Malaria remains a challenging prospect for researchers and health workers, but there is encouraging news to report. Malaria research, after many years on the back burner, has risen dramatically up the priority list of donors and policy makers. Much of the credit for this turnaround must go to the Multilateral Initiative on Malaria (MIM; http://www.mim.su.se). MIM’s achievements in the malaria world may indeed be a model for raising the profile of other neglected health issues. [Read more…]
Use of Integrated Malaria Management Reduces Malaria in Kenya
During an entomological survey in preparation for malaria control interventions in Mwea division, the number of malaria cases at the Kimbimbi sub-district hospital was in a steady decline. The underlying factors for this reduction were unknown and needed to be identified before any malaria intervention tools were deployed in the area. We therefore set out to investigate the potential factors that could have contributed to the decline of malaria cases in the hospital by analyzing the malaria control knowledge, attitudes and practices (KAP) that the residents in Mwea applied in an integrated fashion, also known as integrated malaria management (IMM). [Read more…]
A Research Agenda for Malaria Eradication: Vector Control
Abstract: Different challenges are presented by the variety of malaria transmission environments present in the world today. In each setting, improved control for reduction of morbidity is a necessary first step towards the long-range goal of malaria eradication and a priority for regions where the disease burden is high.
For many geographic areas where transmission rates are low to moderate, sustained and well-managed application of currently available tools may be sufficient to achieve local elimination. The research needs for these areas will be to sustain and perhaps improve the effectiveness of currently available tools. For other low-to-moderate transmission regions, notably areas where the vectors exhibit behaviours such as outdoor feeding and resting that are not well targeted by current strategies, new interventions that target predictable features of the biology/ecologies of the local vectors will be required. [Read more…]
A Research Agenda for Malaria Eradication: Drugs
Abstract: Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection.Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. [Read more…]
A Research Agenda for Malaria Eradication: Vaccines
Abstract: Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission.
We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.
Citation: The malERA Consultative Group on Vaccines (2011) A Research Agenda for Malaria Eradication: Vaccines. PLoS Med 8(1): e1000398. doi:10.1371/journal.pmed.1000398
Published: January 25, 2011
Funding: malERA received a grant from the Bill & Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: No competing interests: PLA, CC, VM, AS, DW. GB is the Chair of MALVAC, Chair of the USAID Malaria Vaccine Development Program Scientific Consultants Group, a member of the Board of Roll Back Malaria, and the APMEN Advisory Board. RB is an employee of Glaxo SmithKline (GSK) and owns GSK stock. GSK is developing malaria vaccines. At the time of the malERA meetings, RB was employed by the Bill & Melinda Gates Foundation. CL states that the PATH Malaria Vaccine Initiative has partnerships with several commercial entities developing malaria vaccines. Each partnership has defined access conditions.
Abbreviations: TBV, transmission-blocking vaccine; TPP, target product profile; VIMT, vaccines that interrupt malaria transmission
Copyright: © 2011 The malERA Consultative Group on Vaccines. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
More information:
A Research Agenda for Malaria Eradication: Vaccines (PDF)
Toxic Sugar Bait Can Help Control Mosquitos
An improved knowledge of mosquito life history could strengthen malaria vector control efforts that primarily focus on killing mosquitoes indoors using insecticide treated nets and indoor residual spraying.
Natural sugar sources, usually floral nectars of plants, are a primary energy resource for adult mosquitoes but their role in regulating the dynamics of mosquito populations is unclear. To determine how the sugar availability impacts Anopheles sergentii populations, mark-release-recapture studies were conducted in two oases in Israel with either absence or presence of the local primary sugar source, flowering Acacia raddiana trees.
Compared with population estimates from the sugar-rich oasis, An. sergentii in the sugar-poor oasis showed smaller population size (37,494 vs. 85,595), lower survival rates (0.72 vs. 0.93), and prolonged gonotrophic cycles (3.33 vs. 2.36 days). The estimated number of females older than the extrinsic incubation period of malaria (10 days) in the sugar rich site was 4 times greater than in the sugar poor site.
