21.09.2007
Suriname has 'already hit' malaria MDG [SciDev.net - UK] — (English)
The country of Suriname in northern South America has already exceeded its 2015 Millennium Development Goal target for the reduction of malaria...
Artesunate: link in fighting malaria [EUROPA - Brussels,Belgium] — (English)
Funded by the European and Developing Countries Clinical Trials Partnership, (EDCTP) in collaboration with Medicines for Malaria Venture (MMV), the EUR 5.3 million trial is a culmination of activity by European and international organisations in pursuit of better treatments for malaria...
Insecticide-treated bednet halves malarial death risk for infants [AFP] — (English)
Using insecticide-treated bednets can nearly halve deaths from malaria among children aged under five, according to a study in Kenya published in Saturday's Lancet...
Mit Insektiziden imprägnierte Moskitonetze senken Kinderste [Wissenschaft - Germany ] — (Deutsch)
Die Gebrauch von Insektizid-präparierten Moskitonetzen (ITNs) verringert die Kindersterblichkeit um 44 Prozent. Darüber hinaus hat eine kombinierte Vorgehensweise von Social Marketing und freier Abgabe von ITNs ähnliche Effekte auf die Überlebensrate der Kinder, wie sie in vorangegangenen randomisierten kontrollierten Studien ermittelt wurden...
Ranbaxy's Partner Pulls Out of Malaria Drug Research, Mint Says [ Bloomberg - United Kingdom ] — (English)
The Medicines for Malaria Venture has decided to stop funding the development of a malaria drug by India's Ranbaxy Laboratories Ltd., the Mint reported, citing an unidentified official from the agency...
Kenya saving children's lives with bed nets: study [Reuters] — (English)
Kenya is saving children's lives with a national program to distribute insecticide-treated bed nets to prevent malaria, a study showed on Thursday...
The Doomsday Spray: To fight malaria, African nations are turning to DDT [Newsweek - USA] — (English)
Fifty years ago Africa had a coherent strategy to fight malaria. It involved spraying large amounts of the pesticide dichlorodiphenyltrichloroethane, or DDT, to curb the mosquito that carries malaria. This campaign was hugely successful, but it came to a halt shortly after the 1962 publication of Rachel Carson's "Silent Spring," which described the environmental consequences of DDT running off into lakes and rivers. Malaria cases soared on the continent, except in South Africa, which continued to spray. Finally, in 1996, pressured by environmental groups, South Africa dropped DDT for a less toxic alternative. Four years later, the country was facing its first malaria epidemic in half a century...
Surfography show to aid malaria prevention
[ The Argonaut - United States ] — (English)
SurfAid International, a humanitarian aid organization that focuses on getting much-needed healthcare and malaria prevention technologies to underprivileged communities mainly located in the Sumatran Islands, will team up with fine art photographers locally for its latest charity benefit event...
Malaria-related mortality based on verbal autopsy in an area of low endemicity in a predominantly rural population in Ethiopia [Malaria Journal 2007, 6:128 (21 September 2007)] — (English)
Measuring the magnitude of malaria-attributed deaths at community level poses a considerable difficulty and verbal autopsy, despite its low sensitivity and specificity, can be a helpful technique as demonstrated by this study in rural Ethiopia...
20.09.2007
Ending Malaria Deaths in Africa (extended version) [Scientific American - USA] — (English)
For Africa, the epicenter of the world’s malaria scourge, an historic breakthrough in health and economic development is now within reach. A combination of new technologies, new methods of disease control and rising public awareness is poised to bring malaria deaths down by 90 percent or more—if we will follow through...
Gates gives ND $20M for malaria study [Indianapolis Star - United States] — (English)
The Bill & Melinda Gates Foundation awarded the University of Notre Dame a $20 million grant today to support research aimed at evaluating and improving malaria control programs...
Nigeria: Country Set to Produce Drugs for Malaria [Daily Champion (Lagos) via AllAfrica.com] — (English)
Nigeria may become the first country in Sub-Saharan Africa to locally extract active ingredients from Artemisia Annua, for the production of Artemisinin-based anti-malaria drugs, including combination therapies (ACTs)...
Researchers' work from the People's Republic of China and the United States adds to malaria body of knowledge [Calibre MacroWorld - United States ] — (English)
Malaria data are the focus of recent research from the People's Republic of China and the United States...
Nurses Benefited from Malaria Workshop in Sierra Leone [Awareness Times - Freetown,Sierra Leone] — (English)
About 38 Nurses in the Moyamba District are said to have benefited from a one day malaria prevention workshop conducted at the Moyamba Government Hospital...
Cameroun: La lutte contre le paludisme monte d'un cran [Le Messager (Douala) via AllAfrica.com] — (Français)
Coarsucam s'ajoute à une gamme déjà variée de produits. Les malades peuvent choisir leur traitement...
19.09.2007
Paludisme: le Bénin va distribuer 1,4 million de moustiquaires en octobre [Le Monde - France] — (English)
Le gouvernement du Bénin va distribuer gratuitement en octobre 1.400.000 moustiquaires imprégnées d'insecticide aux femmes enceintes et aux enfants de moins de 5 ans, pour limiter les cas graves de paludisme, a annoncé le ministre de la Santé Késillé Tchalla...
Deutschland will mehr tun für die Bekämpfung von Aids, Malaria und TBC [ Deutscher Bundestag - Germany ] — (Deutsch)
Ab 2008 will Deutschland jährlich 200 Millionen Euro für die Arbeit des Globalen Fonds zur Bekämpfung von Aids, Tuberkulose und Malaria beisteuern. Seit 2002 hat die Bundesregierung für diesen Zweck insgesamt 394 Millionen Euro ausgegeben...
Positive Data From Early Stage Clinical Trial Of GenVec Malaria Vaccine Presented At Malaria Conference - Update [GNVC] [RTT News - Williamsville,NY,USA] — (English)
GenVec Inc. (GNVC) announced that encouraging data gathered from early stage clinical trial of its investigational malaria vaccine were presented at the Malaria Vaccines for the World Conference at the Royal Society of Medicine in London, U.K., September 17-19, 2007...
PROMISING EARLY DATA FROM PHASE I/II CLINICAL TRIAL USING GENVEC VACCINE PRESENTED AT MALARIA CONFERENCE [GenVec Press Release] — (English)
GenVec, Inc. announced today that encouraging data from malaria vaccine studies using the company's adenovector technologies were reported in multiple presentations by scientists representing GenVec and its collaborators at the Malaria Vaccines for the World Conference at the Royal Society of Medicine in London, U.K., September 17-19, 2007...
Global warming to increase infectious disease: study [AFP] — (English)
Global warming likely will lead to an increase in infectious disease around the world, as viruses, microbes and the agents that spread them flourish, experts at a medical conference warned Tuesday...
