Imperial College London

ProfessorAzraGhani

Faculty of MedicineSchool of Public Health

Chair in Infectious Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 5764a.ghani Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

362 results found

Challenger JD, Bruxvoort K, Ghani AC, Okell LCet al., 2017, ASSESSING THE IMPACT OF IMPERFECT ADHERENCE TO ARTEMETHER-LUMEFANTRINE ON MALARIA TREATMENT OUTCOMES USING WITHIN-HOST MODELLING, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 521-521, ISSN: 0002-9637

Conference paper

Watson OJ, Verity R, Okell L, Ghani Aet al., 2017, CHARACTERIZING THE POTENTIAL BIAS WITHIN GENOMIC TOOLS FOR INFERRING CHANGES IN <i>PLASMODIUM FALCIPARUM</i> TRANSMISSION INTENSITIES, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 418-418, ISSN: 0002-9637

Conference paper

Sherrard-Smith E, Sala KA, Betancourt M, Upton LM, Angrisano F, Morin MJ, Ghani AC, Churcher TS, Blagborough AMet al., 2017, USING ANTIBODIES TO SIMULATE THE CO-ADMINISTRATION OF TRANSMISSION-BLOCKING AND PRE-ERYTHROCYTIC VACCINES ACCELERATES MALARIA ELIMINATION IN MICE, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 532-532, ISSN: 0002-9637

Conference paper

Winskill P, Slater HC, Griffin JT, Ghani AC, Walker PGet al., 2017, THE IMPORTANCE OF US FOREIGN AID FOR GLOBAL MALARIA CONTROL AND ELIMINATION, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 217-217, ISSN: 0002-9637

Conference paper

Parr JB, Verity R, Doctor SM, Janko M, Carey-Ewend K, Turman BJ, Keeler C, Slater HC, Whitesell AN, Mwandagalirwa K, Ghani AC, Likwela JL, Tshefu AK, Emch M, Juliano JJ, Meshnick SRet al., 2016, Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey, Journal of Infectious Diseases, Vol: 216, Pages: 36-44, ISSN: 0022-1899

Background.Rapid diagnostic tests (RDTs) account for more than two-thirds of malaria diagnoses in Africa. Deletions of the Plasmodium falciparum hrp2 (pfhrp2) gene cause false-negative RDT results and have never been investigated on a national level. Spread of pfhrp2-deleted P. falciparum mutants, resistant to detection by HRP2-based RDTs, would represent a serious threat to malaria elimination efforts.Methods.Using a nationally representative cross-sectional study of 7,137 children under five years of age from the Democratic Republic of Congo (DRC), we tested 783 subjects with RDT-/PCR+ results using PCR assays to detect and confirm deletions of the pfhrp2 gene. Spatial and population genetic analyses were employed to examine the distribution and evolution of these parasites.Results.We identified 149 pfhrp2-deleted parasites, representing 6.4% of all P. falciparum infections country-wide (95% confidence interval 5.1–8.0%). Bayesian spatial analyses identified statistically significant clustering of pfhrp2 deletions near Kinshasa and Kivu. Population genetic analysis revealed significant genetic differentiation between wild-type and pfhrp2-deleted parasite populations (GST = .046, p ≤ .00001).Conclusions.Pfhrp2-deleted P. falciparum is a common cause of RDT-/PCR+ malaria among asymptomatic children in the DRC and appears to be clustered within select communities. Surveillance for these deletions is needed, and alternatives to HRP2-specific RDTs may be necessary.

Journal article

Slater HC, Okell LC, Ghani AC, 2016, Mathematical Modelling to Guide Drug Development for Malaria Elimination, Trends in Parasitology, Vol: 33, Pages: 175-184, ISSN: 1471-5007

Mathematical models of the dynamics of a drug within the host are now frequently used to guide drug development. These generally focus on assessing the efficacy and duration of response to guide patient therapy. Increasingly, antimalarial drugs are used at the population level, to clear infections, provide chemoprevention, and to reduce onward transmission of infection. However, there is less clarity on the extent to which different drug properties are important for these different uses. In addition, the emergence of drug resistance poses new threats to longer-term use and highlights the need for rational drug development. Here, we argue that integrating within-host pharmacokinetic and pharmacodynamic (PK/PD) models with mathematical models for the population-level transmission of malaria is key to guiding optimal drug design to aid malaria elimination.

