Potential #impact of the #COVID19 pandemic on #HIV, #tuberculosis, and #malaria in low-income and middle-income countries: a modelling study (Lancet Glob Health, abstract)

[Source: Lancet Global Health, full page: (LINK). Abstract, edited.]

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study

Alexandra B Hogan, PhD †, Britta L Jewell, PhD †, Ellie Sherrard-Smith, PhD †, Juan F Vesga, PhD †, Oliver J Watson, PhD †, Charles Whittaker, MSc †, Arran Hamlet, PhD, Jennifer A Smith, DPhil, Peter Winskill, PhD, Robert Verity, PhD, Marc Baguelin, PhD, John A Lees, PhD, Lilith K Whittles, PhD, Kylie E C Ainslie, PhD, Samir Bhatt, DPhil, Adhiratha Boonyasiri, MD, Nicholas F Brazeau, PhD, Lorenzo Cattarino, PhD, Laura V Cooper, MPhil, Helen Coupland, MRes, Gina Cuomo-Dannenburg, MMath, Amy Dighe, MRes, Bimandra A Djaafara, MRes, Prof Christl A Donnelly, ScD, Jeff W Eaton, PhD, Sabine L van Elsland, PhD, Richard G FitzJohn, PhD, Han Fu, PhD, Katy A M Gaythorpe, PhD, William Green, MRes, David J Haw, PhD, Sarah Hayes, MSc, Wes Hinsley, PhD, Natsuko Imai, PhD, Daniel J Laydon, PhD, Tara D Mangal, PhD, Thomas A Mellan, PhD, Swapnil Mishra, PhD, Gemma Nedjati-Gilani, PhD, Kris V Parag, PhD, Hayley A Thompson, MPH, H Juliette T Unwin, PhD, Michaela A C Vollmer, PhD, Caroline E Walters, PhD, Haowei Wang, MSc, Yuanrong Wang, Xiaoyue Xi, MSc, Prof Neil M Ferguson, DPhil, Lucy C Okell, PhD, Thomas S Churcher, PhD, Nimalan Arinaminpathy, DPhil, Prof Azra C Ghani, PhD, Patrick G T Walker, PhD, Prof Timothy B Hallett, PhD

Open Access | Published: July 13, 2020 | DOI: https://doi.org/10.1016/S2214-109X(20)30288-6




COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years.


Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic.


In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics.


Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic.


Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Keywords: SARS-CoV-2; COVID-19; HIV/AIDS; Tuberculosis; Malaria.


#Preparedness is essential for #malaria-endemic #regions during the #COVID19 #pandemic (Lancet, summary)

[Source: The Lancet, full page: (LINK). Summary, edited.]

Preparedness is essential for malaria-endemic regions during the COVID-19 pandemic

Jigang Wang, Chengchao Xu, Yin Kwan Wong, Yingke He, Ayôla A Adegnika, Peter G Kremsner, Selidji T Agnandji, Amadou A Sall, Zhen Liang, Chen Qiu, Fu Long Liao, Tingliang Jiang, Sanjeev Krishna, Youyou Tu

Published: March 16, 2020 / DOI: https://doi.org/10.1016/S0140-6736(20)30561-4


The coronavirus disease 2019 (COVID-19) pandemic that first emerged in Wuhan in China’s Hubei province1 has quickly spread to the rest of China and many other countries. Within 3 months, more than 125 000 people have been infected and the death toll had reached over 4600 worldwide on March 12, 2020.2 In an attempt to contain the virus, the Chinese Government has made unprecedented efforts and invested enormous resources and these containment efforts have stemmed the spread of the disease.3
As of March 12, 2020, malaria-endemic regions in Africa have reported a few imported COVID-19 cases including in Nigeria, Senegal, and the Democratic Republic of the Congo.2



We declare no competing interests.

Keywords: COVID-19; SARS-CoV-2; Malaria; Africa Region.


