The role of acquired immunity in the spread of human papillomavirus (HPV): Explorations with a microsimulation model

__Background:__ Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. __Methods:__ We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. __Results:__ A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. __Conclusions:__ Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer

Concerted Efforts to Control or Eliminate Neglected Tropical Diseases

Background: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts

The health impact of human papillomavirus vaccination in the situation of primary human papillomavirus screening: A mathematical modeling study

Background Human papillomavirus (HPV) vaccination and the implementation of primary HPV screening in the Netherlands will lead to a lower cervical disease burden. For evaluation and further improvement of prevention, it is important to estimate the magnitude and timing of health benefits of current and alternative vaccination strategies such as vaccination of boys or adults. Methods and findings We evaluated the impact of the current girls-only vaccination program and alternative strategies on cervical disease burden among the first four vaccinated five-year birth cohorts, given the context of primary HPV screening. We integrated the existing microsimulation models STDSIM (HPV transmission model) and MISCAN-Cervix (cervical cancer screening model). Alternative vaccination strategies include: improved vaccination uptake, including routine boys vaccination, and offering adult vaccination at sexual health clinics. Our models show that the current vaccination program is estimated to reduce cervical cancers and cancer deaths by about 35% compared to primary HPV screening in the absence of vaccination. The number needed to vaccinate (NNV) to gain 1 life year is 45. The most efficient alternative vaccination strategies are: 1) improving coverage of girls to 80% (NNV = 42); and 2) routine vaccination for girls and boys at 80% coverage (incremental NNV = 155), with cervical cancer mortality reductions estimated at 50% and 60% respectively. Conclusions While the current program already substantially reduces cervical cancer incidence and mortality, prevention can be further improved by increasing vaccination uptake and extending vaccination to boys. As not all cervical cancer deaths will be pre

How few countries will do? : Comparative survey analysis from a Bayesian perspective

Meuleman and Billiet (2009) have carried out a simulation study aimed at the question how many countries are needed for accurate multilevel SEM estimation in comparative studies. The authors concluded that a sample of 50 to 100 countries is needed for accurate estimation. Recently, Bayesian estimation methods have been introduced in structural equation modeling which should work well with much lower sample sizes. The current study reanalyzes the simulation of Meuleman and Billiet using Bayesian estimation to find the lowest number of countries needed when conducting multilevel SEM. The main result of our simulations is that a sample of about 20 countries is sufficient for accurate Bayesian estimation, which makes multilevel SEM practicable for the number of countries commonly available in large scale comparative surveys

The role of acquired immunity in the spread of human papillomavirus (HPV): explorations with a microsimulation model

Contains fulltext : 154245.PDF (publisher's version ) (Open Access)BACKGROUND: Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. METHODS: We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. RESULTS: A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. CONCLUSIONS: Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer

Early postnatal calcium and phosphorus metabolism in preterm infants

OBJECTIVES: Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake. METHODS: Preterm infants, included on their first day of life, received standard PN, providing a maximum Ca/P intake of 3/1.92 mmol . kg . day on day 3. Ca/P content of formula was 2.5/1.6 mmol/dL, and fortified human milk was 2.4/1.95 mmol/dL. PN supplied 80 IU . kg . day vitD. Formula and fortified human milk contained 200 IU/dL of vitD. During a 5-week period, serum concentrations and urinary excretion of Ca/P were registered and related to the intake of minerals and vitD. RESULTS: During 12 months, 79 infants (mean gestational age 29.8 +/- 2.2 weeks, mean birth weight 1248 +/- 371 g) were included. The recommended intake for minerals was achieved by day 5 and for vitD by 4 weeks. Infants developed hypercalcaemia, hypercalciuria, and hypophosphataemia during the first postnatal week, leading to the additional P supplementation in 49 infants. The renal tubular reabsorption of P was >95% until day 9 but decreased <70% after the second week. Alkaline phosphatase was normal at birth, increased to a maximum of 450 IU/L by day 14, and remained above the normal range for the remaining period. CONCLUSIONS: Parenteral intake of P appeared to be too low, leading to mineral imbalances in the early postnatal period, and vitD intake was also below recommendations

Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation A Randomized Clinical Trial

Contains fulltext : 201191.pdf (publisher's version ) (Open Access