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Article ; Online: Quantifying Plasmodium falciparum infections clustering within households to inform household-based intervention strategies for malaria control programs

Gillian Stresman / Charlie Whittaker / Hannah C Slater / Teun Bousema / Jackie Cook

PLoS Medicine, Vol 17, Iss 10, p e

An observational study and meta-analysis from 41 malaria-endemic countries.

2020 Volume 1003370

Abstract: Background Reactive malaria strategies are predicated on the assumption that individuals infected with malaria are clustered within households or neighbourhoods. Despite the widespread programmatic implementation of reactive strategies, little empirical ... ...

Abstract	Background Reactive malaria strategies are predicated on the assumption that individuals infected with malaria are clustered within households or neighbourhoods. Despite the widespread programmatic implementation of reactive strategies, little empirical evidence exists as to whether such strategies are appropriate and, if so, how they should be most effectively implemented. Methods and findings We collated 2 different datasets to assess clustering of malaria infections within households: (i) demographic health survey (DHS) data, integrating household information and patent malaria infection, recent fever, and recent treatment status in children; and (ii) data from cross-sectional and reactive detection studies containing information on the household and malaria infection status (patent and subpatent) of all-aged individuals. Both datasets were used to assess the odds of infections clustering within index households, where index households were defined based on whether they contained infections detectable through one of 3 programmatic strategies: (a) Reactive Case Detection (RACD) classifed by confirmed clinical cases, (b) Mass Screen and Treat (MSAT) classifed by febrile, symptomatic infections, and (c) Mass Test and Treat (MTAT) classifed by infections detectable using routine diagnostics. Data included 59,050 infections in 208,140 children under 7 years old (median age = 2 years, minimum = 2, maximum = 7) by microscopy/rapid diagnostic test (RDT) from 57 DHSs conducted between November 2006 and December 2018 from 23 African countries. Data representing 11,349 infections across all ages (median age = 22 years, minimum = 0.5, maximum = 100) detected by molecular tools in 132,590 individuals in 43 studies published between April 2006 and May 2019 in 20 African, American, Asian, and Middle Eastern countries were obtained from the published literature. Extensive clustering was observed-overall, there was a 20.40 greater (95% credible interval [CrI] 0.35-20.45; P < 0.001) odds of patent infections (according to ...
Keywords	Medicine ; R
Subject code	338 ; 306
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modelling co-infection with malaria and lymphatic filariasis.

Hannah C Slater / Manoj Gambhir / Paul E Parham / Edwin Michael

PLoS Computational Biology, Vol 9, Iss 6, p e

2013 Volume 1003096

Abstract: Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions ... ...

Abstract	Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change), and the associated timescale for such changes, as well as effects on the basic reproduction number R₀ of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings.
Keywords	Biology (General) ; QH301-705.5
Subject code	330
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The US President's Malaria Initiative, Plasmodium falciparum transmission and mortality

Peter Winskill / Hannah C Slater / Jamie T Griffin / Azra C Ghani / Patrick G T Walker

PLoS Medicine, Vol 14, Iss 11, p e

A modelling study.

2017 Volume 1002448

Abstract: BACKGROUND:Although significant progress has been made in reducing malaria transmission globally in recent years, a large number of people remain at risk and hence the gains made are fragile. Funding lags well behind amounts needed to protect all those ... ...

Abstract	BACKGROUND:Although significant progress has been made in reducing malaria transmission globally in recent years, a large number of people remain at risk and hence the gains made are fragile. Funding lags well behind amounts needed to protect all those at risk and ongoing contributions from major donors, such as the President's Malaria Initiative (PMI), are vital to maintain progress and pursue further reductions in burden. We use a mathematical modelling approach to estimate the impact of PMI investments to date in reducing malaria burden and to explore the potential negative impact on malaria burden should a proposed 44% reduction in PMI funding occur. METHODS AND FINDINGS:We combined an established mathematical model of Plasmodium falciparum transmission dynamics with epidemiological, intervention, and PMI-financing data to estimate the contribution PMI has made to malaria control via funding for long-lasting insecticide treated nets (LLINs), indoor residual spraying (IRS), and artemisinin combination therapies (ACTs). We estimate that PMI has prevented 185 million (95% CrI: 138 million, 230 million) malaria cases and saved 940,049 (95% CrI: 545,228, 1.4 million) lives since 2005. If funding is maintained, PMI-funded interventions are estimated to avert a further 162 million (95% CrI: 116 million, 194 million) cases, saving a further 692,589 (95% CrI: 392,694, 955,653) lives between 2017 and 2020. With an estimate of US$94 (95% CrI: US$51, US$166) per Disability Adjusted Life Year (DALY) averted, PMI-funded interventions are highly cost-effective. We also demonstrate the further impact of this investment by reducing caseloads on health systems. If a 44% reduction in PMI funding were to occur, we predict that this loss of direct aid could result in an additional 67 million (95% CrI: 49 million, 82 million) cases and 290,649 (95% CrI: 167,208, 395,263) deaths between 2017 and 2020. We have not modelled indirect impacts of PMI funding (such as health systems strengthening) in this analysis. CONCLUSIONS:Our model ...
Keywords	Medicine ; R
Subject code	360
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions

