Parasitic Diseases Commons^™

Private Sector Opportunities And Threats To Achieving Malaria Elimination In The Greater Mekong Subregion: Results From Malaria Outlet Surveys In Cambodia, The Lao Pdr, Myanmar, And Thailand., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Sochea Phok, Saysana Phanalasy, Si Thu Thein, Asawin Likhitsup

Collected Faculty Scholarship

BACKGROUND: The aim of this paper is to review multi-country evidence of private sector adherence to national regulations, guidelines, and quality-assurance standards for malaria case management and to document current coverage of private sector engagement and support through ACTwatch outlet surveys implemented in 2015 and 2016.

RESULTS: Over 76,168 outlets were screened, and approximately 6500 interviews were conducted (Cambodia, N = 1303; the Lao People's Democratic Republic (PDR), N = 724; Myanmar, N = 4395; and Thailand, N = 74). There was diversity in the types of private sector outlets providing malaria treatment across countries, and the extent to which …

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, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based 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 …

The Malaria Testing And Treatment Landscape In Benin., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Cyprien Zinsou, Adjibabi Bello Cherifath

Collected Faculty Scholarship

BACKGROUND: Since 2004, artemisinin-based combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Benin. In 2016, a medicine outlet survey was implemented to investigate the availability, price, and market share of anti-malarial treatment and malaria diagnostics. Results provide a timely and important benchmark to measure future interventions aimed at increasing access to quality malaria case management services.

METHODS: Between July 5th to August 6th 2016, a cross sectional, nationally-representative malaria outlet survey was conducted in Benin. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was implemented among 30 clusters …

Anti-Malarial Landscape In Myanmar: Results From A Nationally Representative Survey Among Community Health Workers And The Private Sector Outlets In 2015/2016., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Si Thu Thein, Hnin Su Su Khin, Aung Thi

Collected Faculty Scholarship

BACKGROUND: In 2015/2016, an ACTwatch outlet survey was implemented to assess the anti-malarial and malaria testing landscape in Myanmar across four domains (Eastern, Central, Coastal, Western regions). Indicators provide an important benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by 2030.

METHODS: This was a cross-sectional survey, which employed stratified cluster-random sampling across four regions in Myanmar. A census of community health workers (CHWs) and private outlets with potential to distribute malaria testing and/or treatment was conducted. An audit was completed for all anti-malarials, malaria rapid diagnostic tests.

RESULTS: A total of 28,664 outlets were approached and …

Insights Into The Availability And Distribution Of Oral Artemisinin Monotherapy In Myanmar: Evidence From A Nationally Representative Outlet Survey., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Si Thu Thein, Hnin Su Su Khin, Aung Thi

Collected Faculty Scholarship

BACKGROUND: The containment of artemisinin resistance in Myanmar, historically an important probable origin and route of anti-malarial resistance to the India sub-continent and beyond, is crucial to global malaria control and elimination. This paper describes what is currently known about the sale and distribution of oral artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly found.

METHODS: A nationally representative 2015 outlet survey was conducted in the private sector, and among community health workers across four geographical domains. A national sample of outlets was screened for availability of malaria testing and treatment, and an audit was completed for all …

What Happened To Anti-Malarial Markets After The Affordable Medicines Facility-Malaria Pilot? Trends In Act Availability, Price And Market Share From Five African Countries Under Continuation Of The Private Sector Co-Payment Mechanism., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Sarah Tougher, Kara Hanson, Catherine Goodman

Collected Faculty Scholarship

BACKGROUND: The private sector supplies anti-malarial treatment for large proportions of patients in sub-Saharan Africa. Following the large-scale piloting of the Affordable Medicines Facility-malaria (AMFm) from 2010 to 2011, a private sector co-payment mechanism (CPM) provided continuation of private sector subsidies for quality-assured artemisinin combination therapies (QAACT). This article analyses for the first time the extent to which improvements in private sector QAACT supply and distribution observed during the AMFm were maintained or intensified during continuation of the CPM through 2015 in Kenya, Madagascar, Nigeria, Tanzania and Uganda using repeat cross-sectional outlet survey data.

