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https://www.readbyqxmd.com/read/29325068/emergence-of-non-falciparum-plasmodium-infection-despite-regular-artemisinin-combination-therapy-in-a-18-month-longitudinal-study-of-ugandan-children-and-their-mothers
#1
Martha Betson, Sarah Clifford, Michelle Stanton, Narcis B Kabatereine, J Russell Stothard
As part of a longitudinal cohort investigation of intestinal schistosomiasis and malaria in Ugandan children and their mothers on the shorelines of Lakes Victoria and Albert, we documented risk factors and morbidity associated with non-falciparum Plasmodium infections and the longitudinal dynamics of Plasmodium species in children. Host age, household location and P. falciparum infection were strongly associated with non-falciparum Plasmodium infections, and P. malariae infection was associated with splenomegaly...
January 6, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29324864/safety-of-single-low-dose-primaquine-in-glucose-6-phosphate-dehydrogenase-deficient-falciparum-infected-african-males-two-open-label-randomized-safety-trials
#2
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
https://www.readbyqxmd.com/read/29323879/malaria-derived-gpi-anchor-enhances-anti-pfs25-functional-antibodies-that-block-malaria-transmission
#3
Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole Long, Jeff Fairman, Kazutoyo Miura
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties...
January 11, 2018: Biochemistry
https://www.readbyqxmd.com/read/29320160/efforts-aimed-to-reduce-attrition-in-antimalarial-drug-discovery-a-systematic-evaluation-of-current-antimalarial-targets-portfolio
#4
María Jesus Chaparro, Felix Calderon, Pablo Castañeda, Elena Fernandez Alvaro, Raquel Gabarro, Francisco-Javier Gamo, María G Gómez-Lorenzo, Julio Martín, Esther Fernandez
Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (Artemisinin Combination Therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits...
January 10, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29317800/leishmaniasis-in-humans-drug-or-vaccine-therapy
#5
REVIEW
Masoud Ghorbani, Ramin Farhoudi
Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29310655/methylene-blue-induced-morphological-deformations-in-plasmodium-falciparum-gametocytes-implications-for-transmission-blocking
#6
Ishan Wadi, C Radhakrishna Pillai, Anupkumar R Anvikar, Abhinav Sinha, Mahendra Nath, Neena Valecha
BACKGROUND: Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients...
January 8, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29300748/functional-interrogation-of-plasmodium-genus-metabolism-identifies-species-and-stage-specific-differences-in-nutrient-essentiality-and-drug-targeting
#7
Alyaa M Abdel-Haleem, Hooman Hefzi, Katsuhiko Mineta, Xin Gao, Takashi Gojobori, Bernhard O Palsson, Nathan E Lewis, Neema Jamshidi
Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale models (GEMs) of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages...
January 4, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29282143/azithromycin-versus-placebo-for-the-treatment-of-hiv-associated-chronic-lung-disease-in-children-and-adolescents-breathe-trial-study-protocol-for-a-randomised-controlled-trial
#8
Carmen Gonzalez-Martinez, Katharina Kranzer, Grace McHugh, Elizabeth L Corbett, Hilda Mujuru, Mark P Nicol, Sarah Rowland-Jones, Andrea M Rehman, Tore J Gutteberg, Trond Flaegstad, Jon O Odland, Rashida A Ferrand
BACKGROUND: Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation...
December 28, 2017: Trials
https://www.readbyqxmd.com/read/29281988/intravenous-artesunate-plus-artemisnin-based-combination-therapy-act-or-intravenous-quinine-plus-act-for-treatment-of-severe-malaria-in-ugandan-children-a-randomized-controlled-clinical-trial
#9
Pauline Byakika-Kibwika, Jane Achan, Mohammed Lamorde, Carine Karera-Gonahasa, Agnes N Kiragga, Harriet Mayanja-Kizza, Noah Kiwanuka, Sam Nsobya, Ambrose O Talisuna, Concepta Merry
BACKGROUND: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. METHODS: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29280424/treatment-seeking-behavior-after-the-implementation-of-a-unified-policy-of-dihydroartemisinin-piperaquine-for-the-treatment-of-uncomplicated-malaria-in-papua-indonesia
#10
Angela Devine, Enny Kenangalem, Lenny Burdarm, Nicholas M Anstey, Jeanne Rini Poespoprodjo, Ric N Price, Shunmay Yeung
Artemisinin combination therapy is recommended for the treatment of multidrug resistant Plasmodium falciparum and Plasmodium vivax. In March 2006, antimalarial policy in Indonesia was changed to a unified treatment with dihydroartemisinin-piperaquine for all species of malaria because of the low efficacy of previous drug treatments. In 2013, a randomized cross-sectional household survey in Papua was used to collect data on demographics, parasite positivity, treatment-seeking behavior, diagnosis and treatment of malaria, and household costs...
