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  • Journal article
    White MT, Griffin JT, Ghani AC, 2013,

    The design and statistical power of treatment re-infection studies of the association between pre-erythrocytic immunity and infection with Plasmodium falciparum

    , Malaria Journal, Vol: 12, ISSN: 1475-2875

    Background: Understanding the role of pre-erythrocytic immune responses to Plasmodium falciparum parasites iscrucial for understanding the epidemiology of malaria. However, published studies have reported inconsistentresults on the association between markers of pre-erythrocytic immunity and protection from malaria.Methods: The design and statistical methods of studies of pre-erythrocytic immunity were reviewed, and factorsaffecting the likelihood of detecting statistically significant associations were assessed. Treatment re-infectionstudies were simulated to estimate the effects of study size, transmission intensity, and sampling frequency on thestatistical power to detect an association between markers of pre-erythrocytic immunity and protection frominfection.Results: Nine of nineteen studies reviewed reported statistically significant associations between markers ofpre-erythrocytic immunity and protection from infection. Studies with large numbers of participants inhigh-transmission settings, followed longitudinally with active detection of infection and with immune responsesanalysed as continuous variables, were most likely to detect statistically significant associations. Simulation oftreatment re-infection studies highlights that many studies are underpowered to detect statistically significantassociations, providing an explanation for the finding that only some studies report significant associations betweenpre-erythrocytic immune responses and protection from infection.Conclusions: The findings of the review and model simulations are consistent with the hypothesis thatpre-erythrocytic immune responses prevent P. falciparum infections, but that many studies are underpowered toconsistently detect this effect.
  • Journal article
    Blagborough AM, Churcher TS, Upton LM, Ghani AC, Gething PW, Sinden REet al., 2013,

    Transmission-blocking interventions eliminate malaria from laboratory populations

    , Nature Communications, Vol: 4, ISSN: 2041-1723

    Transmission-blocking interventions aim to reduce the prevalence of infection in endemic communities by targeting Plasmodium within the insect host. Although many studies have reported the successful reduction of infection in the mosquito vector, direct evidence that there is an onward reduction in infection in the vertebrate host is lacking. Here we report the first experiments using a population, transmission-based study of Plasmodium berghei in Anopheles stephensi to assess the impact of a transmission-blocking drug upon both insect and host populations over multiple transmission cycles. We demonstrate that the selected transmission-blocking intervention, which inhibits transmission from vertebrate to insect by only 32%, reduces the basic reproduction number of the parasite by 20%, and in our model system can eliminate Plasmodium from mosquito and mouse populations at low transmission intensities. These findings clearly demonstrate that use of transmission-blocking interventions alone can eliminate Plasmodium from a vertebrate population, and have significant implications for the future design and implementation of transmission-blocking interventions within the field.
  • Journal article
    Bejon P, White MT, Olotu A, Bojang K, Lusingu JPA, Salim N, Otsyula NN, Agnandji ST, Asante KP, Owusu-Agyei S, Abdulla S, Ghani ACet al., 2013,

    Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data

    , LANCET INFECTIOUS DISEASES, Vol: 13, Pages: 319-327, ISSN: 1473-3099
  • Journal article
    Rao VB, Schellenberg D, Ghani AC, 2013,

    Overcoming health systems barriers to successful malaria treatment

    , TRENDS IN PARASITOLOGY, Vol: 29, Pages: 164-180, ISSN: 1471-4922
  • Journal article
    Walker PGT, Griffin JT, Cairns M, Rogerson SJ, van Eijk AM, ter Kuile F, Ghani ACet al., 2013,

    A model of parity-dependent immunity to placental malaria

    , Nature Communications, Vol: 4, ISSN: 2041-1723

    Plasmodium falciparum placental infection during pregnancy is harmful for both mother andchild. Protection from placental infection is parity-dependent, that is, acquired over consecutivepregnancies. However, the infection status of the placenta can only be assessed atdelivery. Here, to better understand the mechanism underlying this parity-dependence, wefitted a model linking malaria dynamics within the general population to observed placentalhistology. Our results suggest that immunity resulting in less prolonged infection is a greaterdeterminant of the parity-specific patterns than immunity that prevents placental sequestration.Our results also suggest the time when maternal blood first flows into the placenta isa high-risk period. Therefore, preventative strategies implementable before or early inpregnancy, such as insecticide-treated net usage in women of child-bearing age or any futurevaccine, could substantially reduce the number of women who experience placental infection.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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Department of Infectious Disease Epidemiology
MRC Centre for Global Infectious Disease Analysis