Demonstration of anti-disease immunity to Plasmodium vivax malaria in Sri Lanka using a quantitative method to assess clinical disease.

Abstract

Abstract. Clinical immunity to malaria was studied by quantifying the intensity of symptoms as well as by measurement of several hematologic indicators of pathology (the erythrocyte sedimentation rate [ESR], serum bilirubin, reticulocyte count, plasma tumor necrosis factor-␣ [TNF-␣], and blood glucose levels) in 39 Plasmodium vivax malaria patients exposed to endemic malaria in southern Sri Lanka, and for comparison in 43 nonimmune patients who were residents of nonmalarious regions of the country. The intensity of 11 symptoms was scored numerically in all patients using a questionnaire. This clinical score was validated by introducing internal controls to the questionnaire, and by correlating it with the underlying pathology. Both the intensity of clinical disease as well as the degree of underlying pathology were found to be significantly lower in endemic area patients (mean clinical score ϭ 8.8, median ESR ϭ 8 mm) compared with the nonendemic area patients (mean clinical score ϭ 19.0, median ESR 31.5 mm). Endemic area patients also had lower parasite densities (mean ϭ 0.06%) than those from the nonendemic area (0.12%) (P Ͻ 0.05). However, at any parasite density, both clinical disease and pathology were significantly less in the endemic area patients (P Ͻ 0.001, for both clinical score and ESR), indicating that the clinical immunity seen in the endemic area patients was a true tolerance of parasites. Although plasma TNF-␣ levels were elevated in both groups of patients, they were significantly higher in the nonendemic area patients than in patients from the endemic area (P Ͻ 0.01). Furthermore, at comparable levels of plasma TNF-␣, nonendemic area patients had both a higher intensity of clinical disease and an underlying pathology than those from the endemic area, suggesting that if TNF-

Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severeP. falciparummalaria patients in Sri Lanka

“…The third category of patients (UMF) had much higher TNF-alpha levels (median value: 414.5 pg/ml) which were significantly higher (15-fold) than the UM group (P,0.001); however, they were comparable to those of the SM group. TNF-alpha levels in UM patients (median: 27.2 pg/ml) were comparable to that of a non-malarial healthy control groups of a previous study conducted in Sri Lanka (median: 27.0 pg/ml) 27 and in India (mean:…”

“…In all UM patients, the intensity of clinical symptoms was evaluated using a previously validated scoring system. 27 A complete past history was obtained from all patients and the body temperature was measured with a digital thermometer. The patients in the three study groups (UM, UMF, and SM) had comparable parasitemias (percentage of erythrocytes infected) and duration of symptoms (Table 1).…”

CD4+CD25+Foxp3+Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

“…The clinical spectrum of malaria ranged from a very mild illness to full-blown paroxysms, but no patient had severe or complicated malaria (52). The intensity of malaria-associated illness was assessed quantitatively (25). To this end, we interviewed all patients to classify the perceived intensity of 13 common symptoms (fever, chills, sweating, headache, myalgia, arthralgia, abdominal pain, nausea, vomiting, dizziness, cough, dyspnea, and diarrhea) as absent, mild, moderate, or severe (corresponding to numerical scores of 0, 1, 2, and 3).…”

Quantifying genetic and nongenetic contributions to malarial infection in a Sri Lankan population

“…Use of bednets was negligible during this study period. Upon positive diagnosis of malaria based on symptoms and presence of parasites upon microscopic examination of thick blood films, a record of severity of 11 symptom scores, parasitemia, temperature and time since onset of symptoms, and related variables was made (see below) (3). Patients were treated with curative doses of chloroquine and primaquine at this time.…”

“…H umans infected with malaria parasites experience a remarkable range of disease severity, from very mild symptoms to rapid death (1)(2)(3). Understanding the causes of this variation would be useful to clinicians and disease control experts alike.…”