Characterizing mobility patterns of forest goers in southern Lao PDR using GPS loggers.

BACKGROUND: In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programmes' elimination efforts. A better understanding of forest-going populations' mobility patterns and risk associated with specific types of forest-going trips is necessary for countries in the GMS to achieve their objective of eliminating malaria by 2030. METHODS: Between March and November 2018, as part of a focal test and treat intervention (FTAT), 2,904 forest-goers were recruited in southern Lao PDR. A subset of forest-goers carried an "i-Got-U" GPS logger for roughly 2 months, configured to collect GPS coordinates every 15 to 30 min. The utilization distribution (UD) surface around each GPS trajectory was used to extract trips to the forest and forest-fringes. Trips with shared mobility characteristics in terms of duration, timing and forest penetration were identified by a hierarchical clustering algorithm. Then, clusters of trips with increased exposure to dominant malaria vectors in the region were further classified as high-risk. Finally, gradient boosting trees were used to assess which of the forest-goers' socio-demographic and behavioural characteristics best predicted their likelihood to engage in such high-risk trips. RESULTS: A total of 122 forest-goers accepted carrying a GPS logger resulting in the collection of 803 trips to the forest or forest-fringes. Six clusters of trips emerged, helping to classify 385 (48%) trips with increased exposure to malaria vectors based on high forest penetration and whether the trip happened overnight. Age, outdoor sleeping structures and number of children were the best predictors of forest-goers' probability of engaging in high-risk trips. The probability of engaging in high-risk trips was high (~ 33%) in all strata of the forest-going population. CONCLUSION: This study characterized the heterogeneity within the mobility patterns of forest-goers and attempted to further segment their role in malaria transmission in southern Lao People's Democratic Republic (PDR). National control programmes across the region can leverage these results to tailor their interventions and messaging to high-risk populations and accelerate malaria elimination.

A quasi-experimental study estimating the impact of long-lasting insecticidal nets with and without piperonyl butoxide on pregnancy outcomes.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed. METHODS: Birth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW; <2500 g) before-and-after the campaign. Poisson regression with robust standard errors modeled campaign effects, adjusting for health facility-level differences, seasonal variation, and time-varying maternal characteristics. Comparisons between PBO and conventional LLINs were estimated using difference-in-differences estimators. RESULTS: ITSAs estimated the campaign was associated with a 26% [95% CI: 7-41] reduction in stillbirth incidence (incidence rate ratio (IRR) = 0.74 [0.59-0.93]) and a 15% [-7, 33] reduction in LBW incidence (IRR=0.85 [0.67-1.07]) over a 9-month period. The effect on stillbirth incidence was greatest for women delivering 7-9 months after the campaign (IRR=0.60 [0.41-0.87]) for whom the LLINs would have covered most of their pregnancy. The IRRs estimated from difference-in-differences analyses comparing PBO to conventional LLINs was 0.78 [95% CI: 0.52, 1.16] for stillbirth incidence and 1.15 [95% CI: 0.87, 1.52] for LBW incidence. CONCLUSIONS: In this region of Uganda, where pyrethroid resistance is high, this study found that a mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, suggesting malaria protection early in pregnancy can have important benefits that are not necessarily realized through antenatal malaria services. Results from the exploratory analyses comparing PBO and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals that crossed the null. Thus, future studies with larger sample sizes are needed.

Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial.

BACKGROUND: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). METHODS: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400. FINDINGS: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported. INTERPRETATION: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria. FUNDING: Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.

Active Case Finding for Malaria: A 3-Year National Evaluation of Optimal Approaches to Detect Infections and Hotspots Through Reactive Case Detection in the Low-transmission Setting of Eswatini.

