Publications (11)19.05 Total impact
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Article: Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria.
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ABSTRACT: Sequestration of parasitized erythrocytes in the microcirculation is considered the central pathophysiological process in severe falciparum malaria. Hypovolemia with reduced oxygen delivery and microvascular obstruction have different implications for patient management; however, their relative contributions to disease severity are uncertain. Adult patients (n = 28) with severe Plasmodium falciparum malaria were enrolled in a prospective hemodynamic study. Volume status and oxygen delivery were assessed using transpulmonary thermodilution. Microvascular sequestration was measured using orthogonal polarized spectroscopy. Duration of therapy before study enrollment was correlated with the amount of directly visualized and quantitated microvascular sequestration (P = .03). The amount of sequestration correlated with plasma lactate (r(s )= 0.55; P = .003) and disease severity (r(s )= 0.41; P = .04). In patients who had received artesunate for <10 hours, sequestration was higher in fatal cases than in survivors: median (range) 45% (32-50) vs 15% (0-40); P = .03). Parasite biomass estimated from plasma P. falciparum histidine-rich protein 2 correlated positively with disease severity (r(s )= 0.48; P = .01) and was significantly higher in patients who died (P = .046). There was no relationship between oxygen delivery and disease severity (P = .64) or outcome (P = .74). Vital organ dysfunction in severe malaria results primarily from sequestration of parasitized erythrocytes in the microvasculature rather than reduction in circulating blood volume and oxygen delivery.The Journal of Infectious Diseases 06/2012; 206(4):571-9. · 6.41 Impact Factor -
Article: Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial.
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ABSTRACT: Early start of enteral feeding is an established treatment strategy in intubated patients in intensive care since it reduces invasive bacterial infections and length of hospital stay. There is equipoise whether early enteral feeding is also beneficial in non-intubated patients with cerebral malaria in resource poor settings. We hypothesized that the risk of aspiration pneumonia might outweigh the potential benefits of earlier recovery and prevention of hypoglycaemia. A randomized trial of early (day of admission) versus late (after 60 hours in adults or 36 hours in children) start of enteral feeding was undertaken in patients with cerebral malaria in Chittagong, Bangladesh from May 2008 to August 2009. The primary outcome measures were incidence of aspiration pneumonia, hypoglycaemia and coma recovery time. The trial was terminated after inclusion of 56 patients because of a high incidence of aspiration pneumonia in the early feeding group (9/27 (33%)), compared to the late feeding group (0/29 (0%)), p = 0.001). One patient in the late feeding group, and none in the early group, had hypoglycaemia during admission. There was no significant difference in overall mortality (9/27 (33%) vs 6/29 (21%), p = 0.370), but mortality was 5/9 (56%) in patients with aspiration pneumonia. In conclusion, early start of enteral feeding is detrimental in non-intubated patients with cerebral malaria in many resource-poor settings. Evidence gathered in resource rich settings is not necessarily transferable to resource-poor settings. Controlled-Trials.com ISRCTN57488577.PLoS ONE 01/2011; 6(11):e27273. · 4.09 Impact Factor -
Dataset: the use of placebo in a trial of rectal artesunate as initial treatment of severe malaria patients en route to referral clinics: ethical issues
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Article: The use of placebo in a trial of rectal artesunate as initial treatment for severe malaria patients en route to referral clinics: ethical issues.
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ABSTRACT: Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere.Journal of medical ethics 02/2010; 36(2):116-20. · 1.21 Impact Factor -
Article: Retinopathy and microcirculation in adult severe malaria
Malaria Journal. 01/2010; -
Article: The spectrum of retinopathy in adults with Plasmodium falciparum malaria.
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ABSTRACT: A specific retinopathy has been described in African children with cerebral malaria, but in adults this has not been extensively studied. Since the structure and function of the retinal vasculature greatly resembles the cerebral vasculature, study of retinal changes can reveal insights into the pathophysiology of cerebral malaria. A detailed observational study of malarial retinopathy in Bangladeshi adults was performed using high-definition portable retinal photography. Retinopathy was present in 17/27 adults (63%) with severe malaria and 14/20 adults (70%) with cerebral malaria. Moderate or severe retinopathy was more frequent in cerebral malaria (11/20, 55%) than in uncomplicated malaria (3/15, 20%; P=0.039), bacterial sepsis (0/5, 0%; P=0.038) or healthy controls (0/18, 0%; P<0.001). The spectrum of malarial retinopathy was similar to that previously described in African children, but no vessel discolouration was observed. The severity of retinal whitening correlated with admission venous plasma lactate (P=0.046), suggesting that retinal ischaemia represents systemic ischaemia. In conclusion, retinal changes related to microvascular obstruction were common in adults with severe falciparum malaria and correlated with disease severity and coma, suggesting that a compromised microcirculation has important pathophysiological significance in severe and cerebral malaria. Portable retinal photography has potential as a valuable tool to study malarial retinopathy.Transactions of the Royal Society of Tropical Medicine and Hygiene 04/2009; 103(7):665-71. · 2.16 Impact Factor -
Article: Does artesunate prolong the electrocardiograph QT interval in patients with severe malaria?
