Medicine and Health Sciences Commons^™

Malaria: Existence Perpetuated By A Counterfeit Drug Industry, Nicholas Black

Undergraduate Research Symposium

Malaria is a mosquito-borne disease that has plagued society for thousands of years. Malaria is often overlooked from the perspective of wealthier industrialized countries due to prevention efforts largely eliminating malaria from these locations. However, overlooking malaria’s continued global relevance is misinformed to the fact that nearly half the global population lives in regions at risk of malarial transmission. According to the CDC and WHO, such a high number of people at risk has subsequently led to an estimated 241 million cases and over 627 thousand deaths in 2020 alone. The purpose for the present research is to examine the …

Transmission Risk Of Malaria Via Gas Flares In Africa, Elle Blake

Health, Human Performance and Recreation Undergraduate Honors Theses

Gas flaring occurs at oil drilling sites around the world. It is a method to get rid of the extra gas, as well as to release pressure in emergency situations. The pollutants that are contributed to the air through routine gas flaring can be extremely harmful. Chemicals such as sulfur dioxide and methane are burned into the air we breathe (Baker Hughes, 2019). Not only does this have a direct impact on our health, but also on greenhouse gas emissions. The effects on greenhouse gas emissions impact diseases such as Malaria by increasing the temperature of our planet. The purpose …

Preclinical Characterization And Target Validation Of The Antimalarial Pantothenamide Mmv693183., Laura E. De Vries, Patrick A. M. Jansen, Catalina Barcelo, Justin Munro, Julie M. J. Verhoef, Charisse Flerida A. Pasaje, Kelly Rubiano, Josefine Striepen, Nada Abla, Luuk Berning, Judith M. Bolscher, Claudia Demarta-Gatsi, Rob W. M. Henderson, Tonnie Huijs, Karin M J Koolen, Patrick K. Tumwebaze, Tomas Yeo, Anna C. C. Aguiar, Iñigo Angulo-Barturen, Alisje Churchyard, Jake Baum, Benigno Crespo Fernández, Aline Fuchs, Francisco-Javier Gamo, Rafael V. C. Guido, María Belén Jiménez-Diaz, Dhelio B. Pereira, Rosemary Rochford, Camille Roesch, Laura M. Sanz, Graham Trevitt, Benoit Witkowski, Sergio Wittlin, Roland A. Cooper, Philip J. Rosenthal, Robert W. Sauerwein, Joost Schalkwijk, Pedro H. H. Hermkens, Roger V. Bonnert, Brice Campo, David A. Fidock, Manuel Llinás, Jacquin C. Niles, Taco W. A. Kooij, Koen J. Dechering

Natural Sciences and Mathematics | Faculty Scholarship

Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient …

Discovery And Preclinical Pharmacology Of Ine963, A Potent And Fast-Acting Blood-Stage Antimalarial With A High Barrier To Resistance And Potential For Single-Dose Cures In Uncomplicated Malaria., Benjamin R. Taft, Fumiaki Yokokawa, Tom Kirrane, Anne-Catherine Mata, Richard Huang, Nicole Blaquiere, Grace Waldron, Bin Zou, Oliver Simon, Subramanyam Vankadara, Wai Ling Chan, Mei Ding, Sandra Sim, Judith Straimer, Armand Guiguemde, Suresh B Lakshminarayana, Jay Prakash Jain, Christopher Bodenreider, Christopher Thompson, Christian Lanshoeft, Wei Shu, Eric Fang, Jafri Qumber, Katherine Chan, Luying Pei, Yen-Liang Chen, Hanna Schulz, Jessie Lim, Siti Nurdiana Abas, Xiaoman Ang, Yugang Liu, Iñigo Angulo-Barturen, María Belén Jiménez-Díaz, Glaxosmithkline Gamo, Benigno Crespo-Fernandez, Philip J. Rosenthal, Roland A. Cooper, Patrick Tumwebaze, Anna Caroline Campos Aguiar, Brice Campo, Simon Campbell, Jürgen Wagner, Thierry T Diagana, Christopher Sarko

