Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Griffing S[original query] |
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Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru.
Akinyi S , Hayden T , Gamboa D , Torres K , Bendezu J , Abdallah JF , Griffing SM , Quezada WM , Arrospide N , De Oliveira AM , Lucas C , Magill AJ , Bacon DJ , Barnwell JW , Udhayakumar V . Sci Rep 2013 3 2797 ![]() The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. |
Public health impact of covid-19 vaccines in the US: observational study.
Suthar AB , Wang J , Seffren V , Wiegand RE , Griffing S , Zell E . BMJ 2022 377 e069317 ![]() OBJECTIVE: To evaluate the impact of vaccine scale-up on population level covid-19 mortality and incidence in the United States. DESIGN: Observational study. SETTING: US county level case surveillance and vaccine administration data reported from 14 December 2020 to 18 December 2021. PARTICIPANTS: Residents of 2558 counties from 48 US states. MAIN OUTCOME MEASURES: The primary outcome was county covid-19 mortality rates (deaths/100 000 population/county week). The secondary outcome was incidence of covid-19 (cases/100 000 population/county week). Incidence rate ratios were used to compare rates across vaccination coverage levels. The impact of a 10% improvement in county vaccination coverage (defined as at least one dose of a covid-19 vaccine among adults ≥18 years of age) was estimated During the eras of alpha and delta variant predominance, the impact of very low (0-9%), low (10-39%), medium (40-69%), and high (≥70%) vaccination coverage levels was compared. RESULTS: In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county weeks. A 10% improvement in vaccination coverage was associated with an 8% (95% confidence interval 8% to 9%) reduction in mortality rates and a 7% (6% to 8%) reduction in incidence. Higher vaccination coverage levels were associated with reduced mortality and incidence rates during the eras of alpha and delta variant predominance. CONCLUSIONS: Higher vaccination coverage was associated with lower rates of population level covid-19 mortality and incidence in the US. |
Counties with High COVID-19 Incidence and Relatively Large Racial and Ethnic Minority Populations - United States, April 1-December 22, 2020.
Lee FC , Adams L , Graves SJ , Massetti GM , Calanan RM , Penman-Aguilar A , Henley SJ , Annor FB , Van Handel M , Aleshire N , Durant T , Fuld J , Griffing S , Mattocks L , Liburd L . MMWR Morb Mortal Wkly Rep 2021 70 (13) 483-489 Long-standing systemic social, economic, and environmental inequities in the United States have put many communities of color (racial and ethnic minority groups) at increased risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, as well as more severe COVID-19-related outcomes (1-3). Because race and ethnicity are missing for a proportion of reported COVID-19 cases, counties with substantial missing information often are excluded from analyses of disparities (4). Thus, as a complement to these case-based analyses, population-based studies can help direct public health interventions. Using data from the 50 states and the District of Columbia (DC), CDC identified counties where five racial and ethnic minority groups (Hispanic or Latino [Hispanic], non-Hispanic Black or African American [Black], non-Hispanic Asian [Asian], non-Hispanic American Indian or Alaska Native [AI/AN], and non-Hispanic Native Hawaiian or other Pacific Islander [NH/PI]) might have experienced high COVID-19 impact during April 1-December 22, 2020. These counties had high 2-week COVID-19 incidences (>100 new cases per 100,000 persons in the total population) and percentages of persons in five racial and ethnic groups that were larger than the national percentages (denoted as "large"). During April 1-14, a total of 359 (11.4%) of 3,142 U.S. counties reported high COVID-19 incidence, including 28.7% of counties with large percentages of Asian persons and 27.9% of counties with large percentages of Black persons. During August 5-18, high COVID-19 incidence was reported by 2,034 (64.7%) counties, including 92.4% of counties with large percentages of Black persons and 74.5% of counties with large percentages of Hispanic persons. During December 9-22, high COVID-19 incidence was reported by 3,114 (99.1%) counties, including >95% of those with large percentages of persons in each of the five racial and ethnic minority groups. The findings of this population-based analysis complement those of case-based analyses. In jurisdictions with substantial missing race and ethnicity information, this method could be applied to smaller geographic areas, to identify communities of color that might be experiencing high potential COVID-19 impact. As areas with high rates of new infection change over time, public health efforts can be tailored to the needs of communities of color as the pandemic evolves and integrated with longer-term plans to improve health equity. |
Primary Indicators to Systematically Monitor COVID-19 Mitigation and Response - Kentucky, May 19-July 15, 2020.
