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13.05.2008
Fake Malaria Drugs Emerging in Vulnerable Countries in Africa [NYT - USA] — (English)
Until recently, fake malaria drugs have been a problem largely confined to Southeast Asia, where a sampling two years ago found 53 percent of the drugs substandard, and drug experts said Asia was facing "an epidemic of counterfeits."...
Executive Director of cbm US congratulates UN on Malaria Campaign [NewsRX] — (English)
Ron Nabors, Chief Executive Officer of cbm US, congratulates the United Nations for teaming up with religious, business and sports leaders in a new effort to send insecticide-treated bed nets to Africa to prevent millions of deaths from malaria, ahead of the first-ever inaugural World Malaria Day on Friday, April 25, 2008...
Chemical biology: Maths and malaria [Nature News] — (English)
A 'guilt by association' test can correctly pinpoint the function of proteins, reports a team led by Elizabeth Winzeler of the Scripps Research Institute in La Jolla, California. An algorithm the researchers wrote found that the malaria-causing parasite Plasmodium falciparum expresses a gene encoding CDPK1 — a protein with an unknown role — at the same time as some other genes involved in cell invasion and movement. These all become active as the parasite prepares for its sexual stage...
Provinces give nod to ‘roll back malaria’ project [The Post - Lahore,Punjab,Pakistan] — (English)
Provincial governments have agreed to launch PC-I of a project titled 'Roll Back Malaria,' costing Rs 658 million, sources said...
12.05.2008
Interoperable grid software to tackle malaria [University of Southampton - Southampton,UK] — (English)
Accelerating the development of drugs to treat malaria and avian flu is one potential benefit from new grid software which has just been released...
Surge in holidays in paradise raises fear of disease [ic Wales - United Kingdom] — (English)
HOLIDAY-MAKERS are being urged to take precautions against malaria amid a 20% increase in people visiting at-risk destinations...
East Anglia malaria warning from the Travel Clinic [Cambridge Network - Cambridge,UK] — (English)
Local health professional warns that travel health advice needs to be taken more seriously. Travellers and holiday-makers in East Anglia are being urged to swat up on malaria as new research reveals that there has been a nearly 200% increase in travel to at-risk destinations such as Goa, Thailand and Africa, in the past ten years...
Rehabilitating Carson [Prospect Magazine - London,UK] — (English)
Rachel Carson launched the modern environmental movement. She was posthumously awarded the US presidential medal of freedom, and has conservation areas, prizes and associations named in her honour...
Africa: $220 Million But Still No Respite From Malaria Deaths []The East African (Nairobi) — (English)
IS THE CURRENT GLOBAL APPROACH to malaria treatment and prevention working? That is what two researchers at the University of Alabama's Birmingham School of Medicine, want malaria experts to consider, given the relentless toll taken by the killer fever...
Uganda: Organic Exporters in DDT Scare [The East African (Nairobi) via allAfrica.com] — (English)
Barely three weeks since spraying of the controversial insecticide DDT to control malaria started in Uganda, the dispute between the government and exporters of organic products is re-emerging, this time over "irregularities" in executing the exercise...
NL student group takes on malaria [Lebanon Daily News - Lebanon,PA,USA] — (English)
A group of students in Northern Lebanon middle and high schools have taken on a project to raise $1,000 to purchase life-saving bed nets for sub-Saharan Africa. We are currently halfway there! ...
11.05.2008
Saving the world in study hall [IHT - USA] — (English)
As a 16-year-old in Melbourne, Florida, Allyson Brown organized a Valentine's dance at her high school, with the proceeds going to fight malaria in Africa. That dance grew into Stayin' Alive, a campaign that has attracted more than 100 schools in 31 states to raise money to buy mosquito bed nets that cost $10 each and protect a family from malaria...
Zambezi malaria expedition [The Post Zambia - Zambia ] — (English)
OFTEN people along the banks of the rivers find space in the mainstream media when the bursting banks of the rivers displace them. But to the people living along the banks of the Zambezi River, they could have probably been the first on the African continent to be protected from the lethal effects of malaria, under the Zambezi Malaria Expedition...
Our man in Africa [The Guardian - UK] — (English)
Jamie Drummond lobbies the richest people on the planet on behalf of the poorest. Tim Adams meets the man with a direct line to the world's most powerful leaders...
(KAKUMDO) CAPE COAST : Druggist to combat malaria [ghanadistricts.com] — (English)
The Malaria Control Programme of the Ministry of Health (MOH) would soon train drug store attendants and other chemists to prescribe malaria drugs at areas where clinics and health centres are not within reach...
Coartem price reduction only for the public sector [New Vision - Uganda] — (English)
NOVARTIS, a Switzerland-based pharmaceutical company, has announced a 20% average reduction in the price of the malaria drug, Coartem.
Hans Rietveld, the Norvartis Global access and marketing director, says the price reduction is only applicable to public sector buyers, such as the Ministry of Health...
DDT use discussed at national workshop [Yemen Times - Yemen] — (English)
In cooperation with the World Health Organization, Yemen’s Public Health and Population Ministry along with the National Malaria Control Program kicked off events for the National Workshop on DDT Reporting held in Sana’a May 6 and 7...
10.05.2008
A third of malaria drugs in Africa are ineffective [Times Online - UK] — (English)
The study of drugs bought in Ghana, Kenya, Nigeria, Rwanda, Tanzania and Uganda shows that 35 per cent contained too little active ingredient or failed to dissolve, rendering them ineffective. Another third of treatments also belonged to a class of drugs that the World Health Organisation (WHO) wants to be banned because they can cause the malaria parasite to develop resistance...
Malaria victim fires warning over disease [Scotsman - United Kingdom] — (English)
A RETIRED Edinburgh banker who contracted malaria on a visit to Uganda is taking part in a campaign to highlight the dangers of the disease...
