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1. Evidence for a role of Anopheles stephensi in the spread of drug and diagnosis-resistant malaria in Africa
Anopheles stephensi, an Asian malaria vector, continues to expand across Africa. The vector is now firmly established in urban settings in the Horn of Africa. Its presence in areas where malaria resurged suggested a possible role in causing malaria outbreaks. Using a prospective case control design, we investigated the role of An. stephensi in transmission following a malaria outbreak in Dire Dawa, Ethiopia in April-July 2022. Screening contacts of malaria patients and febrile controls revealed ... [+]
2023 - Nature MedicineTadele Emiru, Dejene Getachew, Maxwell Murphy, Luigi Sedda, Legesse Alamerie Ejigu, Mikiyas Gebremichael Bulto, Isabel Byrne, Mulugeta Demisse, Melat Abdo, Wakweya Chali, Aaron Elliott, Eric Neubauer Vickers, Andrés Aranda-Díaz, Lina Alemayehu, Sinknesh W. Behaksera, Gutema Jebessa, Hunduma Dinka, Tizita Tsegaye, Hiwot Teka, Sheleme Chibsa, Peter Mumba, Samuel Girma, Jimee Hwang, Melissa Yoshimizu, Alice Sutcliffe, Hiwot Solomon Taffese, Gudissa Aseffa Bayissa, Sarah Zohdy, Jon Eric Tongren, Chris Drakeley, Bryan Greenhouse, Teun Bousema, Fitsum G. Tadesse2. MOIRE: A software package for the estimation of allele frequencies and effective multiplicity of infection from polyallelic data
Malaria parasite genetic data can provide insight into parasite phenotypes, evolution, and transmission. However, estimating key parameters such as allele frequencies, multiplicity of infection (MOI), and within-host relatedness from genetic data has been challenging, particularly in the presence of multiple related coinfecting strains. Existing methods often rely on single nucleotide polymorphism (SNP) data and do not account for within-host relatedness. In this study, we introduce a Bayesian a... [+]
2023 - bioRxivMaxwell Murphy, Bryan Greenhouse3. Inferring person-to-person networks of plasmodium falciparum transmission: are analyses of routine surveillance data up to the task?
Inference of person-to-person transmission networks using surveillance data is increasingly used to estimate spatiotemporal patterns of pathogen transmission. Several data types can be used to inform transmission network inferences, yet the sensitivity of those inferences to different data types is not routinely evaluated.
2022 - Malaria JournalJohn H. Huber, Michelle S. Hsiang, Nomcebo Dlamini, Maxwell Murphy, Sibonakaliso Vilakati, Nomcebo Nhlabathi, Anita Lerch, Rasmus Nielsen, Nyasatu Ntshalintshali, Bryan Greenhouse, T. Alex Perkins4. Association between indoor residual spraying and pregnancy outcomes: a quasi-experimental study from Uganda
Malaria is a risk factor for adverse pregnancy outcomes. Indoor residual spraying with insecticide (IRS) reduces malaria infections, yet the effects of IRS on pregnancy outcomes are not well established. We evaluated the impact of a large-scale IRS campaign on pregnancy outcomes in Eastern Uganda.Birth records (n=59992) were obtained from routine surveillance data at 25 health facilities from five districts that were part of the IRS campaign and six neighbouring control districts ∼27 months befo... [+]
2022 - International Journal of EpidemiologyMichelle E Roh, Arthur Mpimbaza, Brenda Oundo, Amanda Irish, Maxwell Murphy, Sean L Wu, Justin S White, Stephen Shiboski, M Maria Glymour, Roly Gosling, Grant Dorsey, Hugh Sturrock5. Sensitive, highly multiplexed sequencing of microhaplotypes from the plasmodium falciparum heterozygome
Targeted next-generation sequencing offers the potential for consistent, deep coverage of information-rich genomic regions to characterize polyclonal Plasmodium falciparum infections. However, methods to identify and sequence these genomic regions are currently limited.A bioinformatic pipeline and multiplex methods were developed to identify and simultaneously sequence 100 targets and applied to dried blood spot (DBS) controls and field isolates from Mozambique. For comparison, whole-genome sequ... [+]
