11.02.1008
Children for Children: Sweat for Nets Update [Children for Children] — (English)
Children for Children recently updated the Sweat for Nets service-learning toolkit and organizing guide...
Report of the Fourth Meeting of the RBM Partnership's Working Group on Scalable Malaria Vector Control (WIN) [RBM WIN] — (English)
Summary report...
Global Fund Vacancy notices [The Global Fund] — (English)
The positions are now open for competition...
Prolonged Plasmodium falciparum Infection in Immigrants, Paris [Emerg Infect Dis. 2008 Feb;14(2):323-326] — (English)
Few immigrant travelers have Plasmodium falciparum infections >2 months after leaving malaria-endemic areas. We conducted a case–control study to identify factors associated with prolonged P. falciparum infection in immigrant travelers. Results suggest that P. falciparum infection should be systematically suspected, even months after travel, especially in pregnant women and first-arrival immigrants...
Plasmodium falciparum Malaria and Atovaquone-Proguanil Treatment Failure [Emerg Infect Dis. 2008 Feb;14(2):320-2] — (English)
We noticed overrepresentation of atovaquone-proguanil therapeutic failures among Plasmodium falciparum–infected travelers weighing >100 kg. We report here 1 of these cases, which was not due to resistant parasites or impaired drug bioavailability. The follow-up of such patients should be strengthened...
Maurer's clefts of Plasmodium falciparum are secretory organelles that concentrate virulence protein reporters for delivery to the host erythrocyte [Blood - US] — (English)
In blood-stage infection by the human malaria parasite Plasmodium falciparum, export of proteins from the intracellular parasite to the erythrocyte is key to virulence. This export is mediated by a host-targeting (HT) signal present on a "secretome" of hundreds of parasite proteins engaged in remodeling the erythrocyte...
9.02.1008
Non-toxic remedy for malaria [Sunday Vision - Uganda] — (English)
A NEW product that kills the larvae of malaria-causing mosquitoes is being fronted as an environmentally friendly way to curb the spread of malaria...
$23 million grant for malaria control approved [The News - International - Pakistan] — (English)
The Geneva-based Global Fund to fight AIDS, TB and Malaria (GFATM) has approved a grant of US $23 million for the control of malaria in Pakistan, 'The News' learnt here on Friday...
8.02.1008
Tanzania: Vice President of Tanzania Dedicates Olyset Net Factory In Arusha [Sumitomo Chemical (Tokyo)] — (English)
Vice President Dr Ali Mohammed Shein today presided over the dedication of the new Olyset Net factory in Arusha, Tanzania before an audience of distinguished guests...
Cameroon: Experts Say Climate Change is Malaria Vector [The Post (Buea) via allAfrica.com] — (English)
A 30-year-old woman was restless as she gnashed her teeth in malarial pain at Njinikom Hospital, some 60 kilometres from the Northwest Provincial capital, When The Post arrived at the hospital on January 19, more than half of the patients in the general ward were suffering from malaria, which the Northwest Provincial Delegate of Public Health, Dr. Victor Ndiforchu Afanwi, qualified as the greatest killer...
Heading south? Take malaria precautions [Waterloo Record - Waterloo,Ontario,Canada] — (English)
One bite is all it takes. Just one mosquito infected with malaria can cause serious illness, and the disease is more widespread and closer to home than many Canadians realize...
Liberia: USAID Donates U.S. $5,000 Materials To MOH [The Analyst (Monrovia) via allAfrica.com] — (English)
The United States Aid for International Development (USAID), Liberia has donated a consignment of artemisinin-based combination therapy (ACT) to the National Malaria Control Program of the Ministry of Health and Social Welfare...
Angola: Plus de 36 mille cas de malaria enregistrés à Chongoroi [Angola Press Agency (Luanda) via allAfrica.com] — (Français)
36.945 cas de malaria ont été enregistrés en 2007 à l'hôpital municipal de Chongoroi, à 150 Km de la ville de Benguela...
Global Fund extends malaria program in Kalinga [Philippine Information Agency - Philippines] — (English)
The province continues to be a recipient of the Global Fund Malaria Component (GFMC) Project after the Global Fund extended its program in the country giving focus on the 21 province beneficiaries of its Round 2 program...
7.02.1008
Record Label to Save Over 100,000 Lives From Malaria With New Album [PR Web (press release) - Ferndale,WA,USA] — (English)
Compact disc release aimed at fighting malaria and increasing awareness about the fatal disease that kills more than one million people every year. For each album sold, the label will procure and distribute 2 insecticide treated mosquito nets in Africa. Bed nets are the most cost effective way to combat malaria...
How imperialism removed malaria from the developed world [Workers World - USA] — (English)
Malaria and imperialism: A Review of “The Making of a Tropical Disease: A Short History of Malaria” by Randall M. Packard (Johns Hopkins Biographies of Disease)...
First Wesleyan hoopsters take aim at malaria [Gaston Gazette - Gastonia,NC,USA] — (English)
One recent Saturday, the youth of First Wesleyan Church spent their day shooting free throws in the church’s gym. It was fun, but it was also serious business. The free throws were to raise money to buy nets for people who live in malaria-infested areas of Africa. These nets will cover beds and prevent disease-carrying mosquitoes from biting the sleepers...
Church's Nothing But Nets effort targets malaria [DesMoinesRegister.com - Des Moines,IA,USA] — (English)
Tritle, pastor of the West Des Moines United Methodist Church, and members of the church are raising money until Easter for the Nothing But Nets national campaign to buy mosquito nets for families living in Africa, where the disease is most prevalent. The campaign goal is to cut the fatality statistics nearly in half...
