scholarly journals Plasmodium chabaudi Infection Alters Intestinal Morphology and Mucosal Innate Immunity in Moderately Malnourished Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 913
Author(s):  
Noah Joseph Murr ◽  
Tyler B. Olender ◽  
Margaret R. Smith ◽  
Amari S. Smith ◽  
Jennifer Pilotos ◽  
...  
Keyword(s):  
Small Intestine ◽  
Malaria Infection ◽  
Parasite Burden ◽  
Protozoan Parasite ◽  
Innate Immune ◽  
Intestinal Morphology ◽  
Sub Saharan Africa ◽  
Gut Immunity ◽  
Sub Saharan ◽  
Moderate Malnutrition

Plasmodium falciparum is a protozoan parasite which causes malarial disease in humans. Infections commonly occur in sub-Saharan Africa, a region with high rates of inadequate nutrient consumption resulting in malnutrition. The complex relationship between malaria and malnutrition and their effects on gut immunity and physiology are poorly understood. Here, we investigated the effect of malaria infection in the guts of moderately malnourished mice. We utilized a well-established low protein diet that is deficient in zinc and iron to induce moderate malnutrition and investigated mucosal tissue phenotype, permeability, and innate immune response in the gut. We observed that the infected moderately malnourished mice had lower parasite burden at the peak of infection, but damaged mucosal epithelial cells and high levels of FITC-Dextran concentration in the blood serum, indicating increased intestinal permeability. The small intestine in the moderately malnourished mice were also shorter after infection with malaria. This was accompanied with lower numbers of CD11b+ macrophages, CD11b+CD11c+ myeloid cells, and CD11c+ dendritic cells in large intestine. Despite the lower number of innate immune cells, macrophages in the moderately malnourished mice were highly activated as determined by MHCII expression and increased IFNγ production in the small intestine. Thus, our data suggest that malaria infection may exacerbate some of the abnormalities in the gut induced by moderate malnutrition.

scholarly journals Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gregory C. Davenport ◽  
James B. Hittner ◽  
Vincent Otieno ◽  
Zachary Karim ◽  
Harshini Mukundan ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Parasite Burden ◽  
Sub Saharan Africa ◽  
Mediation Model ◽  
Multiple Mediation ◽  
Mediators Of Inflammation ◽  
Threatening Condition ◽  
Life Threatening ◽  
Sub Saharan

Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[−]) enteric Bacilli andPlasmodium falciparum(Pf[+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/μL), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children (n=206, aged <3 yrs): healthy;Pf[+] alone; G[−] coinfected; and G[+] coinfected.Staphylococcus aureusand non-TyphiSalmonellawere the most frequently isolated G[+] and G[−] organisms, respectively. Coinfected children, particularly those with G[−] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN-γ, and IFN-αand decreased TNF-αrelative to malaria alone. Children with G[−] coinfection had higher IL-1βand IL-1Ra and lower IL-10 than thePf[+] group and higher IFN-γthan the G[+] group. To determine how the immune response to malaria regulates parasitemia, cytokine production was investigated with a multiple mediation model. Cytokines with the greatest mediational impact on parasitemia were IL-4, IL-10, IL-12, and IFN-γ. Results here suggest that enhanced immune activation, especially in G[−] coinfected children, acts to reduce malaria parasite burden.

scholarly journals How Eliminating Malaria May Also Prevent Iron Deficiency in African Children

2018 ◽  
Vol 11 (4) ◽  
pp. 96 ◽  
Author(s):  
John Muriuki ◽  
Sarah Atkinson
Keyword(s):  
Iron Deficiency ◽  
Malaria Infection ◽  
Iron Status ◽  
Causal Link ◽  
Sub Saharan Africa ◽  
African Children ◽  
Sub Saharan ◽  
Factor Α ◽  
Epidemiology Studies ◽  
Necrosis Factor