RESULTS: QAACT market share in all …

Evidence On Anti-Malarial And Diagnostic Markets In Cambodia To Guide Malaria Elimination Strategies And Policies, Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Sochea Phok, Dysoley Lek

Collected Faculty Scholarship

BACKGROUND: Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities.

METHODS: From August 17th to October 1st, 2015, a cross sectional, nationally-representative malaria outlet survey was conducted in Cambodia. A census of all …

The Malaria Testing And Treatment Landscape In Mainland Tanzania, 2016., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Daniel Michael, Sigsbert Patila Mkunde

Collected Faculty Scholarship

BACKGROUND: Understanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and …

Sudan : Malaria, Olivia Jilek

Global Public Health

Sudan faces a great number of public health issues, however one of the most prevalent diseases within the country is Malaria. An estimated nine million cases were reported in 2002, with the total number of deaths at 44,000, in a country that has a population of 37,345,935. The research done on Malaria in Sudan looks at the basic epidemiology of the region, how to identify the disease, and major risks factors present. Other major challenges that Sudan faces are included, as well as suggestions for preventing further illness from the disease.

Geographically-Weighted Regression Of Knowledge And Behaviour Determinants To Anti-Malarial Recommending And Dispensing Practice Among Medicine Retailers In Western Kenya: Capacitating Targeted Interventions, Andria Rusk, Linda Highfield, J. Michael Wilkerson, Melissa Harrell, Andrew Obala, Benjamin Amick

Collected Faculty Scholarship

Background

Most patients with malaria seek treatment first in retail drug shops. Myriad studies have examined retailer behaviours and characteristics to understand the determinants to these behaviours. Geospatial methods are helpful in discovering if geographic location plays a role in the relationship between determinants and outcomes. This study aimed to discover if spatial autocorrelation exists in the relationship between determinants and retailer behaviours, and to provide specific geographic locations and target behaviours for tailoring future interventions.

Methods

Retailer behaviours and characteristics captured from a survey deployed to medicine retailers in the Webuye Demographic and Health Surveillance Site were analysed using …

Evaluation Of Interleukin-3 In Blood-Stage Immunity Against Murine Malaria Plasmodium Yoelii, Haley E. Davis

Senior Honors Projects, 2010-2019

Malaria is a mosquito-borne infection caused by the parasitic protozoan Plasmodium. This disease infects over 200-300 million people and causes nearly 400,000 deaths every year. Our laboratory previously examined malarial infection caused by Plasmodium berghei NK65, a lethal rodent strain that induces symptoms similar to those observed in humans. The results of this previous study indicated that the hematopoietic growth factor and immunoregulatory cytokine interleukin-3 (IL-3) suppressed protective immunity against infection with P. berghei NK65. However, the extent to which IL-3 contributes to host defense against blood-stage malaria infection caused by other Plasmodium species remains to be determined. In …

Role Of Interleukin-3 In An Experimental Model Of Mouse Cerebral Malaria Caused By Plasmodium Berghei Anka, Brendon R. Perry

Senior Honors Projects, 2010-2019

Malaria is a life-threatening mosquito-borne disease caused by parasites of the genus Plasmodium, with about 200 million new cases reported each year. In rodent models of malaria, a variety of immune proteins called cytokines have been noted to either promote or suppress protective immunity. While the cytokine interleukin-3 (IL-3) clearly promotes host defense against some intestinal nematode parasites, few studies have reported a similar function for IL-3 in the pathophysiology of malaria. In this study, we investigated the role of IL-3 in a mouse model of cerebral malaria caused by Plasmodium berghei ANKA. We infected wild-type (WT) and IL-3 …

Expression Of Complement And Toll-Like Receptor Pathway Genes Is Associated With Malaria Severity In Mali: A Pilot Case Control Study, Rafal S. Sobota, Antoine Dara, Jessica E. Manning, Amadou Niangaly

Dartmouth Scholarship

Background: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.

