Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-14 (of 14 Records) |
Query Trace: Teka H[original query] |
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Evidence for a role of Anopheles stephensi in the spread of drug and diagnosis-resistant malaria in Africa
Emiru T , Getachew D , Murphy M , Sedda L , Ejigu LA , Bulto MG , Byrne I , Demisse M , Abdo M , Chali W , Elliott A , Vickers EN , Aranda-Díaz A , Alemayehu L , Behaksera SW , Jebessa G , Dinka H , Tsegaye T , Teka H , Chibsa S , Mumba P , Girma S , Hwang J , Yoshimizu M , Sutcliffe A , Taffese HS , Bayissa GA , Zohdy S , Tongren JE , Drakeley C , Greenhouse B , Bousema T , Tadesse FG . Nat Med 2023 29 (12) 3203-3211 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. Here, 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 patients with malaria and febrile controls revealed spatial clustering of Plasmodium falciparum infections around patients with malaria in strong association with the presence of An. stephensi in the household vicinity. Plasmodium sporozoites were detected in these mosquitoes. This outbreak involved clonal propagation of parasites with molecular signatures of artemisinin and diagnostic resistance. To our knowledge, this study provides the strongest evidence so far for a role of An. stephensi in driving an urban malaria outbreak in Africa, highlighting the major public health threat posed by this fast-spreading mosquito. |
Effects of COVID-19 pandemic on voluntary medical male circumcision services for HIV prevention, Sub-Saharan Africa, 2020
Peck ME , Ong KS , Lucas T , Prainito A , Thomas AG , Brun A , Kiggundu V , Yansaneh A , Busang L , Kgongwana K , Kelaphile D , Seipone K , Letebele MH , Makadzange PF , Marwiro A , Sesinyi M , Lapidos T , Lukhele N , Maziya V , Mkhontfo M , Gultie T , Mulatu D , Shimelis M , Zegeye T , Teka T , Bulterys M , Njenga JN , Odoyo-June E , Juma AW , Soo L , Talam N , Brown M , Chakare T , Nonyana N , Khoabane MA , Auld AF , Maida A , Msungama W , Kapito M , Nyirenda R , Matchere F , Odek J , Canda M , Malimane I , Come J , Gaspar N , Langa A , Aupokolo MA , Vejorerako KC , Kahindi L , Mali D , Zegeye A , Mangoya D , Zemburuka BL , Bamwesigye J , Kankindi I , Kayirangwa E , Malamba SS , Roels T , Kayonde L , Zimulinda E , Ndengo E , Nsanzimana S , Remera E , Rwibasira GN , Sangwayire B , Semakula M , Rugira E , Rugwizangoga E , Tubane E , Yoboka E , Lawrence J , Loykissoonlal D , Maphothi N , Achut V , Bunga S , Moi M , Amuri M , Kazaura K , Simbeye D , Fida N , Kayange AA , Seleman M , Akao J , Alamo ST , Kabuye G , Kyobutungi S , Makumbi FE , Mudiope P , Nantez B , Chituwo O , Godfrey L , Muyunda B , Kamboyi R , Masiye J , Lifuka E , Mandisarisa J , Mhangara M , Xaba S , Toledo C . Emerg Infect Dis 2022 28 (13) S262-s269 Beginning in March 2020, to reduce COVID-19 transmission, the US President's Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic. |
Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated Plasmodium vivax infection in Ethiopia
Assefa A , Mohammed H , Anand A , Abera A , Sime H , Minta AA , Tadesse M , Tadesse Y , Girma S , Bekele W , Etana K , Alemayehu BH , Teka H , Dilu D , Haile M , Solomon H , Moriarty LF , Zhou Z , Svigel SS , Ezema B , Tasew G , Woyessa A , Hwang J , Murphy M . Malar J 2022 21 (1) 359 BACKGROUND: Routine monitoring of anti-malarial drugs is recommended for early detection of drug resistance and to inform national malaria treatment guidelines. In Ethiopia, the national treatment guidelines employ a species-specific approach. Artemether-lumefantrine (AL) and chloroquine (CQ) are the first-line schizonticidal treatments for Plasmodium falciparum and Plasmodium vivax, respectively. The National Malaria Control and Elimination Programme in Ethiopia is considering dihydroartemisinin-piperaquine (DHA/PPQ) as an alternative regimen for P. falciparum and P. vivax. METHODS: The study assessed the clinical and parasitological efficacy of AL, CQ, and DHA/PPQ in four arms. Patients over 6 months and less than 18 years of age with uncomplicated malaria mono-infection were recruited and allocated to AL against P. falciparum and CQ against P. vivax. Patients 18 years or older with uncomplicated malaria mono-infection were recruited and randomized to AL or dihydroartemisinin-piperaquine (DHA/PPQ) against