2022 - The Journal of Infectious DiseasesSofonias K Tessema, Nicholas J Hathaway, Noam B Teyssier, Maxwell Murphy, Anna Chen, Ozkan Aydemir, Elias M Duarte, Wilson Simone, James Colborn, Francisco Saute, Emily Crawford, Pedro Aide, Jeffrey A Bailey, Bryan Greenhouse6. Within‐household clustering of genetically related plasmodium falciparum infections in a moderate transmission area of Uganda
Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rat... [+]
2021 - Malaria JournalJessica Briggs, Alison Kuchta, Max Murphy, Sofonias Tessema, Emmanuel Arinaitwe, John Rek, Anna Chen, Joaniter I. Nankabirwa, Chris Drakeley, David Smith, Teun Bousema, Moses Kamya, Isabel Rodriguez-Barraquer, Sarah Staedke, Grant Dorsey, Philip J. Rosenthal, Bryan Greenhouse7. Assessment of plasmodium antigens and CRP in dried blood spots with multiplex malaria array
Dried blood spots (DBS) typically prepared on filter papers are an ideal sample type for malaria surveillance by offering easy and cost-effective methods in terms of sample collection, storage, and transport. The objective of this study was to evaluate the applicability of DBS with a commercial multiplex malaria assay, developed to concurrently measure Plasmodium antigens, histidine-rich protein 2 (HRP2), Plasmodium lactate dehydrogenase (pLDH), and a host inflammatory biomarker, C-reactive prot... [+]
2021 - Journal of Parasitic DiseasesIhn Kyung Jang, Sara Aranda, Rebecca Barney, Andrew Rashid, Muhammad Helwany, John C. Rek, Emmanuel Arinaitwe, Harriet Adrama, Maxwell Murphy, Mallika Imwong, Stephane Proux, Warat Haohankhunnatham, Xavier C. Ding, François Nosten, Bryan Greenhouse, Dionicia Gamboa, Gonzalo J. Domingo8. Active case finding for malaria: a 3-year national evaluation of optimal approaches to detect infections and hotspots through reactive case detection in the low-transmission setting of Eswatini
BACKGROUND: Reactive case detection (RACD) is a widely practiced malaria elimination intervention whereby close contacts of index cases receive malaria testing to inform treatment and other interventions. However, the optimal diagnostic and operational approaches for this resource-intensive strategy are not clear.
METHODS: We conducted a 3-year prospective national evaluation of RACD in Eswatini, a malaria elimination setting. Loop-mediated isothermal amplification (LAMP) was compared to traditi... [+]
2020 - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of AmericaMichelle S. Hsiang, Nyasatu Ntshalintshali, Mi-Suk Kang Dufour, Nomcebo Dlamini, Nomcebo Nhlabathi, Sibonakaliso Vilakati, Calsile Malambe, Zulisile Zulu, Gugu Maphalala, Joseph Novotny, Maxwell Murphy, Alanna Schwartz, Hugh Sturrock, Roly Gosling, Grant Dorsey, Simon Kunene, Bryan Greenhouse9. Multiplex human malaria array: quantifying antigens for malaria rapid diagnostics
Malaria antigen detection through rapid diagnostic tests (RDTs) is widely used to diagnose malaria and estimate prevalence. To support more sensitive next-generation RDT development and screen asymptomatic malaria, we developed and evaluated the Q-Plex™ Human Malaria Array (Quansys Biosciences, Logan, UT), which quantifies the antigens commonly used in RDTs—Plasmodium falciparum–specific histidine-rich protein 2 (HRP2), P. falciparum-specific lactate dehydrogenase (Pf LDH), Plasmodium vivax–spec... [+]
2020 - The American Journal of Tropical Medicine and HygieneIhn Kyung Jang, Abby Tyler, Chris Lyman, John C. Rek, Emmanuel Arinaitwe, Harriet Adrama, Maxwell Murphy, Mallika Imwong, Stephane Proux, Warat Haohankhunnatham, Rebecca Barney, Andrew Rashid, Michael Kalnoky, Maria Kahn, Allison Golden, François Nosten, Bryan Greenhouse, Dionicia Gamboa, Gonzalo J. Domingo10. Confirmation of the absence of local transmission and geographic assignment of imported falciparum malaria cases to china using microsatellite panel
Current methods to classify local and imported malaria infections depend primarily on patient travel history, which can have limited accuracy. Genotyping has been investigated as a complementary approach to track the spread of malaria and identify the origin of imported infections.