Journal article

Walker PG, Griffin JT, Ferguson NM, Ghani ACet al., 2016, Estimating the most efficient allocation of interventions to achieve reductions in Plasmodium falciparum malaria burden and transmission in Africa: a modelling study, Lancet Global Health, Vol: 4, Pages: e474-e484, ISSN: 2214-109X

BACKGROUND: Reducing the burden of malaria is a global priority, but financial constraints mean that available resources must be allocated rationally to maximise their effect. We aimed to develop a model to estimate the most efficient (ie, minimum cost) ordering of interventions to reduce malaria burden and transmission. We also aimed to estimate the efficiency of different spatial scales of implementation. METHODS: We combined a dynamic model capturing heterogeneity in malaria transmission across Africa with financial unit cost data for key malaria interventions. We combined estimates of patterns of malaria endemicity, seasonality in rainfall, and mosquito composition to map optimum packages of these interventions across Africa. Using non-linear optimisation methods, we examined how these optimum packages vary when control measures are deployed and assessed at national, subnational first administrative (provincial), or fine-scale (5 km(2) pixel) spatial scales. FINDINGS: The most efficient package in a given setting varies depending on whether disease reduction or elimination is the target. Long-lasting insecticide-treated nets are generally the most cost-effective first intervention to achieve either goal, with seasonal malaria chemoprevention or indoor residual spraying added second depending on seasonality and vector species. These interventions are estimated to reduce malaria transmission to less than one case per 1000 people per year in 43·4% (95% CI 40·0-49·0) of the population at risk in Africa. Adding three rounds of mass drug administration per year is estimated to increase this proportion to 90·9% (95% CI 86·9-94·6). Further optimisation can be achieved by targeting policies at the provincial level, achieving an estimated 32·1% (95% CI 29·6-34·5) cost saving relative to adopting country-wide policies. Nevertheless, we predict that only 26 (95% CI 22-29) of 41 countries could reduce transmissio

Journal article

Marshall JM, Touré M, Ouédraogo AL, Ndhlovu M, Kiware SS, Rezai A, Nkhama E, Griffin JT, Hollingsworth TD, Doumbia S, Govella NJ, Ferguson NM, Ghani ACet al., 2016, Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries, Malaria Journal, Vol: 15, ISSN: 1475-2875

Journal article

White MT, Shirreff G, Karl S, Ghani A, Mueller Iet al., 2016, Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria, Proceedings of the Royal Society of London. Series B, Biological Sciences, Vol: 283, ISSN: 0080-4649

There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.

Journal article

Pothin E, Ferguson NM, Drakeley CJ, Ghani ACet al., 2016, Estimating malaria transmission intensity from Plasmodium falciparum serological data using antibody density models, Malaria Journal, Vol: 15, ISSN: 1475-2875

Background: Serological data are increasingly being used to monitor malaria transmission intensity and havebeen demonstrated to be particularly useful in areas of low transmission where traditional measures such as EIR andparasite prevalence are limited. The seroconversion rate (SCR) is usually estimated using catalytic models in whichthe measured antibody levels are used to categorize individuals as seropositive or seronegative. One limitationof this approach is the requirement to impose a fixed cut-off to distinguish seropositive and negative individuals.Furthermore, the continuous variation in antibody levels is ignored thereby potentially reducing the precision of theestimate.Methods: An age-specific density model which mimics antibody acquisition and loss was developed to make fulluse of the information provided by serological measures of antibody levels. This was fitted to blood-stage antibodydensity data from 12 villages at varying transmission intensity in Northern Tanzania to estimate the exposure rate asan alternative measure of transmission intensity.Results: The results show a high correlation between the exposure rate estimates obtained and the estimated SCRobtained from a catalytic model (r = 0.95) and with two derived measures of EIR (r = 0.74 and r = 0.81). Estimates ofexposure rate obtained with the density model were also more precise than those derived from catalytic models.Conclusion: This approach, if validated across different epidemiological settings, could be a useful alternative frameworkfor quantifying transmission intensity, which makes more complete use of serological data.

Journal article

Griffi JT, Bhatt S, Sinka ME, Gething PW, Lynch M, Patouillard E, Shutes E, Newman RD, Alonso P, Cibulskis RE, Ghani ACet al., 2016, Potential for reduction of burden and local elimination of malaria by reducing Plasmodium falciparum malaria transmission: a mathematical modelling study, Lancet Infectious Diseases, Vol: 16, Pages: 465-472, ISSN: 1473-3099

Journal article

Slater HC, Griffin JT, Ghani AC, Okell LCet al., 2016, Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa., Malaria Journal, Vol: 15, ISSN: 1475-2875