P. falciparum and CQ or DHA/PPQ for P. vivax. Patients were followed up for 28 (for CQ and AL) or 42 days (for DHA/PPQ) according to the WHO recommendations. Polymerase chain reaction (PCR)-corrected and uncorrected estimates were analysed by Kaplan Meier survival analysis and per protocol methods. RESULTS: A total of 379 patients were enroled in four arms (n = 106, AL-P. falciparum; n = 75, DHA/PPQ- P. falciparum; n = 142, CQ-P. vivax; n = 56, DHA/PPQ-P. vivax). High PCR-corrected adequate clinical and parasitological response (ACPR) rates were observed at the primary end points of 28 days for AL and CQ and 42 days for DHA/PPQ. ACPR rates were 100% in AL-Pf (95% CI: 96-100), 98% in CQ-P. vivax (95% CI: 95-100) at 28 days, and 100% in the DHA/PPQ arms for both P. falciparum and P. vivax at 42 days. For secondary endpoints, by day three 99% of AL-P. falciparum patients (n = 101) cleared parasites and 100% were afebrile. For all other arms, 100% of patients cleared parasites and were afebrile by day three. No serious adverse events were reported. CONCLUSION: This study demonstrated high therapeutic efficacy for the anti-malarial drugs currently used by the malaria control programme in Ethiopia and provides information on the efficacy of DHA/PPQ for the treatment of P. falciparum and P. vivax as an alternative option. |
Evaluation of the effect of targeted mass drug administration and reactive case detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: A cluster randomized control trial
Abdelmenan S , Teka H , Hwang J , Girma S , Chibsa S , Tongren E , Murphy M , Haile M , Dillu D , Kassim J , Behaksra S , Tadesse FG , Yukich J , Berhane Y , Worku A , Keating J , Zewde A , Gadisa E . Trials 2022 23 (1) 267 BACKGROUND: Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention. METHODS: The study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach. DISCUSSION: This randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04241705 . Registration date: January 27, 2020. |
Seroprevalence and risk factors for SARS-CoV-2 Infection in selected urban areas in Ethiopia: a cross-sectional evaluation during July 2020.
Tadesse EB , Endris AA , Solomon H , Alayu M , Kebede A , Eshetu K , Teka G , Seid BE , Ahmed J , Abayneh SA , Moges B , Gerawork H , Sugerman D , Assefa Z , Abayneh A , Abate E , Taddese L . Int J Infect Dis 2021 111 179-185 BACKGROUND: Ethiopia reported the first case of COVID-19 on 13(th) March, 2020 with community transmission ensuing by mid-May. A national, population-based serosurvey against anti-SARS-CoV-2 IgG was conducted to measure the prevalence of prior COVID-19 infections and better approximate the burden across major towns in Ethiopia. METHODS: We conducted a cross-sectional, population-based serosurvey from June 24 to July 8, 2020 in 14 major urban areas. Two-stage cluster sampling was used to randomly select enumeration areas and households. All persons aged ≥15 years were enrolled. Serum samples were tested by Abbott™ ARCHITECT™ assay for SARS-CoV-2 IgG antibodies. National COVID-19 surveillance data on the median date of the serosurvey is analyzed for comparison. FINDINGS: Adjusted seroprevalence was 3.5% (95% CI: 3.2%-3.8%) after controlling for age, sex and test kit performance. Males (3.7%) and females (3.3%) were nearly equally infected, while middle-aged adults '40-65 years' had the highest (4.0%) prevalence. Gambella (7.5%), Dire Dawa (6.2%) and Jigjiga (6.1%) were the most affected towns. About 6.7% and 8.0% of seropositives had symptoms and chronic underlying illness, respectively. A surveillance system had identified 4,416 RT-PCR confirmed cases in Addis Ababa. INTERPRETATION: This serosurvey shows that a majority of urban Ethiopians remain uninfected with SARS-CoV-2. Most anti-SARS-CoV-2 IgG positive cases were asymptomatic with no underlying illness, keeping case detection to a minimum. |
An update on the distribution, bionomics, and insecticide susceptibility of Anopheles stephensi in Ethiopia, 2018-2020