Chippewa students open hearts, wallets to fight malaria [Pioneer Local - US] — (English)
Some sixth graders at Des Plaines District 62's Chippewa elementary school have hearts much bigger than their wallets. So when the 25 youngsters in Amy Cengel's English as a Second Language social studies class learned that more than one million Africans die every year because of malaria, they were determined to help...
6.02.1008
Supplements 'reduce malaria toll' [BBC News - UK] — (English)
The study, published in Nutrition Journal, found giving children vitamin A and zinc cut incidence of illness by a third...
African Scientists discuss progress on development of malaria vaccines [Ghana Broadcasting Corporation - Accra,Ghana] — (English)
About 40 scientists have met in Tanzania to discuss progress made so far to develop malaria vaccines. Ten African countries are currently testing a malaria vaccine, RTSS, that could protect children and pregnant women from malaria. The meeting brought together leaders of the 10 sites as well as donors and International NGOs in malaria research in Africa...
Slideshow: Fighting to save children from malaria in Sierra Leone [Medecins Sans Frontieres - Brussels,Belgium] — (English)
Pediatrician Leo Ho worked in the intensive care unit of the MSF-run Gondama Hospital in the Bo region of Sierra Leone in 2007. During his assignment, Dr. Ho was continually treating the most severe malaria cases: children brought to the hospital who had already fallen into a coma; those who were severely malnourished; or also suffering from tuberculosis or HIV/AID...
Malaria in Mozambique worries SA [The Times - Johannesburg,Gauteng,South Africa] — (English)
An increase in reported cases of malaria in Mozambique has South African health authorities worried...
5.02.1008
Net Benefits: Bed Netting, Drugs Stem Malaria Deaths [Scientific American - USA] — (English)
Four African countries saw significantly fewer childhood deaths from malaria after distributing insecticide-treated bed nets and combination drug therapy, according to a new report released by the World Health Organization (WHO)...
Humans are evolving to resist disease [Telegraph.co.uk - United Kingdom] — (English)
A survey of the human genetic code has shown that our resistance to malaria, diabetes and other diseases is changing in response to our environment...
Novel malaria vaccine is tested at Oxford [UPI] — (English)
British scientists have started testing a new malaria vaccine that utilizes, for the first time, a virus found in chimpanzees to boost its efficacy. The trials being conducted at the University of Oxford's Jenner Institute are being led by Professor Adrian Hill...
Stanford researchers find two potential drug targets to thwart malaria [Media Newswire (press release) - New York,NY,USA] — (English)
The team, led by Matthew Bogyo, PhD, assistant professor of pathology, identified two enzymes that enable malaria parasites to escape host blood cells. They also identified compounds that block those enzymes, which could provide a way to keep the parasites sequestered in blood cells long enough that they die before they have a chance to wreak havoc on the body. The research is published in the online issue of Nature Chemical Biology...
Lorne hosts malaria meet [Geelong Advertiser - Geelong,Victoria,Australia] — (English)
ELITE scientists from across the globe have gathered in Lorne for the world's premier conference on malaria...
Why don't health workers prescribe ACT? A qualitative study of factors affecting the prescription of artemether-lumefantrine [Malaria Journal 2008, 7:29 (5 February 2008)] — (English)
A qualitative study of reasons for prescribers' non-adherence to policy, including particularly enlightening quotations verbatim of health worker's replies...
Articles requiring subscription
Impact comparatif de trois schémas de prévention du paludisme pendant la grossesse sur l’anémie maternelle, associée à l’infection palustre au Burkina Faso [Médecine et Maladies Infectieuses, In Press, Corrected Proof, Available online 8 February 2008] — (Français)
Le gain en hémoglobine était plus important dans le groupe de traitement préventif intermittent à la sulfadoxine–pyriméthamine, où le taux d’hémoglobine est passé de 10,3 g/dl à l’inclusion à 11,4 g/dl à la troisième consultation prénatale. Comparé aux deux autres groupes, une réduction sensible de la prévalence de l’anémie modérée a été notée dans le même groupe (65,6 à 36,7 %), aussi bien à la deuxième consultation prénatale (p = 0,069) qu’à la troisième consultation (p = 0,014). En revanche, les réductions étaient peu marquées dans les groupes chloroquine (deuxième consultation, p = 0,72 ; troisième consultation p = 0,55). La prévalence de l’infection palustre a également régressé dans les trois groupes de traitement, mais elle était beaucoup plus prononcée dans le groupe ayant bénéficié du traitement intermittent à la sulfadoxine–pyriméthamine où elle était de 44,3 %...
Blood coagulation, inflammation, and malaria [Microcirculation. 2008 Feb;15(2):81-107] — (English)
Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic system; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article (i) reviews the literature related to blood coagulation and malaria in a historic perspective, (ii) describes basic mechanisms of coagulation, anticoagulation, and fibrinolysis, (iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), (iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falciparum infected patients, and (v) emphasizes the procoagulant role of parasitized red blood cells (RBCs) and activated platelets in the pathogenesis of malaria. This article also presents the Tissue Factor Model (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell (EC) activation, blood coagulation disorder, and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis...
