RESUMEN
Introduction: tuberculosis remains a major public health problem, with continuing high levels of prevalence, and mortality. In Niger, the incidence of tuberculosis remains high. This study aims to investigate the epidemiology of pulmonary tuberculosis at the National Anti-Tuberculosis Center of Niamey in Niger. Methods: this study used a quantitative approach with a retrospective and descriptive design. Data were obtained from positive pulmonary tuberculosis cases detected by microscopy on Ziehl-Neelsen stained sputum at the National Anti-Tuberculosis Center (NATC) in Niamey, Niger covered the period between June 2017 and January 2020. 955 pulmonary TB patients were recorded whose diagnosis was based either on clinical-radiological arguments (thus negative microscopy) or positive microscopy. This form was used to collect data recorded in the clinical case registers, registers, and Excel files of the GeneXpert platform of the NATC laboratory. Results: eighty-nine-point eleven percent (89.11%) of the patients were microscopy-positive. Among the study population, men were the most affected by tuberculosis with 80.03%. The 25-34 age group, representing 23.77%, was the most affected. 6.93% of patients were co-infected with tuberculosis and HIV. All patients were put on treatment, with a therapeutic success rate of 72.38% and a therapeutic failure rate of 10.95%. Among the cases of therapeutic failure, 80.90% had Mycobacterium tuberculosis complex detected and 27.14% were resistant to Rifampicin. Conclusion: Niger continues to have a tuberculosis epidemic which requires monitoring. Improving the diagnostic system for more effective management of the disease is important for appropriate diagnosis and treatment.
Asunto(s)
Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Estudios Retrospectivos , Masculino , Niger/epidemiología , Femenino , Adulto , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/diagnóstico , Antituberculosos/farmacología , Antituberculosos/administración & dosificación , Adulto Joven , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Adolescente , Resultado del Tratamiento , Niño , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Preescolar , Anciano , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Esputo/microbiología , Prevalencia , Coinfección/epidemiología , Coinfección/tratamiento farmacológico , Lactante , IncidenciaRESUMEN
This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4-20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p < 0.05). The findings suggest re-evaluating the necessity of antibiotics in COVID-19 cases based on clinical assessments, focusing on the presence of bacterial infections rather than empirical treatment. Further research is necessary to more accurately identify patients with bacterial co-infections who would benefit from antibiotic treatment.
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Antibacterianos , Tratamiento Farmacológico de COVID-19 , COVID-19 , Humanos , Turquía/epidemiología , Masculino , Antibacterianos/uso terapéutico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , COVID-19/mortalidad , COVID-19/epidemiología , Coinfección/tratamiento farmacológico , SARS-CoV-2/aislamiento & purificación , Adulto , Infecciones Bacterianas/tratamiento farmacológico , Resultado del Tratamiento , Unidades de Cuidados Intensivos/estadística & datos numéricosRESUMEN
BACKGROUND: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. CASE PRESENTATION: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. INFECTION: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. CONCLUSION: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.
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Anfotericina B , Antifúngicos , Broncoscopía , Mucormicosis , Aspergilosis Pulmonar , Humanos , Masculino , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Persona de Mediana Edad , Mucormicosis/tratamiento farmacológico , Mucormicosis/diagnóstico , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Aspergilosis Pulmonar/tratamiento farmacológico , Aspergilosis Pulmonar/diagnóstico , Coinfección/tratamiento farmacológico , Mucor/aislamiento & purificación , Tomografía Computarizada por Rayos XRESUMEN
Chronic immune activation promotes tuberculosis (TB) reactivation in the macaque Mycobacterium tuberculosis (M. tuberculosis)/SIV coinfection model. Initiating combinatorial antiretroviral therapy (cART) early lowers the risk of TB reactivation, but immune activation persists. Studies of host-directed therapeutics (HDTs) that mitigate immune activation are, therefore, required. Indoleamine 2,3, dioxygenase (IDO), a potent immunosuppressor, is one of the most abundantly induced proteins in NHP and human TB granulomas. Inhibition of IDO improves immune responses in the lung, leading to better control of TB, including adjunctive to TB chemotherapy. The IDO inhibitor D-1 methyl tryptophan (D1MT) is, therefore, a bona fide TB HDT candidate. Since HDTs against TB are likely to be deployed in an HIV coinfection setting, we studied the effect of IDO inhibition in M. tuberculosis/SIV coinfection, adjunctive to cART. D1MT is safe in this setting, does not interfere with viral suppression, and improves the quality of CD4+ and CD8+ T cell responses, including reconstitution, activation and M. tuberculosis-specific cytokine production, and access of CD8+ T cells to the lung granulomas; it reduces granuloma size and necrosis, type I IFN expression, and the recruitment of inflammatory IDO+ interstitial macrophages (IMs). Thus, trials evaluating the potential of IDO inhibition as HDT in the setting of cART in M. tuberculosis/HIV coinfected individuals are warranted.