Methods: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression …

Lack Of Resistance Of Plasmodium Falciparum To Dihydroartemisinin In Uganda Based On Parasitogolgical And Molecular Assays, Roland A. Cooper, Melissa D. Conrad, Quentin D. Watson, Stephanie J. Huezo, Harriet Ninsiima, Patrick Tumwebaze, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty Scholarship

• Artemisinin-­‐based combination therapy is now standard treatment for falciparum malaria. However, this regimen is threatened by resistance to artemisinins, manifest as delayed clearance of parasitemia after therapy, in southeast Asia.

• Artemisinin resistance in southeast Asia is associated with increased parasitemias in culture, compared to those in sensi0ve parasites, 72 hours a=er a 6 hour pulse with 700 nM dihydroartemisinin (DHA), and with propeller domain polymorphisms in the Plasmodium falciparum kelch (K13; PF3D7_1343700) gene

• Given that artemether/lumefantrine has been adopted as standard therapy for malaria within the last decade in Uganda, we characterized artemisinin sensiBvity in fresh P. falciparum isolates from …

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Impact Of Antimalarial Treatment And Chemoprevention On The Drug Sensitivity Of Malaria Parasites Isolated From Ugandan Children, Patrick Tumwebaze, Melissa D. Conrad, Andrew Walakira, Norbert Leclair, Oswald Byaruhanga, Christine Nakazibwe, Benjamin Kozak, Jessica Bloome, Jaffer Okiring, Abel Kakuru, Victor Bigira, James Kapisi, Jennifer Legac, Jiri Gut, Roland A. Cooper, Moses R. Kamya, Diane V. Havlir, Grant Dorsey, Bryan Greenhouse, Samuel L. Nsobya, Philip J. Rosenthal

Collected Faculty Scholarship

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. …

Slavery, Agriculture, And Malaria In The Arabian Peninsula, Benjamin Reilly

Ohio University Press Open Access Books

In Slavery, Agriculture, and Malaria in the Arabian Peninsula, Benjamin Reilly illuminates a previously unstudied phenomenon: the large-scale employment of people of African ancestry as slaves in agricultural oases within the Arabian Peninsula. The key to understanding this unusual system, Reilly argues, is the prevalence of malaria within Arabian Peninsula oases and drainage basins, which rendered agricultural lands in Arabia extremely unhealthy for people without genetic or acquired resistance to malarial fevers. In this way, Arabian slave agriculture had unexpected similarities to slavery as practiced in the Caribbean and Brazil.

This book synthesizes for the first time a body of …

Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott

USF Tampa Graduate Theses and Dissertations

Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …

A Comparison Of Five Malaria Transmission Models: Benchmark Tests And Implications For Disease Control, Dorothy I. Wallace, Ben S. Southworth, Xun Shi, Jonathan W. Chipman, Andrew K. Githeko

Dartmouth Scholarship

Background: Models for malaria transmission are usually compared based on the quantities tracked, the form taken by each term in the equations, and the qualitative properties of the systems at equilibrium. Here five models are compared in detail in order to develop a set of performance measures that further illuminate the differences among models.

Methods: Five models of malaria transmission are compared. Parameters are adjusted to correspond to similar biological quantities across models. Nine choices of parameter sets/initial conditions are tested for all five models. The relationship between malaria incidence in humans and (1) malaria incidence in vectors, (2) man-biting …

Malaria: The Story Of Struggle, Suffering, And Eradication, Stevey Willey

Honors Projects

Every year over two million men, women, and children around the world are affected by malaria, a disease that can easily be prevented with awareness, education, and support. In April 2014 I held a malaria event in which guests had the opportunity to witness the effects malaria has on people, not just physically, but emotionally and economically as well. The death rate has moved from one person every 30 seconds to one every 60 seconds since 2010. The improvement in the rate of deaths has resulted from the increase in awareness of this disease. It is my goal with this …

Expanding Access To Malaria Diagnosis Through Retail Shops In Western Kenya: What Do Shop Workers Think?, Andria Rusk, Catherine Goodman, Violet Naanyu, Beatrice Koech, Andrew Obala, Wendy Prudhomme O'Meara

