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1.
Virol J ; 21(1): 21, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243289

RESUMO

BACKGROUND: Sentinel laboratory surveillance for diarrheal disease determined norovirus to be the most common cause of non-bacterial gastroenteritis in people during the COVID-19 pandemic in Thailand. An increase in patients presenting with diarrhea and vomiting in hospitals across Chanthaburi province between December 2021 and January 2022 led to the need for the identification of viral pathogens that may be responsible for the outbreak. METHODS: Fecal samples (rectal swabs or stool) from 93 patients, of which 65 patients were collected during the December 2021 to January 2022 outbreak, were collected and screened for viral infection by real-time RT-PCR. Positive samples for norovirus GII were then genotyped by targeted amplification and sequencing of partial polymerase and capsid genes. Full genome sequencing was performed from the predominant strain, GII.3[P25]. RESULTS: Norovirus was the most common virus detected in human fecal samples in this study. 39 of 65 outbreak samples (60%) and 3 of 28 (10%) non-outbreak samples were positive for norovirus genogroup II. One was positive for rotavirus, and one indicated co-infection with rotavirus and norovirus genogroups I and II. Nucleotide sequences of VP1 and RdRp gene were successfully obtained from 28 of 39 positive norovirus GII and used for dual-typing; 25/28 (89.3%) were GII.3, and 24/28 (85.7) were GII.P25, respectively. Norovirus GII.3[P25] was the predominant strain responsible for this outbreak. The full genome sequence of norovirus GII.3[P25] from our study is the first reported in Thailand and has 98.62% and 98.57% similarity to norovirus found in China in 2021 and the USA in 2022, respectively. We further demonstrate the presence of multiple co-circulating norovirus genotypes, including GII.21[P21], GII.17[P17], GII.3[P12] and GII.4[P31] in our study. CONCLUSIONS: An unusual diarrhea outbreak was found in December 2021 in eastern Thailand. Norovirus strain GII.3[P25] was the cause of the outbreak and was first detected in Thailand. The positive rate during GII.3[P25] outbreak was six times higher than sporadic cases (GII.4), and, atypically, adults were the primary infected population rather than children.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Criança , Adulto , Humanos , Gastroenterite/epidemiologia , Norovirus/genética , Pandemias , Tailândia/epidemiologia , Infecções por Caliciviridae/epidemiologia , Filogenia , Diarreia/epidemiologia , Genótipo , Fezes , Surtos de Doenças
2.
J Hum Genet ; 67(5): 295-301, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35013560

RESUMO

Host genetic factors have been shown to play a role in SARs-CoV-2 infection in diverse populations. However, the genetic landscape differs among various ethnicities; therefore, we explored the host genetic factors associated with COVID-19 disease susceptivity and disease severity in a Thai population. We recruited and genotyped 212 unrelated COVID-19 Thai patients and 36 controls using AxiomTM Human Genotyping SARs-COV-2 array, including 847,384 single nucleotide polymorphisms related to SARs-COV-2 pathogenesis, immune response, and related comorbidity No SNPs passed the genome-wide significance threshold of p value <1 × 10-8. However, with a threshold of p value <1 × 10-5, a locus on chromosome 5q32 was found to have a suggestive association with COVID-19 disease susceptibility (p value 6.9 × 10-6; Q-Q plot λ = 0.805, odds ratio 0.02). Notably, IL17B is a gene located in this linkage disequilibrium block and is previously shown to play a part in inflammation and pneumonia. Additionally, a suggestive locus on chromosome 12q22, harboring EEA1 and LOC643339, was associated with COVID-19 disease severity (p value 1.3 × 10-6 - 4.4 × 10-6, Q-Q plot λ = 0.997, odds ratio 0.28-0.31). EEA1 is involved in viral entry into cells, while LOC643339 is a long non-coding RNA. In summary, our study suggested loci on chromosomes 5q32 and 12q22 to be linked to COVID-19 disease susceptibility and disease severity, respectively. The small sample size of this study may lessen the likelihood that the association found is real, but it could still be true. Further study with a larger cohort is required to confirm these findings.


