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N T Mai

Publications and source records attributed to N T Mai.

15 recordsLinked to original sources
PubMed2004

The role of the polymerase chain reaction in the diagnosis of bacterial meningitis in Vietnam.

Bacterial meningitis remains an important cause of morbidity and mortality in Vietnam. Diagnosis is hampered by the ready availability of antibiotics in the community, leading to late presentation, masked clinical signs, and poor organism detection during the microscopical examination and culture of cerebrospinal fluid (CSF). In order to improve organism detection at the Hospital for Tropical Diseases in Ho Chi Minh City, a diagnostic PCR-based protocol was developed. This protocol was followed in the investigation of CSF samples from 36 patients with clinical signs of bacterial meningitis. Each sample was first tested in a semi-nested PCR using primers for the 16sRNA gene common to all bacteria. The products of this reaction were then amplified using a 16sru8 primer and primers specific for Neisseria meningitidis, Haemophilus influenzae or Streptococcus spp. The samples found positive for Streptococcus were further investigated in a nested PCR using primers specific for the pneumolysin gene of S. pneumoniae. The sensitivity of detection was increased from 36% with culture to 44% with PCR. Although the sample size was small, the results indicate that PCR would be a feasible and useful adjunct in the diagnosis of bacterial meningitis, particularly in areas where community antibiotic use is common.

Antigens, Bacterial↗
PubMed2001

Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria.

Immunohistochemical techniques have been used to investigate specific patterns of potentially reversible cellular injury, DNA damage, and apoptosis in the brainstems of Vietnamese patients who died of severe Plasmodium falciparum malaria. The degree and pattern of neuronal and glial stress responses were compared between patients with cerebral and non-cerebral malaria (CM), and appropriate non-malaria infected controls. The following markers were examined: (i) heat shock protein 70 (HSP70), for reversible injury; (ii) heme oxygenase-1, for oxidative stress; (iii & iv) two DNA-repair proteins, poly(ADP) ribose polymerase (PARP) and DNA-dependent protein kinase catalytic subunit; (v) poly(ADP) ribose, an end-product of PARP activity; and (vi) caspase-3-active, for apoptosis. Stress responses were found in a range of cell types as reflected by the widespread expression of HSP70. Oxidative stress predominated in the vicinity of vessels and haemorrhages. Some degree of DNA damage was found in the majority of malaria patients, but the distribution and frequency of the damage was much less than that observed in controls with irreversible neuronal injury. Similarly, caspase-3-active expression, as a measure of apoptosis, was no higher in the majority of malaria patients than the negative control cases, although 40% of CM cases expressed caspase-3-active in a small number of neurones of the pontine nuclei or within swollen axons of the pontocerebellar and corticospinal tracts. In conclusion, cells within the brainstem of all patients who died from severe malaria showed staining patterns indicative of considerable stress response and reversible neuronal injury. There was no evidence for a specific pattern of widespread irreversible cell damage in those patients with cerebral malaria.

Adult↗
PubMed2000

Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam.

BACKGROUND: The intraerythrocytic parasite Plasmodium falciparum induces the life-threatening neurologic syndrome of cerebral malaria (CM) from within cerebral blood vessels, without entering the brain parenchyma. OBJECTIVES: 1) To assess the use of CSF as an indicator of specific pathologic processes occurring in the brain during CM; 2) to compare this with other neurologic and infectious diseases to understand the distinct pathogenic features of CM; 3) to test the hypothesis that CM involves a specific functional breakdown of the blood-brain barrier (BBB). METHODS: 1) Radial immunodiffusion assays to detect albumin and IgG in matched plasma and CSF samples as indicators of BBB integrity and intrathecal IgG production; and 2) ELISA for soluble intracellular adhesion molecule-1 and sE-selectin, the cytokines tumor necrosis factor-alpha and transforming growth factor-beta1, and the matrix metalloproteinase MMP-9, to detect cellular activation and inflammatory responses within the brain. RESULTS: Albumin and IgG indices implied only minimal degree of BBB breakdown in a few cases of CM, with most remaining within the normal range. In contrast, cryptococcal, tubercular, and acute bacterial meningitis produced detectable changes in the composition of the CSF and evidence of BBB breakdown. CONCLUSIONS: CM appears to involve only subtle functional changes in BBB integrity with minimal intraparenchymal inflammatory responses compared with other neurologic infections. This focuses attention on local events within and around the cerebral microvasculature in CM, rather than indicating widespread parenchymal disease.

Adolescent↗
PubMed2000

Dissection of the enzymatic and immunologic functions of macrophage migration inhibitory factor. Full immunologic activity of N-terminally truncated mutants.