UNICEF, W’Bank Seek Sustained Action on Malaria [This Day - Apapa,Lagos,Nigeria] — (English)
United Nations’ Childen’s Fund (UNICEF) Exe-cutive Director, Ann Veneman, has sued for the cooperation of countries around the world in the fight against malaria...
9.05.2008
Waterborne diseases biggest risk [Guardian News - UK] — (English)
Within two weeks there could be outbreaks of malaria and dengue fever, which are both spread by mosquitoes...
WHO warns of cholera, malaria risk in Myanmar [AFP] — (English)
The World Health Organisation warned Friday that victims of the devastating Myanmar cyclone are at risk from cholera, malaria and diarrhea due to a lack of safe drinking water...
Race to prevent disease among Myanmar cyclone victims [AP] — (English)
Fears of mosquito-borne diseases such as malaria and dengue fever, which are endemic to the area, also have heightened. However, outbreaks would not be expected for another week or longer because the mosquitoes need time to breed in stagnant water left from the storm, said Osamu Kunii, UNICEF's chief of health and nutrition in Yangon...
Todes-Mücken kennen keine Grenzen [NWZ - Germany] — (Deutsch)
Ein Deutscher und ein Schweizer beteiligen sich an Aktion zur Bekämpfung der Krankheit...
Danish NGO gets involved in malaria control in Mali [Afrique en ligne - Angers,France] — (English)
A Danish non- governmental organisation, Borne Fonden, plan s to execute a malaria prevention and control project in southern Mali estimated at more than 800 million FCFA, medical sources told PANA on Friday...
Malaria control plan to be validated in Mali [Afrique en ligne - Angers,France] — (English)
The monitoring and evaluation plan of Mali's malaria control programme will be validated 13 to 15 May in Bamako, Mali's capital, the Health Ministry announced here...
Atelier paludisme: an international malaria training course held in Madagascar [Malaria Journal 2008, 7:80 (9 May 2008)] — (English)
Description of an international training course organized by the Institut Pasteur de Madagascar, following an evaluation of the first five years of operation...
Timing of intermittent preventive treatment for malaria during pregnancy and the implications of current policy on early uptake in north-east Tanzania [Malaria Journal 2008, 7:79 (9 May 2008)] — (English)
The paper addresses a common misconception among health care providers and policy makers that late attendance to antenatal care is the single most important limitation for delivering intermittent preventive treatment for malaria. In addition they identify other constraints that may be more amenable to systemwide changes that could improve the delivery of this important health intervention. In particular, a lack of information of health workers on the reasoning for continued use of SP for IPTp, when national policy has replaced it as a first-line treatment...
Côte d'Ivoire: Des agents de santé formés contre le paludisme [Fraternité Matin (Abidjan) via allAfrica.com] — (Français)
Vingt-cinq agents de la santé, venus des différentes formations sanitaires d'Adzopé et Akoupé, ont été formés à la prise en charge du paludisme et au remplissage des outils de collecte des données selon le protocole national...
United States buys DDT for Uganda [New Vision - Uganda] — (English)
US President, George Bush has assisted Uganda to procure DDT being sprayed against malaria-spreading mosquitoes, the Director General of Health Services Dr. Sam Zaramba, said on Thursday...
Southern Africa: SADC to Intensify Malaria Interventions [The Herald (Harare) via allAfrica.com] — (English)
Countries in the Sadc region will submit a joint proposal seeking funding for malaria interventions to the Global Fund to Fight HIV and Aids, Tuberculosis and Malaria Round Eight...
8.05.2008
WHO: More than one million people die of malaria per year [Xinhua - China] — (English)
The World Health Organization said that more than one million people out of 500 million cases die of malaria per year, Subhash R. Salunke, the organization representative to Indonesia, said here Thursday...
Malaria Showing Signs of Resurgence [chosun.com - South Korea] — (English)
Health authorities are stepping up efforts to fight malaria, which has shown signs of resurgence since 2005. According to the Korea Centers for Disease Control and Prevention(KCDC) on Wednesday, malaria was eradicated in the country in the late 1970s but resurged in Paju, Gyeonggi Province in 1993, when an active-duty soldier was infected after being bitten by a malaria mosquito which had come from North Korea...
President calls for greater joint efforts to fight malaria [Antara - Antara,Indonesia] — (English)
President Susilo Bambang Yudhoyono called on all parties in the country to strive jointly to lower the incidence of malaria...
DDT will stop malaria-Government [New Vision - Kampala,Uganda] — (English)
THE government has asked Members of Parliament to sensitize their electorate on the spray of DDT...
BASF: Mosquito nets protect against malaria [individual.com - USA] — (English)
Malaria is one of last three major epidemic diseases, killing well over a million people a year. Only AIDS and tuberculosis claim more victims..
Mosquito nets save lives [Web Wire -USA] — (English)
Mosquito nets protect against malaria
Malaria is one of last three major epidemic diseases, killing well over a million people a year. Only AIDS and tuberculosis claim more victims. Malaria is caused by tiny single-celled organisms called plasmodia transmitted by mosquitoes of the Anopheles genus. Ninety percent of these cases are concentrated in Africa, with young children being most affected. Every 30 seconds a child dies of malaria in Africa and almost every second victim is under five...
Henry addresses 'Norman Gets Malaria' night [Norman Transcript - USA] — (English)
NorthHaven Church partnered with His Nets, a Norman-based organization to host "Norman Gets Malaria" night...
Two-thirds of Indonesia's districts in malaria endemic area [Earthtimes - USA] — (English)
More than two-thirds of the 576 districts in Indonesia have been classified as malaria endemic areas, with more than 100 million people at risk of catching the disease, the country's health minister said Thursday...