Oliver John Watson / Robert Verity / Azra C Ghani / Tini Garske / Jane Cunningham / Antoinette Tshefu / Melchior K Mwandagalirwa / Steven R Meshnick / Jonathan B Parr / Hannah C Slater

eLife, Vol

2019 Volume 8

Abstract: Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in ... ...

Abstract	Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.
Keywords	radid diagnostic tests ; pfhrp2-deletion ; mapping ; mathematical modelling ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ultra-sensitive RDT performance and antigen dynamics in a high-transmission Plasmodium falciparum setting in Mali

Emily N. Reichert / Jen C. C. Hume / Issaka Sagara / Sara A. Healy / Mahamadoun H. Assadou / Merepen A. Guindo / Rebecca Barney / Andy Rashid / Ihn Kyung Yang / Allison Golden / Gonzalo J. Domingo / Patrick E. Duffy / Hannah C. Slater

Malaria Journal, Vol 19, Iss 1, Pp 1-

2020 Volume 10

Abstract: Abstract Background The recent expansion of tools designed to accurately quantify malaria parasite-produced antigens has enabled us to evaluate the performance of rapid diagnostic tests (RDTs) as a function of the antigens they detect—typically histidine ...

Abstract	Abstract Background The recent expansion of tools designed to accurately quantify malaria parasite-produced antigens has enabled us to evaluate the performance of rapid diagnostic tests (RDTs) as a function of the antigens they detect—typically histidine rich protein 2 (HRP2) or lactate dehydrogenase (LDH). Methods For this analysis, whole blood specimens from a longitudinal study in Bancoumana, Mali were used to evaluate the performance of the ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT). The samples were collected as part of a transmission-blocking vaccine trial in a high transmission region for Plasmodium falciparum malaria. Furthermore, antigen dynamics after successful anti-malarial drug treatment were evaluated in these samples using the Q-Plex Human Malaria Array (4-Plex) to quantify antigen concentrations. Results The uRDT had a 50% probability of a positive result at 207 pg/mL HRP2 [95% credible interval (CrI) 160–268]. Individuals with symptomatic infection remained positive by uRDT for a median of 33 days [95% confidence interval (CI) 28–47] post anti-malarial drug treatment. Biphasic exponential decay models accurately captured the population level post-treatment dynamics of both HRP2 and Plasmodium LDH (pLDH), with the latter decaying more rapidly. Motivated by these differences in rates of decay, a novel algorithm that used HRP2:pLDH ratios to predict if an individual had active versus recently cleared P. falciparum infection was developed. The algorithm had 77.5% accuracy in correctly classifying antigen-positive individuals as those with and without active infection. Conclusions These results characterize the performance of the ultra-sensitive RDT and demonstrate the potential for emerging antigen-quantifying technologies in the field of malaria diagnostics to be helpful tools in distinguishing between active versus recently cleared malaria infections.
Keywords	Malaria ; Ultra-sensitive RDT ; Antigenemia ; HRP2 ; pLDH ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel model fitted to multiple life stages of malaria for assessing efficacy of transmission-blocking interventions

Ellie Sherrard-Smith / Thomas S. Churcher / Leanna M. Upton / Katarzyna A. Sala / Sara E. Zakutansky / Hannah C. Slater / Andrew M. Blagborough / Michael Betancourt

Malaria Journal, Vol 16, Iss 1, Pp 1-

2017 Volume 10

Abstract: Abstract Background Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to ... ...

