Displaying publications 1 - 20 of 54 in total

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  1. Hu TH, Rosli N, Mohamad DSA, Kadir KA, Ching ZH, Chai YH, et al.
    Sci Rep, 2021 10 11;11(1):20117.
    PMID: 34635723 DOI: 10.1038/s41598-021-99644-8
    Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. There are two genetically distinct subpopulations of Plasmodium knowlesi in Malaysian Borneo, one associated with long-tailed macaques (termed cluster 1) and the other with pig-tailed macaques (cluster 2). A prospective study was conducted to determine whether there were any between-subpopulation differences in clinical and laboratory features, as well as in epidemiological characteristics. Over 2 years, 420 adults admitted to Kapit Hospital, Malaysian Borneo with knowlesi malaria were studied. Infections with each subpopulation resulted in mostly uncomplicated malaria. Severe disease was observed in 35/298 (11.7%) of single cluster 1 and 8/115 (7.0%) of single cluster 2 infections (p = 0.208). There was no clinically significant difference in outcome between the two subpopulations. Cluster 1 infections were more likely to be associated with peri-domestic activities while cluster 2 were associated with interior forest activities consistent with the preferred habitats of the respective macaque hosts. Infections with both P. knowlesi subpopulations cause a wide spectrum of disease including potentially life-threatening complications, with no implications for differential patient management.
  2. Tai MS, Viswanathan S, Rahmat K, Nor HM, Kadir KA, Goh KJ, et al.
    Sci Rep, 2016 12 13;6:38802.
    PMID: 27958312 DOI: 10.1038/srep38802
    Tuberculous meningitis (TBM) causes significant morbidity and mortality. The primary objective was to re-examine the concept of "TB zone" and "ischaemic zone" in cerebral infarction in patients with tuberculous meningitis. The secondary objective was to evaluate cerebral infarction, vasculitis and vasospasm in tuberculous meningitis infections. Between 2009 and 2014, TBM patients were recruited. Neuroimaging was performed and findings of cerebral infarction, vasculitis and vasospasm were recorded. Infarcts were classified based on arterial supply and Hsieh's classification. Fifty-one TBM patients were recruited of whom 34 patients (67%) had cerebral infarction. Based on Hsieh's classification, 20 patients (59%) had infarcts in both "TB zone" and "ischaemic zones". 12 patients (35%) had infarcts in "ischaemic zone" and two (6%) patients had infarcts in "TB zone". In terms of vascular supply, almost all patients (35/36) had infarcts involving perforators and cortical branches. 25 patients (73%) and 14 patients (41%) had infarcts supplied by lateral lenticulostriate and medial lenticulostriate arteries respectively. 15 patients (37%) had vasculitis. Vasospasm was present in six patients (15%). 29 patients (85%) with cerebral infarction also had leptomeningeal enhancement (p = 0.002). In summary, infarcts involved mainly perforators and cortical branches, rather than "TB zone" versus "ischaemic zone".
  3. Mohamed M, Lim SC, Mumtaz M, Uppal S, Mukherjee D, Kassim MSM, et al.
    J ASEAN Fed Endocr Soc, 2023;38(1):37-44.
    PMID: 37252419 DOI: 10.15605/jafes.038.01.12
    OBJECTIVES: Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings.

    METHODOLOGY: ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS).

    RESULTS: Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: -1.3% [95% CI: -1.61 to -0.90]) and fasting plasma glucose levels (ED: -1.8 mmol/L [95% CI: -2.49 to -1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients.

