Praveen Weeratunga

A Diagnostic Scoring Model for Leptospirosis in Resource Limited Settings

Background Leptospirosis is a zoonotic infection with significant morbidity and mortality. The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers. Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination test (MAT), direct demonstration of the organism, and isolation by culture and DNA detection by polymerase chain reaction (PCR) amplification. However these methods of confirmation are not widely available in resource limited settings where the infection is prevalent, and reliance is placed on clinical features for provisional diagnosis. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis, based on clinical features and standard laboratory test results. Methods The diagnostic score was developed based on data from a prospective multicentre study in two hospitals in the Western Province of Sri Lanka. All patients presenting to these hospitals with a suspected diagnosis of leptospirosis, based on the WHO surveillance criteria, were recruited. Confirmed disease was defined as positive genus specific MAT (Leptospira biflexa). A derivation cohort and a validation cohort were randomly selected from available data. Clinical and laboratory manifestations associated with confirmed leptospirosis in the derivation cohort were selected for construction of a multivariate regression model with correlation matrices, and adjusted odds ratios were extracted for significant variables. The odds ratios thus derived were subsequently utilized in the criteria model, and sensitivity and specificity examined with ROC curves. Results A total of 592 patients were included in the final analysis with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to a possible source of leptospirosis (adjusted OR = 2.827; 95% CI = 1.517–5.435; p = 0.001) serum creatinine > 150 micromol/l (adjusted OR = 2.735; 95% CI = 1.374–4.901; p = 0.001), neutrophil differential percentage > 80.0% of total white blood cell count (adjusted OR 2.163; 95% CI = 1.309–3.847; p = 0.032), serum bilirubin > 30 micromol/l (adjusted OR = 1.717; 95% CI 0.938–3.456; p = 0.049) and platelet count < 85,000/mm3 (adjusted OR = 2.350; 95% CI = 1.481–4.513; p = 0.006). Hosmer-Lemeshow test for goodness of fit was 0.931. The Nagelkerke R2 was 0.622. The area under the curve (AUC) was noted as 0.762. A score value of 14 reflected a sensitivity of 0.803, specificity of 0.602, a PPV of 0.54, NPV of 0.84, a positive LR of 2.01 and a negative LR of 0.32. Conclusions The above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.

Clinical manifestations of scrub typhus

The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures.

Prophylaxis of human toxoplasmosis: a systematic review

Abstract Toxoplasmosis is an infection caused by the intracellular protozoan parasite Toxoplasma gondii, and is associated with clinically significant infection in immunocompromised individuals. Vertical transmission during pregnancy can manifest as congenital toxoplasmosis in the neonate, and can have serious consequences. This review aims to describe the modalities for prophylaxis of toxoplasmosis in susceptible populations, and focuses on the following: (1) prophylaxis of congenital toxoplasmosis; (2) prophylaxis of toxoplasmosis in patients with HIV/AIDS; and (3) prophylaxis of toxoplasmosis in transplant recipients.

Prophylactic and therapeutic interventions for bleeding in dengue: a systematic review

The global incidence of dengue has increased sevenfold between 1990 and 2013. Despite a low case fatality rate (<1%), during epidemics, due to the large number of people affected, overall mortality rates can be significant. The risk of clinically significant bleeding in dengue is unpredictable and often contributes to an adverse outcome. This systematic review focuses on the evidence for prophylactic and therapeutic interventions for bleeding in dengue infection. PubMed, CINAHL, Cochrane Library, Embase and Google Scholar were searched for randomized, quasi-randomized and non-randomized, prospective or retrospective studies that had a control group alongside an intervention aimed at stopping or preventing bleeding in dengue infection. Eleven studies that included 1904 patients in 12 study arms were eligible. These assessed the role of platelet transfusion [two randomized controlled trials (RCTs) and three non-randomized studies], plasma transfusion (one RCT), recombinant activated factor VII (one RCT), anti-D globulin (two RCTs), immunoglobulin (one RCT) and interleukin 11 (one RCT) as prevention or treatment for bleeding. Due to significant heterogeneity in study design and outcome reporting, a meta-analysis was not performed. Currently there is no evidence that any of the above interventions would have a beneficial effect in preventing or treating clinically significant bleeding in dengue.

