R. Premaratna

The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths

Background Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites. Methods and Findings The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually. Conclusions Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.

Evaluation of Six Commercial Point-of-Care Tests for Diagnosis of Acute Dengue Infections: the Need for Combining NS1 Antigen and IgM/IgG Antibody Detection To Achieve Acceptable Levels of Accuracy

ABSTRACT Six assays were evaluated in this study to determine their suitability for the diagnosis of acute dengue infection using samples from 259 Sri Lankan patients with acute fevers (99 confirmed dengue cases and 160 patients with other confirmed acute febrile illnesses): (i) the Merlin dengue fever IgG & IgM combo device (Merlin), (ii) the Standard Diagnostics Dengue Duo nonstructural 1 (NS1) antigen and IgG/IgM combo device (Standard Diagnostics, South Korea), (iii) the Biosynex Immunoquick dengue fever IgG and IgM (Biosynex, France) assay, (iv) the Bio-Rad NS1 antigen strip (Bio-Rad, France), (v) the Panbio Dengue Duo IgG/IgM Cassette (Inverness, Australia), and (vi) the Panbio dengue NS1 antigen strip (Inverness, Australia). The median number of days of fever prior to admission sample collection was 5 days (interquartile range, 3 to 7 days). Sensitivity and specificity of the NS1 antigen tests ranged from 49 to 59% and from 93 to 99%, respectively, and sensitivity and sensitivity of the IgM antibody test ranged from 71 to 80% and from 46 to 90%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics Dengue Duo test gave the best compromise of sensitivity and specificity (93% and 89%, respectively) and provided the best sensitivity in patients presenting at different times after fever onset. The Merlin IgM/IgG antibody tests correctly classified 64% and 86% of the primary and secondary dengue infection cases, respectively, and the Standard Diagnostics IgM/IgG antibody tests correctly classified 71% and 83% of the primary and secondary dengue infection cases, respectively. This study provides strong evidence of the value of combining dengue antigen- and antibody-based test results in the rapid diagnostic test (RDT) format for the acute diagnosis of dengue.

Comparison of Seven Commercial Antigen and Antibody Enzyme-Linked Immunosorbent Assays for Detection of Acute Dengue Infection

ABSTRACT Seven commercial assays were evaluated to determine their suitability for the diagnosis of acute dengue infection: (i) the Panbio dengue virus Pan-E NS1 early enzyme-linked immunosorbent assay (ELISA), second generation (Alere, Australia); (ii) the Panbio dengue virus IgM capture ELISA (Alere, Australia); (iii) the Panbio dengue virus IgG capture ELISA (Alere, Australia); (iv) the Standard Diagnostics dengue virus NS1 antigen ELISA (Standard Diagnostics, South Korea); (v) the Standard Diagnostics dengue virus IgM ELISA (Standard Diagnostics, South Korea); (vi) the Standard Diagnostics dengue virus IgG ELISA (Standard Diagnostics, South Korea); and (vii) the Platelia NS1 antigen ELISA (Bio-Rad, France). Samples from 239 Thai patients confirmed to be dengue virus positive and 98 Sri Lankan patients negative for dengue virus infection were tested. The sensitivities and specificities of the NS1 antigen ELISAs ranged from 45 to 57% and 93 to 100% and those of the IgM antibody ELISAs ranged from 85 to 89% and 88 to 100%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics ELISAs gave the best compromise between sensitivity and specificity (87 and 96%, respectively), as well as providing the best sensitivity for patients presenting at different times after fever onset. The Panbio IgG capture ELISA correctly classified 67% of secondary dengue infection cases. This study provides strong evidence of the value of combining dengue virus antigen- and antibody-based test results in the ELISA format for the diagnosis of acute dengue infection.

Poor Diagnostic Accuracy of Commercial Antibody-Based Assays for the Diagnosis of Acute Chikungunya Infection

ABSTRACT A Sri Lankan fever cohort (n = 292 patients; 17.8% prevalence) was used to assess two standard diagnostic Chikungunya IgM tests. The immunochromatographic test (ICT) acute sample sensitivity (SN) was 1.9 to 3.9%, and specificity (SP) was 92.5 to 95.0%. The enzyme-linked immunosorbent assay (ELISA) gave an acute sample SN of 3.9% and an SP of 92.5% and a convalescent sample SN of 84% and an SP of 91%. These assays are not suitable for the acute diagnosis of Chikungunya virus infection.