Neurological Involvement in Acute Falciparum Malaria in Kenyan Children - Reply [Journal of American Medical Association - Chicago,IL,USA] — (English)
Dr Rossi raises a question about the potential influence of salicylate toxicity and Reye syndrome on our estimate of the burden of neurological involvement in children with falciparum malaria. He notes that administration of salicylates to febrile African children is a common practice; exposure to salicylates can predispose to Reye syndrome; metabolic acidosis, respiratory distress, coma, and hypoglycemia are clinical features that are common to salicylate toxicity and Reye syndome as well as cerebral malaria; and suggests that it is therefore necessary to measure salicylate levels in all children with clinical features of cerebral malaria and history of salicylate use to avoid a misdiagnosis between these conditions...
Malaria Chemoprophylaxis for Coalition Troops in Afghanistan [Journal of American Medical Association - Chicago,IL,USA] — (English)
As members of the public health authority that issues recommendations for malaria chemoprophylaxis for the Canadian Forces members, we were interested in the Research Letter by Dr Croft and colleagues1 regarding the differences in the approach to malaria prevention among armed forces deployed to Afghanistan. However, the data reported for Canada are inaccurate in that, after a reassessment of risk, the Canadian Forces discontinued the use of malaria chemoprophylaxis for members in Kabul in April 2005 and at Kandahar Air Field (from where the Canadian Forces primarily operates) in May 2006. Malaria chemoprophylaxis is still recommended outside these locations during the malaria season. Although mefloquine may be the drug most often selected, Canadian Forces members have the option of using either mefloquine weekly or doxycycline daily, with atovaquone/proguanil preferred when protection of short duration is needed...
Kerteszia subgenus of Anopheles associated with the Brazilian Atlantic rainforest: current knowledge and future challenges [Malaria Journal 2007, 6:127 (19 September 2007)] — (English)
Current state of knowledge about Kerteszia species in relation to the Atlantic Rainforest ecosystem, with emphasis on ecological characteristics related to epidemiological aspects of this group of species...
Interdependence of domestic malaria prevention measures and mosquito-human interactions in urban Dar es Salaam, Tanzania [Malaria Journal 2007, 6:126 (19 September 2007)] — (English)
In a situation of changing mosquito and human behaviour, ITNs may confer lower levels of personal protection which need to be supplemented by measures of environmental management in the community, including mosquito-proofing of houses and larviciding...
Rwanda: Jehovah's Witness Backs Spraying [New Times (Kigali) via AllAfrica.com] — (English)
A Jehovah's Witnesses of God believer has said that the religion has not rejected the ongoing anti-malaria spraying campaign as recent field reports from the spraying teams said...
WHO warns of malaria in Asia-Pacific [Bangkok Post - Thailand] — (English)
The World Health Organisation (WHO) has issued a warning to all countries in the Asia-Pacific region, including Thailand, about the threat of malaria...
AMC records 50% drop in malaria cases [Times of India - India] — (English)
Some good news for Amdavadis. Ahmedabad Municipal Corporation’s (AMC) malaria department has recorded a drastic reduction in malaria cases by 50 per cent between January and September 2007 when compared to same period last year...
18.09.2007
Angola: Bié - Minsa Distributes 30,000 Mosquito Nets in Chinguar Locality [Angola Press Agency (Luanda) via AllAfrica.com] — (English)
At least 30,000 mosquito nets treated with insecticide were distributed from last January by the Health Ministry to pregnant women and children under five years old, in Chinguar district, 75 kilometres to the south of Kuito city, central Bié province...
Antimalarials 'give children an edge' at school [ SciDev.Net - United Kingdom ] — (English)
Preventative malaria treatment could improve schoolchildren's performance in endemic areas, a study suggests...
SA sees 'dramatic reduction in malaria cases' [SABC News - Auckland Park,South Africa] — (English)
Health minister, Manto Tshabalala-Msimang, says cooperation between South Africa, Swaziland and Mozambique has led to a 90% reduction in new malaria infections in the three countries...
Mozambique: Church urged to organize, seize outreach opportunities [Adventist News Network - Silver Spring,MD,USA] — (English)
"We are doing evangelism, building new churches, fighting malaria and digging wells for the community," Ratsara told church leaders. "Isn't this a testimony that Mozambique is in focus for our church in this region?"...
Deutsche Post World Net und UNICEF verstärken Zusammenarbeit im Kampf gegen Kindersterblichkeit [Deutsche Post - Germany ] — (English)
In Kenia sterben in einzelnen Regionen 15 Prozent der Kinder vor ihrem fünften Geburtstag. Malariaerkrankungen sind dabei oft Todesursache. Laut Weltgesundheitsorganisation (WHO) konnte jedoch die Zahl der malariabedingten Todesfälle bei Kindern in Kenia von 34.000 im Jahr 2005 bereits auf 16.000 in 2006 gesenkt werden...
Sénégal: 100.000 moustiquaires bientôt distribuées à Kolda [Agence de Presse Sénégalaise (Dakar via AllAfrica.com] — (Français)
Quelque 100.000 moustiquaires imprégnées de longue durée (trois ans) seront mises à la disposition des mères d'enfants des 0 à 5 ans dès le mois de novembre prochain, a annoncé, mardi à Kolda, le responsable régional du Programme de renforcement de la nutrition (PRN)...
17.09.2007
Sugary Site Of Malarial Invasion [Chemical & Engineering News - USA] — (English)
Malaria parasites infect mosquitoes by clutching onto a newly identified sugar chain in the insects’ guts. This revelation could facilitate the development of new strategies to thwart transmission of the deadly mosquito-borne disease to humans....
New Drug Institute to Tackle Tuberculosis, Malaria, HIV/AIDS [Associated Content - Denver,CO,USA] — (English)
According to the International Drug Discovery Institute (IDDI), a new non-profit international institute formed of leading drug researchers will help fight certain issues concerning tuberculosis (TB), malaria, and HIV/AIDS. The institute plans to attract many of the extremely talented professionals, scientists, activists, and drug researchers from the established and renowned research laboratories around the world...
Neue Forschungsprojekte zur Bekämpfung von Malaria [LaborPraxis - Germany ] — (Deutsch)
Bayer CropScience und das Innovative Vector Control Consortium (IVCC) haben einen Kooperationsvertrag für zwei Projekte zur Erforschung neuer effektiver Lösungen im Kampf gegen Malaria und andere Krankheiten, die durch Insekten übertragen werden, unterzeichnet...
Ipca receives WHO nod for anti-malarial drug [PTI/Hindu Business Line] — (English)
Pharmaceutical company Ipca Laboratories on Friday said that it has received approval from World Health Organisation (WHO) for its anti-malarial drug. The approval was for the finished product formulation, Artesunate 50 mg tablet, under World He alth Organisation's prequalification programme, the company said in a filing to the BSE. Artesunate 50 mg tablet is an artemisinin-based formulation, which is recommended by WHO to be used in combination with other anti-malarials like Amodiaquine, Meflo quine or Sulfadoxine and Pyrimethamine, it said...
Students to Host Fundraising Malaria Awareness Week on Campus [Wesleyan Connection - Middletown,CT,USA] — (English)
Malaria Awareness Week will begin with an educational lecture on the causes of malaria, and how the disease can be prevented. Mid-week, a documentary about malaria will be shown, and Wesleyan students will speak about their own experiences having the disease. Erika Taylor, assistant professor of chemistry, and Bill Johnston, professor of East Asian Studies, professor and chair of history, will lead a discussion panel. Other activities include a week-long bake sale and a dance party, with donation proceeds going towards the cause...