Varela K , Scott B , Prather J , Blau E , Rock P , Vaughan A , Halldin C , Griffing S , Pfeiffer H , Hines J , Dirlikov E , Thoroughman D . MMWR Morb Mortal Wkly Rep 2020 69 (34) 1173-1176 State and local health departments in the United States are using various indicators to identify differences in rates of reported coronavirus disease 2019 (COVID-19) and severe COVID-19 outcomes, including hospitalizations and deaths. To inform mitigation efforts, on May 19, 2020, the Kentucky Department for Public Health (KDPH) implemented a reporting system to monitor five indicators of state-level COVID-19 status to assess the ability to safely reopen: 1) composite syndromic surveillance data, 2) the number of new COVID-19 cases,* 3) the number of COVID-19-associated deaths,(†) 4) health care capacity data, and 5) public health capacity for contact tracing (contact tracing capacity). Using standardized methods, KDPH compiles an indicator monitoring report (IMR) to provide daily analysis of these five indicators, which are combined with publicly available data into a user-friendly composite status that KDPH and local policy makers use to assess state-level COVID-19 hazard status. During May 19-July 15, 2020, Kentucky reported 12,742 COVID-19 cases, and 299 COVID-19-related deaths (1). The mean composite state-level hazard status during May 19-July 15 was 2.5 (fair to moderate). IMR review led to county-level hotspot identification (identification of counties meeting criteria for temporal increases in number of cases and incidence) and facilitated collaboration among KDPH and local authorities on decisions regarding mitigation efforts. Kentucky's IMR might easily be adopted by state and local health departments in other jurisdictions to guide decision-making for COVID-19 mitigation, response, and reopening. |
Update: COVID-19 Among Workers in Meat and Poultry Processing Facilities - United States, April-May 2020.
Waltenburg MA , Victoroff T , Rose CE , Butterfield M , Jervis RH , Fedak KM , Gabel JA , Feldpausch A , Dunne EM , Austin C , Ahmed FS , Tubach S , Rhea C , Krueger A , Crum DA , Vostok J , Moore MJ , Turabelidze G , Stover D , Donahue M , Edge K , Gutierrez B , Kline KE , Martz N , Rajotte JC , Julian E , Diedhiou A , Radcliffe R , Clayton JL , Ortbahn D , Cummins J , Barbeau B , Murphy J , Darby B , Graff NR , Dostal TKH , Pray IW , Tillman C , Dittrich MM , Burns-Grant G , Lee S , Spieckerman A , Iqbal K , Griffing SM , Lawson A , Mainzer HM , Bealle AE , Edding E , Arnold KE , Rodriguez T , Merkle S , Pettrone K , Schlanger K , LaBar K , Hendricks K , Lasry A , Krishnasamy V , Walke HT , Rose DA , Honein MA . MMWR Morb Mortal Wkly Rep 2020 69 (27) 887-892 Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts(dagger) across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry. |
COVID-19 Among Workers in Meat and Poultry Processing Facilities - 19 States, April 2020.
Dyal JW , Grant MP , Broadwater K , Bjork A , Waltenburg MA , Gibbins JD , Hale C , Silver M , Fischer M , Steinberg J , Basler CA , Jacobs JR , Kennedy ED , Tomasi S , Trout D , Hornsby-Myers J , Oussayef NL , Delaney LJ , Patel K , Shetty V , Kline KE , Schroeder B , Herlihy RK , House J , Jervis R , Clayton JL , Ortbahn D , Austin C , Berl E , Moore Z , Buss BF , Stover D , Westergaard R , Pray I , DeBolt M , Person A , Gabel J , Kittle TS , Hendren P , Rhea C , Holsinger C , Dunn J , Turabelidze G , Ahmed FS , deFijter S , Pedati CS , Rattay K , Smith EE , Luna-Pinto C , Cooley LA , Saydah S , Preacely ND , Maddox RA , Lundeen E , Goodwin B , Karpathy SE , Griffing S , Jenkins MM , Lowry G , Schwarz RD , Yoder J , Peacock G , Walke HT , Rose DA , Honein MA . MMWR Morb Mortal Wkly Rep 2020 69 (18) Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4). |
Plasmodium falciparum Drug-Resistant Haplotypes and Population Structure in Postearthquake Haiti, 2010.
