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1.
Sci Rep ; 11(1): 13945, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230563

RESUMO

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.


Assuntos
Disbiose/microbiologia , Disbiose/virologia , Gastroenterite/microbiologia , Gastroenterite/virologia , Microbioma Gastrointestinal , Adolescente , Adulto , Bactérias/classificação , Biodiversidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/microbiologia , Diarreia/virologia , Fezes/microbiologia , Feminino , Gana , Humanos , Masculino , Filogenia , Rotavirus/fisiologia
3.
Front Microbiol ; 11: 559255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281757

RESUMO

Background: Pro- and anti-inflammatory cytokines are important mediators of immunity and are associated with malaria disease outcomes. However, their role in the establishment of asymptomatic infections, which may precede the development of clinical symptoms, is not as well-understood. Methods: We determined the association of pro and anti-inflammatory cytokines and other immune effector molecules with the development of asymptomatic malaria. We measured and compared the plasma levels of pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-6, IL-12p70, IL-17A, and granzyme B, the anti-inflammatory cytokine IL-4 and the regulatory cytokine IL-10 from children with asymptomatic malaria infections (either microscopic or submicroscopic) and uninfected controls using Luminex. Results: We show that individuals with microscopic asymptomatic malaria had significantly increased levels of TNF-α and IL-6 compared to uninfected controls. Children with either microscopic or submicroscopic asymptomatic malaria exhibited higher levels of IFN-γ, IL-17A, and IL-4 compared to uninfected controls. The levels of most of the pro and anti-inflammatory cytokines were comparable between children with microscopic and submicroscopic infections. The ratio of IFN-γ/IL-10, TNF-α/IL-10, IL-6/IL-10 as well as IFN-γ/IL-4 and IL-6/IL-4 did not differ significantly between the groups. Additionally, using a principal component analysis, the cytokines measured could not distinguish amongst the three study populations. This may imply that neither microscopic nor submicroscopic asymptomatic infections were polarized toward a pro-inflammatory or anti-inflammatory response. Conclusion: The data show that asymptomatic malaria infections result in increased plasma levels of both pro and anti-inflammatory cytokines relative to uninfected persons. The balance between pro- and anti-inflammatory cytokines are, however, largely maintained and this may in part, explain the lack of clinical symptoms. This is consistent with the generally accepted observation that clinical symptoms develop as a result of immunopathology involving dysregulation of inflammatory mediator balance in favor of pro-inflammatory mediators.

4.
BMC Infect Dis ; 17(1): 743, 2017 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-29197331

RESUMO

BACKGROUND: Mycobacterium tuberculosis complex (MTBC) and Non-tuberculosis Mycobacterium (NTM) infections differ clinically, making rapid identification and drug susceptibility testing (DST) very critical for infection control and drug therapy. This study aims to use World Health Organization (WHO) approved line probe assay (LPA) to differentiate mycobacterial isolates obtained from tuberculosis (TB) prevalence survey in Ghana and to determine their drug resistance patterns. METHODS: A retrospective study was conducted whereby a total of 361 mycobacterial isolates were differentiated and their drug resistance patterns determined using GenoType Mycobacterium Assays: MTBC and CM/AS for differentiating MTBC and NTM as well MTBDRplus and NTM-DR for DST of MTBC and NTM respectively. RESULTS: Out of 361 isolates, 165 (45.7%) MTBC and 120 (33.2%) NTM (made up of 14 different species) were identified to the species levels whiles 76 (21.1%) could not be completely identified. The MTBC comprised 161 (97.6%) Mycobacterium tuberculosis and 4 (2.4%) Mycobacterium africanum. Isoniazid and rifampicin monoresistant MTBC isolates were 18/165 (10.9%) and 2/165(1.2%) respectively whiles 11/165 (6.7%) were resistant to both drugs. Majority 42/120 (35%) of NTM were M. fortuitum. DST of 28 M. avium complex and 8 M. abscessus complex species revealed that all were susceptible to macrolides (clarithromycin, azithromycin) and aminoglycosides (kanamycin, amikacin, and gentamicin). CONCLUSION: Our research signifies an important contribution to TB control in terms of knowledge of the types of mycobacterium species circulating and their drug resistance patterns in Ghana.


Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Micobactérias não Tuberculosas/genética , Tuberculose/microbiologia , Adolescente , Adulto , Idoso , Claritromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Genótipo , Gana , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Micobactérias não Tuberculosas/efeitos dos fármacos , Micobactérias não Tuberculosas/isolamento & purificação , Prevalência , Estudos Retrospectivos , Rifampina/farmacologia , Inquéritos e Questionários
5.
Int J Mycobacteriol ; 6(1): 27-33, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28317801

RESUMO

OBJECTIVE/BACKGROUND: Introduction of the interferon gamma (IFN-γ) release assays with their higher sensitivity and specificity over the traditional tuberculin skin test has improved testing for latent tuberculosis infection (LTBI). None of the IFN-γ release assays has ever been used to screen for LTBI in Ghana. This study set out to determine the utility of the QuantiFERON TB Gold-in-Tube (QFT-GIT) test for the diagnosis of LTBI among close household contacts of newly diagnosed sputum smear-positive tuberculosis (TB) patents in Accra, Ghana, and the associated risk factors for a positive QFT-GIT test. MATERIALS AND METHODS: Close household contacts of newly diagnosed sputum smear-positive patients receiving anti-TB therapy from three hospitals in Accra were recruited, after providing written informed consent, between April 2012 and December 2014. In addition to demographic details, 2 mL of blood was collected from all participants for the QFT-GIT test for LTBI diagnosis. RESULTS: Out of 112 eligible consenting participants, the QFT-GIT test was performed for 100 participants. The prevalence of LTBI (QFT-GIT positive) was 65%, with 32% being QFT-GIT negative and 3% indeterminate results. Contacts aged >15 years were more likely to be QFT-GIT positive than those aged >15 years, regardless of their Bacillus Calmette-Guerin status. There was significantly higher QFT-GIT test positivity in adult contacts who were parents, siblings, or spouses to index cases than in child contacts (P = 0.0016, P = 0.04, and P = 0.0003, respectively). CONCLUSION: The QFT-GIT test will be a useful tool for screening of TB contacts for LTBI in Ghana.


Assuntos
Busca de Comunicante , Características da Família , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Teste Tuberculínico/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Gana/epidemiologia , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Escarro/microbiologia , Tuberculose/epidemiologia , Tuberculose/microbiologia , Adulto Jovem
6.
Int J Infect Dis ; 56: 126-129, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27979782

RESUMO

Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host-pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)-those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data from previous and ongoing research studies on MTBC may be inaccurate and inappropriate. A major rethink is required regarding the design and structure of future clinical trials of new interventions. The West, Central, East, and Southern African EDCTP Networks of Excellence provide opportunities to take forward these pan-Africa studies. More investments into molecular, epidemiological, clinical, diagnostic, and immunological studies across the African continent are required to enable further understanding of host-M. africanum interactions, leading to the development of more specific diagnostics, biomarkers, host-directed therapies, and vaccines for TB.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Mycobacterium/imunologia , Mycobacterium/patogenicidade , Vacinas contra a Tuberculose/imunologia , Tuberculose , África Ocidental/epidemiologia , Genótipo , Humanos , Tipagem Molecular , Mycobacterium/classificação , Mycobacterium/genética , Filogenia , Prevalência , Escarro/microbiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Tuberculose/terapia
7.
BMC Infect Dis ; 14: 495, 2014 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-25209422

RESUMO

BACKGROUND: There has been a long held belief that patients with drug-susceptible TB are non-infectious after two weeks of therapy. Recent microbiological and epidemiological evidence has challenged this dogma, however, the nature of the Mtb-specific cellular immune response during this period has not been adequately investigated. This knowledge could be exploited in the development of immunological biomarkers of early treatment response. METHODS: Cellular response to four Mtb infection phase-dependent antigens, ESAT-6/CFP-10 fusion protein and three DosR encoded proteins (Rv1733c, Rv2029c, Rv2628) were evaluated in a Ghanaian TB cohort (n=20) before and after 2 weeks of anti TB therapy. After 6-days in vitro stimulation, Peripheral blood mononuclear cell (PBMC) culture supernatant was harvested and the concentration of IFN-γ, Granzyme B, IL-10, IL-17, sIL2Rα and TNF-α were determined in a 6-plex Luminex assay. Frequencies of IFN-γ + CD4 and CD8 T cells were also determined in an intracellular cytokine assay. RESULTS: All antigens induced higher levels of IFN-γ, followed by Granzyme B, TNF-α and IL-17 and low levels of IL-10 and sIL-2R-α in PBMC before treatment and after 2 weeks of treatment. Median cytokine levels of IFN-γ, Granzyme B, IL-17 and sIL-2R-α increased during week two, but it was significant for only Rv1733-specific production of Granzyme B (P = 0. 013). The median frequency of antigen specific IFN-γ + CD4 T cells increased at week two; however, only the increase in the ESAT-6/CFP-10-specific response was significant (P = 0. 0008). In contrast, the median frequency of ESAT-6/CFP-10- specific IFN-γ + CD8 T cell responses declined during week two (P = 0. 0024). Additionally, wide inter-individual variation with three distinct patterns were observed; increase in all cytokine levels, decrease in all cytokine levels and fluctuating cytokine levels after 2 weeks of treatment. CONCLUSION: The second week of effective chemotherapy was characterized by a general increase in cytokine response to Mtb-specific antigens suggestive of an improvement in cellular response with therapy. However, the wide inter-individual variation observed would limit the utility of cytokine biomarkers during this period.


