Population genomics and evidence of clonal replacement of Plasmodium falciparum in the Peruvian Amazon

AbstractPrevious studies have shown that P. falciparum parasites in South America have undergone population bottlenecks resulting in clonal lineages that are differentially distributed and that have been responsible for several outbreaks different endemic regions. In this study, we explored the genomic profile of 18 P. falciparum samples collected in the Peruvian Amazon Basin (Loreto) and 6 from the Peruvian North Coast (Tumbes). Our results showed the presence of three subpopulations that matched previously typed lineages in Peru: Bv1 (n = 17), Clonet D (n = 4) and Acre-Loreto type (n = 3). Gene coverage analysis showed that none of the Bv1 samples presented coverage for pfhrp2 and pfhrp3. Genotyping of drug resistance markers showed a high prevalence of Chloroquine resistance mutations S1034C/N1042D/D1246Y in pfmdr1 (62.5%) and K45T in pfcrt (87.5%). Mutations associated with sulfadoxine and pyrimethamine treatment failure were found on 88.8% of the Bv1 samples which were triple mutants for pfdhfr (50R/51I/108N) and pfdhps (437G/540E/581G). Analysis of the pfS47 gene that allows P. falciparum to evade mosquito immune responses showed that the Bv1 lineage presented one pfS47 haplotype exclusive to Loreto and another haplotype that was present in both Loreto and Tumbes. Furthermore, a possible expansion of Bv1 was detected since 2011 in Loreto. This replacement could be a result of the high prevalence of CQ resistance polymorphisms in Bv1, which could have provided a selective advantage to the indirect selection pressures driven by the use of CQ for P. vivax treatment.

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HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting

Journal of the International Association of Providers of AIDS Care (JIAPAC) ◽

10.1177/2325958219849061 ◽

2019 ◽

Vol 18 ◽

pp. 232595821984906

Author(s):

Nawaid Hussain Khan ◽

Mikashmi Kohli ◽

Kartik Gupta ◽

Bimal Kumar Das ◽

Ravindra Mohan Pandey ◽

...

Keyword(s):

Reverse Transcriptase ◽

Drug Resistant ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

First Line Therapy ◽

Resource Limited ◽

High Prevalence ◽

Hiv 1 ◽

Limited Setting

Introduction: The present study aimed to report the prevalent HIV-1 drug-resistant mutations in patients with HIV-1 alone and tuberculosis (TB) coinfection alone to improve our understanding of the mutation patterns and aid treatment decisions. Methods: Patients with HIV-1 and HIV-TB on treatment for more than 1 year with suspected failure were recruited. Sequencing of protease and two-thirds of the region of reverse transcriptase gene was done for drug-resistant mutations. Results: In the HIV-TB group (n = 25), 88%, 92%, and 12% had mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), respectively. In the HIV-alone group (n = 25), 84%, 100%, and 4% had mutations to NRTIs, NNRTIs, and PIs, respectively. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. Conclusion: There is a high prevalence of drug-resistant mutations in HIV and HIV-TB coinfected patients.

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Low Levels of Pyrethroid Resistance in Hybrid Offspring of a Highly Resistant and a More Susceptible Mosquito Strain

Journal of Insect Science ◽

10.1093/jisesa/ieaa060 ◽

2020 ◽

Vol 20 (4) ◽

Author(s):

Matthew Pinch ◽

Stacy D Rodriguez ◽

Soumi Mitra ◽

Yashoda Kandel ◽

Emily Moore ◽

...