    CONCLUSION: Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

  4. Assefa S, Lim C, Preston MD, Duffy CW, Nair MB, Adroub SA, et al.
    Proc Natl Acad Sci U S A, 2015 Oct 20;112(42):13027-32.
    PMID: 26438871 DOI: 10.1073/pnas.1509534112
    Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10(-3)) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean FST values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.
  5. Phipps ME, Chan KK, Naidu R, Mohamad NW, Hoh BP, Quek KF, et al.
    BMC Public Health, 2015 Jan 31;15:47.
    PMID: 25636170 DOI: 10.1186/s12889-015-1384-3
    BACKGROUND: South East Asia (SEA) is home to over 30 tribes of indigenous population groups who are currently facing rapid socio-economic change. Epidemiological transition and increased prevalence of non-communicable diseases (NCD) has occured. In Peninsular Malaysia, the Orang Asli (OA) indigenous people comprise 0 · 6% (150,000) of the population and live in various settlements. OA comprise three distinct large tribes with smaller sub-tribes. The three large tribes include Proto-Malay (sub-tribes: Orang Seletar and Jakun), Senoi (sub-tribes: Mahmeri and Semai), and Negrito (sub-tribes: Jehai, Mendriq and Batek).

    METHODS: We studied the health of 636 OA from seven sub-tribes in the Peninsular. Parameters that were assessed included height, weight, BMI and waist circumference whilst blood pressure, cholesterols, fasting blood glucose and HbA1c levels were recorded. We then analysed cardio-metabolic risk factor prevalences and performed multiple pair-wise comparisons among different sub-tribes and socio-economic clusters.

    RESULTS: Cardio-metabolic risk factors were recorded in the seven sub-tribes.. Prevalence for general and abdominal obesity were highest in the urbanized Orang Seletar (31 · 6 ± 5 · 7%; 66 · 1 ± 5 · 9%). Notably, hunter gatherer Jehai and Batek tribes displayed the highest prevalence for hypertension (43 · 8 ± 9 · 29% and 51 · 2 ± 15 · 3%) despite being the leanest and most remote, while the Mendriq sub-tribe, living in the same jungle area with access to similar resources as the Batek were less hypertensive (16.3 ± 11.0%), but displayed higher prevalence of abdominal obesity (27.30 ± 13.16%).

    CONCLUSIONS: We describe the cardio-metabolic risk factors of seven indigenous communities in Malaysia. We report variable prevalence of obesity, cholesterol, hypertension and diabetes in the OA in contrast to the larger ethnic majorities such as Malays, Chinese and Indians in Malaysia These differences are likely to be due to socio-economic effects and lifestyle changes. In some sub-tribes, other factors including genetic predisposition may also play a role. It is expected that the cardio-metabolic risk factors may worsen with further urbanization, increase the health burden of these communities and strain the government's resources.