Asunto(s)
Coinfección , Indolamina-Pirrol 2,3,-Dioxigenasa , Macaca mulatta , Mycobacterium tuberculosis , Síndrome de Inmunodeficiencia Adquirida del Simio , Triptófano , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Animales , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Coinfección/tratamiento farmacológico , Coinfección/inmunología , Triptófano/metabolismo , Triptófano/análogos & derivados , Tuberculosis/inmunología , Tuberculosis/tratamiento farmacológico , Virus de la Inmunodeficiencia de los Simios/inmunología , Modelos Animales de Enfermedad , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/complicaciones , Antirretrovirales/uso terapéutico , Antirretrovirales/farmacología , Masculino , Pulmón/inmunología , Pulmón/patología , Humanos , Linfocitos T CD4-Positivos/inmunologíaRESUMEN
Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.
Asunto(s)
Coinfección , Infecciones por VIH , Herpesvirus Humano 8 , Sarcoma de Kaposi , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Humanos , Sarcoma de Kaposi/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Herpesvirus Humano 8/genética , Femenino , Adulto , Persona de Mediana Edad , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Coinfección/virología , Coinfección/tratamiento farmacológico , VIH-1/genética , VIH-1/efectos de los fármacos , Variación Genética , Carga Viral , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4RESUMEN
BACKGROUND: Parasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome. METHODS: A matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community. RESULTS: In simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia. CONCLUSION: The findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.
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Helmintiasis , Malaria , Suelo , Humanos , Tanzanía/epidemiología , Preescolar , Estudios de Casos y Controles , Masculino , Helmintiasis/tratamiento farmacológico , Helmintiasis/epidemiología , Helmintiasis/parasitología , Femenino , Malaria/tratamiento farmacológico , Malaria/epidemiología , Lactante , Resultado del Tratamiento , Niño , Suelo/parasitología , Animales , Helmintos/aislamiento & purificación , Helmintos/fisiología , Helmintos/efectos de los fármacos , Helmintos/clasificación , Antimaláricos/uso terapéutico , Coinfección/parasitología , Coinfección/tratamiento farmacológico , Coinfección/epidemiologíaRESUMEN
Introduction: tuberculosis (TB) remains a leading cause of death in South Africa. KwaZulu-Natal (KZN) is one of the provinces with a high burden of TB/drug-resistant TB cases and deaths. We determined predictors for mortality among drug-resistant TB patients on treatment in KZN province. Methods: we conducted a retrospective cohort study using secondary data from the Electronic Drug-Resistant Tuberculosis Register. We used a modified Poisson regression model with robust standard errors to determine predictors for drug-resistant TB mortality. Results: of the 7,692 eligible patients, 1,234 (16.0%) died. Males predominated (707, 57.3%) and the median age was 36 years (Interquartlile Range: 29-45 years). The majority (978, 79.2%) were HIV-TB co-infected with 911 (93%) on antiretroviral treatment (ART). The predictors included HIV-TB co-infection without ART (aIRR 3.4; 95% CI: 2.3-5.1), unknown ART status (aIRR: 1.8; 95% CI: 1.4-2.3), aged ≥60 years (aIRR: 2.1; 95% CI: 1.6-2.7), previous drug-resistant TB (aIRR: 1.5; 95% CI: 1.2-1.8) and exposure to second-line drugs (aIRR: 1.7; 95% CI: 1.4-2.0). Other predictors were hospitalization during treatment initiation (aIRR 2.5; 95% CI 2.0-3.1), initiation in other treatment facilities (aIRR: 2.2; 95% CI: 1.6-2.9) and rifampicin-resistant (aIRR: 1.2; 95% CI: 1.1-1.4). Bedaquiline fumarate was a significant protective factor against death (aIRR: 0.5; 95% CI: 0.4-0.5). Conclusion: older age, HIV co-infection without ART, hospitalization for treatment initiation, exposure to second-line drugs and a previous episode of drug-resistant TB were predictors for DR-TB mortality. Early treatment initiation and provision of antiretroviral treatment for all co-infected patients may reduce DR-TB mortality in the Province.