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ABSTRACT: Several antimalarials can cause significant prolongation of the electrocardiograph QT interval, which can be associated with an increased risk of potentially lethal ventricular arrhythmias. High doses of artemether and artemotil have been associated with QT prolongation in dogs, raising the possibility of a class effect with the artemisinin derivatives. Serial electrocardiograms were recorded, and QTc interval was calculated before and after administration of artesunate by intravenous injection in patients with severe falciparum malaria in Bangladesh. Of 21 adult patients with severe malaria enrolled, 8 (38%) died. The mean QTc interval was unaffected by bolus intravenous artesunate (2.4 mg/kg). In two patients, the QTc interval exceeded 0.5 seconds, but in both cases, an alternative explanation was plausible. No effect was observed on the JTc or PR interval, QRS width, blood pressure, or heart rate. Intravenous artesunate does not have significant cardiovascular effects in patients with severe falciparum malaria.The American journal of tropical medicine and hygiene 02/2009; 80(1):126-32. · 2.59 Impact Factor -
Article: Hyponatremia in severe malaria: evidence for an appropriate anti-diuretic hormone response to hypovolemia.
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ABSTRACT: Although hyponatremia occurs in most patients with severe malaria, its pathogenesis, prognostic significance, and optimal management have not been established. Clinical and biochemical data were prospectively collected from 171 consecutive Bangladeshi adults with severe malaria. On admission, 57% of patients were hyponatremic. Plasma sodium and Glasgow Coma Score were inversely related (r(s) = -0.36, P < 0.0001). Plasma antidiuretic hormone concentrations were similar in hyponatremic and normonatremic patients (median, range: 6.1, 2.3-85.3 versus 32.7, 3.0-56.4 pmol/L; P = 0.19). Mortality was lower in hyponatremic than normonatremic patients (31.6% versus 51.4%; odds ratio [95% confidence interval]: 0.44 [0.23-0.82]; P = 0.01 by univariate analysis). Plasma sodium normalized with crystalloid rehydration from (median, range) 127 (123-140) mmol/L on admission to 136 (128-149) mmol/L at 24 hours (P = 0.01). Hyponatremia in adults with severe malaria is common and associated with preserved consciousness and decreased mortality. It likely reflects continued oral hypotonic fluid intake in the setting of hypovolemia and requires no therapy beyond rehydration.The American journal of tropical medicine and hygiene 01/2009; 80(1):141-5. · 2.59 Impact Factor -
Article: Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series.
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ABSTRACT: Barium, a heavy divalent alkaline metal, has long been known to cause human toxicity. The common mode is accidental ingestion and the common compound is Barium carbonate. Here we report an incident of food poisoning in 27 law enforcement personnel with rapidly developing sequelae and a high mortality due to ingestion of Barium carbonate contaminated flour. One midnight, 27 adult males were rushed to emergency department of Chittagong Medical College Hospital with abdominal pain, vomiting, loose motion, cramps and generalized paraesthesia. The ailment started 1-2 hours after Iftar (evening meal to break day long fast during Ramadan) which included fried vegetables coated with a flour paste. On admission, twenty of them were restless, agitated. 22 reported weakness of limbs and were unable to walk. 10 had hypotension. 22 had rapid and shallow respiration. 5 had carpopedal spasm. Different grades of limb weakness were noted with loss of tendon jerks. Ten (N12) patients had hypokalaemia, three had hypoglycaemia, 4 patients had high creatine kinase. Electrocardiogram showed flat ST with U waves in 4 patients. Potassium containing intravenous fluid and Oxygen was administered. Due to limited availability of mechanical ventilators patients were put on artificial respiration using Ambu bag; manually maintained by doctors, paramedics and attendants. Four patients were transferred to another hospital for mechanical ventilation. A total of 12 patients died over next 16 hours, 4 within 3 hrs. Other patients gradually improved. Chemical analysis of the vomitus, blood and flour used for preparation of meal revealed the presence of Barium. It was assumed that the flour was contaminated with the similar looking Barium carbonate powder which was kept in the kitchen as a rodenticide. This event exemplifies the weakness of usual health care facility in resource poor settings to cope with this kind of massive poisoning event. The multiple reported incidences of accidental Barium poisoning due to unintentional mixing with food signifies the fact that the use and availability of Barium carbonate should be restricted. We hope to draw attention to this relatively uncommon poisoning and to the need for development of poison information centre in resource poor countries.Cases Journal 01/2009; 2:9327. -
Article: Malaria in southeast Bangladesh: a descriptive study.
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ABSTRACT: Malaria in Asia is thought to be grossly under-reported and this is evident from previously published statistics from Bangladesh. Malaria screening data from four Upazillas was analysed alongside census data to assess the trends in malaria incidence over time and distribution of malaria by age and gender. Malaria incidence in this area has decreased by around two thirds since 2003, although control measures were not significantly increased until 2005. Malaria occurred in people of all ages with the highest incidence being in young adults. This is consistent with higher occupational exposure in this group. The probability of being screened for malaria decreased with age suggesting significant numbers of adults with malaria may be being missed.Bangladesh Medical Research Council Bulletin 01/2009; 34(3):87-9. -
Article: Retinopathy and microcirculation in adult severe malaria
Top co-authors
Top Journals
Institutions
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2009–2011
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Mahidol University
- Faculty of Tropical Medicine
Bangkok, Bangkok, Thailand -
University of Oxford
- Nuffield Department of Clinical Medicine
Oxford, ENG, United Kingdom
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