BACKGROUND: Artemisinin and partner drug resistant malaria parasites have emerged in Southeast Asia. If resistance were to emerge in Africa it could have a devastating impact on malaria-related morbidity and mortality. This study estimates the potential impact of artemisinin and partner drug resistance on disease burden in Africa if it were to emerge. METHODS: Using data from Asia and Africa, five possible artemisinin and partner drug resistance scenarios are characterized. An individual-based malaria transmission model is used to estimate the impact of each resistance scenario on clinical incidence and parasite prevalence across Africa. Artemisinin resistance is characterized by slow parasite clearance and partner drug resistance is associated with late clinical failure or late parasitological failure. RESULTS: Scenarios with high levels of recrudescent infections resulted in far greater increases in clinical incidence compared to scenarios with high levels of slow parasite clearance. Across Africa, it is estimated that artemisinin and partner drug resistance at levels similar to those observed in Oddar Meanchey province in Cambodia could result in an additional 78 million cases over a 5 year period, a 7 % increase in cases compared to a scenario with no resistance. A scenario with high levels of slow clearance but no recrudescence resulted in an additional 10 million additional cases over the same period. CONCLUSION: Artemisinin resistance is potentially a more pressing concern than partner drug resistance due to the lack of viable alternatives. However, it is predicted that a failing partner drug will result in greater increases in malaria cases and morbidity than would be observed from artemisinin resistance only.

Journal article

Ghani AC, Walker PG, 2015, Provision of malaria treatment for Ebola case contacts., Lancet Infectious Diseases, Vol: 16, Pages: 391-392, ISSN: 1473-3099

Journal article

Floyd J, Wu L, Burgess DH, Izadnegahdar R, Mukanga D, Ghani ACet al., 2015, Evaluating the impact of pulse oximetry on childhood pneumonia mortality in resource-poor settings, Nature, Vol: 528, Pages: S53-S59, ISSN: 0028-0836

Journal article

Wu L, van den Hoogen LL, Slater H, Walker PGT, Ghani AC, Drakeley CJ, Okell LCet al., 2015, Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies, Nature, Vol: 528, Pages: S86-S93, ISSN: 0028-0836

The global burden of malaria has been substantially reduced over the past two decades. Future efforts to reduce malaria further will require moving beyond the treatment of clinical infections to targeting malaria transmission more broadly in the community. As such, the accurate identification of asymptomatic human infections, which can sustain a large proportion of transmission, is becoming a vital component of control and elimination programmes. We determined the relationship across common diagnostics used to measure malaria prevalence — polymerase chain reaction (PCR), rapid diagnostic test and microscopy — for the detection of Plasmodium falciparum infections in endemic populations based on a pooled analysis of cross-sectional data. We included data from more than 170,000 individuals comparing the detection by rapid diagnostic test and microscopy, and 30,000 for detection by rapid diagnostic test and PCR. The analysis showed that, on average, rapid diagnostic tests detected 41% (95% confidence interval = 26–66%) of PCR-positive infections. Data for the comparison of rapid diagnostic test to PCR detection at high transmission intensity and in adults were sparse. Prevalence measured by rapid diagnostic test and microscopy was comparable, although rapid diagnostic test detected slightly more infections than microscopy. On average, microscopy captured 87% (95% confidence interval = 74–102%) of rapid diagnostic test-positive infections. The extent to which higher rapid diagnostic test detection reflects increased sensitivity, lack of specificity or both, is unclear. Once the contribution of asymptomatic individuals to the infectious reservoir is better defined, future analyses should ideally establish optimal detection limits of new diagnostics for use in control and elimination strategies.

Journal article

Slater HC, Ross A, Ouedraogo AL, White LJ, Nguon C, Walker PGT, Ngor P, Aguas R, Silal SP, Dondorp AM, La Barre P, Burton R, Sauerwein RW, Drakeley C, Smith TA, Bousema T, Ghani ACet al., 2015, Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies, Nature, Vol: 528, Pages: S94-S101, ISSN: 0028-0836

Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using polym

Journal article

Ghani AC, Burgess DH, Reynolds A, Rousseau Cet al., 2015, Expanding the role of diagnostic and prognostic tools for infectious diseases in resource-poor settings, Nature, Vol: 528, Pages: S50-S52, ISSN: 0028-0836

Journal article

Penny MA, Verity RV, Bever C, Sauboin C, Galactionova K, Flasche S, White MT, Wenger EA, Van de Velde N, Pemberton-Ross P, Griffin JT, Smith TA, Eckhoff PA, Muhib F, Jit M, Ghani ACet al., 2015, Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models, The Lancet, Vol: 387, Pages: 367-375, ISSN: 0140-6736

