Kala-Azar at high altitude Mahajan, Sanjay K; Machhan, Prem; Kanga, Anil ...
Journal of communicable diseases
36, Številka:
2
Journal Article
Kala-azar or Visceral leishmaniasis (VL) is a disease of low altitude (approximately 500 meters mean sea level). In India, however cases have been reported from sub-Himalayan region (350-960 meters ...MSL) of Kumaon region of Uttaranchal. We present two patients of VL, natives of tribal district of Kinnnaur (2000-3000 meters MSL), Himachal Pradesh, who had never visited known endemic area for Leishmaniasis. These are probably first indigenous cases of VL being reported from an area situated at an altitude of 3000 meters and 2300 meters MSL.
Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a ...chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required.
Of 781 patients <18-year-old of aHUS in the nationwide database from 2007 to 2018, 436 (55.8%) had anti-FH antibodies. Clinical features and outcome of patients managed in the last 6-year (
= 317) were compared to before (
= 119). In plasma samples of 44 patients, levels of serial circulating FH immune complexes (CIC), free FH, soluble terminal complement complex (sC5b-9), sheep red blood cell (SRBC) lysis and epitope specificity (
= 8) were examined. Functional renal reserve, ambulatory hypertension, left ventricular hypertrophy (LVH), and proteinuria were evaluated in a subset.
Patients presented with markedly elevated anti-FH titers (10,633.2 ± 998.5 AU/ml). Management varied by center, comprising plasma exchange (PEX; 77.5%) and immunosuppression (73.9%). Patients managed in the last 6-year showed better renal survival at mean 28.5 ± 27.3 months (log rank
= 0.022). Mean anti-FH titers stayed 700-1,164 AU/ml during prolonged follow-up, correlating with CIC. Patients with relapse had lower free-FH during remission Generalized estimating equations (GEE),
= 0.001; anti-FH levels ≥1,330 AU/ml and free FH ≤440 mg/l predicted relapse (hazards ratio, HR 6.3;
= 0.018). Epitope specificity was similar during onset, remission and relapse. Antibody titer ≥8,000 AU/ml (HR 2.23;
= 0.024), time to PEX ≥14 days (HR 2.09;
= 0.071) and PEX for <14 days (HR 2.60;
= 0.017) predicted adverse renal outcomes. Combined PEX and immunosuppression improved long-term outcomes (HR 0.37;
= 0.026); maintenance therapy reduced risk of relapses (HR 0.11;
< 0.001). At 4.4±2.5 year, median renal reserve was 15.9%; severe ambulatory, masked and pre-hypertension were found in 38, 30, and 18%, respectively. Proteinuria and LVH occurred in 58 and 28% patients, respectively.
Prompt recognition and therapy with PEX and immunosuppression, is associated with satisfactory outcomes. Free-FH predicts early relapses in patients with high anti-FH titers. A significant proportion of impaired functional reserve, ambulatory hypertension, proteinuria and LVH highlight the need for vigilant long-term follow-up.
Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the ...differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes,
., myocardial infarction, renal failure and prostate cancer. We sought to ask whether or not any DEGs harbor pathogenic variants common in these conditions, attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.
Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the ...differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes, viz., myocardial infarction, renal failure and prostate cancer. We sought to ask whether or not any DEGs harbor pathogenic variants common in these conditions, attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.
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