Balkew M , Mumba P , Yohannes G , Abiy E , Getachew D , Yared S , Worku A , Gebresilassie A , Tadesse FG , Gadisa E , Esayas E , Ashine T , Yewhalaw D , Chibsa S , Teka H , Murphy M , Yoshimizu M , Dengela D , Zohdy S , Irish S . Malar J 2021 20 (1) 263 BACKGROUND: Anopheles stephensi, an invasive malaria vector, was first detected in Africa nearly 10 years ago. After the initial finding in Djibouti, it has subsequently been found in Ethiopia, Sudan and Somalia. To better inform policies and vector control decisions, it is important to understand the distribution, bionomics, insecticide susceptibility, and transmission potential of An. stephensi. These aspects were studied as part of routine entomological monitoring in Ethiopia between 2018 and 2020. METHODS: Adult mosquitoes were collected using human landing collections, pyrethrum spray catches, CDC light traps, animal-baited tent traps, resting boxes, and manual aspiration from animal shelters. Larvae were collected using hand-held dippers. The source of blood in blood-fed mosquitoes and the presence of sporozoites was assessed through enzyme-linked immunosorbent assays (ELISA). Insecticide susceptibility was assessed for pyrethroids, organophosphates and carbamates. RESULTS: Adult An. stephensi were collected with aspiration, black resting boxes, and animal-baited traps collecting the highest numbers of mosquitoes. Although sampling efforts were geographically widespread, An. stephensi larvae were collected in urban and rural sites in eastern Ethiopia, but An. stephensi larvae were not found in western Ethiopian sites. Blood-meal analysis revealed a high proportion of blood meals that were taken from goats, and only a small proportion from humans. Plasmodium vivax was detected in wild-collected An. stephensi. High levels of insecticide resistance were detected to pyrethroids, carbamates and organophosphates. Pre-exposure to piperonyl butoxide increased susceptibility to pyrethroids. Larvae were found to be susceptible to temephos. CONCLUSIONS: Understanding the bionomics, insecticide susceptibility and distribution of An. stephensi will improve the quality of a national response in Ethiopia and provide additional information on populations of this invasive species in Africa. Further work is needed to understand the role that An. stephensi will have in Plasmodium transmission and malaria case incidence. While additional data are being collected, national programmes can use the available data to formulate and operationalize national strategies against the threat of An. stephensi. |
Malaria prevention and treatment in migrant agricultural workers in Dangur district, Benishangul-Gumuz, Ethiopia: social and behavioural aspects
Tadesse Y , Irish SR , Chibsa S , Dugassa S , Lorenz LM , Gebreyohannes A , Teka H , Solomon H , Gezahegn E , Petros Y , Haile M , Eshetu M , Murphy M . Malar J 2021 20 (1) 224 BACKGROUND: Sixty percent of the Ethiopia population is at risk of malaria, with the highest prevalence reported in Gambella (6%) and Benishangul-Gumuz (3%) regions. Within these regions are large agricultural developments with high numbers of seasonal migrant workers. The migrant workers are believed to be at increased risk for malaria infection due to their poor living conditions and outdoor activities, but there is little information on their specific behaviours and health risks. This study was conducted to address this gap. METHODS: Quantitative observations were conducted from September to December 2017 in the Benishangul-Gumuz Region. The nightly routines of mobile migrant workers were observed every month for 4 consecutive months. The study team collected quantitative data including nocturnal behavioural observations of worker living conditions, malaria prevention efforts, and work activities and surveys of worker representatives. Qualitative data was collected from migrant workers, farm managers and local health providers using focus group discussions and semi-structured interviews. RESULTS: Migrant workers arrived in the study area during the peak malaria transmission season and the workers in focus groups reported repeated cases of malaria during their stay on the farms. Overall, less than a quarter of the migrant workers were sleeping under a mosquito net by midnight in all 4 observation months. Some work activities also took place outdoors at night. The study additionally found a lack of access to malaria prevention and treatment at the farms and challenges in utilizing local public health facilities. CONCLUSIONS: There is a need to better address malaria prevention and treatment needs among migrant workers in Ethiopia through outreach from existing healthcare infrastructure and within the farms themselves. This will help prevent malaria transmission both within this population and prevent transmission of malaria back to home communities in lower burden areas in Ethiopia. |