Vaccinations and malaria prophylaxis recommended for staff deployed to Myanmar [ReliefWeb - UK] — (English)
Staff and consultants need to bear in mind that situations may change in emergency context with potential risks for epidemics and, if they are sent initially to one particular area, they can be redeployed to another area at short notice...
Eritrea: Country Wins Broad Acclaim for Achievements in Reducing Child And Mother Mortality Rate And Controlling Malaria Epidemic [Shabait.com (Asmara) via allAfrica.com] — (English)
Eritrea won broad acclaim and was cited as an exemplary nation at the Burkina Faso International Conference on Basic Health Care for the major achievements it has registered in reducing child and mother mortality rate as well as controlling malaria epidemic...
Sénégal: Paludisme - La morbidité baisse de 20% à Louga... [Le Soleil (Dakar) via allAfrica.com] — (Français)
Le paludisme connaît une régression dans la région de Louga, même s'il reste toujours le premier motif de consultations. Le taux de morbidité connaît ainsi une baisse de 20% ces dernières années...
7.05.2008
GlobalHealthReporting.org Weekly TB/Malaria Report [GlobalHealthReporting.org] — (English)
News and events...
Feature - WISDOM unplugged: malaria drug-leads graduate to the wet lab [International Science Grid This Week - Geneva,Geneva,Switzerland] — (English)
Hot on the heels of their initial success, WISDOM collaborators have high hopes as their anti-malaria drug-leads move from computer processers to petri dishes...
Photojournal: Burden of malaria [BBC] — (English)
Malaria is endemic in most of Uganda, but basic preventive gear like bed nets is beyond the reach of many, as photographer Jake Price found out on a visit to northern areas badly affected by the long years of war with rebels...
Queries over ITN's effectiveness in urban settings [Africa Science] — (English)
Malaria vectors in Africa's cities appear to have adapted to high coverage with insecticide treated bed nets and improved housing--- by predominantly feeding outdoors and have thus, reduced effectiveness of the much-touted insecticide-treated nets compared to rural areas, a Dar es Salaam , Tanzania study published in the malaria journal of January shows...
Microbiologist Malaria swim raises £500 [NHS - UK] — (English)
Dr Guy Robinson of the Cryptosporidium Reference Unit in Swansea was one of 300,000 people to take part in the annual World Swim Against Malaria last month...
Study finds Africans get substandard malaria drugs [Reuters India - Mumbai,India] — (English)
Many Africans are getting substandard malaria drugs, with more than a third of the pills tested failing quality tests, according to a report published on Tuesday...
The use of mosquito nets and the prevalence of Plasmodium falciparum infection in rural South Central Somalia [PLOS One] — (English)
Bed nets confer high protection against parasite infection in South Central Somalia. In such areas where baseline transmission is low, however, the absolute reductions in parasitaemia due to wide-scale net use will be relatively small raising questions on the cost-effectiveness of covering millions of people living in such settings in Africa with nets. Further understanding of the progress of disease upon infection against the cost of averting its consequent burden in low transmission areas of Africa is therefore required...
Iron incorporation and post-malaria anaemia [PLOS One] — (English)
Post-malaria anaemia is associated with a better haemoglobin recovery despite a significant depressant effect on oral iron incorporation which may indicate that early erythropoetic iron need is met by iron recycling rather than oral iron. Supplemental iron administration is of questionable utility within 2 weeks of clinical malaria in children with mild or moderate anaemia...
Antimalarial drug quality in the most severely malarious parts of Africa - a six country study [PLOS One] — (English)
A range of antimalarial drugs were procured from private pharmacies in urban and peri-urban areas in the major cities of six African countries, situated in the part of that continent and the world that is most highly endemic for malaria. Semi-quantitative thin-layer chromatography (TLC) and dissolution testing were used to measure active pharmaceutical ingredient content against internationally acceptable standards. 35% of all samples tested failed either or both tests, and were substandard. Further, 33% of treatments collected were artemisinin monotherapies, most of which (78%) were manufactured in disobservance of an appeal by the World Health Organisation (WHO) to withdraw these clinically inappropriate medicines from the market. The high persistence of substandard drugs and clinically inappropriate artemisinin monotherapies in the private sector risks patient safety and, through drug resistance, places the future of malaria treatment at risk globally...
Pyruvate kinase deficiency protects against malaria in humans [Haematologica. 2008 May 6] — (English)
The association between inherited erythrocyte disorders in humans and resistance to malaria is well documented and includes enzyme deficiencies, hemoglobinopathies and membrane protein abnormalities. The association between pyruvate kinase (PK) deficiency and resistance to
malaria has been demonstrated in vivo using a murine model1 and it has been suggested that this phenomenon may extend to humans....
Study finds Africans get substandard malaria drugs [Reuters - UK] — (English)
Many Africans are getting substandard malaria drugs, with more than a third of the pills tested failing quality tests, according to a report published on Tuesday...
Africa: Effective Strategies Needed to Combat Malaria [Business Daily (Nairobi) via allAfrica.com] — (English)
Kenya is one of the countries that have the best knowledge about malaria in the world today. Paradoxically, it is also one of the countries with the highest number of people who succumb to the disease...
Malaria hits 46 in Siolim [Times of India - India] — (English)
The monsoon hasn’t arrived yet, but strains of malaria have already shown up in Siolim’s primary health centre of Siolim...
6.05.2008
WHO fears Myanmar disease outbreaks in wake of cyclone [Newsweek - USA] — (English)
Disease outbreaks spread by mosquitoes, dirty water and poor sanitation were among the World Health Organization's biggest concerns after a devastating cyclone hit Myanmar, home to one of the world's shoddiest health care systems...
Firm 'misled' over malaria drug [BBC News - UK] — (English)
Cosmetics chain Neal's Yard has dropped the sale of a homeopathic drug after watchdogs said customers were being misled that it could treat malaria...
