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Determinants of iron status in Malaysian adolescents from a rural community

Foo LH, Khor GL, Tee ES, Dhanaraj P

Int J Food Sci Nutr, 2004 Sep;55(6):517-25.
PMID: 15762316

Iron deficiency anaemia is the most common micronutrient deficiency worldwide. The prevalence of anaemia in the developing countries is three to four times higher than that in the developed countries. The iron status was assessed in 199 apparently healthy male and female adolescents aged 12-19 years living in a fishing community in Sabah, Malaysia. Data on socio-economic characteristics, lifestyles, anthropometry measurements, iron status, and dietary intake were gathered. Dietary intake of energy, iron, and most nutrients (with the exception of protein and vitamin C) were below the recommended levels for Malaysian adolescents. Three-quarters of the iron was derived from plant foods. The mean haemoglobin value for the male was 13.9 +/- 1.3 g/dl with 9.5% having less than 12 g/dl, while the respective figures for the female were 12.4 +/- 1.6 g/dl and 28.6%. The mean serum ferritin concentrations for male and female adolescents were 21.5 and 15.4 microg/l, respectively; with 25.7% of the males and 49.5% of the females having deficient levels of ferritin. Dietary intake of total energy and iron, and gender were found to be independent determinants of serum ferritin and haemoglobin levels, accounting for over 40% of the variations for each of these iron indicators. In males, but not in females, the intake of dietary protein and iron, and physical activity were also found to be significant determinants of serum ferritin. The age of subjects and household size were significant determinants of haemoglobin levels for male subjects, but not for female subjects. The findings indicate the importance of adequate intake of energy and dietary iron for improving the iron status of adolescents.
Fulltext Translation, Cross-Cultural Adaptation to Malay, and psychometric evaluation of the AIM-IAM-FIM questionnaire: Measuring the implementation outcome of a community-based intervention programme

Salleh H, Avoi R, Abdul Karim H, Osman S, Kaur N, Dhanaraj P

PLoS One, 2023;18(11):e0294238.
PMID: 37972041 DOI: 10.1371/journal.pone.0294238

BACKGROUND: The implementation outcomes determine the success and progress of a community-based intervention programme. The community is an important stakeholder whose effects should be assessed. Nevertheless, Malaysia has limited instruments for determining outcome measurements. This research aimed to develop Malay versions of the Acceptability, Appropriateness, and Feasibility Intervention Measures (AIM-IAM-FIM) questionnaire, which evaluates the implementation outcome of the programme.
METHODS: A methodological study of the translation and validation of the implementation outcome measures was conducted from March 2022 until December 2022. Three key analyses were conducted: (1) translation and validation; (2) factor investigation and extraction (n = 170); and (3) scale evaluation (n = 235).
RESULT: The Malay version measuring the implementation outcome measures of a community-based intervention programme was produced after extensive translation and modification, and it consisted of a single dimension with seven items. The content validity index was 0.9, the exploratory factor analysis showed that the KMO measure of sample adequacy was 0.9277, and Bartlett's sphericity test was statistically significant. Cronbach's alpha was good, with a level of 0.938. The single factor structure fitted the data satisfactorily [χ2 (p-value of 0.002), SRMR = 0.030, CFI = 0.999, RMSEA = 0.079, TLI = 0.998]. Factor loading for all items was > 0.7.
CONCLUSION: The 7-item Malay version of the AIM-IAM-FIM survey instrument is valid and reliable for assessing the acceptability of a community-based intervention study and is applicable to other fields. Future studies in psychometric evaluation are recommended in other states due to the variety of Malay dialects spoken across Asia. The scale may also benefit other areas where the language is spoken.
Fulltext A study protocol for a randomised open-label clinical trial of artesunate-mefloquine versus chloroquine in patients with non-severe Plasmodium knowlesi malaria in Sabah, Malaysia (ACT KNOW trial)

Grigg MJ, William T, Dhanaraj P, Menon J, Barber BE, von Seidlein L, et al.

BMJ Open, 2014 Aug 19;4(8):e006005.
PMID: 25138814 DOI: 10.1136/bmjopen-2014-006005

INTRODUCTION: Malaria due to Plasmodium knowlesi is reported throughout South-East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates every 24 h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits. P. knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or P. vivax, with a high proportion of the latter two species being chloroquine-resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all Plasmodium species.
METHODS AND ANALYSIS: ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24 h between treatment arms (clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (α 0.05) to determine the primary end point using intention-to-treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis.
ETHICS AND DISSEMINATION: This study has been approved by relevant institutional ethics committees in Malaysia and Australia. Results will be disseminated to inform knowlesi malaria treatment policy in this region through peer-reviewed publications and academic presentations.
TRIAL REGISTRATION NUMBER: NCT01708876.
Fulltext Combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria Due to Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia

Grigg MJ, William T, Barber BE, Parameswaran U, Bird E, Piera K, et al.

