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Retrospective study on clinical manifestation, thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy

Zhonghua Nei Ke Za Zhi. 2022 Oct 1;61(10):1144-1151. doi: 10.3760/cma.j.cn112138-20211124-00845.

ABSTRACT

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP+) group, anti-HMGCR antibody positive (HMGCR+) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP+, 8 (25.0%) with HMGCR+, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP+group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb (P<0.01). The axial muscle score was lower than the distal limb score (P<0.05).(3) Extramuscular manifestations of HMGCR+ group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups (P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP+ group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR+ group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP+ group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR+group were more prone to myotonia potential and CRDs.

PMID:36207969 | DOI:10.3760/cma.j.cn112138-20211124-00845

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Clinical features and survival analysis of microscopic polyangiitis-associated interstitial lung disease:a retrospective study of 28 patients

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Oct 12;45(10):1022-1030. doi: 10.3760/cma.j.cn112147-20220208-00097.

ABSTRACT

Objective: To explore the clinical features, laboratory examination and imaging features of microscopic polyangiitis (MPA)-associated interstitial lung disease (ILD), and to perform survival analysis. Methods: The records of 28 patients with MPA-ILD who were treated at the Affiliated Hospital of Medical School of Ningbo University were reviewed retrospectively from August 2014 to November 2021. The patients’ clinical features, laboratory parameters, pulmonary function test, echocardiography, chest CT scan findings and therapeutic regimen were analyzed, and the relevant data were statistically analyzed. Results: There were 18 males and 10 females, with an average age of (70.1±9.3) years. Among them, 13 patients had a history of smoking. The main clinical manifestations were cough (14/28), fever (12/28), chest tightness, shortness of breath (12/28) and hemoptysis (3/28). Sixteen patients had renal involvement, and 78.57% (22/28) and 89.28% (25/28) of the patients had elevated C-reactive protein (CRP) and ESR respectively. Sixteen (16/28) patients had increased rheumatoid factor (RF), and the positive rate of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) was 82.12% (23/28). 96.43% (27/28) of ILDs were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly usual interstitial pneumonia (UIP) or UIP-like (15/28), followed by nonspecific interstitial pneumonia (NSIP) (8/28). Compared with non-UIP-like patients, UIP or UIP-like patients were older (P=0.018), and had higher serum LDH level (P=0.041), but serum creatinine level was significantly lower (P=0.041). Univariate and multivariate survival analysis showed that inappropriate treatment (HR=9.81, 95%CI: 1.68-57.29, P=0.011) and elevated serum LDH (HR=4.11, 95%CI: 0.99-17.00, P=0.051) were independent risk factors for shortened survival of MPA-ILD, while elevated RF (HR=0.22, 95%CI: 0.06-0.91, P=0.037) was a protective factor for prolonged survival. Conclusions: MPA-ILD patients had fewer systemic vasculitis symptoms. Most of the ILD patients were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly UIP or UIP-like, followed by NSIP. Early use of glucocorticoids combined with immunosuppressant or rituximab could improve the survival rate of MPA-ILD. The elevated serum LDH was an independent risk factor for shortened survival of MPA-ILD, while elevated RF was a protective factor for prolonged survival.

PMID:36207959 | DOI:10.3760/cma.j.cn112147-20220208-00097

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The diagnostic potential of Golgi protein 73 for cirrhosis in patients with chronic hepatitis C

Zhonghua Gan Zang Bing Za Zhi. 2022 Aug 20;30(8):879-884. doi: 10.3760/cma.j.cn501113-20200415-00186.

ABSTRACT

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.

PMID:36207945 | DOI:10.3760/cma.j.cn501113-20200415-00186

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Study of magnetic resonance imaging based on liver imaging reporting and data system for evaluating phosphatidylinositol proteoglycan-3 expression in hepatocellular carcinoma

Zhonghua Gan Zang Bing Za Zhi. 2022 Aug 20;30(8):866-872. doi: 10.3760/cma.j.cn501113-20210506-00222.