Angola: Children, Pregnant Women Get Mosquito Nets [Angola Press Agency (Luanda) via AllAfrica.com] — (English)
13,000 insecticide treated mosquito nets were distributed last August to children under five years old and pregnant women at Caála District, central Huambo Province, in the light of the governmental programme aimed at reducing the mortality caused by malaria...
Sierra Leone: Bed Nets Not the Answer to Malaria - MCH Nurse [Concord Times (Freetown) via AllAfrica.com] — (English)
Maternal Child Health (MCH) nurse attached to the Gbado Health Post in Kandu Leppyiama chiefdom, Kenema district, Marian Pajue, Saturday claimed that treated mosquito bed nets distributed to pregnant women and lactating mothers is not the answer to prevent malaria...
Annual child survival rate improves globally, but... [Vanguard - Apapa,Lagos,Nigeria] — (English)
THE global world of health has been agog since the announcement, last week, that the burden of death among children under age five worldwide reached a record low of about 9.7 million in 2006. For the first time in modern history, the number of children dying before the age of five has fallen below 10 million per year. This rare feat, according to a UNICEF report, was largely attributable to global efforts of promoting malaria prevention measures, childhood immunization and breast-feeding...
Should we allow DDT? [East African - Nairobi,Kenya] — (English)
While DDT has long been the most effective and cheapest insecticide to kill mosquitoes that transmit malaria, Western pressure saw it removed from anti-malaria projects in sub-Saharan Africa, writes TIM QUERENGESSER ...
Free anti-malarial drugs producing results, says Gabriel [Jamaica Observer - Kingston,Jamaica] — (English)
Countries affected by malaria outbreaks can access anti-malarial drugs free of cost through a partnership between the World Health Organisaton (WHO) and Swiss pharmaceutical company Novartis...
16.09.2007
DNA barcoding on track to revolutionise malaria control [Natural History Museum - London,UK] — (English)
By accurately identifying the carrier species, it is possible to target the larval habitats or adult resting sites of the mosquito in question, minimising cost and making disease control more efficient and more effective. As Yvonne-Marie Linton explains this week at the second International Barcode of Life Conference in Taipei, 'The MBI has already made more than 3000 DNA records for more than 250 species available since we started six months ago, but there is still lots of work to be done.'...
A fishy treatment for malaria [LabnewsOnline - London,UK] — (English)
Pesticide resistance is an increasing problem for malarial control methods but new research has provided a unique solution - a fish...
Malaria − an overview [FEBS Journal, Volume 274 Issue 18 Page 4670-4679, September 2007] — (English)
Malaria is caused by protozoan parasites of the genus Plasmodium and is a major cause of mortality and morbidity worldwide. These parasites have a complex life cycle in their mosquito vector and vertebrate hosts. The primary factors contributing to the resurgence of malaria are the appearance of drug-resistant strains of the parasite, the spread of insecticide-resistant strains of the mosquito and the lack of licensed malaria vaccines of proven efficacy. This minireview includes a summary of the disease, the life cycle of the parasite, information relating to the genome and proteome of the species lethal to humans, Plasmodium falciparum, together with other recent developments in the field...
Plasmodium falciparum gametocytes: still many secrets of a hidden life [Molecular Microbiology (OnlineEarly Articles), doi:10.1111/j.1365-2958.2007.05904.x] — (English)
Sexual differentiation and parasite transmission are intimately linked in the life cycle of malaria parasites. The specialized cells providing this crucial link are the Plasmodium gametocytes. These are formed in the vertebrate host and are programmed to mature into gametes emerging from the erythrocytes in the midgut of a blood-feeding mosquito. The ensuing fusion into a zygote establishes parasite infection in the insect vector. Although key mechanisms of gametogenesis and fertilization are becoming progressively clear, the fundamental biology of gametocyte formation still presents open questions, some of which are specific to the human malaria parasite Plasmodium falciparum. Developmental commitment to sexual differentiation, regulation of stage-specific gene expression, the profound molecular and cellular changes accompanying gametocyte specialization, the requirement for tissue-specific sequestration in P. falciparum gametocytogenesis are proposed here as areas for future investigation. The epidemiological relevance of parasite transmission from humans to mosquito in the spread of malaria and of Plasmodium drug resistance genes indicates that understanding molecular mechanisms of gametocyte formation is highly relevant to design strategies able to interfere with the transmission of this disease...
A killer flies out of its nest [Hindustan Times - India] — (English)
Having identified malaria as one of the biggest health threats to humanity, along with tuberculosis and HIV/AIDS, scientists at the UN have decided to nuke mosquitoes. Their grand plan: to expose the killer mosquito radiation to sterilise it so that the female produces unfertilised eggs. Called Sterile Insect Technique (SIT), this method of mosquito annihilation is being developed by UN’s International Atomic Energy Agency (IAEA)...
About Town: Nothing But Nets rings up $8,000 to battle malaria [Bryan College Station Eagle - TX, United States] — (English)
A&M United Methodist Church, along with members of Texas A&M University's men's and women's basketball teams, hosted a Nothing But Nets fund raiser on Sept. 9. The effort raised about $8,000...
Bénin: Une réponse positive contre le paludisme [L'Autre Quotidien] — (Français)
L'enlèvement et le convoyage des moustiquaires pour la campagne nationale intégrée de distribution gratuite est désormais lancé. La cérémonie de lancement officiel a eu lieu samedi dernier , dans l'enceinte du Port Autonome de Cotonou, en présence des ministres de la santé, des finances ; de la micro finance, de la famille, et de quelques partenaires au développement...
15.09.2007
UNICEF's good news [Newsday - Long Island,NY,USA] — (English)
Immunizations, mosquito nets and breast-feeding cut child mortality rate...
S. Korea-based soldiers report malaria-protection issues [Stars and Stripes - Washington,DC,USA] — (English)
The soldier said he nearly passed out from the chills, the nausea and the pounding in his head. At least three other soldiers in his battalion would follow with the symptoms, he said. None were provided with repellent-treated uniforms or mosquito nets, nor had he seen anyone issued military-grade skin lotion to protect themselves in an area known for malaria-carrying mosquitoes, he said...
US Scientists Make Important Discovery in Battle Against Malaria [Voice of America - USA] — (English)
University scientists in the United States have taken what they say is an important step in the effort to end malaria. At Johns Hopkins Malaria Research Institute, scholars recently identified a sugar in mosquitoes that helps explain, for the first time, the mechanism of the malaria parasite invasion. The finding could be a key element for a vaccine development in the fight against malaria. Producer Zulima Palacio spoke with the authors of the research and files this report. Carol Pearson narrates it...
The Cost of Malaria Treatment is 256 Million Dollars [Sudanese Media Center - Sudan] — (English)
According to a report from malaria administration at ministry of health, the cost of implementing the national strategy 5 year plan [2007-2012] for malaria control is 256 million dollars. The report reveals that the free treatment coverage for health foundations is 41% as states fail to transport medicines from headquarters to different localities. The report also warned from the epidemic spread of the disease...
