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Journal ArticleDOI

Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria.

01 Mar 2003-Transactions of The Royal Society of Tropical Medicine and Hygiene (Oxford University Press)-Vol. 97, Iss: 2, pp 198-199
TL;DR: Results suggest that, compared with those infected, individuals free of helminths had the same degree of protection against malaria as that provided by sickle-cell trait, the most potent factor of resistance to malaria identified to date.
Abstract: The influence of intestinal worm infections on malaria was studied in individuals from Dielmo, Senegal in 1998. Results suggest that, compared with those infected, individuals free of helminths had the same degree of protection against malaria as that provided by sickle-cell trait, the most potent factor of resistance to malaria identified to date.
Citations
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Journal ArticleDOI
TL;DR: It is hypothesized that parasites have evolved specific molecular strategies to induce this conducive landscape, and the foremost candidate immunomodulators released by helminths are reviewed, including cytokine homologs, protease inhibitors, and an intriguing set of novel products implicated in immune suppression.
Abstract: Summary: Immune regulation by parasites is a global concept that includes suppression, diversion, and conversion of the host immune response to the benefit of the pathogen. While many microparasites escape immune attack by antigenic variation or sequestration in specialized niches, helminths appear to thrive in exposed extracellular locations, such as the lymphatics, bloodstream, or gastrointestinal tract. We review here the multiple layers of immunoregulation that have now been discovered in helminth infection and discuss both the cellular and the molecular interactions involved. Key events among the host cell population are dominance of the T-helper 2 cell (Th2) phenotype and the selective loss of effector activity, against a background of regulatory T cells, alternatively activated macrophages, and Th2-inducing dendritic cells. Increasingly, there is evidence of important effects on other innate cell types, particularly mast cells and eosinophils. The sum effect of these changes to host reactivity is to create an anti-inflammatory environment, which is most favorable to parasite survival. We hypothesize therefore that parasites have evolved specific molecular strategies to induce this conducive landscape, and we review the foremost candidate immunomodulators released by helminths, including cytokine homologs, protease inhibitors, and an intriguing set of novel products implicated in immune suppression.

864 citations


Cites background from "Increased frequency of malaria atta..."

  • ...Alternatively, the additional burden of helminth infection may increase the severity of malaria infection (180)....

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Journal ArticleDOI
TL;DR: It is argued that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.
Abstract: Hotez et al. argue that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.

785 citations


Cites background from "Increased frequency of malaria atta..."

  • ...Druilhe et al. [62] have hypothesized that the STHs and schistosomes immunomodulate the host to increase malaria susceptibility by shifting their humoral responses from malaria-protective, cytophilic humoral antibodies (IgG1 and IgG3) to nonprotective, noncytophilic subclasses (IgG2 , IgG4, and IgM)....

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  • ...These studies include those from Senegal showing enhanced risk or increased incidence of clinical malaria resulting from either STH [64,66] or schistosome [68] infections, unpublished studies from Malawi showing that women infected with hookworms were at 1.8 times higher risk of having malaria than uninfected women [89], and studies from Thailand showing increased susceptibility to malaria in patients with STH infections [90–93]....

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  • ...In addition to affecting STH and schistosome deworming, ectoparasite control, and control or elimination of LF and onchocerciasis, the three anthelmintics would help to reduce anemia as well as the progression of disease resulting from HIV/AIDS, tuberculosis, and malaria [62,65]....

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  • ...Each of the three major STHs (Ascaris lumbricoides, Trichuris trichiura, and the hookworms, Necator americanus and Ancylostoma duodenale) and the two schistosomes (Schistosoma haematobium and Schistosoma mansoni) are highly endemic to sub-Saharan Africa, where they adversely affect childhood growth and physical fi tness [18–24]....

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  • ...In Senegal, deworming for STH infections was shown to be equivalent to the protection from malaria conferred by the sickle cell trait [62,64], and has the added effect of restoring T cell responses to mycobacterial antigens in helminth-exposed individuals before and after BCG vaccination [107,108]....