Malaria and iron deficiency are common among children living in sub-Saharan Africa. Several studies have linked a child’s iron status to their future risk of malaria infection; however, few have examined whether malaria might be a cause of iron deficiency. Approximately a quarter of African children at any one time are infected by malaria and malaria increases hepcidin and tumor necrosis factor-α concentrations leading to poor iron absorption and recycling. In support of a hypothetical link between malaria and iron deficiency, studies indicate that the prevalence of iron deficiency in children increases over a malaria season and decreases when malaria transmission is interrupted. The link between malaria and iron deficiency can be tested through the use of observational studies, randomized controlled trials and genetic epidemiology studies, each of which has its own strengths and limitations. Confirming the existence of a causal link between malaria infection and iron deficiency would readjust priorities for programs to prevent and treat iron deficiency and would demonstrate a further benefit of malaria control.

scholarly journals Malaria in Tunisian Military Personnel after Returning from External Operation

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Faïda Ajili ◽  
Riadh Battikh ◽  
Janet Laabidi ◽  
Rim Abid ◽  
Najeh Bousetta ◽  
...  
Keyword(s):  
Military Personnel ◽  
Malaria Infection ◽  
Imported Malaria ◽  
Sub Saharan Africa ◽  
Military Hospital ◽  
Imported Cases ◽  
Male Patients ◽  
Sub Saharan ◽  
The Military

Introduction. Malaria had been eliminated in Tunisia since 1979, but there are currently 40 to 50 imported cases annually. Soldiers are no exception as the incidence of imported malaria is increasing in Tunisian military personnel after returning from malaria-endemic area, often in Sub-Saharan Africa. Methods. We retrospectively analyzed the clinical and biological presentations, treatment, and outcomes of 37 Tunisian military personnel hospitalized at the Department of Internal Medicine, the Military Hospital of Tunis, between January 1993 and January 2011, for imported malaria. The clinical and laboratory features were obtained from the medical records and a questionnaire was filled by the patients about the compliance of malaria prophylaxis. Results. Thirty-seven male patients, with a mean age of 41 years, were treated for malaria infection. Twenty-two were due to Plasmodium falciparum. The outcome was favourable for all patients, despite two severe access. The long-term use of chemoprophylaxis has been adopted by only 21 (51%) of expatriate military for daily stresses. Moreover, poor adherence was found in 32 patients. Conclusion. The risk of acquiring malaria infection in Tunisian military personnel can largely be prevented by the regular use of chemoprophylactic drugs combined with protective measures against mosquito bites.

scholarly journals Pyrethroid resistance in Anopheles gambiae not associated with insecticide-treated mosquito net effectiveness across sub-Saharan Africa

2020 ◽  
Author(s):  
David A. Larsen ◽  
Rachael L. Church
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Vector ◽  
Malaria Infection ◽  
Pyrethroid Resistance ◽  
Sub Saharan Africa ◽  
Malaria Vector Control ◽  
Lr Test ◽  
Meta Regression ◽  
Sub Saharan ◽  
The Impact

AbstractBackgroundPyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITN). Contradictory results of the impact of resistance have been observed in field studies.MethodsWe combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006-2017 with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We utilized both a pooled-data approach and meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes in children aged 6-59 months.FindingsITN ownership reduced the risk of malaria outcomes in both pooled and meta-regression approaches. In the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (Likelihood ratio [LR] test = 1.127 for the outcome of rapid diagnostic test confirmed malaria infection, p = 0.2885; LR test = 0.161 for the outcome of microscopy confirmed malaria infection, p = 0.161; LR test = 0.646 for the outcome of moderate or severe anemia, p = 0.4215). In the meta-regression approach the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes.InterpretationITNs decreased risk of malaria outcomes independent of the levels of pyrethroid resistance in the malaria vector populations.FundingDAL did not receive funding and RC received a SOURCE grant from Syracuse University for this project.

scholarly journals Retrospective study of toxoplasmosis prevalence in pregnant women in Benin and its relation with malaria

