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Dengue-specific IgA in different body fluids: a prospective alternative for dengue diagnosis in resource-poor settings
... The remaining six articles were excluded for reasons mentioned in Table 2. Of these, one article was excluded because denguenegative samples were not included in the study while another article was excluded because the data was based on capillary blood samples [18,20]. Four other articles were excluded due to the use of inappropriate gold standard assays [19,25,27,28]. ...
Immunoglobulin A (IgA)-based tests have been evaluated in different studies for their utility in diagnosing dengue infections. In most of the studies, the results were inconclusive because of a small sample size. Hence, a meta-analysis involving nine studies with 2096 samples was performed to assess the diagnostic accuracy of IgA-based tests in diagnosing dengue infections. The analysis was conducted using Meta-Disc software. The results revealed that IgA-based tests had an overall sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios of 73·9%, 95·2%, 66·7, 22·0 and 0·25, respectively. Significant heterogeneity was observed between the studies. The type of test, infection status and day of sample collection influenced the diagnostic accuracy. The IgA-based diagnostic tests showed a greater accuracy when the samples were collected 4 days after onset of symptoms and for secondary infections. The results suggested that IgA-based tests had a moderate level of accuracy and are diagnostic of the disease. However, negative results cannot be used alone for dengue diagnosis. More prospective studies comparing the diagnostic accuracy of combinations of antigen-based tests with either IgA or IgM are needed and might be useful for suggesting the best strategy for dengue diagnosis.
Abdominal pain is a commonly reported symptom in DF. The reported causes of abdominal pain in DF include hepatitis, pancreatitis, acaculous cholecystitis and peptic ulcer disease. Till to date, there has been no planned study to evaluate the cause of pain abdomen in DF. This study was planned to evaluate the etiology of abdominal pain in DF. Patients presenting with fever and pain abdomen to our hospital from July to November 2003 and July to November 2004 were included in the study. A probable diagnosis of DF was made based on the presence of acute febrile illness with two or more of the following manifestations: headache, retro- orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestation and leukopenia. The diagnosis was confirmed by enzyme immunoassay-based serology. DHF was diagnosed based on WHO criteria. The cause of pain abdomen was ascertained by blood tests (amylase, lipase and liver function test), radiology (X-ray abdomen-erect and supine, USG, CECT) and/or endoscopy. Out of the 100 patients presenting with fever and pain abdomen, 55 patients were diagnosed to have DF. The remaining 45 patients had other causes of fever with pain abdomen. The various causes of pain abdomen diagnosed in patients with DF were: acute hepatitis, acalculus cholecystitis, acute pancreatitis, appendicitis, spontaneous bacterial peritonitis, enteritis, peptic ulcer disease and gastric erosions in 20 (36.4%), 9 (16.4%), 8 (14.5%), 3 (5.45%), 2 (3.63%), 8 (14.54%), 2 (3.63%) and 3 (5.45%) of the patients respectively. In patients with dengue fever, the etiology of abdominal pain should be aggressively looked into for
To measure the impact on the dengue vector population (Aedes aegypti) and disease transmission of window curtains and water container covers treated with insecticide.
Cluster randomised controlled trial based on entomological surveys and, for Trujillo only, serological survey. In addition, each site had a non-randomised external control.
18 urban sectors in Veracruz (Mexico) and 18 in Trujillo (Venezuela).
4743 inhabitants (1095 houses) in Veracruz and 5306 inhabitants (1122 houses) in Trujillo.
Sectors were paired according to entomological indices, and one sector in each pair was randomly allocated to receive treatment. In Veracruz, the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips (an insect growth regulator). In Trujillo, the intervention comprised curtains treated with longlasting deltamethrin (PermaNet) plus water jar covers of the same material. Follow-up surveys were conducted at intervals, with the final survey after 12 months in Veracruz and nine months in Trujillo.
Reduction in entomological indices, specifically the Breteau and house indices.
