Naomi W Lucchi

• PhD
• Centers for Disease Control and Prevention

Background Indoor residual spraying (IRS) has been implemented in Rwanda in districts with high malaria transmission, including Ngoma District. The first IRS campaign (IRS-1) was conducted in March 2019, ahead of the peak malaria season, followed by a second campaign (IRS-2) in August 2020, targeting 89,331 structures. This study assessed factors i...

Rwanda achieved unprecedented malaria control gains from 2000 to 2010, but cases increased 20-fold between 2011 and 2017. Vector control challenges and environmental changes were noted as potential explanations, but no studies have investigated causes of the resurgence or identified which vector species drove transmission. We conducted a retrospect...

Background. Plasmodium falciparum multidrug resistance transporter 1 (Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapies (ACTs), particularly those containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies of Pfmd...

Background Indoor residual spraying (IRS) was implemented in Rwanda among districts with high transmission of malaria, including Ngoma District, which received the first IRS (IRS-1) in March 2019 before the peak season, and the second IRS (IRS-2) campaign in August 2020, which targeted 89,331 structures. This study was conducted to assess factors a...

Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrin...

Introduction: Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine u...

Malaria remains a public health priority in Rwanda. The use of insecticide-treated nets (ITNs) is a key malaria prevention tool. However, expanding pyrethroid resistance threatens the gains made in malaria control. In 2018, the Rwandan malaria program strategic approach included the use of newer types of ITNs such as pyrethroid plus piperonyl butox...

Problem/condition: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. Most malaria infections in the United States and its territories occur among persons who have traveled to regions with ongoing malaria transmission. How...

The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic diversity contributes to imm...

Following publication of the original article [1], it was brought to the publisher’s attention that incorrect details had been provided in the trial registration information of the article. Where it should read: Trial registration: The trial was also registered with the Pan African Clinical Trial Registry (https:// pactr. samrc. ac. za/) with study...

The state of Roraima, in Brazil, has recently seen an increase in the number of reported Plasmodium falciparum infections believed to be imported from neighboring countries. The objective of this study was to determine the prevalence of Plasmodium species among patients attending malaria health posts in Roraima and quantify the infections attributa...

Background In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistanc...

Objective In this study, the performance of a commercially available malaria LAMP assay (Alethia® Malaria Plus LAMP) was evaluated using retrospective clinical samples obtained from travelers returning to the United States of America (USA). Recently, several laboratories in non-malaria endemic countries evaluated the use of the loop mediated isothe...

Background Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular marke...

Background Due to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and t...

Background In Uganda, artemether-lumefantrine (AL) is the first-line therapy and dihydroartemisinin-piperaquine (DP) the second-line therapy for the treatment of uncomplicated malaria. We evaluated the efficacy and safety of AL and DP in the management of uncomplicated Plasmodium falciparum malaria and measured the prevalence of molecular markers o...

The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using...

Background: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated Plasmodium falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and mol...

Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Programme in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015 to 2016, an in vivo study was carried out to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods C...

Background: Recent studies show the first emergence of the R561H artemisinin-associated resistance marker in Africa, which highlights the importance of continued molecular surveillance to assess the selection and spread of this and other drug resistance markers in the region. Method: In this study, we used targeted deep amplicon sequencing (TADS...

Background Partial artemisinin resistance is suspected if delayed parasite clearance (ie, persistence of parasitaemia on day 3 after treatment initiation) is observed. Validated markers of artemisinin partial resistance in southeast Asia, Plasmodium falciparum kelch13 (Pfkelch13) R561H and P574L, have been reported in Rwanda but no association with...

In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagno...

Problem/condition: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, mal...

Background: In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleot...

Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Program in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015–2016, we conducted an in vivo study to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods Children...

Background Chile is one of the South American countries certified as malaria-free since 1945. However, the recent increase of imported malaria cases and the presence of the vector Anopheles pseudopunctipennis in previously endemic areas in Chile require an active malaria surveillance programme. Methods Specimens from 268 suspected malaria cases—al...