2020 - Malaria JournalYaobao Liu, Sofonias K. Tessema, Maxwell Murphy, Sui Xu, Alanna Schwartz, Weiming Wang, Yuanyuan Cao, Feng Lu, Jianxia Tang, Yaping Gu, Guoding Zhu, Huayun Zhou, Qi Gao, Rui Huang, Jun Cao, Bryan Greenhouse11. Simultaneous quantification of plasmodium antigens and host factor C-reactive protein in asymptomatic individuals with confirmed malaria by use of a novel multiplex immunoassay
Malaria rapid diagnostic tests (RDTs) primarily detect Plasmodium falciparum antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for P. vivax and other malaria species. The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens. A multiplexed immunoassay for the quantification... [+]
2019 - Journal of Clinical MicrobiologyIhn Kyung Jang, Abby Tyler, Chris Lyman, Maria Kahn, Michael Kalnoky, John C. Rek, Emmanuel Arinaitwe, Harriet Adrama, Maxwell Murphy, Mallika Imwong, Clare L. Ling, Stephane Proux, Warat Haohankhunnatham, Melissa Rist, Annette M. Seilie, Amelia Hanron, Glenda Daza, Ming Chang, Smita Das, Rebecca Barney, Andrew Rashid, Jordi Landier, David S. Boyle, Sean C. Murphy, James S. McCarthy, François Nosten, Bryan Greenhouse, Gonzalo J. Domingo12. Genetic evidence of focal plasmodium falciparum transmission in a pre-elimination setting in Southern Province, Zambia
BACKGROUND: Southern Province, Zambia has experienced a dramatic decline in Plasmodium falciparum malaria transmission in the past decade and is targeted for elimination. Zambia's National Malaria Elimination Program recommends reactive case detection (RCD) within 140 m of index households to enhance surveillance and eliminate remaining transmission foci.
METHODS: To evaluate whether RCD captures local transmission, we genotyped 26 microsatellites from 106 samples collected from index (n = 27) a... [+]
2019 - The Journal of Infectious DiseasesJulia C. Pringle, Sofonias Tessema, Amy Wesolowski, Anna Chen, Maxwell Murphy, Giovanna Carpi, Timothy M. Shields, Harry Hamapumbu, Kelly M. Searle, Tamaki Kobayashi, Ben Katowa, Michael Musonda, Jennifer C. Stevenson, Philip E. Thuma, Bryan Greenhouse, William J. Moss, Douglas E. Norris13. FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences
The growing prevalence of deadly microbes with resistance to previously life-saving drug therapies is a dire threat to human health. Detection of low abundance pathogen sequences remains a challenge for metagenomic Next Generation Sequencing (NGS). We introduce FLASH (Finding Low Abundance Sequences by Hybridization), a next-generation CRISPR/Cas9 diagnostic method that takes advantage of the efficiency, specificity and flexibility of Cas9 to enrich for a programmed set of sequences. FLASH-NGS a... [+]
2019 - Nucleic Acids ResearchJenai Quan, Charles Langelier, Alison Kuchta, Joshua Batson, Noam Teyssier, Amy Lyden, Saharai Caldera, Aaron McGeever, Boris Dimitrov, Ryan King, Jordan Wilheim, Maxwell Murphy, Lara Pesce Ares, Katherine A Travisano, Rene Sit, Roberto Amato, Davis R Mumbengegwi, Jennifer L Smith, Adam Bennett, Roly Gosling, Peter M Mourani, Carolyn S Calfee, Norma F Neff, Eric D Chow, Peter S Kim, Bryan Greenhouse, Joseph L DeRisi, Emily D Crawford14. High genetic diversity of plasmodium falciparum in the low-transmission setting of the kingdom of Eswatini
In contrast to the commonly held perception that P. falciparum diversity declines with decreasing transmission intensity, infections from Eswatini exhibited high parasite diversity consistent with high rates of malaria importation and limited local transmission.
