Geostatistical design and analysis for estimating local variations in malaria disease burden

Geostatistical design and analysis methods are increasingly used in disease mapping, particularly in resource-limited settings where uniformly precise mapping may be unrealistically costly and the priority is often to identify critical areas where interventions can have the most health impact. In this thesis, which is based on four papers, we address the problem of geostatistical sampling design. In the first paper, we consider the problem of sampling design for efficient spatial prediction taking account of uncertain covariance structure, in the context of nonadaptive designs. We propose two classes of designs, namely: simple inhibitory and inhibitory plus close pairs. We evaluate the performance of these designs using an average prediction variance criterion and show how the findings are applied to the design of a rolling Malaria Indicator Survey (rMIS) in an ongoing large-scale, five-year malaria transmission reduction project in Malawi. In the second paper, we address the problem of efficient spatial prediction in the context of adaptive geostatistical designs (AGD). We propose two classes of designs based on singleton and batch sampling. We show how our findings inform an AGD of rMIS, in the perimeter of Majete Wildlife Reserve (MWR) in Chikwawa, southern Malawi. The third paper is a commentary on a paper by Ferreira and Gamerman (2015), which addressed the effect of preferential sampling of the locations at which to measure a spatial process. In the fourth paper, we present the first epidemiological field application of AGD sampling in a malaria prevalence survey. We give an in-depth description of the project, the study area and practical implementation of our adaptive sampling strategy. We present prevalence maps for children 6–59 months in MWR perimeter, showing high malaria transmission areas, often called “hotspots”, that could be targeted with interventions

Inhibitory geostatistical designs for spatial prediction taking account of uncertain covariance structure

The problem of choosing spatial sampling designs for investigating an unobserved spatial phenomenon S arises in many contexts, for example, in identifying households to select for a prevalence survey to study disease burden and heterogeneity in a study region D. We studied randomized inhibitory spatial sampling designs to address the problem of spatial prediction while taking account of the need to estimate covariance structure. Two specific classes of design are inhibitory designs and inhibitory designs plus close pairs. In an inhibitory design, any pair of sample locations must be separated by at least an inhibition distance δ. In an inhibitory plus close pairs design, n − k sample locations in an inhibitory design with inhibition distance δ are augmented by k locations each positioned close to one of the randomly selected n − k locations in the inhibitory design, uniformly distributed within a disk of radius ζ. We present simulation results for the Matérn class of covariance structures. When the nugget variance is non-negligible, inhibitory plus close pairs designs demonstrate improved predictive efficiency over designs without close pairs. We illustrate how these findings can be applied to the design of a rolling Malaria Indicator Survey that forms part of an ongoing large-scale, 5-year malaria transmission reduction project in Malawi

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022

Background Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda. Methods A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2–10 years (PfPR 2–10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood methods. District level prevalence estimates adjusted for population are calculated for the years 2000 to 2022. Results A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modeled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region. Conclusions The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data

Variation in excess all-cause mortality by age, sex, and province during the first wave of the COVID-19 pandemic in Italy

Although previous evidence suggests that the infection fatality rate from COVID-19 varies by age and sex, and that transmission intensity varies geographically within countries, no study has yet explored the age-sex-space distribution of excess mortality associated with the COVID pandemic. By applying the principles of small-area estimation to existing model formulations for excess mortality, this study develops a novel method for assessing excess mortality across small populations and assesses the pattern of COVID excess mortality by province, year, week, age group, and sex in Italy from March through May 2020. We estimate that 53,200 excess deaths occurred across Italy during this time period, compared to just 35,500 deaths where COVID-19 was registered as the underlying cause of death. Out of the total excess mortality burden, 97% of excess deaths occurred among adults over age 60, and 68% of excess deaths were concentrated among adults over age 80. The burden of excess mortality was unevenly distributed across the country, with just three of Italy’s 107 provinces accounting for 32% of all excess mortality. This method for estimating excess mortality can be adapted to other countries where COVID-19 diagnostic capacity is still insufficient, and could be incorporated into public health rapid response systems

Elite athletes\u27 perceptions of the effects of illicit drugs use on athletic performance

Objective: To investigate the perceived risks and benefits that elite athletes associate with illicit drugs and their beliefs concerning the effects of recreational drug use on athletic performance.Design: Self-administered survey.Participants: Nine hundred seventy-four elite athletes (mean age, 23 years; range, 18-30 years) were recruited from 8 national sporting organizations in Australia and the Australian Institute of Sport.Interventions: Participants completed a self-administered survey that included questions exploring participants&rsquo; perceptions regarding the effects of illicit drug use on physical performance.Setting: National sporting organization meetings or competitions.Main Outcome Measures: The main outcome measure was risk perception on athletic performance associated with illicit drug use.Results: The majority of athletes believed that illicit drug use would impact negatively on athletic performance. The main perceived effects of illicit drugs on athletic performance were physical and mental functioning. A minority of athletes indicated that drug use would not impact on physical performance when taken during the offseason or in moderation.Conclusions: The main risks perceived in association with illicit drug use were short-term consequences, such as physical and mental functioning, rather than long-term health consequences. The current findings may contribute to the development of harm reduction strategies that communicate drug-related consequences to elite athletes in an appropriate and effective manner.<br /

Geostatistical analysis of Malawi’s changing malaria transmission from 2010 to 2017 [version 1; peer review: awaiting peer review]