BACKGROUND: Reactive case detection (RACD) is a widely practiced malaria elimination intervention whereby close contacts of index cases receive malaria testing to inform treatment and other interventions. However, the optimal diagnostic and operational approaches for this resource-intensive strategy are not clear. METHODS: We conducted a 3-year prospective national evaluation of RACD in Eswatini, a malaria elimination setting. Loop-mediated isothermal amplification (LAMP) was compared to traditional rapid diagnostic testing (RDT) for the improved detection of infections and for hotspots (RACD events yielding ≥1 additional infection). The potential for index case-, RACD-, and individual-level factors to improve efficiencies was also evaluated. RESULTS: Among 377 RACD events, 10 890 participants residing within 500 m of index cases were tested. Compared to RDT, LAMP provided a 3-fold and 2.3-fold higher yield to detect infections (1.7% vs 0.6%) and hotspots (29.7% vs 12.7%), respectively. Hotspot detection improved with ≥80% target population coverage and response times within 7 days. Proximity to the index case was associated with a dose-dependent increased infection risk (up to 4-fold). Individual-, index case-, and other RACD-level factors were considered but the simple approach of restricting RACD to a 200-m radius maximized yield and efficiency. CONCLUSIONS: We present the first large-scale national evaluation of optimal RACD approaches from a malaria elimination setting. To inform delivery of antimalarial drugs or other interventions, RACD, when conducted, should utilize more sensitive diagnostics and clear context-specific operational parameters. Future studies of RACD's impact on transmission may still be needed.

Unnatural selection of salmon life histories in a modified riverscape.

Altered river flows and fragmented habitats often simplify riverine communities and favor non-native fishes, but their influence on life-history expression and survival is less clear. Here, we quantified the expression and ultimate success of diverse salmon emigration behaviors in an anthropogenically altered California river system. We analyzed two decades of Chinook salmon monitoring data to explore the influence of regulated flows on juvenile emigration phenology, abundance, and recruitment. We then followed seven cohorts into adulthood using otolith (ear stone) chemical archives to identify patterns in time- and size-selective mortality along the migratory corridor. Suppressed winter flow cues were associated with delayed emigration timing, particularly in warm, dry years, which was also when selection against late migrants was the most extreme. Lower, less variable flows were also associated with reduced juvenile and adult production, highlighting the importance of streamflow for cohort success in these southernmost populations. While most juveniles emigrated from the natal stream as fry or smolts, the survivors were dominated by the rare few that left at intermediate sizes and times, coinciding with managed flows released before extreme summer temperatures. The consistent selection against early (small) and late (large) migrants counters prevailing ecological theory that predicts different traits to be favored under varying environmental conditions. Yet, even with this weakened portfolio, maintaining a broad distribution in migration traits still increased adult production and reduced variance. In years exhibiting large fry pulses, even marginal increases in their survival would have significantly boosted recruitment. However, management actions favoring any single phenotype could have negative evolutionary and demographic consequences, potentially reducing adaptability and population stability. To recover fish populations and support viable fisheries in a warming and increasingly unpredictable climate, coordinating flow and habitat management within and among watersheds will be critical to balance trait optimization versus diversification.

Evaluation of loop-mediated isothermal amplification as a surveillance tool for malaria in reactive case detection moving towards elimination.

BACKGROUND: As malaria transmission decreases, the proportion of infections that are asymptomatic at any given time increases. This poses a challenge for diagnosis as routinely used rapid diagnostic tests (RDTs) miss asymptomatic malaria cases with low parasite densities due to poor sensitivity. Yet, asymptomatic infections can contribute to onward transmission of malaria and therefore act as infectious reservoirs and perpetuate malaria transmission. This study compared the performance of RDTs to loop-mediated isothermal amplification (LAMP) in the diagnosis of malaria during reactive active case detection surveillance. METHODS: All reported malaria cases in the Engela Health District of Namibia were traced back to their place of residence and persons living within the four closest neighbouring houses to the index case (neighbourhood) were tested for malaria infection with RDTs and dried blood spots (DBS) were collected. LAMP and nested PCR (nPCR) were carried out on all RDTs and DBS. The same procedure was followed in randomly selected control neighbourhoods. RESULTS: Some 3151 individuals were tested by RDT, LAMP and nPCR. Sensitivity of RDTs and LAMP were 9.30 and 95.50%, respectively, and specificities were 99.27 and 99.92%, respectively, compared to nPCR. LAMP carried out on collected RDTs showed a sensitivity and specificity of 95.35 and 99.85% compared to nPCR carried out on DBS. There were 2 RDT samples that were negative by LAMP but the corresponding DBS samples were positive by PCR. CONCLUSION: The study showed that LAMP had the equivalent performance as nPCR for the identification of Plasmodium falciparum infection. Given its relative simplicity to implement over more complex and time-consuming methods, such as PCR, LAMP is particularly useful in elimination settings where high sensitivity and ease of operation are important.

Subpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia.

