10.12.2007
World 'must do more' for children [BBC - UK] — (English)
More must be done more quickly to make the world fit for children by 2015, the UN children's agency, Unicef, has said...
Afrique: Contribution du secteur privé à la lutte contre le sida, la tuberculose et le paludisme - L'initiative (Product) Red remporte la palme [Le Soleil (Dakar) via AllAfrica.com] — (Français)
L'Initiative (Product) Red a franchi une étape historique dans le financement des programmes de lutte contre le Sida, la tuberculose et le paludisme. Elle vient de dépasser le cap de 50 millions de dollars à titre de contribution...
Malaria cases on the rise in Phoolnagar [The Post - Lahore,Punjab,Pakistan] — (English)
The cases of malaria are on the rise in Phoolnagar and adjoining areas while the Tehsil Municipal Authority (TMA) and local administration is not paying attention to it...
9.12.2007
As world warms and mosquitoes thrive, malaria climbs into New Guinea highlands [IHT] — (English)
In one New Guinea hilltop village the message was rooted deep in lore: If you hunt in the valley below and sleep there overnight, evil spirits will possess you, you'll become sick, and you'll die...
Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi) [Malaria Journal 2007, 6:163 (9 December 2007)] — (English)
The IPTi application schedule was originally evaluated in Tanzania based on a single-dose sulphadoxine-pyrimethamine and pragmatically linked to the expanded programme on immunization. In reality, considerable differences in the effectiveness of this intervention from site to site have since been shown. The aim of this study was to determine how far the protective efficacy of IPTi depends on spatio-temporal variations of the prevailing incidence of malaria...
Dynamo star heads for Africa for anti-malaria campaign [Houston Chronicle - United States] — (English)
All it took was a conversation with fellow Major League Soccer player Diego Gutierrez and a glance at the sobering statistics, and Dwayne De Rosario knew he couldn't pass up the opportunity...
‘Cheaper malaria drugs under way’ [Nigerian Tribune - Ibadan,Nigeria] — (English)
AS part of efforts at meeting the health related Millennium Development Goals target, the Federal Government will soon make available cheaper malaria drugs to Nigerians. The Minister of Health, Professor Adenike Grange who stated this at the weekend in Addis Ababa, Ethiopia, at the 13th “Roll Back Malaria Partnership Board Meeting”, bemoaned the rising burden of malaria disease on the African sub region especially Nigeria where minimal achievement has been made towards mitigating malaria impact on its economic development...
8.12.2007
Fight malaria [Dispatch.com] — (English)
More than a year after the World Health Organization gave its blessing to the limited indoor use of DDT to fight malaria, a report by the American Enterprise Institute says the effort has stalled. No new country has taken up DDT against malaria-carrying mosquitoes since the health group's announcement in September 2006, according to American Enterprise resident fellow Roger Bate. About 10 African countries were then and still are spraying with DDT...
Annual Malaria Infection Rate Down [Yemen Observer - Sana'a,Yemen] — (English)
Malaria is one of the most serious health problems in Yemen. Approximately 60 percent of the population lives in malaria-infested areas. The 2005 Annual Report issued by the National Malaria Program of the Ministry of Public Health and Population estimates that between one and two million people are newly infected with malaria each year in Yemen, and of these about one percent will die from the disease. As a result, as many as 15,000 to 20,000 Yemenis die from malaria every year...
Malaria-causing Parasites' Evading Tactics of Immune System Exposed [MedIndia - Chennai,India] — (English)
Researchers at the Walter and Eliza Hall Institute of Medical Research, Australia, have found the evasion tactics of the malaria causing parasite Plasmodium falciparum...
7.12.2007
Did They Really Say … Eradication? [Science, 7 December 2007, Vol. 318. no. 5856, pp. 1544 - 1545] — (English)
The malaria world is all abuzz about a call by Bill and Melinda Gates to wipe the scourge from the planet. Even if it proves unfeasible, their idea could have a big impact ...
President's Malaria Initiative E-Newsletter, November [President's Malaria Initiative E-Newsletter] — (English)
News, Country-Specific Activities, Technical Areas ...
Malcolm X Daughter Travels to Ancestral Home; Joins Muslim-American Leadership to Fight Malaria in Mali [Reuters - USA] — (English)
This December 9 - 14, Ms. Shabazz will visit her ancestral home for the
first time as part of a Muslim delegation hosted by Malaria No More, an
organization working to end malaria-related deaths in Africa...
Uganda: Mbale Residents to Benefit From Malaria Project [The Monitor (Kampala) via AllAfrica.com] — (English)
ABOUT 56 villages in Bungokho Sub-county will benefit from a local initiative aimed at stamping malaria out of households, the LC 3 chairman, Mr Ahmed Washaki, has said...
