scholarly journals Dynamic changes in genetic diversity, drug resistance mutations, and treatment outcomes of falciparum malaria from the low-transmission to the pre-elimination phase on the islands of São Tomé and Príncipe

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying-An Chen ◽  
Tsen-Ju Shiu ◽  
Lien-Fen Tseng ◽  
Chien-Fu Cheng ◽  
Wei-Liang Shih ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Outcomes ◽  
Parasite Density ◽  
Resistance Mutations ◽  
Dynamic Changes ◽  
Low Transmission ◽  
Drug Resistance Mutations ◽  
Sao Tome And Principe ◽  
Younger Age

Abstract Background With effective vector control and case management, substantial progress has been made towards eliminating malaria on the islands of São Tomé and Príncipe (STP). This study assessed the dynamic changes in the genetic diversity of Plasmodium falciparum, the anti-malarial drug resistance mutations, and malaria treatment outcomes between 2010 and 2016 to provide insights for the prevention of malaria rebounding. Methods Polymorphic regions of merozoite surface proteins 1 and 2 (msp1 and msp2) were sequenced in 118 dried blood spots (DBSs) collected from malaria patients who had visited the Central Hospital in 2010–2016. Mutations in the multi-drug resistance I (pfmdr1), chloroquine resistance transporter (pfcrt), and kelch 13 (pfk13) genes were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and sequencing in 111 DBSs. A total of 7482 cases that completed a 28-day follow-up were evaluated for treatment outcomes based on the microscopic results. Regression models were used to characterize factors associated with levels of parasite density and treatment failures. Results Parasite strains in STP showed significant changes during and after the peak incidence in 2012. The prevalent allelic type in msp1 changed from K1 to MAD20, and that in msp2 changed from 3D7/IC to FC27. The dominant alleles of drug-resistance markers were pfmdr1 86Y, 184F, D1246, and pfcrt 76 T (Y-F-D-T, 51.4%). The average parasite density in malaria cases declined threefold from low-transmission (2010–2013) to pre-elimination period (2014–2016). Logistic regression models showed that patients with younger age (OR for age = 0.97–0.98, p < 0.001), higher initial parasite density (log10-transformed, OR = 1.44, p < 0.001), and receiving quinine treatment (compared to artemisinin-based combination therapy, OR = 1.91–1.96, p < 0.001) were more likely to experience treatment failures during follow-up. Conclusions Plasmodium falciparum in STP had experienced changes in prevalent strains, and increased mutation frequencies in drug-resistance genes from the low-transmission to the pre-elimination settings. Notably, patients with younger age and receiving quinine treatment were more likely to show parasitological treatment failure during follow-up. Therapeutic efficacy should be carefully monitored to inform future treatment policy in STP.

scholarly journals Dynamic changes in genetic diversity, drug resistance mutations, and treatment outcomes of falciparum malaria from the low-transmission to the pre-elimination phase on the isolated islands of São Tomé and Príncipe

2021 ◽  
Author(s):  
Ying-An Chen ◽  
Tsen-Ju Shiu ◽  
Lien-Fen Tseng ◽  
Chien-Fu Cheng ◽  
Wei-Liang Shih ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Treatment Outcomes ◽  
Resistance Mutations ◽  
Antimalarial Drug Resistance ◽  
Elimination Phase ◽  
Logistic Regression Models ◽  
Drug Resistance Mutations ◽  
Sao Tome And Principe

Abstract Background With effective vector control and case management, substantial progress has been made in the elimination of malaria on the islands of São Tomé and Príncipe (STP). During the critical period from the low-transmission to the pre-elimination phase, this study tracked the dynamic changes in the genetic diversity in Plasmodium falciparum, the distribution of antimalarial drug-resistance genes, and the treatment outcomes in patients to provide insights for the prevention of rebounded malaria in STP. Methods Dried blood spots (DBSs) and case follow-up data were collected from malaria patients who had visited the Central Hospital between 2010 and 2016. Genomic DNA of P. falciparum was extracted from DBSs. The polymorphic regions on the genes for merozoite surface proteins 1 and 2 (msp1 and msp2) were amplified in 118 pre-treatment samples to identify the genetic diversity of the infected parasites. Anti-malarial drug resistance mutations in the multi-drug resistance (pfmdr1), chloroquine resistance transporter (pfcrt), and kelch 13 (pfK13) genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing in 111 samples. Treatment outcomes were categorized based on the parasitological results from microscopy during the 28-day follow-up after treatment. Factors related to malaria recurrence were characterized by logistic regression models using case follow-up data (total number = 7,482). Results The circulating parasite strains in STP showed significant changes at the recent peak incidence in 2012, during which the prevalent allelic type in MSP1 changed from K1 to MAD20, and that in MSP2 changed from 3D7/IC to FC27. Genotyping results for antimalarial drug-resistance markers showed that the dominant alleles of pfmdr1 86 + 184 + 1246-pfcrt 76 were YFD-T (51.4%). Logistic regression models showed that significant factors related to parasitological failure after treatment were age (protective factor, OR = 0.97–0.98), log10-transformed parasite density (OR = 1.07–1.44), and treatment (quinine vs. artemisinin-based combination therapy, OR = 1.91–1.96). Overall, younger patients, those with higher parasitemia levels at enrollment, and those treated with quinine had a higher risk of recurrence during follow-up. Conclusions Although malaria treatment efficacy remained acceptable in STP, this study showed temporal changes in the dominant strains and the development of drug resistance mutations in the local parasite population. Therapeutic efficacy should be carefully monitored to adequately adjust the policy in the future.

