Letter to the Editor
Categorization of dengue fever according to phase of illness—a suggestion for clinical studies using single diagnostic sample
Emmanuel Bhaskara,
, Raveendran Praveenab, Gopalan Sowmyaa, Swathy Moorthya
Corresponding author
drmeb1974@yahoo.co.in
Corresponding author at: Sri Ramachandra Medical College and Research Institute, Porur, Chennai 600116, India.
Corresponding author at: Sri Ramachandra Medical College and Research Institute, Porur, Chennai 600116, India.
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"documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Braz J Infect Dis. 2013;17:619-21" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1960 "formatos" => array:3 [ "EPUB" => 235 "HTML" => 1168 "PDF" => 557 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Lymphocytic myocarditis at autopsy in patients with dengue fever" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "619" "paginaFinal" => "621" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1728 "Ancho" => 1382 "Tamanyo" => 1028158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Chronic inflammatory infiltrates with lymphocytic and eosinophilic predominance. There is an area of myocyte necrosis and mild interstitial scarring (arrow), (B) diffuse myocardial inflammatory infiltrates, mainly lymphocytes and scattered giant cells, (C) perivascular inflammation with associated endocardial fibrosis. There is myocyte necrosis and endothelial hyperplasia and (D) focal lymphocytic myocarditis. This focus and other foci were the only relevant findings in this case, raising the question of focal myocarditis as the cause of sudden death.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alba Fabiola Torres, Deborah Nunes Braga, Felipe Muniz, Cindy Mendonça, Denise Nunes Oliveira, Emilia Tome de Souza, Allen Burke, Fabio Tavora" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Alba Fabiola" "apellidos" => "Torres" ] 1 => array:2 [ "nombre" => "Deborah Nunes" "apellidos" => "Braga" ] 2 => array:2 [ "nombre" => "Felipe" "apellidos" => "Muniz" ] 3 => array:2 [ "nombre" => "Cindy" "apellidos" => "Mendonça" ] 4 => array:2 [ "nombre" => "Denise Nunes" "apellidos" => "Oliveira" ] 5 => array:2 [ "nombre" => "Emilia Tome" "apellidos" => "de Souza" ] 6 => array:2 [ "nombre" => "Allen" "apellidos" => "Burke" ] 7 => array:2 [ "nombre" => "Fabio" "apellidos" => "Tavora" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1413867013001876?idApp=UINPBA00003Y" "url" => "/14138670/0000001700000005/v4_201503030410/S1413867013001876/v4_201503030410/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Categorization of dengue fever according to phase of illness—a suggestion for clinical studies using single diagnostic sample" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "622" "paginaFinal" => "623" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Emmanuel Bhaskar, Raveendran Praveena, Gopalan Sowmya, Swathy Moorthy" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Emmanuel" "apellidos" => "Bhaskar" "email" => array:1 [ 0 => "drmeb1974@yahoo.co.in" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Raveendran" "apellidos" => "Praveena" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Gopalan" "apellidos" => "Sowmya" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Swathy" "apellidos" => "Moorthy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Medicine, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, India" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Microbiology, Sree Balaji Medical College and Hospital, Chrompet, Chennai, India" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author at</span>: Sri Ramachandra Medical College and Research Institute, Porur, Chennai 600116, India." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In 2008, World Health Organization (WHO) experts agreed that “dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome”.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The development of a spectrum of laboratory methods to detect the first of seven non-structural proteins in dengue virus, NS1 (non-structural protein-1) leads us toward an opportunity to observe the features of dengue during viremic phase which corresponds to the first 3 days of illness.