Simulation of the cost-effectiveness of malaria vaccines

<p>Abstract</p> <p>Background</p> <p>A wide range of possible malaria vaccines is being considered and there is a need to identify which vaccines should be prioritized for clinical development. An important element of the information needed for this prioritization is a prediction of the cost-effectiveness of potential vaccines in the transmission settings in which they are likely to be deployed. This analysis needs to consider a range of delivery modalities to ensure that clinical development plans can be aligned with the most appropriate deployment strategies.</p> <p>Methods</p> <p>The simulations are based on a previously published individual-based stochastic model for the natural history and epidemiology of <it>Plasmodium falciparum </it>malaria. Three different vaccine types: pre-erythrocytic vaccines (PEV), blood stage vaccines (BSV), mosquito-stage transmission-blocking vaccines (MSTBV), and combinations of these, are considered each delivered via a range of delivery modalities (Expanded Programme of Immunization – EPI-, EPI with booster, and mass vaccination combined with EPI). The cost-effectiveness ratios presented are calculated for four health outcomes, for assumed vaccine prices of US$2 or US$ 10 per dose, projected over a 10-year period.</p> <p>Results</p> <p>The simulations suggest that PEV will be more cost-effective in low transmission settings, while BSV at higher transmission settings. Combinations of BSV and PEV are more efficient than PEV, especially in moderate to high transmission settings, while compared to BSV they are more cost-effective in moderate to low transmission settings. Combinations of MSTBV and PEV or PEV and BSV improve the effectiveness and the cost-effectiveness compared to PEV and BSV alone only when applied with EPI and mass vaccinations. Adding booster doses to the EPI is unlikely to be a cost-effective alternative to delivering vaccines via the EPI for any vaccine, while mass vaccination improves effectiveness, especially in low transmission settings, and is often a more efficient alternative to the EPI. However, the costs of increasing the coverage of mass vaccination over 50% often exceed the benefits.</p> <p>Conclusion</p> <p>The simulations indicate malaria vaccines might be efficient malaria control interventions, and that both transmission setting and vaccine delivery modality are important to their cost-effectiveness. Alternative vaccine delivery modalities to the EPI may be more efficient than the EPI. Mass vaccination is predicted to provide substantial health benefits at low additional costs, although achieving high coverage rates can lead to substantial incremental costs.</p

Country specific predictions of the cost-effectiveness of malaria vaccine RTS,S/AS01 in endemic Africa

RTS,S/AS01 is a safe and moderately efficacious vaccine considered for implementation in endemic Africa. Model predictions of impact and cost-effectiveness of this new intervention could aid in country adoption decisions.; The impact of RTS,S was assessed in 43 countries using an ensemble of models of Plasmodium falciparum epidemiology. Informed by the 32months follow-up data from the phase 3 trial, vaccine effectiveness was evaluated at country levels of malaria parasite prevalence, coverage of control interventions and immunization. Benefits and costs of the program incremental to routine malaria control were evaluated for a four dose schedule: first dose administered at six months, second and third - before 9months, and fourth dose at 27months of age. Sensitivity analyses around vaccine properties, transmission, and economic inputs were conducted.; If implemented in all 43 countries the vaccine has the potential to avert 123 (117;129) million malaria episodes over the first 10years. Burden averted averages 18,413 (range of country median estimates 156-40,054) DALYs per 100,000 fully vaccinated children with much variation across settings primarily driven by differences in transmission intensity. At a price of $5 per dose program costs average$39.8 per fully vaccinated child with a median cost-effectiveness ratio of $188 (range$78-$22,448) per DALY averted; the ratio is lower by one third -$136 (range $116-$220) - in settings where parasite prevalence in children aged 2-10years is at or above 10%.; RTS,S/AS01has the potential to substantially reduce malaria burden in children across Africa. Conditional on assumptions on price, coverage, and vaccine properties, adding RTS,S to routine malaria control interventions would be highly cost-effective. Implementation decisions will need to further consider feasibility of scaling up existing control programs, and operational constraints in reaching children at risk with the schedule

Optical spectra of the heavy fermion uniaxial ferromagnet UGe2_2

We report a detailed study of UGe$_{2}$ single crystals using infrared reflectivity and spectroscopic ellipsometry. The optical conductivity suggests the presence of a low frequency interband transition and a narrow free-carrier response with strong frequency dependence of the scattering rate and effective mass. We observe sharp changes in the low frequency mass and scattering rate below the upper ferromagnetic transition $T_C = 53 K$. The characteristic changes are exhibited most strongly at an energy scale of around 12 meV (100 cm$^{-1}$). They recover their unrenormalized value above $T_C$ and for $\omega >$ 40 meV. In contrast no sign of an anomaly is seen at the lower transition temperature of unknown nature $T_x \sim$ 30 K, observed in transport and thermodynamic experiments. In the ferromagnetic state we find signatures of a strong coupling to the longitudinal magnetic excitations that have been proposed to mediate unconventional superconductivity in this compound

Acceptability of a prime vendor system in public healthcare facilities in Tanzania

