Senanayake A. M. Kularatne

Acute yellow oleander ( Thevetia peruviana ) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital

OBJECTIVE To describe the cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside levels seen in patients presenting to hospital with acute yellow oleander (Thevetia peruviana) poisoning and to compare these with published reports of digitalis poisoning. DESIGN Case series. SETTING Medical wards of Anuradhapura District General Hospital, Sri Lanka, and coronary care unit of the Institute of Cardiology, National Hospital of Sri Lanka, Colombo, the national tertiary referral centre for cardiology. PATIENTS 351 patients with a history of oleander ingestion. MEASUREMENTS ECG and blood sample analysis on admission. RESULTS Most symptomatic patients had conduction defects affecting the sinus node, the atrioventricular (AV) node, or both. Patients showing cardiac arrhythmias that required transfer for specialised management had significantly higher mean serum cardiac glycoside and potassium but not magnesium concentrations. Although there was considerable overlap between groups, those with conduction defects affecting both sinus and AV nodes had significantly higher mean serum cardiac glycoside levels. CONCLUSIONS Most of these young previously healthy patients had conduction defects affecting the sinus or AV nodes. Relatively few had the atrial or ventricular tachyarrhythmias or ventricular ectopic beats that are typical of digoxin poisoning. Serious yellow oleander induced arrhythmias were associated with higher serum cardiac glycoside concentrations and hyperkalaemia but not with disturbances of magnesium.

Frequent and potentially fatal envenoming by hump-nosed pit vipers (Hypnale hypnale and H. nepa) in Sri Lanka: lack of effective antivenom

In a prospective study of snake bites involving 10 hospitals in Sri Lanka, 302 (35%) of 860 patients with bites by identified snakes proved to have been bitten by hump-nosed pit vipers (301 by Hypnale hypnale and 1 by H. nepa). Most victims were males aged between 11 years and 50 years who had been bitten on their feet or ankles while walking at night close to their homes. There was local swelling in 276 (91%) and local necrosis in 48 (16%). Eleven (4%) required amputation of fingers or toes and 12 (4%) received skin grafts. In 117 patients (39%) blood incoagulability was first detected between 15 min and 48 h after the bite, and in 116 of them this was present on admission to hospital. Spontaneous systemic bleeding was observed in 55 patients (18%). Acute renal failure developed in 10%, five of whom died to give an overall case fatality rate of 1.7%. Thus, bites by hump-nosed pit vipers can cause debilitating local and fatal systemic envenoming. In Sri Lanka and southwestern India where bites by these snakes are common, the only available antivenoms (raised against cobra, krait, Russells viper and saw-scaled viper venoms) are ineffective and carry a high risk of reactions.

Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model

OBJECTIVE To investigate the potential role of fresh Carica papaya (C. papaya) leaf extract on haematological and biochemical parameters and toxicological changes in a murine model. METHODS In total 36 mice were used for the trial. Fresh C. papaya leaf extract [0.2 mL (2 g)/mouse] was given only to the test group (18 mice). General behavior, clinical signs and feeding patterns were recorded. Blood and tissue samples were collected at intervals. Haematological parameters including platelet, red blood cell (RBC), white blood cell (WBC), packed cell volume (PCV), serum biochemistry including serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were determined. Organs for possible histopathological changes were examined. RESULTS Neither group exhibited alteration of behavior or reduction in food and water intake. Similarly, no significant changes in SGOT, SGPT and serum creatinine levels were detected in the test group. Histopathological organ changes were not observed in either group of mice except in three liver samples of the test group which had a mild focal necrosis. The platelet count (11.33±0.35)×10⁵/µL (P=0.00004) and the RBC count (7.97±0.61)×10⁶/µL (P=0.00003) were significantly increased in the test group compared to that of the controls. However, WBC count and PCV (%) values were not changed significantly in the test group. The platelet count in the test group started to increase significantly from Day 3 (3.4±0.18×10⁵/µL), reaching almost a fourfold higher at Day 21 (11.3×10⁵/µL), while it was 3.8×10⁵/µL and 5.5×10⁵/µL at Day 3 and Day 21 respectively in the control. Likewise, the RBC count in the test group increased from 6×10⁶/µL to 9×10⁶/ µL at Day 21 while it remained near constant in the control group (6×10⁶/µL). CONCLUSIONS Fresh C. papaya leaf extract significantly increased the platelet and RBC counts in the test group as compared to controls. Therefore, it is very important to identify those chemicals of C. papaya leaves as it can be recommended to be used as a medication to boost thrombopoiesis and erythropoiesis in humans and in animals in which these cell lineages have been compromised.

Prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents in Kandy, Sri Lanka.

Leptospirosis is an important bacterial zoonotic disease globally and one of the notifiable diseases in Sri Lanka. Other than human leptospirosis, little information is available on leptospirosis in domestic and feral animals in Sri Lanka. Thus, this study attempted to determine the prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents to understand the impact of the disease on public health in Kandy, Sri Lanka. Cattle and rodent samples were collected from the Yatinuwara and Udunuwara divisional secretaries in Kandy. Serum samples were analyzed for the presence of antileptospiral antibodies using microscopic agglutination test. DNA was extracted from cattle urine and rodent kidney tissue samples, in which polymerase chain reaction was carried out to detect the Leptospira flaB gene. The cattle in 19 (38.8%) of the 49 farms harbored antileptospiral antibodies. Out of 113 cattle serum samples, 23 (20.3%) were positive; 17 (73.9%) and 6 (26.1%) reacted with serogroups Sejroe and Hebdomadis, respectively. Out of the 74 rodent samples, 13 (17.5%) were positive; 8 (61.5%) and 4 (30.8%) had reactions to serogroups Javanica and Icterohaemorrhagiae, respectively. Leptospiral DNA was detected in one cattle urine sample and identified as Leptospira interrogans. This study revealed a high prevalence of leptospirosis in cattle and rodents in Kandy. These animals were infected with a wide array of leptospiral serogroups, which are consistent with the research findings observed in humans in Kandy. Overall, serological data indicate that relative to rodents, cattle may be a more significant reservoir for human transmission and a greater source of potential risk to local agricultural communities.

Efficacy of low dose dexamethasone in severe thrombocytopenia caused by dengue fever: a placebo controlled study

Background: The use of corticosteroids in the management of thrombocytopenia in dengue fever remains untested. Objectives: To test whether intravenous low dose dexamethasone is efficacious in increasing platelet count in acute severe thrombocytopenia in dengue infection. Methods: We undertook a placebo controlled study at the Teaching Hospital, Peradeniya, Sri Lanka in July 2004. Patients with thrombocytopenia (platelet count <50×109/l) were allocated to the treatment and placebo groups using the sealed envelop method. The treatment group received an initial intravenous dose of 4 mg dexamethasone, followed by 2 mg doses every 8 h for 24 h, and the placebo group received normal saline. The primary outcome was the degree of mean platelet count rise. Results: Each group comprised 100 patients and their baseline data and other variables (headaches, nausea, flush, temperature, pulse, blood pressure, haematocrit, white cell count and haemoglobin) were similar. The primary outcome—mean platelet count (×109/l)—increased steadily in both groups from day 1 to 4 and showed no significant difference between the two groups (p>0.05): day 1, 35 vs 35 (p = 0.70); day 2, 47 vs 43 (p = 0.19); day 3, 64 vs 59 (p = 0.31); day 4, 72 vs 78 (p = 0.55). Analysis of variance (ANOVA) statistics showed a significant linear association of mean platelet counts by days in either group (p<0.001). Regression analysis identified the day of the illness and patient age as the independent predictors of platelet count change. Conclusion: At a low dose regimen, dexamethasone was not effective in achieving a higher rise of platelet count in dengue infection.

