Comparative sensitivity and specificity of Typhidot and Typhidot-M tests in the diagnosis of Enteric fever in Malaysian children

Suntu penelitian untuk mengetahui sensitivitas dan spesifisitas uji Typhidot dan Typhidot-M daLam mendiagnosis demam enterik pada anak-anak Malaysia telah dilakukan. Pasien dibagi dalam dua kelompok: (i) pasien dengan biakan darah dan-/ ataufeses positif S. typhi dan/atau dengan gambaran klinis yang jelas untuk demam enterik; (ii) pasien dengan kedua biakan negatif dan dengan gambaran klinis atau bukti lain adanya demam oleh sebab lain. Hasilnya menunjukkan bahwa Typhidot maupun TyphidorM sama sensitifnya dengan uji Widal. Uji Typhidot-M memiliki spesifisins yang sedikit Lebih tinggi daripada uji Typhido4 keduanya memiliki spesifisitas sekitar l0% Iebih baik daripada uji Widal. Data juga menunjukkan bahwa uji Typhidot-M mungkin dapat meningkntkan ketepatan diagnosis demam oleh sebab lain pada anak-anak, yang dibuktikan dengan perbaikan spesifitas. Baik uji Typhidot maupun Typhidot-M adalah alat bantu diagnosis yang cepat dan dapat diandalkan dalam penatalaksanaan demam enterik. Uji Typhidot-M mungkin lebih disukai daripada uji Typhidot dalam mengidentifikasi pasien yang menderita demam oleh sebab lain sementara ia daLam masa penyembuhan demam enterik. A study was carcied out to compare the sensitivity and specificity of Typhidot and Typhidot-M tests in the diagnosis of enteric fever in Malaysian children. The patients were divided into two groups: (i) those who were bLood and /or stool culture positive for S. typhi and/or who had clinical features strongly suggestive of enteric fever; (ii) those who were both culture - negative and had clinical or other evidence of another febrile illness. The results showed both Typhidot and Typhidot-M tests.were as sensitive as WidaL test. The Typhidot-M test hnd slightly greater specificity than the Typhidot test; both had around l07a better specificity than the Widal test. The data aLso suggest that the Typhidot-M test may, as evidenced by improved specificity, increase diagnostic accuracy for other febrile iLlnesses in children. The Typhidot and Typhidot-M are both prompt and reliable diagnostic aids in the management of enteric fever The typhidot-M test may be more preferable to the orginal Typhidot test in identifiing patients who develop other febrile illnesses whilst recovering from enteric fever

Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy Volunteers

To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. 12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications

Dynamic assessment of parathyroid function in acute malaria

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 L21 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

Clinical and Laboratory Features of Human Plasmodium knowlesi Infection

Background—Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections. Methods—In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction–confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008. Results—Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/μL (interquartile range, 6–222,570 parasites/μL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (P < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%–6.6%). Conclusions—Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications

A comparison of the clinical, laboratory and epidemiological features of two divergent subpopulations of Plasmodium knowlesi

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

Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as -23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.Peer reviewe

Non-radioisotopic Glucose turnover in children with Falciparum Malaria and Enteric fever

To determine whether glucose turnover is increased in acute falciparum malaria compared to enteric fever in children, steady-state 6,6-D-2-glucose turnover was measured in 9 Malaysian children with uncomplicated malaria (6 males and 3 females; median age 10 years, body weight 22 kg) and in 12 with uncomplicated enteric fever (8 males and 4 females; median age 10 years, body weight 24 kg) in acute illness, after quinine (5 malaria patients) and in convalescence. Baseline plasma glucose concentrations in malaria and enteric fever were similar (all values are medians ranges in brackets) 5.6 3.2-11.3 vs. 5.5 4.2-8.0 mmol/L), as were serum insulin levels (5.6 0.4-26.5 vs. 6.8 1.1-22.5 milliunits/L; P>0.4). Glucose turnover in the malaria patients was higher than in patients with enteric fever (6.27 2.71-6.87 vs. 5.20 4.50-6.08 mg/kg.min; P=0.02) and in convalescence (4.74 3.35-6.79 mg/kg.min; P=0.05 vs, acute malaria study), and fell after quinine together with a rise in serum insulin (P=0.03). Basal plasma lactate concentrations were higher in enteric fever than in malaria (3.4 1.8-6.4 vs. 0.8 0.3-3.8 mmol/L; P<0.0001) and correlated inversely with glucose turnover in this group (r(s)=-0.60; n=12; P=0.02). These data suggest that glucose turnover is 20% greater in malaria than in enteric fever. This might reflect increased non-insulin-mediated glucose uptake in falciparum malaria and/or impaired gluconeogenesis in enteric fever, and may have implications for metabolic complications and their clinical management in both infections