ABSTRACT
Since 1996, autochthonous cases of emerging leishmaniasis caused by Leishmania (Mundinia) martiniquensis and Leishmania (Mundinia) orientalis have been more frequently reported, especially in the northern and southern parts of Thailand. However, the accurate identification of their natural vectors and reservoirs remains unconfirmed. Previous studies have suggested that these emerging parasites might be transmitted by other non-phlebotomine vectors. Herein, we speculated that Culicoides biting midges might act as the competent vectors responsible for autochthonous leishmaniasis in southern Thailand. In this research, 187 non-engorged, parous and gravid Culicoides females and 47 blood-engorged ones were trapped from the residences of two recently diagnosed visceral leishmaniasis patients in Sadao District and the unaffected site in Rattaphum District, Songkhla Province, southern Thailand. Species diversity and abundance of biting midges varied among the trapping sites. Using ITS1-PCR and BLASTn analysis, L. martiniquensis was predominantly detected in several Culicoides species, including C. peregrinus, C. oxystoma, C. mahasarakhamense, and C. huffi from the vicinity of patients' houses; and in C. fordae and C. fulvus from the unaffected site. L. orientalis was also co-circulated in C. peregrinus and C. oxystoma caught near the second patient's house. Additionally, Crithidia sp. were also detected using SSU rRNA-PCR across Culicoides spp. Host blood meal analysis of eight different Culicoides species from the unaffected site also revealed that all trapped Culicoides had fed on cows and goats, indicating the possible role of these mammalian species as reservoir hosts. Essentially, this study is the first entomological investigation, revealing the co-circulation of emerging trypanosomatids among several species of Culicoides biting midges and strongly supporting the potential role of this insect group as the main vectors responsible for the epidemiology of autochthonous leishmaniasis in southern Thailand.
ABSTRACT
Leptospirosis is one of the most life-threatening tropical diseases caused by pathogenic Leptospira. To date, a diagnostic device that offers rapid and sensitive detection of leptospires has been still in demand for proper treatment to reduce the mortality rate. Herein, we create a resistance-based lateral flow immunosensor diagnosis device (R-LFI) that integrates near-field communication (NFC) with a portable smartphone for leptospiral detection in clinical samples. A specific monoclonal antibody against the pathogen was coated on a nitrocellulose membrane (NCM) where the test line was collocated. Two electrodes with a sandwich-like configuration were installed employing a conductive double-sided adhesive tape and connected with a NFC smartphone-based detection system. A half-sandwich immunocomplex formation induced high proton conduction, resulting in a considerable decrement in resistive response. The performance of the R-LFI sensor was evaluated using recombinant LipL32 (rLipL32), Leptospira interrogans, and clinical samples. The R-LFI device exhibited linear responses toward rLipL32 protein in phosphate buffer and L. interrogans-spiked healthy human serum samples within the concentration ranging from 1 to 1000 ng mL-1 (limit of detection (LOD): 0.29 ng mL-1) and from 104 to 106 cell mL-1 (LOD: 4.89 × 103 cell mL-1), respectively. Our R-LFI sensor successfully detected L. interrogans-positive clinical samples as confirmed by polymerase chain reaction (PCR). This platform offers high specificity, selectivity, simplicity, miniscule sample volume, and no labeling element requirement. These desirable features make it particularly suitable for countries where medical facilities and resources are limited.
Subject(s)
Biosensing Techniques , Leptospira , Leptospirosis , Humans , Smartphone , Collodion , Protons , Bacterial Outer Membrane Proteins , Immunoassay , Leptospirosis/diagnosis , Antibodies, Monoclonal , PhosphatesABSTRACT
Background: Tenofovir disoproxil fumarate (TDF) can induce proximal renal tubulopathy (PRT) and necessitate changes in treatment regimen. This prospective study aimed to compare tubular function recovery following early switching versus late switching of TDF in human immunodeficiency virus (HIV)-infected patients with TDF-induced PRT.Methods: For this prospective study, conducted during 2017-2019, we enrolled HIV-1-infected, virologically suppressed adults undergoing TDF-containing combination antiretroviral therapy. Patients were separated into a late-switching group (LSG) and an early-switching group (ESG). The LSG included patients having an estimated glomerular filtration rate (eGFR) decrease ≥25% from the pretreatment level or Fanconi syndrome. The ESG included patients having ≥2 of the following indicators of PRT: fractional excretion of phosphate (FEUP) ≥10%, low tubular maximum reabsorption of phosphate (TmP)/GFR, or uricosuria; fractional uric acid excretion ≥10%; urine protein-creatinine index (UPCI) ≥500 mg/g creatinine, normoglycemic glycosuria, or decrease in eGFR of 15%-24%. Recovery of proximal tubular function at 6 and 12 months after TDF discontinuation was assessed. Complete recovery was defined as normalization of all abnormal tubular markers.Results: Thirty-three HIV-infected patients were enrolled (70% male). Except for tubular function markers, baseline characteristics were not significantly different between the two groups. The proportion of patients having complete recovery was significantly higher in the ESG (p = 0.007, log-rank test). FEUP improved significantly in the ESG after TDF discontinuation; improvements of eGFR and UPCI were greater in the LSG. An eGFR change of 10% from baseline was the only independent predictor of failure to achieve complete recovery after switching. After median follow-up of 2.25 years post-trial, sustained recovery of eGFR within 5% of pre-TDF eGFR was achieved only in the ESG.Conclusions: Early-switching of TDF in HIV patients with PRT may allow complete recovery of proximal renal tubular function.
