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1.
Clin Lab ; 68(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36125137

RESUMO

BACKGROUND: Hepatitis B and hepatitis C viruses are common infections and main causative agents of chronic liver diseases, cirrhosis, and hepatocellular carcinoma. The liver is the major site of hormone and glucose metabolism which have deep interconnection with diabetes. Hepatitis-B and hepatitis-C virus infection and diabetes are prevalent diseases worldwide associated with increased morbidity and mortality. High prevalence of DM, HCV, and HBV showed that there is a higher chance of coexisting in an individual. Therefore, our study tried to assess the coexistence of hepatitis viruses and diabetes mellitus among DM patients at the University of Gondar comprehensive specialized hospital. METHODS: The hospital-based, cross-sectional study was conducted from November 01 to December 30, 2019 to as-sess the prevalence and associated factors of HBV and HCV among diabetes patients attending at University of Gondar referral hospital. Sociodemographic data was collected using a semi-structured questionnaire. Four milliliters of blood were collected using an anticoagulant free test tube for measurement of biochemical parameters and detection of hepatitis viruses. HBsAg and anti-HCV antibody detection was performed using One Step Cassette Style HBsAg Rapid Test and EUGENE® anti-HCV rapid test, respectively. Binary and multivariable logistic regression models were used to evaluate associated risk factors for the outcome variable. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 288 diabetes patients were included in this study and the prevalence of HBV and HCV was 7 (2.43%) and 18 (6.25%), respectively. Hepatitis B virus showed similar prevalence for type 1 and type 2 diabetes at 2.6% and 2.3%, respectively, but HCV showed a wide variation with 17.5% and 4.3% prevalence, respectively, for both diabetes types. In a multivariable logistic regression model compared with younger age (≤ 24 years), older age ≥ 65 years (AOR: 19.545, 95% CI: 2.577 - 22.827) age groups and poor glycemic control (AOR: 18.84, 95% CI: 17.83 - 20.39) showed significant association with HBV. CONCLUSIONS: A considerably large number of diabetes patients tested positive for anti-HCV antibody as a marker of Hepatitis C virus infection. None of the variables showed significant association with active Hepatitis B virus infection whereas older ages (≥ 65 years) and diabetes patients with poor glycemic control showed significant association with anti-HCV antibody positivity.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatite B , Hepatite C , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Etiópia/epidemiologia , Glucose , Hepacivirus , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C , Hormônios , Hospitais , Humanos , Estudos Soroepidemiológicos , Adulto Jovem
2.
Sci Rep ; 14(1): 3297, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331983

RESUMO

Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. However, its effectiveness in CD4+ T-cells count recovery and viral load suppression has not been studied yet in Ethiopia, where HIV is endemic. Therefore, we aimed to conduct a pilot assessment on the effect of DTG-based therapy on CD4+ T-cell count and viral load count among people living with HIV (PLWH) in Ethiopia. A longitudinal prospective cohort study was conducted from July 2020 to February 2021. 109 PLWH who are ART naive but plan to initiate DTG-based therapy were recruited. HIV viral ribonucleic acid (RNA) copies were determined using polymerase chain reaction. To compute the difference in viral load and CD4+ T-cell counts between the baseline, 3rd, and 6th months, a Friedman test was used. The study included 109 PLWH who had never received antiretroviral medication. Participants taking DTG-based treatment showed significantly decreasing median (IQR) values of viral load count (copies/mL) from 446,812 (237649.5-732994.5) at baseline to 34 (23.5-46) at 3 months and 0.0 (0-19) at 6 months of treatment follow-up. Although the treatment increases the proportion of participants with HIV-1 RNA 50 copies/mL from 0 (0% at baseline) to 87 (79.8%) and 100 (91.7%) at the 3rd and 6th months of treatment, respectively, On the other hand, the CD4+ T-cell count increased significantly during treatment: median (IQR): 209 (81.5-417.5) versus 291 (132-522) versus 378 (181-632.5) cells/L at baseline, the 3rd and 6th months of the treatment follow-up period, respectively. We found dolutegravir-based therapy was a promising option with high virological suppression rates and CD4+ T-cell count recovery, demonstrating a restoration of cellular immunity. Moreover, Viral load suppression rates were high after the initiation of the treatment. We recommend further research should be conducted with a larger number of participants to acquire greater awareness of the treatment outcomes.


Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Humanos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Estudos Prospectivos , Carga Viral , Projetos Piloto , Contagem de Linfócito CD4 , Fármacos Anti-HIV/farmacologia , HIV-1/genética , Linfócitos T CD4-Positivos , RNA/farmacologia
3.
PLoS Negl Trop Dis ; 17(1): e0011094, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36662839

RESUMO

BACKGROUND: Interferon-γ (IFN-γ) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-γ production by T cells, although its connection with disease severity and immune recovery during treatment is unexplored. We investigated the species-specific effect of helminths on the IFN-γ production by T cells in relation to disease severity during active and latent TB infection (LTBI). METHODS: In this study, 69 active pulmonary TB patients (PTB), 28 with LTBI and 66 healthy controls were included. Active TB was diagnosed using GenXpert MTB/RIF while QuantiFERON test (QFT) was used for the screening of healthy community controls (CCs) and for the diagnosis of LTBI. Helminth infection was identified by routine diagnosis whereas clinical disease severity was evaluated by the TB score. Intracellular IFN-γ production of T cells in stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry using TB antigens (PPD), the polyclonal T cell activator staphylococcal enterotoxin B (SEB), or medium as unstimulated control. RESULTS: Helminth infected CCs and LTBI subjects showed a significant reduction of IFN-γ+ CD4+ T cells by PPD-stimulation compared to non-helminth infected control groups. The significant reduction in the frequency of IFN-γ+ T cells in both latent and active PTB patients following SEB stimulation was mostly attributed to Schistosoma mansoni infection, whereas Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection contributed equally in CCs. Following anti-helminthic and anti-TB treatment for 2 months, the frequency of IFN-γ+ CD4 T cells in helminth coinfected PTB was restored to levels of helminth negative PTB before treatment. Helminth coinfected PTB patients with an intermediate and severe clinical course had reduced capacity for production of IFN-γ+ T cells compared to the corresponding non-helminth infected PTB. CONCLUSION: We found a reduction in IFN-γ producing T cells by helminth coinfection which was restored following anti-helminthic treatment. This reduction was helminth species-dependent in an exploratory sub-analysis and correlated to increased disease severity.


Assuntos
Helmintos , Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Humanos , Animais , Interferon gama , Tuberculina , Leucócitos Mononucleares , Tuberculose/diagnóstico , Linfócitos T CD4-Positivos , Antígenos de Bactérias
4.
PLoS Negl Trop Dis ; 16(8): e0010721, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35976976

RESUMO

Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and QuantiFERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.


Assuntos
Coinfecção , Citocinas , Helmintíase , Interleucina-17 , Tuberculose , Animais , Citocinas/imunologia , Helmintíase/imunologia , Helmintos/classificação , Humanos , Interleucina-17/imunologia , Leucócitos Mononucleares/imunologia , Células Th1/imunologia , Células Th17/imunologia , Tuberculina , Tuberculose/complicações , Tuberculose/imunologia , Fator de Necrose Tumoral alfa
5.
Tuberculosis (Edinb) ; 131: 102126, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34601265

RESUMO

Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-ß producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients (PTB) and 69 community controls (CCs) from Gondar, Ethiopia, were included. Clinical disease severity was graded by TB score, and flow cytometry used to characterize Treg frequency and functionality measured as their TGF-ß-producing capacity. In helminth positive PTB patients (Helminth+PTB+) compared to helminth negative PTB or CCs, TGF-ß+ Tregs were significantly increased mainly in hookworm coinfection whereas S. mansoni increased TGF-ß+ Tregs in CCs. Treatment of TB and helminths decreased TGF-ß+ Tregs in Helminth+PTB+ at 2 months follow-up. There were no overall differences in the frequency of Tregs in CCs or PTB unless stratification on TB disease severity was performed. At inclusion Helminth+PTB+ had increased frequency of Tregs already at low disease severity, and TGF-ß+ Tregs correlated to intermediate-to-high disease severity. In conclusion, helminth specific increase of TGF-ß+ Tregs in PTB patients was correlated to TB disease severity and was restored following anti-helminth treatment.


