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Article ; Online: Artemisinin-Resistant HRP2-Negative Malaria in Eritrea.

Bayih, Abebe G / Feleke, Sindew M / Pillai, Dylan R

2023 Volume 389, Issue 26, Page(s) 2497

MeSH term(s)	Humans ; Eritrea/epidemiology ; Prevalence ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/epidemiology ; Plasmodium falciparum/genetics ; Artemisinins/pharmacology ; Artemisinins/therapeutic use
Chemical Substances	artemisinin (9RMU91N5K2) ; Artemisinins
Language	English
Publishing date	2023-12-29
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2312559
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Article ; Online: Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia.

Fola, Abebe A / Feleke, Sindew M / Mohammed, Hussein / Brhane, Bokretsion G / Hennelly, Christopher M / Assefa, Ashenafi / Crudal, Rebecca M / Reichert, Emily / Juliano, Jonathan J / Cunningham, Jane / Mamo, Hassen / Solomon, Hiwot / Tasew, Geremew / Petros, Beyene / Parr, Jonathan B / Bailey, Jeffrey A

Nature microbiology

2023 Volume 8, Issue 10, Page(s) 1911–1919

Abstract: Diagnosis and treatment of Plasmodium falciparum infections are required for effective malaria control and are pre-requisites for malaria elimination efforts; hence we need to monitor emergence, evolution and spread of drug- and diagnostics-resistant ... ...

Abstract	Diagnosis and treatment of Plasmodium falciparum infections are required for effective malaria control and are pre-requisites for malaria elimination efforts; hence we need to monitor emergence, evolution and spread of drug- and diagnostics-resistant parasites. We deep sequenced key drug-resistance mutations and 1,832 SNPs in the parasite genomes of 609 malaria cases collected during a diagnostic-resistance surveillance study in Ethiopia. We found that 8.0% (95% CI 7.0-9.0) of malaria cases were caused by P. falciparum carrying the candidate artemisinin partial-resistance kelch13 (K13) 622I mutation, which was less common in diagnostic-resistant parasites mediated by histidine-rich proteins 2 and 3 (pfhrp2/3) deletions than in wild-type parasites (P = 0.03). Identity-by-descent analyses showed that K13 622I parasites were significantly more related to each other than to wild type (P < 0.001), consistent with recent expansion and spread of this mutation. Pfhrp2/3-deleted parasites were also highly related, with evidence of clonal transmissions at the district level. Of concern, 8.2% of K13 622I parasites also carried the pfhrp2/3 deletions. Close monitoring of the spread of combined drug- and diagnostic-resistant parasites is needed.
MeSH term(s)	Humans ; Plasmodium falciparum/metabolism ; Antimalarials/pharmacology ; Ethiopia/epidemiology ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Artemisinins/pharmacology ; Malaria, Falciparum/diagnosis ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/drug therapy
Chemical Substances	Antimalarials ; Protozoan Proteins ; artemisinin (9RMU91N5K2) ; Artemisinins
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-023-01461-4
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Article ; Online: Prevalence of G6PD deficiency and distribution of its genetic variants among malaria-suspected patients visiting Metehara health centre, Eastern Ethiopia.

Shenkutie, Tassew Tefera / Nega, Desalegn / Hailu, Asrat / Kepple, Daniel / Witherspoon, Logan / Lo, Eugenia / Negash, Meshesha Tsigie / Adamu, Aderaw / Gebremichael, Shewayiref Geremew / Gidey, Bokretsion / Tasew, Geremew / Feleke, Sindew M / Kebede, Tadesse

Malaria journal

2022 Volume 21, Issue 1, Page(s) 260

Abstract: Background: Glucose-6-phosphate dehydrogenase (G6PD) is cytosolic enzyme, which has a vital role for the integrity and functioning of red blood cells. Lower activity of this enzyme leads to the occurrence of acute haemolytic anaemia after exposure to ... ...