Assuntos
COVID-19 , COVID-19/epidemiologia , COVID-19/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Índice de Gravidade de Doença , Tailândia/epidemiologia
3.
BMC Infect Dis ; 22(1): 472, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578171

RESUMO

BACKGROUND: Interactions between humans and animals are the key elements of zoonotic spillover leading to zoonotic disease emergence. Research to understand the high-risk behaviors associated with disease transmission at the human-animal interface is limited, and few consider regional and local contexts. OBJECTIVE: This study employed an integrated behavioral-biological surveillance approach for the early detection of novel and known zoonotic viruses in potentially high-risk populations, in an effort to identify risk factors for spillover and to determine potential foci for risk-mitigation measures. METHOD: Participants were enrolled at two community-based sites (n = 472) in eastern and western Thailand and two hospital (clinical) sites (n = 206) in northeastern and central Thailand. A behavioral questionnaire was administered to understand participants' demographics, living conditions, health history, and animal-contact behaviors and attitudes. Biological specimens were tested for coronaviruses, filoviruses, flaviviruses, influenza viruses, and paramyxoviruses using pan (consensus) RNA Virus assays. RESULTS: Overall 61/678 (9%) of participants tested positive for the viral families screened which included influenza viruses (75%), paramyxoviruses (15%), human coronaviruses (3%), flaviviruses (3%), and enteroviruses (3%). The most salient predictors of reporting unusual symptoms (i.e., any illness or sickness that is not known or recognized in the community or diagnosed by medical providers) in the past year were having other household members who had unusual symptoms and being scratched or bitten by animals in the same year. Many participants reported raising and handling poultry (10.3% and 24.2%), swine (2%, 14.6%), and cattle (4.9%, 7.8%) and several participants also reported eating raw or undercooked meat of these animals (2.2%, 5.5%, 10.3% respectively). Twenty four participants (3.5%) reported handling bats or having bats in the house roof. Gender, age, and livelihood activities were shown to be significantly associated with participants' interactions with animals. Participants' knowledge of risks influenced their health-seeking behavior. CONCLUSION: The results suggest that there is a high level of interaction between humans, livestock, and wild animals in communities at sites we investigated in Thailand. This study highlights important differences among demographic and occupational risk factors as they relate to animal contact and zoonotic disease risk, which can be used by policymakers and local public health programs to build more effective surveillance strategies and behavior-focused interventions.


Assuntos
Doenças Transmissíveis Emergentes , Animais , Animais Selvagens , Bovinos , Doenças Transmissíveis Emergentes/epidemiologia , Humanos , Aves Domésticas , Suínos , Tailândia/epidemiologia , Zoonoses/epidemiologia
4.
Blood Purif ; 51(1): 47-54, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33857940

RESUMO

INTRODUCTION: Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. METHODS: We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. RESULTS: Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO2/FiO2 ratio and decreased EAA level after EA therapy. CONCLUSIONS: We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.


Assuntos
COVID-19/terapia , Endotoxemia/terapia , Hemoperfusão/métodos , SARS-CoV-2 , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adsorção , COVID-19/complicações , Cuidados Críticos/métodos , Endotoxemia/etiologia , Feminino , Heparina/administração & dosagem , Humanos , Masculino , Membranas Artificiais , Pessoa de Meia-Idade , Polimixina B/administração & dosagem , Terapia de Substituição Renal , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Resultado do Tratamento
5.
Asian Pac J Allergy Immunol ; 40(3): 269-277, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34717527

RESUMO

BACKGROUND: Inactivated SARS-CoV-2 (CoronaVac®, Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs). OBJECTIVE: To determine the short-term immune response after the SV and AZ vaccinations in HCWs. METHODS: In this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included. Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody. Blood samples were analyzed at 4 and 12 weeks after the complete vaccination. The primary outcome was the seroconversion rate at 4-weeks after complete immunization. RESULTS: Overall, 185 HCWs with a median (IQR) age of 40.5 (30.3-55.8) years (94 HCWs in the SV group and 91 in the AZ group) were included. At 4 weeks after completing the SV vaccination, 60.6% (95%CI: 50.0-70.6%) had seroconversion evaluated by sVNT (≥ 68% inhibition), comparable to the patients recovered from mild COVID-19 infection (69.0%), with a rapid reduction to 12.2% (95%CI: 6.3-20.8) at 12 weeks. In contrast, 85.7% (95%CI: 76.8-92.2%) HCWs who completed two doses of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients (92.5%), with a reduction to 39.2% (95%CI: 28.4-50.9%) at 12 weeks. When using the anti-SARS-CoV-2 total antibody level (≥ 132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group at 4 weeks. CONCLUSIONS: A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SARS-CoV-2 variants of concern.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Pessoal de Saúde , Humanos , Imunidade , Pessoa de Meia-Idade , Estudos Prospectivos , Vacinação
6.
Emerg Infect Dis ; 27(12): 3178-3180, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34559045