BACKGROUND: Subpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized. METHODS: Using a two-stage cluster sampling, cross-sectional design, subjects of all age were enrolled during the end of the 2015 malaria transmission season in Zambezi region, located in northeast Namibia. Malaria RDTs were performed with subsequent gold standard testing by loop-mediated isothermal amplification (LAMP) using dried blood spots. Infection prevalence was measured and the diagnostic accuracy of RDT calculated. Relationships between recent fever, demographics, epidemiological factors, and infection were assessed. RESULTS: Prevalence of Plasmodium falciparum malaria infection was low: 0.8% (16/1919) by RDT and 2.2% (43/1919) by LAMP. All but one LAMP-positive infection was RDT-negative. Using LAMP as gold standard, the sensitivity and specificity of RDT were 2.3% and 99.2%, respectively. Compared to LAMP-negative infections, a higher portion LAMP-positive infections were associated with fever (45.2% vs. 30.4%, p = 0.04), though 55% of infections were not associated with fever. Agricultural occupations and cattle herding were significantly associated with LAMP-detectable infection (Adjusted ORs 5.02, 95% CI 1.77-14.23, and 11.82, 95% CI 1.06-131.81, respectively), while gender, travel, bed net use, and indoor residual spray coverage were not. CONCLUSIONS: This study presents results from the first large-scale malaria cross-sectional survey from Namibia using molecular testing to characterize subpatent infections. Findings suggest that fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.

Spatial Distribution of Falciparum Malaria Infections in Zanzibar: Implications for Focal Drug Administration Strategies Targeting Asymptomatic Parasite Carriers.

Background: Optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. We therefore studied spatial distribution of Plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting. Methods: P. falciparum rapid diagnostic tests (RDTs) and molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked immunosorbent assay) analyses were performed on finger-prick blood samples from a population-based survey in 3 adjacent communities. Results: Among 5278 persons screened, 13 (0.2%) were positive by RDT and 123 (2.3%) by PCR. PCR-positive individuals were scattered over the study area, but logistic regression analysis suggested a propensity of these infections to cluster around RDT-positive individuals. The odds ratios for being PCR positive was 7.4 (95% confidence interval, 2.8-19.9) for those living in the household of an RDT-positive individual and 1.64 (1.0-2.8; P = .06) for those living within <300 m, compared with >1000 m. Treating everyone within households of RDT-positive individuals (1% population) would target 13% of those who are PCR positive. Treating all living within a radius of <300 or <1000 m (14% or 58% population) would target 30% or 66% of infections, respectively. Among 4431 serologically screened individuals, 26% were seropositive. Treating everyone within seropositive households (63% population) would target 77% of PCR-positive individuals. Conclusions: Presumptive malaria treatment seemed justified within RDT-positive households and potentially worth considering within, for example, a radius of <300 m. Serology was not discriminative enough in identifying ongoing infections for improving focal interventions in this setting but may rather be useful to detect larger transmission foci.

Malaria risk in young male travellers but local transmission persists: a case-control study in low transmission Namibia.

BACKGROUND: A key component of malaria elimination campaigns is the identification and targeting of high risk populations. To characterize high risk populations in north central Namibia, a prospective health facility-based case-control study was conducted from December 2012-July 2014. Cases (n = 107) were all patients presenting to any of the 46 health clinics located in the study districts with a confirmed Plasmodium infection by multi-species rapid diagnostic test (RDT). Population controls (n = 679) for each district were RDT negative individuals residing within a household that was randomly selected from a census listing using a two-stage sampling procedure. Demographic, travel, socio-economic, behavioural, climate and vegetation data were also collected. Spatial patterns of malaria risk were analysed. Multivariate logistic regression was used to identify risk factors for malaria. RESULTS: Malaria risk was observed to cluster along the border with Angola, and travel patterns among cases were comparatively restricted to northern Namibia and Angola. Travel to Angola was associated with excessive risk of malaria in males (OR 43.58 95% CI 2.12-896), but there was no corresponding risk associated with travel by females. This is the first study to reveal that gender can modify the effect of travel on risk of malaria. Amongst non-travellers, male gender was also associated with a higher risk of malaria compared with females (OR 1.95 95% CI 1.25-3.04). Other strong risk factors were sleeping away from the household the previous night, lower socioeconomic status, living in an area with moderate vegetation around their house, experiencing moderate rainfall in the month prior to diagnosis and living <15 km from the Angolan border. CONCLUSIONS: These findings highlight the critical need to target malaria interventions to young male travellers, who have a disproportionate risk of malaria in northern Namibia, to coordinate cross-border regional malaria prevention initiatives and to scale up coverage of prevention measures such as indoor residual spraying and long-lasting insecticide nets in high risk areas if malaria elimination is to be realized.