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Antituberculosos , Coinfección , Infecciones por VIH , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/mortalidad , Estudios Retrospectivos , Adulto , Sudáfrica/epidemiología , Persona de Mediana Edad , Infecciones por VIH/tratamiento farmacológico , Antituberculosos/administración & dosificación , Coinfección/tratamiento farmacológico , Estudios de Cohortes , Factores de Riesgo , Adulto Joven , Adolescente , Factores de EdadRESUMEN
Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Since the coronavirus disease 2019 (COVID-19) pandemic, immunocompromised individuals face an increased risk of HEV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection, posing a threat of liver failure and prolonged illness. A 69-year-old male, with a history of chronic lymphocytic leukemia, was co-infected with HEV and SARS-CoV-2. Given the progressive decline in liver function post-admission, steroid therapy was initiated, which led to treatment-related complications. Additionally, the patient experienced an aggravation of COVID-19 symptoms due to persistent SARS-CoV-2 infection, effectively managed through a combination of antiviral medications and corticosteroids. This case describes the intricate clinical trajectory and therapeutic approach for managing HEV and SARS-CoV-2 co-infection, underscoring the potential efficacy of short-term corticosteroid intervention alongside comprehensive antiviral treatment.
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Antivirales , COVID-19 , Coinfección , Virus de la Hepatitis E , Hepatitis E , Huésped Inmunocomprometido , SARS-CoV-2 , Humanos , Masculino , Hepatitis E/tratamiento farmacológico , Hepatitis E/complicaciones , COVID-19/complicaciones , COVID-19/inmunología , Anciano , Coinfección/tratamiento farmacológico , Coinfección/virología , Antivirales/uso terapéutico , Virus de la Hepatitis E/inmunología , Corticoesteroides/uso terapéutico , Tratamiento Farmacológico de COVID-19RESUMEN
Coinfections with human pegivirus 1 (HPgV-1) are common in chronic hepatitis C virus (HCV) patients. However, little is known about whether HPgV-1 is affected by direct-acting antivirals during HCV treatment. Metagenomic analysis and reverse transcriptase-quantitative PCR (RT-qPCR) were performed on RNA from the plasma of 88 selected chronic HCV patients undergoing medical treatment. Twenty (23%) of these HCV patients had HPgV-1 coinfections and were followed by RT-qPCR during treatment and follow-up to investigate HPgV-1 RNA titers. Recovered sequences could be assembled to complete HPgV-1 genomes, and most formed a genotype 2 subclade. All HPgV-1 viral genomic regions were under negative purifying selection. Glecaprevir/pibrentasvir treatment in five patients did not consistently lower the genome titers of HPgV-1. In contrast, a one log10 drop of HPgV-1 titers at week 2 was observed in 10 patients during treatment with sofosbuvir-containing regimens, sustained to the end of treatment (EOT) and in two cases decreasing to below the detection limit of the assay. For the five patients treated with ledipasvir/sofosbuvir with the inclusion of pegylated interferon, titers decreased to below the detection limit at week 2 and remained undetectable to