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Journal ArticleDOI
TL;DR: Current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of the various populations of regulatory T cells that arise during infection are discussed.
Abstract: Surviving a given infection requires the generation of a controlled immune response. Failure to establish or restore homeostatic conditions during or following the onset of an infection can lead to tissue damage. Investigation of the immunoregulatory network that arises in response to the infectious process or that is induced by the pathogen itself should provide insight into therapeutic approaches for the control of infection and any subsequent immunopathology. In this Review, I discuss current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of the various populations of regulatory T cells that arise during infection.

738 citations

Journal ArticleDOI
TL;DR: How techniques from community ecology can be used to restructure the approaches used to study parasite communities are highlighted and insights offered are discussed that will be crucial for predicting the impact on wildlife and human health of disease control measures, climate change or novel parasite species introductions.
Abstract: In natural systems, individuals are often co-infected by many species of parasites. However, the significance of interactions between species and the processes that shape within-host parasite communities remain unclear. Studies of parasite community ecology are often descriptive, focusing on patterns of parasite abundance across host populations rather than on the mechanisms that underlie interactions within a host. These within-host interactions are crucial for determining the fitness and transmissibility of co-infecting parasite species. Here, we highlight how techniques from community ecology can be used to restructure the approaches used to study parasite communities. We discuss insights offered by this mechanistic approach that will be crucial for predicting the impact on wildlife and human health of disease control measures, climate change or novel parasite species introductions.

522 citations

Journal ArticleDOI
TL;DR: Controlling seven tropical infections in Africa would cost just 40 cents per person per year, and would permanently benefit hundreds of millions of people.
Abstract: Over the past two decades there have been significant achievements in the control of a handful of important human tropical infections [1]. These achievements include the substantive reductions in the prevalence and incidence of the so-called neglected diseases such as lymphatic filariasis, onchocerciasis, guinea worm, leprosy, and trachoma (Box 1) [2]. Each of these neglected diseases is a poverty-promoting and often stigmatizing condition occurring primarily in rural areas of low-income countries (Box 2) [3]. They are ancient afflictions, described in the Bible and other ancient texts, which have burdened humanity for millennia [3]. But now, as a result of aggressive regional vertical interventions, there is a possibility that some neglected tropical infections could be eventually controlled to the point of elimination in some areas of endemicity [2–8]. In the case of guinea worm infection, disease eradication might also soon be possible [9]. Box 2. Common Features of the Neglected Tropical Diseases Ancient afflictions that have burdened humanity for centuries Poverty-promoting conditions Associated with stigma Rural areas of low-income countries and fragile states No commercial markets for products that target these diseases Interventions, when applied, have a history of success

518 citations


Cites background from "Increased frequency of malaria atta..."

  • ...], especially by reducing the frequency of malaria fevers, the frequency of severe and cerebral malaria, and the prevalence of anaemia [...

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References
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Journal ArticleDOI
TL;DR: The findings suggest that sterile immunity and clinical protection are never fully achieved in humans continuously exposed since birth to intense transmission.
Abstract: The Dielmo project, initiated in 1990, consisted of long-term investigations on host-parasite relationships and the mechanisms of protective immunity in the 247 residents of a Senegalese village in which malaria is holoendemic. Anopheles gambiae s.l. and An. funestus constituted more than 98% of 11,685 anophelines collected and were present all year round. Inoculation rates of Plasmodium falciparum, P. malariae, and P. ovale averaged respectively 0.51, 0.10, and 0.04 infective bites per person per night. During a four-month period of intensive parasitologic and clinical monitoring, Plasmodium falciparum, P. malariae, and P. ovale were observed in 72.0%, 21.1% and 6.0%, respectively, of the 8,539 thick smears examined. Individual longitudinal data revealed that 98.6% of the villagers harbored trophozoites of P. falciparum at least once during the period of the study. Infections by P. malariae and P. ovale were both observed in individuals of all age groups and their cumulative prevalences reached 50.5% and 40.3%, respectively. Malaria was responsible for 162 (60.9%) of 266 febrile episodes; 159 of these attacks were due to P. falciparum, three to P. ovale, and none to P. malariae. The incidence of malaria attacks was 40 times higher in children 0–4 years of age than in adults more than 40 years old. Our findings suggest that sterile immunity and clinical protection are never fully achieved in humans continuously exposed since birth to intense transmission.