The changing epidemiology of malaria elimination: new strategies for new challenges.

Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map.

The independent effect of living in malaria hotspots on future malaria infection: an observational study from Misungwi, Tanzania.

BACKGROUND: As malaria transmission declines, continued improvements of prevention and control interventions will increasingly rely on accurate knowledge of risk factors and an ability to define high-risk areas and populations at risk for focal targeting of interventions. This paper explores the independent association between living in a hotspot and prospective risk of malaria infection. METHODS: Malaria infection status defined by nPCR and AMA-1 status in year 1 were used to define geographic hotspots using two geospatial statistical methods (SaTScan and Kernel density smoothing). Other malaria risk factors for malaria infection were explored by fitting a multivariable model. RESULTS: This study demonstrated that residing in infection hotspot of malaria transmission is an independent predictor of malaria infection in the future. CONCLUSION: It is likely that targeting such hotspots with better coverage and improved malaria control strategies will result in more cost-efficient uses of resources to move towards malaria elimination.

Fine-scale malaria risk mapping from routine aggregated case data.

BACKGROUND: Mapping malaria risk is an integral component of efficient resource allocation. Routine health facility data are convenient to collect, but without information on the locations at which transmission occurred, their utility for predicting variation in risk at a sub-catchment level is presently unclear. METHODS: Using routinely collected health facility level case data in Swaziland between 2011-2013, and fine scale environmental and ecological variables, this study explores the use of a hierarchical Bayesian modelling framework for downscaling risk maps from health facility catchment level to a fine scale (1 km x 1 km). Fine scale predictions were validated using known household locations of cases and a random sample of points to act as pseudo-controls. RESULTS: Results show that fine-scale predictions were able to discriminate between cases and pseudo-controls with an AUC value of 0.84. When scaled up to catchment level, predicted numbers of cases per health facility showed broad correspondence with observed numbers of cases with little bias, with 84 of the 101 health facilities with zero cases correctly predicted as having zero cases. CONCLUSIONS: This method holds promise for helping countries in pre-elimination and elimination stages use health facility level data to produce accurate risk maps at finer scales. Further validation in other transmission settings and an evaluation of the operational value of the approach is necessary.

Hot spot or not: a comparison of spatial statistical methods to predict prospective malaria infections.

BACKGROUND: Within affected communities, Plasmodium falciparum infections may be skewed in distribution such that single or small clusters of households consistently harbour a disproportionate number of infected individuals throughout the year. Identifying these hotspots of malaria transmission would permit targeting of interventions and a more rapid reduction in malaria burden across the whole community. This study set out to compare different statistical methods of hotspot detection (SaTScan, kernel smoothing, weighted local prevalence) using different indicators (PCR positivity, AMA-1 and MSP-1 antibodies) for prediction of infection the following year. METHODS: Two full surveys of four villages in Mwanza, Tanzania were completed over consecutive years, 2010-2011. In both surveys, infection was assessed using nested polymerase chain reaction (nPCR). In addition in 2010, serologic markers (AMA-1 and MSP-119 antibodies) of exposure were assessed. Baseline clustering of infection and serological markers were assessed using three geospatial methods: spatial scan statistics, kernel analysis and weighted local prevalence analysis. Methods were compared in their ability to predict infection in the second year of the study using random effects logistic regression models, and comparisons of the area under the receiver operating curve (AUC) for each model. Sensitivity analysis was conducted to explore the effect of varying radius size for the kernel and weighted local prevalence methods and maximum population size for the spatial scan statistic. RESULTS: Guided by AUC values, the kernel method and spatial scan statistics appeared to be more predictive of infection in the following year. Hotspots of PCR-detected infection and seropositivity to AMA-1 were predictive of subsequent infection. For the kernel method, a 1 km window was optimal. Similarly, allowing hotspots to contain up to 50% of the population was a better predictor of infection in the second year using spatial scan statistics than smaller maximum population sizes. CONCLUSIONS: Clusters of AMA-1 seroprevalence or parasite prevalence that are predictive of infection a year later can be identified using geospatial models. Kernel smoothing using a 1 km window and spatial scan statistics both provided accurate prediction of future infection.

Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics.

BACKGROUND: At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. METHODS: Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). RESULTS: Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. CONCLUSION: The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings.