Researchers from New York University, Department of Pathology describe findings in malaria [Calibre MacroWorld - United States ] — (English)
New investigation results, 'Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite,' are detailed in a study published in Cell (see also Malaria). "The liver stages of malaria are clinically silent but have a central role in the Plasmodium life cycle. Liver stages of the parasite containing thousands of merozoites grow inside hepatocytes for several days without triggering an inflammatory response," scientists in the United States report...
Scientists at Osaka University, Research Institute for Microbial Disease release new data on falciparum malaria [Calibre MacroWorld - United States] — (English)
Data detailed in 'Oleic acid is indispensable for intraerythrocytic proliferation of Plasmodium falciparum' have been presented (see also Falciparum Malaria). According to recent research from Suita, Japan, "Serum-derived fatty acids are essential for the intraerythrocytic proliferation of Plasmodium falciparum in humans. We previously reported that only limited combinations of fatty acids can support long-term parasite culture, and palmitic acid (C16:0)/oleic acid (C18:1, n-9), palmitic acid (C16:0)/vaccenic acid (C18:1, n-7), or stearic acid (C18:0) are required in these combinations, implying that these fatty acids are key molecules for intraerythrocytic parasite growth (Mi-Ichi et al. 2006)."...
Here's how Malaria-causing parasite evades immune system [Economic Times - Gurgaon,Haryana,India] — (English)
Researchers at the Walter and Eliza Hall Institute of Medical Research, Australia, have found the evasion tactics of the malaria causing parasite Plasmodium falciparum. James Beeson and colleagues found that Plasmodium falciparum uses various red blood cell invasion mechanisms to evade the human immune response, which eventually causes the disease...
Gloria grants P1 million for malaria, dengue drive [Manila Standard Today - Philippines] — (English)
PRESIDENT Gloria Macapagal Arroyo has earmarked P1 million to bankroll the campaign against malaria and dengue in Metro Manila including Antipolo City in Rizal and Lian, Batangas...
6.12.2007
Less May Be More When Treating Malaria [Voice of America - USA] — (English)
Read realized that the common medical practice of flooding a patient's body with anti-malarial drugs might actually have the paradoxical effect of making drug resistance worse. He explains that what may be happening is that drug resistant malaria is able to grow without any competition once the medicine has killed drug sensitive strains. And then… it's the drug resistant strain that's more likely to get spread from person to person...
Künstliche Blume bekämpft schonend Malaria [Die Welt - Germany ] — (Deutsch)
Eine gesunde Mücke ist auch gesund für den Menschen. Diese simple Idee machten sich Forscher zunutze und entwickelten eine Impfstoff für Mücken, der diese vor Malaria schützen soll. Eine künstliche Blume soll die Tiere mit Signalen anlocken und den Impfstoff aufnehmen lassen...
When a spoonful of sugar won't do [Economist - UK] — (English)
The WHO wants some of its proposed fund to pay for the basic research necessary to create children's formulations. It will initially focus on a small group of diseases that account for most deaths among the under-fives, including HIV/AIDS, malaria, tuberculosis, pneumonia and various forms of diarrhoea. The biggest problems in children's medicine concern diseases that afflict the poor. But the shortage of child-friendly medicine is not confined to poor countries. Even in Europe, fewer than half of the drugs administered to children have been tested and authorised for their use. And there are gaps in the treatment of diseases not unusual among rich-world children, including epilepsy and psychotic conditions...
Canadians Make a Difference in Fight against Malaria [Epoch Times - New York,NY,USA] — (English)
Today, the registered nurse and mother of four passionately champions the cause of the millions of helpless and voiceless African children dying of the mosquito-borne disease...
Afghan farmers could grow new anti-malarial drug instead of opium poppies: report [Canadian Press/Google.com] — (English)
Afghan farmers could grow a new anti-malaria crop as part of an effort to wean them away from the illegal drug trade, an international think tank said Wednesday...
Climate prediction of El Nino malaria epidemics in north-west Tanzania [Malaria Journal 2007, 6:162 (6 December 2007)] — (English)
A topic of considerable interest to the climate and health community. It adds further analysis on climate and malaria interactions – a subject already well covered by a number of research groups in East Africa, with the added novelty of an evaluation of seasonal forecasting models...
Health Protection News from UK and Europe [ NHS England - United Kingdom ] — (English)
Malaria risk for travellers in Dominican Republic...
5.12.2007
A Virosomal Malaria Peptide Vaccine Elicits a Long-Lasting Sporozoite-Inhibitory Antibody Response in a Phase 1a Clinical Trial [PLOS One] — (English)
Virosomal delivery of a short, conformationally constrained peptide derived from P. falciparum CSP induced a long-lived parasite-inhibitory antibody response in humans. Combination with a second virosomally-formulated peptide derived from P. falciparum AMA-1 did not interfere with the immunogenicity of either peptide, demonstrating the potential of influenza virosomes as a versatile, human-compatible antigen delivery platform for the development of multivalent subunit vaccines...