Exposure to #Ebola Virus and #Risk for #Infection with #Malaria Parasites, Rural #Gabon (Emerg Infect Dis., abstract)

[Source: US Center for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research

Exposure to Ebola Virus and Risk for Infection with Malaria Parasites, Rural Gabon

Jessica L. Abbate  , Pierre Becquart, Eric Leroy, Vanessa O. Ezenwa1, and Benjamin Roche1

Author affiliations: Institut de Recherche pour le Développement, Unité Mixte de Recherche MIVEGEC, Montpellier, France (J.L. Abbate, P. Becquart, E. Leroy, B. Roche); Institut de Recherche pour le Développement, Unité Mixte Internationale UMMISCO, Bondy, France (J.L. Abbate, B. Roche); CIRMF, Franceville, Gabon (E. Leroy); The University of Georgia, Athens, Georgia, USA (V.O. Ezenwa); Universidad National Autonoma de Mexico, Mexico City, Mexico (B. Roche)



An association between malaria and risk for death among patients with Ebola virus disease has suggested within-host interactions between Plasmodium falciparum parasites and Ebola virus. To determine whether such an interaction might also influence the probability of acquiring either infection, we used a large snapshot surveillance study from rural Gabon to test if past exposure to Ebola virus is associated with current infection with Plasmodium spp. during nonepidemic conditions. We found a strong positive association, on population and individual levels, between seropositivity for antibodies against Ebola virus and the presence of Plasmodium parasites in the blood. According to a multiple regression model accounting for other key variables, antibodies against Ebola virus emerged as the strongest individual-level risk factor for acquiring malaria. Our results suggest that within-host interactions between malaria parasites and Ebola virus may underlie epidemiologic associations.

Keywords: Malaria; Ebola; Gabon.


#Amazon #deforestation drives #malaria #transmission, and malaria burden reduces #forest clearing (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Amazon deforestation drives malaria transmission, and malaria burden reduces forest clearing

Andrew J. MacDonald and Erin A. Mordecai

PNAS first published October 14, 2019 / DOI: https://doi.org/10.1073/pnas.1905315116

Edited by Burton H. Singer, University of Florida, Gainesville, FL, and approved September 17, 2019 (received for review March 27, 2019)



Widespread human impacts on the environment are expected to harm human health, which may in turn alter our interactions with the environment. However, evidence for impacts of environmental changes on health, and for feedbacks between environmental change and health, remains locally specific and context dependent. Using a large, geospatial dataset encompassing the Brazilian Amazon rainforest across 13 y, we identify strong evidence for a feedback between deforestation and malaria: Deforestation significantly increases malaria transmission, while high malaria burden simultaneously reduces forest clearing. Our results put into broader context the contradictory effects of deforestation on malaria found in earlier studies and provide evidence useful to land use policy and public health interventions that provide win–win solutions for conservation and health.



Deforestation and land use change are among the most pressing anthropogenic environmental impacts. In Brazil, a resurgence of malaria in recent decades paralleled rapid deforestation and settlement in the Amazon basin, yet evidence of a deforestation-driven increase in malaria remains equivocal. We hypothesize an underlying cause of this ambiguity is that deforestation and malaria influence each other in bidirectional causal relationships—deforestation increases malaria through ecological mechanisms and malaria reduces deforestation through socioeconomic mechanisms—and that the strength of these relationships depends on the stage of land use transformation. We test these hypotheses with a large geospatial dataset encompassing 795 municipalities across 13 y (2003 to 2015) and show deforestation has a strong positive effect on malaria incidence. Our results suggest a 10% increase in deforestation leads to a 3.3% increase in malaria incidence (∼9,980 additional cases associated with 1,567 additional km2 lost in 2008, the study midpoint, Amazon-wide). The effect is larger in the interior and absent in outer Amazonian states where little forest remains. However, this strong effect is only detectable after controlling for a feedback of malaria burden on forest loss, whereby increased malaria burden significantly reduces forest clearing, possibly mediated by human behavior or economic development. We estimate a 1% increase in malaria incidence results in a 1.4% decrease in forest area cleared (∼219 fewer km2 cleared associated with 3,024 additional cases in 2008). This bidirectional socioecological feedback between deforestation and malaria, which attenuates as land use intensifies, illustrates the intimate ties between environmental change and human health.

Brazil – Plasmodium falciparum – Plasmodium vivax – instrumental variables – environmental change



1 To whom correspondence may be addressed. Email: andy.j.macdon@gmail.com.

Author contributions: A.J.M. designed research; A.J.M. performed research; A.J.M. analyzed data; A.J.M. and E.A.M. wrote the paper; and E.A.M. helped in the development of the project.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1905315116/-/DCSupplemental.