Plasmodium falciparum and Mycoplasma pneumoniae co-infection presenting with cerebral malaria manifesting orofacial dyskinesia and haemophagocytic lymphohistiocytosis

BackgroundMalaria is a mosquito-borne infectious disease with diverse clinical manifestations caused by a parasitic protozoan of the genus Plasmodium. Complex inter-relationships between Mycoplasma species and Plasmodium parasites have been previously noted in vitro. This is the first report of Plasmodium falciparum and Mycoplasma pneumoniae co-infection in a human host presenting with cerebral malaria manifesting orofacial dyskinesias and haemophagocytic lymphohistiocytosis.Case presentationA 55-year-old Sri Lankan man with a recent visit to South Africa presented with an acute febrile illness, cough and worsening dyspnoea with alveolar-interstitial infiltrates on chest radiography. Serological evaluation confirmed a diagnosis of Mycoplasma infection. He subsequently developed encephalopathy with orofacial dyskinesia. A diagnosis of severe P. falciparum infection with significant parasitaemia was established. Peripheral blood cytopaenia occurred due to haemophagocytic lymphohistiocytosis in the bone marrow. Complete clinical and haematological recovery was achieved with intravenous artesunate.ConclusionsPlasmodium falciparum and Mycoplasma pneumoniae co-infection occurring in vivo manifests clinical features that are plausibly a result of the interaction between the two microorganisms. This is the first report of orofacial dyskinesia in either infection.

Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed leptospirosis: a prospective study

BACKGROUND Leptospirosis results in significant morbidity and mortality. This study elucidates markers of severity in a cohort of Sri Lankan patients. METHODS Patients presenting to three healthcare institutions in the Western province of Sri Lanka with leptospirosis serological confirmed by the microscopic agglutination test (MAT) were included. Prospective data regarding demographic, clinical and laboratory parameters was extracted. Univariate associations and subsequent multivariate logistic regression models were constructed. RESULTS The study included 232 patients, with 68.5% (159) demonstrating severe disease. Significant associations of severe disease at a significance level of p<0.05 were fever >38.8°C on presentation, age >40 years, muscle tenderness, tachycardia on admission, highest white cell count >12 350/mm(3) and <7900/mm(3), highest neutrophil percentage >84%, haemoglobin >11.2 g/dL and <10.2 g/dL, packed cell volume (PCV) >33.8% and <29.8%, lowest platelet count <63 500/mm(3), highest alanine transaminase (ALT) >70 IU/L and hyponatremia with sodium <131 mEq/L. On multivariate analysis, PCV <29.8% (p=0.011; OR 3.750; CI: 1.394-10.423), ALT >70 IU/L (p=0.044; OR 2.639; CI: 1.028-6.774) and hyponatremia <131 mEq/L (p=0.019; OR 6.413; CI: 1.353-30.388) were independent associations of severe disease. CONCLUSIONS Severity associations were demonstrated with both clinical and laboratory parameters. There is a need for novel biomarkers for prediction of severity in leptospirosis.

Reversible splenial lesion syndrome associated with dengue fever: a case report

AbstractBackgroundDengue virus infection in humans can lead to a wide range of clinical manifestations, from mild fever to potentially fatal dengue shock syndrome. The incidence of dengue fever is on the rise in tropical countries. Due to the increasing incidence of dengue fever worldwide, atypical manifestations of the disease are increasingly reported. In this article we report a patient with dengue haemorrhagic fever who presented with reversible splenial lesion syndrome. Case presentationA 24-year-old Sri Lankan man who presented with fever and confusion was eventually diagnosed to have reversible splenial lesion syndrome based on brain imaging. Clinical, serological and haematological parameters confirmed a diagnosis of dengue haemorrhagic fever. His presentation, assessment, and management are described in this case report. ConclusionReversible splenial lesion syndrome is a condition which is radiologically characterized by reversible lesion in the splenium of the corpus callosum. It is associated with infectious and non-infectious aetiologies. This case report highlights the occurrence of reversible splenial lesion syndrome as a presenting feature of the expanding list of unusual neurological manifestations of dengue infection.