Natural Sciences and Mathematics | Faculty Scholarship

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves "artemisinin-like" kill kinetics in vitro with a parasite clearance time of/kg is fully curative in the Pf-humanized severe combined immunodeficient mouse model. INE963 (1) also exhibits a high barrier to resistance …

Rationalization Of The Laboratory Diagnosis For Good Management Of Malaria: Lessons From Transitional Methods, Neguemadji N. Ngaba, Imteyaz A. Khan, Namrata Hange, Maria Kezia Lourdes Ligsay Pormento, Manoj Kumar Reddy Somagutta, Ajay Kumar, Youssouf Abdelkerim, Alarangue Djindimadje, Samia Jahan

Ateneo School of Medicine and Public Health Publications

Introduction. Malaria is an endemic disease in sub-Saharan Africa. In clinical practice, the main concern is the overdiagnosis of malaria leading to inappropriate drug prescription without laboratory confirmation. Objective. This study aimed to evaluate clinical examination reliability compared with translational laboratory methods of malaria diagnosis. Methods. The study was conducted in Goundi Hospital among hospitalized patients over a seven-month period. Patients were interviewed, and malaria tests done included the Giemsa-stained thick and thin blood smears. Diagnostic accuracy was analysed by calculating sensitivity, specificity, and predictive values. Results. Among 1,874 participants, 674 (35.96%) patients had positive Giemsa-stained …

Can Repurposing Drugs Play A Role In Malaria Control?, Roland A. Cooper, Laura Kirkman

Natural Sciences and Mathematics | Faculty Scholarship

Innovative drug treatments for malaria, optimally with novel targets, are needed to combat the threat of parasite drug resistance. As drug development efforts continue, there may be a role for a host-targeting, repurposed cancer drug administered together with an artemisinin combination therapy that was shown to improve the speed of recovery from a malaria infection.

The Efficacy Of Insecticide-Treated Window Screens And Eaves Against Anopheles Mosquitoes: A Scoping Review, Beverly Anaele, Karan Varshney, Francis S O Ugwu, Rosemary Frasso

College of Population Health Faculty Papers

Background: Female mosquitoes serve as vectors for a host of illnesses, including malaria, spread by the Plasmodium parasite. Despite monumental strides to reduce this disease burden through tools such as bed nets, the rate of these gains is slowing. Ongoing disruptions related to the COVID-19 pandemic may also negatively impact gains. The following scoping review was conducted to examine novel means of reversing this trend by exploring the efficacy of insecticide-treated window screens or eaves to reduce Anopheles mosquito bites, mosquito house entry, and density.

Methods: Two reviewers independently searched PubMed, Scopus, and ProQuest databases on 10 July, 2020 for …

Associations Between Varied Susceptibilities To Pfatp4 Inhibitors And Genotypes In Ugandan Plasmodium Falciparum Isolates., Oriana Kreutzfeld, Stephanie A. Rasmussen, Aarti A. Ramanathan, Patrick K. Tumwebaze, Oswald Byaruhanga, Thomas Katairo, Victor Asua, Martin Okitwi, Stephen Orena, Jennifer Legac, Melissa D. Conrad, Samuel L. Nsobya, Ozkan Aydemir, Jeffrey Bailey, Maelle Duffey, Brett R. Bayles, Akhil B. Vaidya, Roland A. Cooper, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda, from 2016 to 2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many nonsynonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K …

Drug Susceptibility Of Plasmodium Falciparum In Eastern Uganda: A Longitudinal Phenotypic And Genotypic Study, Patrick K. Tumwebaze, Thomas Katairo, Martin Okitwi, Oswald Byaruhanga, Stephen Orena, Victor Asua, Marvin Duvalsaint, Jennifer Legac, Sevil Chelebieva, Frida G. Ceja, Stephanie A. Rasmussen, Melissa D. Conrad, Samuel L. Nsobya, Ozkan Aydemir, Jeffrey A. Bailey, Brett R. Bayles, Philip J. Rosenthal, Roland A. Cooper

Natural Sciences and Mathematics | Faculty Scholarship

Background: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The aim of this study was to characterise antimalarial drug susceptibility of Plasmodium falciparum isolates from Tororo and Busia districts in Uganda.