Published under the PNAS license.

Keywords: Malaria; Environmental disasters; Brazil.


#Dengue and #chikungunya among outpatients with acute undifferentiated #fever in #Kinshasa, #DRC: A cross-sectional study (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Dengue and chikungunya among outpatients with acute undifferentiated fever in Kinshasa, Democratic Republic of Congo: A cross-sectional study

Sam Proesmans , Freddy Katshongo, John Milambu, Blaise Fungula, Hypolite Muhindo Mavoko, Steve Ahuka-Mundeke, Raquel Inocêncio da Luz, Marjan Van Esbroeck, Kevin K. Ariën, Lieselotte Cnops, Birgit De Smet, Pascal Lutumba, Jean-Pierre Van geertruyden, Veerle Vanlerberghe

Published: September 5, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007047 / This is an uncorrected proof.




Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis.


We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections.


Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue–caused by DENV-1 and/or DENV-2 –and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment.


Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will–ultimately and hopefully–improve the clinical care of outpatients in low-resource settings.

Trial registration ClinicalTrials.gov NCT02656862.


Author summary

Malaria remains one of the most important causes of fever in sub-Saharan Africa. However, its share is declining, since the diagnosis and treatment of malaria have improved significantly over the years. Hence leading to an increase in the number of patients presenting with non-malarial fever. Often, obvious clinical signs and symptoms like cough or diarrhea are absent, probing the question: “What causes the fever?” Previous studies have shown that the burden of arboviral infections–like dengue and chikungunya–in sub-Saharan Africa is underestimated, which is why we screened for four common arboviral infections in patients presenting with ‘undifferentiated fever’ at an outpatient clinic in suburban Kinshasa, Democratic Republic of Congo. Among the patients tested, we found that one in ten presented with an acute arboviral infection and that almost one in three patients had been infected in the past. These findings suggest that clinicians should think about arboviral infections more often, thereby refraining from the prescription of antibiotics, a practice increasingly problematic given the global rise of antimicrobial resistance.


Citation: Proesmans S, Katshongo F, Milambu J, Fungula B, Muhindo Mavoko H, Ahuka-Mundeke S, et al. (2019) Dengue and chikungunya among outpatients with acute undifferentiated fever in Kinshasa, Democratic Republic of Congo: A cross-sectional study. PLoS Negl Trop Dis 13(9): e0007047. https://doi.org/10.1371/journal.pntd.0007047

Editor: Stuart D. Blacksell, Mahidol Univ, Fac Trop Med, THAILAND

Received: November 28, 2018; Accepted: August 6, 2019; Published: September 5, 2019

Copyright: © 2019 Proesmans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This study was co-funded by the framework agreement between the Institute of Tropical Medicine and the Belgian development cooperation (https://www.itg.be/E/cooperation) to VV and Vlaamse Interuniversitaire Raad – Universitaire Ontwikkelingssamenwerking (https://www.vliruos.be/en) (VLIR-UOS, Grant reference ZRDC2014MP083) to JPVG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Arbovirus; Dengue fever; Chikungunya fever; Malaria; Serology; Seroprevalence; DRC.


Emergence of #Plasmodium vivax #resistance to #chloroquine in French #Guiana (Antimicrob Agents Chemother., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Emergence of P. vivax resistance to chloroquine in French Guiana

Lise Musset, Christophe Heugas, Richard Naldjinan, Denis Blanchet, Pascal Houze, Philippe Abboud, Béatrice Volney, Gaëlle Walter, Yassamine Lazrek, Loïc Epelboin, Stephane Pelleau,Pascal Ringwald, Eric Legrand, Magalie Demar, Félix Djossou

DOI: 10.1128/AAC.02116-18



In South America, Plasmodium vivax resistance to chloroquine was recently reported in Brazil and Bolivia. The objective of this study was to collect data on chloroquine resistance in French Guiana by associating a retrospective evaluation of the therapeutic efficacy and an analysis of recurrent parasitemia from any patients.