Assuntos
Ascaris lumbricoides/patogenicidade , Schistosoma mansoni/patogenicidade , Esquistossomose/complicações , Linfócitos T Reguladores/imunologia , Tuberculose/imunologia , Análise de Variância , Animais , Etiópia , Esquistossomose/fisiopatologia , Linfócitos T Reguladores/metabolismo
6.
PLoS Negl Trop Dis ; 15(3): e0009194, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33651797

RESUMO

Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.


Assuntos
Helmintíase/patologia , Leucócitos Mononucleares/metabolismo , Tuberculose Pulmonar/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Animais , Antígenos de Helmintos , Estudos de Casos e Controles , Coinfecção , Etiópia , Feminino , Helmintíase/imunologia , Helmintos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Tuberculose Pulmonar/patologia
7.
Open Forum Infect Dis ; 7(9): ofaa364, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32939358

RESUMO

Current sampling methods to diagnose cutaneous leishmaniasis are invasive and painful. An alternative and minimally invasive microbiopsy device was evaluated in a diverse range of cutaneous leishmaniasis lesions in Ethiopia. Using polymerase chain reaction-based diagnosis, the microbiopsy outperformed the routine skin slit sample by detecting more patients while pain scores were significantly lower.

8.
J Immunol Res ; 2020: 8385672, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377538

RESUMO

Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.


Assuntos
Citocinas/metabolismo , Leishmania donovani/fisiologia , Leishmaniose Visceral/imunologia , Adolescente , Adulto , Células Cultivadas , Estudos de Coortes , Doenças Endêmicas , Etiópia/epidemiologia , Feminino , Seguimentos , Humanos , Imunização , Leishmaniose Visceral/epidemiologia , Masculino , Monitorização Fisiológica , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
9.
BMC Res Notes ; 12(1): 515, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420007

RESUMO

OBJECTIVE: Immuno-compromised individuals with latent tuberculosis infection (LTBI) are at an increased risk for tuberculosis reactivation compared with the general population. The aim of this study was to determine the prevalence of latent tuberculosis infection among people living with human immunodeficiency virus (PLWH) and apparently healthy blood donors. Human Immunodeficiency Virus positive individuals and for the purpose of comparison apparently healthy blood donors were enrolled. Blood sample was collected and tested for LTBI using QuantiFeron-TB Gold In-Tube assay (QFT-GIT) and CD4+ T cell count was determined by using BD FACS count. RESULTS: The overall prevalence of LTBI regardless of HIV status was 46%. The prevalence of LTBI among PLWH was 44% and that of blood donors 48%. ART naïve HIV positive patients were three times more likely to have LTBI than patients under ART treatment (P = 0.04). Data also showed statistically significant negative association between previous or current preventive INH therapy and LTBI among HIV positive cases (P = 0.005). The proportion of LTBI was slightly lower among HIV positive individuals than apparently healthy blood donors. Nevertheless, HIV positive individuals should be screened for LTBI and take INH prophylaxis.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Infecções por HIV/epidemiologia , Hospitais Universitários , Tuberculose Latente/epidemiologia , Encaminhamento e Consulta , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Comorbidade , Etiópia/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/diagnóstico , Masculino , Prevalência , Fatores de Risco , Teste Tuberculínico , Adulto Jovem
10.
PLoS Negl Trop Dis ; 10(3): e0004468, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26962865

RESUMO

One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation.


Assuntos
Antígenos de Protozoários/imunologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/patologia , Linfócitos T/imunologia , Adolescente , Adulto , Arginase/metabolismo , Estudos Transversais , Etiópia , Granulócitos/imunologia , Humanos , Índia , Masculino , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
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