BACKGROUND: Pharmaceutical supply chain management in low- and middle-income countries has received substantial attention to address the shortage of medicines at peripheral facilities. The focus has been on health system interventions, including the establishment of public-private partnerships (PPPs). In 2014, the United Republic of Tanzania began implementing the Jazia prime vendor system (Jazia PVS) with a contracted private wholesale supplier to complement the national medicines supply chain in public facilities. Few studies have investigated the acceptability of such a prime vendor system. This study analyses factors that contributed to the acceptability of Jazia PVS introduced in Tanzania. We used qualitative analytical methods to study experiences of Jazia PVS implementers in 4 districts in mid-2018. METHODS: Data were drawn from 14 focus group discussions (FGDs), 7 group discussions (GDs) and 30 in-depth interviews (IDIs) with a range of actors involved in Jazia PVS. The study analysed 7 acceptability dimensions as defined in the acceptability framework by Sekhon et al. Framework analysis was adopted to summarise the results using a deductive and an inductive approach. RESULTS: The findings show that participants' acceptability of Jazia PVS was influenced by the increased availability of essential medicines at the facilities, higher order fulfilment rates, and timely delivery of the consignment. Furthermore, acceptability was also influenced by the good reputation of the prime vendor, close collaboration with district managers, and participants' understanding that the prime vendor was meant to complement the existing supply chain. Intervention coherence, experienced opportunity cost and intervention burden, affective attitude and self-efficacy were also important in explaining the acceptability of the Jazia PVS. CONCLUSION: In conclusion, the most critical factor contributing to the acceptability of the Jazia PVS was the perceived effectiveness of the system in achieving its intended purpose. Districts purchasing directly from the prime vendor have a policy based on the possibility to increase availability of essential medicines at peripheral facilities in a low income setting; however, it is crucial to select a reputable and competent vendor, as well as to abide by the contractual agreements

Towards a comprehensive simulation model of malaria epidemiology and control

Planning of the control of Plasmodium falciparum malaria leads to a need for models of malaria epidemiology that provide realistic quantitative prediction of likely epidemiological outcomes of a wide range of control strategies. Predictions of the effects of control often ignore medium- and long-term dynamics. The complexities of the Plasmodium life-cycle, and of within-host dynamics, limit the applicability of conventional deterministic malaria models. We use individual-based stochastic simulations of malaria epidemiology to predict the impacts of interventions on infection, morbidity, mortality, health services use and costs. Individual infections are simulated by stochastic series of parasite densities, and naturally acquired immunity acts by reducing densities. Morbidity and mortality risks, and infectiousness to vectors, depend on parasite densities. The simulated infections are nested within simulations of individuals in human populations, and linked to models of interventions and health systems. We use numerous field datasets to optimise parameter estimates. By using a volunteer computing system we obtain the enormous computational power required for model fitting, sensitivity analysis, and exploration of many different intervention strategies. The project thus provides a general platform for comparing, fitting, and evaluating different model structures, and for quantitative prediction of effects of different interventions and integrated control programme

Costing interventions in the field: preliminary cost estimates and lessons learned from an evaluation of community-wide mass drug administration for elimination of soil-transmitted helminths in the DeWorm3 trial

OBJECTIVE: To present a costing study integrated within the DeWorm3 multi-country field trial of community-wide mass drug administration (cMDA) for elimination of soil-transmitted helminths. DESIGN: Tailored data collection instruments covering resource use, expenditure and operational details were developed for each site. These were populated alongside field activities by on-site staff. Data quality control and validation processes were established. Programmed routines were used to clean, standardise and analyse data to derive costs of cMDA and supportive activities. SETTING: Field site and collaborating research institutions. PRIMARY AND SECONDARY OUTCOME MEASURES: A strategy for costing interventions in parallel with field activities was discussed. Interim estimates of cMDA costs obtained with the strategy were presented for one of the trial sites. RESULTS: The study demonstrated that it was both feasible and advantageous to collect data alongside field activities. Practical decisions on implementing the strategy and the trade-offs involved varied by site; trialists and local partners were key to tailoring data collection to the technical and operational realities in the field. The strategy capitalised on the established processes for routine financial reporting at sites, benefitted from high recall and gathered operational insight that facilitated interpretation of the estimates derived. The methodology produced granular costs that aligned with the literature and allowed exploration of relevant scenarios. In the first year of the trial, net of drugs, the incremental financial cost of extending deworming of school-aged children to the whole community in India site averaged US$1.14 (USD, 2018) per person per round. A hypothesised at-scale routine implementation scenario yielded a much lower estimate of US$0.11 per person treated per round. CONCLUSIONS: We showed that costing interventions alongside field activities offers unique opportunities for collecting rich data to inform policy toward optimising health interventions and for facilitating transfer of economic evidence from the field to the programme. TRIAL REGISTRATION NUMBER: NCT03014167; Pre-results

Evidence for strongly coupled charge-density-wave ordering in three-dimensional RE5Ir4Si10 compounds by optical measurements

We report optical spectra of Lu$_5$Ir$_4$Si$_{10}$ and Er$_5$Ir$_4$Si$_{10}$, exhibiting the phenomenon of coexisting superconductivity or antiferromagnetism and charge density wave (CDW) order. We measure the maximum value of the charge density wave gap present on part of the Fermi surface of Lu5Ir4Si10, corresponding to a ratio 2\Delta/k_B T_CDW \approx 10, well above the value in the limit of weak electron-phonon coupling. Strong electron-phonon coupling was confirmed by analyzing the optical conductivity with the Holstein model describing the electron-phonon interactions, indicating the coupling to phonons centered at 30 meV, with a coupling constant \lambda \approx 2.6. Finally we provide evidence that approximately 16 % of the Fermi surface of Lu5Ir4Si10 becomes gapped in the CDW state.Comment: 11 pages, 14 figure