<i>Plasmodium falciparum</i>K76T<i>pfcrt</i>Gene Mutations and Parasite Population Structure, Haiti, 2006–2009

Charles, Macarthur; Das, Sanchita; Daniels, Rachel F.; Kirkman, Laura A.; Delva, Glavdia G.; Destiné, Rodney; Escalante, Ananías A.; Villegas, Leopoldo; Daniels, Noah M.; Shigyo, Kristi; Volkman, Sarah K.; Pape, Jean William; Golightly, Linnie M.

doi:10.3201/eid2205.150359

Cited by 11 publications

(17 citation statements)

References 18 publications

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“…Nevertheless, in previous studies. 26 The samples used were collected from different sites in multiple departments in Haiti, and the results obtained were concordant with those of this study.…”

Section: Discussionsupporting

confidence: 82%

“…During the months after the 2010 earthquake, it was not clear whether the influx of emergency-aid workers from various parts of the world would introduce new parasite populations including CQ-resistant parasites. According to this study, and other reports, 26 the prevalence of CQ-resistant mutations has remained very low or is nonexistent in Haiti. [8][9][10] Of the 108 samples that we tested, there was only a single P. falciparum isolate that carried numerous pfcrt, pfdhps, and pfdhfr mutations associated with drug resistance.…”

Section: Discussionsupporting

confidence: 65%

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Plasmodium falciparum Drug-Resistant Haplotypes and Population Structure in Postearthquake Haiti, 2010

Morton

Huber

Okoth

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. 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.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 65%

Plasmodium falciparum Drug-Resistant Haplotypes and Population Structure in Postearthquake Haiti, 2010

Morton

Huber

Okoth

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…The two studies by Charles and others and Morton and others together contributed results from 1,009 samples that were collected over the consecutive years from 2005 to 2010 from multiple sites. 21 , 22 The analysis for mutations in the pfcrt gene found three of 1,009 (0.3%) samples with chloroquine-resistant haplotypes, of which two could not be unequivocally verified. Additional studies on the population genetics of the parasites revealed that the P. falciparum clones in Haiti are highly related and distinct from other countries.…”

Section: Ensuring Efficacy Of Antimalarial Drugs and Preventive Intermentioning

confidence: 98%

Haiti’s Commitment to Malaria Elimination: Progress in the Face of Challenges, 2010–2016

Lemoine¹,

Boncy²,

Filler

et al. 2017

The American Journal of Tropical Medicine and Hygiene

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Abstract.Haiti is committed to malaria elimination by 2020. Following a 2010 earthquake and cholera epidemic, Haiti capitalized on investments in its health system to refocus on malaria elimination. Efforts, including expanding diagnostics, ensuring efficacy of standard treatments, building institutional capacity, and strengthening surveillance were undertaken to complement the broad health system strengthening activities. These efforts led to the adoption and scale-up of malaria rapid diagnostic tests as a diagnostic modality. In addition, drug-resistant monitoring has been established in the country, along with the development of molecular testing capacity for the Plasmodium falciparum parasite at the National Public Health Laboratory. The development and piloting of surveillance activities to include an enhanced community-based approach for testing and treatment of patients has increased the ability of the Ministry of Health to map foci of transmission and respond promptly to outbreaks. The reinforcement of evidence-based approaches coupled with strong collaboration among the Ministry of Health and partners has demonstrated that malaria elimination by 2020 is a realistic prospect.

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“…falciparum (Pf) is the one and only cause of endemic malaria on Hispaniola (there is a lack other Plasmodium species associated with human infection on the island) and thus elimination efforts are being concentrated on this one organism [4]; 3) chloroquine resistance to P . falciparum is rarely reported in Haiti, despite wide use as the standard of treatment for both Haiti and the Dominican Republic [5–7]. …”

Section: Introductionmentioning

confidence: 99%

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

Lehmann

Campo

Cicéron³

et al. 2017

PLoS ONE

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Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects. Plasma samples were analyzed with a P. falciparum protein microarray, which demonstrated serologic reactivity to 3,877 P. falciparum proteins of known serologic reactivity; however, no antigen-antibody reactions delineating asymptomatics from symptomatics were identified. In contrast, differences in cellular responses were observed. Flow cytometric analysis of patient peripheral blood mononuclear cells co-cultured with P. falciparum infected erythrocytes demonstrated a statistically significant increase in the proportion of T regulatory cells (CD4+ CD25+ CD127-), and increases in unique populations of both NKT-like cells (CD3+ CD8+ CD56+) and CD8mid T cells in asymptomatics compared to symptomatics. Also, CD38+/HLA-DR+ expression on γδ T cells, CD8mid (CD56-) T cells, and CD8mid CD56+ NKT-like cells decreased upon exposure to infected erythrocytes in both groups. Cytometric bead analysis of the co-culture supernatants demonstrated an upregulation of monocyte-activating chemokines/cytokines in asymptomatics, while immunomodulatory soluble factors were elevated in symptomatics. Principal component analysis of these expression values revealed a distinct clustering of individual responses within their respective phenotypic groups. This is the first comprehensive investigation of immune responses to P. falciparum in Haiti, and describes unique cell-mediated immune repertoires that delineate individuals into asymptomatic and symptomatic phenotypes. Future investigations using large scale biological data sets analyzing multiple components of adaptive immunity, could collectively define which cellular responses and molecular correlates of disease outcome are malaria region specific, and which are truly generalizable features of asymptomatic Plasmodium immunity, a research goal of critical priority.

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Plasmodium falciparumK76TpfcrtGene Mutations and Parasite Population Structure, Haiti, 2006–2009

Abstract: Low genetic diversity and low levels of chloroquine resistance among parasites suggest exogenous origin of reported cases.

Cited by 11 publications

References 18 publications

Plasmodium falciparum Drug-Resistant Haplotypes and Population Structure in Postearthquake Haiti, 2010

Plasmodium falciparum Drug-Resistant Haplotypes and Population Structure in Postearthquake Haiti, 2010

Haiti’s Commitment to Malaria Elimination: Progress in the Face of Challenges, 2010–2016

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

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