Methods: In this prospective longitudinal study, P falciparum isolates were collected from patients aged 6 months or older presenting at the Tororo District Hospital (Tororo district, a site with relatively low malaria incidence) or Masafu General Hospital (Busia district, a high-incidence site) in eastern Uganda …

The Antimalarial Mmv688533 Provides Potential For Single-Dose Cures With A High Barrier To, James M. Murithi, Cécile Pascal, Jade Bath, Xavier Boulenc, Nina F. Gnädig, Charisse Flerida A. Pasaje, Kelly Rubiano, Tomas Yeo, Sachel Mok, Sylvie Klieber, Paul Desert, María Belén Jiménez-Díaz, Jutta Marfurt, Mélanie Rouillier, Mohammed H. Cherkaoui-Rbati, Nathalie Gobeau, Sergio Wittlin, Anne-Catrin Uhlemann, Ric N. Price, Grennady Wirjanata, Rintis Noviyanti, Patrick Tumwebaze, Roland A. Cooper, Philip J. Rosenthal, Laura M. Sanz, Francisco-Javier Gamo, Jayan Joseph, Shivendra Singh, Sridevi Bashyam, Jean Michel Augereau, Elie Giraud, Tanguy Bozec, Thierry Vermat, Gilles Tuffal, Jean-Michel Guillon, Jérôme Menegotto, Laurent Sallé, Guillaume Louit, Marie-José Cabanis, Marie Françoise Nicolas, Michel Doubovetzky, Rita Merino, Nadir Bessila, Iñigo Angulo-Barturen, Delphine Baud, Lidiya Bebrevska, Fanny Escudié, Jacquin C. Niles, Benjamin Blasco, Simon Campbell, Gilles Courtemanche, Laurent Fraisse, Alain Pellet, David A. Fidock, Didier Leroy

Natural Sciences and Mathematics | Faculty Scholarship

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in …

The Antimalarial Mmv688533 Provides Potential For Single-Dose Cures With A High Barrier To, James M. Murithi, Cécile Pascal, Jade Bath, Xavier Boulenc, Nina F. Gnädig, Charisse Flerida A. Pasaje, Kelly Rubiano, Tomas Yeo, Sachel Mok, Sylvie Klieber, Paul Desert, María Belén Jiménez-Díaz, Jutta Marfurt, Mélanie Rouillier, Mohammed H. Cherkaoui-Rbati, Nathalie Gobeau, Sergio Wittlin, Anne-Catrin Uhlemann, Ric N. Price, Grennady Wirjanata, Rintis Noviyanti, Patrick K. Tumwebaze, Roland A. Cooper, Philip J. Rosenthal, Laura M. Sanz, Francisco-Javier Gamo, Jayan Joseph, Shivendra Singh, Sridevi Bashyam, Jean Michel Augereau, Elie Giraud, Tanguy Bozec, Thierry Vermat, Gilles Tuffal, Jean-Michel Guillon, Jérôme Menegotto, Laurent Sallé, Guillaume Louit, Marie-José Cabanis, Marie Françoise Nicolas, Michel Doubovetzky, Rita Merino, Nadir Bessila, Iñigo Angulo-Barturen, Delphine Baud, Lidiya Bebrevska, Fanny Escudié, Jacquin C. Niles, Benjamin Blasco, Simon Campbell, Gilles Courtemanche, Laurent Fraisse, Alain Pellet, David A. Fidock, Didier Leroy

