Professor François H Nosten
|Research Area:||Global Health|
|Scientific Themes:||Tropical Medicine & Global Health|
|Keywords:||malaria, pregnancy, HIV, AIDS and drug resistance|
Dr Nosten’s work concentrates on uncomplicated malaria and he has conducted the largest ever drug trials in malaria in an area which has the world’s most drug-resistant parasites, including a detailed study of the SPf66 malaria vaccine. Recent studies have concentrated on the efficacy and effectiveness of combination anti malarial therapy. Dr Nosten has also investigated malaria prophylaxis and antimalarial treatment in pregnancy and the identification of thiamine deficiency (beri-beri) as a major cause of infant mortality amongst Karen refugees.
|Professor Richard Price||Tropical Medicine||University of Oxford||United Kingdom|
|Tim ANDERSON||Southwest Foundation Texas||United States|
|Laurent RENIA||Singapore Immunology Network||Singapore|
Here we present molecular evidence demonstrating that malaria parasites bearing high-level pyrimethamine resistance originally arrived in Africa from southeast Asia. The resistance alleles carried by these migrants are now spreading across Africa at an alarming rate, signaling the end of affordable malaria treatment and presenting sub-Saharan Africa with a public health crisis. Hide abstract
In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval [CI], 1.1-8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14-30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P< or =.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria. Hide abstract
Unless new strategies are deployed to combat malaria, the already enormous health and economic burden related to the disease in tropical countries is bound to worsen. The main obstacle to malaria control is the emergence of drug resistant strains of Plasmodium falciparum. As for HIV/AIDS and tuberculosis, the use of combinations of antimalarial drugs reduces the risk of selecting for resistant mutants of the plasmodial parasites. In large field trials, the combination of an artemisinin derivative and a partner drug with an unrelated mode of action (in this case mefloquine), has shown a remarkable double effect: preventing the emergence and spread of drug resistance, and interrupting the transmission of P. falciparum. This has opened the way for a new approach to the deployment of antimalarial drugs. Coupled with early detection and confirmed diagnosis, this strategy represents the only way forward in the chemotherapy of malaria. Massive economic assistance will be needed to detect and treat adequately the estimated 500 million cases of malaria per year, but without radical action there is no prospect of 'Rolling Back' malaria. Hide abstract
BACKGROUND: Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P. falciparum malaria. METHODS: We assessed incidence of P. falciparum malaria and the in-vivo responses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thailand. During this time, the standard mefloquine dose was first increased, and then combined artesunate and mefloquine was introduced as first-line treatment for uncomplicated P. falciparum malaria. FINDINGS: Early detection and treatment controlled P. falciparum malaria initially while mefloquine was effective (cure rate with mefloquine [15 mg/kg] and sulphadoxine-pyrimethamine in 1985, 98% [95% CI 97-100]), but as mefloquine resistance developed, the cure rate fell (71% [67-77] in 1990). A similar pattern was seen for high-dose (25 mg/kg) mefloquine monotherapy from 1990-94. Since the general deployment of the artesunate-mefloquine combination in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of P. falciparum malaria in the study area. In-vitro susceptibility of P. falciparum to mefloquine has improved significantly (p=0.003). INTERPRETATION: In this area of low malaria transmission, early diagnosis and treatment with combined artesunate and mefloquine has reduced the incidence of P. falciparum malaria and halted the progression of mefloquine resistance. We recommend that antimalarial drugs should be combined with artemisinin or a derivative to protect them against resistance. Hide abstract
BACKGROUND: Plasmodium vivax is more common than P. falciparum as a cause of malaria in many parts of the tropics outside Africa. P. falciparum infection has harmful effects in pregnancy, but the effects of P. vivax have not been characterised. We investigated the effects of P. vivax infection during pregnancy. METHODS: Since 1986, pregnant Karen women living in camps for displaced people on the western border of Thailand have been encouraged to attend antenatal clinics. Karen women were screened for malaria and anaemia at each week of pregnancy until delivery, and pregnancy outcome recorded. We compared the effects of P. vivax infection on anaemia and pregnancy outcome with those of P. falciparum and no malaria infection in the first pregnancy recorded at the antenatal clinics. FINDINGS: There were 634 first episodes of pure P. vivax malaria in 9956 women. P. vivax malaria was more common in primigravidae than in multigravidae and was associated with mild anaemia and an increased risk of low birthweight (odds ratio 1.64 [95% CI 1.29-2.08], p<0.001). The birthweight was a mean of 107 g (95% CI 61-154) lower in women with P. vivax infection than in uninfected women. By contrast with P. falciparum malaria, the decrease in birthweight was greater in multigravidae. P. vivax malaria was not associated with miscarriage, stillbirth, or with a shortened duration of pregnancy. INTERPRETATION: P. vivax malaria during pregnancy is associated with maternal anaemia and low birthweight. The effects of P. vivax infection are less striking than those of P. falciparum infection, but antimalarial prophylaxis against P. vivax in pregnancy may be justified. Hide abstract
Nature, 395 (6705), pp. 851-852. | Read more1998. Maternal antibodies block malaria.