EOT. Subsequently, the HPgV-1 titer rebounded to pretreatment levels for all patients. In conclusion, we found that HCV treatment regimens that included the polymerase inhibitor sofosbuvir resulted in decreases in HPgV-1 titers, and the addition of pegylated interferon increased the effect on patients with coinfections. This points to the high specificity of protease and NS5A inhibitors toward HCV and the more broad-spectrum activity of sofosbuvir and especially pegylated interferon. IMPORTANCE: Human pegivirus 1 coinfections are common in hepatitis C virus (HCV) patients, persisting for years. However, little is known about how pegivirus coinfections are affected by treatment with pangenotypic direct-acting antivirals (DAAs) against HCV. We identified human pegivirus by metagenomic analysis of chronic HCV patients undergoing protease, NS5A, and polymerase inhibitor treatment, in some patients with the addition of pegylated interferon, and followed viral kinetics of both viruses to investigate treatment effects. Only during HCV DAA treatment regimens that included the more broad-spectrum drug sofosbuvir could we detect a consistent decline in pegivirus titers that, however, rebounded to pretreatment levels after treatment cessation. The addition of pegylated interferon gave the highest effect with pegivirus titers decreasing to below the assay detection limit, but without clearance. These results reveal the limited effect of frontline HCV drugs on the closest related human virus, but sofosbuvir appeared to have the potential to be repurposed for other viral diseases.
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Antivirales , Bencimidazoles , Coinfección , Infecciones por Flaviviridae , Hepatitis C Crónica , Pegivirus , Sofosbuvir , Humanos , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Bencimidazoles/uso terapéutico , Sofosbuvir/uso terapéutico , Pegivirus/efectos de los fármacos , Coinfección/tratamiento farmacológico , Coinfección/virología , Masculino , Infecciones por Flaviviridae/tratamiento farmacológico , Infecciones por Flaviviridae/virología , Femenino , Genotipo , Quinoxalinas/uso terapéutico , Persona de Mediana Edad , Pirrolidinas , Sulfonamidas/uso terapéutico , ARN Viral/sangre , ARN Viral/genética , Hepacivirus/genética , Hepacivirus/efectos de los fármacos , Genoma Viral , Adulto , Anciano , Carga Viral/efectos de los fármacos , Metagenómica , Ciclopropanos , Ácidos Aminoisobutíricos , Filogenia , Combinación de MedicamentosRESUMEN
BACKGROUND: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. CASE PRESENTATION: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. CONCLUSION: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.
Asunto(s)
Varicela , Coinfección , Infecciones por Citomegalovirus , Citomegalovirus , Humanos , Masculino , Adulto , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/aislamiento & purificación , Varicela/tratamiento farmacológico , Varicela/complicaciones , Varicela/virología , Varicela/diagnóstico , Coinfección/virología , Coinfección/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Hemorragia/virología , Hemorragia/etiología , Herpesvirus Humano 3/aislamiento & purificación , Activación ViralRESUMEN
The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.
