Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

A descriptive study of Forcefully Displaced Myanmar Nationals (FDMN) presenting for care at public health sector hospitals in Bangladesh.

BACKGROUND: In 2017 hundreds of thousands of 'Rohingya' fled to camps for Forcefully Displaced Myanmar Nationals (FDMN) in Cox's Bazar, Bangladesh. OBJECTIVE: To describe the FDMNs presenting for care at public health facilities in Bangladesh so as to understand the health problems faced by the FDMNs and the burden on these public health facilities. METHODS: This study combined a retrospective review of existing hospital and clinic data with prospective surveillance in government health care centres. FINDINGS: The retrospective data showed a 26% increase in the number of consultations at the Kutupalong community clinic, the primary health facility closest to the camps, from 19,567 in 2015 to 26,309 in 2019. There was a corresponding 11% increase in admissions to health facilities in the area, from 80,991 in 2017 to 91,424 in 2019. Prospective surveillance of 9,421 FDMNs seeking health care from July 2018 to December 2019 showed that 29% had an infectious disease, 20% nutritional problems, 12% pregnancy-related conditions and 7% trauma or injury. CONCLUSIONS: Great uncertainty remains regarding the return of FDMN to their home country of Myanmar. The current on-going protests following the military coup adds further insecurity to the status of the Rohingya. The presence of a large migrant population relative to a smaller host community burdens the limited facilities and resources of the public health sector. Continued support by the international public health community and civil society organizations is needed.

Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh.

BACKGROUND: We investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development. METHODS: Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate (SSG), miltefosine (MF), paromomycin intramuscular injection (PMIM), liposomal amphotericin B [AmBisome (AMB)] in a single dose (SDAMB) and in multidose (MDAMB), and combination therapies by AMB+PMIM, AMB+MF, and PMIM+MF. Follow up period was 4 years after treatment. Cohorts were prospective except SSG (retrospective) and MF (partially retrospective). We compared incidence proportion and rate in 100-person-4year of PKDL and VLR by treatment regimens using univariate and multivariate analysis. FINDINGS: 974 of 984 enrolled participants completed the study. Overall incidence proportion for PKDL and VLR was 12.3% (95% CI, 10.4%-14.5%) and 7.0% (95% CI, 5.6%-8.8%) respectively. The incidence rate (95% CI) of PKDL and VLR was 14.0 (8.6-22.7) and 7.6 (4.1-14.7) accordingly. SSG cohort had the lowest incidence rate of PKDL at 3.0 (1.3-7.3) and VLR at 1.8 (0.6-5.6), followed by MDAMB at 8.2 (4.3-15.7) for PKDL and at 2.7 (0.9-8.4) for VLR. INTERPRETATION: Development of PKDL and VLR is related with treatment regimens for VL. SSG and MDAMB resulted in less incidence of PKDL and VLR compared to other treatment regimens. MDAMB should be considered for VL as a first step for prevention of PKDL and VLR since SSG is highly toxic and not recommended for VL.

Prevalence, treatment patterns, and risk factors of hypertension and pre-hypertension among Bangladeshi adults.

In Bangladesh, morbidity and mortality due to non-communicable diseases (NCDs) has increased over the last few decades. Hypertension is an important risk factor for NCDs, specifically cardiovascular disease. The objective of this study was to assess prevalence and risk factors for hypertension and pre-hypertension among adults in Bangladesh. Data for this analysis were collected during the national NCD Risk Factor Survey of Bangladesh conducted in 2010 from a representative sample of men and women, aged 25 years or above. The survey adopted a multistage, geographically clustered, probability-based sampling approach. WHO STEPS questionnaire was used to collect data on demographics, behavioral risk factors, and physical measurements. Overall, 20% of the study population were hypertensive at study measurement. The prevalence of hypertension increased with age and body mass index (BMI). Twelve percent of the population were previously diagnosed with hypertension. Among these individuals, nearly half were not taking any medications to control their hypertension. Additionally, the prevalence of pre-hypertension was 43%, with higher levels among males, older age groups, and those with higher education, higher wealth index and high BMI. Predictors of hypertension, included older age, high BMI, and diabetes comorbidity. Based on this study, we estimate that 1 out of 5 Bangladeshi adults have hypertension. The risk of hypertension increases with older age and high BMI. Additionally, prevalence of pre-hypertension is high in Bangladesh in both rural and urban areas. Findings from this study can be used to inform public health programming to control the spread of NCDs in Bangladesh.

Case Report: Treatment of Widespread Nodular Post kala-Azar Dermal Leishmaniasis with Extended-Dose Liposomal Amphotericin B in Bangladesh: A Series of Four Cases.

Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation which usually appears after visceral leishmaniasis. It is now proved that PKDL patients serve as a reservoir for anthropometric leishmanial transmission. Hence, to achieve the kala-azar elimination target set by the World Health Organization in the Indian Subcontinent, PKDL cases should be given priority. The goal of treatment for PKDL should be early reepithelizlization and rapid cure, but unfortunately this has been difficult to achieve, especially for patients with severe lesions. Therefore, we describe here four cases of PKDL who had widespread nodular and macular lesions and were treated with two cycles of LAmB doses with 20 mg/kg body weight divided into four equal doses (each dose contains 5 mg/kg) administered every alternate day. This treatment schedule achieved 100% treatment success with the minimal safety concern.

Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh.

BACKGROUND: AmBisome therapy for VL has an excellent efficacy and safety profile and has been adopted as a first-line regimen in Bangladesh. Second-line treatment options are limited and should preferably be given in short course combinations in order to prevent the development of resistant strains. Combination regimens including AmBisome, paromomycin and miltefosine have proved to be safe and effective in the treatment of VL in India. In the present study, the safety and efficacy of these same combinations were assessed in field conditions in Bangladesh. METHODS: The safety and efficacy of three combination regimens: a 5 mg/kg single dose of AmBisome + 7 subsequent days of miltefosine (2.5 mg/kg/day), a 5 mg/kg single dose of AmBisome + 10 subsequent days of paromomycin (15 mg/kg/day) and 10 days of paromomycin (15 mg/kg/day) + miltefosine (2.5 mg/kg/day), were compared with a standard regimen of AmBisome 15 mg/kg given in 5 mg/kg doses on days 1, 3 and 5. This was a phase III open label, individually randomized clinical trial. Patients from 5 to 60 years with uncomplicated primary VL were recruited from the Community Based Medical College Bangladesh (CBMC,B) and the Upazila Health Complexes of Trishal, Bhaluka and Fulbaria (all located in Mymensingh district), and randomly assigned to one of the treatments. The objective was to assess safety and definitive cure at 6 months after treatment. RESULTS: 601 patients recruited between July 2010 and September 2013 received either AmBisome monotherapy (n = 158), AmBisome + paromomycin (n = 159), AmBisome + miltefosine (n = 142) or paromomycin + miltefosine (n = 142). At 6 months post- treatment, final cure rates for the intention-to-treat population were 98.1% (95%CI 96.0-100) for AmBisome monotherapy, 99.4% (95%CI 98.2-100) for the AmBisome + paromomycin arm, 94.4% (95%CI 90.6-98.2) for the AmBisome + miltefosine arm, and 97.9% (95%CI 95.5-100) for paromomycin + miltefosine arm. There were 12 serious adverse events in the study in 11 patients that included 3 non-study drug related deaths. There were no relapses or PKDL up to 6 months follow-up. All treatments were well tolerated with no unexpected side effects. Adverse events were most frequent during treatment with miltefosine + paromomycin, three serious adverse events related to the treatment occurred in this arm, all of which resolved. CONCLUSION: None of the combinations were inferior to AmBisome in both the intention-to-treat and per-protocol populations. All the combinations demonstrated excellent overall efficacy, were well tolerated and safe, and could be deployed under field conditions in Bangladesh. The trial was conducted by the International Centre for Diarrhoeal Disease Research (ICDDR,B) and the Shaheed Suhrawardy Medical College (ShSMC), Dhaka, in collaboration with the trial sites and sponsored by the Drugs for Neglected Diseases initiative (DNDi). TRIAL REGISTRATION: ClinicalTrials.gov NCT01122771.

Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh.

BACKGROUND: This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM) as a low-cost treatment option in Bangladesh. METHODOLOGY: This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base) intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen), positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events. PRINCIPAL FINDINGS: A total of 120 subjects (49% pediatric) were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects. CONCLUSIONS/SIGNIFICANCE: PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01328457.

A Study on Health Seeking Behaviors of Patients of Post-Kala-Azar Dermal Leishmaniasis.

Post-Kala-Azar Dermal Leishmaniasis (PKDL) remains a major public health threat in Bangladesh. A cross-sectional study was carried out in Surya Kanta Kala azar Research Centre (SKKRC), Mymensingh, from January 2012 to July 2013 to evaluate the health seeking behaviour and the length of delay of PKDL management. The consecutive 200 diagnosed PKDL cases that got treatment in SKKRC hospital were subjected to evaluation. Most (98%) of the patients were not aware and had no knowledge about PKDL, though 87.5% had a history of history of Kala-azar treatment. Many patients reported first to village doctor (15.5%), the pharmacy shop (10%), or traditional health provider (7.5%) upon recognition of symptom. The time between the initial symptom recognition and first medical consultation (patient delay) ranged from 10 days to 4745 days (13 years) with a median of 373 days (mean: 696; IQR: 138 to 900 days). The time between first medical consultations to definite treatment (system delay) ranged from 0 days to 1971 days (5.4 years), with a median delay of 14 days (mean: 46.48; IQR: 7 to 44 days) that was reported in this study. Age, education, occupation, and residential status had significant association with patient delay (P < 0.05). Educational status, occupation, number of treatment providers, and first health care provider had a significant association with system delay (P < 0.05). Success in PKDL diagnosis and treatment requires specific behavior from patients and health care providers which facilitate those practices.