Gates Foundation gives $30M to combat malaria [Bizjournals.com - Charlotte,NC,USA] — (English)
Seattle's Infectious Disease Research Institute has received a $30 million grant from the Bill & Melinda Gates Foundation to combat malaria...
Malaria Making a Comeback [NewsMax.com - West Palm Beach,FL,USA] — (English)
The voice override of the public service announcement implies mosquito netting should be placed over all of Africa...
Ethiopia launches 1,2bn malaria initiative [AfricaNews - Netherlands] — (English)
Ethiopia became a focus country for the historic 1.2 bln USD, five-year U.S. effort to fight malaria across Africa. United States Ambassador Donald Yamamoto joined Dr. Kebede Worku, State Minister of Health, and retired Rear Admiral Tim Ziemer, U.S. Malaria Coordinator, to launch the President's Malaria Initiative (PMI), a joint effort to fight the disease on November 30, 2007 at the US embassy...
Malawi starts using new drug to treat malaria [Nyasa Times - Blantyre,Southern,Malawi] — (English)
Malawi has officially started using the expensive lumefantrine and artemether (LA) as its first line drug of choice for treating malaria cases at its health facilities countrywide...
Indian Malaria Drug Approved In Ghana [MedHeadlines - Chicago,IL,USA] — (English)
According to the Central Drug Research Institute of India, Food and Drug Board of Ghana has approved a new drug to treat complicated Malaria that affects the functioning of the brain...
Fulbright scholar studies malaria [Edmond Sun - OK,USA] — (English)
Death haunts millions of children each year with malaria. Lindsey Turnbull hopes to provide a healthy future for these children. She has spent the past 16 months researching malaria in England and sub-Saharan Africa...
At least nine people died out of the 1,706 cases of malaria recorded over the first five months in Humpata District, southern Huila Province [Angola Press Agency (Luanda) via AllAfrica.com] — (Français)
L'église Evangélique Anglicane a dépensé, depuis le début de 2007, 2 millions de dollars pour lutter contre la malaria dans la province septentrionale de Uige, à l'initiative du Président Geoerges W. Bush, des Etats-Unis, apprend l'Angop de source religieuse...
Gabon: Ouverture à Libreville d'un séminaire de formation des Organisations non gouvernementales sur les méthodes de lutte contre le paludisme [Gabonews (Libreville) via AllAfrica.com] — (Français)
Le programme national de lutte contre le paludisme, la tuberculose et le Vih/Sida et le Fonds mondial pour le développement offrent aux responsables des ONG gabonaises une formation sur les méthodes de lutte contre le paludisme, a constaté GABONEWS...
Tunisie: 5e réunion régionale du Fonds - Adapter les objectifs aux programmes nationaux de lutte contre ces fléaux [La Presse (Tunis) via AllAfrica.com] — (Français)
La Tunisie abrite, du 3 au 6 décembre, la 5e réunion régionale des commissions nationales de coordination et de suivi des pays d'Afrique du Nord et du Moyen-Orient, bénéficiant des programmes du Fonds mondial de lutte contre le sida, la tuberculose et le paludisme...
Tunisie: Le directeur exécutif du Fonds mondial de lutte contre le sida, la tuberculose et le paludisme reçu à La Kasbah [La Presse (Tunis) via AllAfrica.com] — (Français)
Conjuguer les efforts arabes, islamiques et africains pour lutter contre ces trois pandémies...
Artemisia gegen Malaria [n-tv.de] — (Deutsch)
Die Malariamedizin wächst im Garten der äthiopischen Bauernfamilie, wie auch vor zahlreichen Hütten in Sodo, einem der "Millenniumsdörfer" der Deutschen Welthungerhilfe. Hier soll nachhaltige Entwicklung besonders genau dokumentiert und die Ergebnisse überprüft werden. Doch auch in anderen Projekten, ob auf dem Land oder in städtischen Slums, ermutigen die Helfer der Welthungerhilfe die Äthiopier zum Anbau von Artemisia, dem Beifuß...
4.12.2007
How is childhood development of immunity to Plasmodium falciparum enhanced by certain antimalarial interventions ? [Malaria Journal 2007, 6:161 (4 December 2007)] — (English)
A hypothesis suggesting that low-dose P. falciparum infections enhance the development of immunity, hence that presumptive administration of SP to young children, in moderate to high transmission areas, can accelerate their acquisition of protective immune responses...
Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas [Malaria Journal 2007, 6:160 (4 December 2007)] — (English)
The paper discusses current modalities of application of intermittent preventive treatment and ways in which these could be inprove...
‘350 cases of malaria recorded, but no deaths’ [Siasat Daily - Hyderabad,Andhra Pradesh,India] — (English)
The State Government has admitted that there are 350 cases of malaria and that there is no loss of life since January in the tribal villages of Adilabad district, which are prone to high incidence of fever....
