Search

Abstract Background As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island. Methods We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine rollout. Results C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign. Conclusions Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact.

Abstract Background To calculate hospital surge capacity, achieved via hospital provision interventions implemented for the emergency treatment of coronavirus disease 2019 (COVID-19) and other patients through March to May 2020; to evaluate the conditions for admitting patients for elective surgery under varying admission levels of COVID-19 patients. Methods We analysed National Health Service (NHS) datasets and literature reviews to estimate hospital care capacity before the pandemic (pre-pandemic baseline) and to quantify the impact of interventions (cancellation of elective surgery, field hospitals, use of private hospitals, deployment of former medical staff and deployment of newly qualified medical staff) for treatment of adult COVID-19 patients, focusing on general and acute (G&A) and critical care (CC) beds, staff and ventilators. Results NHS England would not have had sufficient capacity to treat all COVID-19 and other patients in March and April 2020 without the hospital provision interventions, which alleviated significant shortfalls in CC nurses, CC and G&A beds and CC junior doctors. All elective surgery can be conducted at normal pre-pandemic levels provided the other interventions are sustained, but only if the daily number of COVID-19 patients occupying CC beds is not greater than 1550 in the whole of England. If the other interventions are not maintained, then elective surgery can only be conducted if the number of COVID-19 patients occupying CC beds is not greater than 320. However, there is greater national capacity to treat G&A patients: without interventions, it takes almost 10,000 G&A COVID-19 patients before any G&A elective patients would be unable to be accommodated. Conclusions Unless COVID-19 hospitalisations drop to low levels, there is a continued need to enhance critical care capacity in England with field hospitals, use of private hospitals or deployment of former and newly qualified medical staff to allow some or all elective surgery to take place.

Abstract Background After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the USA. This has led to substantial interest in their “test, trace, isolate” strategy. However, it is important to understand the epidemiological peculiarities of South Korea’s outbreak and characterise their response before attempting to emulate these measures elsewhere. Methods We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, R t , using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. Results We estimated that after the initial rapid growth in cases, R t dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64–2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, R t was back below one where it remained until the end of our study (July 13th). Despite less stringent “lockdown” measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. Conclusions Whilst early adoption of testing and contact tracing is likely to be important for South Korea’s successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.

Abstract Background The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. Methods We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. Results We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7–15.7) for AL and 15.2 days (95% CI 12.8–18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7–18.6 days for AL and 10.2–18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated ( 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. Conclusion Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.

Abstract Background The RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5–17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. Work is ongoing to optimise this vaccine, with higher efficacy for a different schedule demonstrated in a phase 2a challenge study. The objective of our study was to investigate the population-level impact of a modified RTS,S/AS01 schedule and dose amount in order to inform the target product profile for a second-generation malaria vaccine. Methods We used a mathematical modelling approach as the basis for our study. We simulated the changing anti-circumsporozoite antibody titre following vaccination and related the titre to vaccine efficacy. We then implemented this efficacy profile within an individual-based model of malaria transmission. We compared initial efficacy, duration and dose timing, and evaluated the potential public health impact of a modified vaccine in children aged 5–17 months, measuring clinical cases averted in children younger than 5 years. Results In the first decade of delivery, initial efficacy was associated with a higher reduction in childhood clinical cases compared to vaccine duration. This effect was more pronounced in high transmission settings and was due to the efficacy benefit occurring in younger ages where disease burden is highest. However, the low initial efficacy and long duration schedule averted more cases across all age cohorts if a longer time horizon was considered. We observed an age-shifting effect due to the changing immunological profile in higher transmission settings, in scenarios where initial efficacy was higher, and the fourth dose administered earlier. Conclusions Our findings indicate that, for an imperfect childhood malaria vaccine with suboptimal efficacy, it may be advantageous to prioritise initial efficacy over duration. We predict that a modified vaccine could outperform the current RTS,S/AS01, although fourth dose timing will affect the age group that derives the greatest benefit. Further, the outcome measure and timeframe over which a vaccine is assessed are important when prioritising vaccine elements. This study provides insight into the most important characteristics of a malaria vaccine for at-risk groups and shows how distinct vaccine properties translate to public health outcomes. These findings may be used to prioritise target product profile elements for second-generation childhood malaria vaccines.