RESUMO

In vitro determination of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies induced in serum samples from recipients of the CoronaVac vaccine showed a short protection period against the original virus strain and limited protection against variants of concern. These data provide support for vaccine boosters, especially variants of concern circulate.


Assuntos
Anticorpos Neutralizantes , COVID-19 , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , SARS-CoV-2
7.
Microbiol Immunol ; 65(10): 405-409, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33835528

RESUMO

In early January 2020, Thailand became the first country where a coronavirus disease 2019 (COVID-19) patient was identified outside China. In this study, 23 whole genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from patients who were hospitalized from January to March 2020 were analyzed, along with their travel histories. Six lineages were identified including A, A.6, B, B.1, B.1.8, and B.58, among which lineage A.6 was dominant. Seven patients were from China who traveled to Thailand in January and early February. Five of them were infected with the B lineage virus, and the other two cases were infected with different lineages including A and A.6. These findings present clear evidence of the early introduction of diverse SARS-CoV-2 clades in Thailand.


Assuntos
COVID-19 , SARS-CoV-2 , China , Genoma Viral , Humanos , Tailândia
8.
Transpl Infect Dis ; 23(1): e13388, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32585765

RESUMO

We report a case of COVID-19 in kidney transplant patient in Thailand. A 58-year-old 2 years post-kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x-ray finding of bilateral multifocal patchy infiltration. COVID-19 infection has been confirmed by reverse real-time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High-flow nasal cannula oxygen therapy was required on days 4-5 of hospitalization. Tocilizumab was administered after rising of serum IL-6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti-viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.


Assuntos
Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Transplante de Rim , Pirazinas/uso terapêutico , Transplantados , Amidas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas/administração & dosagem , SARS-CoV-2
9.
AIDS Res Ther ; 18(1): 28, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952300

RESUMO

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.


Assuntos
Antirretrovirais/uso terapêutico , COVID-19/patologia , Coinfecção/patologia , Infecções por HIV/patologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Adulto , COVID-19/complicações , COVID-19/imunologia , Coinfecção/imunologia , Citocinas/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Hospedeiro Imunocomprometido/fisiologia , Linfopenia/patologia , Pessoa de Meia-Idade , Resultado do Tratamento , Tratamento Farmacológico da COVID-19
10.
J Med Virol ; 92(10): 2193-2199, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32401343

RESUMO

In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , Pandemias , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2/genética , Manejo de Espécimes/métodos , COVID-19/economia , COVID-19/virologia , Teste para COVID-19/economia , Notificação de Doenças/economia , Notificação de Doenças/métodos , Monitoramento Epidemiológico , Humanos , Limite de Detecção , Nasofaringe/virologia , Faringe/virologia , Prevalência , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real/economia , Estudos Retrospectivos , Manejo de Espécimes/economia , Tailândia/epidemiologia , Carga Viral
11.
J Gastroenterol Hepatol ; 29(9): 1706-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24730732

RESUMO

BACKGROUND AND AIM: Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. METHODS: Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS: A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS: HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.