High efficacy of bolus methylprednisolone in severe leptospirosis: a descriptive study in Sri Lanka

Background In 2008, an outbreak of leptospirosis caused high mortality in Sri Lanka. The General Hospital, Peradeniya recorded nine deaths in May, which prompted the medical staff to change the treatment protocol. Addition of intravenous methylprednisolone (MP) to the treatment regimen of severely ill patients was implemented on the basis of immune mediated pathogenesis of the disease to reduce mortality. Methods The day MP commenced (25 May 2008), the study period was divided into a ‘pre-MP period’ and an ‘MP period’. A clinical score ranging from 0–6 was applied to assess the severity of the infection. A score ≥2 was considered severe. Thus, 62 patients received bolus MP 500 mg intravenously for 3 days, followed by oral 8 mg for 5 days (MP given). Ten patients to whom MP was withheld were included in the MP period severe group (n=72). The same score was applied to pre-MP periods and 60 cases were identified as the historical control group (pre-MP period severe). Results There were 78 and 149 cases of leptospirosis in the pre-MP period and MP period, respectively. Of these cases, 17 and 16 patients died, with case death rates of 21.8% and 10.7%, respectively; the difference was significant (p=0.025). The survival rate at score 4 in the MP period severe group was 100% (16 of 16), compared to 38% (5 of 13) in pre-MP period severe group; this difference was highly significant (p<0.001). Six patients who died despite MP therapy had a clinical score of 5 or 6; four were alcohol consumers, and two had heart disease and hypertension. Conclusion MP may reduce mortality in patients with severe leptospirosis, except in cases with established multiple organ dysfunction and comorbidities. Therefore, early administration of MP seems advisable.

Revisiting Russell's viper (Daboia russelii) bite in Sri Lanka: is abdominal pain an early feature of systemic envenoming?

The Russells viper (Daboia russelii) is responsible for 30–40% of all snakebites and the most number of life-threatening bites of any snake in Sri Lanka. The clinical profile of Russells viper bite includes local swelling, coagulopathy, renal dysfunction and neuromuscular paralysis, based on which the syndromic diagnostic tools have been developed. The currently available Indian polyvalent antivenom is not very effective in treating Russells viper bite patients in Sri Lanka and the decision regarding antivenom therapy is primarily driven by clinical and laboratory evidence of envenoming. The non-availability of early predictors of Russells viper systemic envenoming is responsible for considerable delay in commencing antivenom. The objective of this study is to evaluate abdominal pain as an early feature of systemic envenoming following Russells viper bites. We evaluated the clinical profile of Russells viper bite patients admitted to a tertiary care centre in Sri Lanka. Fifty-five patients were proven Russells viper bite victims who produced the biting snake, while one hundred and fifty-four were suspected to have been bitten by the same snake species. Coagulopathy (159, 76.1%), renal dysfunction (39, 18.7%), neuromuscular paralysis (146, 69.9%) and local envenoming (192, 91.9%) were seen in the victims, ranging from mono-systemic involvement to various combinations. Abdominal pain was present in 79.5% of these patients, appearing 5 minutes to 4 hours after the bite. The severity of the abdominal pain, assessed using a scoring system, correlated well with the severity of the coagulopathy (p<0.001) and the neurotoxicity (p<0.001). Its diagnostic validity to predict systemic envenoming is – Sensitivity 81.6%, Specificity 82.4%, Positive predictive value 91.2%. Thus, abdominal pain is an early clinical feature of systemic Russells viper bite envenoming in Sri Lanka. However, it is best to judge abdominal pain together with other clinical manifestations on decision making.