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer [Parasitol Res. 2008 Feb 9] — (English)
The folate derivatives folic acid (FA) and folinic acid (FNA) decrease the in vivo and in vitro activities of antifolate drugs in Plasmodium falciparum. However, the effects of 5-methyl-tetrahydrofolate (5-Me-THF) and tetrahydrofolate (THF), the two dominant circulating folate forms in humans, have not been explored yet. We have investigated the effects of FA, FNA, 5-Me-THF, and THF on the in vitro activity of the antimalarial antifolates pyrimethamine and chlorcycloguanil and the anticancer antifolates methotrexate (MTX), aminopterin, and trimetrexate (TMX), against P. falciparum. The results indicate that these anticancers are potent against P. falciparum, with IC(50) < 50 nM. 5-Me-THF does not significantly decrease the activity of all tested drugs, and none of the tested folate derivatives significantly decrease the activity of these anticancers. Thus, malaria folate metabolism has features different from those in human, and the exploitation of this difference could lead to the discovery of new drugs to treat malaria. For instance, the combination of 5-Me-THF with a low dose of TMX could be used to treat malaria. In addition, the safety of a low dose of MTX in the treatment of arthritis indicates that this drug could be used alone to treat malaria...
Quantification of cationic anti-malaria agent methylene blue in different human biological matrices using cation exchange chromatography coupled to tandem mass spectrometry [J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jan 26] — (English)
Abstract
Selective and sensitive methods for the determination of the cationic dye and anti-malarial methylene blue in human liquid whole blood, dried whole blood (paper spot), and plasma depending on protein precipitation and cation exchange chromatography coupled to electrospray ionisation (ESI) tandem mass spectrometry (MS/MS) have been developed, validated according to FDA standards, and applied to samples of healthy individuals and malaria patients within clinical studies. Acidic protein precipitation with acetonitrile and trifluoroacetic acid was used for liquid whole blood and plasma. For the extraction of methylene blue from paper spots aqueous acetonitrile was used. Sample extracts were chromatographed on a mixed mode column (cation exchange/reversed phase, Uptisphere MM1) using an aqueous ammonium acetate/acetonitrile gradient. Methylene blue was quantified with MS/MS in the selected reaction monitoring mode using ESI and methylene violet 3RAX as internal standard. Depending on the sample volume (whole blood and plasma 250 μL, and 100 μL on paper spots) the method was linear at least within 75 and 10,000 ng/mL and the limit of quantification in all matrices was 75 ng/mL. Batch-to-batch accuracies of the whole blood, plasma, and paper spot methods varied between −4.5 and +6.6%, −3.7 and +7.5%, and −5.8 and +11.1%, respectively, with corresponding precision ranging from 3.8 to 11.8% CV. After a single oral dose (500 mg) methylene blue concentrations were detectable for 72 h in plasma. The methods were applied within clinical studies to samples from healthy individuals and malaria patients from Burkina Faso...
Effects of Local Anthropogenic Changes on Potential Malaria Vector Anopheles hyrcanus and West Nile Virus Vector Culex modestu, Camargue, France [Emerg Infect Dis. 2007 Dec;13(12):1810-1815] — (English)
Using historical data, we highlight the consequences of anthropogenic ecosystem modifications on the abundance of mosquitoes implicated as the current most important potential malaria vector, Anopheles hyrcanus, and the most important West Nile virus (WNV) vector, Culex modestus, in the Camargue region, France. From World War II to 1971, populations of these species increased as rice cultivation expanded in the region in a political context that supported agriculture. They then fell, likely because of decreased cultivation and increased pesticide use to control a rice pest. The species increased again after 2000 with the advent of more targeted pest-management strategies, mainly the results of European regulations decisions. An intertwined influence of political context, environmental constraints, technical improvements, and social factors led to changes in mosquito abundance that had potential consequences on malaria and WNV transmission. These findings suggest that anthropogenic changes should not be underestimated in vectorborne disease recrudescence...
Efficacy model for mosquito stage transmission blocking vaccines for malaria [Parasitology. 2008 Feb 7;:1-10] — (English)
Vaccines that target antigens found on the mosquito stages of Plasmodium falciparum and Plasmodium vivax parasites are under development as transmission blocking vaccines. Antisera from vaccinated animals and humans are able to block oocyst development in artificially fed mosquitoes but it is not clear from these data what level of antibody response would be required for a useful vaccine in a field setting. This paper describes a mathematical model that takes into account the relationship between antibody levels and blocking of oocyst levels in artificial feeds, the distribution of antibody responses seen in human populations and the distribution of oocyst densities in infected mosquitoes in the field to calculate the levels of antibody in the host population that would be required to achieve a level of herd immunity in a vaccinated human population that would give an operationally useful level of transmission blocking. The model predicts that current formulations of Pfs25 are likely to achieve useful reductions in transmission when tested in human field trials...
In silico discovery of transcription regulatory elements in Plasmodium falciparum [BMC Genomics. 2008 Feb 7;9(1):70] — (English)
This GEMS analysis demonstrates that in silico regulatory element discovery can be successfully applied to challenging repeat-sequence-rich, base-biased genomes such as that of P. falciparum. The fact that regulatory elements were predicted from a diverse range of functional gene clusters supports the hypothesis that cis-regulatory elements play a role in the transcriptional control of many P. falciparum biological processes. The putative regulatory elements described represent promising candidates for future biological investigation into the underlying transcriptional control mechanisms of gene regulation in malaria parasites...