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Prior to the availability of NS1 antigen assays for detection of dengue, the illness was confirmed only after the detection of IgM and (or) IgG antibodies. This also helps us infer that studies on dengue fever using positive serology as part of dengue case definition would have identified only features of dengue in the immune phase of the illness. Though inference based on paired sera is the ideal way to confirm dengue, our limited experience in dengue indicates that the concept of utilizing paired sera in dengue diagnosis is difficult to practice since obtaining a sample beyond the 10th day of illness in a patient who is free of symptoms raises consent related issues.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> WHO recommends classification of dengue as dengue fever<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>warning signs and severe dengue.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> We suggest a further laboratory based categorization for dengue illness (both WHO categories) using a single diagnostic sample incorporating aspects related to dengue pathogenesis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A brief overview on the immunology of dengue may help in understanding our classification.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4</span></a> Dengue fever is characterized by an initial viremic phase which corresponds to the first 3 days of illness followed by immune phase (also called critical phase) spanning from 3rd to 6th day of illness. The phase of dengue beyond 6th day of illness is called recovery phase (though a sizable number of patients take longer to recover). When the dengue virus infects a previously non-infected person, it is inferred as primary dengue infection [PDI]. A patient with PDI will demonstrate NS1 antigen till the 3rd day of illness (sometimes as long as the 9th day), IgM antibodies detectable beyond the 3rd day of illness and IgG beyond the 7th day of illness. Though IgM and IgG are detectable by the 7th day of PDI, the dominant antibody is IgM as demonstrated by IgM/IgG optical density ratio of more than the assay cut-off value (studies have used a cut-off value of >1.2 with patient sera in 1/100 dilution or >1.4 with patient sera in 1/20 dilution).<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> When the dengue virus infects a person who had been previously infected by a different dengue serotype it is said to be secondary dengue infection [SDI]. The detection of NS1 in SDI is timed similar to PDI. However an anamnestic IgG response occurs at the onset of SDI earlier to the appearance of IgM antibodies making the onset of the immune phase concomitant with the viremic phase. The challenge in identifying SDI is complicated by two factors. First, a slow IgM rise (sometimes not detectable) during convalescence in SDI. Second, IgG is being the dominant antibody in SDI. These make IgM/IgG optical density ratio less than the assay dependent cut-off value as a laboratory hallmark of SDI. Though serial monitoring of IgG titers helps in SDI diagnosis, the concept is infrequently practised. Studying dengue illness after categorizing it as viremic phase, viremia-immune overlap phase, and immune phase (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) will facilitate better understanding of occurrence and progression of clinical symptoms, signs and laboratory findings. Obtaining these information (especially course of thrombocytopenia and organ dysfunction) gains critical importance since it may help us predicting the course of the illness with current therapies for dengue fever.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The suggested classification may furthermore help identifying the effects of interventions (anti-viral therapy, corticosteroids, immunosuppresants) during viremic phase and viremia-immune overlap which could lessen the complications observed in the immune phase. The classification does have important limitations. First one is the diagnosis of SDI, a factor which is difficult to address taking into account the complex IgM and IgG antibody response observed in secondary infection. Second is the lack of standardization among NS1 assays, though an ELISA based protocol is generally preferred.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> WHO recommendation on methods of NS1 detection will add clarity to the classification. Third, diagnostic accuracy compared to paired sample. Adopting a cut-off value for IgM (>40<span class="elsevierStyleHsp" style=""></span>units) and IgG (>100<span class="elsevierStyleHsp" style=""></span>units) in the classification has partially addressed the non-inclusion of paired sera for dengue diagnosis.