Estimating spatially disaggregated probability of severe COVID-19 and the impact of handwashing interventions: The case of Zimbabwe.

INTRODUCTION: The severity of COVID-19 disease varies substantially between individuals, with some infections being asymptomatic while others are fatal. Several risk factors have been identified that affect the progression of SARS-CoV-2 to severe COVID-19. They include age, smoking and presence of underlying comorbidities such as respiratory illness, HIV, anemia and obesity. Given that respiratory illness is one such comorbidity and is affected by hand hygiene, it is plausible that improving access to handwashing could lower the risk of severe COVID-19 among a population. In this paper, we estimate the potential impact of improved access to handwashing on the risk of respiratory illness and its knock-on impact on the risk of developing severe COVID-19 disease across Zimbabwe. METHODS: Spatial generalized additive models were applied to cluster level data from the 2015 Demographic and Health Survey. These models were used to generate continuous (1km resolution) estimates of risk factors for severe COVID-19, including prevalence of major comorbidities (respiratory illness, HIV without viral load suppression, anemia and obesity) and prevalence of smoking, which were aggregated to district level alongside estimates of the proportion of the population under 50 from Worldpop data. The risk of severe COVID-19 was then calculated for each district using published estimates of the relationship between comorbidities, smoking and age (under 50) and severe COVID-19. Two scenarios were then simulated to see how changing access to handwashing facilities could have knock on implications for the prevalence of severe COVID-19 in the population. RESULTS: This modeling conducted in this study shows that (1) current risk of severe disease is heterogeneous across the country, due to differences in individual characteristics and household conditions and (2) that if the quantifiable estimates on the importance of handwashing for transmission are sound, then improvements in handwashing access could lead to reductions in the risk of severe COVID-19 of up to 16% from the estimated current levels across all districts. CONCLUSIONS: Taken alongside the likely impact on transmission of SARS-CoV-2 itself, as well as countless other pathogens, this result adds further support for the expansion of access to handwashing across the country. It also highlights the spatial differences in risk of severe COVID-19, and thus the opportunity for better planning to focus limited resources in high-risk areas in order to potentially reduce the number of severe cases.

Is the neglected tropical disease mass drug administration campaign approach an effective strategy to deliver universal health coverage? A case study of the Liberia neglected tropical disease programme.

BACKGROUND: Access to affordable, quality healthcare is the key element of universal health coverage (UHC). This study examines the effectiveness of the neglected tropical disease (NTD) mass drug administration (MDA) campaign approach as a means to deliver UHC, using the example of the Liberia national programme. METHODS: We first mapped the location of 3195 communities from the 2019 national MDA treatment data reporting record of Liberia. The association between coverage for onchocerciasis and lymphatic filariasis treatment achieved in these communities was then explored using a binomial geo-additive model. This model employed three key determinants for community 'remoteness': population density and the modelled travel time of communities to their supporting health facility and to their nearest major settlement. RESULTS: Maps produced highlight a small number of clusters of low treatment coverage in Liberia. Statistical analysis suggests there is a complex relationship between treatment coverage and geographic location. CONCLUSIONS: We accept the MDA campaign approach is a valid mechanism to reach geographically marginal communities and, as such, has the potential to deliver UHC. We recognise there are specific limitations requiring further study.

A stitch in time: The importance of water and sanitation services (WSS) infrastructure maintenance for cholera risk. A geospatial analysis in Harare, Zimbabwe.

Understanding the factors associated with cholera outbreaks is an integral part of designing better approaches to mitigate their impact. Using a rich set of georeferenced case data from the cholera epidemic that occurred in Harare from September 2018 to January 2019, we apply spatio-temporal modelling to better understand how the outbreak unfolded and the factors associated with higher risk of being a reported case. Using Call Detail Records (CDR) to estimate weekly population movement of the community throughout the city, results suggest that broader human movement (not limited to infected agents) helps to explain some of the spatio-temporal patterns of cases observed. In addition, results highlight a number of socio-demographic risk factors and suggest that there is a relationship between cholera risk and water infrastructure. The analysis shows that populations living close to the sewer network, with high access to piped water are associated with at higher risk. One possible explanation for this observation is that sewer bursts led to the contamination of the piped water network. This could have turned access to piped water, usually assumed to be associated with reduced cholera risk, into a risk factor itself. Such events highlight the importance of maintenance in the provision of SDG improved water and sanitation infrastructure.