Patients with P. vivax infection, confirmed by microscopy and temperature ≥37.5°C, were retrospectively identified at Cayenne Hospital between 2009 and 2015. Follow-up and treatment responses were performed according to the World Health Organization protocol. Parasite resistance was confirmed after dosage of plasmatic concentration of chloroquine and microsatellite characterization. The pvmdr1 and pvcrt-o genes were analysed for sequence and gene copy-number variation.

Among the 172 patients followed for 28 days, 164 presented adequate clinical and parasitological responses. Eight cases of treatment failures were identified (4.7%, n=8/172), all after 14 days. The therapeutic efficacy of chloroquine was estimated at 95.3% (95% CI 92.5-98.1, n=164/172). Among the eight failures, five were characterized: two cases were true P. vivax chloroquine resistance (1.2%, 95% CI 0-2.6, n=2/172) and three cases were found with subtherapeutic concentrations of chloroquine. No particular polymorphism in the Plasmodium vivax pvmdr1 and pvcrt-o genes was identified in the resistant parasites.

This identified level of resistance of P. vivax to chloroquine in French Guiana does not require a change in therapeutic recommendations. However, primaquine should be administered more frequently to limit the spread of resistance and there is still a need for a reliable molecular marker to facilitate the monitoring of resistance to chloroquine.

Copyright © 2019 Musset et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Malaria; Plasmodium vivax; Drugs Resistance; Chloroquine; French Guyana.


#Antimalarial #drug #resistance in #Africa: the calm before the storm? (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Antimalarial drug resistance in Africa: the calm before the storm?

Melissa D Conrad, PhD, Prof Philip J Rosenthal, MD

Published: July 30, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30261-0



Antimalarial drug resistance, in particular resistance to Plasmodium falciparum, challenges the treatment and control of malaria. In this Review, we summarise evolving patterns of antimalarial drug resistance in Africa. Resistance to aminoquinolines and antifolates is long-standing, yet with greatly decreased use of chloroquine to treat malaria, the prevalence of resistance to chloroquine has decreased. Resistance to antifolates, which are used to prevent malaria in some settings, remains widespread. Resistance to artemisinin-based combination therapies, the standard treatments for malaria in Africa, has emerged in southeast Asia. At present, resistance to artemisinins or key partner drugs included in combination therapies does not appear to be a substantial problem in Africa. However, emergence of resistance to artemisinin-based combination therapies in Africa would probably have devastating consequences, and continued surveillance for the emergence of resistance on this continent is a high priority.

Keywords: Malaria; Plasmodium falciparum; Drugs Resistance; Artemisin; Chloroquine; Aminoquinolines; Antifolates; Africa region.


Molecular #surveillance of #drug #resistance of #Plasmodium falciparum isolates imported from #Angola in #Henan Province, #China (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Molecular surveillance of drug resistance of Plasmodium falciparum isolates imported from Angola in Henan Province, China

Ruimin Zhou, Chengyun Yang, Suhua Li, Yuling Zhao, Ying Liu, Dan Qian, Hao Wang, Deling Lu, Hongwei Zhang, Fang Huang

DOI: 10.1128/AAC.00552-19



Angola was the main origin country for the imported malaria in Henan Province, China. The antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance such as pfcrt, pfmdr1, pfdhfr, pfdhps and K13. This study will evaluate the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR by Sanger sequencing. The prevalence of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164 and pfdhps S436A437A476K540A581 was 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalence of which was 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of K13 gene was rare. Molecular surveillance of artemisinin-resistance (ART-resistance) will be as a tool to evaluate the real time efficacy of the artemisinin-based combination therapies (ACTs) and the ART-resistance situation as well.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Plasmodium falciparum; Malaria; Drugs Resistance; Artemisin; Angola; Henan; China.


Determinants of dihydro- #artemisinin-piperaquine #treatment #failure in #Plasmodium falciparum #malaria in #Cambodia, #Thailand, and #Vietnam: a prospective clinical, pharmacological, and genetic study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study

Rob W van der Pluijm, MD, Prof Mallika Imwong, PhD, Nguyen Hoang Chau, MD, Nhu Thi Hoa, MD, Nguyen Thanh Thuy-Nhien, PhD, Ngo Viet Thanh, MD, et al.