ABSTRACT

Objective: To clarify the diagnostic value of magnetic resonance imaging based on liver imaging reporting and data system (LI-RADS) for phosphatidylinositol proteoglycan-3 (GPC3) expression in hepatocellular carcinoma (HCC). Methods: Clinical and pathological data of 95 HCC cases with positive GPC3 expression (+) and 40 HCC cases with negative GPC3 expression (-) were retrospectively analyzed, and their MRI image features based on the 2018 version of LI-RADS were compared. Multivariate logistic regression analysis was used to determine the main predictors of GPC3 expression. Receiver operating characteristic curve was used further to determine the diagnostic efficacy of combined clinical imaging model to predict GPC3 expression. Enumeration data were compared with χ2 test or Fisher’s exact test. Measurement data were compared using independent samples t-test or Mann-Whitney U-test. Results: There were statistically significant differences between HCC in GPC3 (+) and GPC3(-) group at alpha-fetoprotein (AFP) levels (χ2=31.814, P<0.000 1), and MRI features: capsular enhacement (χ2=4.108, P=0.043), halo type enhancement (χ2=4.847, P=0.028), and lesion apparent dispersion coefficient (ADC) (t=2.552, P=0.011 8). Multivariate regression analysis showed that AFP>20 μg/L (OR=9.358, P<0.000 1) and ADC≤1.404×10-3 mm2/s (OR=1.003, P=0.017) were independent predictors for GPC3 expression in HCC. The combined model and the area under the curve value for the diagnosis of GPC3(+) in HCC was 0.810, and its diagnostic sensitivity and specificity were 76.8% and 77.5%, respectively. Conclusion: AFP>20 μg/L and ADC≤1.404×10-3 mm2/s may indicate the expression of GPC3 in HCC, and the combination of the two diagnostic indicators can provide a simple and effective non-invasive diagnostic method for clinical practice.

PMID:36207943 | DOI:10.3760/cma.j.cn501113-20210506-00222

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Analysis of clinical and endoscopic characteristics of colorectal polyps in children

Zhonghua Yu Fang Yi Xue Za Zhi. 2022 Sep 6;56(9):1327-1332. doi: 10.3760/cma.j.cn112150-20220117-00061.

ABSTRACT

To analyze the clinical and endoscopic characteristics of colorectal polyps in children, and to explore the detection rate, age and gender distribution characteristics, endoscopic treatment effect and follow-up monitoring of colorectal polyps in children, so as to provide reference for disease management of colorectal polyps in children. The clinical and endoscopic characteristics of children with colorectal polyps in Xi ‘an Children’s Hospital from January 2019 to December 2019 were retrospectively analyzed. The patients were divided into 5 groups according to age (y): 0<y<1 years, 1≤ y<4 years, 4≤ y<7 years, 7≤ y<12 years, and 12≤ y ≤18 years. Independent sample t test, Pearson Chi-square test (χ2) were used to compare groups’ differences. The results showed that a total of 724 colonoscopies were completed in 2019, and 160 colorectal polyps were diagnosed, with a detection rate of 22.10%. Among the children with colorectal polyps, 105 were males, accounting for 65.62%, and 55 were females, accounting for 34.38%. The detection rate of male colorectal polyps was 22.68%, and the detection rate of female colorectal polyps was 21.08%. There was no significant difference in the detection rate of colorectal polyps between males and females (χ2 = 0.25, P =0.617). Children with colorectal polyps were most common in the age group of 1≤ y<4 years, 72 cases, accounting for 41.14%(72/175). The detection rate of colorectal polyps in different age groups was statistically significant (χ2=73.929, P<0.05). The main symptom of children with colorectal polyps was hematochezia, accounting for 87.5% (140/160). Colorectal polyps were mainly single polyps in 140 patients, accounting for 87.50%, 15 patients had 2-4 polyps, accounting for 9.38%, and 5 patients had 5 or more polyps, accounting for 3.12%. A total of 210 polyps were removed, and the most common site of polyps was rectum, 123 polyps, accounting for 58.57% (123/210). 111 (52.86%, 111/210) of them were 1 cm to 2 cm in diameter. The Yamada classification was mainly type Ⅲ, 114 pieces, accounting for 54.29% (114/210). Among the 210 polyps with diameter ≥0.5 cm, 165 were removed by endoscopic mucosal resection, accounting for 78.57% (165/210). There were 23 patients with postoperative complications, including hematochezia, abdominal pain, fever, vomiting, diarrhea, dizziness, and no gastrointestinal perforation. Juvenile polyps were the main pathological type, accounting for 88.13% (141/160). The children with juvenile polyps were followed up for 3-30 months, and recurrence was considered in 2 of them. In conclusion, the detection rate of colorectal polyps in children aged 1≤ y<4 years is high, and hematochezia is the main clinical manifestation. Standardized endoscopic treatment and follow-up monitoring are very important for children with colorectal polyps.

PMID:36207899 | DOI:10.3760/cma.j.cn112150-20220117-00061

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Quantifying the Spinal Lordosis Ratio Unique to the Type of Spinal Sagittal Alignment in a Normal Population

Global Spine J. 2022 Oct 7:21925682221133748. doi: 10.1177/21925682221133748. Online ahead of print.