J Clin Microbiol, 2014 Jun;52(6):2053-60.
PMID: 24696029 DOI: 10.1128/JCM.00181-14

Plasmodium knowlesi causes severe and fatal malaria in Malaysia. Microscopic misdiagnosis is common and may delay appropriate treatment. P. knowlesi can cross-react with "species-specific" parasite lactate dehydrogenase (pLDH) monoclonal antibodies used in rapid diagnostic tests (RDTs) to detect P. falciparum and P. vivax. At one tertiary-care hospital and two district hospitals in Sabah, we prospectively evaluated two combination RDTs for malaria diagnosis by using both a pan-Plasmodium-pLDH (pan-pLDH)/P. falciparum-specific-pLDH (Pf-pLDH) RDT (OptiMAL-IT) and a non-P. falciparum VOM-pLDH/Pf-HRP2 RDT (CareStart). Differential cross-reactivity among these combinations was hypothesized to differentiate P. knowlesi from other Plasmodium monoinfections. Among 323 patients with PCR-confirmed P. knowlesi (n = 193), P. falciparum (n = 93), and P. vivax (n = 37) monoinfections, the VOM-pLDH individual component had the highest sensitivity for nonsevere (35%; 95% confidence interval [CI], 27 to 43%) and severe (92%; CI, 81 to 100%) P. knowlesi malaria. CareStart demonstrated a P. knowlesi sensitivity of 42% (CI, 34 to 49%) and specificity of 74% (CI, 65 to 82%), a P. vivax sensitivity of 83% (CI, 66 to 93%) and specificity of 71% (CI, 65 to 76%), and a P. falciparum sensitivity of 97% (CI, 90 to 99%) and specificity of 99% (CI, 97 to 100%). OptiMAL-IT demonstrated a P. knowlesi sensitivity of 32% (CI, 25 to 39%) and specificity of 21% (CI, 15 to 29%), a P. vivax sensitivity of 60% (CI, 42 to 75%) and specificity of 97% (CI, 94 to 99%), and a P. falciparum sensitivity of 82% (CI, 72 to 89%) and specificity of 39% (CI, 33 to 46%). The combination of CareStart plus OptiMAL-IT for P. knowlesi using predefined criteria gave a sensitivity of 25% (CI, 19 to 32%) and specificity of 97% (CI, 92 to 99%). Combining two RDT combinations was highly specific for P. knowlesi malaria diagnosis; however, sensitivity was poor. The specificity of pLDH RDTs was decreased for P. vivax and P. falciparum because of P. knowlesi cross-reactivity and cautions against their use alone in areas where P. knowlesi malaria is endemic. Sensitive P. knowlesi-specific RDTs and/or alternative molecular diagnostic tools are needed in areas where P. knowlesi malaria is endemic.
Fulltext Artesunate-mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial

Grigg MJ, William T, Menon J, Dhanaraj P, Barber BE, Wilkes CS, et al.

Lancet Infect Dis, 2016 Feb;16(2):180-188.
PMID: 26603174 DOI: 10.1016/S1473-3099(15)00415-6

BACKGROUND: The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children.
METHODS: We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate-mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876.
FINDINGS: Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate-mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76-91]) of 115 patients in the artesunate-mefloquine group versus 61 (55% [45-64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0-40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate-mefloquine than in those given chloroquine (18·0 h [range 6·0-48·0] vs 24·0 h [6·0-60·0]; p<0·0001), with faster clearance of ring stages in the artesunate-mefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9-9·4] vs 13·8 h [12·1-15·4]; p<0·0001). Risk of anaemia within 28 days was lower in patients in the artesunate-mefloquine group (71 [62%; 95% CI 52·2-70·6]) than in those in the chloroquine group (83 [75%; 65·6-82·5]; p=0·035). Gametocytaemia as detected by PCR for pks25 was present in 44 (86%) of 51 patients in the artesunate-mefloquine group and 41 (84%) of 49 patients in the chloroquine group at baseline, and in three (6%) of 49 patients and two (4%) of 48 patients, respectively, at day 7. Fever clearance was faster in the artesunate-mefloquine group (mean 11·5 h [95% CI 8·3-14·6]) than in the chloroquine group (14·8 h [11·7-17·8]; p=0·034). Bed occupancy was 2426 days per 1000 patients in the artesunate-mefloquine group versus 2828 days per 1000 patients in the chloroquine group (incidence rate ratio 0·858 [95% CI 0·812-0·906]; p<0·0001). One (<1%) patient in the artesunate-mefloquine group had a serious neuropsychiatric event regarded as probably related to study drug.
INTERPRETATION: Artesunate-mefloquine is highly efficacious for treatment of uncomplicated P knowlesi malaria. The rapid therapeutic response of the drug offers significant advantages compared with chloroquine monotherapy and supports a unified treatment policy for artemisinin-based combination therapy for all Plasmodium species in co-endemic areas.
FUNDING: Malaysian Ministry of Health, Australian National Health and Medical Research Council, and Asia Pacific Malaria Elimination Network.