Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malaria-associated anaemia is a major public-health problem. Although the treatment of uncomplicated, Plasmodium falciparum malaria aims to clear the parasites, relieve the symptoms and permit haematological recovery, data on the impact of antimalarial treatment on haematological recovery are few. Haematological recovery and the prevalence of anaemia were therefore evaluated in 600 Kenyan children with uncomplicated malaria who were randomly assigned to one of three treatment groups. The children were given sulfadoxine-pyrimethamine (SP) on day 0, SP plus artesunate on day 0 (AS1), or SP on day 0 and artesunate on each of days 0-2 (AS3). Haemoglobin (Hb) concentrations were measured on days 0, 7, 14, 21 and 28, with haematological recovery defined as a day-28 Hb concentration of at least 11 g/dl. Only 96 (18%) of the 543 children who were anaemic (i.e. with <11.0 g Hb/dl) at enrolment achieved haematological recovery. The prevalence of anaemia fell from 91% on day 0 to 74% (252/340) by day 28 (P=0.065). Compared with SP alone, neither artesunate regimen resulted in higher Hb concentrations on day 28 (with means of 10.2, 9.9 and 10.2 g/dl for AS3, AS1 and SP, respectively; P=0.254), a higher frequency of haematological recovery (19%, 14% and 20% for AS3, AS1 and SP, respectively; P=0.301) or a greater reduction in the prevalence of anaemia (prevalences in the AS3, AS1 and SP arms falling from 90%, 89% and 93%, respectively, on day 0, to corresponding values of 71%, 82% and 69% on day 28; P=0.40). In fact, between days 0 and 7, the children in the AS3 arm showed a larger drop in mean Hb than the children in the other two treatment arms. In general, haematological recovery was most likely in older children who had mild anaemia at presentation and were parasitologically cured. Overall, the frequencies of haematological recovery were modest and not influenced by the artesunate treatments. Other factors contributing to anaemia need to be explored more fully.
...
PMID:Effect of artesunate plus sulfadoxine-pyrimethamine on haematological recovery and anaemia, in Kenyan children with uncomplicated, Plasmodium falciparum malaria. 1752 43

The huge burden of malaria in developing countries urgently demands the development of novel approaches to fight this deadly disease. Although engineered symbiotic bacteria have been shown to render mosquitoes resistant to the parasite, the challenge remains to effectively introduce such bacteria into mosquito populations. We describe a Serratia bacterium strain (AS1) isolated from Anopheles ovaries that stably colonizes the mosquito midgut, female ovaries, and male accessory glands and spreads rapidly throughout mosquito populations. Serratia AS1 was genetically engineered for secretion of anti-Plasmodium effector proteins, and the recombinant strains inhibit development of Plasmodium falciparum in mosquitoes.
...
PMID:Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria. 2912 Jul 37

The mosquito Culex pipiens is the primary vector of Rift Valley fever, West Nile, encephalitis, and Zika viruses, and periodic lymphatic filariasis. Developing insecticide resistance in mosquitoes demands the development of new approaches to fight these diseases. Paratransgenesis and RNAi approaches by using engineered bacteria have been shown to reduce mosquito vector competence. Serratia-AS1 is a bacterium found in mosquitoes and was genetically modified for expression of antimalaria effector molecules that repress development of malaria parasites in mosquitoes. The aim of this study was to determine how a genetically marked Serratia strain expressing the mCherry fluorescent protein (mCherry-Serratia) affects the colonization potential, life span, blood feeding behavior, fecundity, and fertility of Cx. pipiens. mCherry-Serratia bacteria disseminated into larvae, pupae, and newly emerged adults and dramatically increased in numbers following a blood meal. The bacterium was transmitted to progeny, showing that it can extend horizontally, transstadially, and vertically through the mosquito population. The presence of mCherry-Serratia did not affect blood feeding behavior, survival rate, fecundity, and fertility of Culex mosquitoes. This is the first study to evaluate the effects of an engineered bacteria on the fitness of Cx. pipiens. Although challenges remain, such as producing engineered bacteria to secrete anti-pathogens associated with Cx. pipiens, introducing such bacteria into mosquito populations, our findings of minimal fitness cost caused by Serratia-AS1 bode well for the development of paratransgenesis and RNAi approaches.
...
PMID:Effect of Serratia AS1 (Enterobacteriaceae: Enterobacteriales) on the Fitness of Culex pipiens (Diptera: Culicidae) for Paratransgenic and RNAi Approaches. 3038 21

Recent experimental study suggests that the engineered symbiotic bacteria Serratia AS1 may provide a novel, effective and sustainable biocontrol of malaria. These recombinant bacteria have been shown to be able to rapidly disseminate throughout mosquito populations and to efficiently inhibit development of malaria parasites in mosquitoes in controlled laboratory experiments. In this paper, we develop a climate-based malaria model which involves both vertical and horizontal transmissions of the engineered Serratia AS1 bacteria in mosquito population. We show that the dynamics of the model system is totally determined by the vector reproduction ratio [Formula: see text], and the basic reproduction ratio [Formula: see text]. If [Formula: see text], then the mosquito-free state is globally attractive. If [Formula: see text] and [Formula: see text], then the disease-free periodic solution is globally attractive. If [Formula: see text] and [Formula: see text], then the positive periodic solution is globally attractive. Numerically, we verify the obtained analytic result and evaluate the effects of releasing the engineered Serratia AS1 bacteria in field by conducting a case study for Douala, Cameroon. We find that ideally, by using Serratia AS1 alone, it takes at least 25 years to eliminate malaria from Douala. This implies that continued long-term investment is needed in the fight against malaria and confirms the necessity of integrating multiple control measures.
...
PMID:Modeling the Potential Role of Engineered Symbiotic Bacteria in Malaria Control. 3116 57