Articles requiring subscription
Africa counts greater successes against malaria [The Lancet, Volume 370, Issue 9603, 8 December 2007-14 December 2007, Pages 1895-1896] — (English)
Some of the African countries most affected by malaria are scoring key successes in the fight against the disease thanks to a combination of old and new interventions and a boost in funding—raising hopes that the global malaria burden can be halved by 2010. Wairagala Wakabi reports... Awa Marie Coll-Seck, executive director of the Roll Back Malaria Partnership, an initiative of WHO, UNICEF, the UN Development Programme, and the World Bank, says successes in countries such as Mali, Senegal, Benin, and Togo, are providing optimism that by 2010 the malaria burden will be reduced by half...
The US President's Malaria Initiative: 2 years on [The Lancet, Volume 370, Issue 9603, 8 December 2007-14 December 2007, Pages 1893-1894 ] — (English)
The US President's Malaria Initiative, launched in 2005, seems to be avoiding the pitfalls of its predecessors. Rather than spending money on high-priced consultants, the new programme is winning praise by focusing on implementing effective interventions. Samuel Loewenberg reports...
Efficient Development of Plasmodium Liver Stage–Specific Memory CD8+ T Cells during the Course of Blood-Stage Malarial Infection [The Journal of Infectious Diseases 2007;196:1827–1835 ] — (English)
Immunity to Plasmodium liver stages in individuals in malaria-endemic areas is inextricably linked to concomitant blood-stage parasitemia. Although Plasmodium sporozoite infection induces measurable CD8+ T cell responses, the development of memory T cells during active erythrocytic infection remains uncharacterized. Using transgenic T cells, we assessed antigen-specific effector CD8+ T cell responses induced by normal (NorSpz) and radiation-attenuated (IrrSpz) Plasmodium yoelii sporozoites. The magnitude, phenotypic activation, and differentiation pathway of CD8+ T cells were similarly induced by NorSpz and IrrSpz. Moreover, in normal mice, memory T cells elicited after priming with NorSpz and IrrSpz generated identical recall responses after a heterologous boost strategy. Furthermore, these recall responses exhibited comparable in vivo antiparasite activity. Our results indicate that sporozoites that retain their infective capacity induce memory CD8+ T cells that are robustly recalled by secondary immunization. Thus, erythrocytic infection does not preclude the establishment of memory CD8+ T cell responses to malarial liver stages...
Proceedings of a Consensus Conference: Pathogen Inactivation—Making Decisions About New Technologies [Transfusion Medicine Reviews, Volume 22, Issue 1, January 2008, Pages 1-34 ] — (English)
Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference...
Markedly enhanced immunogenicity of a Pfs25 DNA-based malaria transmission-blocking vaccine by in vivo electroporation [Vaccine, In Press, Corrected Proof, Available online 4 December 2007] — (English)
Pfs25 is a promising target antigen for the development of a malaria transmission-blocking vaccine and prior research has demonstrated induction of high and functionally effective antibodies in mice with IM injection of Pfs25 encoding DNA plasmid. Likewise, Pfs25 DNA vaccine was immunogenic in rhesus macaques but required a protein boost to elicit significant transmission-blocking antibodies. The translation of these encouraging findings to human clinical trials has been impeded largely by the relatively poor immunogenicity of DNA plasmids in larger animals. In vivo electroporation (EP) has revealed significant enhancement of the potency of DNA plasmids. The results reported here compared the immunogenicity and functional transmission-blocking effects of immunization with DNA plasmid (25 μg) by the traditional IM route compared to coupling the IM injection (0.25, 2.5 and 25 μg doses) with in vivo EP. Significantly, a 0.25 μg dose of DNA plasmid, when administered with EP, induced antibody titers (1:160,000) and functional transmission-blocking effects that were equivalent to those achieved by a one hundred fold higher (25 μg) dose of DNA plasmid given without EP. At a 25.0 μg DNA dose with or without EP there was sufficient antigenic stimulation to result in effective antibody titers; however EP method yielded antibody titer of 1:1,280,000 as compared to only 1:160,000 titer without EP. This observed two log reduction in the amount of DNA plasmid required to induce significant transmission-blocking effects makes a compelling argument in favor of further evaluation of DNA vaccines by in vivo EP method in larger animals. Further experiments in non-human primates and eventually in phase I human trials will determine if the use of EP will induce effective and sustained malaria transmission-blocking effects at acceptable doses of plasmid DNA...
Malaria vaccine boost [Current Biology, Volume 17, Issue 23, 4 December 2007, Page R985 ] — (English)
Safety tests suggest a new malaria vaccine is tolerated by very young babies most at risk from the disease, and provides some protection too, encouraging further trials. Nigel Williams reports...
