to support the conclusions.Comment: 11 pages and 6 figure

Widefield laser doppler velocimeter: development and theory.

The widefield laser Doppler velocimeter is a new measurement technique that significantly expands the functionality of a traditional scanning system. This new technique allows full-field velocity measurements without scanning, a drawback of traditional measurement techniques. This is particularly important for tests in which the sample is destroyed or the motion of the sample is non-repetitive. The goal of creating ''velocity movies'' was accomplished during the research, and this report describes the current functionality and operation of the system. The mathematical underpinnings and system setup are thoroughly described. Two prototype experiments are then presented to show the practical use of the current system. Details of the corresponding hardware used to collect the data and the associated software to analyze the data are presented

Investigating the blood-host plasticity and dispersal of Anopheles coluzzii using a novel field-based methodology

Background: The biting behaviour and dispersal of insect vectors in the field underlies the transmission of many diseases. Here, a novel collection methodology coupled with the molecular analysis of blood-meal sources and digestion rates is introduced with the aim of aiding the understanding of two critical and relatively understudied mosquito behaviours: plasticity in blood-host choice and vector dispersal. Results: A collection strategy utilising a transect of mosquito traps placed at 50 m intervals allowed the collection of blood-fed Anopheles coluzzii from a malaria-endemic village of southern Ghana where human host availability ranged from zero (a cattle pen), increasing until humans were the dominant host choice (the middle of the village). Blood-meal analysis using PCR showed statistically significant variation in blood-meal origins for mosquitoes collected across the 250 m transect: with decreasing trend in Bovine Blood Index (OR = 0.60 95% CI: 0.49-0.73, P < 0.01) and correspondingly, an increasing trend in Human Blood Index (OR = 1.50 95% CI: 1.05-2.16, P = 0.028) as the transect approached the village. Using qPCR, the host DNA remaining in the blood meal was quantified for field-caught mosquitoes and calibrated according to timed blood digestion in colony mosquitoes. Time since blood meal was consumed and the corresponding distance the vector was caught from its blood-host allowed the estimation of An. coluzzii dispersal rates. Within 7 hours of feeding, mosquitoes typically remained within 50 m of their blood-host but at 60 hours they had dispersed up to 250 m. Conclusions: Using this methodology the remarkably small spatial scale at which An. coluzzii blood-host choice can change was demonstrated. In addition, conducting qPCR on host blood from field-caught mosquitoes and calibrating with timed experiments with colonised mosquitoes presents a novel methodology for investigating the dispersal behaviour of vectors. Future adaptations to this novel method to make it broadly applicable to other types of setting are also discussed.Universiteit Stellenbosch, National Institute for Health Research, National Health and Medical Research Counci

Soroprevalência do parvovírus humano B19 em população de subúrbio no Estado de São Paulo, Brasil

OBJETIVO: Analisar a prevalência de anticorpos IgG ao parvovírus humano B19. MÉTODOS: Estudo transversal em uma comunidade de subúrbio de São Paulo, Brasil, de novembro 1990 a janeiro de 1991. Amostras aleatórias (N=435) e representativas de soro foram coletadas de crianças sadias a partir de 15 dias de idade e de adultos com até 40 anos. Os anticorpos IgG ao parvovírus humano B19 foram detectados pelo teste ELISA. RESULTADOS: A prevalência de anticorpos IgG ao parvovírus B19 foi de 87% dos recém-nascidos. A prevalência de anticorpos IgG de origem materna decaiu exponencialmente até o 19o mês de idade. Baixa prevalência de anticorpos foi observada nos primeiros quatro anos de vida, aumentando até 72% no grupo etário de 31-40 anos. A idade média de aquisição da primeira infecção nesta comunidade é de 21 &plusmn; 7 anos. A idade ótima para se vacinar as crianças desta comunidade com uma vacina hipotética é de um ano de idade. CONCLUSÕES: A prevalência de anticorpos IgG ao parvovírus B19 foi alta entre recém-nascidos e no grupo etário 31-40 anos. A análise por estrutura etária mostrou padrão similar aos estudos prévios relacionados à baixa prevalência de infecção em crianças que aumenta com a idade.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 &plusmn; 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

Cost risk benefit analysis to support chemoprophylaxis policy for travellers to malaria endemic countries

BACKGROUND: In a number of malaria endemic regions, tourists and travellers face a declining risk of travel associated malaria, in part due to successful malaria control. Many millions of visitors to these regions are recommended, via national and international policy, to use chemoprophylaxis which has a well recognized morbidity profile. To evaluate whether current malaria chemo-prophylactic policy for travellers is cost effective when adjusted for endemic transmission risk and duration of exposure. a framework, based on partial cost-benefit analysis was used. METHODS: Using a three component model combining a probability component, a cost component and a malaria risk component, the study estimated health costs avoided through use of chemoprophylaxis and costs of disease prevention (including adverse events and pre-travel advice for visits to five popular high and low malaria endemic regions) and malaria transmission risk using imported malaria cases and numbers of travellers to malarious countries. By calculating the minimal threshold malaria risk below which the economic costs of chemoprophylaxis are greater than the avoided health costs we were able to identify the point at which chemoprophylaxis would be economically rational. RESULTS: The threshold incidence at which malaria chemoprophylaxis policy becomes cost effective for UK travellers is an accumulated risk of 1.13% assuming a given set of cost parameters. The period a travellers need to remain exposed to achieve this accumulated risk varied from 30 to more than 365 days, depending on the regions intensity of malaria transmission. CONCLUSIONS: The cost-benefit analysis identified that chemoprophylaxis use was not a cost-effective policy for travellers to Thailand or the Amazon region of Brazil, but was cost-effective for travel to West Africa and for those staying longer than 45 days in India and Indonesia