Assuntos
Antibacterianos/uso terapêutico , Antígenos de Bactérias/imunologia , Interferon gama/genética , Mycobacterium tuberculosis/imunologia , Tuberculose/tratamento farmacológico , Tuberculose/genética , Adulto , Estudos de Coortes , Feminino , Gana , Granzimas/genética , Granzimas/imunologia , Humanos , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Linfócitos T/imunologia , Tuberculose/enzimologia , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
8.
PLoS One ; 8(6): e68121, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23826366

RESUMO

BACKGROUND: Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are Mycobacterium tuberculosis (Mtb)-specific antigens that are secreted by actively metabolising bacteria and contribute to the virulence of the bacteria. Their ability to induce Treg and Th2 responses, particularly during the first two weeks of treatment, has not been comprehensively examined to date. The purpose of this work was to characterise Th1, Th2 and Treg responses to rESAT-6-CFP10 fusion protein in TB patients before and during the intensive phase of treatment and in healthy M.bovis BCG vaccinated donors. METHODS: Forty-six newly diagnosed, HIV-negative, smear-positive pulmonary TB patients and 20 healthy donors were recruited in the UK and Ghana. Their peripheral blood mononuclear cells (PBMC) were used in ex vivo ELISPOT and in vitro cultures to identify immunological parameters of interest. RESULTS: The study confirmed that protective immune responses to rESAT-6-CFP10 are impaired in active TB but improved during treatment: circulating antigen-specific IL-4-producing T-cells were increased in untreated TB but declined by two weeks of treatment while the circulating antigen-specific IFN-γ producing T cells which showed a transient rise at one week of treatment, persisted at baseline levels at two months of treatment. In vitro T cell proliferation and IFN-γ production were reduced, while IL-4 and CD4(+)FoxP3(+)CD25(hi) cell expression were increased in response to rESAT-6-CFP10 fusion protein in untreated TB. These responses were reversed during early treatment of TB. CONCLUSIONS: These observations support further investigations into the possible utility of these parameters as markers of active disease and favourable treatment outcomes.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Linfócitos T Reguladores/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Antígenos de Bactérias/metabolismo , Vacina BCG , Proteínas de Bactérias/metabolismo , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Gana , Humanos , Leucócitos Mononucleares/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/metabolismo , Proteínas Recombinantes/metabolismo , Fatores de Transcrição/metabolismo , Tuberculose Pulmonar/tratamento farmacológico , Reino Unido , Adulto Jovem
9.
BMC Public Health ; 10: 35, 2010 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-20102620

RESUMO

BACKGROUND: Ghana has not conducted a national tuberculin survey or tuberculosis prevalence survey since the establishment of the National Tuberculosis Control Programme. The primary objective of this study was therefore to determine the prevalence of tuberculin skin sensitivity in Ghanaian school children aged 6-10 years in 8 out of 10 regions of Ghana between 2004 and 2006. METHODS: Tuberculin survey was conducted in 179 primary schools from 21 districts in 8 regions. Schools were purposively selected so as to reflect the proportion of affluent private and free tuition public schools as well as the proportion of small and large schools. RESULTS: Of the 24,778 children registered for the survey, 23,600 (95.2%) were tested of which 21,861 (92.6%) were available for reading. The age distribution showed an increase in numbers of children towards older age: 11% of the children were 6 years and 25%, 10 years. Females were 52.5% and males 47.5%. The proportion of girls was higher in all age groups (range 51.4% to 54.0%, p < 0.001). BCG scar was visible in 89.3% of the children. The percentage of children with a BCG scar differed by district and by age. The percentage of children with a BCG scar decreased with increasing age in all districts, reflecting increasing BCG vaccination coverage in Ghana in the last ten years. The risk of tuberculosis infection was low in the northern savannah zones compared to the southern coastal zones. Using a cut-off of 15 mm, the prevalence of infection ranged from 0.0% to 5.4% and the Annual Risks of Tuberculosis Infection 0.0% to 0.6%. There was an increase in the proportion of infected children after the age of 7 years. Children attending low and middle-class schools had a higher risk of infection than children attending upper-class schools. CONCLUSION: Tuberculosis infection is still a public health problem in Ghana and to monitor the trend, the survey needs to be repeated at 5 years interval.


Assuntos
Teste Tuberculínico , Tuberculose/epidemiologia , Distribuição por Idade , Vacina BCG , Criança , Feminino , Gana/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Prevalência , Risco , Distribuição por Sexo , Tuberculose/diagnóstico
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