[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
ClinicalTrials.gov identifier: NCT01328457.
[Show abstract][Hide abstract] ABSTRACT: Background:
Hyperlactataemia is a strong predictor of mortality in severe falciparum malaria. Sequestered parasitised erythrocytes and reduced uninfected red blood cell deformability (RCD) compromise microcirculatory flow leading to anaerobic glycolysis.
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 PfHRP2. A multiple linear regression model was constructed to examine their associations with plasma lactate concentrations.
286 patients with falciparum malaria were studied of whom 224 had severe malaria, and 70 died. Hyperlactataemia ≥4 mmol/L was present in 111 cases. RCD at shear stresses (SS) of 1.7 Pa and 30 Pa was reduced significantly in fatal cases compared to survivors, uncomplicated malaria, or healthy individuals (P <0.05, all). Multiple linear regression analysis showed that plasma PfHRP2, parasitaemia, total bilirubin, and RCD at SS 1.7 Pa were each independently correlated with plasma lactate concentrations (n=278, R(2)=0.35).
Sequestration of parasitised red blood cells and reduced RCD both contribute to decreased microcirculatory flow in severe disease.
The Journal of Infectious Diseases 10/2015; DOI:10.1093/infdis/jiv502 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance , and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC 1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC 1/2 and risk of recrudes-cence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC 1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28–63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC 1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC 1/2 >5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC 1/2 by 8.1 % (95 % CI 3.2–12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC 1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC 1/2 (HR = 2.91, 95 % CI 1.95–4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44–3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC 1/2 since 2007. Conclusions: Several factors affect PC 1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC 1/2 data. Studies with frequent parasite count measurements to characterize PC 1/2 should be encouraged. In western Cambodia, where PC 1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
[Show abstract][Hide abstract] ABSTRACT: Severe malaria is a medical emergency mainly caused by falciparum parasite responsible for nearly 584,000 annual deaths globally in 2013.Most deaths in malaria happens in endemic countries before the patient reaches hospitals or within short period after admission; support of Intensive Care Unit (ICU) for optimum treatment of severe malaria is not available in many endemic countries. WHO recommends confirmation of diagnosis by immunochromatographic rapid test or by blood film examination and for treatment to use artemisinin based combination treatment (ACT) for uncomplicated falciparum malaria and thus reduces the incidence of severe malaria. Treatment recommended for severe malaria is IV artesunate for at least 24 hours followed by full dose oral ACT on recovery of per os status. Early feeding in unconscious patient of severe malaria increases the possibility of aspiration pneumonia. A single dose of rectal artesunate reduces death by 25% when used at a community level as pre-referral treatment and completion of treatment follows after admission. Single dose of primaquine 0.25 mg/kg is recommended for reduction of transmission. District hospitals in high endemic area should have facility of dialysis and referral Medical College Hospital should have functional ICU for further reduction of malaria death.Bangladesh Crit Care J September 2015; 3 (2): 57-59
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria.
In this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death.
Patients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6-7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5-7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81).
Newly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.
[Show abstract][Hide abstract] ABSTRACT: To determine the diagnostic accuracy of three rapid diagnostic tests (RDTs) for typhoid fever in febrile hospitalized patients in Bangladesh.
Febrile adults and children admitted to Chittagong Medical College Hospital, Bangladesh were investigated with: BactAlert(®) blood cultures; real-time PCR to detect S.enterica typhi and paratyphi A; and assays for Rickettsia, leptospirosis and dengue fever. Acute serum samples were examined with the LifeAssay (LA) Test-it(™) Typhoid IgM lateral flow assay detecting IgM antibodies against S. typhi O antigen; CTKBiotech Onsite Typhoid IgG/IgM Combo Rapid-test cassette lateral flow assay detecting IgG and IgM antibodies against S. typhi O and H antigens; and SD Bioline line assay for IgG and IgM antibodies against S. typhi proteins.
In 300 malaria smear negative febrile patients (median (IQR) age of 13.5 (5-31) years) 34 (11.3%) had confirmed typhoid fever: 19 positive by blood culture for S. typhi (3 blood PCR positive); 15 blood culture negative but PCR positive for S. typhi in blood. The respective sensitivity and specificity of the three RDTs in patients using a composite reference standard of blood culture and/or PCR confirmed typhoid fever were 36% and 89% for LifeAssay, 54% and 74% for the CTK IgM and/or IgG, and 21% and 97% for the SD Bioline RDT IgM and/or IgG. The LifeAssay RDT had a sensitivity of 63% and a specificity of 91% when modified with a positive cut-off of ≥ 2+ and analysed using a Bayesian latent class model.