The guanylhydrazone CNI-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase [Parasitol Res. 2008 Feb 7] — (English)
Malaria is still a major cause of death in the tropics. There is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. Over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5A (eIF-5A) in Plasmodium. Hypusine biosynthesis involves catalysis of deoxyhypusine synthase (DHS) in the first step of post-translational modification. In a screen for new inhibitors of purified plasmodium DHS, CNI-1493, a novel selective pro-inflammatory cytokine inhibitor used in clinical phase II for the treatment of Crohn’s disease, inhibited the enzyme of the parasite 3-fold at a concentration of 2 μM. In vitro experiments with 200 μM CNI-1493 in Plasmodium-infected erythrocytes, which lack nuclei and DHS protein, showed a parasite clearance within 2 days. This can presumably be attributed to an anti-proliferating effect because of the inhibition of DHS by the parasite. The determined IC50 of CNI-1493 was 135.79 μM after 72 h. In vivo application of this substance in Plasmodium berghei ANKA-infected C57BL/6 mice significantly reduced parasitemia after dosage of 1 mg/kg or 4 mg/kg/body weight and prevented death of mice with cerebral malaria. This effect was paralleled by a decrease in serum TNF levels of the mice. We suggest that the new mechanism of CNI-1493 is caused by a decrease in modified eIF-5A biosynthesis with a downstream effect on the TNF synthesis of the host. From the current data, we consider CNI-1493 to be a promising drug for anti-malarial therapy because of its combined action, i.e., the decrease in eIF-5A biosynthesis of the parasite and host cell TNF biosynthesis...
Identification and Geographic Distribution of the ACE-1R Mutation in the Malaria Vector Anopheles gambiae in South-Western Burkina Faso, West Africa [Am J Trop Med Hyg. 2008 Feb;78(2):298-302] — (English)
Resistance of Anopheles gambiae to organophosphate and carbamate insecticides was first reported in Côte d’Ivoire, West Africa. Subsequent studies revealed that it resulted from a single point mutation in the oxyanion hole of the acetycholinesterase enzyme (ace-1R mutation). We investigated the distribution and prevalence of the ace-1R mutation in An. gambiae s.l. populations from seven locations in south-western Burkina Faso. The ace-1R mutation was found in both M and S molecular forms of An. gambiae s.s., but it was absent in An. arabiensis. Its frequency ranged from 0.25 to 0.5 in S form and 0.04 to 0.13 in M form, though they were sympatric. The lack of homozygous resistance indicated a strong genetic cost associated with the mutation. These data suggest that organophosphate and carbamate resistance conferred by target site insensitivity is spreading in populations of An. gambiae s.s. from West Africa...
Effect of Rice Cultivation on Malaria Transmission in Central Kenya [Am J Trop Med Hyg. 2008 Feb;78(2):270-275] — (English)
A 12-month field study was conducted between April 2004 and March 2005 to determine the association between irrigated rice cultivation and malaria transmission in Mwea, Kenya. Adult mosquitoes were collected indoors twice per month in three villages representing non-irrigated, planned, and unplanned rice agro-ecosystems and screened for blood meal sources and Plasmodium falciparum circumsporozoite proteins. Anopheles arabiensis Patton and An. funestus Giles comprised 98.0% and 1.9%, respectively, of the 39,609 female anophelines collected. Other species including An. pharoensis Theobald, An. maculipalpis Giles, An. pretoriensis Theobald, An. coustani Laveran, and An. rufipes Gough comprised the remaining 0.1%. The density of An. arabiensis was highest in the planned rice village and lowest in the non-irrigated village and that of An. funestus was significantly higher in the non-irrigated village than in irrigated ones. The human blood index (HBI) for An. arabiensis was significantly higher in the non-irrigated village compared with irrigated villages. For An. funestus, the HBI for each village differed significantly from the others, being highest in the non-irrigated village and lowest in the planned rice village. The sporozoite rate and annual entomologic inoculation rate (EIR) for An. arabiensis was 1.1% and 3.0 infective bites per person, respectively with no significant difference among villages. Sporozoite positive An. funestus were detected only in planned rice and non-irrigated villages. Overall, 3.0% of An. funestus samples tested positive for Plasmodium falciparum sporozoites. The annual EIR of 2.21 for this species in the non-irrigated village was significantly higher than 0.08 for the planned rice village. We conclude that at least in Mwea Kenya, irrigated rice cultivation may reduce the risk of malaria transmission by An. funestus but has no effect on malaria transmission by An. arabiensis. The zoophilic tendency of malaria vectors in irrigated areas accounts partly for low malaria transmission rates despite the presence of higher vector densities, highlighting the potential of zooprophylaxis in malaria control...
A description of malaria-related knowledge, perceptions, and practices in the artibonite valley of haiti: implications for malaria control [Am J Trop Med Hyg. 2008 Feb;78(2):262-9] — (English)
A two-stage cluster survey (n = 200 households) was conducted in the Artibonite Valley of Haiti during the high malaria transmission season in November-December 2006. Knowledge, perceptions, and practices related to malaria were obtained from household representatives using a standardized questionnaire. Blood drops were obtained on filter paper from all household members more than one month of age (n = 714). Determinants of malaria infections and correct malaria-related knowledge were assessed using logistic regression. Respondents in households with more assets were significantly more likely than those in households with fewer assets to have correct malaria-related knowledge. Respondents from households with at least one malaria infection were less likely to have correct malaria-related knowledge. Older children (5-9 years of age) were shown to be at increased risk of malaria infection. Results suggest malaria control in Haiti should focus on enhanced surveillance and case management, with expanded information campaigns about malaria prevention and treatment options...
Differential Effect of Regional Drug Pressure on Dihydrofolate Reductase and Dihydropteroate Synthetase Mutations in Southern Mozambique [Am J Trop Med Hyg. 2008 Feb;78(2):256-261] — (English)
The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutations associated with sulfadoxine-pyrimethamine (SP) resistance at 13 sentinel surveillance sites in southern Mozambique were examined regularly between 1999 and 2004. Frequency of the dhfr triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. The dhps double mutation frequency peaked in 2001 (0.22) but declined to baseline levels (0.07) by 2004. Similarly, parasites with both dhfr triple and dhps double mutations had increased in 2001 (0.18) but decreased by 2004 (0.05). The peaking of SP resistance markers in 2001 coincided with a SP-resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dhps (but not dhfr) mutations corresponded with replacement of SP with artemether-lumefantrine as malaria treatment policy in KwaZulu-Natal. Our results show that drug pressure can exert its influence at a regional level rather than merely at a national level...