Assuntos
Alanina Transaminase/sangue , Coinfecção , Infecções por HIV/complicações , Hepatite C/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Deficiência de Vitamina D/complicações , Adulto , Povo Asiático , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Cirrose Hepática/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Tailândia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
12.
HIV Res Clin Pract ; 25(1): 2348935, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38701396

RESUMO

BACKGROUND: Tuberculosis (TB) poses a significant risk to people with HIV (PWH), with heightened incidence and prevalence rates, especially in countries with a high TB burden. This study assesses the prevalence and incidence rates of TB among PWH during the COVID-19 pandemic, and on treatment outcomes in TB-HIV co-infections. METHODS: A retrospective study was conducted at Suddhavej Hospital, Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand, from January 2020 to September 2023, involving newly diagnosed adult PWH. Data were collected on TB prevalence and incidence rates, with TB cases categorized as definite or possible. The primary outcomes were TB prevalence and incidence rates per 100,000 person-years of follow-up. RESULTS: Among 171 newly diagnosed PWH, the prevalence of TB was 5.85%, with an incidence rate of 4,568.71 per 100,000 person-years. All but one TB cases were diagnosed before antiretroviral therapy (ART) initiation. There was no incident TB during the follow-up period during ART. Nearly half of the TB cases required therapeutic trials without microbiological confirmation. CONCLUSIONS: The study revealed a high prevalence and incidence rate of TB among PWH during the COVID-19 pandemic, comparable to pre-pandemic rates in Thailand. The findings highlight the necessity of comprehensive TB screening prior to ART initiation and the cautious implementation of universal TB preventive therapy. The use of molecular diagnostics, in addition to symptom screening, can enhance TB diagnosis among PWH, though accessibility remains an issue in many regions.


Assuntos
COVID-19 , Coinfecção , Infecções por HIV , SARS-CoV-2 , Tuberculose , Humanos , Estudos Retrospectivos , Tailândia/epidemiologia , Incidência , COVID-19/epidemiologia , Masculino , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Adulto , Prevalência , Tuberculose/epidemiologia , Pessoa de Meia-Idade , Coinfecção/epidemiologia
13.
Viruses ; 16(4)2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38675878

RESUMO

Emerging coronaviruses (CoVs) are understood to cause critical human and domestic animal diseases; the spillover from wildlife reservoirs can result in mild and severe respiratory illness in humans and domestic animals and can spread more readily in these naïve hosts. A low-cost CoV molecular method that can detect a variety of CoVs from humans, animals, and environmental specimens is an initial step to ensure the early identification of known and new viruses. We examine a collection of 50 human, 46 wastewater, 28 bat, and 17 avian archived specimens using 3 published pan-CoV PCR assays called Q-, W-, and X-CoV PCR, to compare the performance of each assay against four CoV genera. X-CoV PCR can detect all four CoV genera, but Q- and W-CoV PCR failed to detect δ-CoV. In total, 21 (42.0%), 9 (18.0%), and 21 (42.0%) of 50 human specimens and 30 (65.22%), 6 (13.04%), and 27 (58.70%) of 46 wastewater specimens were detected using Q-, W-, and X-CoV PCR assays, respectively. The X-CoV PCR assay has a comparable sensitivity to Q-CoV PCR in bat CoV detection. Combining Q- and X-CoV PCR assays can increase sensitivity and avoid false negative results in the early detection of novel CoVs.


Assuntos
Coronavirus , Sensibilidade e Especificidade , Humanos , Animais , Coronavirus/genética , Coronavirus/classificação , Coronavirus/isolamento & purificação , Águas Residuárias/virologia , Quirópteros/virologia , Aves/virologia , Reação em Cadeia da Polimerase/métodos , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Infecções por Coronavirus/diagnóstico
14.
J Virol ; 86(2): 1119-28, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22090117