The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections a...

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several...

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several...

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several...

Background: The World Health Organization (WHO) recommends parasite-based diagnosis of malaria. In recent years, there has been surge in the use of various kinds of nucleic-acid amplification based tests (NAATs) for detection and identification of Plasmodium spp. to support clinical care in high-resource settings and clinical and epidemiological r...

Laboratory detection of malaria antigens has proved valuable for research and epidemiological purposes. We recently developed a bead-based multiplex antigen assay for pan-Plasmodium and Plasmodium falciparum targets. Here, we report integration of a Plasmodium vivax-specific target to this multiplex panel: P. vivax lactate dehydrogenase (PvLDH). Wi...

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-6...

Given that the C580Y polymorphism in the Plasmodium falciparum propeller domain of the kelch 13 gene (pfk13) was documented in Guyana, monitoring for mutations associated with antimalarial resistance was undertaken in neighboring Roraima state in Brazil. Polymorphisms in the pfmdr1 and pfk13 genes were investigated in 275 P. falciparum samples. No...

Problem/condition: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, mal...

The vast majority of malaria mortality is attributed to one parasite species: Plasmodium falciparum. Asexual replication of the parasite within the red blood cell is responsible for the pathology of the disease. In Plasmodium, the endoplasmic reticulum (ER) is a central hub for protein folding and trafficking as well as stress response pathways. In...

Background Microscopic detection of malaria parasites is the standard method for clinical diagnosis of malaria in Brazil. However, malaria epidemiological surveillance studies specifically aimed at the detection of low-density infection and asymptomatic cases will require more sensitive and field-usable tools. The diagnostic accuracy of the colorim...

Background The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at...

Dihydroartemisinin-piperaquine (DHA-PPQ) is the artemisinin combination therapy that was recently introduced for the treatment of Plasmodium falciparum uncomplicated malaria, but emerging resistance in South-East Asia is threatening its use. This report describes a case of DHA-PPQ treatment failure in uncomplicated malaria occurring in an immigrant...

[This corrects the article DOI: 10.1371/journal.pmed.1002299.].

Background: Detection of Plasmodium antigens provides evidence of malaria infection status and is the basis for most malaria diagnosis worldwide. Methods: We developed a sensitive bead-based multiplex assay for laboratory use which simultaneously detects the pan-Plasmodium pAldo, pan-Plasmodium pLDH, and P. falciparum PfHRP2 antigens. The assay...

Malaria is a debilitating parasitic disease that causes significant morbidity and mortality. Microscopic detection of parasites is currently the 'gold standard' diagnostic. This technique is limited in its ability to detect low-density infections, is time-consuming, and requires a highly trained microscopist. Malaria epidemiological surveillance st...

The vast majority of malaria mortality is attributed to one parasite species: Plasmodium falciparum. Asexual replication of the parasite within the Red Blood Cell (RBC) is responsible for the pathology of the disease. In Plasmodium, the endoplasmic reticulum (ER) is a central hub for protein folding and trafficking as well as stress response pathwa...

Piperaquine is an important partner drug used in artemisinin-based combination therapies (ACTs). An increase in the plasmepsin 2 and 3 gene copy numbers has been associated with decreased susceptibility of Plasmodium falciparum to piperaquine in Cambodia. Here, we developed a photo-induced electron transfer real-time PCR (PET-PCR) assay to quantify...

Conventional molecular methods, such as nested polymerase chain reaction (PCR), are very sensitive for detection of malaria parasites, but require advanced laboratory equipment and trained personnel. Real-time loop-mediated isothermal amplification (RealAmp), a loop-mediated isothermal amplification-based molecular tool (LAMP), facilitates rapid ta...

Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum (Pf ) malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS), which manifest as slow parasite clearance...