Sugar feeding detected in mosquito guts in the sugar-rich site was significantly higher (73%) than in the sugar-poor site (48%). In contrast, plant tissue feeding (poor quality sugar source) in the sugar-rich habitat was much less (0.3%) than in the sugar-poor site (30%). More important, the estimated vectorial capacity, a standard measure of malaria transmission potential, was more than 250-fold higher in the sugar-rich oasis than that in the sugar-poor site.
Our results convincingly show that the availability of sugar sources in the local environment is a major determinant regulating the dynamics of mosquito populations and their vector potential, suggesting that control interventions targeting sugar-feeding mosquitoes pose a promising tactic for combating transmission of malaria parasites and other pathogens.
Authors: Weidong Gu1*, Günter Müller2, Yosef Schlein2, Robert J. Novak1, John C. Beier3
1 Division of Infectious Diseases, School of Medicine, University of Alabama, Birmingham, Alabama, United States of America, 2 Department of Microbiology and Molecular Genetics, Faculty of Medicine, IMRIC, Kuvin Centre for the Study of Infectious and Tropical Diseases, Hebrew University, Jerusalem, Israel, 3 Department of Epidemiology and Public Health, Miller School of Medicine, Center for Global Health Sciences, University of Miami, Miami, Florida, United States of America
Citation: Gu W, Müller G, Schlein Y, Novak RJ, Beier JC (2011) Natural Plant Sugar Sources of Anopheles Mosquitoes Strongly Impact Malaria Transmission Potential. PLoS ONE 6(1): e15996. doi:10.1371/journal.pone.0015996
Editor: Anne Charlotte Gruner, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore
Copyright: © 2011 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This project was supported by the Bill and Melinda Gates Foundation (grant 47302). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
See full text: Natural Plant Sugar Sources of Anopheles Mosquitoes Strongly Impact Malaria Transmission Potential (PDF)
Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes
Abstract: Metarhizium anisopliae infects mosquitoes through the cuticle and proliferates in the hemolymph. To allow M. anisopliae to combat malaria in mosquitoes with advanced malaria infections, we produced recombinant strains expressing molecules that target sporozoites as they travel through the hemolymph to the salivary glands.
Eleven days after a Plasmodium-infected blood meal, mosquitoes were treated with M. anisopliae expressing salivary gland and midgut peptide 1 (SM1), which blocks attachment of sporozoites to salivary glands; a single-chain antibody that agglutinates sporozoites; or scorpine, which is an antimicrobial toxin. These reduced sporozoite counts by 71%, 85%, and 90%, respectively. M. anisopliae expressing scorpine and an [SM1]8:scorpine fusion protein reduced sporozoite counts by 98%, suggesting that Metarhizium-mediated inhibition of Plasmodium development could be a powerful weapon for combating malaria. [Read more…]
The Dominant Anopheles Vectors of Human Malaria in Africa, Europe and the Middle East
Full Title
The Dominant Anopheles Vectors of Human Malaria in Africa, Europe and the Middle East: Occurrence Data, dDstribution Maps and Bionomic Précis
Background
This is the second in a series of three articles documenting the geographical distribution of 41 dominant vector species (DVS) of human malaria. The first paper addressed the DVS of the Americas and the third will consider those of the Asian Pacific Region. Here, the DVS of Africa, Europe and the Middle East are discussed. [Read more…]
Soil-Transmitted Helminths and Malaria in Pregnant Women on the Thai-Burmese Border
Background: Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border.
Methodology: Routine antenatal care (ANC) included active detection of malaria (weekly blood smear) and anaemia (second weekly haematocrit) and systematic reporting of birth outcomes. In 1996 stool samples were collected in cross sectional surveys from women attending the ANCs. This was repeated in 2007 when malaria incidence had reduced considerably. The relationship between geohelminth infection and the progress and outcome of pregnancy was assessed.
Principal Findings: Stool sample examination (339 in 1996, 490 in 2007) detected a high prevalence of geohelminths 70% (578/829), including hookworm (42.8% (355)), A. lumbricoides (34.4% (285)) and T.trichuria (31.4% (250)) alone or in combination. A lower proportion of women (829) had mild (21.8% (181)) or severe (0.2% (2)) anaemia, or malaria 22.4% (186) (P.vivax monoinfection 53.3% (101/186)). A. lumbricoides infection was associated with a significantly decreased risk of malaria (any species) (AOR: 0.43, 95% CI: 0.23–0.84) and P.vivax malaria (AOR: 0.29, 95% CI: 0.11–0.79) whereas hookworm infection was associated with an increased risk of malaria (any species) (AOR: 1.66, 95% CI: 1.06–2.60) and anaemia (AOR: 2.41, 95% CI: 1.18–4.93). Hookworm was also associated with low birth weight (AOR: 1.81, 95% CI: 1.02–3.23).