Ensuring sustained ACT production and reliable artemisinin supply [Malaria Journal 2007, 6:125 (15 September 2007)] — (English)
This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. A steady and predictable demand for the crop can eliminate wide fluctuations and indirectly contribute to price stability of the herb and, hence, the drug...
Congo-Kinshasa: Paludisme en province Orientale - Le taux de morbidité a augmenté de 30% [Le Potentiel (Kinshasa) via AllAfrica.com] — (English)
La sonnette d'alarme a été tirée le mois dernier par le coordonnateur provincial du Programme de lutte contre le paludisme au cours d'une matinée de sensibilisation organisée à l'Alliance Franco-Congolaise...
Articles requiring subscription
The anatomy of a malaria disaster: drug policy choice and mortality in African children [The Lancet Infectious Diseases, In Press, Corrected Proof, Available online 19 September 2007 ] — (English)
Drug-resistant malaria is a substantial problem throughout Africa and most countries must regularly adapt their antimalarial drug policies to ensure a continued coverage of effective antimalarial treatment. The timing of drug policy change can be guided by several sources of data: molecular markers of resistance, in-vitro parasite sensitivity, parasitological and clinical failure rates, and community morbidity and mortality rates. Through mathematical simulations of the spread of parasite mutations through a population exposed to high-endemic malaria, we explore the causal and chronological relations between these indicators and show which of them are obscured or confounded by other factors. Taking into account the logistical and practical advantages and disadvantages of each type of data collection, we critically appraise the value of each indicator. A major problem is shown to be that drug efficacy as perceived by people at risk will remain high even after drugs have become almost completely ineffective, resulting in a lack of community pressure for drug policy change. We show that parasitological failure is the most sensitive and timely indicator, which allows around 2–3 years for drug policy change to be implemented, so as to prevent the most rapid rise in malaria-related mortality...
Study shows insecticide-treated bednet coverage reduces child mortality by 44% [The Lancet, Volume 370, Number 9592, 22 September 2007] — (English)
A combined approach of social marketing and free distribution of insecticide-treated bednets (ITNs) leads to child survival effect similar to those seen in previous randomised controlled trials. The use of ITNs in Kenya has increased from 7% in 2004 to 67% in 2006. Usage of ITNs leads to a 44% reduction in child mortality...
Science at WHO and UNICEF: the corrosion of trust [The Lancet, Volume 370, Number 9592, 22 September 2007] — (English)
Editorial...
Millennium development goal on child mortality unlikely to be met [The Lancet, Volume 370, Number 9592, 22 September 2007] — (English)
The target for reducing mortality of children under-5 worldwide, which is incorporated into Millennium Development Goal 4 (MDG4), is unlikely to be met. Further to this, the international community is not doing any better a job of reducing child mortality than it was 30 years ago. An article calls for better and timelier child-mortality measurements through existing data and analytical strategies...
MDG4: UNICEF response [The Lancet, Volume 370, Number 9592, 22 September 2007] — (English)
UNICEF have responded to the MDG4 article by Chris Murray and colleagues. In a letter published online Sept 21 they state: 'The work by Murray and colleagues is an interesting and stimulating addition to this broad-based effort to improve child mortality estimates. But it would not have been possible without the existing data and systems supported over many years by UNICEF, WHO, and the interagency partners...
Spanish Travelers to High-Risk Areas in the Tropics: Airport Survey of Travel Health Knowledge, Attitudes, and Practices in Vaccination and Malaria Prevention [Journal of Travel Medicine, Volume 14 Issue 5 Page 297-305, September/October 2007] — (English)
Fifty-eight percent of travelers were male and the mean age was 38 years. Thirty-six percent were traveling to tropical areas for the first time. The main reason for travel was tourism (82%) or business (12%). The mean time preparing the trip was 39 days; 73% looked for information a mean of 19 days in advance and 54% were advised in travelers’ clinics. Fifty-five percent received no travel vaccines. A total of 48.1% of tourists and 30.1% of business travelers were vaccinated (p < 0.00006). The most frequent vaccines administered were as follows: typhoid fever, 32%; yellow fever, 29%; tetanus–diphtheria, 24%; and hepatitis A, 14%. Malaria prophylaxis was taken by 422 travelers including mefloquine (44%), atovaquone–proguanil (17%), chloroquine (16%), chloroquine–proguanil (15%), doxycycline (3%), and unknown (5%)...
Hospitalization Criteria in Imported Falciparum Malaria [Journal of Travel Medicine, Volume 14 Issue 5 Page 306-311, September/October 2007 ] — (English)
Among 400 patients hospitalized with falciparum malaria, mean (range) PCT was 58 (1–189) hours. In multivariate analysis, severe malaria, gastrointestinal signs, initial temperature greater than or equal to 40°C, parasitemia greater than or equal to 1%, and platelet counts less than 50,000/μL were associated with longer PCT. Offering ambulatory care to patients aged 15 to 64 years with none of the factors associated with longer PCT in the study would have resulted in 147 (37%) patients receiving outpatient care...
Structural biology of plasmodial proteins [Current Opinion in Structural Biology, In Press, Corrected Proof, Available online 17 September 2007 ] — (English)
Malaria is a global disease infecting several million individuals annually. Malarial infection is particularly severe in the poorest parts of the world and is a major drain on their limited resources. Development of drug resistance and absence of a preventive vaccine have led to an immediate necessity for identifying new drug targets to combat malaria. Understanding the intricacies of parasite biology is essential to design novel intervention strategies that can prevent the growth of the parasite. The structural biology approach towards this goal involves the identification of key differences in the structures of the human and parasite enzymes and the determination of unique protein structures essential for parasite survival. This review covers the work on structural biology of plasmodial proteins carried out during the period of January 2006 to June 2007...
Connaissances et perceptions du paludisme chez 103 voyageurs à destination intertropicale consultant le centre de conseil aux voyageurs du centre hospitalier universitaire de Bordeaux, France [Médecine et Maladies Infectieuses, In Press, Corrected Proof, Available online 17 September 2007] — (Français)
Les résultats de notre enquête sont en accord avec ceux de la littérature concernant la connaissance des symptômes, le niveau général des connaissances de la maladie et la proportion des voyageurs qui n'appréhendent pas le mode de transmission. Des idées fausses sur la chronicisation inéluctable et inaccessible à un recours thérapeutique efficace et éradicateur, l'absence de catégories plus vulnérables et le rôle exclusif du médicament aux dépens des autres moyens de prophylaxie sont régulièrement observés...
Effects of varying nitrogen doses on yield, yield components and artemisinin content of Artemisia annua L. [Industrial Crops and Products, In Press, Corrected Proof, Available online 14 September 2007 ] — (English)
Artemisia annua L. is an aromatic-antibacterial herb that destroys malarial parasites, lowers fevers and checks bleeding, and of which the secondary compound of interest is artemisinin. The objective of the present study was to determine yield, yield components and artemisinin content of A. annua L. grown under four nitrogen applications (0, 40, 80 and 120 kg ha−1) in the Çukurova region of Turkey in 2004 and 2005. Field trials were conducted at Çukurova University, Agricultural Faculty Field Crops Department. In the study, plant height, number of branches, fresh herbage yield, dry herbage yield, fresh leaf yield, dry leaf yield, essential oil content and artemisinin content (by high performance liquid chromatography, HPLC) were examined. By analysis of variance, nitrogen doses had no any statistical effect on the traits investigated except for artemisinin content. Artemisinin content of the dried leaves were significantly affected by nitrogen applications, which varied from 6.32 to 27.50 mg 100 g−1. Contents were from 120 and 80 kg ha−1 nitrogen for the years of 2004 and 2005, respectively...