RESUMO

HIV CCR5 antagonists select for env gene mutations that enable virus entry via drug-bound coreceptor. To investigate the mechanisms responsible for viral adaptation to drug-bound coreceptor-mediated entry, we studied viral isolates from three participants who developed CCR5 antagonist resistance during treatment with vicriviroc (VCV), an investigational small-molecule CCR5 antagonist. VCV-sensitive and -resistant viruses were isolated from one HIV subtype C- and two subtype B-infected participants; VCV-resistant isolates had mutations in the V3 loop of gp120 and were cross-resistant to TAK-779, an investigational antagonist, and maraviroc (MVC). All three resistant isolates contained a 306P mutation but had variable mutations elsewhere in the V3 stem. We used a virus-cell ß-lactamase (BlaM) fusion assay to determine the entry kinetics of recombinant viruses that incorporated full-length VCV-sensitive and -resistant envelopes. VCV-resistant isolates exhibited delayed entry rates in the absence of drug, relative to pretherapy VCV-sensitive isolates. The addition of drug corrected these delays. These findings were generalizable across target cell types with a range of CD4 and CCR5 surface densities and were observed when either population-derived or clonal envelopes were used to construct recombinant viruses. V3 loop mutations alone were sufficient to restore virus entry in the presence of drug, and the accumulation of V3 mutations during VCV therapy led to progressively higher rates of viral entry. We propose that the restoration of pre-CCR5 antagonist therapy HIV entry kinetics drives the selection of V3 loop mutations and may represent a common mechanism that underlies the emergence of CCR5 antagonist resistance.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antagonistas dos Receptores CCR5 , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Amidas/farmacologia , Fármacos Anti-HIV/farmacologia , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Cinética , Dados de Sequência Molecular , Mutação , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Compostos de Amônio Quaternário/farmacologia
15.
J Virol ; 86(12): 6416-26, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22491471

RESUMO

We previously described an HIV-1-infected individual who developed resistance to vicriviroc (VCV), an investigational CCR5 antagonist, during 28 weeks of therapy (Tsibris AM et al., J. Virol. 82:8210-8214, 2008). To investigate the decay of VCV resistance mutations, a standard clonal analysis of full-length env (gp160) was performed on plasma HIV-1 samples obtained at week 28 (the time of VCV discontinuation) and at three subsequent time points (weeks 30, 42, and 48). During 132 days, VCV-resistant HIV-1 was replaced by VCV-sensitive viruses whose V3 loop sequences differed from the dominant pretreatment forms. A deep-sequencing analysis showed that the week 48 VCV-sensitive V3 loop form emerged from a preexisting viral variant. Enfuvirtide was added to the antiretroviral regimen at week 30; by week 48, enfuvirtide treatment selected for either the G36D or N43D HR-1 mutation. Growth competition experiments demonstrated that viruses incorporating the dominant week 28 VCV-resistant env were less fit than week 0 viruses in the absence of VCV but more fit than week 48 viruses. This week 48 fitness deficit persisted when G36D was corrected by either site-directed mutagenesis or week 48 gp41 domain swapping. The correction of N43D, in contrast, restored fitness relative to that of week 28, but not week 0, viruses. Virus entry kinetics correlated with observed fitness differences; the slower entry of enfuvirtide-resistant viruses corrected to wild-type rates in the presence of enfuvirtide. These findings suggest that while VCV and enfuvirtide select for resistance mutations in only one env subunit, gp120 and gp41 coevolve to maximize viral fitness under sequential drug selection pressures.


Assuntos
Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Replicação Viral , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Enfuvirtida , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/metabolismo , Proteína gp41 do Envelope de HIV/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/classificação , HIV-1/genética , Humanos , Dados de Sequência Molecular , Mutação , Fragmentos de Peptídeos/farmacologia , Filogenia , Internalização do Vírus
16.
J Pharm Policy Pract ; 16(1): 29, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36829248

RESUMO

BACKGROUND: Home isolation has been proposed for coronavirus disease 2019 (COVID-19) patients with mild symptoms to avoid hospital overcrowding. This study aimed to describe the drug-related problems (DRPs) and the pharmaceutical care of home-isolating COVID-19 patients in Thailand. METHODS: Our cross-sectional study was undertaken from July 1 to September 30, 2021, at the King Chulalongkorn Memorial Hospital, Thailand. Patients who were ≥ 18 years old, were diagnosed with mild COVID-19 by real-time polymerase chain reaction (RT-PCR), and were able to isolate at home while receiving an antiviral agent and standard symptomatic treatment were enrolled. Infectious disease pharmacists provided a telepharmacy service on days 1 and 3 after the COVID-19 diagnosis. RESULTS: A total of 197 patients met the study criteria. Their median age was 45 years, and their most common underlying disease was hypertension (44.29%). All patients exhibited excellent anti-COVID-19 drug adherence. We identified 125 DRPs, including adverse reactions (68%), and the unnecessary use of products (62.40%). Moreover, 91 patients (46.19%) reported the use of supplements or herbs, with vitamin C being the main supplement (37.36%). Pharmacists provided 36 recommendations and received 33 questions from COVID-19 patients. CONCLUSIONS: Our study demonstrates that telepharmacy is an essential service for detecting and preventing DRPs in home-isolating COVID-19 patients.