BackgroundThe phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings.MethodsWe compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5–17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10 year olds (PfPR2–10; range 3–65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2–10 per dose.FindingsIn regions with a PfPR2–10 of 10–65%, RTS,S/AS01 is predicted to avert a median of 93 940 (range 20 490–126 540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116 480 (31 450–160 410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. A positive impact is also predicted at a PfPR2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2–10 of 10–65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18–2

Journal article

White MT, Verity R, Churcher TS, Ghani ACet al., 2015, Vaccine approaches to malaria control and elimination: Insights from mathematical models, Vaccine, Vol: 33, Pages: 7544-7550, ISSN: 1873-2518

A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts.Several candidate vaccines targeting different stages ofthe malaria parasite’s lifecycle are currently underdevelopment, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection,having recently completed Phase III trials. Predicting the public health impact of a candidate malariavaccine requires using clinical trial data to estimate the vaccine’s efficacy profile—the initial efficacyfollowing vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacyprofile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematicalmodels.Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocyticvaccines and transmission-blocking vaccines from clinicaltrial data. In the case of RTS,S/AS01, model estimatesfrom Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection,with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waningover the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II orPhase III clinical trials so we review ongoing work investigating how a clinical trial might be designed toensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstratehow parameters estimated from clinical trials can be used to predict the impact of vaccination campaignson malaria using a mathematical model of malaria transmission

Journal article

Walker PG, Griffin JT, Ferguson NM, Ghani ACet al., 2015, ESTIMATING THE MOST RESOURCE-EFFICIENT MALARIA INTERVENTION PACKAGES AND SPATIAL SCALES TO ACHIEVE ELIMINATION ACROSS AFRICA, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 476-477, ISSN: 0002-9637

Conference paper

Floyd J, Wu L, Izadnegahdar R, Burgess D, Mukanga D, Ghani Aet al., 2015, EVALUATING THE IMPACT OF PULSE OXIMETRY ON PNEUMONIA MORTALITY IN CHILDREN UNDER FIVE IN RESOURCE-POOR SETTINGS, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 562-563, ISSN: 0002-9637

Conference paper

Walker P, White M, Griffin JT, Reynolds AM, Ferguson NM, Ghani ACet al., 2015, ESTIMATED INCREASE IN MALARIA MORBIDITY AND MORTALITY IN EBOLA-AFFECTED COUNTRIES DUE TO DECREASED HEALTHCARE CAPACITY AND THE POTENTIAL IMPACT OF MITIGATION STRATEGIES, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 292-292, ISSN: 0002-9637

Conference paper

Slater HC, Drakeley C, Bousema T, Ghani Aet al., 2015, HOW INFECTIOUS IS THE ASYMPTOMATIC RESERVOIR?, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 480-480, ISSN: 0002-9637

Conference paper

Magombedze G, Ghani A, 2015, WHAT IS THE CONTRIBUTION OF AESTIVATION TO THE PERSISTENCE OF ANOPHELES MOSQUITOES AS VECTORS FOR <i>PLASMODIUM FALCIPARUM</i> MALARIA?, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 305-305, ISSN: 0002-9637

Conference paper

Winskill P, Walker PG, Griffin JT, Ghani ACet al., 2015, COST-EFFECTIVE SCALE-UP OF CURRENT INTERVENTIONS AND RTS,S IN SUB-SAHARAN AFRICAN SETTINGS, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 477-477, ISSN: 0002-9637

Conference paper

Sherrard-Smith E, Upton L, Zakutansky S, Sala K, Ghani A, Churcher TS, Blagborough Aet al., 2015, THE COMBINED IMPACT OF TRANSMISSION-BLOCKING DRUGS AND RTS, S VACCINES IS SYNERGISTIC?, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 503-503, ISSN: 0002-9637

Conference paper

Slater HC, Kobylinski K, Foy B, Alout H, Churcher T, Bousema T, Ghani Aet al., 2015, IVERMECTIN FOR MALARIA CONTROL: MODEL VALIDATION TO EXISTING DATA AND DESIGNING TRIALS TO DETECT AN IMPACT USING CLINICAL AND ENTOMOLOGICAL METRICS, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 268-268, ISSN: 0002-9637

Conference paper

White MT, Verity R, Griffin JT, Asante KP, Owusu-Agyei S, Greenwood B, Drakeley C, Gesase S, Lusingu J, Ansong D, Adjei S, Agbenyega T, Ogutu B, Otieno L, Otieno W, Agnandji ST, Lell B, Kremsner P, Hoffman I, Martinson F, Kamthunzu P, Tinto H, Valea I, Sorgho H, Oneko M, Otieno K, Hamel MJ, Salim N, Mtoro A, Abdulla S, Aide P, Sacarlal J, Aponte JJ, Njuguna P, Marsh K, Bejon P, Riley EM, Ghani ACet al., 2015, Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial, Lancet Infectious Diseases, Vol: 15, Pages: 1450-1458, ISSN: 1473-3099