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262018
Author(s):  
Magalie Dambrun ◽  
Célia Dechavanne ◽  
Nicolas Guigue ◽  
Valérie Briand ◽  
Tristan Candau ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Formal Education ◽  
Congenital Toxoplasmosis ◽  
Protozoan Parasite ◽  
Protective Role ◽  
Medical Intervention ◽  
Sub Saharan Africa ◽  
Apical Membrane Antigen 1 ◽  
Serological Status ◽  
Sub Saharan

Background Globally distributed with variable prevalence depending on geography, toxoplasmosis is a zoonosis caused by an obligate intracellular protozoan parasite, Toxoplasma gondii. This disease is usually benign but poses a risk for immunocompromised people and for newborns of mothers with a primary infection during pregnancy because of the risk of congenital toxoplasmosis (CT). CT can cause severe damage to fetuses-newborns. To our knowledge, no study has been conducted in sub-Saharan Africa on toxoplasmosis seroprevalence, seroconversion and CT in a large longitudinal cohort and furthermore, no observation has been made of potential relationships with malaria. Methods We performed a retrospective toxoplasmosis serological study using available samples from a large cohort of 1,037 pregnant women who were enrolled in a malaria follow-up during the 2008–2010 period in a rural area in Benin. We also used some existing data to investigate potential relationships between the maternal toxoplasmosis serological status and recorded malaria infections. Results Toxoplasmosis seroprevalence, seroconversion and CT rates were 52.6%, 3.4% and 0.2%, respectively, reflecting the population situation of toxoplasmosis, without targeted medical intervention. The education level influences the toxoplasmosis serological status of women, with women with little or no formal education have greater immunity than others. Surprisingly, toxoplasmosis seropositive pregnant women tended to present lower malaria infection during pregnancy (number) or at delivery (presence) and to have lower IgG levels to Plasmodium falciparum Apical Membrane Antigen 1, compared to toxoplasmosis seronegative women. Conclusions The high toxoplasmosis seroprevalence indicates that prevention against this parasite remains important to deploy and must be accessible and understandable to and for all individuals (educated and non-educated). A potential protective role against malaria conferred by a preexisting toxoplasmosis infection needs to be explored more precisely to examine the environmental, parasitic and/or immune aspects.

scholarly journals THE QUEST FOR BUILDING LABORATORY CAPACITY TO SUPPORT CONTROLLED HUMAN MALARIA INFECTION (CHMI) STUDIES IN SUB-SAHARAN AFRICA: EXPERIENCE WITH FIVE SITES

2017 ◽  
Vol 2 (Suppl 2) ◽  
pp. A19.2-A19
Author(s):  
Kennedy Awuondo ◽  
Daniel Njenga ◽  
Elizabeth Nyakarungu ◽  
Pauline Titus ◽  
Awalludin Sutamihardja ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Sub Saharan Africa ◽  
Human Malaria ◽  
Laboratory Capacity ◽  
Controlled Human Malaria Infection ◽  
Sub Saharan

Malaria

2017 ◽  
Author(s):  
Kiran Thakur
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Sub Saharan Africa ◽  
Neurological Manifestations ◽  
Significant Morbidity ◽  
Related Factors ◽  
Major Life ◽  
Life Threatening ◽  
Sub Saharan ◽  
Global Eradication

Malaria persists despite efforts for global eradication and vaccine development, and continues to prove lethal in endemic regions. The neurological manifestations of malaria are often devastating, with a high mortality rate and significant morbidity in survivors. A major life threatening complication of malaria infection is cerebral malaria (CM), most commonly occurring in children in sub-Saharan Africa and adults in Southeast Asia. There should be a high suspicion for CM in patients who present in coma residing in or having recently traveled to malaria endemic regions. Other neurological manifestations posing significant morbidity include postmalaria neurological syndrome and side effects due to antimalarial medications. Discussions in this chapter are focused around the neurobiology of malaria infection, and the host- and pathogen-related factors that contribute to neurological manifestations of the mosquito-borne illness.

