A5075636609- Malaria Research and Control
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Parasites and Host Interactions
- Trypanosoma species research and implications
- Drug-Induced Hepatotoxicity and Protection
- HIV/AIDS drug development and treatment
- Drug Transport and Resistance Mechanisms
- Research on Leishmaniasis Studies
- Complement system in diseases
- Hemoglobinopathies and Related Disorders
- Global Maternal and Child Health
- vaccines and immunoinformatics approaches
- Vector-borne infectious diseases
- Evolution and Genetic Dynamics
- Travel-related health issues
- Bacteriophages and microbial interactions
- Physiological and biochemical adaptations
- Pharmacology and Obesity Treatment
- Aquaculture disease management and microbiota
- Parasite Biology and Host Interactions
- Animal Behavior and Reproduction
- Bird parasitology and diseases
- Invertebrate Immune Response Mechanisms
- Hepatitis Viruses Studies and Epidemiology
London School of Hygiene & Tropical Medicine
2014-2024
University of London
2008-2018
University of Copenhagen
2005-2014
Copenhagen University Hospital
2005-2014
Eckernforde Tanga University
2014
Moshi Co-operative University
2014
Rigshospitalet
2014
University of Bamako
2013
Liverpool School of Tropical Medicine
2013
Tampere University
2013
Here we present molecular evidence demonstrating that malaria parasites bearing high-level pyrimethamine resistance originally arrived in Africa from southeast Asia. The alleles carried by these migrants are now spreading across at an alarming rate, signaling the end of affordable treatment and presenting sub-Saharan with a public health crisis.
Malaria parasites are sexually reproducing protozoa, although the extent of effective meiotic recombination in natural populations has been debated. If occurs frequently, compared with point mutation and mitotic rearrangement, linkage disequilibrium between polymorphic sites is expected to decline increasing distance along a chromosome. The rate this should be proportional population. Multiple covering 5-kb region chromosome 9 (the msp1 gene) have typed 547 isolates from six Africa test for...
Background Although the molecular basis of resistance to a number common antimalarial drugs is well known, geographic description emergence and dispersal mutations across Africa has not been attempted. To that end we have characterised evolutionary origins antifolate in dihydropteroate synthase (dhps) gene mapped their contemporary distribution. Methods Findings We used microsatellite polymorphism flanking dhps determine which alleles shared ancestry found five major lineages each had unique...
We have used the nested polymerase chain reaction (PCR) to assay for low level Plasmodium falciparum infections that were below threshold of detection blood film examination. This revealed a substantial group asymptomatic, submicroscopically patent within population Sudanese village present throughout year although clinical malaria episodes almost entirely confined transmission season. In our September, January, April, and June surveys, PCR-detected prevalences 13%, 19%, 24%, respectively....
Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended intermittent preventive of in pregnancy, is being investigated infants (IPTi). High levels drug resistance to SP have been reported from north-eastern Tanzania associated with mutations parasite genes. This study compared the vivo efficacy symptomatic 6-59 month children asymptomatic 2-10 old infants.An open label single arm standard 28 day WHO antimalarial protocol was 6 59 months modified 2 10...
Abstract Malaria is a major public health problem that actively being addressed in global eradication campaign. Increased population mobility through international air travel has elevated the risk of re-introducing parasites to elimination areas and dispersing drug-resistant new regions. A simple genetic marker quickly accurately identifies geographic origin infections would be valuable tool for locating source imported outbreaks. Here we analyse mitochondrion apicoplast genomes 711...
The declining efficacy of chloroquine and pyrimethamine/sulphadoxine in the treatment human malaria has led to use newer antimalarials such as mefloquine artemisinin. Sequence polymorphisms pfmdr1 gene, gene encoding plasmodial homologue mammalian multidrug resistance transporters, have previously been linked some, but not all, studies. In this study, we used a genetic cross between strains HB3 3D7 study inheritance sensitivity structurally unrelated drugs artemisinin, several other...
The antimalarial combination of sulfadoxine and pyrimethamine (SP) was introduced as first-line treatment for uncomplicated malaria in Tanzania during 2001 following 18 years second-line use. genetic determinants vitro resistance to the two drugs individually are shown be point mutations at seven sites dihydrofolate reductase gene (dhfr) conferring five dihydropteroate synthase (dhps) sulfadoxine. Different combinations within each confer differing degrees insensitivity, but information...
Abstract Molecular markers for drug resistant malaria represent public health tools of great but mostly unrealized potential value. A key reason the failure molecular resistance to live up their is that data on prevalence scattered in disparate databases with no linkage clinical, vitro and pharmacokinetic are needed relate genetic relevant phenotypes. The ongoing replacement older monotherapies by new, more effective combination therapies presents an opportunity create open access database...
Although malaria treatment aims primarily to eliminate the asexual blood stages that cause illness, reducing carriage of gametocytes is critical for limiting transmission and spread resistance.Clinical parasitological responses fixed-dose combination sulfadoxine pyrimethamine in patients with uncomplicated falciparum were assessed biannually since implementation this policy 1998 Mpumalanga Province, South Africa.Despite sustained cure rates > 90% (P = .14), duration gametocyte increased from...
In the third article in a six-part <I>PLoS Medicine</I> series on Migration & Health, Cally Roper and Caroline Lynch use case study of migration anti-malarial drug resistance Uganda to discuss specific health risks policy needs associated with transit phase migration.
Abstract Background Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was by artemisinin combination therapy 2006. SP has however, continued be used intermittent preventive treatment malaria pregnancy (IPTp) despite reports high levels due lack alternatives for IPTp. Recent have indicated recovery CQ-susceptibility Malawi,...
Artemether–lumefantrine (AL) and artesunate–amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of Plasmodium falciparum in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) P lasmodium multidrug resistance 1 ( Pfmdr1 ) gene may compromise sensitivity. AL AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 1246Y partially resistant to treatment, while N86, 184 F D1246 favoured...
There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes P. falciparum populations Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this is parasites different parts country consequently fill gap sulfadoxine-pyrimethamine (SP) resistance data we retrospectively analysed 1000 filter paper blood spots collected...