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0020" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-04-01" "fechaAceptado" => "2013-05-02" "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">IgM and IgG detection by enzyme-linked immunosorbent assay (ELISA). NS1 detection by ELISA (further scientific inputs required).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Phase of illness \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Primary infection \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Secondary infection \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Viremic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS1 positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No isolated viremic phase since anamnestic IgG response often present at the onset of illness \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top">Viremia-immune overlap</td><td class="td" title="table-entry " align="left" valign="top">NS1 positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS1 positive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Plus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Plus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">One of the following: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">One of the following \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgM positive (>40<span class="elsevierStyleHsp" style=""></span>units) and IgG negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IgG positive (>100<span class="elsevierStyleHsp" style=""></span>units) and IgM negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgM/IgG optical density ratio<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>cut-off value of assay<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IgM/IgG optical density ratio<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>cut-off value of assay<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Immune</td><td class="td" title="table-entry " align="left" valign="top">IgM positive (>40<span class="elsevierStyleHsp" style=""></span>units) and IgG negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IgM/IgG optical density ratio<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>cut-off value of assay<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">OR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IgM/IgG optical density ratio<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>cut-off value of assay<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab691759.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Studies have used a cut-off value of 1.2 with patient sera in 1/100 dilution or 1.4 with patient sera in 1/20 dilution.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Laboratory based staging for clinical studies using a single diagnostic sample.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Dengue-guidelines for diagnosis treatment prevention and control" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:4 [ "edicion" => "new edition" "fecha" => "2009" "editorial" => "World Health Organization" "editorialLocalizacion" => "Geneva" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => 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Chang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Microbiol Immunol Infect" "fecha" => "2005" "volumen" => "38" "paginaInicial" => "5" "paginaFinal" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15692621" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Altered enzyme-linked immunosorbent assay immunoglobulin M (IgM)/IgG optical density ratios can correctly classify all primary or secondary dengue virus infections 1 day after the onset of symptoms, when all of the viruses can be isolated" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.K. Falconar" 1 => "E. de Plata" 2 => "C.M. Romero-Vivas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Vacc Immunol" "fecha" => "2006" "volumen" => "13" "paginaInicial" => "1044" "paginaFinal" => "1051" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multi-country evaluation of the sensitivity and specificity of two commercially-available NS1 ELISA assays for dengue diagnosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.G. Guzman" 1 => "T. Jaenisch" 2 => "R. Gaczkowski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pntd.0000811" "Revista" => array:5 [ "tituloSerie" => "PLoS