Malaria and HIV: a silent alliance [Trends in Parasitology, In Press, Corrected Proof, Available online 6 September 2007 ] — (English)
HIV and malaria are leading causes of morbidity in sub-Saharan Africa. Recently, Abu-Raddad and colleagues explored the synergy between these diseases through a mathematical model that included all documented interactions. It emerges from the model parameter inputs that concomitant infection of both HIV and malaria fuels the spread of both diseases. For the first time, it is shown that, according to the model, transient but repeatedly elevated HIV viral loads due to recurrent co-infections, such as malaria, can also influence and increase HIV prevalence. Probably, these results are conservative and the true impact of the interaction could be even more important...
Lead decreases parasitemia and enhances survival of Plasmodium berghei-infected mice [Biochemical and Biophysical Research Communications, In Press, Uncorrected Proof, Available online 10 September 2007] — (English)
Malaria, a disease accounting for more than one million deaths per year, is caused by intraerythrocytic growth of Plasmodia. Parasitemia may be blunted by suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and phosphatidylserine exposure. Triggers of eryptosis include lead nitrate (Pb(NO3)2). As shown here, Pb(NO3)2 (10 μM) increased phosphatidylserine exposure of Plasmodium falciparum-infected human erythrocytes, an effect significantly more marked than in noninfected cells. Pb(NO3)2 treatment accelerated the clearance of erythrocytes from circulating blood. Parasitemia in Plasmodium berghei-infected mice was significantly decreased and mouse survival significantly enhanced by 100 μM Pb(NO3)2 (20 ppm) in drinking water. The treatment significantly increased reticulocyte number but did not significantly decrease erythrocyte number in noninfected mice and in infected animals mainly triggered the disappearance of P. berghei harbouring erythrocytes. In conclusion, Pb(NO3)2 accelerates eryptosis and subsequent clearance of infected erythrocytes and thus favourably influences the course of malaria...
Malaria returns to Kenya's highlands as temperatures rise [The Lancet, Volume 370, Issue 9591, 15 September 2007-21 September 2007, Pages 925-926] — (English)
A combination of insecticide and cool temperatures had eradicated malaria from Kenya's highlands in the 1960s. But the disease has returned in recent years—a development that some experts say is linked to subtle changes in the region's climate. Zoe Alsop investigates...
A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria [Tropical Medicine & International Health, Volume 12, Issue 9, Page 1037-1050, Sep 2007] — (English)
There was a high incidence of malaria-associated renal failure in this population (> 40%) and a correlation between this incidence, severe malarial anaemia and shock. Pathological features included PRBC sequestration in glomerular and tubulo-interstitial vessels, acute tubular damage and mild glomerular hypercellularity resulting from the accumulation of host monocytes within glomerular capillaries. No evidence for an immune complex mediated glomerulonephritis was found. There was a correlation between parasite sequestration in the kidney and pre-mortem renal failure, although overall levels of sequestration were relatively low. Levels of sequestration (Knob+ PRBC) were significantly higher in malaria-associated renal failure than in fatal cases without renal failure (P = 0.005). Malaria-associated renal failure is a common and serious complication of severe Plasmodium falciparum malaria in this population, associated with acute tubular injury rather than glomerulonephritis, and linked to localization of host monocytes in the kidney as well as sequestration...
Efficacy of pyrethroid-treated nets against malaria vectors and nuisance-biting mosquitoes in Tanzania in areas with long-term insecticide-treated net use [Tropical Medicine & International Health 12 (9), 1061–1073] — (English)
Anopheles gambiae s.l. and An. funestus s.l. were highly susceptible to permethrin (range 87–100%) and deltamethrin (consistently 100%) in WHO tests in 1999 and 2004, while Culex quinquefasciatus susceptibility to these pyrethroids was much lower (range 7–100% and 0–84% respectively). Efficacy of pyrethroid-treated nets was similarly high against An. gambiae s.l. and An. funestus s.l. (range 82–100%) while efficacy against Cx. quinquefasciatus was considerably lower (range 2–100%). There was no indication of development of resistance in populations of An. gambiae s.l. or An. funestus s.l. where ITNs have been extensively used; however, susceptibility of nuisance-biting Cx. quinquefasciatus mosquitoes declined in some areas between 1999 and 2004...
Molecular analysis of chloroquine resistance in Plasmodium falciparum in Yunnan Province, China [Tropical Medicine & International Health 12 (9), 1051–1060] — (English)
Resistance of Plasmodium falciparum to chloroquine (CQ) is determined by the mutation at K76T of the P. falciparum chloroquine resistance transporter (pfcrt) gene and modified by other mutations in this gene and in the P. falciparum multidrug resistance 1 (pfmdr1) gene. To determine the extent of polymorphisms in these genes in field P. falciparum isolates from Yunnan province of China, we genotyped the pfcrt codon 76, pfmdr1 codons 86 and 1246. Our results showed that although CQ has been withdrawn from treating falciparum malaria for over two decades, 90.3% of the parasites still carried the pfcrt K76T mutation. In contrast, mutations at pfmdr1 codons 86 and 1246 were rare. Sequencing analysis of the pfcrt gene in 34 parasite field isolates revealed CVIET at positions 72–76 as the major type, consistent with the theory of Southeast Asian origin of CQ resistance in the parasite. In addition, two novel pfcrt haplotypes (75D/144Y/220A and 75E/144Y/220A) were identified. Real-time polymerase chain reaction was used to determine pfmdr1 gene amplification, which is associated with mefloquine resistance. Our result indicated that in agreement with that mefloquine has not been used in this area, most (>90%) of the parasites had one pfmdr1 copy. Genotyping at two hypervariable loci showed relatively low levels of genetic diversity of the parasite population. Meanwhile, 28.4% of cases were found to contain mixed clones, which favour genetic recombination. Furthermore, despite a unique history of antimalarial drugs in Yunnan, its geographical connections with three malarious countries facilitate gene flow among parasite populations and evolution of novel drug-resistant genotypes. Therefore, continuous surveillance of drug resistance in this area is necessary for timely adjustment of local drug policies and more effective malaria control...