Evaluation of the ICT whole-blood antigen card test to detect infection due to Wuchereria bancrofti in Sri Lanka

The sensitivity, specificity and cost effectiveness of an immunochromatographic card test (ICT, AMRAD) for the diagnosis of bancroftian filariasis were estimated against 2 standard parasitological techniques: thick blood film (TBF) and Nuclepore membrane filtration (NMF). Individuals were selected from endemic localities in the Western Province (n = 213) and from the non-endemic Central Province (n = 29) of Sri Lanka. Blood was collected between 21:00 and midnight. Sixty microlitre of non-heparinized blood, and 1 mL and 100 microL of heparinized blood were used in TBF, NMF and ICT, respectively. NMF was positive in 31.5% (67/213) of the endemic group, with a mean microfilaria (mf) count of 343/mL (range 8-1782, SD 422). All 67 were positive by ICT (sensitivity 100%), but only 63 by TBF (sensitivity 94%). Among the endemic population there were 12 who were mf negative but antigen positive by ICT. There were, however, no false positives among the non-endemic controls, indicating the possibility that the ICT may in fact be more sensitive and 100% specific. Thus, ICT filariasis test appears to be more effective (both sensitive and specific) than TBF or NMF in diagnosing infection in lymphatic filariasis. The direct unit recurrent costs of the 2 survey tools, TBF and ICT, were US

Intravenous N-acetylcysteine in dengue-associated acute liver failure

0.30 (Rs. 27/=) and US

Lymphoedema management knowledge and practices among patients attending filariasis morbidity control clinics in Gampaha District, Sri Lanka

2.75 (Rs. 248/=), respectively. The high cost of the ICT may be offset by other factors that are difficult to cost.

Unusual pancytopenia secondary to haemophagocytosis syndrome in rickettsioses.

We read with interest the article by Mumtaz et al. [1] on the role of oral N-acetylcysteine (NAC) in adults with non-acetaminophen-induced acute liver failure. We agree that their findings are of particular relevance to many developing countries, where liver transplantation is neither available nor affordable. There has been another recent study in which intravenous NAC has been shown to improve transplant-free survival in early-stage non-acetaminophen-induced acute liver failure in adults [2]. We report our initial experience in treating acute liver failure caused by dengue infection with NAC. Use of NAC in this situation has not been previously described.

Effects of pollution on health of residents in an industrial area in Sri Lanka.

Background Little information is available on methods of treatment practiced by patients affected by filarial lymphoedema in Sri Lanka. The frequency and duration of acute dematolymphangioadenitis (ADLA) attacks in these patients remain unclear. This study reports the knowledge, practices and perceptions regarding lymphoedema management and the burden of ADLA attacks among patients with lymphoedema. Methods A semi-structured questionnaire was used to assess morbidity alleviation knowledge, practices and perceptions. The burden of ADLA attacks was assessed using one-year recall data. Results 66 patients (22 males, 44 females) with mean age 51.18 years (SD ± 13.9) were studied. Approximately two thirds of the patients were aware of the importance of skin and nail hygiene, limb elevation and use of footwear. Washing was practiced on a daily and twice daily basis by 40.9% and 48.5% respectively. However, limb elevation, exercise and use of footwear were practiced only by 21–42.4% (while seated and lying down), 6% and 34.8% respectively. The majority of patients considered regular intake of diethylcarbamazine citrate (DEC) important. Approximately two thirds (65.2%) had received health education from filariasis clinics. Among patients who sought private care (n = 48) the average cost of treatment for an ADLA attack was Rs. 737.91. Only 18.2% had feelings of isolation and reported community reactions ranging from sympathy to fear and ridicule. Conclusions Filariasis morbidity control clinics play an essential role in the dissemination of morbidity control knowledge. Referral of lymphoedema patients to morbidity control clinics is recommended.

A case series of spotted fever rickettsiosis with neurological manifestations in Sri Lanka

We report two patients who presented with a long-lasting febrile illness associated with pancytopenia. Both of them had evidence of hypercellular marrow with haemophagocytosis. They were confirmed as having rickettsial infections by serology and had a rapid haematological recovery with anti-rickettsial antibiotics. We highlight the importance of considering rickettsial infections in patients with such clinical presentations, especially in areas where these infections are endemic or re-emerging. Empirical use of anti-rickettsial antibiotics in such situations could be beneficial, when facilities to diagnose rickettsial diseases are not readily available.