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Pesticide poisoning is a common medical emergency in the rural tropics, with significant associated mortality. Pesticide poisoning is an umbrella term that encompasses a wide variety of substances with differing clinical toxidromes and outcomes. Despite this, confirmation of the specific compound ingested is rarely performed. In this Lessons from the Field, we argue that pesticide-specific management is integral to optimise management. Using data from a quality improvement project in Chittagong, Bangladesh, we demonstrate that identifying the specific compound is possible in most patients through careful history taking and examination of the pesticide bottle. Identification of the specific compound is essential for anticipating and reducing complications, administering appropriate and timely management and reducing the length of hospital stay and cost of unnecessary medical intervention. [ABSTRACT FROM AUTHOR]

Background Experimental murine models and human challenge studies of Salmonella Typhi infection have suggested that the gut microbiome plays an important protective role against the development of typhoid fever. Anaerobic bacterial communities have been hypothesized to mediate colonization resistance against Salmonella species by producing short-chain fatty acids, yet the composition and function of the intestinal microbiota in human patients with typhoid fever remain ill defined. Methods We prospectively collected fecal samples from 60 febrile patients admitted to Chittagong Medical College Hospital, Bangladesh, with typhoid fever or nontyphoidal febrile illness and from 36 healthy age-matched controls. The collected fecal samples were subjected to 16s rRNA sequencing followed by targeted metabolomics analysis. Results Patients with typhoid fever displayed compositional and functional disruption of the gut microbiota compared with patients with nontyphoidal febrile illness and healthy controls. Specifically, typhoid fever patients had lower microbiota richness and alpha diversity and a higher prevalence of potentially pathogenic bacterial taxa. In addition, a lower abundance of short-chain fatty acid–producing taxa was seen in typhoid fever patients. The differences between typhoid fever and nontyphoidal febrile illness could not be explained by a loss of colonization resistance after antibiotic treatment, as antibiotic exposure in both groups was similar. Conclusions his first report on the composition and function of the gut microbiota in patients with typhoid fever suggests that the restoration of these intestinal commensal microorganisms could be targeted using adjunctive, preventive, or therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background. Impaired microvascular perfusion is central to the development of coma and lactic acidosis in severe falciparum malaria. Refractory hypotension is rare on admission but develops frequently in fatal cases. We assessed cardiac function and volume status in severe falciparum malaria and its prognostic significance. Methods. Patients with severe (N = 101) or acute uncomplicated falciparum malaria (N = 83) were recruited from 2 hospitals in India and Bangladesh, and healthy participants (N = 44) underwent echocardiography. Results. Patients with severe malaria had 38% shorter left ventricular (LV) filling times and 25% shorter LV ejection times than healthy participants because of tachycardia; however, stroke volume, LV internal diameter in diastole (LVIDd), and LV internal diameter in systole (LVIDs) indices were similar. A low endocardial fraction shortening (eFS) was present in 17% (9 of 52) of severe malaria patients. Adjusting for preload and afterload, eFS was similar in health and severe malaria. Fatal cases had smaller baseline LVIDd and LVIDs indices, more collapsible inferior vena cavae (IVC), and higher heart rates than survivors. The LVIDs and IVC collapsibility were independent predictors for mortality, together with base excess and Glasgow Coma Scale. Conclusions. Patients with severe malaria have rapid ejection of a normal stroke volume. Fatal cases had features of relative hypovolemia and reduced cardiac index reserve. [ABSTRACT FROM AUTHOR]

