dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors (Publications)
route for therapeutic intervention against malaria. Here we report inhibition and structural studies on the deoxyuridine nucleotidohydrolase from the malaria parasite Plasmodium falciparum (PfdUTPase)
Trisubstituted pyrimidines as efficacious and fast-acting antimalarials (Publications)
mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated
Long-lasting insecticidal net (LLIN) ownership, use and cost of implementation after a mass distribution campaign in Kasai Occidental Province,... (Publications)
BACKGROUND: Long-lasting insecticidal nets (LLIN) are a highly effective means for preventing malaria infection and reducing associated morbidity and mortality. Mass free distribution campaigns have been [...] six months after the mass distribution. Descriptive statistics were used to measure changes in key malaria household indicators. LLIN ownership and use were compared between delivery strategies. Univariate [...] have a significant impact on LLIN use (69.6% [95% CI 63.1-75.5%] versus 65.7%...
Dengue fever in Dar es Salaam, Tanzania: clinical features and outcome in populations of black and non-black racial category (Publications)
are under-reported in Africa and often mistaken for malaria. These results highlight the need to introduce point-of-care tests, beside the one for malaria, to detect outbreaks and orientate diagnosis. TRIAL [...] clinical presentation, including warning signs, was assessed by logistic regression adjusted for age, malaria coinfection, secondary dengue and duration of symptoms at inclusion. The independent association [...] attended care after a slightly longer duration of symptoms (median of 2.9...
Identification of 2,4-disubstituted imidazopyridines as hemozoin formation inhibitors with fast-killing kinetics and <em>in vivo</em> efficacy in the... (Publications)
SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During [...] Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rgamma(null) (NSG)
A novel multiple-stage antimalarial agent that inhibits protein synthesis (Publications)
There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe [...] blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which
Adherence to and acceptability of artemether-lumefantrine as first-line anti-malarial treatment: evidence from a rural community in Tanzania (Publications)
six-dose regimen of artemether-lumefantrine (AL) therapy for uncomplicated Plasmodium falciparum malaria results in cure rates > 95% with good tolerability. MATERIALS AND METHODS: A prospective study was [...] the context of the ALIVE study, a prospective, community-based, observational study in a rural, malaria-endemic area of Tanzania. Following microscopic confirmation of P. falciparum infection, the first
Estimating <em>Plasmodium falciparum</em> transmission rates in low-endemic settings using a combination of community prevalence and health facility... (Publications)
As some malaria control programs shift focus from disease control to transmission reduction, there is a need for transmission data to monitor progress. At lower levels of transmission, it becomes increasingly [...] studies. Many programs conduct regular cross sectional parasite prevalence surveys, and have access to malaria treatment data routinely collected by ministries of health, often in health management information
Prodrugs of reverse fosmidomycin analogues (Publications)
biosynthesis that is essential in Plasmodium falciparum. The drug has been used successfully to treat malaria patients in clinical studies, thus validating IspC as an antimalarial target. However, improvement [...] compounds were also tested for their cytotoxicity toward HeLa cells and in vivo in a Plasmodium berghei malaria model as well as in the SCID mouse P. falciparum model
Imaging of <em>Plasmodium</em> liver stages to drive next-generation antimalarial drug discovery (Publications)
Most malaria drug development focuses on parasite stages detected in red blood cells, even though to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms [...] imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting