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Search Results: 1 - 10 of 302816 matches for " Nicholas J White "
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Modelling Malaria Control
Nicholas J White
PLOS Medicine , 2006, DOI: 10.1371/journal.pmed.0030111
Intermittent Presumptive Treatment for Malaria
Nicholas J White
PLOS Medicine , 2005, DOI: 10.1371/journal.pmed.0020003
Determinants of relapse periodicity in Plasmodium vivax malaria
Nicholas J White
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-297
Abstract: In endemic areas of Asia, Oceania, Central and South America, and in the horn of Africa Plasmodium vivax malaria is a major cause of morbidity. It is an important contributor to early pregnancy loss and reduced birth weight which increases mortality in infancy [1,2]. Plasmodium vivax is a sophisticated and resilient malaria parasite which was once prevalent over much of the inhabited world. It has receded from North America, Europe and Russia, but in the tropics vivax malaria remains a major cause of childhood illness. In most endemic areas, P. vivax cohabits with Plasmodium falciparum. Mixed infections with the two species are common. P. vivax is more difficult to control and eliminate than P. falciparum because of its tendency to relapse after resolution of the primary infection. In endemic areas relapse of vivax malaria is a major cause of malaria in young children, and an important source of malaria transmission. Relapse also occurs in Plasmodium ovale infections and in several of the simian malarias, notably Plasmodium cynomolgi, which has often been used as an animal model of vivax malaria. The factors which control relapse and determine their remarkable periodicity are not known.The history of clinical research on vivax malaria contains a wealth of valuable information that is not widely known or recognised. Most studies were conducted over fifty years ago and are not readily accessible to the modern reader. Indeed more may have been forgotten than has been learned about vivax malaria in recent years. The tendency of malaria infections to recur was well known since Roman times. From the 1630s onwards a specific treatment (Cinchona bark) was available for agues (although for most of those infected it was unaffordable). This treatment was often followed by frequent relapses of the periodic fever, and so opinions differed widely on its efficacy. Following Laveran's discovery of the blood parasite that caused malaria in 1880 [3], understanding of malaria epidemio
How antimalarial drug resistance affects post-treatment prophylaxis
Nicholas J White
Malaria Journal , 2008, DOI: 10.1186/1475-2875-7-9
Abstract: In areas of intense malaria transmission reinfection following antimalarial treatment is inevitable. Antimalarial drug treatments with slowly eliminated drugs provide a variable period, after they have cleared the initial infection, during which subsequent reinfection is suppressed by residual levels of the antimalarial drug. This effect is called post-treatment prophylaxis or PTP [1,2]. PTP can range in duration from months, with very slowly eliminated compounds such as piperaquine and chloroquine, to none at all with rapidly eliminated drugs such as the artemisinin derivatives. PTP should provide additional benefit, above that conferred by effective cure of a symptomatic infection, by allowing a longer disease-free interval for clinical and haematological recovery. The benefits of preventing reinfection depend on the transmission intensity and thus the frequency of infection. It has been argued that preventing reinfection is as important as preventing recrudescence, although this remains to be proved, both at an individual and population level. The two are obviously linked as both are measures of antimalarial efficacy. This individual benefit of longer PTP is balanced against a potential societal harm; the increased propensity of slowly eliminated antimalarials to select for resistance [3-5]. PTP is an important component of intermittent preventive treatment, (also sometimes referred to as intermittent presumptive treatment) in pregnancy (IPTp) and is probably the most important effect of intermittent preventive treatment in infancy (IPTi), and in other high risk sub-groups [1,6,7]. The dose and the pharmacokinetic properties of the drug affect the duration of PTP. For the prevalent malaria parasites, antimalarial drug resistance reduces the duration of PTP.In practice, PTP is measured as the time from drug administration (either treatment of the first, usually symptomatic, infection or administration of IPT to an asymptomatic person) until the next infection is d
The role of anti-malarial drugs in eliminating malaria
White Nicholas J
Malaria Journal , 2008, DOI: 10.1186/1475-2875-7-s1-s8
Abstract: Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and transmissibility coincides with peak asexual parasite densities. Mature Plasmodium falciparum gametocytes are more drug resistant and affected only by artemisinins and 8-aminoquinolines. The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection. Radical treatment with primaquine plays a key role in the eradication of vivax and ovale malaria. More evidence is needed on the safety of primaquine when administered without screening for G6PD deficiency to inform individual and mass treatment approaches in the context of malaria elimination programmes.