HLA-DRB1*04 Allele Is Associated with Severe Malaria in Northern Ghana [Am J Trop Med Hyg. 2008 Feb;78(2):251-5] — (English)
Several associations between specific HLA alleles and susceptibility or resistance to Plasmodium falciparum malaria have been previously reported, but no associations have been confirmed in multiple populations. We studied associations between HLA-A, -B, and DRB1 alleles and severe malaria in northern Ghana. We analyzed HLA-DRB1*04 in 4,032 subjects from a severe malaria case-control study, 790 severe malaria cases, 1,611 mild malaria controls, and 1631 asymptomatic controls. The presence of HLA-DRB1*04 was associated with severe malaria (OR = 2.42, 95% CI = 1.64, 3.58). The allele frequency of DRB1*04 was similar in the two major ethnic groups in the study population, Kassem (4.4%) and Nankam (4.7%), and the OR for the association between DRB1*04 and severe malaria was similar in both ethnic groups. These findings are consistent with results from Gabon suggesting that DRB1*04 is a risk factor for severe malaria...
Rapid Control of Malaria by Means of Indoor Residual Spraying of Alphacypermethrin in the Democratic Republic of Sao Tome and Principe [Am J Trop Med Hyg. 2008 Feb;78(2):248-250] — (English)
A nationwide yearly cycle of indoor residual spraying (IRS) with a pyrethroid, alphacypermethrin, at a dosage of 50 mg/m(2) was instituted in 2004 in the Democratic Republic of São Tomé and Príncipe. Rates of IRS acceptance were high, varying from 82% to 95% for dwellings and outhouses. Epidemiologic surveys of the children > 9 years of age before and after the first IRS cycle revealed a rapid reduction in malaria. Overall prevalence of malaria parasitemia for all districts was lowered from 20.1% to 2.8% at 12 months after the first IRS and reached 0.7% at 8 months after the second IRS. Longer insecticidal persistence was found on wood than on cement with alphacypermethrin...
Treatment of Acute Uncomplicated Falciparum Malaria with Artemether-Lumefantrine in Nonimmune Populations: A Safety, Efficacy, and Pharmacokinetic Study [Am J Trop Med Hyg. 2008 Feb;78(2):241-247] — (English)
The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients...
Hyper-reactive Malarial Splenomegaly in a Patient with Human Immunodeficiency Virus [Am J Trop Med Hyg. 2008 Feb;78(2):239-40] — (English)
Both hyperreactive malarial splenomegaly (HMS) and HIV infection are highly prevalent in sub-Saharan Africa, but the inter-relationships between the two conditions are not clearly defined. Diagnosis of HMS is particularly difficult in HIV-infected patients, and detection of circulating malaria parasites by polymerase chain reaction (PCR) may represent a useful diagnostic tool...
Accuracy and reliability of malaria diagnostic techniques for guiding febrile outpatient treatment in malaria-endemic countries [Am J Trop Med Hyg. 2008 Feb;78(2):217-21] — (English)
The main purpose of this study was to assess the accuracy of various techniques available for diagnosis of malaria. Blood samples were collected from 313 patients with clinical suspicion of uncomplicated malaria in 2 primary health centers in Madagascar. The presence of Plasmodium parasites was assessed by conventional microscopy, 2 rapid diagnostic tests (one HRP2-based test, PALUTOP(+4), and one pLDH-based test, OptiMAL-IT), and real-time polymerase chain reaction (PCR), which is used as the "gold standard" method. The degree of agreement observed was very high for microscopy (0.99) and the HRP2-based test (0.93) and high for the pLDH-based test (0.82). Public-health implications are also discussed in this paper...
An Indigenous Case of Plasmodium ovale Infection in Sri Lanka [Am J Trop Med Hyg. 2008 Feb;78(2):206-207] — (English)
Plasmodium ovale, which is generally prevalent only in the African region, has been emerging in the Asian and southeast Asian regions. It has not been reported in Sri Lanka. We report, to our knowledge, an indigenous case of P. ovale infection in Sri Lanka. This patient, who was diagnosed by a polymerase chain reaction, had no history of travel overseas or receipt of a transfusion of blood or any blood products, which makes this a likely case of indigenous transmission. This incidental finding of a P. ovale infection has implications for malaria control in the country and highlights the need to rigorously monitor malaria incidence, as well as prevalent Plasmodium species, with newer and more reliable diagnostics...
Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria [Am J Trop Med Hyg. 2008 Feb;78(2):198-205] — (English)
Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-alpha levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-alpha production is associated with subsequent neurologic and cognitive morbidity...