Collected Faculty Scholarship

Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, …

Automated Point-Of-Care Image Processing Methodology For The Diagnosis Of Malaria, Michael B. Jorgensen

Master's Theses

Malaria has profoundly influenced human history for over four thousand years and despite numerous attempts at eradication, the prevention, diagnosis, and treatment of malaria have been largely ineffective. More than five hundred million people are affected by malaria every year resulting in over one million deaths. Drug resistance development by the parasite has diminished the effectiveness of numerous treatment options due, in part, to overtreatment of negative patients based on insufficient clinical algorithms and diagnostic methods. The goal of this research was to develop an image analysis algorithm to diagnose malaria with a high degree of sensitivity and specificity in …

Mutation In The Plasmodium Falciparum Crt Protein Determines The Stereospecific Activity Of Antimalarial Cinchona Alkaloids, Carol E. Griffin, Jonathan M. Hoke, Upeka Samarakoon, Junhui Duan, Jianbing Mu, Michael T. Ferdig, David C. Warhurst, Roland Cooper

Collected Faculty Scholarship

The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in vitro susceptibility …

Preventive Zinc Supplementation In Developing Countries: Impact On Mortality And Morbidity Due To Diarrhea, Pneumonia And Malaria, Mohammad Yawar Yakoob, Evropi Theodoratou, Afshan Jabeen, Aamer Imdad, Thomas P. Eisele, Joy Ferguson, Arnoupe Jhass, Igor Rudan, Harry Campbell, Robert E. Black, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. Data sources/review methods: A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 …

Chloroquine Susceptibility And Reversibility In A Plasmodium Falciparum Genetic Cross, Jigar J. Patel, Drew Thacker, Jon C. Tan, Perri Pleeter, Lisa Checkley, Joseph M. Gonzales, Bingbing Deng, Paul D. Roepe, Roland A. Cooper, Michael T. Ferdig

Collected Faculty Scholarship

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT), are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 × Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the Southeast Asiaderived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute with the …

Inhibition Of Yeast Hexokinase By The Antimalarial Drug Artemisinin: Probing Mechanism Of Action With A Model Enzyme, Jennifer S. Spence

Biological Sciences Theses & Dissertations

A leading infectious cause of death, malaria threatens approximately half of the world's population, and drug-resistant strains of Plasmodium falciparum have created immense difficulty in chemotherapy of the disease. The artemisinin (ART) class of antimalarials may represent a powerful solution. In addition to their safety, effectiveness, and moderate cost, they are the only drugs in use for which there has been no widespread evidence of clinical resistance. The exact parasiticidal mechanism of ART is highly contested, but evidence suggests that protein alkylation may play a role in cytotoxicity. in vitro essays were performed using yeast hexokinase (HK) to demonstrate a …

Evaluation Of The Efficacy Of Chloroplast-Derived Antigensagainst Malaria, Melissa Schreiber

Electronic Theses and Dissertations

Malaria is the most prevalent vector-borne parasitic disease worldwide and a major cause of death from infections. There is a great need to develop a low cost vaccine for malaria to control transmission of infection and impact of disease, due to the emergence of anti-malarial resistance. Two leading blood stage malarial vaccine candidates are the apical membrane antigen-1 (AMA-1) and the merozoite surface protein-1 (MSP-1). The aim of this project is to express malarial antigens in tobacco plants via plastid transformation and deliver them by subcutaneous or oral gavage of minimally processed transplastomic tissue to evaluate their efficacy to elicit …

Dr. Nott's Theory Of Insect Causation Of Disease, William A. Riley

Harold W. Manter Laboratory of Parasitology: Library Materials

Excerpt:

The danger in using isolated sentences from an article as a basis for interpreting the author's theories, is generally recognized, but sometimes the most careful workers fall into the trap. Once the mistaken interpretation is published, it may be copied over and over again until it rises to the dignity of a dogma.

A striking illustration is afforded by the practical unanimity with which writers on the subject of insects and disease credit Dr. Josiah Nott with being the earliest to formulate definitely the theory of mosquito transmission of yellow fever.

Nuttall, in his classic monograph On the Role …