Background: The prevalence of malaria infection in time and space provides important information on the likely sub-national epidemiology of malaria burdens and how this has changed following intervention. Model-based geostatitics (MBG) allow national malaria control programmes to leverage multiple data sources to provide predictions of malaria prevalance by district over time. These methods are used to explore the possible changes in malaria prevalance in Malawi from 2010 to 2017. Methods: Plasmodium falciparum parasite prevalence (PfPR) surveys undertaken in Malawi between 2000 and 2017 were assembled. A spatio-temporal geostatistical model was fitted to predict annual malaria risk for children aged 2–10 years (PfPR2–10) at 1×1 km spatial resolutions. Parameter estimation was carried out using the Monte Carlo maximum likelihood methods. Population-adjusted prevalence and populations at risk by district were calculated for 2010 and 2017 to inform malaria control program priority setting. Results: 2,237 surveys at 1,834 communities undertaken between 2000 and 2017 were identified, geo-coded and used within the MBG framework to predict district malaria prevalence properties for 2010 and 2017. Nationally, there was a 47.2% reduction in the mean modelled PfPR2-10 from 29.4% (95% confidence interval (CI) 26.6 to 32.3%) in 2010 to 15.2% (95% CI 13.3 to 18.0%) in 2017. Declining prevalence was not equal across the country, 25 of 27 districts showed a significant decline ranging from a 3.3% reduction to 79% reduction. By 2017, 16% of Malawi’s population still lived in areas that support PfPR2-10 ≥ 25%. Conclusions: Malawi has made substantial progress in reducing the prevalence of malaria over the last seven years. However, Malawi remains in meso-endemic malaria transmission risk. To sustain the gains made and continue reducing the transmission further, universal control interventions need to be maintained at a national level

Access and adequate utilization of malaria control interventions in rural Malawi : A descriptive quantitative study

Background: Despite the availability of cost effective malaria control interventions, such as insecticide-treated bed nets (ITN), diagnosis and effective treatment of malaria, and intermittent preventive treatment during pregnancy (IPTp), the lack of equitable access and coverage affect utilization of these interventions in rural communities. Aggregated rates of access and utilization of malaria interventions in national surveys mask substantial variations in intervention coverage. Utilization of interventions and factors affecting utilization need investigation in rural communities. Methods: One year of quantitative data collected from a rolling Malaria Indicator Survey (April 2015-April 2016) in Chikhwawa District, Malawi, before the ITN distribution campaign, were analysed. Univariate analyses were used to quantify rates of ITN usage, care-seeking for fever in children aged 6-59 months and women aged 15-49 years and IPTp uptake (for women aged 15-49 years with a recent delivery). Results were compared to national survey estimates; factors associated with these outcomes were determined using multivariate regression models. Results: A total of 2046 participants were included from 1328 households; 56.6% were women aged 15-49 years and 43.4% were children aged 6-59 months. Reported ownership of at least one ITN per household and under-five children ITN use the previous night were 35.3 and 33.5% compared to 70.2 and 67.1%, respectively, in the national survey; ITN use was higher in high wealth quintile households than low quintile ones. For participants with recent fever, 37.6 and 19.5% sought care and sought care within 24 h, respectively. Care-seeking was lower for febrile women than febrile children [aOR, 95% CI 0.53 (0.35-0.81)]. Uptake of two and three or more doses of IPTp were 40.6 and 15.0%, respectively, among women with a pregnancy in the last 2 years. Conclusion: To achieve effective malaria control, fine-scale or district-based surveillance should be used to identify and target communities requiring scaling up of interventions. Qualitative research and a participatory community approach should be used to address behavioural factors affecting how people make use of interventions

Malaria Burden Stratification in Malawi- A report of a consultative workshop to inform the 2023-2030 Malawi Malaria Strategic Plan

Background: Malawi's National Malaria Control Programme (NMCP) is developing a new strategic plan for 2023-2030 to combat malaria and recognizes that a blanket approach to malaria interventions is no longer feasible. To inform this new strategy, the NMCP set up a task force comprising 18 members from various sectors, which convened a meeting to stratify the malaria burden in Malawi and recommend interventions for each stratum. Methods: The burden stratification workshop took place from November 29 to December 2, 2022, in Blantyre, Malawi, and collated essential data on malaria burden indicators, such as incidence, prevalence, and mortality. Workshop participants reviewed the malaria burden and intervention coverage data to describe the current status and identified the districts as a appropriate administrative level for stratification and action. Two scenarios were developed for the stratification, based on composites of three variables. Scenario 1 included incidence, prevalence, and under-five all-cause mortality, while Scenario 2 included total malaria cases, prevalence, and under-five all-cause mortality counts. The task force developed four burden strata (highest, high, moderate, and low) for each scenario, resulting in a final list of districts assigned to each stratum. Results: The task force concluded with 10 districts in the highest-burden stratum (Nkhotakota, Salima, Mchinji, Dowa, Ntchisi, Mwanza, Likoma, Lilongwe, Kasungu and Mangochi) 11 districts in the high burden stratum (Chitipa, Rumphi, Nkhata Bay, Dedza, Ntcheu, Neno, Thyolo, Nsanje, Zomba, Mzimba and Mulanje) and seven districts in the moderate burden stratum (Karonga, Chikwawa, Balaka, Machinga, Phalombe, Blantyre, and Chiradzulu). There were no districts in the low-burden stratum. Conclusion: The next steps for the NMCP are to review context-specific issues driving malaria transmission and recommend interventions for each stratum. Overall, this burden stratification workshop provides a critical foundation for developing a successful malaria strategic plan for Malawi

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022 [version 2; peer review: 1 approved, 3 approved with reservations]

Background Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda. Methods A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2–10 years (PfPR 2–10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood method. District-level prevalence estimates adjusted for population are calculated for the years 2000 to 2022. Results A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modelled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region. Conclusions The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale-up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data