Morton LC , Huber C , Okoth SA , Griffing S , Lucchi N , Ljolje D , Boncy J , Oscar R , Townes D , McMorrow M , Chang MA , Udhayakumar V , Barnwell JW . Am J Trop Med Hyg 2016 95 (4) 811-816 ![]() Chloroquine (CQ) remains the first-line treatment of malaria in Haiti. Given the challenges of conducting in vivo drug efficacy trials in low-endemic settings like Haiti, molecular surveillance for drug resistance markers is a reasonable approach for detecting resistant parasites. In this study, 349 blood spots were collected from suspected malaria cases in areas in and around Port-au-Prince from March to July 2010. Among them, 121 samples that were Plasmodium falciparum positive by polymerase chain reaction were genotyped for drug-resistant pfcrt, pfdhfr, pfdhps, and pfmdr1 alleles. Among the 108 samples that were successfully sequenced for CQ resistant markers in pfcrt, 107 were wild type (CVMNK), whereas one sample carried a CQ-resistant allele (CVIET). Neutral microsatellite genotyping revealed that the CQ-resistant isolate was distinct from all other samples in this study. Furthermore, the remaining parasite specimens appeared to be genetically distinct from other reported Central and South American populations. |
A historical perspective on malaria control in Brazil
Griffing SM , Tauil PL , Udhayakumar V , Silva-Flannery L . Mem Inst Oswaldo Cruz 2015 110 (6) 701-718 Malaria has always been an important public health problem in Brazil. The early history of Brazilian malaria and its control was powered by colonisation by Europeans and the forced relocation of Africans as slaves. Internal migration brought malaria to many regions in Brazil where, given suitable Anopheles mosquito vectors, it thrived. Almost from the start, officials recognised the problem malaria presented to economic development, but early control efforts were hampered by still developing public health control and ignorance of the underlying biology and ecology of malaria. Multiple regional and national malaria control efforts have been attempted with varying success. At present, the Amazon Basin accounts for 99% of Brazil’s reported malaria cases with regional increases in incidence often associated with large scale public works or migration. Here, we provide an exhaustive summary of primary literature in English, Spanish and Portuguese regarding Brazilian malaria control. Our goal was not to interpret the history of Brazilian malaria control from a particular political or theoretical perspective, but rather to provide a straightforward, chronological narrative of the events that have transpired in Brazil over the past 200 years and identify common themes. |
Canonical Single Nucleotide Polymorphisms (SNPs) for High-Resolution Subtyping of Shiga-Toxin Producing Escherichia coli (STEC) O157:H7.
Griffing SM , MacCannell DR , Schmidtke AJ , Freeman MM , Hyytia-Trees E , Gerner-Smidt P , Ribot EM , Bono JL . PLoS One 2015 10 (7) e0131967 ![]() The objective of this study was to develop a canonical, parsimoniously-informative SNP panel for subtyping Shiga-toxin producing Escherichia coli (STEC) O157:H7 that would be consistent with epidemiological, PFGE, and MLVA clustering of human specimens. Our group had previously identified 906 putative discriminatory SNPs, which were pared down to 391 SNPs based on their prevalence in a test set. The 391 SNPs were screened using a high-throughput form of TaqMan PCR against a set of clinical isolates that represent the most diverse collection of O157:H7 isolates from outbreaks and sporadic cases examined to date. Another 30 SNPs identified by others were also screened using the same method. Two additional targets were tested using standard TaqMan PCR endpoint analysis. These 423 SNPs were reduced to a 32 SNP panel with the almost the same discriminatory value. While the panel partitioned our diverse set of isolates in a manner that was consistent with epidemiological data and PFGE and MLVA phylogenies, it resulted in fewer subtypes than either existing method and insufficient epidemiological resolution in 10 of 47 clusters. Therefore, another round of SNP discovery was undertaken using comparative genomic resequencing of pooled DNA from the 10 clusters with insufficient resolution. This process identified 4,040 potential SNPs and suggested one of the ten clusters was incorrectly grouped. After its removal, there were 2,878 SNPs, of which only 63 were previously identified and 438 occurred across multiple clusters. Among highly clonal bacteria like STEC O157:H7, linkage disequilibrium greatly limits the number of parsimoniously informative SNPs. Therefore, it is perhaps unsurprising that our panel accounted for the potential discriminatory value of numerous other SNPs reported in the literature. We concluded published O157:H7 SNPs are insufficient for effective epidemiological subtyping. However, the 438 multi-cluster SNPs we identified may provide the additional information required. |