December 26, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29260652/case-report-reversible-cerebral-vasoconstriction-syndrome-in-severe-cerebral-malaria
#11
Kei Yamamoto, Yasuyuki Kato, Koh Shinohara, Satoshi Kutsuna, Nozomi Takeshita, Kayoko Hayakawa, Moritoshi Iwagami, Shigeyuki Kano, Shu Watanabe, Norio Ohmagari
Cerebral malaria is a severe complication of falciparum malaria that occurs infrequently in adults. Here, we describe the case of a 21-year-old man who presented with fever and headache 13 days after returning from a 12-day trip to Kenya and was subsequently diagnosed with falciparum malaria. Complications of cerebral malaria developed within 1 day after the initiation of therapy with intravenous quinine, and the patient entered a deep coma. Magnetic resonance angiography (MRA) revealed multiple vasoconstrictions in his brain...
December 18, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29258508/functional-analysis-of-plasmodium-falciparum-subpopulations-associated-with-artemisinin-resistance-in-cambodia
#12
Ankit Dwivedi, Christelle Reynes, Axel Kuehn, Daniel B Roche, Nimol Khim, Maxim Hebrard, Sylvain Milanesi, Eric Rivals, Roger Frutos, Didier Menard, Choukri Ben Mamoun, Jacques Colinge, Emmanuel Cornillot
BACKGROUND: Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown...
December 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29258448/factors-contributing-to-anaemia-after-uncomplicated-falciparum-malaria-in-under-five-year-old-nigerian-children-ten-years-following-adoption-of-artemisinin-based-combination-therapies-as-first-line-antimalarials
#13
Akintunde Sowunmi, Bayo Fatunmbi, Kazeem Akano, Olubunmi A Wewe, Chimere Agomo, Finomo Finomo, Joy Ebenebe, Nma Jiya, Jose Ambe, Robinson Wammanda, Godwin Ntadom, Olugbenga Mokuolu, George Emechebe, Nnenna Ezeigwe, Adejumoke I Ayede, Elsie O Adewoye, Grace O Gbotosho, Onikepe A Folarin, Christian T Happi, Stephen Oguche, Wellington A Oyibo, Francis Useh
BACKGROUND: Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. METHODS: Malarious <5 year-olds randomized to artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine treatments were followed up clinically for 6 weeks...
December 19, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29250318/do-we-know-enough-to-find-an-adjunctive-therapy-for-cerebral-malaria-in-african-children
#14
REVIEW
Brittany A Riggle, Louis H Miller, Susan K Pierce
Cerebral malaria is the deadliest complication of malaria, a febrile infectious disease caused by Plasmodium parasite. Any of the five human Plasmodium species can cause disease, but, for unknown reasons, in approximately 2 million cases each year P. falciparum progresses to severe disease, ultimately resulting in half a million deaths. The majority of these deaths are in children under the age of five. Currently, there is no way to predict which child will progress to severe disease and there are no adjunctive therapies to halt the symptoms after onset...
2017: F1000Research
https://www.readbyqxmd.com/read/29244829/cost-effectiveness-analysis-of-introducing-malaria-diagnostic-testing-in-drug-shops-a-cluster-randomised-trial-in-uganda
#15
Kristian Schultz Hansen, Siân E Clarke, Sham Lal, Pascal Magnussen, Anthony K Mbonye
BACKGROUND: Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. METHODS: Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm...
