Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes

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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

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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

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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)

Screening Mosquito House Entry Points as a Potential Method for Integrated Control of Malaria

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Partial mosquito-proofing of houses with screens and ceilings has the potential to reduce indoor densities of malaria mosquitoes. We wish to measure whether it will also reduce indoor densities of vectors of neglected tropical diseases.

Methodology: The main house entry points preferred by anopheline and culicine vectors were determined through controlled experiments using specially designed experimental huts and village houses in Lupiro village, southern Tanzania. The benefit of screening different entry points (eaves, windows and doors) using PVC-coated fibre glass netting material in terms of reduced indoor densities of mosquitoes was evaluated compared to the control.

Findings: 23,027 mosquitoes were caught with CDC light traps; 77.9% (17,929) were Anopheles gambiae sensu lato, of which 66.2% were An. arabiensis and 33.8% An. gambiae sensu stricto. The remainder comprised 0.2% (50) An. funestus, 10.2% (2359) Culex spp. and 11.6% (2664) Mansonia spp. Screening eaves reduced densities of Anopheles gambiae s. l. (Relative ratio (RR) = 0.91; 95% CI = 0.84, 0.98; P = 0.01); Mansonia africana (RR = 0.43; 95% CI = 0.26, 0.76; P<0.001) and Mansonia uniformis (RR = 0.37; 95% CI = 0.25, 0.56; P<0.001) but not Culex quinquefasciatus, Cx. univittatus or Cx. theileri. Numbers of these species were reduced by screening windows and doors but this was not significant.

Significance: This study confirms that across Africa, screening eaves protects households against important mosquito vectors of filariasis, Rift Valley Fever and O’Nyong nyong as well as malaria. While full house screening is required to exclude Culex species mosquitoes, screening of eaves alone or fitting ceilings has considerable potential for integrated control of other vectors of filariasis, arbovirus and malaria.

Author Summary: Mosquito vectors that transmit filariasis and several arboviruses such as Rift Valley Fever, Chikungunya and O’Nyong nyong as well as malaria co-occur across tropical Africa. These diseases are co-endemic in most rural African countries where they are transmitted by the same mosquito vectors. The only control measure currently in widespread use is mass drug administration for filariasis. In this study, we used controlled experiments to evaluate the benefit of screening the main mosquito entry points into houses, namely, eaves, windows and doors.

This study aims to illustrate the potential of screening specific house openings with the intention of preventing endophagic mosquitoes from entering houses and thus reducing contact between humans and vectors of neglected tropical diseases. This study confirms that while full house screening is effective for reducing indoor densities of Culex spp. mosquitoes, screening of eaves alone has a great potential for integrated control of neglected tropical diseases and malaria.

Citation: Ogoma SB, Lweitoijera DW, Ngonyani H, Furer B, Russell TL, et al. (2010) Screening Mosquito House Entry Points as a Potential Method for Integrated Control of Endophagic Filariasis, Arbovirus and Malaria Vectors. PLoS Negl Trop Dis 4(8): e773. doi:10.1371/journal.pntd.0000773

Editor: Neal D. E. Alexander, London School of Hygiene and Tropical Medicine, United Kingdom

Funding: SBO was supported by a scholarship kindly provided by Valent Bioscience Corporation. This study was also supported by the Centers for Disease Control and Prevention and the United States Agency for International Development through the U.S. President’s Malaria Initiative (Award Number 621-A-00-08-0007-00), the Addessium Foundation (Reenwijk, The Netherlands) and a Research Career Development Fellowship (076806) provided to GFK by the Wellcome Trust. The funders of this study 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.

Copyright: © 2010 Ogoma 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.

More information: Full text: Screening Mosquito House Entry Points as a Potential Method for Integrated Control of Endophagic Filariasis, Arbovirus and Malaria Vectors (PDF)