Cosmetic chain told to withdraw homeopathic malaria remedy [guardian.co.uk - UK] — (English)
The cosmetic chain Neal's Yard Remedies has been ordered to withdraw a homeopathic remedy for malaria after medicines watchdogs decided its sale was potentially dangerous and misleading...
Temporal correlation between malaria and rainfall in Sri Lanka [7thSpace Interactive (press release) - New York,NY,USA] — (English)
Rainfall data have potential use for malaria prediction. However, the relationship between rainfall and the number of malaria cases is indirect and complex...
Heterogeneous distribution of Plasmodium falciparum drug resistance haplotypes in subsets of the host population [Malaria Journal 2008, 7:78 (6 May 2008)] — (English)
An original and interesting approach where the hypothesis that drug resistant malaria parasites are at a fitness disadvantage compared to susceptible parasites is tested by analysing mutations of parasite genes associated with drug resistance...
Temporal correlation between malaria and rainfall in Sri Lanka [Malaria Journal 2008, 7:77 (6 May 2008)] — (English)
The paper looks at the relationship between rainfall and malaria incidence in Sri Lanka, allowing for spatial variability. The research findings indicate that there is little to be gained from the use of rainfall information in malaria control decision-making because of the relative low correlations observed...
Models for short term malaria prediction in Sri Lanka [Malaria Journal 2008, 7:76 (6 May 2008)] — (English)
A solid contribution towards the development of early warning systems for malaria using a forecasting system based on epidemiological and rainfall data. The difficulties of establishing a forecasting system in a country where there have been dramatic swings in incidence rates over the last century is acknowledged and the authors have taken a pragmatic approach to testing district based forecasting across the country...
Articles requiring subscription
High-dose Primaquine Regimens against Relapse of Plasmodium vivax Malaria [Am J Trop Med Hyg. 2008 May;78(5):736-40] — (English)
Plasmodium vivax causes debilitating but usually non-lethal malaria in most of Asia and South America. Prevention of relapse after otherwise effective therapy for the acute attack requires a standard daily dose of primaquine administered over 14 days. This regimen has < 90% efficacy in Thailand, and is widely regarded as ineffective because of poor compliance over the relatively long duration of dosing. We evaluated the efficacy, safety, and tolerability of alternative primaquine dosing regimens combined with artesunate among 399 Thai patients with acute, symptomatic P. vivax malaria. Patients were randomly assigned to one of six treatment groups: all patients received artesunate, 100 mg once a day for 5 days. Groups 1–5 then received primaquine, 30 mg a day for 5, 7, 9, 11, and 14 days, respectively. Group 6 received primaquine, 30 mg twice a day for 7 days. The 28-day cure rates were 85%, 89%, 94%, 100%, and 96%, respectively. Treatment of P. vivax malaria with artesunate for 5 days followed by high-dose primaquine, 30 mg twice a day for 7 days, was highly effective, well-tolerated, and equivalent or superior to the standard regimen of primaquine therapy...
Detection of Plasmodium falciparum histidine-rich protein II in saliva of malaria patients [Am J Trop Med Hyg. 2008 May;78(5):733-5] — (English)
Detection of Plasmodium falciparum parasites in patients with malaria necessitates drawing blood, which increases the risk of accidental infections and is poorly accepted in communities with blood taboos. Thus, non-invasive, cost-effective malaria tests that minimize the need for blood collection are needed. Plasmodium falciparum histidine-rich protein II (PfHRP II) levels in plasma and saliva were compared in malaria–positive and –negative patients in Ghana. Plasma and saliva obtained from 30 thick-film positive and 10 negative children were evaluated for PfHRP II by ELISA. Among the 30 children with positive blood smear, 16 (53%) were PfHRP II positive in plasma and 13 (43%) had PfHRP II positive saliva. The sensitivity of PfHRP II detection was 53% for plasma and 43% for saliva. The specificity was 100% with no false positive for both plasma and saliva when compared with blood smear. Thus, rapid detection of PfHRP II antigen in saliva may be a useful non-invasive and cost-effective malaria diagnostic technique...
nalysis of naturally acquired antibody responses to the 19-kd C-terminal region of merozoite surface protein-1 of Plasmodium vivax from individuals in Sanliurfa, Turkey [Am J Trop Med Hyg. 2008 May;78(5):729-32] — (English)
Plasmodium vivax is the second most prevalent global Plasmodium species causing malaria after P. falciparum. These two Plasmodium spp. co-exist in most endemic areas, apart from west and central Africa, which has only P. falciparum. However, southeastern Turkey is one of the exceptional regions with the sole presence of P. vivax infection, where a thorough epidemiologic survey has not been performed. Here, we report for the first time the identification of naturally acquired antibodies against the 19-kd C-terminal region of the merozoite surface protein-1 of P. vivax (PvMSP119), using ELISA, from residents in the Sanliurfa region of southeastern Turkey. Among the 82 samples from patients with patent P. vivax malaria, 85% of the individuals were sero-reactive to PvMSP119. Particularly, 69.5% of the subjects were positive for IgM, 53.6% were positive for IgG (predominantly IgG1 and IgG3), and 7.3% were positive for IgA...
In vitro activity of artemisinin in combination with clotrimazole or heat-treated amphotericin B against Plasmodium falciparum [Am J Trop Med Hyg. 2008 May;78(5):721-8] — (English)
Currently available artemisinin-based combination therapies (ACTs) for malaria are inadequate. There remains an enormous unmet need for alternate artemisinin-based combination therapies. One of the fastest methods to identify promising artemisinin-based combination therapies is to look for synergistic or additive antimalarial interaction between artemisinin and an alternate drug against P. falciparum in vitro. Amphotericin B and clotrimazole are known drugs for treatment of human fungal infections. We repurposed clotrimazole or heat-treated amphotericin B in fixed ratio combination with artemisinin for antimalarial properties. Isobologram results show synergistic/additive interaction in both of the cases at therapeutically safe concentrations. Artemisinin, clotrimazole, and their synergistic combinations also decrease hemozoin production in parasitized erythrocytes. New permeation pathways induced in infected cells remain unaffected by drug combinations as indicated by sorbitol lysis. It would be interesting to extend the studies’ in vivo system...
Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania [Am J Trop Med Hyg. 2008 May;78(5):714-20] — (English)
The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area of intense malaria transmission where 202 individuals 0–19 years of age were monitored clinically for a period of 6 months. RBC polymorphisms were assessed with molecular methods, and plasma antibodies to P. falciparum variant surface antigens (anti-VSA IgG) and glutamate-rich protein (anti-GLURP IgG) were measured with flow cytometry and ELISA assays, respectively. Regression analyses showed that alpha-thalassemia was associated with a reduced risk of uncomplicated malaria episodes and that this advantageous effect seemed to be more predominant in children older than 5 years of age, but was independent of levels of antibodies to VSA and GLURP...
Post-malaria neurological syndrome--two cases in patients of African origin [Am J Trop Med Hyg. 2008 May;78(5):699-701] — (English)
Post-malaria neurological syndrome (PMNS) defined by a post-infective encephalopathy occurring within 2 months after an episode of Plasmodium falciparum infection is still a debated entity. We describe 2 cases of PMNS in 2 patients of African origin, born and living in France. Both patients had severe P. falciparum infection, followed by PMNS. They recovered with no sequelae. These are the first-reported cases of PMNS in patients of African ethnicity and living in France...
Transfusion of Blood Components May Improve Survival in Severe Malaria Anemia in Children [Am J Trop Med Hyg. 2008 May;78(5):693; author reply 693-4] — (English)
Leter to the Editor (Nwaneri MO)..
Transfusion of Blood Components May Improve Survival in Severe Malaria Anemia in Children [Am J Trop Med Hyg. 2008 May;78(5):693-694] — (English)
Letter to the Editor (Charles O. Obonyo )...
Chemical target validation studies of aminopeptidase in malaria using alpha-aminoalkylphosphonate and phosphonopeptide inhibitors [Antimicrob. Agents Chemother. doi:10.1128/AAC.01327-07] — (English)
During its intra-erythrocytic phase, the most lethal human malarial parasite Plasmodium falciparum digests host cell hemoglobin as a source of some of the amino acids required for its own protein synthesis. A number of parasite endopeptidases (including plasmepsins and falcipains) process the globin into small peptides. These peptides appear to be further digested to free amino acids by aminopeptidases, enzymes that catalyse the sequential cleavage of N-terminal amino acids from peptides. Aminopeptidases are classified into different evolutionary families according to their sequence motifs and preferred substrates. The aminopeptidase inhibitor bestatin can disrupt parasite development, suggesting that this group of enzymes might be a chemotherapeutic target. Two bestatin-susceptible aminopeptidase activities, associated with gene products belonging to the M1 and M17 families, have been described in blood-stage P. falciparum but it is not known whether one or both is/are required for parasite development. To establish whether inhibition of the M17 aminopeptidase is sufficient to confer antimalarial activity, we evaluated 35 aminoalkylphosphonate and phosphonopeptide compounds designed to be specific inhibitors of M17 aminopeptidases. The compounds had a range of activities against cultured P. falciparum with 50% inhibitory concentrations down to 14 µM. Some of the compounds were also potent inhibitors of parasite aminopeptidase activity, though it appeared that many were capable of inhibiting the M1 enzyme as well as the M17 one. There was a strong correlation between the potency of the compounds against whole parasites and enzyme, suggesting that M17 and/or M1 aminopeptidases may be valid antimalarial drug targets...
Synergy and specificity of two Na+-aromatic amino acid symporters in the model alimentary canal of mosquito larvae [Journal of Experimental Biology 211, 1594-1602 (2008)] — (English)
The nutrient amino acid transporter (NAT) subfamily is the largest subdivision of the sodium neurotransmitter symporter family (SNF; also known as SLC6; HUGO). There are seven members of the NAT population in the African malaria mosquito Anopheles gambiae, two of which, AgNAT6 and AgNAT8, preferably transport indole- and phenyl-branched substrates, respectively. The relative expression and distribution of these aromatic NATs were examined with transporter-specific antibodies in Xenopus oocytes and mosquito larval alimentary canal, representing heterologous and tissue expression systems, respectively. NAT-specific aromatic-substrate-induced currents strongly corresponded with specific accumulation of both transporters in the plasma membrane of oocytes. Immunolabeling revealed elevated expressions of both transporters in specific regions of the larval alimentary canal, including salivary glands, cardia, gastric caeca, posterior midgut and Malpighian tubules. Differences in relative expression densities and spatial distribution of the transporters were prominent in virtually all of these regions, suggesting unique profiles of the aromatic amino acid absorption. For the first time reversal of the location of a transporter between apical and basal membranes was identified in posterior and anterior epithelial domains corresponding with secretory and absorptive epithelial functions, respectively. Both aromatic NATs formed putative homodimers in the larval gut whereas functional monomers were over-expressed heterologously in Xenopus oocytes. The results unequivocally suggest functional synergy between substrate-specific AgNAT6 and AgNAT8 in intracellular absorption of aromatic amino acids. More broadly, they suggest that the specific selectivity, regional expression and polarized membrane docking of NATs represent key adaptive traits shaping functional patterns of essential amino acid absorption in the metazoan alimentary canal and other tissues...