Anopheles stephensi Mosquitoes as Vectors of Plasmodium vivax and falciparum, Horn of Africa, 2019
Tadesse FG , Ashine T , Teka H , Esayas E , Messenger LA , Chali W , Meerstein-Kessel L , Walker T , Wolde Behaksra S , Lanke K , Heutink R , Jeffries CL , Mekonnen DA , Hailemeskel E , Tebeje SK , Tafesse T , Gashaw A , Tsegaye T , Emiru T , Simon K , Bogale EA , Yohannes G , Kedir S , Shumie G , Sabir SA , Mumba P , Dengela D , Kolaczinski JH , Wilson A , Churcher TS , Chibsa S , Murphy M , Balkew M , Irish S , Drakeley C , Gadisa E , Bousema T . Emerg Infect Dis 2021 27 (2) 603-607 Anopheles stephensi mosquitoes, efficient vectors in parts of Asia and Africa, were found in 75.3% of water sources surveyed and contributed to 80.9% of wild-caught Anopheles mosquitoes in Awash Sebat Kilo, Ethiopia. High susceptibility of these mosquitoes to Plasmodium falciparum and vivax infection presents a challenge for malaria control in the Horn of Africa. |
Assessment of subpatent Plasmodium infection in northwestern Ethiopia
Assefa A , Ahmed AA , Deressa W , Wilson GG , Kebede A , Mohammed H , Sassine M , Haile M , Dilu D , Teka H , Murphy MW , Sergent S , Rogier E , Zhiyong Z , Wakeman BS , Drakeley C , Shi YP , Von Seidlein L , Hwang J . Malar J 2020 19 (1) 108 BACKGROUND: Ethiopia has set a goal for malaria elimination by 2030. Low parasite density infections may go undetected by conventional diagnostic methods (microscopy and rapid diagnostic tests) and their contribution to malaria transmission varies by transmission settings. This study quantified the burden of subpatent infections from samples collected from three regions of northwest Ethiopia. METHODS: Sub-samples of dried blood spots from the Ethiopian Malaria Indicator Survey 2015 (EMIS-2015) were tested and compared using microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (nPCR) to determine the prevalence of subpatent infection. Paired seroprevalence results previously reported along with gender, age, and elevation of residence were explored as risk factors for Plasmodium infection. RESULTS: Of the 2608 samples collected, the highest positive rate for Plasmodium infection was found with nPCR 3.3% (95% CI 2.7-4.1) compared with RDT 2.8% (95% CI 2.2-3.5) and microscopy 1.2% (95% CI 0.8-1.7). Of the nPCR positive cases, Plasmodium falciparum accounted for 3.1% (95% CI 2.5-3.8), Plasmodium vivax 0.4% (95% CI 0.2-0.7), mixed P. falciparum and P. vivax 0.1% (95% CI 0.0-0.4), and mixed P. falciparum and Plasmodium malariae 0.1% (95% CI 0.0-0.3). nPCR detected an additional 30 samples that had not been detected by conventional methods. The majority of the nPCR positive cases (61% (53/87)) were from the Benishangul-Gumuz Region. Malaria seropositivity had significant association with nPCR positivity [adjusted OR 10.0 (95% CI 3.2-29.4), P < 0.001]. CONCLUSION: Using nPCR the detection rate of malaria parasites increased by nearly threefold over rates based on microscopy in samples collected during a national cross-sectional survey in 2015 in Ethiopia. Such subpatent infections might contribute to malaria transmission. In addition to strengthening routine surveillance systems, malaria programmes may need to consider low-density, subpatent infections in order to accelerate malaria elimination efforts. |
Multiplex serology demonstrate cumulative prevalence and spatial distribution of malaria in Ethiopia
Assefa A , Ali Ahmed A , Deressa W , Sime H , Mohammed H , Kebede A , Solomon H , Teka H , Gurrala K , Matei B , Wakeman B , Wilson GG , Sinha I , Maude RJ , Ashton R , Cook J , Shi YP , Drakeley C , von Seidlein L , Rogier E , Hwang J . Malar J 2019 18 (1) 246 BACKGROUND: Measures of malaria burden using microscopy and rapid diagnostic tests (RDTs) in cross-sectional household surveys may incompletely describe the burden of malaria in low-transmission settings. This study describes the pattern of malaria transmission in Ethiopia using serological antibody estimates derived from a nationwide household survey completed in 2015. METHODS: Dried blood spot (DBS) samples were collected