Abstract	Background: Glucose-6-phosphate dehydrogenase (G6PD) is cytosolic enzyme, which has a vital role for the integrity and functioning of red blood cells. Lower activity of this enzyme leads to the occurrence of acute haemolytic anaemia after exposure to oxidative stressors like primaquine. Primaquine is an important drug for the radical cure of Plasmodium vivax and blocking transmission of Plasmodium falciparum, and thereby enhancing malaria elimination. However, there is a need to identify G6PD deficient individuals and administer the drug with caution due to its haemolytic side effects. The main objective of this study is to determine the prevalence of G6PD deficiency among malaria-suspected individuals. Methods: A facility-based cross-sectional study was conducted from September 2020 to September 2021 in Metehara Health Centre, Eastern Ethiopia. A structured questionnaire was used to collect the socio-demographic and clinical information of the study participants. Capillary and venous blood samples were collected based on standard procedures for onsite screening, dried blood spot preparation, and malaria microscopy. The G6PD enzyme activity was measured by careSTART™ G6PD biosensor analyzer. Data was entered and analysed by SPSS. Results: A total of 498 study participants were included in the study, of which 62% (309) were males. The overall prevalence of G6PD deficiency based on the biosensor screening was 3.6% (18/498), of which 2.9% and 4.8% were males and females, respectively. Eleven of the G6PD deficient samples had mutations confirmed by G6PD gene sequencing analysis. Mutations were detected in G267 + 119C/T, A376T, and ChrX:154535443. A significant association was found in sex and history of previous malaria infection with G6PD deficiency. Conclusions: The study showed that the G6PD deficient phenotype exists in Metehara even if the prevalence is not very high. G267 + 119C/T mutation is the predominant G6PD variant in this area. Therefore, malaria patient treatment using primaquine should be monitored closely for any adverse effects.
MeSH term(s)	Antimalarials/therapeutic use ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Glucosephosphate Dehydrogenase Deficiency/complications ; Glucosephosphate Dehydrogenase Deficiency/epidemiology ; Glucosephosphate Dehydrogenase Deficiency/genetics ; Hemolysis ; Humans ; Malaria/drug therapy ; Malaria, Vivax/prevention & control ; Male ; Prevalence ; Primaquine/therapeutic use
Chemical Substances	Antimalarials ; Primaquine (MVR3634GX1)
Language	English
Publishing date	2022-09-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2091229-8
ISSN	1475-2875 ; 1475-2875
ISSN (online)	1475-2875
ISSN	1475-2875
DOI	10.1186/s12936-022-04269-5
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Article ; Online: Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia.

Feleke, Sindew M / Reichert, Emily N / Mohammed, Hussein / Brhane, Bokretsion G / Mekete, Kalkidan / Mamo, Hassen / Petros, Beyene / Solomon, Hiwot / Abate, Ebba / Hennelly, Chris / Denton, Madeline / Keeler, Corinna / Hathaway, Nicholas J / Juliano, Jonathan J / Bailey, Jeffrey A / Rogier, Eric / Cunningham, Jane / Aydemir, Ozkan / Parr, Jonathan B

Nature microbiology

2021 Volume 6, Issue 10, Page(s) 1289–1299

Abstract: In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not ... ...

Abstract	In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.
MeSH term(s)	Adolescent ; Adult ; Antigens, Protozoan/genetics ; Antigens, Protozoan/immunology ; Child ; Cross-Sectional Studies ; Diagnostic Tests, Routine/adverse effects ; Ethiopia/epidemiology ; Evolution, Molecular ; Female ; Gene Deletion ; Genotype ; Geography ; Humans ; Malaria, Falciparum/diagnosis ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/parasitology ; Male ; Plasmodium falciparum/genetics ; Plasmodium falciparum/immunology ; Plasmodium falciparum/isolation & purification ; Prevalence ; Prospective Studies ; Protozoan Proteins/genetics ; Protozoan Proteins/immunology ; Selection, Genetic ; Young Adult
Chemical Substances	Antigens, Protozoan ; HRP-2 antigen, Plasmodium falciparum ; HRP3 protein, Plasmodium falciparum ; Protozoan Proteins
Language	English
Publishing date	2021-09-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-021-00962-4
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Article ; Online: Characterizing Reactivity to

Feeser, Karla R / Cama, Vitaliano / Priest, Jeffrey W / Thiele, Elizabeth A / Wiegand, Ryan E / Lakwo, Thomson / Feleke, Sindew M / Cantey, Paul T

The American journal of tropical medicine and hygiene

2017 Volume 97, Issue 3, Page(s) 666–672

Abstract: Multiplex bead assays (MBAs) may provide a powerful integrated tool for monitoring, evaluation, and post-elimination surveillance of onchocerciasis and co-endemic diseases; however, the specificity and sensitivity ... ...

