Prevalence of malaria parasitemia and accuracy of microscopic diagnosis in Haiti, October 1995

In October 1995 the Ministry of Public Health and Population in Haiti surveyed 42 health facilities for the prevalence and distribution of malaria infection. They examined 1 803 peripheral blood smears from patients with suspected malaria; the overall slide positivity rate was 4.0% (range, 0.0% to 14.3%). The rate was lowest among 1- to 4-year-old children (1.6%) and highest among persons aged 15 and older (5.5%). Clinical and microscopic diagnoses of malaria were unreliable; the overall sensitivity of microscopic diagnosis was 83.6%, specificity was 88.6%, and the predictive value of a positive slide was 22.2%. Microscopic diagnoses need to be improved, and adequate surveillance must be reestablished to identify areas where transmission is most intense. The generally low level of malaria is encouraging and suggests that intensified control efforts targeted to the areas of highest prevalence could further diminish the effect of malaria in Haiti

Adaptive differentiation of Plasmodium falciparum populations inferred from single-nucleotide polymorphisms (SNPs) conferring drug resistance and from neutral SNPs.

International audienceBACKGROUND: Theoretical and experimental data support the geographic differentiation strategy as a valuable tool for detecting loci under selection. In the context of Plasmodium falciparum malaria, few populations have been studied, with limited genomic coverage. METHODS: We examined geographic differentiation in P. falciparum populations on the basis of 12 single-nucleotide polymorphisms (SNPs) in 4 genes encoding drug resistance determinants, 5 SNPs in 2 genes encoding antigens, and a set of 17 putatively neutral SNPs dispersed on 13 chromosomes. We sampled 326 parasite isolates representing 7 P. falciparum populations from regions with varied levels of malaria transmission (Gabon, Kenya, Madagascar, Mali, Mayotte, Haiti, and the Philippines). RESULTS: Frequencies of drug resistance alleles varied considerably among populations (mean F(ST), 0.52). In contrast, allele frequencies varied significantly less for antigenic and neutral SNPs (mean F(ST), 0.16 and 0.24, respectively). This contrasting pattern was more pronounced when only the African populations were considered. Signature of selection was detected for most of the resistant SNPs but not for the antigenic SNPs. CONCLUSION: These data further validate the utility of geographic differentiation for identifying loci under strong positive selection, such as drug resistance loci. This study also provides frequencies of molecular makers of resistance in some overlooked populations

Phenotype and Functions of Natural Killer Cells in Critically-Ill Septic Patients

<div><h3>Rationale</h3><p>Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models.</p> <h3>Objective</h3><p>We studied the phenotype and functions of circulating NK cells in critically-ill septic patients.</p> <h3>Methods</h3><p>Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (<em>n</em> = 15) or septic shock (<em>n</em> = 14) (Sepsis group), non-septic SIRS (<em>n</em> = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry.</p> <h3>Results</h3><p>The absolute number of peripheral blood CD3–CD56⁺ NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3–70]%) compared to healthy controls (43.5[32.1–53.1]%) or Sepsis patients (49.2[37.3–62.9]%) (p = 0.002). Compared to healthy (10.2[6.3–13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2–9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1–54.7]%) compared to Sepsis patients (18.4[11.7–35.7]%, p<0.01) or healthy controls (26.8[19.3–44.9]%, p = 0.09) in ADCC condition.</p> <h3>Conclusions</h3><p>Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions.</p> <h3>Trial Registration</h3><p>NTC00699868.</p> </div

Evaluation of NK cell functions in ICU septic patients.

<p>NK degranulation (<b>A</b>) and intracellular production of IFN-γ (<b>B</b>) of ICU patients with Sepsis, SIRS, and healthy controls. <b>A:</b> Degranulation responses by CD107a cell-surface expression (% of positive NK cells) against K562 target cells (natural cytotoxicity) or P815 mouse mastocytoma cells coated with rabbit anti-mouse lymphocyte antibodies (ADCC). <b>B:</b> Intracellular IFN-γ expression (percentage of positive NK cells), against K562 target cells or P815 (ADCC). Number of samples from each group: Sepsis group (<i>n</i> = 29), SIRS group (<i>n</i> = 13), and healthy controls (<i>n</i> = 21). A black bar inside the box-and-whiskers plots indicates the median. <i>p(kw)</i>: Comparison between healthy, SIRS and Sepsis groups by Kruskal-Wallis test. <i>p</i>: pairwise comparisons between groups (healthy, SIRS, Sepsis) by Kruskal-Wallis post–hoc methods for multiple comparisons adjusted by step-up Simes method.</p

Evaluation of cytotoxic functions of NK cells in ICU patients.

<p>Correlation between the direct cytotoxicity CFSE-based assay and the degranulation CD107a expression assay to evaluate cytotoxic functions of NK cells in ICU patients (<i>n</i> = 14). Results are expressed as % lysis of target cell for the CFSE-assay, and as % NK-cell expressing CD107a for the degranulation assay. Effector–target ratio is 50/1 (PBMC/K562) for the CFSE-assay, and 2.5/1 (NK/K562) for the CD107a expression assay.</p

Characteristics on admission and outcome of ICU patients.

<p>Sepsis group includes patients with severe sepsis and septic shock. CMV: cytomegalovirus; ICU: intensive care unit; MV: mechanical ventilation; SIRS: systemic inflammatory response syndrome; SOFA: sepsis-related organ-failure assessment.</p><p><i>p:</i> Comparison between SIRS and Sepsis groups using Mann-Whitney U test or Pearson Chi-Square test. <i>p*:</i> Comparison between severe sepsis and septic shock using Mann-Whitney U test or Pearson Chi-Square test.</p