A Pan-Dengue Virus Reverse Transcription-Insulated Isothermal PCR Assay Intended for Point-of-Need Diagnosis of Dengue Virus Infection by Use of the POCKIT Nucleic Acid Analyzer

ABSTRACT Dengue virus (DENV) infection is considered a major public health problem in developing tropical countries where the virus is endemic and continues to cause major disease outbreaks every year. Here, we describe the development of a novel, inexpensive, and user-friendly diagnostic assay based on a reverse transcription-insulated isothermal PCR (RT-iiPCR) method for the detection of all four serotypes of DENV in clinical samples. The diagnostic performance of the newly established pan-DENV RT-iiPCR assay targeting a conserved 3′ untranslated region of the viral genome was evaluated. The limit of detection with a 95% confidence was estimated to be 10 copies of in vitro-transcribed (IVT) RNA. Sensitivity analysis using RNA prepared from 10-fold serial dilutions of tissue culture fluid containing DENVs suggested that the RT-iiPCR assay was comparable to the multiplex real-time quantitative RT-PCR (qRT-PCR) assay for DENV-1, -3, and -4 detection but 10-fold less sensitive for DENV-2 detection. Subsequently, plasma collected from patients suspected of dengue virus infection (n = 220) and individuals not suspected of dengue virus infection (n = 45) were tested by the RT-iiPCR and compared to original test results using a DENV NS1 antigen rapid test and the qRT-PCR. The diagnostic agreement of the pan-DENV RT-iiPCR, NS1 antigen rapid test, and qRT-PCR tests was 93.9%, 84.5%, and 97.4%, respectively, compared to the composite reference results. This new RT-iiPCR assay along with the portable POCKIT nucleic acid analyzer could provide a highly reliable, sensitive, and specific point-of-need diagnostic assay for the diagnosis of DENV in clinics and hospitals in developing countries.

Parallels between Russell's viper (Daboia russelii) and hump–nosed viper (Hypnale species) bites in the central hills of Sri Lanka amidst the heavy burden of unidentified snake bites

OBJECTIVE To describe the epidemiology of snake bite in the region and attempt to compare proven Russells viper with hump-nosed viper bites. METHODS All snake bite admissions to the Toxicology Unit of Teaching Hospital Peradeniya over three year from 2006 were included. RESULTS Of the 776 snakebites, 665(86%) were unidentified and non-envenomed. Hump-nosed viper and Russells viper accounted for 55(7%) and 40(5%) bites respectively, of them, incriminated snakes were found in 36(65%) and 19(48%) cases. The cobra bites-5, krait bites-0. The median ages: Russells viper bites-41(range 16-66), hump-nosed viper bites-42(range 15-75). The gender incidence, time of bite (>58% daytime) were similar. In hump-nosed viper bite; upper limb involved in 13(36%), happened at home garden in 22(61%), none in paddy fields. In Russells viper bite; 6(33%) occurred in paddy fields. Dry bites were similar at 5%. In hump-nosed viper bite: local effects 94%, coagulopathy 3%, acute renal failure 3% and one patient died. In Russells viper bite; local effects 84%, coagulopathy 53%, neurotoxicity 21%. Abdominal pain occurred only in Russells viper bites 10(53%). CONCLUSIONS Overwhelming numbers of unidentified, non-envenomed snakebites are common in the central hills. Some distinctive differences were observed between Russells viper and hump-nosed viper bites.

No evidence of chikungunya virus and antibodies shortly before the outbreak on Sri Lanka

A massive outbreak of chikungunya disease occurred on Sri Lanka in 2006. Reasons for the explosive nature of the epidemic are being intensively discussed. According to recognised and anecdotal concepts, absence of human population immunity against chikungunya virus (CHIKV) might have supported virus amplification. However, formal proof of concept is lacking. This study determined the prevalence of anti-CHIKV IgG antibodies as well as CHIKV RNA shortly before the outbreak. Two hundred and six human sera were collected from patients with acute febrile illness in 2004/2005. Validated indirect immunofluorescence and real-time RT-PCR assays for dengue as well as CHIKV were employed. Laboratory evidence of dengue virus infection was seen in 67% of patients, indicating virus activity and exposure to Aedes spp. vectors. These vectors are the same as for chikungunya. However, no evidence of acute or previous chikungunya infection could be demonstrated in the same cohort. This study gives formal evidence that the absence of human population immunity correlated with a large chikungunya epidemic.