Keyword(s):

Insecticide Resistance ◽

Pyrethroid Resistance ◽

Resistance Mutations ◽

Human Host ◽

High Prevalence ◽

Rapid Spread ◽

Choice Assay ◽

Low Levels ◽

Control Disease ◽

Different Strains

Abstract The use of insecticides has been a central approach to control disease-transmitting mosquitoes for the last century. The high prevalence of pyrethroid use as public health insecticides has resulted in the evolution of pyrethroid resistance in many populations of Aedes aegypti (Linnaeus) (Diptera: Culicidae), throughout its global distribution range. Insecticide resistance is often correlated with an associated fitness cost. In this project, we studied the phenotypes of hybrid mosquitoes derived from crossing a pyrethroid-resistant strain of Ae. aegypti (Puerto Rico [PR]) with a more susceptible one (Rockefeller [ROCK]). We first sequenced and compared the para gene of both original strains. We then crossed males from one strain with females of the other, creating two hybrids (Puertofeller, Rockorico). We used a Y-tube choice assay to measure the attraction of these strains towards a human host. We then compared the levels of pyrethroid resistance in the different strains. We found three known resistance mutations in the para gene sequence of the PR strain. In our attraction assays, PR females showed lower attraction to humans, than the ROCK females. Both hybrid strains showed strong attraction to a human host. In the insecticide resistance bottle assays, both hybrid strains showed marginal increases in resistance to permethrin compared to the more susceptible ROCK strain. These results suggest that hybrids of sensitive and permethrin-resistant mosquitoes have an incremental advantage compared to more susceptible mosquitoes when challenged with permethrin. This explains the rapid spread of permethrin resistance that was observed many times in the field.

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A Cross-Sectional Study of Seroprevalence of Strongyloidiasis in Pregnant Women (Peruvian Amazon Basin)

Pathogens ◽

10.3390/pathogens9050348 ◽

2020 ◽

Vol 9 (5) ◽

pp. 348

Author(s):

Sonia Ortiz-Martínez ◽

José-Manuel Ramos-Rincón ◽

María-Esteyner Vásquez-Chasnamote ◽

Jhonatan Alarcón-Baldeón ◽

Jorge Parraguez-de-la-Cruz ◽

...

Keyword(s):

Pregnant Women ◽

Negative Predictive Value ◽

Predictive Value ◽

Amazon Basin ◽

Cross Sectional Study ◽

Index Test ◽

Peruvian Amazon ◽

Sectional Study ◽

Cross Sectional ◽

Baermann Technique

Strongyloidiasis is a soil-transmitted helminthiasis with a high global prevalence. Objectives: We aimed to evaluate the prevalence of Strongyloides stercoralis infection and assess strongyloidiasis serology as a screening technique in the Peruvian Amazon. Material and Methods: We performed a cross-sectional study of strongyloidiasis in 300 pregnant women in Iquitos (Peru) from 1 May 2019 to 15 June 2019. Women were tested using serology (Strongyloides IgG IVD-ELISA kit) as an index test and the modified Baermann technique and/or charcoal fecal culture as the parasitological reference standard. Results: The reference tests showed S. stercoralis in the stool of 30 women (prevalence: 10%; 95% confidence interval [CI] 7.1% to 13.9%), while 101 women tested positive on the blood test (prevalence: 33.7%; 95% CI 28.6% to 39.4%). Fourteen of the 15 women (93.3%) with positive results according to the modified Baermann technique, and 14 of the 23 women (56.5%) with positive charcoal cultures also had positive serological results. Serology showed a sensitivity of 63.3% and a negative predictive value of 94.4%. Conclusion: In Iquitos, pregnant women have a high prevalence of S stercoralis. S. stercoralis ELISA could be an excellent tool for population-based screening, as it has a high negative predictive value that can help to rule out the presence of active infection.

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Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz258 ◽

2019 ◽

Vol 74 (9) ◽

pp. 2759-2766 ◽

Cited By ~ 17

Author(s):

Agustin Resendiz-Sharpe ◽

Toine Mercier ◽

Pieter P A Lestrade ◽

Martha T van der Beek ◽

Peter A von dem Borne ◽

...