  6. Mustafa N, Kamarudin NA, Ismail AA, Khir AS, Ismail IS, Musa KI, et al.
    Diabetes Care, 2011 Jun;34(6):1362-4.
    PMID: 21498788 DOI: 10.2337/dc11-0005
    OBJECTIVE:
    To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians.
    RESEARCH DESIGN AND METHODS:
    This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT).
    RESULTS:
    The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors.
    CONCLUSIONS:
    The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.
  7. Mohamud WN, Ismail Aa, Khir AS, Ismail IS, Musa KI, Kadir KA, et al.
    Diabetes Res Clin Pract, 2012 04;96(1):91-7.
    PMID: 22553777 DOI: 10.1016/j.diabres.2011.11.020
    Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk factors among adult Malaysians (>18 years old) based on World Health Organization (WHO), the National Cholesterol Education Program Expert Panel III (ATP III), International Diabetes Federation (IDF) and the 'Harmonized' criteria.Methods: A multi-stage stratified sampling method was used to select 4341 subjects from Peninsular and East Malaysia. Subjects underwent physical and clinical examinations.Results: Based on the WHO, ATP III, IDF and Harmonized definitions, the overall crude prevalences of MetS were 32.1, 34.3, 37.1 and 42.5%, respectively. Regardless of the criteria used, MetS was higher in urban areas, in females, in the Indian population and increased significantly with age. Risk factors also increased with age; abdominal obesity was most prevalent (57.4%), was higher in females (64.2%) and was highest in Indians (68.8%).Hypertension was higher in males (56.5%) and highest among Malays (52.2%). In contrast,the Chinese had the highest prevalence of hypertriglyceridemia (47.4%).Conclusions: Malaysia has a much higher prevalence of MetS compared with other Asian countries and, unless there is immediate intervention to reduce risk factors, this may pose serious implications on the country's healthcare costs and services.
  8. Yap NJ, Hossain H, Nada-Raja T, Ngui R, Muslim A, Hoh BP, et al.
    Emerg Infect Dis, 2021 08;27(8):2187-2191.
    PMID: 34287122 DOI: 10.3201/eid2708.204502
    We detected the simian malaria parasites Plasmodium knowlesi, P. cynomolgi, P. inui, P. coatneyi, P. inui-like, and P. simiovale among forest fringe-living indigenous communities from various locations in Malaysia. Our findings underscore the importance of using molecular tools to identify newly emergent malaria parasites in humans.
  9. Tai ML, Nor HM, Kadir KA, Viswanathan S, Rahmat K, Zain NR, et al.
    Medicine (Baltimore), 2016 Jan;95(1):e1997.
    PMID: 26735523 DOI: 10.1097/MD.0000000000001997
    Paradoxical manifestation is worsening of pre-existing tuberculous lesion or appearance of new lesions in patients whose condition initially improved with antituberculous treatment. Our hypothesis was that paradoxical manifestation in non-HIV tuberculous meningitis (TBM) patients was underestimated and this could contribute to patients' prognosis. This was the first systemic study of paradoxical manifestation in HIV-negative TBM patients. Between 2009 and 2014, TBM patients were studied prospectively in 2 hospitals. Clinical features, cerebrospinal fluid, and radiological findings were monitored. Paradoxical manifestation was divided into definite (4 weeks or more) and probable (between 14 and 27 d) after commencement of antituberculous treatment. Forty-one non-HIV TBM patients were recruited. Definite paradoxical manifestation occurred in 23/41 (56%) of the patients. Time to onset of paradoxical manifestation was between 28 days and 9 months, and majority was between 28 and 50 days. Neuroimaging manifestation in the brain (22/41 patients, 54%) and clinical manifestation (22/41 patients, 54%) were most commonly seen, followed by cerebrospinal fluid manifestation (7/41 patients, 17%). Neuroimaging changes most commonly seen were worsening of leptomeningeal enhancement, new infarcts, new tuberculomas, and enlargement of tuberculoma. Initial Computed Tomography Angiography/magnetic resonance angiography brain showed vasculitis in 14 patients, with 2 (12.5%) showing paradoxical vasculitis during follow-up. Recurrence of the paradoxical manifestation was seen in 7/23 (30%) of the patients. More than half (14/23, 61%) of the patients improved, 6 (26%) patients died, and 3 (13%) patients had persistent neurological deficit. Paradoxical manifestation was very common in non-HIV TBM patients. Neuroimaging paradoxical manifestation of 2-4 weeks may not be paradoxical manifestation but could be delayed treatment response.
  10. Yaw HP, Ton SH, Amanda S, Kong IG, Cheng HS, Fernando HA, et al.
    PMID: 25755839
    Stress and high-calorie diet increase the risk of developing metabolic syndrome. Glycyrrhizic acid (GA) has been shown to improve hyperglycaemia and dyslipidaemia under various physiological conditions. This study was aimed at examining the effects of stress and GA on glucose metabolism under short- or long-term stress. Forty-eight Sprague Dawley rats were divided into two groups with constant stress induced by light (300-400 lux) for either 14 days (short-term stress) or 28 days (long-term stress). Within each group, the rats were subdivided into three treatment groups i.e. Group A (control group): high-calorie diet (HCD) only; Group B: HCD + stress (14 or 28 days) and Group C: HCD + stress (14 or 28 days) + GA (100 mg/kg). The blood glucose concentrations of the rats exposed to 14-day stress were elevated significantly and GA lowered blood glucose concentration significantly in the 14-day exposure group. The 28-day exposure group adapted to stress as shown by the lower adrenaline level and gluconeogenic enzymes activities in most of the tissues than the 14-day exposure group. With regards to adrenaline and corticosterone, GA was found to increased adrenaline significantly in the short-term exposure group while lowering corticosterone in the long-term exposure group. GA-treated short- and long-term exposure groups had significant reduction in hexose-6-phosphate dehydrogenase activities in the visceral adipose tissues and quadriceps femoris respectively. The results may indicate the role of GA in improving blood glucose concentration in individuals exposed to short-term stress who are already on a high-calorie diet via selective action on gluconeogenic enzymes in different tissues.
  11. Ghani RA, Bin Yaakob I, Wahab NA, Zainudin S, Mustafa N, Sukor N, et al.
    J Clin Lipidol, 2013 Sep-Oct;7(5):446-53.
    PMID: 24079286 DOI: 10.1016/j.jacl.2013.04.004
    BACKGROUND: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women.
    OBJECTIVE: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction.
    METHODS: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment.
    RESULTS: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P = .01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study.
    CONCLUSIONS: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.
    KEYWORDS: Endothelial dysfunction; Fenofibrate; High-density lipoprotein cholesterol; Low density lipoprotein; Noninvasive endothelial function assessments; Triglyceride; Vascular cell adhesion molecule-1; hsCRP
  12. Kyaw TZ, Maniam JA, Bee PC, Chin EF, Nadarajan VS, Shanmugam H, et al.
    Turk J Haematol, 2012 Sep;29(3):278-82.
    PMID: 24744674 DOI: 10.5505/tjh.2012.94809
    Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on the vertebral bodies, together with intraspinal masses causing spinal cord compression. The patient immediately underwent radiotherapy, and was treated with all-trans retinoic acid and idarubicin. Reassessment MRI showed complete resolution of all intraspinal masses and the disappearance of most of the bony lesions. Post-treatment bone marrow aspirate showed complete hematological and molecular remission. The motor power of his legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level persisted.
  13. Safari MJ, Wong JH, Kadir KA, Thorpe NK, Cutajar DL, Petasecca M, et al.
    Eur Radiol, 2016 Jan;26(1):79-86.
    PMID: 26002131 DOI: 10.1007/s00330-015-3818-9
    OBJECTIVES: To develop a real-time dose-monitoring system to measure the patient's eye lens dose during neuro-interventional procedures.

