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  1. Barber BE, Russell B, Grigg MJ, Zhang R, William T, Amir A, et al.
    Blood Adv, 2018 02 27;2(4):433-443.
    PMID: 29487058 DOI: 10.1182/bloodadvances.2017013730
    The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi-infected humans and M fascicularis Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.
    Matched MeSH terms: Malaria, Falciparum/blood
  2. Kano S, Onda T, Matsumoto Y, Buchachart K, Krudsood S, Looareesuwan S, et al.
    PMID: 9886125
    It was reported that a 47kDa antigenic polypeptide of Plasmodium falciparum had been strongly presented by the sera from 1) imported Japanese malaria patients with severe symptoms and 2) symptomatic and parasitemic inhabitants in endemic areas in the Sudan, Malaysia and the Philippines. In the present study, we observed the reactivity of the sera from falciparum malaria patients who had been hospitalized in the Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, and compared the antibody response against the 47kDa antigenic polypeptide according to the severity of the patients. It was observed that antibodies to this molecule were more commonly shared in sera from severer patients, although the IFAT titers against the whole P. falciparum parasite antigen were lower in the group, which suggested that this antibody against the 47kDa molecule was playing a specific role at a severe stage of the infection. Determination of the immunological features of the antigenic molecules of parasites by this type of sero-epidemiological study will provide a new assay system for evaluation of immune status of individuals in different severity and suggest a way of vaccine development.
    Matched MeSH terms: Malaria, Falciparum/blood
  3. Davis TM, Singh B, Choo KE, Ibrahim J, Sulaiman SA, Kadir ZA, et al.
    J Intern Med, 1998 May;243(5):349-54.
    PMID: 9651556
    OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers.

    DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min.

    SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years.

    MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations.

    RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment.

    CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.