Macrophage migration inhibitory factor (MIF) is a cytokine with broad regulatory functions in innate immunity. MIF belongs to the few cytokines displaying catalytic activities, i.e. MIF has a Pro2-dependent tautomerase and a Cys-Ala-Leu-Cys (CALC) cysteine-based thiol-protein oxidoreductase activity. Previous studies have addressed the roles of the catalytic site residues and the C-terminus. The two activities have not been directly compared. Here we report on the N-terminal mutational analysis and minimization of MIF and on a dissection of the two catalytic activities by comparing mutants P2AMIF, Delta4MIF, Delta5MIF, Delta6MIF, Delta7MIF, Delta8MIF, and Delta10MIF with the cysteine mutants of MIF. As N-terminal deletion was predicted to interfere with protein structure due to disruption of the central beta sheet, it was surprising that deletion of up to six N-terminal residues resulted in normally expressed proteins with wild-type conformation. Strikingly, such mutants exhibited full MIF-specific immunologic activity. While mutation of Pro2 eliminated tautomerase activity, the CALC cysteine residues had no influence on this activity. However, mutant C81SMIF, which otherwise has full biologic activity, only had 32% tautomerase activity. Deletion of four N-terminal residues did not interfere with insulin reduction by MIF. By contrast, reduction of 2-hydroxyethyldisulfide (HED) was markedly affected by N-terminal manipulation, with P2AMIF and Delta2MIF exhibiting 40% activity, and Delta4MIF completely failing to reduce HED. This study constitutes the first comparison of the two catalytic activities of MIF and should assist in understanding the molecular links between the catalytic and immunologic activities of this cytokine and in providing guidelines for N-terminal protein minimization.

Amino Acid Sequence↗
PubMed2000

Effects of dopamine and epinephrine infusions on renal hemodynamics in severe malaria and severe sepsis.

OBJECTIVE: To describe and compare the effects of dopamine and epinephrine in various doses on renal hemodynamics and oxygen transport in patients with severe malaria and severe sepsis. DESIGN: Prospective, controlled, crossover trial. SETTING: The intensive care unit of an infectious diseases hospital in Viet Nam. PATIENTS: Fourteen patients with severe falciparum malaria and five with severe sepsis. INTERVENTIONS: In an open, crossover design, we observed the effects on renal and systemic hemodynamics and oxygen transport of separate stepped infusions of epinephrine and dopamine. We measured renal blood flow (RBF) and cardiac output by the thermodilution method using fluoroscopically guided catheters. Creatinine clearance at each time point was calculated from the renal plasma flow and the renal arteriovenous difference in plasma creatinine. MEASUREMENTS AND MAIN RESULTS: Dopamine at a "renal" dose (2.5 microg/kg/min) was associated with a mean (95% confidence interval) fractional increase in the absolute renal blood flow index (RBFI) of 37% (13% to 61%) and in RBF as a fraction of cardiac output (RBF/CO) of 35% (10% to 59%; p = .007 and p = .014, respectively). The consequent 39% (14% to 64%) increase in renal oxygen supply (p = .002) was accompanied by a 32% (20% to 44%) decrease in the renal oxygen extraction ratio (p = .0003), leading to no net change in renal oxygen consumption. At higher doses (10 microg/kg/min), both RBF and RBF/CO were not significantly different from baseline values and decreased further as the dose was reduced again. There was no obvious explanation for this hysteresis. There was no change in renal oxygen consumption throughout the study. Because lactic acidosis developed, epinephrine was only given to eight of the 19 patients, and the full stepped epinephrine infusion was given to four patients. Epinephrine infusion was associated, both in absolute terms and when compared with dopamine, with a significant increase in renal vascular resistance (p = .0008 and .0005, respectively), a decrease in RBF/CO (p = .002 and .03), and a compensatory increase in the renal oxygen extraction ratio (p = .005 and .0001). RBFI and renal oxygen consumption remained constant throughout the epinephrine infusion profile. Neither epinephrine nor dopamine significantly affected creatinine clearance or urine output. Twelve patients (63%) were in established renal failure (plasma creatinine, >3 mg/dL) at the time of the study, although the presence or absence of renal failure did not significantly influence the effects of the study drugs. However, overall, the presence of renal failure was associated with a lower mean renal oxygen consumption, a lower mean renal oxygen consumption as a fraction of systemic oxygen consumption, and a higher mean renal vascular resistance. CONCLUSION: Although dopamine increased and epinephrine decreased fractional renal blood flow, there was no evidence that either drug produced either a beneficial or a deleterious effect on renal oxygen metabolism or function at any of the doses investigated.

Adult↗
PubMed2000

The pathophysiologic and prognostic significance of acidosis in severe adult malaria.