Open Access / Published: July 22, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30391-3




The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015–18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam. The immediate public health importance of our findings prompted us to report the efficacy data on dihydroartemisinin-piperaquine and its determinants ahead of the results of the overall trial, which will be published later this year.


Patients aged between 2 and 65 years presenting with uncomplicated P falciparum or mixed species malaria at seven sites in Thailand, Cambodia, and Vietnam were randomly assigned to receive dihydroartemisinin-piperaquine with or without mefloquine, as part of the TRACII trial. The primary outcome was the PCR-corrected efficacy at day 42. Next-generation sequencing was used to assess the prevalence of molecular markers associated with artemisinin resistance (kelch13 mutations, in particular Cys580Tyr) and piperaquine resistance (plasmepsin-2 and plasmepsin-3amplifications and crt mutations). This study is registered with ClinicalTrials.gov, number NCT02453308.


Between Sept 28, 2015, and Jan 18, 2018, 539 patients with acute P falciparum malaria were screened for eligibility, 292 were enrolled, and 140 received dihydroartemisinin-piperaquine. The overall Kaplan-Meier estimate of PCR-corrected efficacy of dihydroartemisinin-piperaquine at day 42 was 50·0% (95% CI 41·1–58·3). PCR-corrected efficacies for individual sites were 12·7% (2·2–33·0) in northeastern Thailand, 38·2% (15·9–60·5) in western Cambodia, 73·4% (57·0–84·3) in Ratanakiri (northeastern Cambodia), and 47·1% (33·5–59·6) in Binh Phuoc (southwestern Vietnam). Treatment failure was associated independently with plasmepsin2/3amplification status and four mutations in the crt gene (Thr93Ser, His97Tyr, Phe145Ile, and Ile218Phe). Compared with the results of our previous TRACI trial in 2011–13, the prevalence of molecular markers of artemisinin resistance (kelch13 Cys580Tyr mutations) and piperaquine resistance (plasmepsin2/3 amplifications and crtmutations) has increased substantially in the Greater Mekong subregion in the past decade.


Dihydroartemisinin-piperaquine is not treating malaria effectively across the eastern Greater Mekong subregion. A highly drug-resistant P falciparum co-lineage is evolving, acquiring new resistance mechanisms, and spreading. Accelerated elimination of P falciparum malaria in this region is needed urgently, to prevent further spread and avoid a potential global health emergency.


UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and National Institutes of Health.

Keywords: Malaria; Plasmodium falciparum; Artemisin; Drugs resistance; Thailand; Cambodia; Laos; Vietnam.


#Evolution and #expansion of #MDR #malaria in southeast #Asia: a #genomic #epidemiology study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study

William L Hamilton, PhD †, Roberto Amato, PhD †, Rob W van der Pluijm, MD, Christopher G Jacob, PhD, Huynh Hong Quang, PhD, Nguyen Thanh Thuy-Nhien, PhD, et al.

Open Access / Published: July 22, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30392-5




A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008–13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.


For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project. Previously unpublished samples were provided by two large-scale multisite projects: the Tracking Artemisinin Resistance Collaboration II (TRAC2) and the Genetic Reconnaissance in the Greater Mekong Subregion (GenRe-Mekong) project. By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population.


We analysed 1673 whole genome sequences that passed quality filters, and determined KEL1/PLA1 status in 1615. Before 2009, KEL1/PLA1 was only found in western Cambodia; by 2016–17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos. In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites. KEL1/PLA1 parasites maintained high genetic relatedness and low diversity, reflecting a recent common origin. Several subgroups of highly related parasites have recently emerged within this co-lineage, with diverse geographical distributions. The three largest of these subgroups (n=84, n=79, and n=47) mostly emerged since 2016 and were all present in Cambodia, Laos, and Vietnam. These expanding subgroups carried new mutations in the crt gene, which arose on a specific genetic background comprising multiple genomic regions. Four newly emerging crt mutations were rare in the early period and became more prevalent by 2016–17 (Thr93Ser, rising to 19·8%; His97Tyr to 11·2%; Phe145Ile to 5·5%; and Ile218Phe to 11·1%).


After emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations. These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness. These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating malaria elimination efforts.


Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

Keywords: Malaria; Plasmodium falciparum; Drugs resistance; Artemisin; Cambodia; Laos; Thailand; Vietnam.