Natural Sciences and Mathematics | Faculty Scholarship

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in …

Prevention Of Pediatric Mortality Associated With Malaria: An Exhaustive Literature Review, Taylor Mosley

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Malaria, a disease that is preventable yet frequently fatal, disproportionately affects pediatric African populations at a rate that results in a child under the age of 5 dying every two minutes. Since 1955, the World Health Organization has contributed to a significant reduction in the morbidity and mortality of malaria; however, progress has stalled in recent years. In some countries, particularly those in sub-Saharan Africa, cases have increased since 2015. This literature review seeks to identify factors associated with this incline, as well as what interventions can have the greatest impact to prevent pediatric mortality in areas with the largest …

Etiology Of Acute Undifferentiated Fever In Patients Presenting To The Emergency Department Of A Tertiary Care Center In Karachi, Pakistan, Noman Ali, Nadeem Ullah Khan, Shahid Shahid, Syed Mustahsan

Department of Emergency Medicine

Objective: Our study aimed at identifying the characteristics and etiology of various causes of acute undifferentiated fever in patients presenting to the emergency department of a tertiary care hospital.
Methods: This was a retrospective study conducted at the department of emergency medicine, Aga Khan University Hospital from January to June 2016. Adult patients presenting to Emergency department with acute undifferentiated fever were enrolled. Descriptive statistics were calculated in terms of mean±SD for continuous variables like age of the patients and duration of fever, whereas frequency and percentage were computed for categorical variables like gender and causes of fever.
Results: A …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Malaria Risk On Ancient Roman Roads: A Study And Application To Assessing Travel Decisions In Asia Minor By The Apostle Paul, Daniel C. Browning Jr

Master's Theses

This study models malaria risks for travelers on ancient Roman roads with the goal of providing a tool for historical assessment of travel accounts from antiquity. The project includes: identification of malaria risk factors and associated spatial datasets, malaria risk model construction, verification and validation against available pre-eradication data, overlay of ancient Roman road data, and an initial case-study application to the journeys of the Apostle Paul, as narrated in the New Testament book, Acts of the Apostles (Acts). The project is intentionally cross-disciplinary in bringing the technical capabilities of GIS to the task of evaluating nuanced textual sources for …

Trauma - Striving For Change, Ather Enam, Hasnain Zafar, Rehan Nasir Khan

Section of Neurosurgery

No abstract provided.

Evaluating The Impact Of Malaria Education On Student Missionaries, Julie Mckinney

DNP Research Projects

Malaria has been studied for years, and yet remains one of the most significant vector-borne diseases that travelers encounter in malaria-endemic regions (CDC, 2019). Education is noted to be critical in disease prevention, management, and eradication. Student missionaries are at high risk for infection and can have a global influence that is improved through education. A pilot study was conducted on eleven students with a pre-test and post-test design after a malaria education webinar. The purpose of this pilot study was to assess the baseline level of education in student missionaries, as well as to assess the effect of malaria …

The Impact Of Delayed Treatment Of Uncomplicated P. Falciparum Malaria On Progression To Severe Malaria: A Systematic Review And A Pooled Multicentre Individual-Patient Meta-Analysis, Andria Mousa, Abdullah Al-Taiar, Nicholas M. Anstey, Cyril Badaut, Bridget E. Barber, Quique Bassat, Joseph D. Challenger, Aubrey J. Cunnington, Dibyadyuti Datta, Chris Drakeley, Azra C. Ghani, Victor R. Gordeuk, Matthew J. Grigg, Pierre Hugo, Chandy C. John, Alfredo Mayor, Florence Migot-Nabias, Robert O. Opoka, Geoffrey Pasvoi, Claire Rees, Hugh Reyburn, Eleanor M. Riley, Binal N. Shah, Antonio Sitoe, Colin J. Sutherland, Philip E. Thuma, Stefan A. Unger, Firmine Viwami, Michael Walther, Christopher J.M. Whitty, Timothy William, Lucy C. Okell

Community & Environmental Health Faculty Publications

BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM.

METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase …

Observing The Effects Of Antimalarial Drug Availability On Women’S Work Absenteeism, Rei Imada

CMC Senior Theses

This study aims to provide insight on how availability of antimalarial drugs can help alleviate the economic burden of malaria. Much of the existing literature that looks into the effects of antimalarial drug availability focuses on the associated health benefits, but fails to draw a link to the economic benefits that may also be incurred. Using data from the 2015-2016 Tanzania Demographic and Health Survey and Malaria Indicator Survey, this study performs a series of multiple regressions to observe how increased availability of artemisinin-based combination therapies (ACTs), a front-line antimalarial drug in most African countries, affects likelihood of work absenteeism …

Evaluation Of The Carestarttm Glucose-6-Phosphate Dehydrogenase (G6pd) Rapid Diagnostic Test At Community And Health Center Level, Cambodia, Bertha Nyagaya-Wojnarski, Dnp, Fnp-Bc, Mph

Doctor of Nursing Practice Projects

Background: Primaquine (PQ) is the only FDA-approved drug for radical cure of Plasmodium vivax (P.v) malaria, but treatment can result in life-threatening hemolysis if given to a glucose-6- phosphate dehydrogenase deficient (G6PDd) patient. Therefore, the G6PD status of the patient with P.v must be known prior to prescribing PQ. However, patient G6PD status in rural malaria endemic settings is generally unknown, illuminating the need for reliable point of care G6PD diagnostic tests as a prerequisite to safely administer PQ. To increase community PQ access in Cambodia, performance of CareStartTM G6PD rapid diagnostic tests (RDTs) needs to be evaluated in healthcare …

Guinea : Malaria, Madeleine Jacobson

Global Public Health

This brief analyzes malaria in Guinea and its impacts on individuals and the society. It consists of a geographic and demographic presentation of Guinea which includes information about its location, climate, natural resources, ethnic groups, politics and social internal and external challenges where human trafficking, lack of healthcare and refugees are discussed. The brief analyzes malaria´s transmission, diagnosis, preventions and a suggestion for an intervention.

Malaria is a vector-borne disease, which means that living organisms that can transmit infectious diseases between humans or from animals to humans, spread malaria. 70 percent of all malaria deaths occur in age years, but …

Comoros: Malaria, Elizabeth Rennolds

Global Public Health

After human settlement and migration took place throughout the world, a disease known as malaria broke out within many countries. Malaria is a disease that comes from a fever where a parasite takes over one’s red blood cells with mosquitoes being the ones that transmit this disease. The symptoms of this disease are as follows: fever (typical cycles of fever, chills, sweating), joint pain, headaches, vomiting, convulsions, and coma. Malaria is a big issue in the Comoros, an island which can be seen in the Indian Ocean between the eastern coast of Africa and Madagascar, because of the many occurrences …

Myanmar: Malaria, Michelle Grevengoed

Global Public Health

Myanmar is an underdeveloped country that struggles with the problem of lack of medical access and expensive healthcare. The endemic of Malaria has been going on for several years in this country and many efforts have been made to try and decrease the Public Health issue. However, Myanmar still has the highest number of Malaria-related deaths. The Myanmar government is continuously working at improving the healthcare system to help with the Malaria endemic. However, the poor country still continues to struggle with this issue. The parasite, P. falciparum, has been an ongoing issue since it is resistant to the …

Uganda: Malaria, Sui Hnem

Global Public Health

Malaria is an infectious disease caused by mosquito bite. It is a major health problem in Uganda and is a major cause of mortality and morbidity. Pregnant women and children are the most infected groups in the country. The Ugandan government did their best to keep children and women healthy by providing clinics near the villages and advocating home treatment for malaria. Although, the government is very supportive in preventing and promoting the malaria, people did not seek healthcare as much as they should. The reason for not seeking healthcare was because they feel healthy, or the clinic had long …