OBJECTIVE: To investigate the pathophysiology and prognostic significance of acidosis in severe adult malaria. DESIGN: Cohort study. SETTING: The intensive care unit of an infectious diseases hospital in southern Vietnam. PATIENTS: Three hundred forty-six consecutive adult patients with severe falciparum malaria. INTERVENTIONS: Measurements of baseline venous lactate and pyruvate concentrations and an extensive range of clinical and laboratory variables were made, and patients were followed up carefully until death or discharge from the hospital. Admission arterial blood pH and gas tensions were recorded in 296 patients, and hepatic venous sampling was done in 12 patients. MEASUREMENTS AND MAIN RESULTS: Overall, 198 (67%) patients were acidotic (standard base deficit [SBD], >3.3 mmol/L [n = 196], or arterial Pco2, >45 torr [6 kPa] [n = 3]). Hyperlactatemia (plasma lactate, >4 mmol/L) occurred in 120 (35%) of the 346 patients and was associated significantly with acidosis (p < .0001). The hepatosplanchnic lactate extraction ratio was negatively correlated with mixed venous plasma lactate (r2 = .50; p = .006). Hyperlactatemia, metabolic acidosis (SBD, >3.3), and acidemia (pH <7.35) were strongly positively associated with a fatal outcome (relative risks [95% confidence interval], 4.3 [range, 1.8-10.6], 5.0 [range, 3.0-8.1], and 2.7 [range, 1.8-4.1], respectively). The SBD was the single best clinical or laboratory predictor of fatal outcome. The overall median lactate/pyruvate ratio was raised at 30.6 (range, 20.6-62.3; normal range, <15), suggesting hypoxia and anaerobic glycolysis, and was significantly higher in fatal cases (p < .0001). In an additive multivariate model, the two main independent contributors to metabolic acidosis were plasma creatinine, as a measure of renal dysfunction, and venous plasma lactate, together accounting for 63% of the variance in SBD. In univariate analyses, they contributed 29% and 38%, respectively. CONCLUSIONS: These results confirm the importance of acidosis in the pathophysiology of severe adult malaria and suggest a multifactorial origin involving tissue hypoxia, liver dysfunction, and impaired renal handling of bicarbonate.

Acidosis↗
PubMed1999

A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain.

Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1, VCAM-1, E-selectin, and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0-90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0-36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria.

Adolescent↗
PubMed1999

Evidence of blood-brain barrier dysfunction in human cerebral malaria.

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM-1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood-brain barrier was tested. Immunohistochemistry was used to examine the blood-brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins. It was concluded that functional changes to the blood-brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.

Adolescent↗
PubMed1999

The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria.

Pro- and antiinflammatory cytokines were measured on admission in 287 consecutive Vietnamese adults with severe falciparum malaria. Plasma interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha concentrations and the IL-6: IL-10 ratio were significantly higher in patients who died than in survivors (P<.001). On multivariate analysis, hyperparasitemia, jaundice, and shock were all associated independently with raised IL-6, IL-10, and interferon-gamma, and acute renal failure specifically with raised TNF-alpha levels. Cerebral malaria patients, particularly those without other vital organ dysfunction, had significantly lower levels of these cytokines (P=.006), reflecting a more localized pathology. Serial IL-6 and IL-10 measurements made on 43 patients who died and matched survivors indicated a relative deficiency in IL-10 production as death approached. Elevated plasma cytokines in severe malaria are associated with systemic pathologic abnormalities, not cerebral involvement. Both the overall magnitude of the cytokine responses and the eventual imbalance between the pro- and antiinflammatory responses are important determinants of mortality.

Acute Kidney Injury↗
PubMed1996

Post-malaria neurological syndrome.

BACKGROUND: Neurological signs and symptoms are common in malaria, but observations in Vietnam and Thailand have pointed to a discrete transient neurological syndrome after recovery from severe infections. METHODS: A prospective study of the post-malaria neurological syndrome (PMNS) was conducted at two centres in Vietnam over four years. Criteria for inclusion were recent symptomatic malaria infection with parasites cleared from blood (and in cases of cerebral malaria full recovery of consciousness), and development of neurological or psychiatric symptoms within two months after the acute illness. Half of the patients with severe falciparum malaria had been taking part in a randomised trial of antimalarials. FINDINGS: Of 18,124 patients with falciparum malaria treated (1176 of whom had severe infections) 19 adults and three children had subsequent PMNS; in one patient it followed uncomplicated malaria and in 21 it followed severe malaria. The overall incidence (95% confidence interval) of PMNS after falciparum malaria at the main study centre was 1.2 per 1000 (0.7 to 1.8 per 1000) and relative risk (95% CI) for developing PMNS after severe versus uncomplicated falciparum malaria was 299 (40 to 2223). 13 patients had an acute confusional state or psychosis, six had one or more generalised convulsions, two had generalised convulsions followed by a long period of acute confusion, and one developed a fine tremor. At the time of PMNS diagnosis all patients were aparasitaemic. The syndrome was self-limiting, median duration 60 h (range 24-240). PMNS was associated with the use of oral mefloquine. In the randomised trial 4.4% (10/228) of patients with severe malaria who received mefloquine after parenteral treatment developed PMNS compared with 0.5% (1/210) of those who received quinine; relative risk 9.2 (95% CI 1.2 to 71.3, p = 0.012). INTERPRETATION: Mefloquine is not the only risk factor for PMNS but it is a strong one. Where an effective alternative drug is available, mefloquine should not be used after treatment of severe malaria.