    METHODS: Radiation dose received at left outer canthus (LOC) and left eyelid (LE) were measured using Metal-Oxide-Semiconductor Field-Effect Transistor dosimeters on 35 patients who underwent diagnostic or cerebral embolization procedures.

    RESULTS: The radiation dose received at the LOC region was significantly higher than the dose received by the LE. The maximum eye lens dose of 1492 mGy was measured at LOC region for an AVM case, followed by 907 mGy for an aneurysm case and 665 mGy for a diagnostic angiography procedure. Strong correlations (shown as R(2)) were observed between kerma-area-product and measured eye doses (LOC: 0.78, LE: 0.68). Lateral and frontal air-kerma showed strong correlations with measured dose at LOC (AKL: 0.93, AKF: 0.78) and a weak correlation with measured dose at LE. A moderate correlation was observed between fluoroscopic time and dose measured at LE and LOC regions.

    CONCLUSIONS: The MOSkin dose-monitoring system represents a new tool enabling real-time monitoring of eye lens dose during neuro-interventional procedures. This system can provide interventionalists with information needed to adjust the clinical procedure to control the patient's dose.

    KEY POINTS: Real-time patient dose monitoring helps interventionalists to monitor doses. Strong correlation was observed between kerma-area-product and measured eye doses. Radiation dose at left outer canthus was higher than at left eyelid.