Vanuatu: Malaria, Cody Wheeler

Global Public Health

Vanuatu is a small archipelago near Australia with a population of over 280,000. This nation consists of almost all native Vanuatuans, who live in rural areas. This young nation, only 40 years of independence, has many issues ranging from infantile mortality to an underdeveloped infrastructure, water and sanitation issues. This brief’s focus is the endemic of malaria, specifically the Plasmodium falciparum and P. vivax strains of the disease. The nation is attempting to manage the issue through implementation of screening and better testing for malaria. The use of insecticide treated nets (ITNs) is also prevalent, but in some areas the …

Malaria: Sub-Saharan Africa, Caroline Morris

Global Issues in Public Health

Sub-Saharan Africa is the large area situated south of the Saharan desert. It is considered one of the poorest regions in the world; the territory faces many challenges in respect to public health. One of the most important issues that sub-Saharan Africa faces is malaria. It is spread through the female Anopheles mosquito. Environmental factors of sub-Saharan Africa heavily influence the rates of incidence in the region due to high populations of mosquitoes. Social determinants of health affect risk in the sub-Saharan populations. Little access to healthcare, built environment, and education all impact incidence of malaria in the region. Children …

Frequency Of G6pd Mediterranean In Individuals With And Without Malaria In Southern Pakistan, Bushra Moiz, Haroon Muhammad Arshad, Ahmed Raheem Raheem, Hasan Hayat, Najia Karim Ghanchi, M Asim Beg

Department of Pathology and Laboratory Medicine

Background: Pakistan has an estimated annual burden of 1.5 million malaria cases. The current situation calls for an efective malaria control and eradication programme in this country. Currently, primaquine is an attractive option for eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of Plasmodium falciparum. However, this drug causes haemolysis in individuals who are glucose-6-phosphate (G6PD) defcient. It is important to map G6PD defciency and malaria distribution in Pakistan to design an efective malaria eradication regimen. Frequency of G6PD defciency (G6PDd) in malaria patients has not been reported from Pakistan in any meaningful way. The purpose of this study …

Private Sector Role, Readiness And Performance For Malaria Case Management In Uganda, 2015., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Henry Kaula, Peter Buyungo, Jimmy Opigo

Collected Faculty and Staff Scholarship

BACKGROUND: Several interventions have been put in place to promote access to quality malaria case management services in Uganda's private sector, where most people seek treatment. This paper describes evidence using a mixed-method approach to examine the role, readiness and performance of private providers at a national level in Uganda. These data will be useful to inform strategies and policies for improving malaria case management in the private sector.

METHODS: The ACTwatch national anti-malarial outlet survey was conducted concurrently with a fever case management study. The ACTwatch nationally representative anti-malarial outlet survey was conducted in Uganda between May 18th 2015 …

Testing Times: Trends In Availability, Price, And Market Share Of Malaria Diagnostics In The Public And Private Healthcare Sector Across Eight Sub-Saharan African Countries From 2009 To 2015., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Kara Hanson, Catherine Goodman

Collected Faculty and Staff Scholarship

BACKGROUND: The World Health Organization guidelines have recommended that all cases of suspected malaria should receive a confirmatory test with microscopy or a malaria rapid diagnostic test (RDT), however evidence from sub-Saharan Africa (SSA) illustrates that only one-third of children under five with a recent fever received a test. The aim of this study was to evaluate availability, price and market share of microscopy and RDT from 2009/11 to 2014/15 in 8 SSA countries, to better understand barriers to improving access to malaria confirmatory testing in the public and private health sectors.

RESULTS: Repeated national cross-sectional quantitative surveys were conducted …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Ann N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Collected Faculty and Staff Scholarship

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisininbased combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nucleasebased gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC90) or 50% parasite killing (50% lethal dose [LD50]). This mutation also reversed Dd2-mediated CQ …