Asunto(s)
Fármacos Anti-VIH , Coinfección , Infecciones por VIH , Lamivudine , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Polimorfismo de Nucleótido Simple , Tenofovir , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Femenino , Masculino , Adulto , Lamivudine/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Tenofovir/uso terapéutico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Persona de Mediana Edad , Coinfección/tratamiento farmacológico , Coinfección/genética , Leucocitos Mononucleares/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , Organofosfatos/uso terapéutico , Organofosfatos/farmacocinética , Hepatitis B/tratamiento farmacológico , Hepatitis B/genética , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/farmacocinética , Polifosfatos/metabolismo , Farmacogenética/métodosRESUMEN
Antiretroviral regimens for human immunodeficiency virus (HIV) infection have continuously evolved; however, antiretrovirals can cause severe adverse reactions. Two-drug regimen therapy can decrease lifetime cumulative drug exposure and long-term toxicities associated with multiple antiretrovirals. The preferred 2-drug regimen constitutes dolutegravir (DTG) and lamivudine (3TC). This study determined the rate of virological suppression and incidence of adverse events at week 48 in treatment-naïve people living with HIV initiated on DTGâ +â 3TC. This was a single-center, retrospective, observational study. Treatment-naïve people aged ≥18 years who received at least 1 DTGâ +â 3TC dose between May 2020 and May 2022 were included. Eighty-nine people living with HIV were enrolled. Twenty-five (28.1%) patients with a DTGâ +â 3TC regimen at baseline were analyzed because of comorbidities, and 48% because of concomitant tuberculosis (TB). Viral suppression at 48 weeks was achieved in 91.67% of patients, and TB was well controlled. At week 48, 84 (94.38%) patients had viral loadsâ <â 50 copies/mL, and 21 (91.31%) of the 23 participants with a baseline HIV-1-RNA levelâ ≥â 1â ×â 105 copies/mL achieved virological success. Fifteen (88.23%) of the 17 participants with a baseline CD4â +â cell count of <200 cells/µL achieved virological suppression. The median CD4â +â cell count change from baseline was 539.5 cells/µL. No significant changes in triglycerides, low-density lipoprotein cholesterol, weight, or creatinine were observed from baseline to 48 weeks. One patient had severe insomnia at 4 weeks. Our findings support the real-world effectiveness and low metabolic impact of DTGâ +â 3TC. Using DTGâ +â 3TC in patients coinfected with TB and HIV has favorable therapeutic outcomes.
Asunto(s)
Fármacos Anti-VIH , Quimioterapia Combinada , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Lamivudine , Oxazinas , Piperazinas , Piridonas , Tuberculosis , Humanos , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Piridonas/efectos adversos , Lamivudine/uso terapéutico , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Masculino , Estudios Retrospectivos , Adulto , Piperazinas/uso terapéutico , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , China , Persona de Mediana Edad , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/administración & dosificación , Carga Viral/efectos de los fármacos , Coinfección/tratamiento farmacológico , Resultado del Tratamiento , Recuento de Linfocito CD4Asunto(s)
Antivirales , Coinfección , Infecciones por VIH , Humanos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicacionesRESUMEN
Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.
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Coinfección , Inflamación , Macaca mulatta , Malaria , Neutrófilos , Plasmodium , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Coinfección/tratamiento farmacológico , Coinfección/parasitología , Coinfección/virología , Malaria/tratamiento farmacológico , Malaria/inmunología , Malaria/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Proyectos Piloto , Neutrófilos/inmunología , Antirretrovirales/uso terapéutico , Carga Viral , Biomarcadores/sangre , Citocinas/sangre , Modelos Animales de Enfermedad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunologíaRESUMEN
This study presents the clinical profile of a 74-year-old male patient admitted to the hospital due to a 20-day history of coughing, chest tightness, and dyspnea. Upon admission, the patient presented with fever, tachycardia, and tachypnea. Clinical examination revealed evidence of lung infection, sepsis, and multi-organ dysfunction, alongside abnormal blood gas analysis and elevated C-reactive protein (CRP) levels. Pathogen testing confirmed Chlamydia psittaci (C. psittaci), infection. Throughout the treatment course, the patient developed concurrent fungal and viral infections, necessitating a comprehensive approach involving combined antibiotic and antifungal therapy. Despite encountering treatment-related complications, the patient demonstrated clinical improvement with aggressive management. This case underscores the importance of recognizing immune suppression subsequent to Chlamydia infection, emphasizing the critical role of early diagnosis, intervention, and standardized treatment protocols in enhancing patient prognosis.