2019 - The Journal of Infectious DiseasesMichelle E Roh, Sofonias K Tessema, Maxwell Murphy, Nomcebo Nhlabathi, Nomcebo Mkhonta, Sibonakaliso Vilakati, Nyasatu Ntshalintshali, Manik Saini, Gugu Maphalala, Anna Chen, Jordan Wilheim, Lisa Prach, Roly Gosling, Simon Kunene, Michelle S. Hsiang, Bryan Greenhouse15. Using parasite genetic and human mobility data to infer local and cross-border malaria connectivity in Southern Africa
Local and cross-border importation remain major challenges to malaria elimination and are difficult to measure using traditional surveillance data. To address this challenge, we systematically collected parasite genetic data and travel history from thousands of malaria cases across northeastern Namibia and estimated human mobility from mobile phone data. We observed strong fine-scale spatial structure in local parasite populations, providing positive evidence that the majority of cases were due ... [+]
2019 - eLifeSofonias Tessema, Amy Wesolowski, Anna Chen, Maxwell Murphy, Jordan Wilheim, Anna-Rosa Mupiri, Nick W Ruktanonchai, Victor A Alegana, Andrew J Tatem, Munyaradzi Tambo, Bradley Didier, Justin M Cohen, Adam Bennett, Hugh JW Sturrock, Roland Gosling, Michelle S Hsiang, David L Smith, Davis R Mumbengegwi, Jennifer L Smith, Bryan Greenhouse, Ben Cooper, Neil M Ferguson, Samir Bhatt, Thomas S Churcher16. Safety of single-dose primaquine in G6PD-deficient and G6PD-normal males in mali without malaria: an open-label, phase 1, dose-adjustment trial
Background: The World Health Organization recommendation on the use of a single low dose of primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data.
Methods: We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11-17 years and those aged 5-10 years, including ... [+]
2018 - The Journal of Infectious DiseasesIngrid Chen, Halimatou Diawara, Almahamoudou Mahamar, Koualy Sanogo, Sekouba Keita, Daouda Kone, Kalifa Diarra, Moussa Djimde, Mohamed Keita, Joelle Brown, Michelle E. Roh, Jimee Hwang, Helmi Pett, Maxwell Murphy, Mikko Niemi, Bryan Greenhouse, Teun Bousema, Roly Gosling, Alassane Dicko17. Laboratory challenges of plasmodium species identification in Aceh Province, Indonesia, a malaria elimination setting with newly discovered P. knowlesi
The discovery of the life-threatening zoonotic infection Plasmodium knowlesi has added to the challenges of prompt and accurate malaria diagnosis and surveillance. In this study from Aceh Province, Indonesia, a malaria elimination setting where P. knowlesi endemicity was not previously known, we report the laboratory investigation and difficulties encountered when using molecular detection methods for quality assurance of microscopically identified clinical cases. From 2014 to 2015, 20 (49%) P. ... [+]
2018 - PLoS neglected tropical diseasesFarah N. Coutrier, Yusrifar K. Tirta, Chris Cotter, Iska Zarlinda, Iveth J. González, Alanna Schwartz, Cut Maneh, Jutta Marfurt, Maxwell Murphy, Herdiana Herdiana, Nicholas M. Anstey, Bryan Greenhouse, Michelle S. Hsiang, Rintis Noviyanti18. A new highly sensitive enzyme-linked immunosorbent assay for the detection of plasmodium falciparum histidine-rich protein 2 in whole blood
The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensiti... [+]
2018 - Malaria JournalIhn Kyung Jang, Smita Das, Rebecca S. Barney, Roger B. Peck, Andrew Rashid, Stephane Proux, Emmanuel Arinaitwe, John Rek, Maxwell Murphy, Katherine Bowers, Samuel Boadi, Julie Watson, Francois Nosten, Bryan Greenhouse, Peter L. Chiodini, Gonzalo J. Domingo19. Subpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia
Subpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized.
