Malaria vector research and control in Haiti: a systematic review

BACKGROUND: Haiti has a set a target of eliminating malaria by 2020. However, information on malaria vector research in Haiti is not well known. This paper presents results from a systematic review of the literature on malaria vector research, bionomics and control in Haiti. METHODS: A systematic search of literature published in French, Spanish and English languages was conducted in 2015 using Pubmed (MEDLINE), Google Scholar, EMBASE, JSTOR WHOLIS and Web of Science databases as well other grey literature sources such as USAID, and PAHO. The following search terms were used: malaria, Haiti, Anopheles, and vector control. RESULTS: A total of 132 references were identified with 40 high quality references deemed relevant and included in this review. Six references dealt with mosquito distribution, seven with larval mosquito ecology, 16 with adult mosquito ecology, three with entomological indicators of malaria transmission, eight with insecticide resistance, one with sero-epidemiology and 16 with vector control. In the last 15 years (2000–2015), there have only been four published papers and three-scientific meeting abstracts on entomology for malaria in Haiti. Overall, the general literature on malaria vector research in Haiti is limited and dated. DISCUSSION: Entomological information generated from past studies in Haiti will contribute to the development of strategies to achieve malaria elimination on Hispaniola. However it is of paramount importance that malaria vector research in Haiti is updated to inform decision-making for vector control strategies in support of malaria elimination

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

<div><p>Asymptomatic <i>Plasmodium falciparum</i> 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 <i>P</i>. <i>falciparum</i> protein microarray, which demonstrated serologic reactivity to 3,877 <i>P</i>. <i>falciparum</i> 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 <i>P</i>. <i>falciparum</i> 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 CD8^mid T cells in asymptomatics compared to symptomatics. Also, CD38⁺/HLA-DR⁺ expression on γδ T cells, CD8^mid (CD56^-) T cells, and CD8^mid 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 <i>P</i>. <i>falciparum</i> 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 <i>Plasmodium</i> immunity, a research goal of critical priority.</p></div

Map of the department of Sud-Est Haiti displaying sites of asymptomatic and symptomatic malaria patients were collected.

<p>Map of the Department of Sud-Est, Haiti with clinical sites La Brésilienne (LB) and Anse à Boeuf (AB) where individuals’ samples were collected from these two respective villages. The two sites were over 70 km apart in distance, and had poorly traversable roads between the two villages. Map of the island of Hispaniola (insert) displaying the two countries Haiti and the Dominican Republic is included. A topographic scale is provided for reference purposes. Maps were provided by Wikipedia and Wikimedia Commons, and were modified to display sample sites accurately.</p

Demographics of the participants from Sud-Est, Haiti.

<p>Demographics of the participants from Sud-Est, Haiti.</p

Heat map and principal component analysis of reciprocally expressed cytokines.

<p><b>(A)</b> A heat map was generating using log₂-transformed concentration values of 15 differentially expressed cytokines identified using multiplex analysis to visualize differences between symptomatic and asymptomatic malaria patient groups. Values were centered by subtracting the mean cytokine concentration from all samples from each individual data point. <b>(B)</b> Scatter plot of the first two principal components (comprising 66.1% of total variance) calculated using singular value decomposition (SVD) with imputation. Symptomatic patient values (blue closed circles) and asymptomatic patient values (red closed circles) cluster separately. Colored ellipses denote calculated 95% confidence levels of new observations from other patients from this population structure (symptomatic vs. asymptomatic) falling within the respective regions. There is minimal overlap between the confidence levels between patient populations. Both the heat map and PCA were constructed using ClustVis [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0174718#pone.0174718.ref039" target="_blank">39</a>].</p

<i>P. falciparum</i> responsive T cell subtypes identify asymptomatic malaria patients.

<p>PBMCs from malaria patients were co-cultured for 6 days with lysate from uRBC or <i>P</i>. <i>falciparum</i> schizonts (iRBC lysate) at a lymphocyte to parasite ratio of 1:2. Changes in the percentages of T cell subpopulations during culture were compared between asymptomatic (n = 9, Asymp) and symptomatic (n = 6, Symp) patients in <b>(A)</b> NKT-like T cells, <b>(B)</b> CD8^mid T cells, <b>(C)</b> γδ T cells, <b>(D)</b> CD56⁺ γδ T cells, <b>(E)</b> CD4⁺ T cells, and <b>(F)</b> CD25⁺ CD127^low T regulatory cells. Data are represented as box and whisker plots, with box ends extending from the first to the third quartile and the median in the center. Whiskers extend to the highest and lowest data point. Statistical significance was determined using a two-tailed Wilcoxon matched-pairs signed rank test (iRBC lysate vs. uRBC for each patient). * = p-value < 0.05, ** = p-value < 0.01.</p

Results from Pf protein microarray analysis of IgG & IgM antibody repertoires from asymptomatic and symptomatic malaria patients in Sud-Est, Haiti.

<p>Plasma from asymptomatic (n = 16) and symptomatic (n = 13) malaria patients from the Sud-Est Department in Haiti were reacted with a partial Pf proteome microarrays. Arrays contained 3,877 peptide fragments from 2,704 unique genes, representing approximately 50% coverage of the Pf proteome. <b>(A)</b> Box plots representing antibody breadth score per patient for both IgG and IgM, described as sum of seropositive responses per individual. Breadth did not show an effect on probability of having symptoms. <b>(B)</b> Box plots of IgG responses of asymptomatic and symptomatic patients to top 20 antigens by magnitude. <b>(C)</b> Box plots of IgM responses of asymptomatic and symptomatic patients to top 20 antigens by magnitude. The magnitude of neither IgG nor IgM responses showed an effect on probability of having symptoms. <b>(A-C)</b> box lines represent the median and interquartile ranges, where the whiskers represent all points within 1.5 times the interquartile range, and points represent outliers.</p