Insecticide susceptibility and vector status of natural populations of Anopheles arabiensis from Sudan [Transactions of the Royal Society of Tropical Medicine and Hygiene, In Press, Corrected Proof, Available online 3 December 2007 ] — (English)
Species composition, blood meal source, sporozoite infection rate, insecticide resistance and the kdr mutations were investigated in the Anopheles gambiae complex from 13 sentinel sites in central Sudan. Species identification revealed that 89.5% of 960 specimens were A. arabiensis. Of 310 indoor resting females, 88.1% were found to have fed on humans, while 10.6% had fed on bovines. The overall sporozoite infection rate from the five localities tested was 2.3%, ranging from 0 to 5.5%. Insecticide susceptibility bioassay results showed 100% mortality on bendiocarb, 54.6–94.2% on permethrin, 55.4–99.1% on DDT and 76.8–100% on malathion. The kdr analysis by PCR and sequencing revealed the presence of the Leu–Phe mutation in both permethrin and DDT bioassays. There was no significant difference in the frequency of kdr (P > 0.05) between dead and surviving specimens. These findings have serious implications for the malaria control programmes in Gezira and Sennar states...
New clinical and ultrastructural findings in hydroxychloroquine-induced cardiomyopathy—a report of 2 cases [Human Pathology, Volume 38, Issue 12, December 2007, Pages 1858-1863 ] — (English)
Hydroxychloroquine- or chloroquine -induced cardiomyopathy is a rare but potentially fatal condition. Hydroxychloroquine and chloroquine are often used for long-term treatment of rheumatic diseases and for malaria prophylaxis. Hydroxychloroquine- and chloroquine-induced cardiomyopathy have well-described microscopic features, with the classic electron microscopic findings of myelin figures (myeloid bodies). We report on 2 new cases with novel findings. The first case, in a patient with systemic lupus erythematosus, was found to have megamitochondria in addition to myelin figures seen by electron microscopy. The second report describes the first case of hydroxychloroquine cardiomyopathy described in a patient with scleroderma. These novel findings will add to the present knowledge of hydroxychloroquine-induced cardiomyopathy in its pathology and its implication for treatment of rheumatic diseases...
ABO Blood Group Phenotypes and Plasmodium falciparum Malaria: Unlocking a Pivotal Mechanism [Advances in Parasitology, Volume 65, 2007, Pages 1-50] — (English)
Host susceptibility to Plasmodium falciparum infection is central for improved understanding of malaria in human populations. Red blood cell (RBC) polymorphisms have been proposed as factors associated with malaria infection or its severity, although no systematic appraisal of ABO phenotypes and malaria risk has been undertaken. This analysis summarises epidemiological, clinical and immunological evidence on the nature of ABO histo-blood antigens and their interaction with malaria in terms of population genetics, infection risk, severe malaria and placental malaria. In non-pregnant subjects, a meta-analysis showed no conclusive evidence associating ABO phenotypes with risk of uncomplicated malaria. There was stronger evidence that ABO phenotype modulates severity of P. falciparum malaria, with group A associated with severe disease and blood group O with milder disease. Among pregnant subjects, group O was associated with increased risk of placental malaria in primigravidae and reduced risk in multigravidae. The biological basis for ABO-related susceptibility to malaria is reviewed. Several mechanisms relate to these associations including affinity for Anopheles gambiae; shared ABO antigens with P. falciparum; impairment of merozoite penetration of RBCs; and cytoadherence, endothelial activation and rosetting. ABO phenotypic associations with malaria are related to its pathogenesis and improved understanding of these interactions is required for understanding the glycobiology of malaria infection...
Reply to comment on: Co-infection with subclinical HIV and Wuchereria bancrofti, and the role of malaria and hookworms, in adult Tanzanians: infection intensities, CD4/CD8 counts and cytokine responses [Transactions of the Royal Society of Tropical Medicine and Hygiene, In Press, Corrected Proof, Available online 28 November 2007] — (English)
We appreciate Dr Eisenhut's interest in our paper (Nielsen et al., 2007), which evolved from a previous cross-sectional study (Nielsen et al., 2006) in which a negative association between hookworm and HIV infection was found...
In vitro Interaktionsstudien mit Azithromycin und Dihydroartemisinin in Plasmodium falciparum Isolaten aus Bangladesh [Wien Klin Wochenschr. 2007 Nov;119 Suppl 3:71-5] — (Deutsch)
In jüngsten klinischen Studien erwies sich Azithromycin in Kombination mit Artemisininderivaten als vielversprechende Kombination für die Behandlung der unkomplizierten falciparum Malaria mit in-differenter bis synergistischer Interaktion. Das Ziel der vorliegenden Studie war die Ermittlung von optimalen Wirkstoffverhältnissen für Azithromycin und Dihydroartemisinin für die Behandlung der unkomplizierten falciparum Malaria. Die Plasmodium falciparum Isolate wurden im Rahmen einer klinischen Studie in der MARIB Feldstation im Bandarban Sadar Hospital, im Südosten Bangladeshs gewonnen und für 72 Stunden kultiviert. Die Analyse erfolgte mittels des HRP2 Medikamentensensibilitätstest. Die Auswertung der Daten ergab eine im Großen und Ganzen indifferente Interaktion für Dihydroartemisinin in Kombination mit Azithromycin mit einem optimalen Konzentrationsverhältnis bei einem Mischungsverhältnis von etwa 1 : 500. Die summarischen fraktionellen Hemmkonzentrationen (SFICs) lagen bei 95 prozentiger Hemmung zwischen 0,89 und 1,16 für die Mischverhältnisse 1 : 500 und 1 : 5000. Ein deutlicher Trend zu niedrigeren SFICs zeigte sich bei höheren Hemmkonzentrationen. Die Korrelationsanalyse legt für Azithromycin einen von den bisher verwendeten Therapeutika unterschiedlichen Wirkmechanismus nahe...