Malaria control and elimination, Venezuela, 1800s-1970s
Griffing SM , Villegas L , Udhayakumar V . Emerg Infect Dis 2014 20 (10) 1697-1704 Venezuela had the highest number of human malaria cases in Latin American before 1936. During 1891-1920, malaria was endemic to >600,000 km2 of this country; malaria death rates led to major population decreases during 1891-1920. No pathogen, including the influenza virus that caused the 1918 pandemic, caused more deaths than malaria during 1905-1945. Early reports of malaria eradication in Venezuela helped spark the world's interest in global eradication. We describe early approaches to malaria epidemiology in Venezuela and how this country developed an efficient control program and an approach to eradication. Arnoldo Gabaldon was a key policy maker during this development process. He directed malaria control in Venezuela from the late 1930s to the end of the 1970s and contributed to malaria program planning of the World Health Organization. We discuss how his efforts helped reduce the incidence of malaria in Venezuela and how his approach diverged from World Health Organization guidelines. |
The history of 20th century malaria control in Peru
Griffing SM , Gamboa D , Udhayakumar V . Malar J 2013 12 303 Malaria has been part of Peruvian life since at least the 1500s. While Peru gave the world quinine, one of the first treatments for malaria, its history is pockmarked with endemic malaria and occasional epidemics. In this review, major increases in Peruvian malaria incidence over the past hundred years are described, as well as the human factors that have facilitated these events, and concerted private and governmental efforts to control malaria. Political support for malaria control has varied and unexpected events like vector and parasite resistance have adversely impacted morbidity and mortality. Though the ready availability of novel insecticides like DDT and efficacious medications reduced malaria to very low levels for a decade after the post eradication era, malaria reemerged as an important modern day challenge to Peruvian public health. Its reemergence sparked collaboration between domestic and international partners towards the elimination of malaria in Peru. |
Historical shifts in Brazilian P. falciparum population structure and drug resistance alleles.
Griffing SM , Viana GM , Mixson-Hayden T , Sridaran S , Alam MT , de Oliveira AM , Barnwell JW , Escalante AA , Povoa MM , Udhayakumar V . PLoS One 2013 8 (3) e58984 ![]() Previous work suggests that Brazilian Plasmodium falciparum has limited genetic diversity and a history of bottlenecks, multiple reintroductions due to human migration, and clonal expansions. We hypothesized that Brazilian P. falciparum would exhibit clonal structure. We examined isolates collected across two decades from Amapa, Rondonia, and Para state (n = 190). By examining more microsatellites markers on more chromosomes than previous studies, we hoped to define the extent of low diversity, linkage disequilibrium, bottlenecks, population structure, and parasite migration within Brazil. We used retrospective genotyping of samples from the 1980s and 1990s to explore the population genetics of SP resistant dhfr and dhps alleles. We tested an existing hypothesis that the triple mutant dhfr mutations 50R/51I/108N and 51I/108N/164L developed in southern Amazon from a single origin of common or similar parasites. We found that Brazilian P. falciparum had limited genetic diversity and isolation by distance was rejected, which suggests it underwent bottlenecks followed by migration between sites. Unlike Peru, there appeared to be gene flow across the Brazilian Amazon basin. We were unable to divide parasite populations by clonal lineages and pairwise FST were common. Most parasite diversity was found within sites in the Brazilian Amazon, according to AMOVA. Our results challenge the hypothesis that triple mutant alleles arose from a single lineage in the Southern Amazon. SP resistance, at both the double and triple mutant stages, developed twice and potentially in different regions of the Brazilian Amazon. We would have required samples from before the 1980s to describe how SP resistance spread across the basin or describe the complex internal migration of Brazilian parasites after the colonization efforts of past decades. The Brazilian Amazon basin may have sufficient internal migration for drug resistance reported in any particular region to rapidly spread to other parts of basin under similar drug pressure. |
South American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids.