407 citations

Journal ArticleDOI
TL;DR: The hypothesis that nonprotected subjects have antibodies to epitopes critical for protection, but that these antibodies are nonfunctional is formed, bringing some clues to the very long delay required to reach protection against malaria and clearly stress the need to investigate immune responses in both quantitative and qualitative terms.
Abstract: In view of the recent demonstration that antibodies that are protective against Plasmodium falciparum malaria may act in collaboration with blood monocytes, we investigated the isotype content of sera from individuals with defined clinical states of resistance or susceptibility to malaria. Profound differences in the distribution of each immunoglobulin subclass were found. Immunoglobulin G1 (IgG1) and IgG3, two cytophilic isotypes, predominated in protected subjects. In nonprotected subjects, i.e., children and adults that have sustained a primary malarial attack, four different situations were encountered: (i) an imbalance in which IgG2, a noncytophilic class, predominated (mostly seen in primary attacks), (ii) an imbalance also concerning IgG2 but only of a given antigenic specificity, (iii) an imbalance in which mostly IgM antibodies predominated (a frequent event in children), and, less frequently, (iv) an overall low level of antimalarial antibodies. Of 33 nonimmune subjects studied, all but one had one of the above defects. The function of total immunoglobulin presenting such an isotype imbalance was studied in vitro in antibody-dependent cellular inhibition assays. IgG from protected subjects cooperated efficiently with blood monocytes, whereas IgG from nonprotected groups did not. Also, the latter could inhibit the in vitro effect of the former: in competition assays whole IgG from primary-attack cases with increased IgG2 content and IgG or IgM from children from endemic areas competed with IgG from immune adults. This led us to formulate the hypothesis that nonprotected subjects have antibodies to epitopes critical for protection, but that these antibodies are nonfunctional. These results bring some clues to the very long delay required to reach protection against malaria and clearly stress the need to investigate immune responses in both quantitative and qualitative terms.

330 citations

Journal ArticleDOI
TL;DR: Evidence is provided for an age-dependent threshold effect of parasitemia that allows parasite density to be used to distinguish malaria attacks from other causes of fever within an individual and should facilitate the accurate evaluation of the incidence of clinical malaria in highly endemic areas.
Abstract: The high prevalence of asymptomatic malaria infections and the nonspecific signs and symptoms of the disease make the individual diagnosis of clinical malaria uncertain in highly endemic areas. Longitudinal data obtained during a four-month period from a daily survey of 200 permanent inhabitants (one month-83 years old) living in a holoendemic area were analyzed in a random-effects logistic regression model to investigate the relationship between the level of Plasmodium falciparum parasitemia and risk of fever. It was not possible to build a model that described/summarized correctly this relationship by a continuous function. Findings provide evidence for an age-dependent threshold effect of parasitemia on the occurrence of fever. The level of this threshold varied by 2.45 trophozoites per leukocyte, maximum at one year of age, to 0.5 trophozoites per leukocyte, minimum at 60 years of age. When the parasite density of a person crossed the threshold level corresponding to his or her age, the individual's risk of fever was multiplied by 44 (95% confidence interval = 13.6–144.8). The existence of this threshold effect allows parasite density to be used to distinguish malaria attacks from other causes of fever within an individual and should facilitate the accurate evaluation of the incidence of clinical malaria in highly endemic areas.

201 citations