Haemoglobin S and haemoglobin C: ‘quick but costly’ versus ‘slow but gratis’ genetic adaptations to Plasmodium falciparum malaria [Hum Mol Genet. 2007 Nov 28] — (English)
Haemoglobin S (HbS; β6GluVal) and HbC (β6GluLys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (SBenin) and the C alleles are common (0.05 and 0.13). Here we show that: both C and SBenin are monophyletic; C has accumulated a fourfold higher recombinational and DNA slippage haplotypic variability than the SBenin allele (P = 0.003) implying higher antiquity; for a long initial lag period the C alleles did apparently remain very few. These results, consistently with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a ‘slow but gratis’ genetic adaptation to malaria through a transient polymorphism, compared to the polycentric ‘quick but costly’ adaptation through balanced polymorphism of HbS...
Anopheles kleini, Anopheles pullus, and Anopheles sinensis: potential vectors of Plasmodium vivax in the Republic of Korea [J Med Entomol 2007 Nov; 44(6):1086-90] — (English)
Anopheles sinensis Wiedemann (63.3%) was the most abundant Anopheles mosquito captured at cowshed resting collections in malaria high-risk areas (northern Gyeonggi Province) near the demilitarized zone (DMZ) in Korea during 2005, followed by Anopheles kleini Rueda (24.7%) and Anopheles pullus M. Yamada (8.7%). At cowshed resting collections in malaria low-risk areas (Jeonnam and Gyeongnam provinces), An. sinensis accounted for 96.8% of all Anopheles spp. collected, followed by An. kleini Rueda (2.7%), whereas no An. pullus were collected. Three species, An. kleini (50.9%), An. pullus (29.0%), and An. sinensis (13.8%), accounted for nearly all of the 224 Anopheles spp. captured by New Jersey light trap near the DMZ. In addition, An. pullus and An. kleini captured by New Jersey light trap near the DMZ and assayed by enzyme linked immunosorbent assay for Plasmodium vivax circumsporozoite antigen concentrations were higher than An. sinensis sensu stricto (s.s.), indicating higher levels of sporozoites. In laboratory studies of four concurrent artificial membrane feedings on malaria-infected blood from patients, F1 progeny of An. kleini and An. pullus had higher infection rates (8.8 and 7.5%, respectively) than An. sinensis s.s. (4.2%). These data suggest that An. kleini and An. pullus and An. sinensis are vectors of malaria in Korea. Further studies are required to determine the role of these species in the transmission of P. vivax in the Republic of Korea...
Comparative studies on effects of three chitin synthesis inhibitors on common malaria mosquito (Diptera: Culicidae) [J Med Entomol 2007 Nov; 44(6):1047-53] — (English)
Toxicities of three chitin synthesis inhibitors (diflubenzuron, nikkomycin Z and polyoxin D) were evaluated using second instars of the common malaria mosquito, Anopheles quadrimaculatus Say (Diptera: Culicidae). Neither nikkomycin Z nor polyoxin D at 50 microg/liter caused significant larval mortality, although they reduced the body weight of the survivors by 20.5 and 33.8%, respectively, in 48 h. In contrast, exposures of the larvae to diflubenzuron at 12.5 microg/liter for 48 h resulted in 86.7% larval mortality and reduced the body weight of the survivors by 29.1%. Exposure of the pupae (<12 h old) to diflubenzuron at 100 microg/liter for 48 h caused 18.9% pupal mortality and consequently reduced the adult emergence by 24.7% from the surviving pupae. Furthermore, exposure of third instars to diflubenzuron at 4, 20, 100, and 500 microg/liter for 24 h resulted in the reduction of larval chitin contents by 4.25, 33.2, 35.2, and 57.7%, respectively. Such an effect seemed to be associated with only cuticular chitin synthesis because the same exposures did not significantly affect chitin contents in the guts. Our results indicated that diflubenzuron was highly toxic to second instars by not only causing high larval mortality but also by affecting their growth. Diflubenzuron was also fairly toxic to pupae by not only causing pupal mortality but also affecting the adult emergence. Our results suggest that diflubenzuron might affect only chitin synthesis in the cuticle but not in the peritrophic matrix, which is probably due to diflubenzuron's direct contact to mosquito larvae in water, slow distribution in insect body, rapid degradation in the insect gut, or a combination...