2018 - Malaria JournalPatrick McCreesh, Davis Mumbengegwi, Kathryn Roberts, Munyaradzi Tambo, Jennifer Smith, Brooke Whittemore, Gerard Kelly, Caitlin Moe, Max Murphy, Mukosha Chisenga, Bryan Greenhouse, Henry Ntuku, Immo Kleinschmidt, Hugh Sturrock, Petrina Uusiku, Roland Gosling, Adam Bennett, Michelle S. Hsiang20. Antibody profiling by proteome microarray with multiplex isotype detection reveals overlap between human and aotus nancymaae controlled malaria infections
The development of vaccines against malaria and serodiagnostic tests for detecting recent exposure requires tools for antigen discovery and suitable animal models. The protein microarray is a high-throughput, sample sparing technique, with applications in infectious disease research, clinical diagnostics, epidemiology, and vaccine development. We recently demonstrated Qdot-based indirect immunofluorescence together with portable optical imager ArrayCAM using single isotype detection could replic... [+]
2018 - ProteomicsOmid Taghavian, Aarti Jain, Chester J. Joyner, Sunny Ketchum, Rie Nakajima, Algis Jasinskas, Li Liang, Rich Fong, Christopher King, Bryan Greenhouse, Maxwell Murphy, Jason Bailey, Mary R. Galinski, John W. Barnwell, Christopher V. Plowe, D. Huw Davies, Philip L. Felgner21. THE REAL McCOIL: a method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites
As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous me... [+]
2017 - PLOS Computational BiologyHsiao-Han Chang, Colin J. Worby, Adoke Yeka, Joaniter Nankabirwa, Moses R. Kamya, Sarah G. Staedke, Grant Dorsey, Maxwell Murphy, Daniel E. Neafsey, Anna E. Jeffreys, Christina Hubbart, Kirk A. Rockett, Roberto Amato, Dominic P. Kwiatkowski, Caroline O. Buckee, Bryan Greenhouse22. Performance of a high-sensitivity rapid diagnostic test for plasmodium falciparum malaria in asymptomatic individuals from Uganda and Myanmar and naive human challenge infections
Sensitive field-deployable diagnostic tests can assist malaria programs in achieving elimination. The performance of a new Alere™ Malaria Ag P.f Ultra Sensitive rapid diagnostic test (uRDT) was compared with the currently available SD Bioline Malaria Ag P.f RDT in blood specimens from asymptomatic individuals in Nagongera, Uganda, and in a Karen Village, Myanmar, representative of high- and low-transmission areas, respectively, as well as in pretreatment specimens from study participants from fo... [+]
2017 - The American Journal of Tropical Medicine and HygieneSmita Das, Ihn Kyung Jang, Becky Barney, Roger Peck, John C. Rek, Emmanuel Arinaitwe, Harriet Adrama, Maxwell Murphy, Mallika Imwong, Clare L. Ling, Stephane Proux, Warat Haohankhunnatham, Melissa Rist, Annette M. Seilie, Amelia Hanron, Glenda Daza, Ming Chang, Tomoka Nakamura, Michael Kalnoky, Paul Labarre, Sean C. Murphy, James S. McCarthy, Francois Nosten, Bryan Greenhouse, Sophie Allauzen, Gonzalo J. Domingo23. Performance of loop-mediated isothermal amplification for the identification of submicroscopic plasmodium falciparum infection in Uganda
Accurately identifying and targeting the human reservoir of malaria parasitemia is critical for malaria control, and requires a reliable and sensitive diagnostic method. Loop-mediated isothermal amplification (LAMP) is increasingly used to diagnose submicroscopic parasitemia. Although most published studies report the sensitivity of LAMP compared with nested polymerase chain reaction (PCR) as ≥ 80%, they have failed to use a consistent, sensitive diagnostic as a comparator. We used cross-section... [+]
2017 - The American Journal of Tropical Medicine and HygieneShereen Katrak, Maxwell Murphy, Patience Nayebare, John Rek, Mary Smith, Emmanuel Arinaitwe, Joaniter I. Nankabirwa, Moses Kamya, Grant Dorsey, Philip J. Rosenthal, Bryan Greenhouse24. Limitations of rapid diagnostic testing in patients with suspected malaria: a diagnostic accuracy evaluation from Swaziland, a low-endemicity country aiming for malaria elimination
Background: The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized.
Methods: Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (... [+]
2017 - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of AmericaNikhil Ranadive, Simon Kunene, Sarah Darteh, Nyasatu Ntshalintshali, Nomcebo Nhlabathi, Nomcebo Dlamini, Stanley Chitundu, Manik Saini, Maxwell Murphy, Adam Soble, Alanna Schwartz, Bryan Greenhouse, Michelle S. Hsiang