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria
Kasia Stepniewska, Nicholas J White
Malaria Journal , 2006, DOI: 10.1186/1475-2875-5-127
Abstract: The importance of adequate follow-up is presented and the advantages and disadvantages of non-inferiority trials are discussed. The different methods of interpreting trial results are described, and the difficulties created by loss to follow-up and missing or indeterminate genotyping results are reviewed.To characterize cure rates adequately assessment of antimalarial drug efficacy in uncomplicated malaria requires a minimum of 28 days and as much as 63 days follow-up after starting treatment. The longer the duration of follow-up in community-based assessments, the greater is the risk that this will be incomplete, and in endemic areas, the greater is the probability of reinfection. Recrudescence can be distinguished from reinfection using PCR genotyping but there are commonly missing or indeterminate results. There is no consensus on how these data should be analysed, and so a variety of approaches have been employed. It is argued that the correct approach to analysing antimalarial drug efficacy assessments is survival analysis, and patients with missing or indeterminate PCR results should either be censored from the analysis, or if there are sufficient data, results should be adjusted based on the identified ratio of new infections to recrudescences at the time of recurrent parasitaemia. Where the estimated cure rates with currently recommended treatments exceed 95%, individual comparisons with new regimens should generally be designed as non-inferiority trials with sample sizes sufficient to determine adequate precision of cure rate estimates (such that the lower 95% confidence interval bound exceeds 90%).For a patient ill with malaria, rapid resolution of illness without complications from the disease or its treatment is the first priority. Preventing return of the illness is a second priority. In a high transmission setting reinfection is inevitable, so the longer that subsequent illness can be delayed, the better. Those who deploy antimalarial drugs have simila
The practicality and sustainability of a community advisory board at a large medical research unit on the Thai-Myanmar border  [PDF]
Khin Maung Lwin, Thomas J. Peto, Nicholas J. White, Nicholas P. J. Day, Francois Nosten, Michael Parker, Phaik Yeong Cheah
Health (Health) , 2013, DOI: 10.4236/health.2013.52031

Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB’s goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.

A review of mixed malaria species infections in anopheline mosquitoes
Mallika Imwong, Supatchara Nakeesathit, Nicholas PJ Day, Nicholas J White
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-253
Abstract: The biomedical literature was searched for studies of malaria infection and species identification in trapped wild mosquitoes and artificially infected mosquitoes. The study location and year, collection methods, mosquito species, number of specimens, parasite stage examined (oocysts or sporozoites), and the methods of parasite detection and speciation were tabulated. The entomological results in South East Asia were compared with mixed infection rates documented in patients in clinical studies.In total 63 studies were identified. Individual anopheline mosquitoes were examined for different malaria species in 28 of these. There were 14 studies from Africa; four with species evaluations in individual captured mosquitoes (SEICM). One study, from Ghana, identified a single mixed infection. No mixed infections were identified in Central and South America (seven studies, two SEICM). 42 studies were conducted in Asia and Oceania (11 from Thailand; 27 SEICM). The proportion of anophelines infected with Plasmodium falciparum parasites only was 0.51% (95% CI: 0.44 to 0.57%), for P. vivax only was 0.26% (95% CI: 0.21 to 0.30%), and for mixed P. falciparum and P. vivax infections was 0.036% (95% CI: 0.016 to 0.056%). The proportion of mixed infections in mosquitoes was significantly higher than expected by chance (P < 0.001), but was one fifth of that sufficient to explain the high rates of clinical mixed infections by simultaneous inoculation.There are relatively few data on mixed infection rates in mosquitoes from Africa. Mixed species malaria infections may be acquired by simultaneous inoculation of sporozoites from multiply infected anopheline mosquitoes but this is relatively unusual. In South East Asia, where P. vivax infection follows P. falciparum malaria in one third of cases, the available entomological information suggests that the majority of these mixed species malaria infections are acquired from separate inoculations.Where transmission of both vivax and falcipar
New Medicines for Tropical Diseases in Pregnancy: Catch-22
Nicholas J White ,Rose M McGready,Fran?ois H Nosten
PLOS Medicine , 2008, DOI: 10.1371/journal.pmed.0050133
Mathematical Models for a New Era of Malaria Eradication
Maciej F Boni ,Caroline O Buckee,Nicholas J White
PLOS Medicine , 2008, DOI: 10.1371/journal.pmed.0050231
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