Behavioral responses of malaria vectors, Anopheles minimus complex, to three classes of agrochemicals in Thailand [J Med Entomol 2007 Nov; 44(6):1032-9] — (English)
Behavioral responses of two wild-caught populations of Anopheles minimus complex, species A and C, exposed to operational field doses of three commonly used agricultural insecticides, carbaryl (carbamate), malathion (organophosphate) and cypermethrin (pyrethroid), were characterized using an excito-repellency test system. Test populations were collected from different localities in Kanchanaburi Province, western Thailand. Both populations showed strong irritancy by quickly escaping test chambers after direct contact with individual surfaces treated with each insecticide compared with match-paired untreated controls. Noncontact repellency response to cypermethrin and carbaryl was significantly pronounced in both A and C populations, but comparatively weak when exposed to malathion. Noncontact repellency produced much weaker escape response in both populations, but in some species-chemical combinations, it remained significant compared with controls. We conclude that contact irritancy is a major behavioral response of both A and C when exposed directly to any of the three compounds, whereas only cypermethrin produced a significant repellency response in species A...
Anopheles funestus (Diptera: Culicidae) in a humid savannah area of western Burkina Faso: bionomics, insecticide resistance status, and role in malaria transmission [J Med Entomol 2007 Nov; 44(6):990-7] — (English)
An entomological survey was carried out in three humid savannah sites of western Burkina Faso (Bama, Lena, and Soumousso) to (1) update the taxonomy of the Anopheles funestus Giles group, (2) examine the role of each species in malaria transmission, (3) characterize the insecticide resistance status of this malaria vector, and (4) determine the distribution of An. funestus chromosomal forms in these areas. Polymerase chain reaction identification of the members showed the occurrence of An. leesoni Evans in Lena and An. rivulorum-like in Soumousso in addition to An. funestus s.s. Malaria transmission was ensured mainly by An. funestus s.s. both in Soumousso and Lena and by An. gambiae s.s. Giles in Bama, the rice-growing area. The insecticide resistance status performed only on An. funestus indicated that this mosquito was susceptible to pyrethroids irrespective of the study area, but it was resistant to dieldrin. Furthermore, the occurrence of the two chromosomal forms of An. funestus, namely, Kiribina and Folonzo, seemed to follow ecological setups where Kiribina predominated in the irrigated area and Folonzo was more frequent in classic savannah. This study revealed that the problematic of An. funestus taxonomy was closer to that of An. gambiae requiring more structured studies to understand its genetic ecology...
Estimating dispersal and survival of Anopheles gambiae and Anopheles funestus along the Kenyan coast by using mark-release-recapture methods [J Med Entomol 2007 Nov; 44(6):923-9] — (English)
Mark-release-recapture (MRR) experiments were conducted with emerging Anopheles gambiae s.l. and Anophelesfunestus Giles at Jaribuni and Mtepeni in Kilifi, along the Kenyan Coast. Of 739 and 1246 Anopheles released at Jaribuni and Mtepeni, 24.6 and 4.33% were recaptured, respectively. The daily survival probability was 0.96 for An. funestus and 0.95 for An. gambiae in Jaribuni and 0.83 and 0.95, respectively, in Mtepeni. The maximum flight distance recorded was 661 m. The high survival probability of An. gambiae and An. funestus estimated accounts for the continuous transmission of malaria along the Kenyan coast. This study also shows that the release of young, emergent female Anopheles improves the recapture rates and may be a better approach to MRR studies...
Malaria and anaemia among pregnant women at first antenatal clinic visit in Kisumu, western Kenya [Tropical Medicine & International Health, Volume 12 Issue 12 Page 1515-1523, December 2007] — (English)
Malaria and anaemia are established problems by the time of the first ANC visit. Mechanisms to deliver ITNs to women of child-bearing age before they become pregnant need to be explored. Early ANC visits are warranted in order for women to benefit from policies aimed at reducing the burden of malaria and anaemia...
Viewpoint: Evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa [Tropical Medicine & International Health, Volume 12 Issue 12 Page 1524-1539, December 2007] — (English)
Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added...
Hepatosplenomegaly in Kenyan schoolchildren: exacerbation by concurrent chronic exposure to malaria and Schistosoma mansoni infection [Tropical Medicine & International Health, Volume 12 Issue 12 Page 1442-1449, December 2007] — (English)
Children chronically exposed to malaria but without S. mansoni infection can have hepatosplenomegaly, which even light S. mansoni infections can exacerbate in an intensity-dependent manner. Thus, concurrent chronic exposure to S. mansoni and Plasmodium falciparum can have an additive or synergistic effect on childhood morbidity...
