Malaria
http://hdl.handle.net/10144/11651
2019-08-22T22:09:08ZCompeting risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis.
http://hdl.handle.net/10144/619463
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis.
Dahal, P; Simpson, JA; Abdulla, S; Achan, J; Adam, I; Agarwal, A; Allan, R; Anvikar, AR; Arinaitwe, E; Ashley, EA; Awab, GR; Bassat, Q; Bjorkman, A; Bompart, F; Borrmann, S; Bousema, T; Broek, I; Bukirwa, H; Carrara, VI; Corsi, M; Cot, M; D'Alessandro, U; Davis, TME; de Wit, M; Deloron, P; Desai, M; Dimbu, PR; Djalle, D; Djimde, A; Dorsey, G; Doumbo, OK; Drakeley, CJ; Duparc, S; Edstein, MD; Espie, E; Faiz, A; Falade, C; Fanello, C; Faucher, JF; Faye, B; de Jesus Fortes, F; Gadalla, NB; Gaye, O; Gil, JP; Greenwood, B; Grivoyannis, A; Hamed, K; Hien, TT; Hughes, D; Humphreys, G; Hwang, J; Ibrahim, ML; Janssens, B; Jullien, V; Juma, E; Kamugisha, E; Karema, C; Karunajeewa, HA; Kiechel, JR; Kironde, F; Kofoed, PE; Kremsner, PG; Lameyre, V; Lee, SJ; Marsh, K; Martensson, A; Mayxay, M; Menan, H; Mens, P; Mutabingwa, TK; Ndiaye, JL; Ngasala, BE; Noedl, H; Nosten, F; Offianan, AT; Oguike, M; Ogutu, BR; Olliaro, P; Ouedraogo, JB; Piola, P; Plowe, CV; Plucinski, MM; Pratt, OJ; Premji, Z; Ramharter, M; Rogier, C; Rombo, L; Rosenthal, PJ; Sawa, P; Schramm, P; Sibley, C; Sinou, V; Sirima, S; Smithuis, F; Staedke, SG; Sutanto, I; Talisua, AO; Tarning, J; Taylor, WRJ; Temu, E; Thriemer, KL; Thuy, NN; Udhayakumar, V; Ursing, J; van Herp, M; van Vugt, M; Whitty, C; William, Y; Winnips, C; Zongo, I; Guerin, P; Price, RN; Stepniewska, K
BACKGROUND:
Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.
METHODS:
Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.
RESULTS:
Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [ρ: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.
CONCLUSIONS:
The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
2019-07-05T00:00:00ZAdapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia.
http://hdl.handle.net/10144/619434
Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia.
Rossi, G; Van den Bergh, R; Nguon, C; Debackere, M; Vernaeve, L; Khim, N; Kim, S; Menard, D; De Smet, M; Kindermans, JM
Reactive case detection around falciparum malaria cases in Cambodia presents a low output. We improved it by including individuals occupationally coexposed with index case patients and using polymerase chain reaction-based diagnosis. The positivity rate increased from 0.16% to 3.9%.
2018-01-06T00:00:00ZMalaria in pregnancy: a call for a safe, efficient, and patient-centred approach to first-trimester treatment.
http://hdl.handle.net/10144/619433
Malaria in pregnancy: a call for a safe, efficient, and patient-centred approach to first-trimester treatment.
Rao, VB; Jensen, TO; Jimenez, BC; Robays, J; Lasry, E; Sterk, E; de Smet, M
2018-06-06T00:00:00ZSevere acute malnutrition results in lower lumefantrine exposure in children treated with artemether-lumefantrine for uncomplicated malaria
http://hdl.handle.net/10144/619406
Severe acute malnutrition results in lower lumefantrine exposure in children treated with artemether-lumefantrine for uncomplicated malaria
Chotsiri, P; Denoeud-Ndam, L; Baudin, E; Guindo, O; Diawara, H; Attaher, O; Smit, M; Guerin, PJ; Duombo, OK; Weisner, L; Barnes, KI; Hoglund, RM; Dicko, A; Etard, JF; Tarning, J
Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub‐Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic‐pharmacodynamic study included 131 SAM and 266 non‐SAM children administered artemether‐lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit‐absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the pharmacokinetic model. Mid‐upper arm circumference (MUAC) was associated with decreased absorption of lumefantrine (25.4% decrease per 1 cm reduction). Risk of recurrent malaria episodes (i.e. reinfection) were characterised by an interval‐censored time‐to‐event model with a sigmoid EMAX‐model describing the effect of lumefantrine. SAM children were at risk of under‐exposure to lumefantrine and an increased risk of malaria reinfection compared to well‐nourished children. Research on optimised regimens should be considered for malaria treatment in malnourished children.
2019-06-01T00:00:00Z