Mapping malaria incidence using routine health facility surveillance data in Uganda.

INTRODUCTION: Maps of malaria risk are important tools for allocating resources and tracking progress. Most maps rely on cross-sectional surveys of parasite prevalence, but health facilities represent an underused and powerful data source. We aimed to model and map malaria incidence using health facility data in Uganda. METHODS: Using 24 months (2019-2020) of individual-level outpatient data collected from 74 surveillance health facilities located in 41 districts across Uganda (n=445 648 laboratory-confirmed cases), we estimated monthly malaria incidence for parishes within facility catchment areas (n=310) by estimating care-seeking population denominators. We fit spatio-temporal models to the incidence estimates to predict incidence rates for the rest of Uganda, informed by environmental, sociodemographic and intervention variables. We mapped estimated malaria incidence and its uncertainty at the parish level and compared estimates to other metrics of malaria. To quantify the impact that indoor residual spraying (IRS) may have had, we modelled counterfactual scenarios of malaria incidence in the absence of IRS. RESULTS: Over 4567 parish-months, malaria incidence averaged 705 cases per 1000 person-years. Maps indicated high burden in the north and northeast of Uganda, with lower incidence in the districts receiving IRS. District-level estimates of cases correlated with cases reported by the Ministry of Health (Spearman's r=0.68, p<0.0001), but were considerably higher (40 166 418 cases estimated compared with 27 707 794 cases reported), indicating the potential for underreporting by the routine surveillance system. Modelling of counterfactual scenarios suggest that approximately 6.2 million cases were averted due to IRS across the study period in the 14 districts receiving IRS (estimated population 8 381 223). CONCLUSION: Outpatient information routinely collected by health systems can be a valuable source of data for mapping malaria burden. National Malaria Control Programmes may consider investing in robust surveillance systems within public health facilities as a low-cost, high benefit tool to identify vulnerable regions and track the impact of interventions.

Spatial parasite ecology and epidemiology: a review of methods and applications.

The distributions of parasitic diseases are determined by complex factors, including many that are distributed in space. A variety of statistical methods are now readily accessible to researchers providing opportunities for describing and ultimately understanding and predicting spatial distributions. This review provides an overview of the spatial statistical methods available to parasitologists, ecologists and epidemiologists and discusses how such methods have yielded new insights into the ecology and epidemiology of infection and disease. The review is structured according to the three major branches of spatial statistics: continuous spatial variation; discrete spatial variation; and spatial point processes.

Association between indoor residual spraying and pregnancy outcomes: a quasi-experimental study from Uganda.

BACKGROUND: Malaria is a risk factor for adverse pregnancy outcomes. Indoor residual spraying with insecticide (IRS) reduces malaria infections, yet the effects of IRS on pregnancy outcomes are not well established. We evaluated the impact of a large-scale IRS campaign on pregnancy outcomes in Eastern Uganda. METHODS: Birth records (n = 59 992) were obtained from routine surveillance data at 25 health facilities from five districts that were part of the IRS campaign and six neighbouring control districts ∼27 months before and ∼24 months after the start of the campaign (January 2013-May 2017). Campaign effects on low birthweight (LBW) and stillbirth incidence were estimated using the matrix completion method (MC-NNM), a machine-learning approach to estimating potential outcomes, and compared with the difference-in-differences (DiD) estimator. Subgroup analyses were conducted by HIV and gravidity. RESULTS: MC-NNM estimates indicated that the campaign was associated with a 33% reduction in LBW incidence: incidence rate ratio (IRR) = 0.67 [95% confidence interval (CI): 0.49-0.93)]. DiD estimates were similar to MC-NNM [IRR = 0.69 (0.47-1.01)], despite a parallel trends violation during the pre-IRS period. The campaign was not associated with substantial reductions in stillbirth incidence [IRRMC-NNM = 0.94 (0.50-1.77)]. HIV status modified the effects of the IRS campaign on LBW [ßIRSxHIV = 0.42 (0.05-0.78)], whereby HIV-negative women appeared to benefit from the campaign [IRR = 0.70 (0.61-0.81)], but not HIV-positive women [IRR = 1.12 (0.59-2.12)]. CONCLUSIONS: Our results support the effectiveness of the campaign in Eastern Uganda based on its benefit to LBW prevention, though HIV-positive women may require additional interventions. The IRS campaign was not associated with a substantively lower stillbirth incidence, warranting further research.