2017: PloS One
https://www.readbyqxmd.com/read/29229871/antifolate-drug-resistance-novel-mutations-and-haplotype-distribution-in-dhps-and-dhfr-from-northeast-india
#16
N P Sarmah, K Sarma, D R Bhattacharyya, A A Sultan, D Bansal, N Singh, P K Bharti, R Sehgal, P K Mohapatra, P Parida, J Mahanta
Malaria is a major public health concern in Northeast India with a preponderance of drug-resistant strains. Until recently the partner drug for artemisinin combination therapy (ACT) was sulphadoxine pyrimethamine (SP). Antifolate drug resistance has been associated with the mutations at dihydropteroate synthase (dhps) and dihydrofolatereductase (dhfr) genes. This study investigated antifolate drug resistance at the molecular level. A total of 249 fever cases from Arunachal Pradesh, NE India, were screened for malaria, and of these, 75 were found to be positive for Plasmodium falciparum...
December 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/29219134/does-infant-feeding-method-influence-the-incidence-and-pattern-of-morbidities-among-human-immunodeficiency-virus-exposed-uninfected-nigerian-infants
#17
Olusoga Babatunde Ogunfowora, Tinuade Adetutu Ogunlesi, Abiodun Folashade Adekanmbi, Victor Ayodeji Ayeni
BACKGROUND: Human immunodeficiency virus (HIV)-exposed infants enrolled into the prevention of mother-to-child transmission of HIV program generally receive antiretroviral therapy (ARV), but the feeding methods differ based on several socioeconomic and cultural differences. OBJECTIVE: The objective of the study was to examine the incidence and pattern of morbidities among HIV-exposed uninfected (HEU) Nigerian infants and determine any relationship with infant feeding methods...
October 2017: Indian Journal of Public Health
https://www.readbyqxmd.com/read/29215279/design-and-synthesis-of-orally-bioavailable-piperazine-substituted-4-1h-quinolones-with-potent-antimalarial-activity-structure-activity-and-structure-property-relationship-studies
#18
Raghupathi Neelarapu, Jordany R Maignan, Cynthia L Lichorowic, Andrii Monastyrskyi, Tina S Mutka, Alexis N LaCrue, Lynn D Blake, Debora Casandra, Sherwin Mashkouri, Jeremy N Burrows, Paul A Willis, Dennis E Kyle, Roman Manetsch
Malaria deaths have been decreasing over the last 10-15 years, with global mortality rates having fallen by 47% since 2000. While the World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs) to combat malaria, the emergence of artemisinin resistant strains underscores the need to develop new antimalarial drugs. Recent in vivo efficacy improvements of the historical antimalarial ICI 56,780 have been reported, however with the poor solubility and rapid development of resistance, this compound requires further optimization...
December 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29211247/immunoproteomics-of-plasmodium-falciparum-infected-red-blood-cell-membrane-fractions
#19
Fernanda J Cabral, Luciana G Vianna, Marcia M Medeiros, Bianca Cechetto Carlos, Rosimeire D Martha, Nadia Maria Silva, Luiz Hildebrando P da Silva, Rodrigo G Stabeli, Gerhard Wunderlich
BACKGROUND: The surface of infected red blood cells (iRBCs) has been widely investigated because of the molecular complexity and pathogenesis mechanisms involved. Asymptomatic individuals are important in the field because they can perpetuate transmission as natural reservoirs and present a challenge for diagnosing malaria because of their low levels of circulating parasites. Recent studies of iRBC antibody recognition have shown that responses are quantitatively similar in symptomatic and asymptomatic infections, but no studies have characterised the plasmodial proteins targeted by this response...
December 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29206727/assessment-of-myocardial-function-and-injury-by-echocardiography-and-cardiac-biomarkers-in-african-children-with-severe-plasmodium-falciparum-malaria
#20
Simon Kotlyar, Peter Olupot-Olupot, Julius Nteziyaremye, Samuel O Akech, Sophie Uyoga, Rita Muhindo, Christopher L Moore, Kathryn Maitland
OBJECTIVES: Perturbed hemodynamic function complicates severe malaria. The Fluid Expansion as Supportive Therapy trial demonstrated that fluid resuscitation, involving children with severe malaria, was associated with increased mortality, primarily due to cardiovascular collapse, suggesting that myocardial dysfunction may have a role. The aim of this study was to characterize cardiac function in children with severe malaria. DESIGN: A prospective observational study with clinical, laboratory, and echocardiographic data collected at presentation (T0) and 24 hours (T1) in children with severe malaria...
December 4, 2017: Pediatric Critical Care Medicine
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