Keyword(s):

Invasive Aspergillosis ◽

Resistance Mutations ◽

Icu Patients ◽

High Prevalence ◽

High Risk Populations ◽

Haematology Patients ◽

Culture Positive ◽

Very High ◽

Multicentre Cohort ◽

Overall Mortality

Abstract Background Increasing resistance of Aspergillus fumigatus to triazoles in high-risk populations is a concern. Its impact on mortality is not well understood, but rates from 50% to 100% have been reported. Objectives To determine the prevalence of voriconazole-resistant A. fumigatus invasive aspergillosis (IA) and its associated mortality in a large multicentre cohort of haematology patients with culture-positive IA. Methods We performed a multicentre retrospective study, in which outcomes of culture-positive haematology patients with proven/probable IA were analysed. Patients were stratified based on the voriconazole susceptibility of their isolates (EUCAST broth microdilution test). Mycological and clinical data were compared, along with survival at 6 and 12 weeks. Results We identified 129 A. fumigatus culture-positive proven or probable IA cases; 103 were voriconazole susceptible (79.8%) and 26 were voriconazole resistant (20.2%). All but one resistant case harboured environment-associated resistance mutations in the cyp51A gene: TR34/L98H (13 cases) and TR46/Y121F/T289A (12 cases). Triazole monotherapy was started in 75.0% (97/129) of patients. Mortality at 6 and 12 weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P = 0.20; and 57.7% versus 36.9%, P = 0.064) and in non-ICU patients (36.4% versus 21.6%, P = 0.16; and 54.4% versus 30.7%; P = 0.035), compared with susceptible ones. ICU patient mortality at 6 and 12 weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P = 0.99; and 75.0% versus 73.3%, P = 0.99). Conclusions A very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12 weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA.

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Decline in Sulfadoxine-Pyrimethamine-Resistant Alleles after Change in Drug Policy in the Amazon Region of Peru

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00975-07 ◽

2007 ◽

Vol 52 (2) ◽

pp. 739-741 ◽

Cited By ~ 33

Author(s):

Zhiyong Zhou ◽

Sean M. Griffing ◽

Alexandre Macedo de Oliveira ◽

Andrea M. McCollum ◽

Wilmer Marquino Quezada ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Drug Policy ◽

Amazon Basin ◽

Microsatellite Analysis ◽

Amazon Region ◽

Common Origin ◽

Line Treatment ◽

Peruvian Amazon ◽

First Line ◽

First Line Treatment

ABSTRACT The frequency of alleles with triple mutations conferring sulfadoxine-pyrimethamine (SP) resistance in the Peruvian Amazon Basin has declined (16.9% for dhfr and 0% for dhps compared to 47% for both alleles in 1997) 5 years after SP was replaced as the first-line treatment for Plasmodium falciparum malaria. Microsatellite analysis showed that the dhfr and dhps alleles are of common origin.

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High Prevalence of Antiretroviral Drug Resistance Mutations in HIV-1 Non-B Subtype Strains From African Children Receiving Antiretroviral Therapy Regimen According to the 2006 Revised WHO Recommendations

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0b013e318183acae ◽

2008 ◽

Vol 49 (5) ◽

pp. 566-569 ◽

Cited By ~ 28

Author(s):

Jean-Chrysostome Gody ◽

Charlotte Charpentier ◽

Olivia Mbitikon ◽

Ali Si-Mohamed ◽

Jérome LeGoff ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Resistance Mutations ◽

Therapy Regimen ◽

Antiretroviral Drug Resistance ◽

Drug Resistance Mutations ◽

African Children ◽

Antiretroviral Drug ◽

High Prevalence ◽

Hiv 1

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Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure

eLife ◽

10.7554/elife.01229 ◽

2013 ◽

Vol 2 ◽

Cited By ~ 63

Author(s):

Stephen Baker ◽

Pham Thanh Duy ◽

Tran Vu Thieu Nga ◽

Tran Thi Ngoc Dung ◽

Voong Vinh Phat ◽

...

Keyword(s):

Target Genes ◽

Systemic Infection ◽

Critical Factor ◽

Selective Advantage ◽

Salmonella Typhi ◽

Antimicrobial Treatment ◽

Resistance Mutations ◽

Resistant Strains ◽

And Control

Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced.

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