scholarly journals Generation of neuroinflammation in human African trypanosomiasis

2019 ◽  
Vol 6 (6) ◽  
pp. e610 ◽  
Author(s):  
Jean Rodgers ◽  
Israel Steiner ◽  
Peter G. E Kennedy
Keyword(s):  
Human African Trypanosomiasis ◽  
Clinical Symptoms ◽  
Parasite Burden ◽  
Brain Inflammation ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Peripheral Tissues ◽  
Neuroinflammatory Response ◽  
Proinflammatory Mediators ◽  
Sub Saharan

Human African trypanosomiasis (HAT) is caused by infection due to protozoan parasites of the Trypanosoma genus and is a major fatal disease throughout sub-Saharan Africa. After an early hemolymphatic stage in which the peripheral tissues are infected, the parasites enter the CNS causing a constellation of neurologic features. Although the CNS stage of HAT has been recognized for over a century, the mechanisms generating the neuroinflammatory response are complex and not well understood. Therefore a better understanding of the mechanisms utilized by the parasites to gain access to the CNS compartment is critical to explaining the generation of neuroinflammation. Contrast-enhanced MRI in a murine model of HAT has shown an early and progressive deterioration of blood-CNS barrier function after trypanosome infection that can be reversed following curative treatment. However, further studies are required to clarify the molecules involved in this process. Another important determinant of brain inflammation is the delicate balance of proinflammatory and counterinflammatory mediators. In mouse models of HAT, proinflammatory mediators such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and CXCL10 have been shown to be crucial to parasite CNS invasion while administration of interleukin (IL)-10, a counter inflammatory molecule, reduces the CNS parasite burden as well as the severity of the neuroinflammatory response and the clinical symptoms associated with the infection. This review focuses on information, gained from both infected human samples and animal models of HAT, with an emphasis on parasite CNS invasion and the development of neuroinflammation.

scholarly journals Transcriptional differentiation of Trypanosoma brucei during in vitro acquisition of resistance to acoziborole

2021 ◽  
Vol 15 (11) ◽  
pp. e0009939
Author(s):  
Pieter C. Steketee ◽  
Federica Giordani ◽  
Isabel M. Vincent ◽  
Kathryn Crouch ◽  
Fiona Achcar ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Morphological Changes ◽  
Protozoan Parasite ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Surface Proteins ◽  
Sub Saharan Africa ◽  
Cross Resistance ◽  
Sub Saharan

Subspecies of the protozoan parasite Trypanosoma brucei are the causative agents of Human African Trypanosomiasis (HAT), a debilitating neglected tropical disease prevalent across sub-Saharan Africa. HAT case numbers have steadily decreased since the start of the century, and sustainable elimination of one form of the disease is in sight. However, key to this is the development of novel drugs to combat the disease. Acoziborole is a recently developed benzoxaborole, currently in advanced clinical trials, for treatment of stage 1 and stage 2 HAT. Importantly, acoziborole is orally bioavailable, and curative with one dose. Recent studies have made significant progress in determining the molecular mode of action of acoziborole. However, less is known about the potential mechanisms leading to acoziborole resistance in trypanosomes. In this study, an in vitro-derived acoziborole-resistant cell line was generated and characterised. The AcoR line exhibited significant cross-resistance with the methyltransferase inhibitor sinefungin as well as hypersensitisation to known trypanocides. Interestingly, transcriptomics analysis of AcoR cells indicated the parasites had obtained a procyclic- or stumpy-like transcriptome profile, with upregulation of procyclin surface proteins as well as differential regulation of key metabolic genes known to be expressed in a life cycle-specific manner, even in the absence of major morphological changes. However, no changes were observed in transcripts encoding CPSF3, the recently identified protein target of acoziborole. The results suggest that generation of resistance to this novel compound in vitro can be accompanied by transcriptomic switches resembling a procyclic- or stumpy-type phenotype.

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