HIV and malaria co-infection: interactions and consequences of chemotherapy [Trends Parasitol. 2008 May 2] — (English)
The global epidemiology of HIV/AIDS and malaria overlap because a significant number of HIV-infected individuals live in regions with different levels of malaria transmission. Although the consequences of co-infection with HIV and malaria parasites are not fully understood, available evidence suggests that the infections act synergistically and together result in worse outcomes. The importance of understanding chemotherapeutic interactions during malaria and HIV co-infection is now being recognized. We know that some antimalarial drugs have weak antiretroviral effects; however, recent studies have also demonstrated that certain antiretroviral agents can inhibit malaria-parasite growth. Here, we discuss recent findings on the impact of HIV/AIDS and malaria co-infection and the possible roles of chemotherapy in improving the treatment of these diseases...
Effects of malaria double infection in birds: one plus one is not two [Journal of Evolutionary Biology, 2008 May 5] — (English)
Avian malaria parasites are supposed to exert negative effects on host fitness because these intracellular parasites affect host metabolism. Recent advances in molecular genotyping and microscopy have revealed that coinfections with multiple parasites are frequent in bird–malaria parasite systems. However, studies of the fitness consequences of such double infections are scarce and inconclusive. We tested if the infection with two malaria parasite lineages has more negative effects than single infection using 6 years of data from a natural population of house martins. Survival was negatively affected by both types of infections. We found an additive cost from single to double infection in body condition, but not in reproductive parameters (double-infected had higher reproductive success). These results demonstrate that malaria infections decrease survival, but also have different consequences on the breeding performance of single- and double-infected wild birds...
VAR2CSA Domains Expressed in Escherichia coli Induce Cross-Reactive Antibodies to Native Protein [The Journal of Infectious Diseases 2008;197:1119–1123 ] — (English)
The variant surface antigen VAR2CSA is a pregnancy malaria vaccine candidate, but its size and polymorphism are obstacles to development. We expressed 3D7-type VAR2CSA domains in Escherichia coli as insoluble His-tagged proteins (Duffy binding-like [DBL] domains DBL1, DBL3, DBL4, and DBL5) that were denatured and refolded or as soluble glutathione S-transferase-tagged protein (DBL6). Anti-DBL5 antiserum cross-reacted with surface proteins of chondroitin sulfate A (CSA)-binding laboratory strains (3D7-CSA and FCR3-CSA) and a clinical pregnancy malaria isolate, whereas anti-DBL6 antiserum reacted only to 3D7 surface protein. This is the first report that E. coli-expressed VAR2CSA domains induce antibody to native VAR2CSA...
A Prodomain Peptide of Plasmodium falciparum Cysteine Protease (Falcipain-2) Inhibits Malaria Parasite Development [ASAP J. Med. Chem., ASAP Article, 10.1021/jm070735f ] — (English)
Falcipain-2 (FP-2), a papain family cysteine protease of Plasmodium falciparum, is a promising target for antimalarial chemotherapy. Designing inhibitors that are highly selective for falcipain-2 has been difficult because of broad specificity of different cysteine proteinases. Because propeptide regions of cysteine proteases have been shown to inhibit their cognate enzymes specifically and selectively, in the present study, we evaluated the inhibitory potential of few falcipain-2 proregion peptides. A 15 residue peptide (PP1) inhibited falcipain-2 enzyme activity in vitro. Studies on the uptake of PP1 into the parasitized erythrocytes showed access of peptide into the infected RBCs. PP1 fused with Antennapedia homeoprotein internalization domain blocked hemoglobin hydrolysis, merozoite release and markedly inhibited Plasmodium falciparum growth and maturation. Together, our results identify a peptide derived from the proregion of falcipain-2 that blocks late-stage malaria parasite development in RBCs, suggesting the development of peptide and peptidometric drugs against the human malaria parasite...
Non-electrolyte permeability of deoxygenated sickle cells compared [Blood Cells Mol Dis. 2008 May 2] — (English)
The passive permeability pathways of red cells are poorly defined, with the exception of the Gardos channel. Several cation and anion pathways can be induced by a variety of manoeuvres, however, including treatment with oxidants, low ionic strength (LIS), shrinkage, swelling and also infection with the intra-erythrocytic malaria parasite. Several of these stimuli (malaria, swelling, LIS), in addition, also activate a non-electrolyte this permeability. Sickle cells uniquely show a deoxygenation-induced pathway, which is termed Psickle and is usually considered to be a conductive cationic pathway. In this report, we explore further the extent to which this permeability pathway of deoxygenated sickle cells is available for non-electrolyte transport. We show that a number of solutes are permeable, with greater permeability to sugars (notably lactose and maltose) and smaller molecules, and less to charged or zwitterionic species...
Isolation and antimalarial activity of new morphinan alkaloids on Plasmodium yoelii liver stage [Bioorg Med Chem. 2008 Apr 18] — (English)
Decoction of Strychnopsis thouarsii is used in the Malagasy traditional medicine to combat malaria. We have shown that this traditional remedy prevents malaria infection by targeting Plasmodium at its early liver stage. Bioassay-guided fractionation of S. thouarsii stem barks extracts, using a rodent Plasmodium yoelii liver stage parasites inhibition assay, led to isolate the new morphinan alkaloid tazopsine (1) together with sinococuline (2) and two other new related morphinan analogs, 10-epi-tazopsine (3) and 10-epi-tazoside (4). Structures were characterized by 2D NMR, MS, and CD spectral analysis. Compounds 1–3 were found to fully inhibit the rodent P. yoelii liver stage parasites in vitro...