scholarly journals P027: Emergence of drug resistance mutations in a cohort of HIV-infected children with mother to child transmission, during follow-up

2015 ◽  
Vol 18 (3 (Suppl 2)) ◽  
Author(s):  
Cristina de Jesus Herrera-Castillo ◽  
Angelica Rodríguez ◽  
Othon Rojas-Montes ◽  
Rosalia Lira ◽  
José Guillermo Vazquez-Rosales
Keyword(s):  
Drug Resistance ◽  
Mother To Child Transmission ◽  
Resistance Mutations ◽  
Child Transmission ◽  
Drug Resistance Mutations ◽  
Mother To Child

scholarly journals Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicaise Ndembi ◽  
Fati Murtala-Ibrahim ◽  
Monday Tola ◽  
Jibreel Jumare ◽  
Ahmad Aliyu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virologic Failure ◽  
Resistance Mutations ◽  
First Line ◽  
Drug Resistance Mutations ◽  
Entry Points ◽  
The Mean ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. Methods A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm3 after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program’s own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)—based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07–1.40)] and less common among those who entered care at the program’s VCT center as compared to other entry points [0.79 (0.64–0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16–0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16–0.22)]. Virologic failure was more common among PLWH who entered care at the program’s VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11–1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36–2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. Conclusions In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.

scholarly journals ACQUIRED ANTIRETROVIRAL DRUG RESISTANCE MUTATIONS UPON TREATMENT FAILURE IN HIV-1 INFECTED PEDIATRIC PATIENTS IN CENTRAL BRAZIL

2020 ◽  
Vol 49 (2) ◽  
pp. 79-93
Author(s):  
Maly Albuquerque ◽  
Solomar Martins Marques ◽  
Ricardo Vieira Teles Filho ◽  
Paulo Sergio Sucasas Costa
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Children And Adolescents ◽  
Resistance Mutations ◽  
Central Brazil ◽  
Antiretroviral Drug Resistance ◽  
Drug Resistance Mutations ◽  
Antiretroviral Drug ◽  
Hiv 1

Antiretroviral drug-resistance mutations compromise the successful treatment of children and adolescents infected with human immunodeficiency virus type 1 (HIV-1). We describe the clinical, virological, and immunological follow-up of a cohort of children and adolescents perinatally infected with HIV-1 treated at Hospital Estadual de Doenças Tropicais Dr. Anuar Auad – HDT, in Central Brazil, after therapeutic failure related to drug resistance mutations.We analyzed the results of the genotypic test (protease codons 1–99 and reverse transcriptase codons 1–325) performed from 2003 to 2015. The ARV susceptibility profile was analyzed according to Stanford HIV drug resistance database. A total of 65 patients (median age of 10 years; range, 18 m–18 y) with therapeutic failure (after a median of 55 months of follow up; range, 9 m–13 y) and plasma levels of HIV-1 RNA greater than 1,000 copies/mL which were included and demonstrated mutations in: nucleoside reverse transcriptase inhibitors (NRTIs), 98.5%; non nucleoside reverse transcriptase inhibitors (NNRTIs), 75.4%; and protease inhibitors (PI), 44.6%. The most frequent NRTI mutations were found in codon T215 (83.1%) with a predominance of T215Y (56.9%), followed by M184V (69.3%). In the NNRTI class, mutations K103N (36.9%) and 190A (23.1%) were predominant, and, in the protease, mutations 54VL (35.4%) and 82ASTL (32.3%) were found in approximately the same proportion, with a predominance of the M54V mutation. These results demonstrate the high levels of resistance to different classes of antiretrovirals in HIV-infected children and adolescents and the importance of genotypic resistance tests in this population.KEY WORDS: HIV; drug resistance; genotypes; child; adolescent.

Sign in / Sign up

Export Citation Format

Share Document