Conclusions / Significance: A. lumbricoides and hookworm appear to have contrary associations with malaria in pregnancy.
Author Summary: Intestinal worms, particularly hookworm and whipworm, can cause anaemia, which is harmful for pregnant women. The WHO recommends deworming in pregnancy in areas where hookworm infections are frequent. Some studies indicate that coinfection with worms and malaria adversely affects pregnancy whereas other studies have shown that coinfection with worms might reduce the severity of malaria. On the Thai-Burmese border malaria in pregnancy has been an important cause of maternal death. We examined the relationship between intestinal helminth infections in pregnant women and their malaria risk in our antenatal care units. In total 70% of pregnant women had worm infections, mostly hookworm, but also roundworm and whipworm; hookworm was associated with mild anaemia although ova counts were not high. Women infected with hookworm had more malaria and their babies had a lower birth weight than women without hookworm. In contrast women with roundworm infections had the lowest rates of malaria in pregnancy. Deworming eliminates all worms. In this area it is unclear whether mass deworming would be beneficial.
Citation: Boel M, Carrara VI, Rijken M, Proux S, Nacher M, et al. (2010) Complex Interactions between Soil-Transmitted Helminths and Malaria in Pregnant Women on the Thai-Burmese Border. PLoS Negl Trop Dis 4(11): e887. doi:10.1371/journal.pntd.0000887
Editor: Simon Brooker, London School of Hygiene & Tropical Medicine, United Kingdom
Copyright: © 2010 Boel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was part of the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme funded by the Wellcome Trust of Great Britain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
More information: Full text: Complex Interactions between Soil-Transmitted Helminths and Malaria in Pregnant Women on the Thai-Burmese Border (PDF)
NITD609 Compound May Be Promising Malaria Drug Candidate, Say Researchers
A chemical that rid mice of malaria-causing parasites after a single oral dose may eventually become a new malaria drug if further tests in animals and people uphold the promise of early findings. The compound, NITD609, was developed by an international team of researchers.
“Although significant progress has been made in controlling malaria, the disease still kills nearly 1 million people every year, mostly infants and young children,” says NIAID Director Anthony S. Fauci, M.D. “It has been more than a decade since the last new class of antimalarials—artemisinins—began to be widely used throughout the world. The rise of drug-resistant malaria parasites further underscores the need for novel malaria therapies.”
Dr. Fauci adds that the compound “appears to target a parasite protein not attacked by any existing malaria drug, and has several other desirable features. This research is also a notable example of successful collaboration between government-supported scientists and private sector researchers.”
The study, in the Sept. 3, 2010 issue of Science, was led by Thierry T. Diagana, Ph.D., of the Novartis Institute for Tropical Diseases (NITD), and Dr. Winzeler. Dr. Winzeler is affiliated with The Scripps Research Institute and the Genomic Institute of the Novartis Research Foundation, La Jolla, Calif.
Work on what eventually became NITD609 began in Dr. Winzeler’s lab in 2007. Scientists screened 12,000 chemicals using an ultra-high throughput robotic screening technique customized to detect compounds active against Plasmodium falciparum, the most deadly malaria parasite. The screen identified a chemical with good parasite-killing abilities and the potential to be modified into a drug. Medicinal chemists at the NITD then synthesized and evaluated about 200 versions of the original compound to arrive at NITD609, which could be formulated as a tablet and manufactured in large quantities. NITD609 is one of a new class of chemicals, the spiroindolones, which have been described in recently published research by Dr. Winzeler and colleagues as having potent effects against two kinds of malaria parasites.
“From the beginning, NITD609 stood out because it looked different, in terms of its structure and chemistry, from all other currently used antimalarials,” says Dr. Winzeler. “The ideal new malaria drug would not just be a modification of existing drugs, but would have entirely novel features and mechanism of action. NITD609 does.”
Source: NIH