Plasmodium falciparum and Plasmodium vivax infections induce similar cytokine responses and similar degrees of anemia in an area of coexisting transmission in the Brazilian Amazon region [Clin Vaccine Immunol. 2008 Feb 6] — (English)
The mechanisms of malarial anemia induction are poorly understood, but cytokines and autoantibodies have been considered as playing important roles. This work aimed at evaluating the degree of anemia and the plasmatic profile of the cytokines TNF-alpha, IFN-gamma, IL-12, MIF, IL-10 and the MCP-1 chemokine, as well as the presence of antibodies directed to components of the normal erythrocyte membrane and to cardiolipin in individuals with malaria from the Brazilian Amazon. No difference was observed in the anemia frequency between patients infected by P. vivax (Pv) or P. falciparum (Pf), and there was no relation between level of parasitemia and manifestation of anemia in Pv or Pf patients. Significant increases in the concentrations of TNF-alpha, IFN-gamma, MIF and MCP-1 were observed in patients with Pf and Pv malaria, whereas the concentrations of IL-10 was increased only in patients with Pv infection. Higher concentrations of IL-12 and IL-10 were observed in the Pf anemic patients, while for TNF-alpha this profile was observed in the non-anemic ones. Pv-infected and Pf-infected patients with positive IgM, or IgM and IgG, responses, respectively, against blood stages had significantly lower hemoglobin levels than with negative responses. There was no correlation between the presence of anti-erythrocyte and anti-cardiolipin antibodies and the presence or the intensity of the anemia. Our data suggest that in areas of low endemicity and unstable transmission of malaria Pv and Pf infections present similar characteristics in what concerns induction of anemia and cytokine responses...
SINGLE DOSE PROTECTION AGAINST P. berghei BY SIMIAN ADENOVIRAL VECTOR USING HUMAN CMV PROMOTER CONTAINING INTRON A [ J Virol. 2008 Feb 6 ] — (English)
Human adenovirus serotype 5 (AdH5) vectored vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a Human Cytomegalovirus (HCMV) immediate-early promoter containing its Intron A sequence. The transcriptional levels of antigen and immune responses to antigen in vectors with the HCMV promoter with Intron A sequence (LP) was greater than those of AdH5 vectors using HCMV promoter sequence without Intron A (SP). We compared E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequence and showed them to be as immunogenic as E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on AdH5 serotype and simian adenoviral vectors offer an attractive option to overcome this. We constructed E1E3-deleted human and simian adenoviral vectors encoding a pre-erythrocytic malarial antigen, P. berghei circumsporozoite protein (Pb.CSP). We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6, in a murine malaria model to AdH5 and pox viral vectors, MVA and FP9. AdC6 induced sterile protection in 90% of mice in contrast to AdH5 (25%) and pox viral vectors MVA and FP9 (0%) from a single dose. Adenoviral vectors maintained potent CD8+ T cell responses for a longer period after immunization compared to pox viral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of pre-existing immunity to AdH5...
Treating severe malaria: artesunate or quinine? [Indian Pediatr. 2008 Jan;45(1):41-2] — (English)
Severe (complicated) malaria caused by Plasmodium falciparum kills over a million people every year. The annual death toll can be as high as one in 100 children under the age of five. Intravenous infusion of quinine is recommended as an initial therapy for these children....
Malaria Parasites Require TLR9 Signaling for Immune Evasion by Activating Regulatory T Cells [J Immunol. 2008 Feb 15;180(4):2496-503] — (English)
Malaria is still a life-threatening infectious disease that continues to produce 2 million deaths annually. Malaria parasites have acquired immune escape mechanisms and prevent the development of sterile immunity. Regulatory T cells (Tregs) have been reported to contribute to immune evasion during malaria in mice and humans, suggesting that activating Tregs is one of the mechanisms by which malaria parasites subvert host immune systems. However, little is known about how these parasites activate Tregs. We herein show that TLR9 signaling to dendritic cells (DCs) is crucial for activation of Tregs. Infection of mice with the rodent malaria parasite Plasmodium yoelii activates Tregs, leading to enhancement of their suppressive function. In vitro activation of Tregs requires the interaction of DCs with parasites in a TLR9-dependent manner. Furthermore, TLR9(-/-) mice are partially resistant to lethal infection, and this is associated with impaired activation of Tregs and subsequent development of effector T cells. Thus, malaria parasites require TLR9 to activate Tregs for immune escape...
Differences in human antibody reactivity to Plasmodium falciparum variant surface antigens dependent on age and malaria transmission intensity in north-eastern Tanzania [Infect Immun. 2008 Feb 4] — (English)
Plasmodium falciparum variant surface antigens (VSA) are involved in the pathogenesis of malaria. Immunoglobulin (Ig) G with specificity for VSA (anti-VSA IgG) are therefore considered important for acquired immunity. To better understand the nature and dynamics of variant-specific IgG responses at population level, we conducted an immuno-epidemiological study in nearby communities in north-eastern Tanzania, situated at different altitude and therefore exposed to different levels of P. falciparum transmission intensity. Samples of plasma and infected red blood cells (IRBC) were collected from 759 individuals aged 0-19 years. Plasma levels of IgG with specificity for VSA expressed by a panel of different parasite isolates were measured with flow cytometry, while the ability of plasma to inhibit IRBC adhesion to CD36 was examined in cellular assays. The level and repertoire of the heterologous anti-VSA IgG response developed dramatically from the age of 1-2 years in the high-transmission area, reaching a maximum level around ten years of age; only a modest further increase was observed among older children and adults. In contrast, at lower levels of malaria transmission, anti-VSA IgG levels were lower and the repertoire more narrow, and similar age- and transmission-dependent differences were observed with regard to the ability of the plasma samples to inhibit adhesion of IRBC to CD36. These differences indicate a strong and dynamic relationship between malaria exposure and functional characteristics of the variant-specific antibody response, likely to be important for protection against malaria...
Evidence for Globally Shared, Cross-reacting Polymorphic Epitopes in the Pregnancy Malaria Vaccine Candidate VAR2CSA [Infect Immun. 2008 Feb 4] — (English)
Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size ( approximately 350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5 and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles, however, anti-sera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines...