ABSTRACT

STUDY DESIGN: Data collection of radiological parameters in non-pathological adult spines.

OBJECTIVES: Establishing a baseline database for measurements of the spinal lordosis ratio between upper and lower arcs of the lumbar spine unique to each type of spine described by Roussouly’s classification. Illustrating the importance of correct rationing of the upper and lower arcs.

METHODS: Standardised standing true lateral plain radiographs of the spine (including base of skull and proximal femurs) from 373 adult volunteers were obtained. Exclusion criteria : any history of disease involving the spine, pelvis, hips or lower limbs. Incidental detection of any spinal deformity on radiography also excluded further participation in this study. Sacro-pelvic parameters data collected : Pelvic Incidence (PI), Pelvic Tilt (PT), Sacral Slope (SS), location of Inflection Point, number of vertebras in the spinal lordosis and type of Roussouly’s spine. Values of upper arc, lower arc and spinal lordosis ratio (SLR) was determined.

RESULTS: Bivariate analysis revealed statistically significant (P < .0001) correlation between the types of sagittal spinal alignments based on Roussouly’s classification and the SLR. Type 1: SLR .76 ± .17, Type 2: SLR .60 ± .18, Type 3 with anteverted pelvis: SLR .53 ± .11, Type 3: SLR .49 ± .12, Type4: SLR .41 ± .11.

CONCLUSION: With this data we are able to quantify the ratio of lumbar lordosis unique to each type of Roussouly’s spine. It functions as a guide when planning lumbar spine surgeries in order to restore the SLR correctly and thus prevent post-op complications such as proximal junction kyphosis.

PMID:36207768 | DOI:10.1177/21925682221133748

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In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials

Biol Direct. 2022 Oct 7;17(1):27. doi: 10.1186/s13062-022-00339-5.

ABSTRACT

RNA-protein interactions are crucial for diverse biological processes. In prokaryotes, RNA-protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA-protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA-protein interactions in the current tools. Here, we investigate the RNA-protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA-protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA-protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.

PMID:36207756 | DOI:10.1186/s13062-022-00339-5

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Investigation and analysis of four countries’ recalls of osteosynthesis implants and joint replacement implants from 2011 to 2021

J Orthop Surg Res. 2022 Oct 7;17(1):443. doi: 10.1186/s13018-022-03332-w.

ABSTRACT

BACKGROUND: Medical devices are used in almost all orthopedic surgical subspecialties, and the frequency of adverse events is increasing, which should not be ignored. To provide suggestions on how to avoid implant recalls from the perspective of manufacturers, medical institutions and supervisions, as well as how to respond promptly to adverse events.

METHODS: The research extracted recalls of osteosynthesis implants and joint replacement implants from January 1, 2011, to June 30, 2021, in the CNMPA, FDA, HC and ATGA websites and collected the information on device name, recall time, recall class, recall manufacturer, device classification and affected areas. Moreover, the McKinsey 7S model and fishbone diagram were used to analyze recall reasons.

RESULTS: A total of 315 cases of osteosynthesis implants and 286 cases of joint replacement implants were reported in China, the USA, Canada and Australia. The recalls number from 2016 to 2021 was more than that from 2011 to 2015 for osteosynthesis implant (p = 0.012) and joint replacement implant (p = 0.002), and both mainly focused on class II (76.19% and 78.32%). There were statistical differences in the four countries for both implants (p = 0.000), especially osteosynthesis implant between China and the USA (p = 0.000), China and Canada (p = 0.001), the USA and Australia (p = 0.002), and joint replacement implant between China and Australia (p = 0.000).

CONCLUSIONS: To avoid the recalls of such implants, manufacturers should strictly select implant materials and components, develop detailed labels and instructions, severely control the packaging process and establish the integrity of medical device data. Medical institutions should standardize procurement procedures, use qualified equipment and train medical workers. It also requires supervisions to conduct premarket safety assessments. In addition, regulators should strengthen supervision and establish reporting systems to deal with the occurrence of adverse events promptly.

PMID:36207755 | DOI:10.1186/s13018-022-03332-w

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Estimating disability-adjusted life years for breast cancer and the impact of screening in female populations in China, 2015-2030: an exploratory prevalence-based analysis applying local weights

Popul Health Metr. 2022 Oct 7;20(1):19. doi: 10.1186/s12963-022-00296-1.