Background: Liberal fluid resuscitation has proved harmful in adults with severe malaria, but the level of restriction has not been defined.Methods: In a prospective observational study in adults with severe falciparum malaria, restrictive fluid management was provided at the discretion of the treating physician. The relationships between the volume of fluid and changes in renal function or tissue perfusion were evaluated.Results: A total of 154 patients were studied, 41 (26.6%) of whom died. Median total fluid intake during the first 6 and 24 hours from enrollment was 3.3 (interquartile range [IQR], 1.8-5.1) mL/kg per hour and 2.2 (IQR, 1.6-3.2) mL/kg per hour, respectively. Total fluid intake at 6 hours was not correlated with changes in plasma creatinine at 24 hours (n = 116; rs = 0.16; P = .089) or lactate at 6 hours (n = 94; rs = -0.05; P = .660). Development of hypotensive shock or pulmonary edema within 24 hours after enrollment were not related to the volume of fluid administration.Conclusions: Restrictive fluid management did not worsen kidney function and tissue perfusion in adult patients with severe falciparum malaria. We suggest crystalloid administration of 2-3 mL/kg per hour during the first 24 hours without bolus therapy, unless the patient is hypotensive. [ABSTRACT FROM AUTHOR]

Background: In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon. We hypothesized that low nitric oxide bioavailability due to the presence of cell-free hemoglobin (CFH) increases vascular tone in severe malaria.Methods: Patients with severe malaria (n = 119), uncomplicated malaria (n = 91), or suspected bacterial sepsis (n = 56), as well as healthy participants (n = 50), were recruited. The systemic vascular resistance index (SVRI) was estimated from the echocardiographic cardiac index and the mean arterial pressure.Results: SVRI and hematocrit levels were lower and plasma CFH and asymmetric dimethylarginine levels were higher in patients with malaria, compared with healthy participants. In multivariate linear regression models for mean arterial pressure or SVRI in patients with severe malaria, hematocrit and CFH but not asymmetric dimethylarginine were significant predictors. The SVRI was lower in patients with suspected bacterial sepsis than in those with severe malaria, after adjustment for hematocrit and age. Plasma CFH levels correlated positively with the core-peripheral temperature gradient and plasma lactate levels and inversely with the perfusion index. Impaired peripheral perfusion, as reflected by a low perfusion index or a high core-peripheral temperature gradient, predicted mortality in patients with severe malaria.Conclusions: CFH is associated with mean arterial pressure, SVRI, and peripheral perfusion in patients with severe malaria. This may be mediated through the nitric oxide scavenging potency of CFH, increasing basal vascular tone and impairing tissue perfusion. [ABSTRACT FROM AUTHOR]

Background: Acidosis in severe Plasmodium falciparum malaria is associated with high mortality, yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of metabolic acids contributing to acidosis in patients with severe falciparum malaria.Methods: A prospective observational study was conducted to characterize circulating acids in adults with P. falciparum malaria (n = 107) and healthy controls (n = 45) from Bangladesh using high-resolution liquid chromatography-mass spectrometry metabolomics. Additional in vitro P. falciparum culture studies were performed to determine if parasites release the acids detected in plasma from patients with severe malaria acidosis.Results: We identified previously unmeasured plasma acids strongly associated with acidosis in severe malaria. Metabolomic analysis of P. falciparum parasites in vitro showed no evidence that these acids are released by the parasite during its life cycle. Instead, 10 of the plasma acids could be mapped to a gut microbial origin. Patients with malaria had low L-citrulline levels, a plasma marker indicating reduced gut barrier integrity. Longitudinal data showed the clearance of these newly identified acids was delayed in fatal cases.Conclusions: These data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria.Clinical Trials Registration: NCT02451904. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury independently predicts mortality in falciparum malaria. It is unknown whether acetaminophen’s capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods This phase 2, open-label, randomized controlled trial conducted at two hospitals in Bangladesh assessed effects on renal function, safety, pharmacokinetic (PK) properties and pharmacodynamic (PD) effects of acetaminophen. Febrile patients (>12 years) with severe falciparum malaria were randomly assigned to receive acetaminophen (1 g 6–hourly for 72 hours) or no acetaminophen, in addition to intravenous artesunate. Primary outcome was the proportional change in creatinine after 72 hours stratified by median plasma hemoglobin. Results Between 2012 and 2014, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31). Median (interquartile range) reduction in creatinine after 72 hours was 23% (37% to 18%) in patients assigned to acetaminophen, versus 14% (29% to 0%) in patients assigned to no acetaminophen (P =.043). This difference in reduction was 37% (48% to 22%) versus 14% (30% to −71%) in patients with hemoglobin ≥45000 ng/mL (P =.010). The proportion with progressing kidney injury was higher among controls (subdistribution hazard ratio, 3.0; 95% confidence interval, 1.1 to 8.5; P =.034). PK–PD analyses showed that higher exposure to acetaminophen increased the probability of creatinine improvement. No patient fulfilled Hy’s law for hepatotoxicity. Conclusions In this proof-of-principle study, acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, particularly in those with prominent intravascular hemolysis. Clinical Trials Registration NCT01641289. [ABSTRACT FROM AUTHOR]