In both study sites, indices at the end of the trial were significantly lower than those at baseline, though with no significant differences between control and intervention arms. The mean Breteau index dropped from 60% (intervention clusters) and 113% (control) to 7% (intervention) and 12% (control) in Veracruz and from 38% to 11% (intervention) and from 34% to 17% (control) in Trujillo. The pupae per person and container indices showed similar patterns. In contrast, in nearby communities not in the trial the entomological indices followed the rainfall pattern. The intervention reduced mosquito populations in neighbouring control clusters (spill-over effect); and houses closer to treated houses were less likely to have infestations than those further away. This created a community effect whereby mosquito numbers were reduced throughout the study site. The observed effects were probably associated with the use of materials treated with insecticide at both sites because in Veracruz, people did not accept and use the pyriproxyfen chips.
Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission.
With the example of dengue, an evidence-based approach to prospectively develop a case classification is described, gathering evidence for identifying strength and weaknesses of the existing model, collecting new data describing the disease as it occurs globally, further developing a new model that can be applied in practice and field testing the newly developed model in comparison to the previous model. For each step in this process, the highest available level of evidence has been applied. This process has been initiated by the World Health Organization's (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) and WHO's Department for Control of Neglected Tropical Diseases (NTD), developing the following for dengue. Since the early 1970s, dengue has been classified into dengue fever, dengue haemorrhagic fever grades I and II and dengue shock syndrome grades III and IV (DF/DHF/DSS). However, in recent years, a growing number of dengue clinicians have questioned the shortcomings of this scheme. The issues have revolved around the complexity of confirming DHF in clinical practice, misclassifying severe cases as DF, and the emphasis on haemorrhage rather than plasma leakage as the underlying problem in most severe dengue cases. Step 1: A systematic literature review highlighted the shortcomings of the DF/DHF/DSS scheme: (1) difficulties in applying the criteria for DHF/DSS; (2) the tourniquet test has a low sensitivity for distinguishing between DHF and DF; and (3) most DHF criteria had a large variability in frequency of occurrence. Step 2: An analysis of regional and national dengue guidelines and their application in the clinical practice showed a need to re-evaluate and standardize guidelines as the actual ones showed a large variation of definitions, an inconsistent application by medical staff, and a lack of diagnostic facilities necessary for the DHF diagnosis in frontline services. Step 3: A prospective cohort study in seven countries, confirmed the difficulties in applying the DF/DHF/DSS criteria even in tertiary care hospitals, that DF/DHF/DSS do not represent levels of disease severity and that a clear distinction between severe dengue (defined by plasma leakage and/or severe haemorrhage, and/or organ failure) and (non-severe) dengue can be made using highly sensitive and specific criteria. In contrast, the sub-grouping of (non-severe) dengue into two further severity levels was only possible with criteria that gave approximately 70% sensitivity and specificity. Step 4: Three regional expert consensus groups in the Americas and Asia concluded that 'dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome' and that, revising the results of Step 3, DF/DHF/DSS is not related to disease severity. Step 5: In a global expert consensus meeting at WHO in Geneva/Switzerland the evidence collected in Steps 1-4 was reviewed and a revised scheme was developed and accepted, distinguishing: dengue with or without warning signs and severe dengue; the further field testing and acquisition of further prospective evidence of the revised scheme was recommended. Step 6: In 18 countries, the usefulness and applicability of the revised classification compared to the DF/DHF/DSS scheme were tested showing clear results in favour of the revised classification. Step 7: Studies are under way on the predictive value of warning signs for severe dengue and on criteria for the clinical diagnosis of dengue which will complete the evidence foundation of the revised classification. The analysis has shown that the revised dengue case classification is better able to standardize clinical management, raise awareness about unnecessary interventions, match patient categories with specific treatment instructions, and make the key messages of patient management understandable for all health care staff dealing with dengue patients. Furthermore, the evidence-based approach to develop prospectively the dengue case classification could be a model approach for other disease classifications.
Dengue is the most important arboviral disease worldwide. We report the complete genome sequence of a dengue virus serotype
4, genotype II strain isolated in 2010 from a patient with classical dengue fever in Boa Vista, Roraima, Brazil.