Negl Trop Dis" "fecha" => "2010" "volumen" => "4" "paginaInicial" => "e811" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20824173" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dengue in the early febrile phase: viremia and antibody responses" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.W. Vaughn" 1 => "S. Green" 2 => "S. Kalayanarooj" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "1997" "volumen" => "176" "paginaInicial" => "322" "paginaFinal" => "330" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9237696" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/14138670/0000001700000005/v4_201503030410/S1413867013001530/v4_201503030410/en/main.assets" "Apartado" => array:4 [ "identificador" => "19368" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/14138670/0000001700000005/v4_201503030410/S1413867013001530/v4_201503030410/en/main.pdf?idApp=UINPBA00003Y&text.app=https://bjid.org.br/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1413867013001530?idApp=UINPBA00003Y" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 309 | 10 | 319 |
| 2024 September | 496 | 34 | 530 |
| 2024 August | 413 | 36 | 449 |
| 2024 July | 384 | 37 | 421 |
| 2024 June | 180 | 35 | 215 |
| 2024 May | 78 | 29 | 107 |
| 2024 April | 96 | 27 | 123 |
| 2024 March | 110 | 37 | 147 |
| 2024 February | 150 | 34 | 184 |
| 2024 January | 709 | 30 | 739 |
| 2023 December | 199 | 42 | 241 |
| 2023 November | 380 | 59 | 439 |
| 2023 October | 752 | 43 | 795 |
| 2023 September | 941 | 61 | 1002 |
| 2023 August | 563 | 31 | 594 |
| 2023 July | 507 | 34 | 541 |
| 2023 June | 255 | 32 | 287 |
| 2023 May | 182 | 36 | 218 |
| 2023 April | 136 | 37 | 173 |
| 2023 March | 184 | 44 | 228 |
| 2023 February | 156 | 54 | 210 |
| 2023 January | 259 | 38 | 297 |
| 2022 December | 413 | 58 | 471 |
| 2022 November | 1490 | 49 | 1539 |
| 2022 October | 3822 | 53 | 3875 |
| 2022 September | 3839 | 50 | 3889 |
| 2022 August | 1569 | 55 | 1624 |
| 2022 July | 970 | 44 | 1014 |
| 2022 June | 754 | 56 | 810 |
| 2022 May | 621 | 58 | 679 |
| 2022 April | 433 | 60 | 493 |
| 2022 March | 431 | 52 | 483 |
| 2022 February | 525 | 56 | 581 |
| 2022 January | 587 | 44 | 631 |
| 2021 December | 938 | 73 | 1011 |
| 2021 November | 2363 | 49 | 2412 |
| 2021 October | 3273 | 56 | 3329 |
| 2021 September | 1120 | 59 | 1179 |
| 2021 August | 795 | 42 | 837 |
| 2021 July | 363 | 24 | 387 |
| 2021 June | 199 | 54 | 253 |
| 2021 May | 172 | 47 | 219 |
| 2021 April | 415 | 129 | 544 |
| 2021 March | 253 | 41 | 294 |
| 2021 February | 179 | 34 | 213 |
| 2021 January | 210 | 45 | 255 |
| 2020 December | 176 | 26 | 202 |
| 2020 November | 177 | 18 | 195 |
| 2020 October | 156 | 25 | 181 |
| 2020 September | 137 | 31 | 168 |
| 2020 August | 137 | 44 | 181 |
| 2020 July | 120 | 40 | 160 |
| 2020 June | 87 | 26 | 113 |
| 2020 May | 73 | 41 | 114 |
| 2020 April | 68 | 14 | 82 |
| 2020 March | 101 | 33 | 134 |
| 2020 February | 168 | 34 | 202 |
| 2020 January | 92 | 35 | 127 |
| 2019 December | 106 | 16 | 122 |
| 2019 November | 193 | 18 | 211 |
| 2019 October | 261 | 32 | 293 |
| 2019 September | 160 | 32 | 192 |
| 2019 August | 112 | 39 | 151 |
| 2019 July | 136 | 35 | 171 |
| 2019 June | 118 | 24 | 142 |
| 2019 May | 163 | 36 | 199 |
| 2019 April | 126 | 44 | 170 |
| 2019 March | 95 | 18 | 113 |
| 2019 February | 129 | 21 | 150 |
| 2019 January | 151 | 27 | 178 |
| 2018 December | 111 | 49 | 160 |
| 2018 November | 218 | 37 | 255 |
| 2018 October | 410 | 42 | 452 |
| 2018 September | 127 | 18 | 145 |
| 2018 July | 0 | 0 | 0 |
| 2018 June | 1 | 1 | 2 |
| 2018 May | 56 | 5 | 61 |
| 2018 April | 157 | 29 | 186 |
| 2018 March | 114 | 20 | 134 |
| 2018 February | 107 | 21 | 128 |
| 2018 January | 115 | 19 | 134 |
| 2017 December | 230 | 17 | 247 |
| 2017 November | 598 | 22 | 620 |
| 2017 October | 1058 | 25 | 1083 |
| 2017 September | 756 | 25 | 781 |
| 2017 August | 618 | 15 | 633 |
| 2017 July | 512 | 10 | 522 |
| 2017 June | 314 | 14 | 328 |
| 2017 May | 290 | 17 | 307 |
| 2017 April | 427 | 14 | 441 |
| 2017 March | 475 | 24 | 499 |
| 2017 February | 533 | 15 | 548 |
| 2017 January | 60 | 19 | 79 |
| 2016 December | 312 | 22 | 334 |
| 2016 November | 608 | 12 | 620 |
| 2016 October | 1397 | 17 | 1414 |
| 2016 September | 1225 | 10 | 1235 |
| 2016 August | 822 | 9 | 831 |
| 2016 July | 307 | 20 | 327 |
| 2016 June | 1 | 0 | 1 |
| 2016 February | 1 | 0 | 1 |
| 2015 December | 2 | 0 | 2 |
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