The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug resistant parasites. To take advantage of this technology an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance inP. falciparum,calledMalariaResis...

Background Artemisinin-based combination therapy is the first-line anti-malarial treatment for uncomplicated Plasmodium falciparum infection in Angola. To date, the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin resistance, and pfmdr1, associated with lumefantrine resistance, have not been systematically studied in Angol...

Introduction: The loop-mediated isothermal amplification (LAMP) technique holds substantial promise as an alternative easy-to-use molecular test for malaria parasite detection. Several modifications to the initial malaria LAMP assay have been made in an effort to make the LAMP platform more field-friendly. Areas covered: A PubMed literature search...

Background: Response to antimalarial treatment is assessed using serial microscopy. New techniques for accurate measurement of the Plasmodium falciparum histidine rich protein 2 (HRP2) antigen have made monitoring antigen concentration over time a potential alternative for assessing treatment response. Methods: Post-treatment HRP2 concentration...

We evaluated the therapeutic efficacy of artemether-lumefantrine (AL) fixed-dose combination to treat uncomplicated Plasmodium falciparum malaria in Cruzeiro do Sul, Acre State, in the Amazon region of Brazil. Between December 2015 and May 2016, we enrolled 79 patients, 5-79 years old with fever or history of fever in the previous 48 hours and P. f...

Antimalarial drug resistance is an evolving global health security threat to malaria control. Early detection of Plasmodium falciparum resistance through therapeutic efficacy studies and associated genetic analyses may facilitate timely implementation of intervention strategies. The US President’s Malaria Initiative–supported Antimalarial Resistanc...

The Caribbean island of Hispaniola is targeted for malaria elimination. Currently, this is the only island with ongoing transmission of malaria in the Caribbean. In 2015, six patients from Puerto Rico and one from Massachusetts, who traveled to Punta Cana, Dominican Republic, were confirmed to be infected with Plasmodium falciparum. Additional mole...

In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum . We genotyped the PfK13 propeller domain of P. falciparum in forty samples as well as other mutations proposed to be associated with artemisinin resistant mutants. We did not find any...

Accurate diagnosis of malaria infections continues to be challenging and elusive, especially in the detection of submicroscopic infections. Developing new malaria diagnostic tools that are sensitive enough to detect low-level infections, user friendly, cost effective and capable of performing large scale diagnosis, remains critical. We have designe...

Background Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized co...

Detection of histidine-rich protein 2 (HRP2) from the malaria parasite Plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs. Here we present a new HRP2 immunoassay based on a...

Selected epitope sequences and frequency within rHRP2s used in study. (DOCX)

Data from Recombinant HRP2s as Tested by the Bead Assay and ELISA. (XLSX)

Data from Mozambique Cross-Sectional Surveys. (XLSX)

Recombinant HRP2 proteins used for analysis. (A) Polyacrylamide gel. (B) Sequences for Type A and Type B proteins used in study. (TIF)

Statistical modeling of distribution of MFI-bg values in probable HRP2 negative populations from Haiti and Mozambique. For each dataset, samples with a MFI-bg value of >35 (positivity cutoff as determined by S4 Fig) were eliminated from analysis, and parametric distributions attempted to fit to remaining data. (A) Histograms for all ‘negative’ pers...

Loess curves for all persons from Mozambique survey as divided by a positive or negative RDT result with age maintained as continuous. Red and blue shadings represent 95% confidence intervals. (TIF)

Data from P. falciparum Culture Strains as Tested by the Bead Assay and ELISA. (XLSX)

Data from Angola Health Facility Survey. (XLSX)

Statistical modeling the distribution of MFI-bg signal from non-infected persons to determine bead assay signal appropriate to define HRP2 positivity. (A) Histogram of the bead assay signal from the 85 non-infected individuals in Fig 2 and overlay of various distributions fitted to the data. (B) Estimates of mean and standard deviation (s.d.) as pr...