Abstract	Multiplex bead assays (MBAs) may provide a powerful integrated tool for monitoring, evaluation, and post-elimination surveillance of onchocerciasis and co-endemic diseases; however, the specificity and sensitivity of
MeSH term(s)	Animals ; Antibodies, Helminth/immunology ; Antigens, Helminth/chemistry ; Antigens, Helminth/immunology ; False Positive Reactions ; Humans ; Immunoassay/methods ; Immunoglobulin G/immunology ; Onchocerca volvulus/chemistry ; Onchocerca volvulus/immunology ; Onchocerciasis/diagnosis ; Onchocerciasis/immunology ; Sensitivity and Specificity
Chemical Substances	Antibodies, Helminth ; Antigens, Helminth ; Immunoglobulin G
Language	English
Publishing date	2017-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.16-0519
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Article ; Online: Evaluation of an OV-16 IgG4 Enzyme-Linked Immunosorbent Assay in Humans and Its Application to Determine the Dynamics of Antibody Responses in a Non-Human Primate Model of

Cama, Vitaliano A / McDonald, Circe / Arcury-Quandt, Alice / Eberhard, Mark / Jenks, M Harley / Smith, Jared / Feleke, Sindew M / Abanyie, Francisca / Thomson, Lakwo / Wiegand, Ryan E / Cantey, Paul T

The American journal of tropical medicine and hygiene

2018 Volume 99, Issue 4, Page(s) 1041–1048

Abstract: Onchocerciasis is a neglected parasitic disease targeted for elimination. Current World Health Organization guidelines for elimination include monitoring antibody responses to the ... ...

Abstract	Onchocerciasis is a neglected parasitic disease targeted for elimination. Current World Health Organization guidelines for elimination include monitoring antibody responses to the recombinant
MeSH term(s)	Animals ; Antibodies, Helminth/blood ; Antigens, Helminth/administration & dosage ; Antigens, Helminth/biosynthesis ; Antigens, Helminth/immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Immune Sera/analysis ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Microfilariae/immunology ; Onchocerca volvulus/immunology ; Onchocerciasis/blood ; Onchocerciasis/diagnosis ; Onchocerciasis/immunology ; Onchocerciasis/parasitology ; Primates ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/immunology ; Sensitivity and Specificity
Chemical Substances	Antibodies, Helminth ; Antigens, Helminth ; Immune Sera ; Immunoglobulin G ; Immunoglobulin M ; Recombinant Proteins
Language	English
Publishing date	2018-07-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.18-0132
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Article ; Online: Prevalence and Epidemiological Characteristics of Asymptomatic Malaria Based on Ultrasensitive Diagnostics: A Cross-sectional Study.

Girma, Seble / Cheaveau, James / Mohon, Abu Naser / Marasinghe, Dewdunee / Legese, Ruth / Balasingam, Nirujah / Abera, Adugna / Feleke, Sindew M / Golassa, Lemu / Pillai, Dylan R

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2018 Volume 69, Issue 6, Page(s) 1003–1010

Abstract: Background: As the global public-health objectives for malaria evolve from malaria control towards malaria elimination, there is increasing interest in the significance of asymptomatic infections and the optimal diagnostic test to identify them.: ... ...