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Chlamydophila psittaci , Coinfección , Psitacosis , Anciano , Humanos , Masculino , Antibacterianos/uso terapéutico , Coinfección/microbiología , Coinfección/tratamiento farmacológico , Psitacosis/complicaciones , Psitacosis/tratamiento farmacológico , Tolerancia Inmunológica , Micosis/etiología , Virosis/etiologíaRESUMEN
Introduction: Management of patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (AIDS) (PLWHA) still represents a challenge for doctors in various medical fields. The presence of co-infections, with different degrees of immune system impairment, raises the need for a multi-disciplinary approach to the PLWHA. Methods: In this paper, we present three cases of PLWHA with various ophthalmological conditions, who were admitted to "Prof. Dr. Matei BalÈ" National Institute for Infectious Diseases (INBIMB). Three of them were late presenters, recently diagnosed with AIDS. All three were in immuno-virological failure. The ophthalmic conditions were either related to the HIV infection, or the result of other complications. Discussion: The diversity and complexity of ocular involvement in PLWHA were deeply linked to the patient's immunological status at the ophthalmological evaluation moment. Thus, antiretroviral therapy (ART) played an important immune status recovery role. Encountered ocular conditions vary, some being directly caused by the presence of the virus, and the others were the result of opportunistic infections (cytomegalovirus, Varicella virus) or other co-infections (Treponema pallidum). Neurological conditions disturbing the natural defense mechanism, prolonged hospital stay, and exposure to multiple antibiotic regimens are risk factors for difficult-to-treat eye infections with multidrug-resistant bacteria. Some ocular conditions can be the reason that leads to HIV infection diagnosis, while others can appear during the time, especially in patients with low ART adherence. The prognostic is conditioned by the early recognition and correct management of the disease and the immunological status recovery under ART. Conclusions: Correct and early diagnosis of HIV-related eye conditions is mandatory to establish the most appropriate medical management to obtain an increase in the quality of life of the patient. Abbreviations: HIV = Human Immunodeficiency Virus, AIDS = Acquired Immunodeficiency Syndrome, ART = Antiretroviral Therapy.
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Oftalmopatías , Infecciones del Ojo , Infecciones por VIH , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Linfocito CD4 , Oftalmopatías/diagnóstico , Oftalmopatías/etiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/diagnóstico , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Coinfección/diagnóstico , Coinfección/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones del Ojo/diagnóstico , Infecciones del Ojo/tratamiento farmacológico , Infecciones del Ojo/inmunologíaRESUMEN
In adults requiring protease inhibitor (PI)-based antiretroviral therapy (ART), replacing rifampicin with rifabutin is a preferred option, but there is lack of evidence to guide rifabutin dosing in children, especially with PIs. We aimed to characterize the population pharmacokinetics of rifabutin and 25-O-desacetyl rifabutin (des-rifabutin) in children and optimize its dose. We included children from three age cohorts: (i) <1-year-old cohort and (ii) 1- to 3-year-old cohort, who were ART naïve and received 15- to 20-mg/kg/day rifabutin for 2 weeks followed by lopinavir/ritonavir (LPV/r)-based ART with 5.0- or 2.5 mg/kg/day rifabutin, respectively, while the (iii) >3-year-old cohort was ART-experienced and received 2.5-mg/kg/day rifabutin with LPV/r-based ART. Non-linear mixed-effects modeling was used to interpret the data. Monte Carlo simulations were performed to evaluate the study doses and optimize dosing using harmonized weight bands. Twenty-eight children were included, with a median age of 10 (range 0.67-15.0) years, a median weight of 11 (range 4.5-45) kg, and a median weight-for-age z score of -3.33 (range -5.15 to -1.32). A two-compartment disposition model, scaled allometrically by weight, was developed for rifabutin and des-rifabutin. LPV/r increased rifabutin bioavailability by 158% (95% confidence interval: 93.2%-246.0%) and reduced des-rifabutin clearance by 76.6% (74.4%-78.3%). Severely underweight children showed 26% (17.9%-33.7%) lower bioavailability. Compared to adult exposures, simulations resulted in higher median steady-state rifabutin and des-rifabutin exposures in 6-20 kg during tuberculosis-only treatment with 20 mg/kg/day. During LPV/r co-treatment, the 2.5-mg/kg/day dose achieved similar exposures to adults, while the 5-mg/kg/day dose resulted in higher exposures in children >7 kg. All study doses maintained a median Cmax of <900 µg/L. The suggested weight-band dosing matches adult exposures consistently across weights and simplifies dosing.