These typhoid RDTs demonstrated moderate diagnostic accuracies and better tests are needed. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Tropical Medicine & International Health 06/2015; 20(10). DOI:10.1111/tmi.12559 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Microvascular obstruction and endothelial dysfunction have both been linked to tissue hypoperfusion in falciparum malaria, but their relative contributions to the disease’s pathogenesis and outcome are unknown.
Microvascular blood flow was quantified in adults with severe falciparum malaria on their admission to hospital; plasma biomarkers of endothelial function were measured simultaneously. The relationship between these indices and the patients’ clinical findings and in-hospital course was examined.
Microvascular obstruction was observed in 119/142 (84 %) patients; a median (interquartile range (IQR)) of 14.9 % (6.6–34.9 %) of capillaries were obstructed in patients that died versus 8.3 % (1.7–26.6 %) in survivors (P = 0.039). The proportion of obstructed capillaries correlated with the estimated parasite biomass (rs = 0.25, P = 0.004) and with plasma lactate (rs = 0.38, P <0.0001), the strongest predictor of death in the series. Plasma angiopoietin-2 (Ang-2) concentrations were markedly elevated suggesting widespread endothelial activation; the median (IQR) Ang-2 concentration was 21.9 ng/mL (13.4–29.4 ng/mL) in patients that died versus 14.9 ng/mL (9.8–29.3 ng/mL) in survivors (P = 0.035). Ang-2 concentrations correlated with estimated parasite biomass (rs = 0.35, P <0.001) and plasma lactate (rs = 0.37, P <0.0001). Microvascular obstruction and Ang-2 concentrations were not significantly correlated with each other (rs = 0.17, P = 0.06), but were independently associated with plasma lactate (P <0.001 and P = 0.002, respectively).
Microvascular obstruction and systemic endothelial activation are independently associated with plasma lactate, the strongest predictor of death in adults with falciparum malaria. This supports the hypothesis that the two processes make an independent contribution to the pathogenesis and clinical manifestations of the disease.
BMC Medicine 05/2015; 13(1). DOI:10.1186/s12916-015-0365-9 · 7.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined.
Clinical and laboratory data from 647 adults with severe falciparum malaria were analysed retrospectively to determine the relationship between a patient's platelet count on admission to hospital and their subsequent clinical course.
On admission, 614 patients (94.9%) were thrombocytopenic (platelet count <150 × 10(9)/L) and 328 (50.7%) had a platelet count <50 × 10(9)/L. The admission platelet count was inversely correlated with parasite biomass (estimated from plasma PfHRP2 concentrations, rs = -0.28, P = 0.003), the degree of microvascular sequestration (measured with orthogonal polarizing spectral imaging, rs = -0.31, P = 0.001) and disease severity (the number of World Health Organization severity criteria satisfied by the patient, rs = -0.21, P <0.001). Platelet counts were lower on admission in the patients who died (median: 30 (interquartile range 22 to 52) × 10(9)/L versus 50 (34 to 78) × 10(9)/L in survivors; P <0.001), but did not predict outcome independently from other established laboratory and clinical prognostic indices. The 39 patients (6%) with profound thrombocytopenia (platelet count <20 × 10(9)/L) were more likely to die (odds ratio: 5.00, 95% confidence interval: 2.56 to 9.75) than patients with higher platelet counts, but these high-risk patients could be identified more rapidly with simple bedside clinical assessment. The admission platelet count did not reliably identify the 50 patients (7.7%) with major bleeding during the study.
Thrombocytopenia is a marker of disease severity in adults with falciparum malaria, but has limited utility in prognostication, triage and management.
BMC Medicine 04/2015; 13(1):97. DOI:10.1186/s12916-015-0324-5 · 7.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model.
S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury.
S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice.