Background: Hyperlactatemia is a strong predictor of mortality in severe falciparum malaria. Sequestered parasitized erythrocytes and reduced uninfected red blood cell deformability (RCD) compromise microcirculatory flow, leading to anaerobic glycolysis.Methods: In a cohort of patients with falciparum malaria hospitalized in Chittagong, Bangladesh, bulk RCD was measured using a laser diffraction technique, and parasite biomass was estimated from plasma concentrations of Plasmodium falciparum histidine-rich protein 2 (PfHRP2). A multiple linear regression model was constructed to examine their associations with plasma lactate concentrations.Results: A total of 286 patients with falciparum malaria were studied, of whom 224 had severe malaria, and 70 died. Hyperlactatemia (lactate level, ≥ 4 mmol/L) was present in 111 cases. RCD at shear stresses of 1.7 Pa and 30 Pa was reduced significantly in patients who died, compared with survivors, individuals with uncomplicated malaria, or healthy individuals (P < .05, for all comparisons). Multiple linear regression analysis showed that the plasma PfHRP2 level, parasitemia level, total bilirubin level, and RCD at a shear stress of 1.7 Pa were each independently correlated with plasma lactate concentrations (n = 278; R(2) = 0.35).Conclusions: Sequestration of parasitized red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease. [ABSTRACT FROM AUTHOR]

Background. Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine.Methods. Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate.Results. Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0–28 025) parasites/µL × hour in patients treated with levamisole and 5489 (IQR, 192–25 848) parasites/µL × hour in controls (P = .25). The “sequestration ratios” at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P > .40). The median time to normalization of plasma lactate (<2 mmol/L) was 24 (IQR, 12–30) hours with levamisole vs 28 (IQR, 12–36) hours without levamisole (P = .15).Conclusions. There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole. [ABSTRACT FROM PUBLISHER]

Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29 960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (β-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A2. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies. [ABSTRACT FROM PUBLISHER]

Abstract: Melioidosis (Burkholderia pseudomallei infection) has yet to be demonstrated systematically in Bangladesh. A prospective, cross-sectional serological survey was conducted in 2010 at six Bangladeshi hospitals. Age, gender, occupation and residential address were recorded. Of 1244 patients, 359 (28.9%) were positive for B. pseudomallei by indirect haemagglutination assay. Farmers had an increased risk of seropositivity (risk ratio=1.4, 95% CI 1.0–1.8; p=0.03). There was no clear geographic clustering of seropositives. Melioidosis should be considered as a possible cause of febrile illness in Bangladesh. Further studies are needed to establish the incidence of clinical disease and distribution of environmental risk. [Copyright &y& Elsevier]

Patients presenting with severe falciparum malaria in a Bangladeshi tertiary hospital had higher total parasite burden, estimated by parasitemia and plasma PfHRP2, than uncomplicated malaria patients despite shorter fever duration. This suggests that higher parasite multiplication rates (PMR) contribute to causing the higher biomass found in severe disease. Compared with patients without a history of previous malaria, patients with previous malaria carried a lower parasite biomass with similar fever duration at presentation, suggesting that host immunity reduces the PMR. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an editorial by G. D. Shanks, which asserted that clinical studies on severe malaria may no longer be possible found in the 49th issue of the periodical "Clinical Infectious Diseases."