Browsing by Subject "malaria"

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    Barriers to malaria prevention and chemoprophylaxis use among travelers who visit friends and relatives in Sub-Saharan Africa: A cross-sectional, multi-setting survey addressing behaviors, systems, and comparator populations
    (2019-05) Volkman, Hannah
    Despite achievements in the reduction of malaria morbidity and mortality globally, imported malaria cases to the US by travelers continue to grow. Imported malaria occurs disproportionately among individuals who travel to visit friends and relatives (VFRs) in malarious countries. This dissertation examines behavioral and structural barriers to chemoprophylaxis use and malaria prevention among VFR travelers to the African continent. This survey-based study is one component of a broader, multi-methodologic project aimed to reduce malaria in VFR travelers. Barriers are identified through a cross-sectional, three-setting survey of knowledge, attitudes and practices of diagnosed malaria cases, community VFRs, and patients at a specialty travel clinic. Subgroup analyses are performed comparing VFRs traveling to different regions and across survey settings, as well as to non-VFR travelers to generate a deeper understanding of the heterogeneity and breadth of barriers. In all, 489 surveys were completed, 351 among VFRs. VFRs face significant barriers between intending and actualizing malaria prevention; while 95.2% of VFRs planned to take an antimalarial, just 59.4% reported using chemoprophylaxis. Having a primary care provider is strongly positively associated with seeking pre-travel care and improved perceptions of the health care system among VFRs. Compared to VFRs, non-VFR travelers are more successful at preventive approaches including antimalarial use, wearing long clothing, and bed net use. Yet travel clinic VFRs more commonly report certain prevention approaches than VFRs in the community; heterogeneity exists both among VFRs and across traveler populations. A novel conceptual framework is proposed to explain correlations between predictors of malaria illness, integrating concern for malaria, malaria prevention, and travel frequency. Engaging policy leaders in travel medicine is necessary for a deeper understanding of structural barriers to malaria prevention. These findings and call for future partnerships will be central to the development of targeted, evidence-based barrier reduction interventions and policies which may reduce imported malaria over time. A reduction in malaria among VFRs would not only lessen morbidity among the nearly 1,500 travelers with malaria in the US each year, but also decrease health care costs to payers, and reduce risk of local malaria transmission and the subsequent intensive public health response.
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    Investigating the mechanisms underlying antibody-mediated effector functions in malaria and Multisystem Inflammatory Syndrome in Children (MIS-C)
    (2024-06) Dick , Jenna
    Antibodies have multiple functions within the body to provide host protection, including interacting with Fc receptors on innate immune cells to destroy pathogens or cells infected by pathogens. We studied antibody-mediated cellular responses in the context of two infections: malaria, a parasitic infection, and SARS-CoV-2, a viral infection. Plasmodium falciparum (P.f) is the main cause of malaria worldwide and is major cause of morbidity and mortality. Deaths occur because of the blood stage of the P.f. life cycle. To date, there is no effective blood stage malaria vaccine. Natural killer (NK) cells inhibit the growth in the blood through interacting with antibodies via antibody dependent cellular cytotoxicity (ADCC). A subset of NK cells in malaria, known as adaptive NK cells, lack the FcR chain and have enhanced ADCC. However, it is unclear if the lack of FcRchain is the reason for increased functionality or if it only serves as a marker. Using CRIPSR/Cas9, we found that ablating the FcR chain did not enhance ADCC. Using cohort of subjects from a malaria clinical study in Mali, we then searched for other alterations in malaria NK cells that could explain the enhanced functionality. We found that the expression of Sigelc-7, an inhibitory receptor, is decreased on NK cells from individuals with malaria and that decreased expression of Siglec-7 correlates with increased ADCC. These data provide evidence that the host may increase the number of Siglec-7 negative NK cells to aide in the clearance of infected RBCs through ADCC. I then investigated antibody-mediated effector functions in Multisystem Inflammatory Syndrome in Children (MIS-C), a rare and severe complication of SARS-CoV-2 infection that is characterized by multi-organ involvement and substantial inflammation. Little is known about antibody-mediated cellular responses in MIS-C. We show that monocytes in MIS-C were hyperfunctional while NK cells were hypofunctional for antibody-dependent cellular destruction and cytokine production. We also show multiple ways leading to decreased cytotoxicity for NK cells, including phenotypic exhaustion of NK cells and cytokine-induced associations. Together, our results reveal unique dysregulation in antibody-mediated responses in MIS-C that contribute to the immune pathology of this disease and may be amenable to immunomodulation. Overall, this thesis provides insight into the mechanisms underlying antibody-mediated cellular functions in malaria and MIS-C that can be utilized in developing therapeutics and vaccine targets for these diseases .
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    Malaria: Diagnosis and Prevention
    (2010-07-29) Jubert, Nicholas
    Malaria is one of the most common infectious diseases around the world. It causes fever, chills, and sweats, and can have severe renal and cerebral manifestations. It is important that all patients understand the risk associated with malaria, even those who have previously been exposed when living in endemic areas. This pamphlet identifies at risk travelers, signs and symptoms of malaria infection, and gives ideas for malaria prevention.