  14. Roethlisberger M, Jayapalan RR, Hostettler IC, Bin Abd Kadir KA, Mun KS, Brand Y, et al.
    World Neurosurg, 2020 Jan;133:381-391.e2.
    PMID: 31476461 DOI: 10.1016/j.wneu.2019.08.102
    BACKGROUND: Data on the endonasal endoscopic approach (EEA) to treat sellar/parasellar synchronous tumors remain sparse. This work aims to describe a minimally invasive approach with intraoperative magnetic resonance imaging (MRI) to remove a large sellar/parasellar synchronous tumor, and presents a systematic literature review.

    METHODS: The preoperative MRI of a 54-year-old woman revealed a sellar lesion (28 × 19 × 16 mm), presumably a pituitary macroadenoma, and a second extra-axial lesion (22 × 36 × 20 mm) expanding from the tuberculum sellae to the planum sphenoidale with encasement of the anterior communicating complex, presumably a meningioma. We used intraoperative MRI to assess the extent of the resection before reconstructing the large skull base defect. Furthermore, we systematically reviewed pertinent articles retrieved by a PubMed/Embase database search between 1961 and December 2018.

    RESULTS: Out of 63 patients with synchronous tumors reported in 43 publications, we found 3 patients in which the tumor was removed by EEA. In these 3 patients and the presented case, the resection of both lesions was successful, without major approach-related morbidity or mortality. More extensive removal of endonasal structures to gain an adequate tumor exposure was not necessary. We did not find any previous reports describing the benefits of intraoperative MRI in the presented setting.

    CONCLUSIONS: In the rare case of a synchronous meningioma and pituitary adenoma of the sellar region, intraoperative MRI might be beneficial in confirming residual disease before skull base reconstruction, and therefore radiologic follow-up.

  15. Müller-Sienerth N, Shilts J, Kadir KA, Yman V, Homann MV, Asghar M, et al.
    Malar J, 2020 Jan 17;19(1):31.
    PMID: 31952523 DOI: 10.1186/s12936-020-3111-5
    BACKGROUND: Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information.

    METHODS: Using the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species.

    RESULTS: Using sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38.

    CONCLUSIONS: Using the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.

  16. Zhang X, Kadir KA, Quintanilla-Zariñan LF, Villano J, Houghton P, Du H, et al.
    Malar J, 2016 09 02;15(1):450.
    PMID: 27590474 DOI: 10.1186/s12936-016-1494-0
    BACKGROUND: Plasmodium knowlesi and Plasmodium cynomolgi are two malaria parasites naturally transmissible between humans and wild macaque through mosquito vectors, while Plasmodium inui can be experimentally transmitted from macaques to humans. One of their major natural hosts, the long-tailed macaque (Macaca fascicularis), is host to two other species of Plasmodium (Plasmodium fieldi and Plasmodium coatneyi) and is widely distributed in Southeast Asia. This study aims to determine the distribution of wild macaques infected with malarial parasites by examining samples derived from seven populations in five countries across Southeast Asia.

    METHODS: Plasmodium knowlesi, P. cynomolgi, P. coatneyi, P. inui and P. fieldi, were detected using nested PCR assays in DNA samples from 276 wild-caught long-tailed macaques. These samples had been derived from macaques captured at seven locations, two each in the Philippines (n = 68) and Indonesia (n = 70), and one each in Cambodia (n = 54), Singapore (n = 40) and Laos (n = 44). The results were compared with previous studies of malaria parasites in long-tailed macaques from other locations in Southeast Asia. Fisher exact test and Chi square test were used to examine the geographic bias of the distribution of Plasmodium species in the macaque populations.

    RESULTS: Out of 276 samples tested, 177 were Plasmodium-positive, with P. cynomolgi being the most common and widely distributed among all long-tailed macaque populations (53.3 %) and occurring in all populations examined, followed by P. coatneyi (20.4 %), P. inui (12.3 %), P. fieldi (3.4 %) and P. knowlesi (0.4 %). One P. knowlesi infection was detected in a macaque from Laos, representing the first documented case of P. knowlesi in wildlife in Laos. Chi square test showed three of the five parasites (P. knowlesi, P. coatneyi, P. cynomolgi) with significant bias in prevalence towards macaques from Malaysian Borneo, Cambodia, and Southern Sumatra, respectively.