[Show abstract][Hide abstract] ABSTRACT: The ongoing outbreak of Ebola virus infection in West Africa is the largest on record in terms of the unprecedented number of reported cases (n=18,603 at Dec 2014) and deaths (n=6915 at Dec 2014) and its' rapid transmission in dense urban populations. With an estimated mortality at around 70%, including massive death tolls in 365 health care workers (up to Dec 14, 2014), the epidemic has undermined fragile health-care systems and presented public health challenges that have never encountered before which is further constrained with the absence of treatment and vaccination options. Fast tracked testing of new or existing vaccines and drugs are currently being planned but are yet to be implemented in endemic countries. The development pipelines would offer a complementary approach to conventional outbreak control efforts. In an era of extreme global interconnectedness, a coordinated international response to improve public health capacity and clinical management in the worst affected countries needs to be scaled up urgently. The global community is in the midst of the worst Ebola epidemic in history. The outbreak of 2014 Ebola virus disease (EVD) mainly affecting the West African countries of Guinea, Liberia, Sierra Leone, Mali (previously affected Nigeria, Senegal) has claimed a death toll of 6915 with 18,603 identified cases (confirmed, probable, suspected), as of December 17 th , 2014. 1 In early August, 2014, the World Health Organization (WHO) declared the West African Ebola outbreak a " public health emergency of international concern (PHEIC). " The outbreak has also been declared a threat to international peace and security by the UN Security Council. The rapid spread of EVD yielding a deadly toll on health care professionals, 365 deaths out of 649 cases as of 14 th
Journal of Medicine 02/2015; 16(1):1-4. DOI:10.3329/jom.v16i1.22363
[Show abstract][Hide abstract] ABSTRACT: In malaria-endemic areas, Plasmodium falciparum parasitemia is common in apparently healthy children and severe malaria is commonly misdiagnosed in patients with incidental
parasitemia. We assessed whether the plasma Plasmodium falciparum DNA concentration is a useful datum for distinguishing uncomplicated from severe malaria in African children and Asian adults.
P. falciparum DNA concentrations were measured by real-time polymerase chain reaction (PCR) in 224 African children (111 with uncomplicated
malaria and 113 with severe malaria) and 211 Asian adults (100 with uncomplicated malaria and 111 with severe malaria) presenting
with acute falciparum malaria. The diagnostic accuracy of plasma P. falciparum DNA concentrations in identifying severe malaria was 0.834 for children and 0.788 for adults, similar to that of plasma P. falciparum HRP2 levels and substantially superior to that of parasite densities (P < .0001). The diagnostic accuracy of plasma P. falciparum DNA concentrations plus plasma P. falciparum HRP2 concentrations was significantly greater than that of plasma P. falciparum HRP2 concentrations alone (0.904 for children [P = .004] and 0.847 for adults [P = .003]). Quantitative real-time PCR measurement of parasite DNA in plasma is a useful method for diagnosing severe falciparum
malaria on fresh or archived plasma samples.
The Journal of Infectious Diseases 10/2014; 211(7). DOI:10.1093/infdis/jiu590 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction An ongoing outbreak of Ebola Virus Disease (EVD) is leading to rapidly mounting cases in West Africa and, as of August 19, 2014 has claimed 1229 lives of 2240 identified cases since the outbreak began, presumed to have emerged in Guinea in December 2013 (1). The rapid spread of EVD in the West African countries of Guinea, Liberia, Sierra Leone, and more recently Nigeria, Africa's most populous nation, has led to the death of 80 health care workers and has attracted global attention and public health concern. On August 8, 2014 the World Health Organization (WHO) declared the 2014 West African Ebola outbreak a "Public Health Emergency of International Concern (PHEIC)." Of great worry is the potential for urban spread, including the vulnerability of capital cities which might make contact tracing daunting. Taxonomy Ebolavirus was discovered in 1976 in Yambuku, the Democratic Republic of Congo (then Zaire) and Nzara, South Sudan, and named after the Ebola river in Zaire (2). The virus belongs to the family Filoviridae, a taxonomic group of RNA viruses that include the genera Marburgvirus and Ebolavirus. Ebolaviruses comprises five separate species – Zaire, Bundibugyo, Tai Forest, Sudan and Reston Ebolavirus. The known African Ebola viruses are associated with human disease with case-fatality rates of approximately 40% for Bundibugyo ebolavirus and as high as 90% for Zaire ebolavirus (3). The only identified Asian species, Reston ebolavirus, found in the Philippines and the People's Republic of China, can infect humans, but no illness or death in humans have been reported to date. There has been only a single reported nonfatal case by the Tai Forest ebolavirus (previously known as Cote d'Ivoire ebolavirus) in 1994, found in a researcher who performed a necropsy on an infected chimpanzee (4). The 2014 West African outbreak, caused by a Zaire species, carries an estimated case-fatality rate of 60% and has raised some difficult questions. Considering the increased amount of population movement on the African continent, it might be plausible to observe a spread of the Zaire ebolavirus outside of Central Africa. Full-length Genome Sequencing and Phylogenetic Analysis showed that the Zaire ebolavirus identified in Guinea is a distinct strain from that found in Central Africa (1). It could be possible that the region had been harbouring Zaire ebolavirus for decades without this giving way to observable outbreaks. However, contrasting evidence reported the same Zaire ebolavirus lineage that has previously caused outbreaks in Central Africa (5). Thus, the virus might be a newcomer to the region. Does it represent a distinct evolution in West Africa? Is the virus circulating in bats throughout the forests of West Africa?
