Circulating angiotensin converting enzyme 2 and COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.     

A longitudinal study of early childhood caries in 9- to 18-month-old Thai infants

Abstract – Objective: To examine the rate and pattern of early childhood caries (ECC) development and to investigate the transitional changes of the carious lesions during a follow‐up period of 3–9 months. Methods: A longitudinal observational community‐based survey of 599 children, 9–18 months old. The children's dental examinations were first carried out at the age of 9 months with re‐examination at 12 and 18 months by five dentists using standardized methods. The affected rates of dental caries were determined for prevalence, incidence density for risk of caries per person (ID_p) and risk by surface (ID_s). Changes in dental status over time were explored from unerupted (U) to sound (S), including enamel caries (D1), dentine caries (D2) and caries involving pulp (D3) by computing transitional probabilities. Results: The prevalence of caries was 2.0%, 22.8% and 68.1% among 9‐, 12‐ and 18‐month olds, respectively. The ID_p observed for newly affected children 9–12 and 12–18 months old was 10.32 and 15.70 persons/100 person‐months, respectively. The ID_s for children 9–12 months old was 2.17 newly affected surfaces/100 surface‐months whereas it was 2.22 surfaces/100 surface‐months for children 12–18 months old. The buccal surface of maxillary incisors was the most affected (44.9%) followed by lingual, mesial and distal surfaces, respectively. The transitional probability of caries progression ranged between 1.79% and 15.38% during the follow‐up period from 9 to 12 months old. It was 3.43–39.60% from 12 to 18 months old. Conclusions: An extremely high caries‐affected rate was found among the study children even before the age of 18 months. The buccal surface of the maxillary incisors was the most affected. The teeth acquired caries at 3–6 months after initial eruption and carious lesions developed continuously over time.     

Dengue hemorrhagic fever and the liver

Dengue hemorrhagic fever (DHF) is one of the most rapidly emerging infections of tropical and subtropical regions worldwide. It affects more rural and urban areas due to many factors, including climate change. Although most people with dengue viral infection are asymptomatic, approximately 25% experience a self-limited febrile illness with mild to moderate biochemical abnormalities. Severe dengue diseases develop in a small proportion of these patients, and the common organ involvement is the liver. The hepatocellular injury was found in 60%-90% of DHF patients manifested as hepatomegaly, jaundice, elevated aminotransferase enzymes, and critical condition as an acute liver failure (ALF). Even the incidence of ALF in DHF is very low (0.31%-1.1%), but it is associated with a relatively high mortality rate (20%-68.3%). The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis, immune-mediated hepatocyte injury induced hepatitis, and cytokine storm. Hepatic hypoperfusion is another contributing factor in dengue shock syndrome. The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.     

Evaluation of a real-time polymerase chain reaction assay for the diagnosis of malaria in patients from Thailand

We compared the diagnosis of malaria in 297 patients from Thailand by a real-time polymerase chain reaction (PCR) assay using the LightCycler with conventional microscopy using Giemsa-stained thick and thin blood films. The PCR assay can be completed in one hour and has the potential to detect and identify four species of Plasmodium in a single reaction by use of melting temperature curve analysis (however, we did not detect Plasmodium ovale in this study). Blood was collected, stored, and transported on IsoCode STIX, which provide a stable matrix for the archiving and rapid simple extraction of DNA. A genus-specific primer set corresponding to the 18S ribosomal RNA was used to amplify the target sequence. Fluorescence resonance energy technology hybridization probes were designed for P. falciparum over a region containing basepair mismatches, which allowed differentiation of the other Plasmodium species. The PCR results correlated with the microscopic results in 282 (95%) of 297 patient specimens. Most of these were single-species infections caused by P. vivax (150) and P. falciparum (120), along with 5 P. malariae, 2 mixed infections (P. falciparum and P. vivax), and 5 negative specimens. No negative microscopy specimens were positive by PCR (100% specificity for detection of any Plasmodium). The 15 discrepant results could not be resolved, but given the subjective nature of microscopy and the analytical objectivity of the PCR, the PCR results may be correct. The ability of the PCR method to detect mixed infections or to detect P. ovale could not be determined in this study. Within the limitations of initial equipment costs, this real-time PCR assay is a rapid, accurate, and efficient method for the specific diagnosis of malaria. It may have application in clinical laboratories, as well as in epidemiologic studies and antimalarial efficacy trials.     

Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand

Objective To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia. Methods We measured the Fridericia corrected QT (QTcF) intervals on 12 lead ECGs on days (D) 0, 3, 7 in Plasmodium falciparum infected adults, treated with oral artesunate (AS) and MQ as a new fixed dose (n = 25) combination or loose tablets (n = 25) over 3 days. Target total doses were 12 mg/kg of AS and 24–25 mg/kg of MQ. MQ concentrations ([MQ]) were measured by HPLC. Results All ECG intervals were similar between drug arms and were combined for analysis. Mean QTcF values were 389 (D0), 407 (D3) and 399 (D7) ms (Ps < 0.003 vs. D0); corresponding heart rates and [MQ]s were 83, 67 and 73 beats/minute (Ps≤0.0003 vs. D0) and 0, 3095 and 1721 ng/ml. One male patient (loose arm) had a D3 QTcF 504 ms (D0 406 ms, D7 433 ms). In the modelling of QTcF and JTcF from D0 to D7, significant effects were observed individually for [MQ], temperature and heart rate (HR). The MQ AUC_0‐∞ was not a significant factor. Using a manual descending, model building approach to select variables, the HR was the only significant variable (P = 0.001) over time in the model that best explained the changes in the QTcF and JTcF intervals. Conclusions In this small group of patients, slowing heart rates due to malaria resolution best explained the observed increases in the QTcF intervals.     

Emergence and clearance of gametocytes in uncomplicated Plasmodium falciparum malaria

We reviewed the records of 1,175 patients with uncomplicated Plasmodium falciparum malaria to determine the prevalence of gametocytemia. All patients were admitted and received artemisinin combination therapy. Blood films were checked daily until discharge. Circulating gametocytes were observed in 240 (20.2%) of patients and in most cases (222 of 240, 92.5%) gametocytemia was detected during the first 24 hours after admission. Gametocytes were first seen in 174 cases on admission, in 24 cases at 12 hours, and in 24 cases at 24 hours. The longest interval between admission and first appearance of gametocytes was 192 hours. The median gametocyte clearance time was 163 hours (range = 12-806) in the 219 patients in whom gametocytemia resolved. However, 21 patients (9.8%) still had gametocytemia on discharge. Gametocytemia generally is present within the first 24 hours after admission, and emerges in only 1.9% of patients later on during treatment with artemisinin.     

Heterosexual transmission of novel CRF01_AE and subtype B recombinant forms of HIV type 1 in northern Thailand

The increased proportion of CRFO1_AE/subtype B recombinant infections among injecting drug users raised a concern that such recombinant forms may also spread in a heterosexual population in Thailand. Using the BootScan method, we reanalyzed pol gene sequences among 114 heterosexually infected individuals in northern Thailand, who were tested for a drug-resistance genotype between July 2000 and July 2001. Two individuals were suspected of carrying a recombinant HIV-1. Thus we analyzed a nearly full-length HIV genome in the two individuals and their spouses. An identical recombinant form of CRF01_AE and subtype B was found in one couple, indicating that this recombinant virus was heterosexually transmitted. Interestingly, this recombinant form had multiple breakpoints in the core protein of Gag and both infected individuals had a high CD4+ cell count without antiretroviral therapy. CRFO1/subtype B recombinant forms exist in a heterosexual population in northern Thailand. Some recombinant virus may be associated with a slow rate of HIV disease progression.     

Short report: detection of Orientia tsutsugamushi in clinical samples by quantitative real-time polymerase chain reaction

Orientia tsutsugamushi infection causes scrub typhus, a common zoonosis of rural Asia. Orientia tsutsugamushi was recently detected by a real-time quantitative polymerase chain reaction (qPCR) assay in animal specimens. We evaluated the same qPCR assay in specimens obtained from patients with serologically proven scrub typhus infections. The 47-kDa qPCR assay was more sensitive than was mouse inoculation; it was reactive in whole blood specimens from all 10 isolate-positive patients and in 7 of 17 isolate-negative individuals (P = 0.003, Fisher's two-tailed exact test). As few as 1,076 O. tsutsugamushi copies/microL were detected in whole blood. Four of 7 sera from isolate-proven scrub typhus infections were also reactive by qPCR. The assay was unreactive in all 12 individuals without scrub typhus infection. This is the first demonstration of a sensitive and specific real-time qPCR assay for human scrub typhus infection.