Abstract	Abstract Background Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. Measuring intervention efficacy can be problematic because there is substantial variation in the number of parasites in both the host and vector populations, which can impact transmission even in laboratory settings. Methods A statistically robust empirical method is introduced for estimating intervention efficacy from standardised population assay experiments. This method will be more reliable than simple summary statistics as it captures changes in parasite density in different life-stages. It also allows efficacy estimates at a finer resolution than previous methods enabling the impact of the intervention over successive generations to be tracked. A major advantage of the new methodology is that it makes no assumptions on the population dynamics of infection. This enables both host-to-vector and vector-to-host transmission to be density-dependent (or other) processes and generates easy-to-understand estimates of intervention efficacy. Results This method increases the precision of intervention efficacy estimates and demonstrates that relying on changes in infection prevalence (the proportion of infected hosts) alone may be insufficient to capture the impact of TBIs, which also suppress parasite density in secondarily infected hosts. Conclusions The method indicates that potentially useful, partially effective TBIs may require multiple infection cycles before substantial reductions in prevalence are observed, despite more rapidly suppressing parasite density. Accurate models to quantify efficacy will have important ...
Keywords	Atovaquone ; Plasmodium berghei ; Transmission-blocking drugs ; Transmission-blocking vaccines ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Subject code	310
Language	English
Publishing date	2017-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa

Oliver J Watson / Hannah C Slater / Robert Verity / Jonathan B Parr / Melchior K Mwandagalirwa / Antoinette Tshefu / Steven R Meshnick / Azra C Ghani

eLife, Vol

2017 Volume 6

Abstract: Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent P. falciparum RDTs detect histidine-rich protein 2 (PfHRP2). However, pfhrp2 gene deletions yielding false-negative RDTs, first reported in South America in 2010, have ... ...

Abstract	Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent P. falciparum RDTs detect histidine-rich protein 2 (PfHRP2). However, pfhrp2 gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of pfhrp2-deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed pfhrp2-deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% pfhrp2-deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of pfhrp2-deletion, and identify the geographic regions in which surveillance for pfhrp2-deletion should be prioritised.
Keywords	pfhrp2-deletion ; rapid diagnostic tests ; mathematical modelling ; mapping ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2017-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Model-Based Geostatistical Mapping of the Prevalence of Onchocerca volvulus in West Africa.

Simon J O'Hanlon / Hannah C Slater / Robert A Cheke / Boakye A Boatin / Luc E Coffeng / Sébastien D S Pion / Michel Boussinesq / Honorat G M Zouré / Wilma A Stolk / María-Gloria Basáñez

PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e

2016 Volume 0004328

Abstract: The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the ... ...

Abstract	The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions.Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson's correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2-90%) in 1975.This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	333
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Model citizen – Authors' reply

Oliver J Brady / Hannah C Slater / Peter Pemberton-Ross / Edward Wenger / Richard J Maude / Azra C Ghani / Melissa A Penny / Jaline Gerardin / Lisa J White / Nakul Chitnis / Ricardo Aguas / Simon I Hay / David L Smith / Erin M Stuckey / Emelda A Okiro / Thomas A Smith / Lucy C Okell

The Lancet Global Health, Vol 5, Iss 10, p e

2017 Volume 974

Keywords	Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of mass drug administration in elimination of Plasmodium falciparum malaria

Oliver J Brady, DPhil / Hannah C Slater, PhD / Peter Pemberton-Ross, PhD / Edward Wenger, PhD / Richard J Maude, MD / Prof Azra C Ghani, PhD / Melissa A Penny, PhD / Jaline Gerardin, PhD / Prof Lisa J White, PhD / Nakul Chitnis, PhD / Ricardo Aguas, PhD / Simon I Hay, DSc / Prof David L Smith, PhD / Erin M Stuckey, PhD / Emelda A Okiro, PhD / Prof Thomas A Smith, PhD / Dr Lucy C Okell, PhD

The Lancet Global Health, Vol 5, Iss 7, Pp e680-e

a consensus modelling study

2017 Volume 687

Abstract: Background: Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria ... ...

Abstract	Background: Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. Methods: We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. Findings: The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Interpretation: Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing ...
Keywords	Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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