[Show abstract][Hide abstract] ABSTRACT: Scrub and murine typhus infections are under-diagnosed causes of febrile illness across the tropics, and it is not known how common they are in Bangladesh. We conducted a prospective seroepidemiologic survey across six major teaching hospitals in Bangladesh by using an IgM enzyme-linked immunosorbent assay. Results indicated recent exposure (324 of 1,244, 26% seropositive for Orientia tsutsugamushi and 840 of 1,244, 67.5% seropositive for Rickettsia typhi). Seropositive rates were different in each region. However, there was no geographic clustering of seropositive results for both organisms. There was no difference between those from rural or urban areas. Rickettsia typhi seroreactivity was positively correlated with age. Scrub typhus and murine typhus should be considered as possible causes of infection in Bangladesh.
The American journal of tropical medicine and hygiene 08/2014; 91(3). DOI:10.4269/ajtmh.13-0570 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies.
Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined.
The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days.
Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).
New England Journal of Medicine 07/2014; 371(5):411-23. DOI:10.1056/NEJMoa1314981 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Magnetic resonance imaging (MRI) allows detailed study of structural and functional changes in the brain in patients with cerebral malaria.
In a prospective observational study in adult Bangladeshi patients with severe falciparum malaria, MRI findings in the brain were correlated with clinical and laboratory parameters, retinal photography and optic nerve sheath diameter (ONSD) ultrasound (a marker of intracranial pressure).
Of 43 enrolled patients, 31 (72%) had coma and 12 (28%) died. MRI abnormalities were present in 79% overall with mostly mild changes in a wide range of anatomical sites. There were no differences in MRI findings between patients with cerebral and non-cerebral or fatal and non-fatal disease. Subtle diffuse cerebral swelling was common (n = 22/43), but mostly without vasogenic oedema or raised intracranial pressure (ONSD). Also seen were focal extracellular oedema (n = 11/43), cytotoxic oedema (n = 8/23) and mildly raised brain lactate on magnetic resonance spectroscopy (n = 5/14). Abnormalities were much less prominent than previously described in Malawian children. Retinal whitening was present in 36/43 (84%) patients and was more common and severe in patients with coma.
Cerebral swelling is mild and not specific to coma or death in adult severe falciparum malaria. This differs markedly from African children. Retinal whitening, reflecting heterogeneous obstruction of the central nervous system microcirculation by sequestered parasites resulting in small patches of ischemia, is associated with coma and this process is likely important in the pathogenesis.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
PLoS ONE 01/2014; 9(1):e87020. DOI:10.1371/journal.pone.0087020 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A cross sectional analysis of chest radiograph was performed in 100 patients with tuberculosis to observe the recent trends of radiographic presentation. The study was done from April to December, 2009, in Sir Salimullah Medical College and Mitford Hospital, Dhaka, Bangladesh.The chest x-ray findings were analyzed and zonal involvement and pattern of opacities were catagorized and compared. Majority of patients (45%) showed involvement of the upper zone. Dominating lesion was consolidation (25%). Most of the patients were between 15-40 Years. Forty-four percent patients were sputum positive for acid fast bacilli and cavitation was dominant lesion among them. Chest x-ray of patients with post-primary tuberculosis shows involvement predominantly in the upper zone of lung. The most common opacity was consolidation. This correlates with different student. done over different population.
Mymensingh Medical Journal 10/2013; 22(4):721-726.