Embolizing pulmonary aspergillosis, mycobacterial & aspergillous splenic abscess and cytomegalovirus co-infection following steroid induced immunosuppression: a case report

BackgroundAspergillosis is a serious infection particularly affecting the immunodeficient host. Its co-infection with tuberculosis and cytomegalovirus has not been reported before. Embolic events are well recognized with aspergillous endocarditis and aortitis. Splenic abscess is a rare serious complication of disseminated aspergillosis and is difficult to treat. We report the first case of multiple embolic events and splenic abscess in a patient with pulmonary aspergillosis and cytomegaloviral and tuberculous co-infection, without endocarditis or aortitis.Case presentationThirty-year-old male presented with fever and non-productive cough while on glucocorticoids for glomerulonephritis. He was found to have pulmonary aspergillosis and subsequently developed bilateral lower limb and cerebral fungal emboli and fungal abscess in the spleen. He had IgM and B cell deficiency and cytomegalovirus (CMV) and tuberculous co-infections. He recovered after prolonged course of antimicrobials, splenectomy and cessation of glucocorticoid therapy which also lead to the resolution of immune deficiencies.ConclusionThis report illustrates rare combination of B and T cell suppressive effects of glucocorticoids leading to co-infections with CMV, Mycobacterium tuberculosis and Aspergillus and systemic fungal embolization from pulmonary aspergillosis.

THU0331 Do EEG Changes in SLE Correlate with SLE Disease Activity

Background Subclinical electroencephalographic (EEG) changes are seen in patients with systemic lupus erythematosus (SLE), including those without central nervous system (CNS) involvement [1]. Baseline and paroxysmal EEG changes are seen in the majority, but temporo-limbic changes occur more commonly in those with seizures [2]. It is yet unknown if SLE disease activity correlates with EEG changes seen in SLE. Moreover, no particular EEG patterns have been described in in SLE patients with and without CNS involvement. An EEG marker of disease activity or CNS involvement will be critical in selecting patients with CNS lupus for aggressive immune suppression. Objectives Describe the association of EEG changes with (1) SLE disease activity (2)CNS and non-CNS disease flares Methods 70 subjects fulfilling the American College of Rheumatologists criteria for SLE were evaluated over one year. Patients with previous seizures not due to SLE including CNS infections, head injury & previous neurosurgical procedures were excluded. Socio demographic data, disease characteristics, British Isles Lupus Activity Group (BILAG) disease activity assessment, neuropsychiatric lupus screening questionnaire (NPSLEQ) and 30 minute awake EEGs were collected. Subjects were categorized to two groups depending on current disease activity: Group A-high disease activity (BILAG scores of A and B), Group B-low disease activity. 30min EEGs were read by an investigator blinded to patient information and group allocation. Results Group A comprised of 20 (Mean age 32 (SD = 7.7)) and Group B comprised of 50 patients (Mean Age 33 (SD = 8.1). The majority were female (95% in Group A; 96% in Group B). In Group A, 50 % had CNS flares at assessment with the remainder having renal flares: 85% & 15% of group A had BILAG scores of A & B respectively. In Group B, 30% & 70% had previous CNS & renal involvement respectively. Of them 2%, 80% and 8% had BILAG scores of C, D, E respectively. The mean NPSLEQ score was 22 in active CNS SLE and 10 in renal flares. Abnormal EEG findings were more common in Group A (70%) compared to Group B (12%) (p =0.002). In group A, those with CNS (90%) and renal flares (50%) had abnormal EEGs (p=0.58). But, temporal lobe changes were more common in active CNS flares (44%) compared to renal flares (0%) (p=0.032). Higher scores on NPSLQ screening were significantly associated with CNS flares (p=0.021) and focal temporal activity (p= 0.038). Temporal changes were also seen in 50% of patients with previous CNS lupus. Lateralisation was not detected in those with focal changes. Conclusions Abnormal EEGs in SLE were associated with high disease activity and high NPSLQ score. Subjects with active and chronic CNS involvement were more likely to have temporal changes on EEG than those with renal involvement. Temporal EEG changes may be useful in differentiating patients with CNS involvement from those with other system flares. References Gora MK et al. Wiad Lek. 2003; 56(5-6):220-226. Glanz BI et al. Clin Electroencephalogr. 1998 Jul; 29(3):128-131. Disclosure of Interest None Declared