Griffing SM , Mixson-Hayden T , Sridaran S , Alam MT , McCollum AM , Cabezas C , Marquino Quezada W , Barnwell JW , Macedo De Oliveira A , Lucas C , Arrospide N , Escalante AA , Bacon DJ , Udhayakumar V . PLoS One 2011 6 (9) e23486 ![]() Malaria has reemerged in many regions where once it was nearly eliminated. Yet the source of these parasites, the process of repopulation, their population structure, and dynamics are ill defined. Peru was one of malaria eradication's successes, where Plasmodium falciparum was nearly eliminated for two decades. It reemerged in the 1990s. In the new era of malaria elimination, Peruvian P. falciparum is a model of malaria reinvasion. We investigated its population structure and drug resistance profiles. We hypothesized that only populations adapted to local ecological niches could expand and repopulate and originated as vestigial populations or recent introductions. We investigated the genetic structure (using microsatellites) and drug resistant genotypes of 220 parasites collected from patients immediately after peak epidemic expansion (1999-2000) from seven sites across the country. The majority of parasites could be grouped into five clonal lineages by networks and AMOVA. The distribution of clonal lineages and their drug sensitivity profiles suggested geographic structure. In 2001, artesunate combination therapy was introduced in Peru. We tested 62 parasites collected in 2006-2007 for changes in genetic structure. Clonal lineages had recombined under selection for the fittest parasites. Our findings illustrate that local adaptations in the post-eradication era have contributed to clonal lineage expansion. Within the shifting confluence of drug policy and malaria incidence, populations continue to evolve through genetic outcrossing influenced by antimalarial selection pressure. Understanding the population substructure of P. falciparum has implications for vaccine, drug, and epidemiologic studies, including monitoring malaria during and after the elimination phase. |
Selective sweeps and genetic lineages of Plasmodium falciparum drug -resistant alleles in Ghana.
Alam MT , de Souza DK , Vinayak S , Griffing SM , Poe AC , Duah NO , Ghansah A , Asamoa K , Slutsker L , Wilson MD , Barnwell JW , Udhayakumar V , Koram KA . J Infect Dis 2011 203 (2) 220-7 ![]() BACKGROUND: In 2005, Ghana adopted artemisinin-based combination therapy (ACT) for primary treatment of falciparum malaria. A comprehensive study of the drug-resistance-associated mutations and their genetic lineages will lead to a better understanding of the evolution of antimalarial drug resistance in this region. METHODS: The pfcrt, pfmdr1, dhps, and dhfr mutations associated with chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance and the microsatellite loci flanking these genes were genotyped in Plasmodium falciparum isolates from Ghana. RESULTS: The prevalence of mutations associated with both CQ and SP resistance was high in Ghana. However, we observed a decrease in prevalence of the pfcrt K76T mutation in northern Ghana after the change in drug policy from CQ to ACT. Analysis of genetic diversity and differentiation at microsatellite loci flanking all 4 genes indicated that they have been under strong selection, because of CQ and SP use. The triple-mutant pfcrt and dhfr alleles in Ghana were derived from Southeast Asia, whereas the double-mutant dhfr, dhps, and pfmdr1 alleles were of African lineage. CONCLUSION: Because of the possible role of pfmdr1 in amodiaquine and mefloquine resistance, demonstrating selection on pfmdr1 and defining lineages of resistant alleles in an African population holds great importance. |
Pfmdr1 amplification and fixation of chloroquine resistant pfcrt alleles in Venezuela
Griffing S , Syphard L , Sridaran S , McCollum AM , Mixson-Hayden T , Vinayak S , Villegas L , Barnwell JW , Escalante AA , Udhayakumar V . Antimicrob Agents Chemother 2010 54 (4) 1572-9 Molecular tools are valuable for determining evolutionary history and the prevalence of drug-resistant malaria parasites. These tools have helped to predict decreased sensitivity to antimalarials and fixation of multidrug resistant genotypes in some regions. In order to assess how historical drug policies impacted Venezuelan Plasmodium falciparum, we examined molecular changes to genes associated with drug resistance. We examined pfmdr1 and pfcrt in samples from Sifontes, Venezuela and integrated our findings with earlier work describing dhfr and dhps in these samples. We characterized pfmdr1 genotypes and copy number variation, pfcrt genotypes, and proximal microsatellites in 93 samples originating from 2003-2004 surveillance. Multicopy pfmdr1 was found in 12% of the samples. Two pfmdr1 alleles, Y184F/N1042D/D1246Y (37%) and Y184F/S1034C/N1042D/D1246Y (63%), were found. These alleles share ancestry and no evidence of strong selective pressure on mutations was found. Chloroquine resistant pfcrt alleles are fixed with two alleles: StctVMNT (91%) and SagtVMNT (9%). These alleles are associated with strong selection. There was also an association between pfcrt, pfmdr1, dhfr, and dhps genotypes/haplotypes. Duplication of pfmdr1 suggests a potential shift in mefloquine sensitivity in this region, which warrants further study. A bottleneck occurred in P. falciparum in Sifontes and multidrug resistant genotypes are present. This population could be targeted for malaria elimination programs to prevent the possible spread of multidrug resistant parasites. |
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