Antimalarial Drug Susceptibility and Point Mutations Associated with Drug Resistance in 248 Plasmodium falciparum Isolates Imported from Comoros to Marseille, France in 2004–2006 [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 431-437] — (English)
A total of 248 Plasmodium falciparum isolates were sampled in travelers with malaria who came to Marseille, France from Comoros to investigate in vitro activities of antimalarial drugs and molecular markers of drug resistance. Of the 248 isolates, 126 were maintained in culture. Of these, 53% were resistant to chloroquine, and 3% had reduced susceptibility to quinine, mefloquine, and atovaquone; 1% had reduced susceptibility to halofantrine and dihydroartemisinin; 7% had reduced susceptibility to monodesethylamodiaquine; 37% had reduced susceptibility to cycloguanil; and none had reduced susceptibility to lumefantrine. Resistance-associated point mutations were screened in 207 isolates. No mutations in the cytochrome b gene were found. Of the 207 isolates, 119 (58%) had a mutation in the P. falciparum dihydrofolate reductase (Pfdhfr) gene at codon 108, 6 (5%) had mutations in both Pfdhfr codon 108 and the P. falciparum dihydropteroate synthase codon 437, and 115 (56%) had the chloroquine resistance–associated K76T mutation in the P. falciparum chloroquine resistance transporter gene. This study represents a unique opportunity to improve surveillance of P. falciparum drug resistance in Comoros with consequences for treatment and chemoprophylaxis guidelines...
Impact of Intermittent Preventive Anti-Malarial Treatment on the Growth and Nutritional Status of Preschool Children in Rural Senegal (West Africa) [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 411-417] — (English)
Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel. We report the impact of a randomized, double-blind, placebo-controlled trial of seasonal intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children. A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November. In the intervention arm, mean weight gain was significantly greater (122.9 ± 340 versus 42.9 ± 344 [SD] g/mo, P < 0.0001) and losses in triceps and subscapular skinfold measurements were less (–0.39 ± 1.01 versus –0.66 ± 1.01 mm/mo, and –0.15 ± 0.64 versus –0.36 ± 0.62 mm/mo, respectively, P < 0.0001 for both). There was no difference in height increments. The prevalence of wasting increased significantly in the control arm (4.6% before versus 9.5% after, P < 0.0001), but remained constant in intervention children: 5.6% versus 7.0% (P = 0.62). The prevention of malaria would improve child nutritional status in areas with seasonal transmission...
Malaria in Pregnancy Before and After the Implementation of a National IPTp Program in Gabon [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 418-422] — (English)
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine has recently been adopted by many African countries to reduce maternal and neonatal morbidity and mortality associated with malaria in pregnancy. We assessed the impact of a newly established national IPTp program on maternal and neonatal health in Gabon. Data on prevalence of maternal Plasmodium falciparum infection, anemia, premature birth, and birth weight were collected in cross-sectional surveys in urban and rural regions of Gabon before and after the implementation of IPTp in a total of 1403 women and their offspring. After introduction of IPTp, the prevalence of maternal Plasmodium falciparum infection decreased dramatically (risk ratio 0.16, P < 0.001). Whereas only a modest effect on the rate of anemia in pregnant women was observed, there was a marked benefit on the prevalence of low birth weight and premature birth for women adhering to national recommendations. These effects were most pronounced in primi- and secundigravid women...
Comparison of Artemether-Lumefantrine with Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria in Eastern Nepal [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 423-430] — (English)
Because available data suggest that resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) is increasing in Nepal, an open-label, parallel-group efficacy/safety study was conducted in 99 Nepalese patients with uncomplicated falciparum malaria randomized 2:1 to artemetherlumefantrine (AL) or SP. Efficacy was assessed from clinical and microscopic evidence of treatment failure. Four SP-treated patients (12.1%; 95% CI, 4.0–29.1%) redeveloped parasitemia during the 28-day follow-up versus 0% (95% CI, 0–6.9%) in the AL group (P = 0.011), a difference that was confirmed by polymerase chain reaction (PCR) analysis of parasite DNA. PCR detected an additional six patients (two SP and four AL) with sub-microscopic gametocytemia or breakthrough parasitemia between Days 14 and 28, suggesting that AL efficacy was lower than estimated by microscopy. Dhfr and dhps mutations were not associated with outcome. AL is more effective than SP for uncomplicated malaria in Nepal, but regular monitoring of its efficacy should be carried out if this combination therapy is introduced...
Selection of Antifolate-Resistant Plasmodium falciparum by Sulfadoxine-Pyrimethamine Treatment and Infectivity to Anopheles Mosquitoes [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 438-443] — (English)
Resistance-conferring mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Plasmodium falciparum are selected by treatment with sulfadoxine pyrimethamine (SP). We assessed the association between these mutations and transmission capacity of parasites to Anopheles mosquitoes on the Pacific coast of Colombia. Patients with uncomplicated P. falciparum malaria received SP treatment and were followed-up to compare the prevalence of DHFR and DHPS mutations before and after SP treatment. Membrane feeding assays were used to measure infectivity to mosquitoes of post-treatment gametocytes with and without these mutations. Per-protocol treatment efficacy was 95.0% (132 of 139). Gametocytes carrying resistance-conferring mutations were selected after SP treatment and were infective to mosquitoes. Seven days after treatment, infections with two DHFR mutations had a 10-fold higher probability of infecting mosquitoes than infections with no DHFR mutations (odds ratio = 10.23, P < 0.05). Low-level drug resistance mutations have the potential to enhance transmission of P. falciparum and spread resistant parasites...
Polymerase Chain Reaction Detection of Plasmodium vivax and Plasmodium falciparum DNA from Stored Serum Samples: Implications for Retrospective Diagnosis of Malaria [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 444-446] — (English)
Polymerase chain reaction (PCR) detection of Plasmodium DNA is highly sensitive in diagnosing malaria. The specimen of choice for this assay has been whole blood samples from malaria patients. To retrospectively determine malaria infection rates in populations or cohorts for whom stored serum samples are available, we determined the ability of a nested PCR assay to detect Plasmodium DNA in stored serum samples. The PCR result was positive in 20 of 23 serum samples from patients with microscopy-confirmed malaria and negative in 8 of 8 healthy controls, resulting in a sensitivity of 87% and specificity of 100%. In all positive samples, species were correctly identified by PCR except for one case where a mixed infection was detected. The PCR is able to detect Plasmodium DNA in serum samples frozen up to 2.5 years and has the potential for the retrospective identification of malaria parasitemia in patient cohorts to determine potential interactions of malaria and other diseases such as human immunodeficiency virus/acquired immunodeficiency syndrome...
Electrocardiographic Safety Evaluation of Dihydroartemisinin–Piperaquine in the Treatment of Uncomplicated falciparum Malaria [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 447-450] — (English)
Dihydroartemisinin–piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett’s correction) were 2 (–6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram...
Prevalence and Risk of Plasmodium falciparum and P. vivax Malaria among Pregnant Women Living in the Hypoendemic Communities of the Peruvian Amazon [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 451-457] — (English)
The Amazon region of Iquitos, Peru is hypoendemic for Plasmodium vivax and P. falciparum. There is limited information regarding the epidemiology of malaria during pregnancy in this region. Passive surveillance for clinical malaria among pregnant women was conducted in eight health posts in 2004 and 2005. Community-based active surveillance was conducted to determine the incidence of malarial infection among pregnant women in the community of Zungarococha in 2004 and 2005. Passive surveillance demonstrated that pregnant women had a prevalence of clinical malaria of 7.5% in 2004 and 6.6% in 2005 compared with 20.6% and 22.4% of the total population. Active surveillance showed that pregnant women were 2.3 (95% confidence interval = 1.32–3.95, P = 0.004) times more likely to have a P. falciparum infection compared with non-pregnant women. This study demonstrated that because of detection bias, passive surveillance underestimates the burden of malarial infection during pregnancy, and that subclinical malarial infections may occur frequently among pregnant women in this region. Furthermore, pregnant women in this low-transmission and P. vivax–dominant setting, experience an increased risk for P. falciparum infection, but not P. vivax infection...
