Is the recent increment in attributable deaths to type-2 diabetes (T2D) associated with the latest chikungunya outbreak in a major epidemic area in Brazil?

<div><p>Abstract INTRODUCTION: Chikungunya virus (CHIKV) can negatively influence outcomes in patients with pre-existing conditions. We investigated the association between the recent CHIKV outbreak and increased type 2 diabetes (T2D)-attributable deaths. METHODS: Monthly averages of T2D-attributable deaths between 2001 and 2016 were determined and compared to the equivalent data for 2017 and the recent CHIKV outbreak. RESULTS: CHKV outbreak peaked in April 2017 with 4,394.4 cases/100,000 inhabitants, while T2D-attributable deaths in the same period increased by 35.2%. CONCLUSIONS: T2D-attributable deaths significantly increased compared to the previous data, which overlapped with CHIKV incidence. The pathophysiology of this association warrants further investigations.</p></div

Detailed clinical information from 24 children 0–14 years old, admitted to any of the pediatric or neonatal ICUs in Manaus, from 2004 to 2009, with parasitological diagnosis of <i>P. vivax</i>.

<p>y years; mo: months; d: days; NA: Non-available; ARDS: Acute Respiratory Distress Syndrome; ARF: Acute Renal Failure; PIM: Pediatric Index of Mortality; ITP: Immune Trombocytopenic Purpura.</p>*<p><b>Viral encephalitis</b> confirmed by autopsy; diagnosis of <b>malnutrition</b> confirmed by body mass index (BMI) Z-score <−2; <b>rotavirus gastroenteritis</b> confirmed by immunochromatographic rapid test in the stool; <b>cystic fibrosis</b> suggested by lung biopsy; <b>sepsis</b> confirmed by two positive blood cultures; <b>G6PD deficiency</b> confirmed by qualitative Brewer's test; <b>lung empyema</b> confirmed by computed tomography; <b>urosepsis</b> confirmed by both positive urine and blood culture; <b>ITP</b> confirmed by ASH criteria; ARDS defined as acute bilateral lung infiltrates and a PaO₂∶FiO₂<200 mmHg.</p

Detailed laboratorial information from 24 children 0–14 years old, at the moment of admission to any of the pediatric or neonatal ICUs in Manaus, from 2004 to 2009, with parasitological diagnosis of <i>P. vivax</i>.

<p>Hb: hemoglobin; ALT: alanine aminotransferase; AST: aspartate aminotrasferase.</p

Clinical information from 10 children 0–14 years of age admitted to any of the pediatric or neonatal ICUs in Manaus, from January 2004 to December 2009, with parasitological diagnosis of <i>P. falciparum</i> or mixed infection (<i>P. falciparum/P. vivax</i>).

<p>Y: years; mo: months; d: days; NA: Non-available; ARDS: acute respiratory distress syndrome; ARF: acute renal failure; PIM: Pediatric Index of Mortality.</p>*<p><b>Malnutrition</b> confirmed by body mass index (BMI) Z-score <−2; <b>rotavirus gastroenteritis</b> confirmed by immunochromatographic rapid test in the stool; <b>sepsis</b> confirmed by two positive blood cultures; <b>G6PD deficiency</b> confirmed by qualitative Brewer's test; <b>congenital cardiopathy</b> confirmed by echocardiogram; <b>sickle cell anemia</b> confirmed by electrophoresis; ARDS defined as acute bilateral lung infiltrates and a PaO₂:FiO₂<200 mmHg.</p>**<p>Blackwater fever.</p

Flow diagram of patients admitted to ICUs enrolled in the analysis.

<p>Flow diagram of patients admitted to ICUs enrolled in the analysis.</p

Univariate and multivariate (logistic regression) analysis of factors associated to the admission in the ICUs of children 0–14 years old with <i>P. vivax</i> infection, in Manaus, from 2004 to 2009.

<p>Univariate and multivariate (logistic regression) analysis of factors associated to the admission in the ICUs of children 0–14 years old with <i>P. vivax</i> infection, in Manaus, from 2004 to 2009.</p

Spleen Rupture in a Case of Untreated <em>Plasmodium vivax</em> Infection

Spleen Rupture in a Case of Untreated <em>Plasmodium vivax</em> Infectio

Immunohistochemical staining of <i>P. vivax</i>–infected and normal spleen sections.

<p>HE staining of the normal (A) and <i>P. vivax</i>–infected (B) spleen sections evidencing, respectively, periarteriolar lymphoid cuffs and red pulp cords depleted of lymphoid cells (inset 20× normal) and a prominent white pulp expansion with hyperplastic germinal centers in secondary lymphoid follicles highlighting in the inset a striking red cord infiltration by immunoblasts and reactive plasma cells (20× <i>P. vivax</i>–infected). (C) The normal spleen reveals a scattered CD138 positive plasma cell distribution in the subcapsular and perivascular compartments (2×); higher magnification view shown in the inset (40×). (D) In contrast, a marked increase of CD138 positive plasma cells is observed in the <i>P. vivax</i>–infected spleen (2×), including the detection of mitotic activity among several CD138 positive plasma cells shown in the inset (40×). (E) Double immunostaining with CD138 (brown) and Ki-67 (red) demonstrated the lack of proliferation in plasma cells in the normal spleen (20×). (F) In contrast, there is a significant increase in CD138 and Ki67 positive plasmablasts in the <i>P. vivax</i>–infected spleen (20×).</p

Immunohistofluorescence images of <i>P. vivax</i>–infected spleen sections.

<p>(A) Spleen section showing <i>P. vivax</i> parasites mostly in the cords of the red pulp as detected by polyclonal antibodies against Vir proteins. (B) Negative control using preimmune sera. Nuclei are shown in blue and the bright field image of the tissue in gray. Scale bar: 20 µm. (C) Double staining showing CD68 macrophages in red and parasites stained in green. Scale bar is 10 µm. (D) Reflection contrast (magenta) was used to detect parasite pigment.</p

Genotype and allele frequencies of the TLRs and CD14 polymorphisms in patients with <i>Pv</i>-malaria and healthy controls.

<p>Genotype and allele frequencies of the TLRs and CD14 polymorphisms in patients with <i>Pv</i>-malaria and healthy controls.</p