Abstract	Background: As the global public-health objectives for malaria evolve from malaria control towards malaria elimination, there is increasing interest in the significance of asymptomatic infections and the optimal diagnostic test to identify them. Method: We conducted a cross-sectional study of asymptomatic individuals (N = 562) to determine the epidemiological characteristics associated with asymptomatic malaria. Participants were tested by rapid diagnostic tests (CareStart, Standard Diagnostics [SD] Bioline, and Alere ultrasensitive RDT [uRDT]), loop-mediated isothermal amplification (LAMP), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine malaria positivity. Hemoglobin values were recorded, and anemia was defined as a binary variable, according to World Health Organization guidelines. Results: Compared to reference qRT-PCR, LAMP had the highest sensitivity (92.6%, 95% confidence interval [CI] 86.4-96.5), followed by uRDT Alere Malaria (33.9%, 95% CI 25.5-43.1), CareStart Malaria (14.1%, 95% CI 8.4-21.5), microscopy (5.0%, 95% CI 1.8-10.5), and SD Bioline (5.0%, 95% CI 1.8-10.5). For Plasmodium falciparum specimens only, the sensitivity for uRDT Alere Malaria was 50.0% (95% CI 38.8-61.3) and SD Bioline was 7.3% (95% CI 2.7-15.3). Based on multivariate regression analysis with qRT-PCR as the gold standard, for every 3.2% increase in the prevalence of asymptomatic malaria, hemoglobin decreased by 1 gram per deciliter (prevalence ratio 0.968, 95% CI 0.940-0.997; P = .032). Deletions (4.8%) in hrp2 were noted. Conclusions: While uRDT Alere Malaria has superior sensitivity to rapid diagnostic tests and microscopy in detecting asymptomatic malaria, LAMP is superior still. Ultrasensitive diagnostics provide the accurate prevalence estimates of asymptomatic malaria required for elimination.
MeSH term(s)	Adolescent ; Antigens, Protozoan/genetics ; Asymptomatic Infections/epidemiology ; Child ; Cross-Sectional Studies ; Diagnostic Tests, Routine/methods ; Diagnostic Tests, Routine/standards ; Female ; Humans ; Malaria/diagnosis ; Malaria/epidemiology ; Malaria/parasitology ; Male ; Molecular Diagnostic Techniques ; Nucleic Acid Amplification Techniques ; Plasmodium/classification ; Plasmodium/genetics ; Population Surveillance ; Prevalence ; Protozoan Proteins/genetics ; Reproducibility of Results ; Sensitivity and Specificity
Chemical Substances	Antigens, Protozoan ; HRP-2 antigen, Plasmodium falciparum ; Protozoan Proteins
Language	English
Publishing date	2018-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciy1005
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Article ; Online: The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

Katabarwa, Moses N / Zarroug, Isam M A / Negussu, Nebiyu / Aziz, Nabil M / Tadesse, Zerihun / Elmubark, Wigdan A / Shumo, Zainab / Meribo, Kadu / Kamal, Hashim / Mohammed, Aderajew / Bitew, Yewondwossen / Seid, Tewodros / Bekele, Firdaweke / Yilak, Abebual / Endeshaw, Tekola / Hassen, Mohammed / Tillahun, Abate / Samuel, Fikresilasie / Birhanu, Henok /

Asmare, Tadesse / Boakye, Daniel / Feleke, Sindew M / Unnasch, Thomas / Post, Rory / Higazi, Tarig / Griswold, Emily / Mackenzie, Charles / Richards, Frank

PLoS neglected tropical diseases

2020 Volume 14, Issue 2, Page(s) e0007830

Abstract: Background: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented.: Methods/principle findings: The Galabat-Metema focus involves ...

Abstract	Background: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. Methods/principle findings: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. Conclusion: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed.
MeSH term(s)	Animals ; Child ; Child, Preschool ; Emigration and Immigration ; Ethiopia/epidemiology ; Female ; Humans ; Ivermectin/administration & dosage ; Male ; Mass Drug Administration ; Onchocerca volvulus/drug effects ; Onchocerca volvulus/genetics ; Onchocerca volvulus/isolation & purification ; Onchocerca volvulus/physiology ; Onchocerciasis/drug therapy ; Onchocerciasis/epidemiology ; Onchocerciasis/parasitology ; Onchocerciasis/transmission ; Simuliidae/parasitology ; Simuliidae/physiology ; Sudan/epidemiology
Chemical Substances	Ivermectin (70288-86-7)
Language	English
Publishing date	2020-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0007830
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Article ; Online: Artemisinin-Resistant HRP2-Negative Malaria in Eritrea.

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Article ; Online: Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia.

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Article ; Online: Prevalence of G6PD deficiency and distribution of its genetic variants among malaria-suspected patients visiting Metehara health centre, Eastern Ethiopia.

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Article ; Online: Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia.

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Article ; Online: Characterizing Reactivity to

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Article ; Online: Evaluation of an OV-16 IgG4 Enzyme-Linked Immunosorbent Assay in Humans and Its Application to Determine the Dynamics of Antibody Responses in a Non-Human Primate Model of

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Article ; Online: Prevalence and Epidemiological Characteristics of Asymptomatic Malaria Based on Ultrasensitive Diagnostics: A Cross-sectional Study.

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Article ; Online: The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

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