    Matched MeSH terms: Malaria, Falciparum/blood
  4. Mak JW, Normaznah Y, Chiang GL
    Singapore Med J, 1992 Oct;33(5):452-4.
    PMID: 1455266
    The quantitative buffy coat (QBC) technique was compared with the conventional thick blood film technique in a malaria survey carried out in a mesoendemic area of malaria in Betau, Pahang, Malaysia. The QBC technique was found to be a rapid technique but had a sensitivity of about 56% and a specificity of 95%, using the thick blood film method as the "gold standard". Malaria species identification was unsatisfactory with the QBC technique as it could identify parasites correctly in only about 60% of specimens. It was unable to detect as positive about 58% of specimens which had parasite counts < or = 500 per ul but could detect about 94% of those with counts > 500 per ul. This difference in positive detection rate was significantly different (p < 0.05). It cannot quantify parasitemia easily and the specimens cannot be stored for future reference and for quality control purposes. It is therefore concluded that the QBC technique cannot replace the classical thick blood film technique for use in malaria control programmes. Its use may be appropriate in situations like busy blood banks and outpatient clinics where rapid screening of malaria infection is needed but where experienced malaria microscopists may not be available.
    Matched MeSH terms: Malaria, Falciparum/blood
  5. Ramanathan S, Karupiah S, Nair NK, Olliaro PL, Navaratnam V, Wernsdorfer WH, et al.
    PMID: 16046285
    A new approach using a simple solid-phase extraction technique has been developed for the determination of pyronaridine (PND), an antimalarial drug, in human plasma. After extraction with C18 solid-phase sorbent, PND was analyzed using a reverse phase chromatographic method with fluorescence detection (at lambda(ex)=267 nm and lambda(em)=443 nm). The mean extraction recovery for PND was 95.2%. The coefficient of variation for intra-assay precision, inter-assay precision and accuracy was less than 10%. The quantification limit with fluorescence detection was 0.010 microg/mL plasma. The method described herein has several advantages over other published methods since it is easy to perform and rapid. It also permits reducing both, solvent use and sample preparation time. The method has been used successfully to assay plasma samples from clinical pharmacokinetic studies.
    Matched MeSH terms: Malaria, Falciparum/blood
  6. Zainudin NS, Othman N, Muhi J, Abdu Sani AA, Noordin R
    Am J Trop Med Hyg, 2015 Dec;93(6):1268-73.
    PMID: 26392156 DOI: 10.4269/ajtmh.15-0333
    This study was performed to identify circulating Plasmodium falciparum proteins in patient serum, which may be useful as diagnostic markers. Depletion of highly abundant proteins from each pooled serum sample obtained from P. falciparum-infected patients and healthy individuals was performed using the Proteoseek Antibody-Based Albumin/IgG Removal Kit (Thermo Scientific, Rockford, IL). In analysis 1, the depleted serum was analyzed directly by NanoLC-MS/MS. In analysis 2, the depleted serum was separated by two-dimensional electrophoresis followed by western blot analysis. Subsequently, the selected band was analyzed by NanoLC-MS/MS. The result of analysis 1 revealed the presence of two mature erythrocyte surface antigen (MESA) proteins and chloroquine resistance transporter protein (PfCRT). In addition, analysis 2 revealed an antigenic 75-kDa band when the membrane was probed with purified IgG from the pooled serum obtained from P. falciparum-infected patients. MS/MS analysis of this protein band revealed fragments of P. falciparum MESA proteins. Thus, in this study, two different analyses revealed the presence of Plasmodium MESA protein in pooled serum from malaria patients; thus, this protein should be further investigated to determine its usefulness as a diagnostic marker.
    Matched MeSH terms: Malaria, Falciparum/blood
  7. Foo LC, Rekhraj V, Chiang GL, Mak JW
    Am J Trop Med Hyg, 1992 Sep;47(3):271-5.
    PMID: 1524139
    The malaria parasite rates and densities were compared in 79 ovalocytic-normocytic pairs of Malayan Aborigines matched for age, sex, proximity of residence to each other, and use of bed nets when sleeping in their jungle settlement in central Peninsular Malaysia. Malaria infection was determined from thick and thin Giemsa-stained blood films collected monthly for a period of six months. Blood films from ovalocytic individuals were found to be positive for malaria less often than in persons with normal red blood cells (P less than 0.05). Malaria infections per 100 person-months at risk were 9.7 in the ovalocytic group compared with 15.19 in the normocytic group. Among individuals parasitemic at any time, heavy infections (greater than or equal to 10,000 parasites/mm3 of blood) with Plasmodium falciparum, P. vivax, and P. malariae were encountered only in normocytic subjects, which comprised approximately 12.5% of the malaria-positive individuals in this group. In an earlier survey of 629 settlers that identified subjects for the above study, the prevalence of ovalocytosis was found to increase significantly with age. The above field observations support the view that ovalocytic individuals might have a survival advantage in the face of malaria. Consideration of the ovalocytic factor is indicated in future evaluations of malaria control measures in areas where ovalocytosis is prevalent.
    Matched MeSH terms: Malaria, Falciparum/blood
  8. Lokman Hakim S, Sharifah Roohi SW, Zurkurnai Y, Noor Rain A, Mansor SM, Palmer K, et al.
    Trans R Soc Trop Med Hyg, 1996 5 1;90(3):294-7.
    PMID: 8758083
    Uncomplicated falciparum malaria patients were randomly assigned to receive either 25 mg/kg chloroquine (CHL) over 3 d or a statim dose of 25 mg/kg sulfadoxine (SDX) plus 1.25 mg/kg pyrimethamine (PYR). Patients were followed up for 28 d and the parasite response graded according to World Health Organization criteria. Overall resistance to CHL was 63.3% and 47.4% to SDX/PYR. RI, RII and RIII rates were 9.1%, 42.4% and 12.1% for CHL and 10.5%, 21.1% and 15.8% for SDX/PYR, respectively. Degree and rates of resistance to CHL were significantly correlated with pre-treatment parasite density, but not those to SDX/PYR. Plasma CHL and SDX/PYR levels were within the reported ranges and were not significantly different in patients with sensitive and resistant responses.
    Matched MeSH terms: Malaria, Falciparum/blood
  9. Khammanee T, Sawangjaroen N, Buncherd H, Tun AW, Thanapongpichat S
    Korean J Parasitol, 2019 Aug;57(4):369-377.
    PMID: 31533403 DOI: 10.3347/kjp.2019.57.4.369
    Artemisinin-based combination therapy (ACT) resistance is widespread throughout the Greater Mekong Subregion. This raises concern over the antimalarial treatment in Thailand since it shares borders with Cambodia, Laos, and Myanmar where high ACT failure rates were reported. It is crucial to have information about the spread of ACT resistance for efficient planning and treatment. This study was to identify the molecular markers for antimalarial drug resistance: Pfkelch13 and Pfmdr1 mutations from 5 provinces of southern Thailand, from 2012 to 2017, of which 2 provinces on the Thai- Myanmar border (Chumphon and Ranong), one on Thai-Malaysia border (Yala) and 2 from non-border provinces (Phang Nga and Surat Thani). The results showed that C580Y mutation of Pfkelch13 was found mainly in the province on the Thai-Myanmar border. No mutations in the PfKelch13 gene were found in Surat Thani and Yala. The Pfmdr1 gene isolated from the Thai-Malaysia border was a different pattern from those found in other areas (100% N86Y) whereas wild type strain was present in Phang Nga. Our study indicated that the molecular markers of artemisinin resistance were spread in the provinces bordering along the Thai-Myanmar, and the pattern of Pfmdr1 mutations from the areas along the international border of Thailand differed from those of the non-border provinces. The information of the molecular markers from this study highlighted the recent spread of artemisinin resistant parasites from the endemic area, and the data will be useful for optimizing antimalarial treatment based on regional differences.
    Matched MeSH terms: Malaria, Falciparum/blood
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