ABSTRACT

BACKGROUND: Most cancer disability-adjusted life year (DALY) studies worldwide have used broad, generic disability weights (DWs); however, differences exist among populations and types of cancers. Using breast cancer as example, this study aimed to estimate the population-level DALYs in females in China and the impact of screening as well as applying local DWs.

METHODS: Using multisource data, a prevalence-based model was constructed. (1) Overall years lived with disability (YLDs) were estimated by using numbers of prevalence cases, stage-specific proportions, and local DWs for breast cancer. Numbers of females and new breast cancer cases as well as local survival rates were used to calculate the number of prevalence cases. (2) Years of life lost (YLLs) were estimated using breast cancer mortality rates, female numbers and standard life expectancies. (3) The prevalence of and mortality due to breast cancer and associated DALYs from 2020 to 2030 were predicted using Joinpoint regression. (4) Assumptions considered for screening predictions included expanding coverage, reducing mortality due to breast cancer and improving early-stage proportion for breast cancer.

RESULTS: In Chinese females, the estimated number of breast cancer DALYs was 2251.5 thousand (of 17.3% were YLDs) in 2015, which is predicted to increase by 26.7% (60.3% among those aged ≥ 65 years) in 2030 (2852.8 thousand) if the screening coverage (25.7%) stays unchanged. However, if the coverage can be achieved to 40.7% in 2030 (deduced from the “Healthy China Initiative”), DALYs would decrease by 1.5% among the screened age groups. Sensitivity analyses found that using local DWs would change the base-case values by ~ 10%.

CONCLUSION: Estimates of DALYs due to breast cancer in China were lower (with a higher proportion of YLDs) than Global Burden of Disease Study numbers (2527.0 thousand, 8.2% were YLDs), suggesting the importance of the application of population-specific DWs. If the screening coverage remains unchanged, breast cancer-caused DALYs would continue to increase, especially among elderly individuals.

PMID:36207752 | DOI:10.1186/s12963-022-00296-1

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High prevalence of Pfcrt 76T and Pfmdr1 N86 genotypes in malaria infected patients attending health facilities in East Shewa zone, Oromia Regional State, Ethiopia

Malar J. 2022 Oct 7;21(1):286. doi: 10.1186/s12936-022-04304-5.

ABSTRACT

BACKGROUND: Plasmodium falciparum resistance to series of anti-malarial drugs is a major challenge in efforts to control and/or eliminate malaria globally. In 1998, following the widespread of chloroquine (CQ) resistant P. falciparum, Ethiopia switched from CQ to sulfadoxine-pyrimethamine (SP) and subsequently in 2004 from SP to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria. Data on the prevalence of CQ resistance markers after more than two decades of its removal is important to map the selection pressure behind the targets codons of interest. The present study was conducted to determine the prevalence of mutations in Pfcrt K76T and Pfmdr1 N86Y codons among malaria-infected patients from Adama, Olenchiti and Metehara sites of East Shewa zone, Oromia Regional State, Ethiopia.

METHODS: Finger-prick whole blood samples were collected on 3MM Whatman ® filter papers from a total of 121 microscopically confirmed P. falciparum infected patients. Extraction of parasite DNA was done by Chelex-100 method from dried blood spot (DBS). Genomic DNA template was used to amplify Pfcrt K76T and Pfmdr1 N86Y codons by nested PCR. Nested PCR products were subjected to Artherobacter protophormiae-I (APoI) restriction enzyme digestion to determine mutations at codons 76 and 86 of Pfcrt and Pfmdr1 genes, respectively.

RESULTS: Of 83 P. falciparum isolates successfully genotyped for Pfcrt K76T, 91.6% carried the mutant genotypes (76T). The prevalence of Pfcrt 76T was 95.7%, 92.5% and 84.5% in Adama, Metehara and Olenchiti, respectively. The prevalence of Pfcrt 76T mutations in three of the study sites showed no statistical significance difference (χ2 = 1.895; P = 0.388). On the other hand, of the 80 P. falciparum samples successfully amplified for Pfmdr1, all carried the wild-type genotypes (Pfmdr1 N86).

CONCLUSION: Although CQ officially has been ceased for the treatment of falciparum malaria for more than two decades in Ethiopia, greater proportions of P. falciparum clinical isolates circulating in the study areas carry the mutant 76T genotypes indicating the presence of indirect CQ pressure in the country. However, the return of Pfmdr1 N86 wild-type allele may be favoured by the use of AL for the treatment of uncomplicated falciparum malaria.

PMID:36207750 | DOI:10.1186/s12936-022-04304-5