'He is now like a brother, I can even give him some blood' - Relational ethics and material exchanges in a malaria vaccine 'trial community' in The Gambia [Soc Sci Med. 2008 May 1] — (English)
This paper explores social relations within the ‘trial community’ (staff and volunteers) of a Malaria Vaccine Trial (MVT), implemented by the Medical Research Council (MRC) in The Gambia between 2001 and 2004. It situates ethical concerns with medical research within the everyday life of scientific fieldwork. Based upon discussions with volunteers and staff, we explore processes of mediation between scientific project and study population, and between formal ethics, local ethical debates and everyday practice. We observe that material contact and substantial transactions, notably of blood and medicine, are central to the construction of the MVT...
Comparison of Anopheles gambiae and Culex pipiens acetycholinesterase 1 biochemical properties [Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2008 Mar 28] — (English)
Selection of insensitive acetycholinesterase 1 (AChE1) has occurred in several mosquito species controlled with carbamate (CX) and organophosphate (OP) insecticides. In case of pyrethroid resistance, these insecticides represent an alternative for disease vector control program. Their heavy use in agriculture has selected resistant populations of Anopheles gambiae in West Africa. The evolution of resistance has to be studied to prevent, or at least slow down, the spread of resistant mosquito in wild populations. An. gambiae shares the same resistance mechanism to CX and OP insecticides as Culex pipiens, which was attributed to the G119S substitution in the AChE1 enzyme. By comparing resistant AChE1 from both species, we show here that similar resistance levels are obtained toward 10 insecticides of both classes. Moreover, similar AChE1 activity levels are recorded between either susceptible or resistant mosquitoes of both species. Enzymes belonging to both species seem thus to share identical properties. Consequently, we hypothesize that fitness cost associated with AChE1 insensitivity in C. pipiens mosquitoes should be similar in An. gambiae and thus be used in strategies to control resistant populations where malaria is prevalent...
Molecular diagnosis of malaria in the field: development of a novel 1-step nucleic acid lateral flow immunoassay for the detection of all 4 human Plasmodium spp. and its evaluation in Mbita, Kenya [Diagnostic Microbiology and Infectious Disease, 2008 Apr 30] — (English)
Microscopy is frequently used for malaria diagnosis, but at low parasitemia, it becomes less sensitive and time consuming. Molecular tools allow for specific/sensitive diagnosis, but current formats, such as polymerase chain reaction (PCR) combined with gel electrophoresis and real-time PCR assays, are difficult to implement in resource-poor settings. Development of a simple, fast, sensitive, and specific detection system, nucleic acid lateral flow immunoassay (NALFIA) for amplified pan-Plasmodium PCR products, is described. The NALFIA lower detection limit is 0.3 to 3 parasites/μL, 10-fold more sensitive than gel electrophoresis analysis. Evaluating 650 clinically suspected malaria cases with the pan-Plasmodium assay under field conditions (rural Kenya) revealed that NALFIA detected more positives than microscopy (agreement, 95%; κ value = 0.85), and there was an excellent agreement between gel electrophoresis and NALFIA (98.5%; κ value = 0.96). In conclusion, NALFIA is more sensitive than microscopy and a good alternative to detect PCR products while circumventing using electricity or expensive equipment, making NALFIA the 1st step toward molecular field diagnosis...
Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-gamma and antibody responses in mice [Vaccine. 2008 Apr 16] — (English)
Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation...
Assessing the polyamine metabolism of Plasmodium falciparum as chemotherapeutic target [Mol Biochem Parasitol. 2008 Mar 25] — (English)
More than 30 years ago the potent ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) was designed as new anticancer drug. Its efficacy was not as expected since the polyamine metabolism in mammalian cells seemed to be far more complex. However when DFMO was applied to African trypanosomes its effect on this protozoan parasite was highly convincing. Thenceforward many researchers tested DFMO and also other polyamine synthesis inhibitors against different parasites among them the causative agent of malaria Plasmodium. This review recapitulates the different attempts to interfere chemically with the plasmodial polyamine metabolism, the impact on the disease as well as its biochemical and molecular background. It will show that this fast proliferating organism depends for growth on high amounts of polyamines and that Plasmodium has its own and unique polyamine synthesis, differing highly from the mammalian one mainly in the arrangement of the key enzymes, S-adenosylmethionine decarboxylase and ornithine decarboxylase (AdoMetDC/ODC), on a bifunctional protein...
Malaria in pregnancy: a literature review [Journal of Midwifery & Women's Health, Volume 53, Issue 3, May-June 2008, Pages 209-215] — (English)
Pregnant women are more likely than nonpregnant women to become infected with malaria and to have severe infection. The effects of malaria during pregnancy include spontaneous abortion, preterm delivery, low birth weight, stillbirth, congenital infection, and maternal death. Malaria is caused by the four species of the protozoa of the genus Plasmodium, which is transmitted by the bite of the female Anopheline mosquito, congenitally, or through exposure to infected blood products. This article reviews the epidemiology, pathology, clinical symptoms, diagnosis, and treatment of malaria in pregnant women. Interventions to prevent malaria include intermittent preventive treatment, insecticide-treated nets, and case management of malaria infection and anemia...
Silencing an Anopheles gambiae catalase and sulfhydryl oxidase increases mosquito mortality after a blood meal [Arch Insect Biochem Physiol. 2008 May 2] — (English)
Catalase is a potent antioxidant, likely involved in post-blood meal homeostasis in mosquitoes. This enzyme breaks down H2O2, preventing the formation of the hydroxyl radical (HO·). Quiescins are newly classified sulfhydryl oxidases that bear a thioredoxin motif at the N-terminal and an ERV1-like portion at the C-terminal. These proteins have a major role in generating disulfides in intra- or extracellular environments, and thus participate in redox reactions. In the search for molecules to serve as targets for novel anti-mosquito strategies, we have silenced a catalase and a putative quiescin/sulfhydryl oxidase (QSOX), from the African malaria vector Anopheles gambiae, through RNA interference (RNAi) experiments. We observed that the survival of catalase- and QSOX-silenced insects was reduced over controls following blood digestion, most likely due to the compromised ability of mosquitoes to scavenge and/or prevent damage caused by blood meal-derived oxidative stress. The higher mortality effect was more accentuated in catalase-silenced mosquitoes, where catalase activity was reduced to low levels. Lipid peroxidation was higher in QSOX-silenced mosquitoes suggesting the involvement of this protein in redox homeostasis following a blood meal. This study points to the potential of molecules involved in antioxidant response and redox metabolism to serve as targets of novel anti-mosquito strategies and offers a screening methodology for finding targetable mosquito molecules...