There has been confusion regarding the clinical classification of dengue. The current WHO classification used since the 70s classifies dengue into dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS). In 2009, a new classification of dengue proposed by WHO Tropical Disease Research (TDR) was published in the WHO TDR 2009 dengue guidelines. This new classification classifies dengue into dengue (D), dengue with warning signs (DW) and severe dengue (SD).
To compare the effectiveness in clinical management between the current WHO classification and the newly suggested classification (TDR) and to assess the 4 criteria of the DHF case definition of the current WHO classification for possible modification.
A prospective study of suspected dengue patients admitted to the Dengue Unit, Queen Sirikit National Institute of Child Health between June-August 2009 was done. All cases were managed according to the Thai National Dengue Guidelines 2008. The final diagnoses were based on the current WHO Classification together with dengue laboratory confirmation. TDR classification was applied later by the author, using the data from the present study case report forms of each patient. Statistical analysis comparing clinical and laboratory data between each group of patients was done by using SPSS version 14.
Total 274 confirmed dengue patients and 24 non-dengue febrile illnesses (ND) were used for analysis. There were 180 DF (65.7%), 53 DHF grade I (19.3%), 19 DHF grade II (6.9%), 19 DHF grade II (6.9%) and 3 DHF grade IV (1.1%) as classified by the current WHO classification while the suggested TDR classified 85 (31%), 160 (58.4%) and 29 (1.1%) as D, DW and SD respectively. At least one of the warning signs were found in 50, 53.3, 83, 88.2, 100 and 100% of ND, DF, DHF grade I, DHF grade II, DHF grade III and DHF grade IV patients. Vomiting and abdominal pain were the 2 most common warning signs found in both ND and dengue patients. Intensive monitoring and careful medical and i.v. fluid management were needed for 94 DHF patients compared to 189 DW and SD patients by the new TDR classification. There were 8 DSS patients who had AST > 1,000U and one patient presented with encephalopathy. These 8 patients cannot be classified properly in the current WHO classification. One non-dengue patient who presented with gastrointestinal bleeding was classified as SD. Bleeding and/or positive tourniquet test was found in and 69.7% of DHF patients. Plasma leakage detected using hemoconcentration, chest x-ray (CXR) and ultrasonography. Hemoconcentration could detect plasma leakage in 44.7% and CXR added up evidence of plasma leakage to 86.3%. Ultrasonography was the most sensitive technique to add evidence of plasma leakage up to 100%. Platelet < or = 100,000 cells/mm3 was found in 93.5% of DHF patients.
Current WHO classification is recommended for continuing use because the newly suggested TDR classification creates about 2 times the workload to health care personnel. In addition, the TDR classification needs dengue confirmatory tests. More than 90% of DHF defined by WHO case definition are dengue confirmed. However, current WHO classification needs to be modified for more simple and friendly use. The suggested modification is to address plasma leakage as the major criteria. Tourniquet test positive or bleeding symptoms can be considered as minor criteria. Unusual dengue is proposed to be added to the current WHO classification to cover those patients who do not fit with the current WHO classification.
In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification systems regarding applicability in clinical practice and surveillance, as well as user-friendliness and acceptance by health staff.
A mix of quantitative (prospective and retrospective review of medical charts by expert reviewers, formal staff interviews), semi-quantitative (open questions in staff interviews) and qualitative methods (focus group discussions) were used in 18 countries. Quality control of data collected was undertaken by external monitors.
The applicability of the DF/DHF/DSS classification was limited, even when strict DHF criteria were not applied (13.7% of dengue cases could not be classified using the DF/DHF/DSS classification by experienced reviewers, compared to only 1.6% with the revised classification). The fact that some severe dengue cases could not be classified in the DF/DHF/DSS system was of particular concern. Both acceptance and perceived user-friendliness of the revised system were high, particularly in relation to triage and case management. The applicability of the revised classification to retrospective data sets (of importance for dengue surveillance) was also favourable. However, the need for training, dissemination and further research on the warning signs was highlighted.
The revised dengue classification has a high potential for facilitating dengue case management and surveillance.