Epidemiology of congenital malaria in Nigeria: a multi-centre study [Tropical Medicine & International Health, Volume 12 Issue 11, Page 1279-1287, November 2007] — (English)
Congenital malaria is often asymptomatic, clears spontaneously and may not warrant treatment. However, newborns with unexplained fever and refusal to feed in malaria endemic areas should be tested for malaria...
Comparison of the therapeutic efficacy of chloroquine and sulphadoxine-pyremethamine in children and pregnant women [Tropical Medicine & International Health, Volume 12 Issue 11, Page 1288-1297, November 2007] — (English)
Parasitological failure rates were significantly lower in asymptomatic pregnant women, particularly in multigravidae, compared with symptomatic children. Reliance on drug sensitivity results observed in children only to decide on antimalarial regimes for pregnant women may not be appropriate...
Molecular markers as indicators of antimalarial drug failure rates [Tropical Medicine & International Health, Volume 12 Issue 11, Page 1298-1301, November 2007] — (English)
Several mutations have been identified in Plasmodium falciparum that cause, or contribute to, drug resistance. It is relatively easy to measure their prevalence in human blood samples, so they are often used to infer drug failure rates, clinical and parasitological, that will occur in the human population. One current method of making this inference is through the use of genotypic resistance and genotypic failure indices. These indices are rather sensitive to background drug failures rates (i.e. failures not caused by the mutation), to mutation prevalence, and to the genetic background in which the marker occurs. Extreme care should therefore be taken in the construction and interpretation of these indices...
GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives [Expert Rev Vaccines. 2007 Oct;6(5):723-39] — (English)
The need for potentiating immune responses to recombinant or subunit antigens has prompted GlaxoSmithKline (GSK) Biologicals to develop various Adjuvant Systems for the design of prophylactic and therapeutic vaccines. Adjuvant Systems are formulations of classical adjuvants mixed with immunomodulators, specifically adapted to the antigen and the target population. They can activate the appropriate innate immune system and subsequently impact on adaptive immune responses. AS04 is an Adjuvant System that has demonstrated significant achievements in several vaccines against viral diseases. AS02, another Adjuvant System, is being evaluated in various contexts, where a strong T-cell response is needed to afford protection. Likewise, AS01 has been developed for vaccines where the induction of a yet stronger T-cell-mediated immune response is required. Altogether, the promising clinical results strongly support the concept of Adjuvant Systems and allow for further development of new vaccines, best adapted to the target population and the immune mechanisms of protection...
Deoxycholic Acid-Derived Tetraoxane Antimalarials and Antiproliferatives [J. Med. Chem., 50 (21), 5118 -5127, 2007. 10.1021] — (English)
The synthesis of deoxycholic acid (DCA)- and cholic acid (CA)-derived mixed tetraoxanes revealed that N-(2-dimethylamino)ethyl derivatives are potent antimalarials in vitro and in vivo. The tetraoxanes presented in this paper are dual inhibitors: besides curing mice in vivo without observed toxic effects, they kill cancer cell lines at very low concentrations. For example, DCA and CA derivatives 16 and 25 cured 3/5 (160 mg/kg/day) and 2/5 (40 mg/kg/day, MTD >960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively...
Efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of Plasmodium falciparum protein farnesyltransferase [Antimicrob. Agents Chemother..2007; 51: 3659-3671 ] — (English)
New antimalarials are urgently needed. We have shown that tetrahydroquinoline (THQ) protein farnesyltransferase (PFT) inhibitors (PFTIs) are effective against the Plasmodium falciparum PFT and are effective at killing P. falciparum in vitro. Previously described THQ PFTIs had limitations of poor oral bioavailability and rapid clearance from the circulation of rodents. In this paper, we validate both the Caco-2 cell permeability model for predicting THQ intestinal absorption and the in vitro liver microsome model for predicting THQ clearance in vivo. Incremental improvements in efficacy, oral absorption, and clearance rate were monitored by in vitro tests; and these tests were followed up with in vivo absorption, distribution, metabolism, and excretion studies. One compound, PB-93, achieved cure when it was given orally to P. berghei-infected rats every 8 h for a total of 72 h. However, PB-93 was rapidly cleared, and dosing every 12 h failed to cure the rats. Thus, the in vivo results corroborate the in vitro pharmacodynamics and demonstrate that 72 h of continuous high-level exposure to PFTIs is necessary to kill plasmodia. The metabolism of PB-93 was demonstrated by a novel technique that relied on double labeling with a radiolabel and heavy isotopes combined with radiometric liquid chromatography and mass spectrometry. The major liver microsome metabolite of PB-93 has the PFT Zn-binding N-methyl-imidazole removed; this metabolite is inactive in blocking PFT function. By solving the X-ray crystal structure of PB-93 bound to rat PFT, a model of PB-93 bound to malarial PFT was constructed. This model suggests areas of the THQ PFTIs that can be modified to retain efficacy and protect the Zn-binding N-methyl-imidazole from dealkylation...
Prepared in cooperation with WHO ANGOLA INFO.
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