Adolescent↗
PubMed1996

The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection.

BACKGROUND: Adrenaline is used increasingly in the management of septic shock, but its efficacy and safety are uncertain. METHODS: In an open, randomised, crossover study we compared the effects of stepped doses of adrenaline 0.1 to 0.5 microgram/kg per min and dopamine 2.5 to 10 micrograms/kg per min on the haemodynamic and acid-base status of 23 patients critically ill with severe sepsis (n = 10) or severe malaria (n = 13). FINDINGS: All patients completed the dopamine study whereas in 16 (84%) patients the adrenaline infusion had to be terminated before reaching, or during, the maximum dose because of lactic acidosis (p < 0.0002). Adrenaline was associated with a mean (95% CI) increase in plasma lactate of 3.2 (2.6 to 3.8) mmol/L, and mean falls in arterial pH of 0.052 (0.035-0.068) pH units and base excess of 3.8 (2.8-4.7) mmol/L. The geometric mean (95% CI) lactate increment per unit adrenaline dose was 8.2 (5.8-10.5) mmol/L per microgram/kg per min. In contrast dopamine was associated with a fall in lactate of 1.0 (0.4-1.5) mmol/L, a rise in base excess of 1.4 (0.7 to 2.0) mmol/L (p < 0.0001 in each case), and no effect on arterial pH. Both drugs induced significant increases in cardiac index and oxygen delivery with smaller increases in oxygen consumption and falls in systemic vascular resistance which were similar in severe malaria and severe sepsis (p > 0.1 in each case) [corrected]. INTERPRETATION: Infusion of inotropic doses of adrenaline in severe infections causes lactic acidosis.

Acid-Base Equilibrium↗
PubMed1992

Acute renal failure in patients with severe falciparum malaria.

Since 1988 in this referral center for severe cases of malaria for South Vietnam, a specialist team has managed malaria-associated renal failure (MARF) with peritoneal dialysis, and the mortality rate of MARF has fallen from 75% (78 of 104) to 26% (27 of 104) (P < .0002). Sixty-four patients with MARF (of whom 12 died) were compared to 66 patients with severe malaria whose serum creatinine levels remained < 250 mumol/L (six died). MARF had the clinical and biochemical features of acute tubular necrosis and was significantly associated with liver dysfunction (P < .05). A fatal outcome was associated significantly with anuria, a short history of illness, multisystem involvement, and high parasitemia. Most patients died from complications related to renal failure. Recovery of renal function was unrelated to parasitemia or hemoglobinuria; the median (range) time until urine output exceeded 20 mL/(kg.d) was 4 (0-19) days, and the time (mean +/- SD) for serum creatinine level to return to normal was 17 +/- 6 days. MARF can be managed effectively by prompt and careful peritoneal dialysis, but more effective dialysis or diafiltration might reduce the mortality rate further.

Acute Kidney Injury↗
PubMedDate not supplied

Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria.

Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated.

Adolescent↗
PubMedDate not supplied

An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria.

An open paired randomized comparison of intramuscular and intravenous artesunate was conducted in 28 adult patients with severe falciparum malaria. The dose regimen in both groups was 2 mg/kg given immediately followed by 1 mg/kg at 12 and 24 h, and then daily until the patient could swallow. Both routes of administration were well tolerated and there was no evidence of toxicity. One patient in each treatment group died. Clinical and parasitological measures of recovery in survivors were similar in the 2 groups with mean fever clearance times of 37.3 h (standard deviation [SD] = 26.1 h) and 31.5 h (SD = 24.2 h) and mean parasite clearance times of 33.4 h (SD = 13.9 h) and 29.4 h (SD = 12.7 h) in the intravenous and intramuscular groups respectively. Artesunate is equally effective and well tolerated when given by the intravenous or intramuscular routes.

Adolescent↗