Dengue fever, a mosquito-borne viral infection, causes significant morbidity and has become endemic in the Indian subcontinent. Virus strains currently circulating in many parts of the country are not well studied at the molecular level. In the present study, genetic characterization of virus strains from a dengue outbreak that occurred in and around a tertiary care hospital in Ernakulam, Kerala in the year 2008 has been reported. By reverse transcription polymerase chain reaction (RT-PCR), 37 out of 75 (49.3%) clinically suspected cases were positive for dengue viral RNA. Among these, 21 (56.8%) samples showed concurrent infection with multiple serotypes of the virus. Majority of the combined infections were caused by dengue serotype 2 and 3. Co-infections with type 1 and 2 in two patients, and type 1, 2 and 3 in one patient were also observed. The core-pre-Membrane (CprM) junction nucleotide sequencing and phylogenetic analysis revealed that the type 1 strains were related to the viral strains reported from Delhi-2001 and Gwalior-2002 dengue outbreaks, while the type 2 strains were related to the strains from Gwalior-2001 epidemic. Sequences of type 3 strains did not show clear relation to any of the previous Indian isolates, and in the phylogenetic analysis, they formed a distinct lineage within the Indian type 3 strains. This study indicates hyperendemicity of dengue in the region with the presence of multiple serotypes and high rates of co-infection, and local genomic evolution of the viral strains involved in this outbreak.
Infection with hepatitis C virus (HCV) is usually established by detection of serum antibodies (anti-HCV). This study was conducted in order to evaluate whether saliva and urine may substitute serum for anti-HCV detection. Serum, saliva, and urine were obtained simultaneously from 141 patients with a variety of liver diseases and from 52 patients with autoimmune diseases (systemic lupus erythematosus n = 27 and rheumatoid arthritis n = 25). The cell free fraction of saliva and urine samples was tested for anti-HCV using a modification of a serum anti-HCV kit. Western blot analysis was used as a confirmation method. Of the patients with liver diseases, 73 were anti-HCV-seropositive. Salivary and urinary anti-HCV could be detected in 66 (90%) and 36 (49%) of the anti-HCV-serpositive patients, respectively. The presence of anti-HCV in saliva or urine was not related to the severity of liver disease. All the anti-HCV-seronegative liver patients were negative for salivary anti-HCV and 22 (32%) had urinary anti-HCV. The patients with autoimmune diseases were all anti-HCV-seronegative. None had detectable salivary anti-HCV while 33 (63%) were positive for urinary anti-HCV. Western Blot analysis confirmed the presence of anti-HCV in all serum and saliva samples tested but only in 2/12 urine samples. The results suggest that saliva, but not urine, may serve as a substitute for serum for the determination of anti-HCV positivity. J. Med. Virol. 55:24–27, 1998. © 1998 Wiley-Liss, Inc.
Susceptibility to Bacillus thuringiensis of mosquito and lepidopteran larvae is affected by feeding behaviour and nutritional value of the available food. Reduced mortality is attributed to feeding inhibition and dilution of the pathogen in the presence of nutritional and inert particles, which limit the amount of ingested toxin. These reasons are, however, not sufficient to explain the data presented here. Values of LC50 (the concentration that kills 50% of exposed population) of B. thuringiensis subsp. israelensis (Berliner) against Aedes aegypti (L.) larvae and of B. thuringiensis subsp. kenyae (Berliner) against Spodoptera littoralis (Boisduval) larvae were about 20–217 and 2.3–44-fold higher, respectively, in the presence of nutritional or biologically inert (non-nutritional) particles than without. The number of B. thuringiensis spores in carcasses of B. thuringiensis -killed A. aegypti and S. littoralis larvae were between 1.9 and 5.6-fold and between 8.5 and 12-fold higher, respectively, in the presence of particles than without. In all cases, non-nutritional particles better protected the exposed larvae than nutritious particles. We propose that another basic mechanism exists, that ingested particles protect midgut epithelial cells by covering their surface and thus preventing availability of the toxin to the gut receptors. Understanding the defence mechanisms of insects against B. thuringiensis toxicity may lead to improved pest management methods.