Elevated IFN-{gamma} producing NK cells, CD45RO memory-like T cells and CD4 T cells are associated with protection against malaria infection in pregnancy [Infect Immun. 2008 Feb 4] — (English)
Previous studies have shown that IFN-gamma production in the placenta is associated with protection against placental malaria. However, it remains unknown which IFN-gamma producing cell subpopulations are involved in this protection and whether the cellular immune components of protection are the same in the peripheral and the placental blood compartments. We investigated cell subpopulations for CD4, CD8, CD45RO memory-like T cells and CD56+/CD3- Natural Killer (NK) cells, and IFN-gamma production by these cells in maternal peripheral and placental intervillous blood in relation to status of malaria infection in pregnancy. Of 52 HIV-negative enrolled pregnant women residing in western Kenya, 20 had placental parasitemia. We found that the percentages of CD45RO memory-like and CD4 T cells were significantly higher in the periphery than in the placenta, while the CD56/CD3- NK cell percentage was higher in the placenta than in the periphery suggesting differences in immune cell profiles between the two blood compartments. Furthermore, the percentages of peripheral CD45RO memory-like and CD4 T cells were significantly elevated in aparasitemic women compared to parasitemic group, with aparasitemic multigravid women having the highest percentages of CD45RO memory-like and CD4 T cells. In contrast, at the placental level IFN-gamma production by innate NK cells was significantly increased in aparasitemic women as compared to parasitemic women, regardless of gravidity. These results suggest that the elevated IFN-gamma producing NK cells in the placenta and CD45RO memory-like and CD4 T cells in peripheral blood may be involved in protection against malaria infection in pregnancy...
A three-genome phylogeny of malaria parasites (Plasmodium and closely related genera): Evolution of life-history traits and host switches [Mol Phylogenet Evol. 2007 Dec 3] — (English)
Phylogenetic analysis of genomic data allows insights into the evolutionary history of pathogens, especially the events leading to host switching and diversification, as well as alterations of the life cycle (life-history traits). Hundreds, perhaps thousands, of malaria parasite species exploit squamate reptiles, birds, and mammals as vertebrate hosts as well as many genera of dipteran vectors, but the evolutionary and ecological events that led to this diversification and success remain unresolved. For a century, systematic parasitologists classified malaria parasites into genera based on morphology, life cycle, and vertebrate and insect host taxa. Molecular systematic studies based on single genes challenged the phylogenetic significance of these characters, but several significant nodes were not well supported. We recovered the first well resolved large phylogeny of Plasmodium and related haemosporidian parasites using sequence data for four genes from the parasites' three genomes by combining all data, correcting for variable rates of substitution by gene and site, and using both Bayesian and maximum parsimony analyses. Major clades are associated with vector shifts into different dipteran families, with other characters used in traditional parasitological studies, such as morphology and life-history traits, having variable phylogenetic significance. The common parasites of birds now placed into the genus Haemoproteus are found in two divergent clades, and the genus Plasmodium is paraphyletic with respect to Hepatocystis, a group of species with very different life history and morphology. The Plasmodium of mammal hosts form a well supported clade (including Plasmodium falciparum, the most important human malaria parasite), and this clade is associated with specialization to Anopheles mosquito vectors. The Plasmodium of birds and squamate reptiles all fall within a single clade, with evidence for repeated switching between birds and squamate hosts...
Dynamics of insecticide resistance in the malaria vector Anopheles gambiae s.l. from an area of extensive cotton cultivation in Northern Cameroon [Trop Med Int Health. 2008 Feb 1] — (English)
Throughout the survey, An. gambiae s.l. populations were completely susceptible to carbamate and organophosphate, whereas a significant decrease of susceptibility to organochlorine and pyrethroids was observed during spraying in cotton-growing areas. Tolerance to these insecticides was associated with a slight increase of knockdown times compared to the reference strain. Among survivor mosquitoes, the East and West African Kdr mutations were detected only in two specimens of An. gambiae s.s. (n = 45) and not in Anopheles arabiensis (n = 150), suggesting metabolic-based resistance mechanisms...
Actin is required for endocytic trafficking in the malaria parasite Plasmodium falciparum [Cellular Microbiology, Volume 10 Issue 2 Page 452-464, February 2008 ] — (English)
The intra-erythrocytic stages of the malaria parasite endocytose large quantities of the surrounding erythrocyte cytoplasm and deliver it to a digestive food vacuole via endocytic vesicles. Digestion provides amino acids for parasite protein synthesis and is required to maintain the osmotic integrity of the host cell. The parasite endocytic pathway has been described morphologically by electron microscopy, but the molecular mechanisms that mediate and regulate it remain elusive. Given the involvement of actin in endocytosis in other eukaryotes, we have used actin inhibitors to assess the requirement for this protein in the endocytic pathway of the human malaria parasite, Plasmodium falciparum. Treatment of cultures with cytochalasin D did not affect haemoglobin levels in the parasites when co-administered with protease inhibitors, and neither did it affect the uptake of the endocytic tracer horseradish peroxidase, suggesting the absence of actin in the mechanism of endocytosis. However, in the absence of protease inhibitors, treated parasites contained increased levels of haemoglobin due to an accumulation of enlarged endocytic vesicles, as determined by immunofluorescence and electron microscopy, suggesting a role for actin in vesicle trafficking, possibly by mediating vesicle maturation and/or fusion to the digestive vacuole. In contrast to cytochalasin D, treatment with jasplakinolide led to an inhibition of endocytosis, an accumulation of vesicles closer to the plasma membrane and a marked concentration of actin in the parasite cortex. We propose that the stabilization of cortical actin filaments by jasplakinolide interferes with normal endocytic vesicle formation and migration from the cell periphery...