17.
Vaccine X ; 14: 100334, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37361052

RESUMO

Immunity against SARS-CoV-2 infection in vaccinated individuals varies based on the vaccine type, duration after vaccination or infection, and SARS-CoV-2 variant type. We conducted a prospective observational study to evaluate the immunogenicity of a booster vaccination with AZD1222 after two doses of CoronaVac (booster group) compared to individuals who had SARS-CoV-2 infection after receiving two doses of CoronaVac (infection group). We used a surrogate virus neutralization test (sVNT) to evaluate immunity against wild-type and Omicron variant (BA.1) at 3 and 6 months after infection or booster dose. Of the 89 participants, 41 were in the infection group, and 48 were in the booster group. At 3 months post-infection or booster vaccination, the median (IQR) sVNT against wild-type was 97.87 % (97.57-97.93 %) and 97.65 % (95.38-98.00 %), p = 0.66, respectively, while the sVNT against Omicron was 18.8 % (0-47.10 %) and 24.46 (11.69-35.47 %), p = 0.72 respectively. At 6 months, the median (IQR) sVNT against wild-type was 97.68 % (95.86-97.92 %) in the infection group, higher than 94.7 % (95.38-98.00 %) in the booster group (p = 0.03). Results showed no significant difference in immunity against wild-type and Omicron at 3 months between the two groups. However, the infection group exhibited better immunity than the booster group at 6 months.

18.
J Int Assoc Provid AIDS Care ; 22: 23259582231220513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38115729

RESUMO

This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.


Outcomes after switching to second line antiretroviral regimens in the Thai National Treatment programWe assessed the rates of virological failure, losses to follow-up and death in 29,015 people who switched to second line antiretroviral therapy in Thailand. The cumulative rate of virological failure was a 9.8% at 6 years, loss to follow-up occurred in 18.3% (5% who remained alive) and 15.9% died. Women and those with lower CD4 counts at switch had the highest risk of virological failure.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Feminino , Humanos , Adolescente , Adulto , Falha de Tratamento , Tailândia/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Resultado do Tratamento , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Carga Viral , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico
19.
Res Sq ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36711810

RESUMO

The rapid emergence of SARS-CoV-2 variants with high severity and transmutability adds further urgency for rapid and multiplex molecular testing to identify the variants. A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/ µl. The panel has shown a 100% concordant with the Next Generation Sequencing (NGS) results testing on 256 clinical specimens with real-time PCR cycle threshold (Ct) values less than 26. It showed a higher sensitivity over NGS; 25/28 samples were positive by PMA but not NGS in the clinical samples with PCR Ct higher than 26. Due to the mass of nucleotide used to differentiate between wild-type and mutation strains, the co-infection or recombination of multiple variants can be determined by the PMA method. This method is flexible in adding a new primer set to identify a new emerging mutation site among the current circulating VOCs and the turnaround time is less than 8 hours. However, the spike gene sequencing or NGS retains the advantage of detecting newly emerged variants.

20.
Sci Rep ; 13(1): 2089, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36747014

RESUMO

The rapid emergence of SARS-CoV-2 variants with high severity and transmutability adds further urgency for rapid and multiplex molecular testing to identify the variants. A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/µl. The panel has shown a 100% concordant with the Next Generation Sequencing (NGS) results testing on 256 clinical specimens with real-time PCR cycle threshold (Ct) values less than 26. It showed a higher sensitivity over NGS; 25/28 samples were positive by PMA but not NGS in the clinical samples with PCR Ct higher than 26. Due to the mass of nucleotide used to differentiate between wild-type and mutation strains, the co-infection or recombination of multiple variants can be determined by the PMA method. This method is flexible in adding a new primer set to identify a new emerging mutation site among the current circulating VOCs and the turnaround time is less than 8 h. However, the spike gene sequencing or NGS retains the advantage of detecting newly emerged variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Reação em Cadeia da Polimerase Multiplex , COVID-19/diagnóstico , Nucleotídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tecnologia , Teste para COVID-19
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