during the Ethiopian Malaria Indicator Survey in 2015 from malarious areas across Ethiopia. Samples were analysed using bead-based multiplex assays for IgG antibodies for six Plasmodium antigens: four human malaria species-specific merozoite surface protein-1 19kD antigens (MSP-1) and Apical Membrane Antigen-1 (AMA-1) for Plasmodium falciparum and Plasmodium vivax. Seroprevalence was estimated by age, elevation and region. The seroconversion rate was estimated using a reversible catalytic model fitted with maximum likelihood methods. RESULTS: Of the 10,278 DBS samples available, 93.6% (9622/10,278) had valid serological results. The mean age of participants was 15.8 years and 53.3% were female. National seroprevalence for antibodies to P. falciparum was 32.1% (95% confidence interval (CI) 29.8-34.4) and 25.0% (95% CI 22.7-27.3) to P. vivax. Estimated seroprevalences for Plasmodium malariae and Plasmodium ovale were 8.6% (95% CI 7.6-9.7) and 3.1% (95% CI 2.5-3.8), respectively. For P. falciparum seroprevalence estimates were significantly higher at lower elevations (< 2000 m) compared to higher (2000-2500 m) (aOR 4.4; p < 0.01). Among regions, P. falciparum seroprevalence ranged from 11.0% (95% CI 8.8-13.7) in Somali to 65.0% (95% CI 58.0-71.4) in Gambela Region and for P. vivax from 4.0% (95% CI 2.6-6.2) in Somali to 36.7% (95% CI 30.0-44.1) in Amhara Region. Models fitted to measure seroconversion rates showed variation nationally and by elevation, region, antigen type, and within species. CONCLUSION: Using multiplex serology assays, this study explored the cumulative malaria burden and regional dynamics of the four human malarias in Ethiopia. High malaria burden was observed in the northwest compared to the east. High transmission in the Gambela and Benishangul-Gumuz Regions and the neglected presence of P. malariae and P. ovale may require programmatic attention. The use of a multiplex assay for antibody detection in low transmission settings has the potential to act as a more sensitive biomarker. |
Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study
Assefa A , Ali A , Deressa W , Tsegaye W , Abebe G , Sime H , Kebede A , Jima D , Kassa M , Abreha T , Teka H , Solomon H , Malone J , Shi YP , Zhou Z , Reithinger R , Hwang J . Malar J 2018 17 (1) 388 BACKGROUND: Building on the declining trend of malaria in Ethiopia, the Federal Ministry of Health aims to eliminate malaria by 2030. As Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia, the use of primaquine is indicated for both transmission interruption and radical cure, respectively. However, the limited knowledge of the local prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its associated variants has hindered the use of primaquine. METHODS: Some 11,138 dried blood spot (DBS) samples were collected in 2011 as part of a national, household Malaria Indicator Survey, a multi-stage nationally representative survey of all malaria-endemic areas of Ethiopia. A randomly selected sub-set of 1414 DBS samples was successfully genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Considering the geographical position and ethnic mix of the country, three common variants: G6PD*A (A376G), G6PD*A- (G202A) and Mediterranean (C563T) were investigated. RESULTS: Of the 1998 randomly selected individuals, 1429 (71.5%) DBS samples were genotyped and merged to the database, of which 53.5% were from females. G6PD*A (A376G) was the only genotype detected. No sample was positive for either G6PD*A- (G202A) or Mediterranean (C563T) variants. The prevalence of G6PD*A (A376G) was 8.9% [95% confidence interval (CI) 6.7-11.2] ranging from 12.2% in the Southern Nations, Nationalities and Peoples' (95% CI 5.7-18.7) to none in Dire Dawa/Harari Region. CONCLUSION: The common G6PD*A- (G202A) or Mediterranean (C563T) variants were not observed in this nationwide study. The observed G6PD*A (A376G) mutation has little or no clinical significance. These findings supported the adoption of primaquine for P. falciparum transmission interruption and radical cure of P. vivax in Ethiopia. As the presence of other clinically important, less common variants cannot be ruled out, the implementation of radical cure will be accompanied by active haematological and adverse events monitoring in Ethiopia. |
HCV adaptation to HIV coinfection.