Placental Expression of alpha2,6-Linked Sialic Acid is Upregulated in Malaria [Placenta. 2008 Feb 1] — (English)
In Africa, approximately 25 million pregnant women are at risk of Plasmodium falciparum infection each year, one in four has evidence of placental involvement and up to half of these may be associated with low birth weight outcomes. In infected pregnant women, the placenta is an ideal site for the accumulation of the parasites, and this reduces in extent in subsequent pregnancies. Recent data indicate that terminal alpha2,3 sialic acid-dependent routes are central to the efficient invasion of erythrocytes with P. falciparum, however, the role in placental malaria of sialylated, or other glycoconjugates, on syncytiotrophoblast has not previously been assessed. Placental biopsies from Zambian women showed the Neu5Ac(alpha2,6)Gal/GalNAc sequences bound by the lectin from Sambucus nigra (SNA-1) to have greatly increased expression on microvillous membranes in samples with chronic P. falciparum infection showing, by electronic image analysis, a significant trend (p=0.002) compared to samples with past or no infection. This suggests a specific placental membrane response to falciparum malaria. Expression of alpha2,6-linked sialic acid, demonstrated by the binding of SNA-1, has been associated with intercellular repulsion in tissues from patients with cancer, and such repulsion resulting from increased alpha2,6 sialylation of chorionic villi could influence intervillous placental parasite density. Sialic acid expression should be examined in placental malaria to identify if this is a malaria-specific phenomenon, and to determine its relation to placental inflammation and pregnancy outcomes...
The relationship between terrorist activities and cases of malaria in the eastern and south-eastern regions of Turkey, 1984-1998 [Trans R Soc Trop Med Hyg. 2008 Feb 1] — (English)
The objective of this study was to determine whether cases of malaria are related to terrorist activities that have occurred in the eastern and south-eastern regions of Turkey. Some of the determinants related to malaria have been investigated using a national dataset for 11 provinces located in these regions of Turkey. In these regions, both terrorist activity and cases of malaria were common from 1984 to 1998. A multiple regression technique was used to identify the variables that are significantly associated with cases of malaria. Annual incidence of malaria was chosen as the dependent variable along with three independent (explanatory) variables: annual number of terrorist incidences, people per healthcare technician and number of thick blood films per 100 000 people. Based on this analysis, it is determined that the annual number of terrorist incidences has been associated with the annual number of malaria cases in these regions of Turkey since the beginning of terrorist activity in 1984...
Hyperreactive malarial splenomegaly is associated with low levels of antibodies against red blood cell and Plasmodium falciparum derived glycolipids in Yanomami Amerindians from Venezuela [Acta Trop. 2007 Dec 27] — (English)
The immunological basis of the aberrant immune response in hyperreactive malarial splenomegaly (HMS) is poorly understood, but believed to be associated with polyclonal B cell activation by an unidentified malaria mitogen, leading to unregulated immunoglobulin and autoantibody production. HMS has been previously reported in Yanomami communities in the Upper Orinoco region of the Venezuelan Amazon. To investigate a possible association between antibody responses against Plasmodium falciparum and uninfected red blood cell (URBC) glycolipids and splenomegaly, a direct comparison of the parasite versus host anti-glycolipid antibody responses was made in an isolated community of this area. The anti-P. falciparum glycolipid (Pfglp) response was IgG3 dominated, whereas the uninfected red blood cell glycolipid (URBCglp) response showed a predominance of IgG1. The levels of IgG1 against Pfglp, and of IgG4 and IgM against URBCglp were significantly higher in women, while the anti-Pfglp or URBCglp IgM levels were inversely correlated with the degree of splenomegaly. Overall, these results suggest differential regulation of anti-parasite and autoreactive responses and that these responses may be linked to the development and evolution of HMS in this population exposed to endemic malaria. The high mortality rates associated with HMS point out that its early diagnosis together with the implementation of malaria control measures in these isolated Amerindian communities are a prior...
Placental Expression of α2,6-Linked Sialic Acid is Upregulated in Malaria [Placenta, In Press, Corrected Proof, Available online 4 February 2008] — (English)
In Africa, approximately 25 million pregnant women are at risk of Plasmodium falciparum infection each year, one in four has evidence of placental involvement and up to half of these may be associated with low birth weight outcomes. In infected pregnant women, the placenta is an ideal site for the accumulation of the parasites, and this reduces in extent in subsequent pregnancies. Recent data indicate that terminal α2,3 sialic acid-dependent routes are central to the efficient invasion of erythrocytes with P. falciparum, however, the role in placental malaria of sialylated, or other glycoconjugates, on syncytiotrophoblast has not previously been assessed. Placental biopsies from Zambian women showed the Neu5Ac(α2,6)Gal/GalNAc sequences bound by the lectin from Sambucus nigra (SNA-1) to have greatly increased expression on microvillous membranes in samples with chronic P. falciparum infection showing, by electronic image analysis, a significant trend (p = 0.002) compared to samples with past or no infection. This suggests a specific placental membrane response to falciparum malaria. Expression of α2,6-linked sialic acid, demonstrated by the binding of SNA-1, has been associated with intercellular repulsion in tissues from patients with cancer, and such repulsion resulting from increased α2,6 sialylation of chorionic villi could influence intervillous placental parasite density. Sialic acid expression should be examined in placental malaria to identify if this is a malaria-specific phenomenon, and to determine its relation to placental inflammation and pregnancy outcomes...
Prepared in cooperation with WHO ANGOLA INFO.
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