Influence of NO Synthase Inhibitor L-NAME on Parasitemia and Survival of Plasmodium berghei Infected Mice [Cell Physiol Biochem 2008;21:481-488 (DOI: 10.1159/000129641)] — (English)
Accelerated suicidal death or eryptosis of infected erythrocytes may delay development of parasitemia in malaria. Eryptosis is inhibited by nitric oxide (NO). The present study has been performed to explore, whether inhibition of NO synthase by L-NAME modifies the course of malaria. We show here that L-NAME (>10 µM) increased phosphatidylserine exposure of Plasmodium falciparum infected human erythrocytes, an effect significantly more marked than in noninfected human erythrocytes. We further show that parasitemia in Plasmodium berghei infected mice was significantly decreased (from 50% to 18% of circulating erythrocytes 20 days after infection) by addition of 1 mg/ml L-NAME to the drinking water. According to CFSE labelling L-NAME treatment accelerated the clearance of both, noninfected and infected, erythrocytes from circulating blood, but did not significantly extend the life span of infected animals. In conclusion, treatment with L-NAME shortens the life span of circulating erythrocytes and thus delays development of parasitemia during malaria...
Coinfection with Nonlethal Murine Malaria Parasites Suppresses Pathogenesis Caused by Plasmodium berghei NK65 [The Journal of Immunology, 2008, 180: 6877-6884] — (English)
Mixed infection with different Plasmodium species is often observed in endemic areas, and the infection with benign malaria parasites such as Plasmodium vivax or P. malariae has been considered to reduce the risk of developing severe pathogenesis caused by P. falciparum. However, it is still unknown how disease severity is reduced in hosts during coinfection. In the present study, we investigated the influence of coinfection with nonlethal parasites, P. berghei XAT (Pb XAT) or P. yoelii 17X (Py 17X), on the outcome of P. berghei NK65 (Pb NK65) lethal infection, which caused high levels of parasitemia and severe pathogenesis in mice. We found that the simultaneous infection with nonlethal Pb XAT or Py 17X suppressed high levels of parasitemia, liver injury, and body weight loss caused by Pb NK65 infection, induced high levels of reticulocytemia, and subsequently prolonged survival of mice. In coinfected mice, the immune response, including the expansion of B220intCD11c+ cells and CD4+ T cells and expression of IL-10 mRNA, was comparable to that in nonlethal infection. Moreover, the suppression of liver injury and body weight loss by coinfection was reduced in IL-10–/– mice, suggesting that IL-10 plays a role for a reduction of severity by coinfection with nonlethal malaria parasites...
No genetic bottleneck in Plasmodium falciparum wild-type Pfcrt alleles reemerging in Hainan Island, China, following high-level chloroquine resistance [Antimicrobial Agents and Chemotherapy, January 2008, p. 345-347, Vol. 52, No. 1] — (English)
Chloroquine-resistant Plasmodium falciparum was highly prevalent in Hainan, China, in the 1970s. Twenty-five years after cessation of chloroquine therapy, the prevalence of P. falciparum wild-type Pfcrt alleles has risen to 36% (95% confidence interval, 22.1 to 52.4%). The diverse origins of wild-type alleles indicate that there was no genetic bottleneck caused by high chloroquine resistance...
Vaccination strategy to target lysyl oxidase-like 4 in dendritic cell based immunotherapy for head and neck cancer [Int J Oncol. 2008 Feb;32(2):317-22] — (English)
Overexpression of lysyl oxidase (LOX) is associated with the invasive potential of metastatic breast and head and neck cancer (HNC) cells and reduced metastasis-free and overall survival. Recently, we have demonstrated up-regulation of a new member of the LOX family, lysyl oxidase-like 4 (LOXL4), in invasive HNC revealed a significant correlation between LOXL4 expression and local lymph node metastases and higher tumour stages. The objective of this study was to examine whether cellular LOXL4 may provide an effective target for cell-meditated immunotherapy in invasive tumours associated with LOXL4 overexpression. As a feasibility study we expressed LOXL4 mRNA in immature dendritic cells derived from human peripheral blood mononuclear cells (PBMC). LOXL4 protein expression was ascertained using Western blotting and immunocytochemistry with polyclonal rabbit anti-LOXL4 antibody. The successfully transfected immature dendritic cells (DCs) were induced to mature with GM-CSF, IL-4, IL-1β, TNF-α, IL-6, and PGE2, and then used to stimulate T cell enriched non-adherent fraction of PBMC. LOXL4 specific T cell stimulation induced cytotoxic T lymphocyte (CTL) response was monitored using IFN-γ secretion from the non-adherent PBMC fraction exposed to mature, LOXL4 transfected DCs acting as the antigen presenting target cells. LOXL4-DC stimulated T cells produced higher IFN-γ secretion compared to unstimulated T cells and T cells stimulated with untransfected DCs, in the presence of the pan-DR-epitope (PADRE). These initial results demonstrated the potential for LOXL4-transfected DCs to serve as efficient tumour vaccine and support their suitability as a vaccination strategy applicable to cancer patients with tumour specific up-regulation of LOXL4...
Prepared in cooperation with WHO ANGOLA INFO.
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