Financial Implications of Refugee Malaria: The Impact of Pre-Departure Presumptive Treatment with Anti-Malarial Drugs [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 458-463] — (English)
This study is a cost-benefits analysis of the recommendations of the Centers for Disease Control and Prevention for presumptive anti-malarial treatment among departing West African refugees. We conducted a retrospective chart review of symptomatic, blood smear–positive cases of malaria seen in Minneapolis, Minnesota, from 1996 through 2005. Billing charges of U.S. care were compared with estimates of implementation costs for overseas treatment. Fifty-eight symptomatic malaria infections occurred among West African refugees. After overseas pre-departure presumptive treatment, symptomatic malaria in arriving refugees decreased from 8.2% to 0%. The pre-departure number needed to treat to prevent one case of symptomatic malaria is 13.9 (95% confidence interval = 9.8–24). The average U.S. billing charge for each malaria case is $1,730. Overseas implementation costs for presumptive treatment are estimated to be between $141 and $346 to prevent one U.S. malaria case. Overseas presumptive pre-departure anti-malarial therapy prevents clinical malaria in refugees and results in cost-benefits when the malaria prevalence is > 1%. Overseas presumptive therapy has greater cost-benefits than U.S. based screening and treatment strategies...
Development of a Molecular Assay to Detect Predation on Anopheles gambiae Complex Larval Stages [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 464-466] — (English)
We developed a molecular assay to detect predation on Anopheles gambiae sensu lato (s.l.) mosquitoes. This intergenic spacer ribosomal DNA polymerase chain reaction assay and restriction enzyme analysis uses An. gambiae-specific primers to detect mosquito DNA in the DNA extracts from whole invertebrate predators, which enables identification of species (An. gambiae s.s. versus An. arabiensis) and molecular forms (M versus S in An. gambiae s.s.). We show that An. gambiae s.l. DNA can be detected after ingestion by members of the families Lestidae (order Odonata) after four hours, Libellulidae (order Odonata) after six hours, and Notonectidae (order Hemiptera) after 24 hours. This method is an improvement over previously published methods because of ease of execution and increased time of detection after ingestion...
A New Robust Diagnostic Polymerase Chain Reaction for Determining the Mating Status of Female Anopheles gambiae Mosquitoes [Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 485-487] — (English)
The principal malaria vector in Africa, Anopheles gambiae, contains two pairs of autosomes and one pair of sex chromosomes. The Y chromosome is only associated with males and other Y chromosome–specific DNA sequences, which are transferred to women during mating. A reliable tool to determine the mating status of dried wild An. gambiae females is currently lacking. DNA was extracted from dried virgin and mated females and used to test whether Y chromosome–specific polymerase chain reaction (PCR) markers can be successfully amplified and used as a predictor of mating. Here we report a new PCR-based method to determine the mating status among successfully inseminated and virgin wild An. gambiae females, using three male-specific primers. This dissection-free method has the potential to facilitate studies of both population demographics and gene flow from dried mosquito samples routinely collected in epidemiologic monitoring and aid existing and new malaria-vector control approaches...
Malaria research should go 'back to basics' [Nature.com (subscription) - London,England,UK] — (English)
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Hitting malaria before it hurts: attenuated Plasmodium liver stages [Cell Mol Life Sci. 2007 Sep 17] — (English)
Continuous natural exposure to Plasmodium transmission by infectious Anopheles mosquitoes leads to a gradual acquisition of immunological competence against malaria. The partial immunity, observed in adolescents and adults living in endemic areas, reduces morbidity and mortality without preventing parasite infection. In experimental animal models, long-lasting sterilizing immunity can be achieved with genetically attenuated Plasmodium liver stages. Can these findings be translated to accomplish sterile protection against natural malaria transmission in the high-risk group, young infants in sub-Saharan Africa? ...
Sulfadoxine-pyrimethamine resistance in Maputo, Mozambique: presence of mutations in the dhfr and dhps genes of Plasmodium falciparum [Rev. Soc. Bras. Med. Trop. vol.40 no.4 Uberaba July/Aug. 2007] — (Prtuguesa)
The frequency and distribution of mutations in Plasmodium falciparum, dihydrofolate reductase and dihydropteroate synthase genes were analyzed, using the polymerase chain reaction and restriction fragment length polymorphism methodology, in infected blood samples from Mozambican children living in Maputo, before and seven days after treatment with sulfadoxine/pyrimethamine (S/P). The results showed the occurrence of point mutations in the genes studied and the presence of combinations of three alleles in dhfr (51Ile, 59Arg and 108Asn) and "quintuple" mutant (dhfr 51Ile, 59Arg, 108Asn and dhps 437Gly, 540Glu). Both of these situations were associated with seven-day therapeutic failure, following treatment with S/P. These findings show the importance of studying S/P resistance in Mozambique, and how molecular markers for antimalarial resistance can provide important data for national malaria control policy...
Pharmacodynamics of Doxycycline in a Murine Malaria Model [Antimicrob Agents Chemother. 2007 Sep 17] — (English)
Doxycycline is reported to impair second generation parasite schizogeny. The effect of doxycycline alone and combined with dihydroartemisinin was investigated in a murine malaria model. Doxycycline slowed the rate of parasite growth within two days, with maximum effect in six days. Addition of dihydroartemisinin led to an additive antimalarial effect...
Antibodies elicited by a virosomally formulated Plasmodium falciparum serine repeat antigen-5 derived peptide detect the processed 47kDa fragment both in sporozoites and merozoites [Peptides. 2007 Aug 17] — (English)
Serine repeat antigen-5 (SERA5) is a candidate antigen for inclusion into a malaria subunit vaccine. During merozoite release and reinvasion the 120 kDa SERA5 precursor protein (P120) is processed, and a complex consisting of an N-terminal 47 kDa (P47) and a C-terminal 18 kDa (P18) processing product associates with the surface of merozoites. This complex is thought to be involved in merozoite invasion of and/or egress from host erythrocytes. Here we describe the synthesis and immunogenic properties of virosomally formulated synthetic phosphatidylethanolamine (PE)–peptide conjugates, incorporating amino acid sequence stretches from the N-terminus of Plasmodium falciparum SERA5. Choosing an appropriate sequence was crucial for the development of a peptide that elicited high titers of parasite cross-reactive antibodies in mice. Monoclonal antibodies (mAbs) raised against the optimized peptide FB-23 incorporating amino acids 57–94 of SERA5 bound to both P120 and to P47. Western blotting analysis proved for the first time the presence of SERA5 P47 in sporozoites. In immunofluorescence assays, the mAbs stained SERA5 in all its predicted localizations. The virosomal formulation of peptide FB-23 is suitable for use in humans and represents a candidate component for a multi-valent malaria subunit vaccine targeting both sporozoites and blood stage parasites...