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Infecciones por VIH , Lopinavir , Rifabutina , Ritonavir , Humanos , Rifabutina/farmacocinética , Rifabutina/uso terapéutico , Lopinavir/uso terapéutico , Lopinavir/farmacocinética , Ritonavir/uso terapéutico , Ritonavir/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Preescolar , Masculino , Femenino , Lactante , Tuberculosis/tratamiento farmacológico , Niño , Coinfección/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/farmacocinética , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Granulomatous amoebic encephalitis due to Acanthamoeba spp is a rare, near-fatal central nervous system infection. It is often seen in immunocompromised individuals. Here we describe a survivor of this infection who was co-infected with multidrug-resistant tuberculosis. He presented to us with features of meningitis and a history of chronic cough. The chest X-ray was classical for pulmonary tuberculosis. Neuroimaging was suggestive of encephalitis; herpes simplex virus PCR was negative. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis. Wet mounts revealed trophozoites of Acanthamoeba Currently, he is being treated with oral bedaquiline, levofloxacin, linezolid, clofazimine, cycloserine and pyridoxine for tuberculosis. He received intravenous amikacin and oral cotrimoxazole and fluconazole for Acanthamoeba infection for 1 month. The resolution was confirmed by repeating the CSF wet mount, culture and neuroimaging. He was then discharged with oral rifampicin, cotrimoxazole and fluconazole. He is currently under our close follow-up.
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Acanthamoeba , Amebiasis , Tuberculosis Meníngea , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Acanthamoeba/aislamiento & purificación , Tuberculosis Meníngea/tratamiento farmacológico , Tuberculosis Meníngea/complicaciones , Tuberculosis Meníngea/diagnóstico , Amebiasis/tratamiento farmacológico , Amebiasis/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Inmunocompetencia , Coinfección/tratamiento farmacológicoRESUMEN
BACKGROUND: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. METHODS: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. RESULTS: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. CONCLUSIONS: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.
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Derrame Pleural , Infecciones Estreptocócicas , Streptococcus pyogenes , Humanos , Preescolar , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Masculino , Niño , Reino Unido/epidemiología , Femenino , Lactante , Derrame Pleural/microbiología , Derrame Pleural/epidemiología , Derrame Pleural/terapia , Streptococcus pyogenes/aislamiento & purificación , Antibacterianos/uso terapéutico , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/virología , Coinfección/tratamiento farmacológico , Adolescente , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológicoRESUMEN
BACKGROUND PAECILOMYCES: and Penicillium are considered as rare opportunistic pathogens in immunocompromised hosts, and pneumonia caused by Paecilomyces and Penicillium is rare. In this study, we present first case of severe pneumonia with pleural effusion caused by co-infection of Paecilomyces variotii (P. variotii) and Penicillium oxalicum (P. oxalicum) in a 66-year-old female with poorly controlled type 2 diabetes. CASE PRESENTATION: A 56-year-old woman patient presented to hospital for nausea, poor appetite, and vomiting for one day. On the second day of admission, blood culture and renal puncture fluid culture grew multidrug-resistant Escherichia coli (imipenem/cilastatin sensitive), and she received combination therapy with imipenem/cilastatin (1 g, every 8 h) and vancomycin (0.5 g, every 12 h). On the fourth day, she developed symptoms of respiratory failure. Pulmonary computed tomography (CT) showed an increase in pneumonia compared to before, with minor pleural effusion on both sides. Two fungi were isolated repeatedly from BALF culture, which were confirmed as P. variotii and P. oxalicum by Internal transcribed spacer (ITS) sequencing. Her pleural effusion was completely absorbed, pneumonia symptoms have significantly improved and discharged with receiving liposomal amphotericin B treatment for four weeks. CONCLUSIONS: It is worth noting that clinicians and laboratory personnel should not simply consider Paecilomyces and Penicillium species as contaminants, especially in immunocompromised patients. Early fungal identification and antifungal drug sensitivity are crucial for clinical drug selection and patient prognosis.