    CONCLUSIONS: The prevalence of malaria parasites, including those that are transmissible to humans, varied among all sampled regional populations of long-tailed macaques in Southeast Asia. The new discovery of P. knowlesi infection in Laos, and the high prevalence of P. cynomolgi infections in wild macaques in general, indicate the strong need of public advocacy in related countries.

  17. Tan GCJ, Tan SMQ, Phang SCW, Ng YT, Ng EY, Ahmad B, et al.
    Ther Adv Endocrinol Metab, 2019;10:2042018819895462.
    PMID: 31903178 DOI: 10.1177/2042018819895462
    Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.
  18. Divis PC, Lin LC, Rovie-Ryan JJ, Kadir KA, Anderios F, Hisam S, et al.
    Emerg Infect Dis, 2017 04;23(4):616-624.
    PMID: 28322705 DOI: 10.3201/eid2304.161738
    Multilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P. knowlesi infections (obtained from 134 humans and 48 wild macaques) from diverse areas of Malaysia, first analyzed separately and then in combination with previous data. All analyses confirmed 2 divergent clusters of human cases in Malaysian Borneo, associated with long-tailed macaques and pig-tailed macaques, and a third cluster in humans and most macaques in peninsular Malaysia. High levels of pairwise divergence between each of these sympatric and allopatric subpopulations have implications for the epidemiology and control of this zoonotic species.
  19. Divis PCS, Hu TH, Kadir KA, Mohammad DSA, Hii KC, Daneshvar C, et al.
    Emerg Infect Dis, 2020 07;26(7):1392-1398.
    PMID: 32568035 DOI: 10.3201/eid2607.190924
    Population genetic analysis revealed that Plasmodium knowlesi infections in Malaysian Borneo are caused by 2 divergent parasites associated with long-tailed (cluster 1) and pig-tailed (cluster 2) macaques. Because the transmission ecology is likely to differ for each macaque species, we developed a simple genotyping PCR to efficiently distinguish between and survey the 2 parasite subpopulations. This assay confirmed differences in the relative proportions in areas of Kapit division of Sarawak state, consistent with multilocus microsatellite analyses. Analyses of 1,204 human infections at Kapit Hospital showed that cluster 1 caused approximately two thirds of cases with no significant temporal changes from 2000 to 2018. We observed an apparent increase in overall numbers in the most recent 2 years studied, driven mainly by increased cluster 1 parasite infections. Continued monitoring of the frequency of different parasite subpopulations and correlation with environmental alterations are necessary to determine whether the epidemiology will change substantially.
  20. Raja TN, Hu TH, Kadir KA, Mohamad DSA, Rosli N, Wong LL, et al.
    Emerg Infect Dis, 2020 08;26(8):1801-1809.
    PMID: 32687020 DOI: 10.3201/eid2608.200343
    To monitor the incidence of Plasmodium knowlesi infections and determine whether other simian malaria parasites are being transmitted to humans, we examined 1,047 blood samples from patients with malaria at Kapit Hospital in Kapit, Malaysia, during June 24, 2013-December 31, 2017. Using nested PCR assays, we found 845 (80.6%) patients had either P. knowlesi monoinfection (n = 815) or co-infection with other Plasmodium species (n = 30). We noted the annual number of these zoonotic infections increased greatly in 2017 (n = 284). We identified 6 patients, 17-65 years of age, with P. cynomolgi and P. knowlesi co-infections, confirmed by phylogenetic analyses of the Plasmodium cytochrome c oxidase subunit 1 gene sequences. P. knowlesi continues to be a public health concern in the Kapit Division of Sarawak, Malaysian Borneo. In addition, another simian malaria parasite, P. cynomolgi, also is an emerging cause of malaria in humans.
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