Retinal changes in visceral leishmaniasis by retinal photography.

BACKGROUND: In visceral leishmaniasis (VL), retinal changes have previously been noted but not described in detail and their clinical and pathological significance are unknown. A prospective observational study was undertaken in Mymensingh, Bangladesh aiming to describe in detail visible changes in the retina in unselected patients with VL. METHODS: Patients underwent assessment of visual function, indirect and direct ophthalmoscopy and portable retinal photography. The photographs were assessed by masked observers including assessment for vessel tortuosity using a semi-automated system. RESULTS: 30 patients with VL were enrolled, of whom 6 (20%) had abnormalities. These included 5 with focal retinal whitening, 2 with cotton wool spots, 2 with haemorrhages, as well as increased vessel tortuosity. Visual function was preserved. CONCLUSIONS: These changes suggest a previously unrecognized retinal vasculopathy. An inflammatory aetiology is plausible such as a subclinical retinal vasculitis, possibly with altered local microvascular autoregulation, and warrants further investigation.

Participants' perceptions and understanding of a malaria clinical trial in Bangladesh.

BACKGROUND: Existing evidence suggests that there is often limited understanding among participants in clinical trials about the informed consent process, resulting in their providing consent without really understanding the purpose of the study, specific procedures, and their rights. The objective of the study was to determine the subjects' understanding of research, perceptions of voluntariness and motivations for participation in a malaria clinical trial. METHODS: In this study semi-structured interviews of adult clinical trial participants with uncomplicated falciparum malaria were conducted in Ramu Upazila Health Complex, in Bangladesh. RESULTS: Of 16 participants, the vast majority (81%) were illiterate. All subjects had a 'therapeutic misconception' i.e. the trial was perceived to be conducted primarily for the benefit of individual patients when in fact the main objective was to provide information to inform public health policy. From the patients' perspective, getting well from their illness was their major concern. Poor actual understanding of trial specific procedures was reported despite participants' satisfaction with treatment and nursing care. CONCLUSION: There is frequently a degree of overlap between research and provision of clinical care in malaria research studies. Patients may be motivated to participate to research without a good understanding of the principal objectives of the study despite a lengthy consent process. The findings suggest that use of a standard consent form following the current ICH-GCP guidelines does not result in achieving fully informed consent and the process should be revised, simplified and adapted to individual trial settings.

Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.

BACKGROUND: Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. METHODS: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determine whether the presence of simple clinical findings might assist patient triage. RESULTS: If present on admission, shock, oligo-anuria, hypo- or hyperglycaemia, an increased respiratory rate, a decreased Glasgow Coma Score and an absence of fever were independently predictive of death. The variables were used to construct a simple clinical algorithm. When applied to the 1801 patients, this algorithm's positive predictive value for survival to 48 hours was 99.4 (95% confidence interval (CI) 97.8-99.9) and for survival to discharge 96.9% (95% CI 94.3-98.5). In the 712 patients receiving artesunate, the algorithm's positive predictive value for survival to 48 hours was 100% (95% CI 97.3-100) and to discharge was 98.5% (95% CI 94.8-99.8). CONCLUSIONS: Simple clinical findings are closely linked to the pathophysiology of severe falciparum malaria in adults. A basic algorithm employing these indices can facilitate the triage of patients in settings where intensive care services are limited. Patients classified as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.

Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia.

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.

Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial.

BACKGROUND: 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. METHOD AND FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN57488577.

Annual incidence of snake bite in rural bangladesh.

BACKGROUND: Snake bite is a neglected public health problem in the world and one of the major causes of mortality and morbidity in many areas, particularly in the rural tropics. It also poses substantial economic burdens on the snake bite victims due to treatment related expenditure and loss of productivity. An accurate estimate of the risk of snake bite is largely unknown for most countries in the developing world, especially South-East Asia. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a national epidemiological survey to determine the annual incidence density of snake bite among the rural Bangladeshi population. Information on frequency of snake bite and individuals' length of stay in selected households over the preceding twelve months was rigorously collected from the respondents through an interviewer administered questionnaire. Point estimates and confidence intervals of the incidence density of snake bite, weighted and adjusted for the multi-stage cluster sampling design, were obtained. Out of 18,857 study participants, over one year a total of 98 snake bites, including one death were reported in rural Bangladesh. The estimated incidence density of snake bite is 623.4/100,000 person years (95% C I 513.4-789.2/100,000 person years). Biting occurs mostly when individuals are at work. The majority of the victims (71%) receive snake bites to their lower extremities. Eighty-six percent of the victims received some form of management within two hours of snake bite, although only three percent of the victims went directly to either a medical doctor or a hospital. CONCLUSIONS/SIGNIFICANCE: Incidence density of snake bite in rural Bangladesh is substantially higher than previously estimated. This is likely due to better ascertainment of the incidence through a population based survey. Poor access to health services increases snake bite related morbidity and mortality; therefore, effective public health actions are warranted.