BackgroundThe RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014.MethodsUsing data from 8922 African children aged 5–17 months and 6537 African infants aged 6–12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time.FindingsRTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5–17 months than in those aged 6–12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6–12 weeks and higher immunogenicity in those aged 5–17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5–17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42–48) and that of the long-lived component was 591 days (557–632). After primary vaccination 12% (11–13) of the response was estimated to be long-lived, rising to 30% (28–32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98–153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and effi

Journal article

Cairns ME, Walker PGT, Okell LC, Griffin JT, Garske T, Asante KP, Owusu-Agyei S, Diallo D, Dicko A, Cisse B, Greenwood BM, Chandramohan D, Ghani AC, Milligan PJet al., 2015, Seasonality in malaria transmission: implications for case-management with long-acting artemisinin combination therapy in sub-Saharan Africa, Malaria Journal, Vol: 14, ISSN: 1475-2875

Background: Long-acting artemisinin-based combination therapy (LACT) offers the potential to prevent recurrentmalaria attacks in highly exposed children. However, it is not clear where this advantage will be most important, anddeployment of these drugs is not rationalized on this basis.Methods: To understand where post-treatment prophylaxis would be most beneficial, the relationship betweenseasonality, transmission intensity and the interval between malaria episodes was explored using data from six cohortstudies in West Africa and an individual-based malaria transmission model. The total number of recurrent malariacases per 1000 child-years at risk, and the fraction of the total annual burden that this represents were estimated forsub-Saharan Africa.Results: In settings where prevalence is less than 10 %, repeat malaria episodes constitute a small fraction of thetotal burden, and few repeat episodes occur within the window of protection provided by currently available drugs.However, in higher transmission settings, and particularly in high transmission settings with highly seasonal transmis‑sion, repeat malaria becomes increasingly important, with up to 20 % of the total clinical burden in children estimatedto be due to repeat episodes within 4 weeks of a prior attack.Conclusion: At a given level of transmission intensity and annual incidence, the concentration of repeat malariaepisodes in time, and consequently the protection from LACT is highest in the most seasonal areas. As a result, thedegree of seasonality, in addition to the overall intensity of transmission, should be considered by policy makers whendeciding between ACT that differ in their duration of post-treatment prophylaxis.

Journal article

Walker PGT, White MT, Griffin JT, Reynolds A, Ferguson NM, Ghani ACet al., 2015, Malaria morbidity and mortality in Ebola-affected countries caused by decreased health-care capacity, and the potential effect of mitigation strategies: a modelling analysis, Lancet Infectious Diseases, Vol: 15, Pages: 825-832, ISSN: 1473-3099

BackgroundThe ongoing Ebola epidemic in parts of west Africa largely overwhelmed health-care systems in 2014, making adequate care for malaria impossible and threatening the gains in malaria control achieved over the past decade. We quantified this additional indirect burden of Ebola virus disease.MethodsWe estimated the number of cases and deaths from malaria in Guinea, Liberia, and Sierra Leone from Demographic and Health Surveys data for malaria prevalence and coverage of malaria interventions before the Ebola outbreak. We then removed the effect of treatment and hospital care to estimate additional cases and deaths from malaria caused by reduced health-care capacity and potential disruption of delivery of insecticide-treated bednets. We modelled the potential effect of emergency mass drug administration in affected areas on malaria cases and health-care demand.FindingsIf malaria care ceased as a result of the Ebola epidemic, untreated cases of malaria would have increased by 45% (95% credible interval 43–49) in Guinea, 88% (83–93) in Sierra Leone, and 140% (135–147) in Liberia in 2014. This increase is equivalent to 3·5 million (95% credible interval 2·6 million to 4·9 million) additional untreated cases, with 10 900 (5700–21 400) additional malaria-attributable deaths. Mass drug administration and distribution of insecticide-treated bednets timed to coincide with the 2015 malaria transmission season could largely mitigate the effect of Ebola virus disease on malaria.InterpretationThese findings suggest that untreated malaria cases as a result of reduced health-care capacity probably contributed substantially to the morbidity caused by the Ebola crisis. Mass drug administration can be an effective means to mitigate this burden and reduce the number of non-Ebola fever cases within health systems.

Journal article

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