Lara J , Teka MA , Sims S , Xia GL , Ramachandran S , Khudyakov Y . Infect Genet Evol 2018 65 216-225 Human immunodeficiency virus (HIV) infection is rising as a leading cause of morbidity and mortality among hepatitis C virus (HCV)-infected patients. Both viruses interact in co-infected hosts, which may affect their intra-host evolution, potentially leading to differing genetic composition of viral populations in co-infected (CIP) and mono-infected (MIP) patients. Here, we investigate genetic differences between intra-host variants of the HCV hypervariable region 1 (HVR1) sampled from CIP and MIP. Nucleotide (nt) sequences of intra-host HCV HVR1 variants (N=28,622) obtained from CIP (N=112) and MIP (n=176) were represented using 148 physical-chemical (PhyChem) indexes of DNA nt dimers. Significant (p<.0001) differences in the means and frequency distributions of 7 PhyChem properties were found between HVR1 variants from both groups. Linear projection analysis of 29 PhyChem features extracted from such PhyChem properties showed that the CIP and MIP HVR1 variants have a distinct distribution in the modeled 2D-space, with only ~1.3% of PhyChem profiles (N=6782), shared by all HVR1 variants, being found in both groups. Probabilistic neural network (PNN) and naive Bayesian (NB) classifiers trained on the PhyChem features accurately classified HVR1 variants by the group in cross-validation experiments (AUROC>/=0.96). Similarly, both models showed a high accuracy (AUROC>/=0.95) when evaluated on a test dataset of HVR1 sequences obtained from 10 patients, data from whom were not used for model building. Both models performed at the expected lower accuracy on randomly labeled datasets in cross-validation experiments (AUROC=0.50). The random-label trained PNN showed a similar drop in accuracy on the test dataset (AUROC=0.48), indicating that the detected associations were unlikely due to random correlations. Marked differences in genetic composition of HCV HVR1 variants sampled from CIP and MIP suggest differing intra-host HCV evolution in the presence of HIV infection. PhyChem features identified here may be used for detection of HIV infection from intra-host HCV variants alone in co-infected patients, thus facilitating monitoring for HIV introduction to high-risk populations with high HCV prevalence. |
Identification of recent cases of hepatitis C virus infection using physical-chemical properties of hypervariable region 1 and a radial basis function neural network classifier.
Lara J , Teka M , Khudyakov Y . BMC Genomics 2017 18 880 BACKGROUND: Identification of acute or recent hepatitis C virus (HCV) infections is important for detecting outbreaks and devising timely public health interventions for interruption of transmission. Epidemiological investigations and chemistry-based laboratory tests are 2 main approaches that are available for identification of acute HCV infection. However, owing to complexity, both approaches are not efficient. Here, we describe a new sequence alignment-free method to discriminate between recent (R) and chronic (C) HCV infection using next-generation sequencing (NGS) data derived from the HCV hypervariable region 1 (HVR1). RESULTS: Using dinucleotide auto correlation (DAC), we identified physical-chemical (PhyChem) features of HVR1 variants. Significant (p < 9.58 x 10(-4)) differences in the means and frequency distributions of PhyChem features were found between HVR1 variants sampled from patients with recent vs chronic (R/C) infection. Moreover, the R-associated variants were found to occupy distinct and discrete PhyChem spaces. A radial basis function neural network classifier trained on the PhyChem features of intra-host HVR1 variants accurately classified R/C-HVR1 variants (classification accuracy (CA) = 94.85%; area under the ROC curve, AUROC = 0.979), in 10-fold cross-validation). The classifier was accurate in assigning individual HVR1 variants to R/C-classes in the testing set (CA = 84.15%; AUROC = 0.912) and in detection of infection duration (R/C-class) in patients (CA = 88.45%). Statistical tests and evaluation of the classifier on randomly-labeled datasets indicate that classifiers' CA is robust (p < 0.001) and unlikely due to random correlations (CA = 59.04% and AUROC = 0.50). CONCLUSIONS: The PhyChem features of intra-host HVR1 variants are strongly associated with the duration of HCV infection. Application of the PhyChem biomarkers to models for detection of the R/C-state of HCV infection in patients offers a new opportunity for detection of outbreaks and for molecular surveillance. The method will be available at https://webappx.cdc.gov/GHOST/ to the authenticated users of Global Hepatitis Outbreak and Surveillance Technology (GHOST) for further testing and validation. |
Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial
Abreha T , Hwang J , Thriemer K , Tadesse Y , Girma S , Melaku Z , Assef A , Kassa M , Chatfield MD , Landman KZ , Chenet SM , Lucchi NW , Udhayakumar V , Zhou Z , Shi YP , Kachur SP , Jima D , Kebede A , Solomon H , Mekasha A , Alemayehu BH , Malone JL , Dissanayake G , Teka H , Auburn S , von Seidlein L , Price RN . PLoS Med 2017 14 (5) e1002299 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 controlled trial in Ethiopia. METHODS AND FINDINGS: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. CONCLUSIONS: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. TRIAL REGISTRATION: ClinicalTrials.gov NCT01680406. |
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