Data from Haiti Nationwide Survey. (XLSX)

Optimization of reagent and sample concentration for HRP2 bead assay. In each comparison, a Blank (non-infected blood) is shown as well as plasma samples from fifteen P. falciparum infected persons. (A) Comparison of sample volume used during assay. (B) Different coupling concentrations of monoclonal IgM anti-HRP2 (clone MPFM-55A) to beads. (C) Dif...

Correlation between P. falciparum parasitemia and circulating HRP2 concentration. (A) Persons from U.S. domestic surveillance with parasitemia quantified by qPCR. (B) Children from 2013 Angola therapeutic efficacy study (TES) with parasitemia quantified by qPCR. (C) Children from 2015 Angola TES with parasitemia quantified by microscopy. (D) Data f...

Data from Bead Assay Testing Human Plasma Samples Non-infected or Infected with Plasmodium. (XLSX)

Isothermal nucleic acid amplification assays such as the loop mediated isothermal amplification (LAMP), are well suited for field use as they do not require thermal cyclers to amplify the DNA. To further facilitate the use of LAMP assays in remote settings, simpler sample preparation methods and lyophilized reagents are required. The performance of...

A large number of proteins in malaria parasites are anchored using glycophosphatidylinositols (GPIs) with lipid tails. These GPIs are structurally distinct from human GPIs. Plasmodium falciparum GPIs have been considered as potential vaccine candidates as these molecules are involved in inducing inflammatory responses in human hosts and natural ant...

Background Plasmodium ovale is rarely described in Senegal. A case of clinical malaria due to P. ovale wallikeri in West Central of Senegal is reported. CaseA 34-year-old male baker in Dakar, with no significant previous medical history, was admitted to a health clinic with fever and vomiting. Fever had been lasting for 4 days with peaks every 48 h...

Chloroquine (CQ) remains the first-line treatment of malaria in Haiti. Given the challenges of conducting in vivo drug efficacy trials in low-endemic settings like Haiti, molecular surveillance for drug resistance markers is a reasonable approach for detecting resistant parasites. In this study, 349 blood spots were collected from suspected malaria...

Collection of surveillance data is essential for monitoring and evaluation of public health programs. Integrated collection of household-based health data, now routinely carried out in many countries through demographic health surveys and multiple indicator surveys, provides critical measures of progress in health delivery. In contrast, biomarker s...

Weighted national estimates for toxoplasmosis and cysticercosis. (DOCX)

STROBE Checklist. (DOC)

Median plots for P. falciparum MSP142 3D7 and FVO antibody responses. (TIF)

Supporting information data file. (XLS)

Malaria elimination efforts are hampered by the lack of sensitive tools to detect infections with low-level parasitemia, usually below the threshold of standard diagnostic methods, microscopy and rapid diagnostic tests. Isothermal nucleic acid amplification assays such as the loop-mediated isothermal amplification (LAMP), are well suited for field...

Background: Efforts have been made to establish sensitive diagnostic tools for malaria screening in blood banks in order to detect malaria asymptomatic carriers. Microscopy, the malaria reference test in Brazil, is time consuming and its sensitivity depends on microscopist experience. Although molecular tools are available, some aspects need to be...

Suspected artemisinin resistance in Plasmodium falciparum can be explored by examining polymorphisms in the Kelch (PfK13) propeller domain. Sequencing of PfK13 and other gene resistance markers was performed on 98 samples from Guyana. Five of these samples carried the C580Y allele in the PfK13 propeller domain, with flanking microsatellite profiles...

Determining the source of malaria outbreaks in Ecuador and identifying remaining transmission foci will help in malaria elimination efforts. In this study, the genetic signatures of Plasmodium falciparum isolates, obtained from an outbreak that occurred in northwest Ecuador from 2012 to 2013, were characterized. Molecular investigation of the outbr...

Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials including current artemisinin-based combination therapies.A...