The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

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 (ß-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.

A simple score to predict the outcome of severe malaria in adults.

BACKGROUND: World Health Organization treatment guidelines recommend that adults with severe malaria be admitted to an intensive care unit (ICU). However, ICU facilities are limited in the resource-poor settings where most malaria occurs. Identification of patients at greater risk of complications may facilitate their triage and resource allocation. METHODS: With use of data from a trial conducted in Southeast Asia (n=868), a logistic regression model was built to identify independent predictors of mortality among adults with severe malaria. A scoring system based on this model was tested in the original dataset and then validated in 2 series from Bangladesh (n=188) and Vietnam (n=292). RESULTS: Acidosis (base deficit) and cerebral malaria (measured as Glasgow Coma Score) were the main independent predictors of outcome. The 5-point Coma Acidosis Malaria (CAM) score was simply derived from these 2 variables. Mortality increased steadily with increasing score. A CAM score <2 predicted survival with a positive predictive value (PPV) of 95.8% (95% confidence interval [CI], 93%- 97.7%). Of the 14 of 331 patients who died with a CAM score <2, 11 (79%) had renal failure and death occurred late after hospital admission (median, 108 h; range, 40-360 h). Substitution of plasma bicarbonate as the measure of acidosis only slightly reduced the prognostic value of the model. Use of respiratory rate was inferior, but a score <2 still predicted survival with a PPV of 92.2% (95% CI, 89.1%-94.7%). CONCLUSIONS: Patients with a CAM score <2 at hospital admission may be safely treated in a general ward, provided that renal function can be monitored.

CMCH and MORU: a Highly Successful Collaboration.

Chittagong Medical College and Hospital (CMCH) in Chittagong, Bangladesh, and Mahidol-Oxford Tropical Medicine Research Unit (MORU) of Bangkok, Thailand, are partners in a highly successful and productive research collaboration that is now heading into its tenth year. It produced arguably one of the most important clinical trials in tropical medicine this decade, the South-East-Asia-Quinine-Artesuante-Malaria-Trial (SEAQUAMAT) study, and has continued to evolve and grow ever since. The collaboration has successfully completed a number of significant clinical studies which have given important new insights into the management and pathogenesis of malaria and, to date, generated 14 peer-reviewed international journal publications. With each passing year, the size of the collaboration continues to increase along with the number and complexity of research studies undertaken. It has also helped to provide valuable postgraduate training to develop clinical services and increase capacity for high quality research in Bangladesh. The partners have complementary knowledge, skills and expertise and share common goals and it is hoped that this will remain a highly successful collaboration long into the future.

Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series.

INTRODUCTION: 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. CASE PRESENTATION: 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. CONCLUSION: 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.

Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series.

INTRODUCTION: 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. CASE PRESENTATION: 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. ECG 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. CONCLUSION: 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.

The relationship between age and the manifestations of and mortality associated with severe malaria.

BACKGROUND: The reported case-fatality rate associated with severe malaria varies widely. Whether age is an independent risk factor is uncertain. METHODS: In a large, multicenter treatment trial conducted in Asia, the presenting manifestations and outcome of severe malaria were analyzed in relation to age. RESULTS: Among 1050 patients with severe malaria, the mortality increased stepwise, from 6.1% in children (age, <10 years) to 36.5% in patients aged >50 years (P<0.001). Compared with adults aged 21-50 years, the decreased risk of death among children (adjusted odds ratio, 0.06; 95% confidence interval, 0.01-0.23; P<0.001) and the increased risk of death among patients aged >50 years (adjusted odds ratio, 1.88; 95% confidence interval, 1.01-3.52; P<0.001) was independent of the variation in presenting manifestations. The incidence of anemia and convulsions decreased with age, whereas the incidence of hyperparasitemia, jaundice, and renal insufficiency increased with age. Coma and metabolic acidosis did not vary with age and were the strongest predictors of a fatal outcome. The number of severity signs at hospital admission also had a strong prognostic value. CONCLUSION: Presenting syndromes in severe malaria depend on age, although the incidence and the strong prognostic significance of coma and acidosis are similar at all ages. Age is an independent risk factor for a fatal outcome of the disease.