Pathogenesis of anemia in malaria: a concise review [Parasitol Res. 2007 Sep 16] — (English)
Anemia is a common complication in malarial infection, although the consequences are more pronounced with Plasmodium falciparum malaria (Ghosh, Indian J Hematol Blood Tranfus 21(53):128–130, 2003). Anemia in this infection is caused by a variety of pathophysiologic mechanisms, and in areas where malaria infection is endemic, co-morbidities like other parasitic infestations, iron, folate and Vitamin B12 deficiency, deficiency of other nutrients, and anemia, which is aggravated by anti-malarial drugs both through immune and non-immune mechanisms, are important considerations. In different endemic areas, β-thalassemia, α-thalassemia, Hb S, Hb E, G6PD deficiency, or ovalocytosis in different proportions interact with this infection. Finally, aberrant immune response to repeated or chronic falciparum malarial infection may produce tropical splenomegaly syndrome, a proportion of which show clonal proliferation of B lymphocytes. Cooperation between chronic malarial infection and infection with E-B virus infection in producing Burkitt’s lymphoma is well known. In this review, the fascinating and multifaceted pathophysiolgoy of malarial anemia has been discussed...
Plasmodium falciparum ookinetes require mosquito midgut chondroitin sulfate proteoglycans for cell invasion [PNAS - U S A] — (English)
Malaria transmission entails development of the Plasmodium parasite in its insect vector, the Anopheles mosquito. Parasite invasion of the mosquito midgut is the critical first step and involves adhesion to host epithelial cell ligands. Partial evidence suggests that midgut oligosaccharides are important ligands for parasite adhesion; however, the identity of these glycans remains unknown. We have identified a population of chondroitin glycosaminoglycans along the apical midgut microvilli of Anopheles gambiae and further demonstrated ookinete recognition of these glycans in vitro. By repressing the expression of the peptide-O-xylosyltransferase homolog of An. gambiae by means of RNA interference, we blocked glycosaminoglycan chain biosynthesis, diminished chondroitin sulfate levels in the adult midgut, and substantially inhibited parasite development. We provide evidence for the in vivo role of chondroitin sulfate proteoglycans in Plasmodium falciparum invasion of the midgut and insight into the molecular mechanisms mediating parasite-mosquito interactions...
Kinetic and biochemical characterization of Plasmodium falciparum guanosine 5'-monophosphate synthetase [Biochem. J. (2007) Immediate Publication, doi:10.1042/BJ20070996] — (English)
Plasmodium falciparum the causative agent of the fatal form of malaria synthesizes GMP primarily from IMP and hence, needs active GMP synthetase (GMPS) for its survival. GMPS, a G-type amidotransferase catalyzes the amination of XMP to GMP with the reaction occurring in two domains, the glutamine amidotransferase (GAT) and ATP pyrophosphatase (ATPPase). The GAT domain hydrolyzes glutamine to glutamate and ammonia while the ATPPase domain catalyzes the formation of the intermediate AMP-XMP from ATP and XMP. Coordination of activity across the two domains, achieved through channeling of ammonia from GAT to the effector domain is the hallmark of amidotransferases. Our studies aimed at understanding the kinetic mechanism of Plasmodium falciparum GMPS (PfGMPS) indicated steady state ordered binding of ATP followed by XMP to the ATPPase domain with glutamine binding in a random manner to the GAT domain. We attribute the irreversible, ping-pong step seen in initial velocity kinetics to the release of glutamate prior to the attack of adenyl-XMP intermediate by ammonia. Specific aspects of the overall kinetic mechanism of PfGMPS are different from that reported for the human and E. coli enzymes. Unlike human GMPS, absence of tight coordination of activity across the two domains was evident in the parasite enzyme. Variations seen in the inhibition by nucleosides and nucleotide analogs between human and P. falciparum GMPS highlighted differences in ligand specificity that could serve as a basis for the design of specific inhibitors. This study forms the first report on recombinant His-tagged GMPS from parasitic protozoa...
A longitudinal investigation of Plasmodium falciparum malaria in children in northern India [Scand J Infect Dis. 2007 Sep] — (English)
A group comprising 27 young children (1-4 y of age) suffering from uncomplicated falciparum malaria were studied to characterize the isolates and to measure humoral immune responses during acute infection and after recovery. Finger prick blood from each individual was collected on d 1. After treatment with chloroquine, a further blood sample was collected from each child on d 7, 30, 90 and 180 for assay of antibody responses to P. falciparum antigens. Isolates from individual patients were incubated in vitro for demonstration of rosette formation, assay of plasmodial growth rate and analysis of Pfcrt gene polymorphism. Out of 27 isolates of P. falciparum, 20 showed formation of rosettes in vitro. The growth rate at 96 h varied widely among the isolates. In Pfcrt gene analysis at 76-codon site, 14 showed wild-type Lys 76, 7 showed mutant type Thr 76 and 6 had mixed type. 14 children, all with anaemia on d 7, showed a positive direct antiglobulin test (DAT). Sera positive by ELISA IgG on d 90 also showed parasite growth inhibitory activity in vitro. Significant levels of IgG, IgG1 and IgG3 subclass antibodies against MSP1 were detected in 14 sera collected on d 90. On d 180, there was a decline in IgG and its subtypes. These findings suggest that a variability in isolates may occur in one and the same seasonal area, making children prone to infection. As a consequence, they develop antibodies during recovery phase from an acute attack, which remain in circulation for a period of 4-5 months. After that, a decline in antibody level may again make them susceptible to the disease. Prevalence of different serotypes in a small area may suggest the complexity of malaria transmission...
Biological Evaluation, Structure-Activity Relationships, and Three-Dimensional Quantitative Structure-Activity Relationship Studies of Dihydro--agarofuran Sesquiterpenes as Modulators of P-Glycoprotein-Dependent Multidrug Resistance [J. Med. Chem., ASAP Article 10.1021/jm070290v S0022-2623(07)00290-7] — (English)
Multidrug resistance (MDR) is one of the main challenges in the chemotherapy of cancer, malaria, and other important diseases. Here, we report the inhibitory activity of a series of 76 dihydro--agarofuran sesquiterpenes, tested on NIH-3T3 cells expressing the human P-glycoprotein (Pgp) multidrug transporter, to establish quantitative comparisons of their respective abilities to block the drug transport activity. The screening was performed on the basis of the ability of sesquiterpenes to modulate the intracellular accumulation of the classical Pgp substrate daunorubicin. To understand the structural basis for inhibitory activity and guide the design of more potent Pgp inhibitors, we have performed a three-dimensional quantitative structure-activity relationship model using the comparative molecular similarity indices analysis (CoMSIA). The most salient features of these requirements are in the region of the substituents at the C-2, C-3, and C-8 positions, which seem to be critical for determining the overall effectiveness of sesquiterpenes as Pgp inhibitors...
Prepared in cooperation with OMS ANGOLA INFO.
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