RESUMO
Over the past few years, meta-analysis has become popular among biomedical researchers for detecting biomarkers across multiple cohort studies with increased predictive power. Combining datasets from different sources increases sample size, thus overcoming the issue related to limited sample size from each individual study and boosting the predictive power. This leads to an increased likelihood of more accurately predicting differentially expressed genes/proteins or significant biomarkers underlying the biological condition of interest. Currently, several meta-analysis methods and tools exist, each having its own strengths and limitations. In this paper, we survey existing meta-analysis methods, and assess the performance of different methods based on results from different datasets as well as assessment from prior knowledge of each method. This provides a reference summary of meta-analysis models and tools, which helps to guide end-users on the choice of appropriate models or tools for given types of datasets and enables developers to consider current advances when planning the development of new meta-analysis models and more practical integrative tools.
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Algoritmos , Análise de Dados , Metanálise como Assunto , Software , Árvores de Decisões , Humanos , Fluxo de TrabalhoRESUMO
BACKGROUND: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS: In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (AzmR) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (AzmR 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes. CONCLUSIONS: Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of AzmR and iMLSB S. aureus. TRIAL REGISTRATION: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008.
Assuntos
Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Macrolídeos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Nasofaringe/microbiologia , Prevalência , Tracoma/tratamento farmacológico , Administração Oral , Adolescente , Antibacterianos/uso terapêutico , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Criança , Estudos Transversais , Farmacorresistência Bacteriana , Feminino , Gâmbia/epidemiologia , Humanos , Programas de Imunização , Masculino , Testes de Sensibilidade Microbiana , Nasofaringite/tratamento farmacológico , Nasofaringite/microbiologia , Fatores de Risco , Manejo de Espécimes/métodos , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Streptococcus pneumoniae/efeitos dos fármacos , Tracoma/complicaçõesRESUMO
BACKGROUND: In West Africa, the carriage of Group B Streptococcus (GBS), among infants is poorly characterised. We investigated co-carriage of GBS with other respiratory pathogens in the infants' nasopharynx in The Gambia. METHODS: We assessed the carriage, serotypes and antibiotic susceptibility of Beta-haemolytic Streptococci (BHS) groups A-G; along with the carriage of Streptococcus pneumoniae; Haemophilus influenzae; Staphylococcus aureus and Moraxella catarrhalis in 1200 two-month old infants. RESULTS: The BHS prevalence was 20.0 % and GBS dominated (13.8 %), particularly serotypes V and II; serotype V being negatively associated with H. Influenzae carriage (OR 0.41 [95 % CI: 0.18-0.93], p = 0.033). Although co-colonization of GBS and other BHS was not seen, colonization with GBS was positively associated with S. aureus (OR 1.89 [95 % CI: 1.33-2.69], P < 0.001) and negatively associated with S. pneumoniae (OR 0.47 [95 % CI: 0.33-0.67], p < 0.001) and M. catarrhalis (OR 0.61 [95 % CI: 0.40-0.92], p = 0.017). ≥ 89 % of GBS isolates were susceptible to most antibiotics tested, except for tetracycline resistance, which was 89 %. CONCLUSION: This study provides baseline data on the carriage of GBS in two month old infants from West Africa. The dominant serotypes of GBS in this setting are serotypes V and II. This may be important for future GBS vaccine development for the West African sub-region.
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Portador Sadio/epidemiologia , Coinfecção/epidemiologia , Nasofaringe/microbiologia , Streptococcus agalactiae/isolamento & purificação , Antibacterianos/farmacologia , Portador Sadio/microbiologia , Coinfecção/microbiologia , Farmacorresistência Bacteriana , Gâmbia/epidemiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Humanos , Lactente , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/isolamento & purificação , Prevalência , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Tetraciclina/farmacologiaRESUMO
In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf- and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with TB-specific antigens. Before treatment, percentages of early secreted antigenic target-6(ESAT-6)/culture filtrate protein-10(CFP-10) and purified protein derivative-specific single-TNF-α-producing CD4(+) and CD8(+) T cells were significantly higher while single-IL-2-producing T cells were significantly lower in Maf- compared with Mtb-infected patients. Purified protein derivative-specific polyfunctional CD4(+) T cells frequencies were significantly higher before than after treatment, but there was no difference between the groups at both time points. Furthermore, the proportion of CD3(+) CD11b(+) T cells was similar in both groups pretreatment, but was significantly lower with higher TNF-α, IL-2, and IFN-γ production in Mtb- compared with that of Maf-infected patients posttreatment. Our data provide evidence of differences in T-cell responses to two mycobacterial strains with differing virulence, providing some insight into TB pathogenesis with different Mtb strains that could be prospectively explored as biomarkers for TB protection or susceptibility.
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Linfócitos T CD4-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Adolescente , Adulto , Idoso , Antígenos de Bactérias/sangue , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/sangue , Proteínas de Bactérias/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/metabolismo , Especificidade da Espécie , Tuberculose/sangue , Tuberculose/patologiaRESUMO
BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated bed nets (ITNs) can reduce the morbidity and mortality associated with malaria in pregnancy. Although the coverage for both IPTp and ITN use have been described in Malawi, the analysis of factors associated with IPTp receipt and ITN use is lacking. This analysis was conducted to assess IPTp and ITN use and predictors of use by women of child-bearing age (WOCBA). METHODS: A two-stage cluster-sample cross-sectional survey was conducted April 16-30, 2009 in eight districts across Malawi. Information on receipt of two or more doses of IPTp, ITN ownership, and ITN use the night before the survey was collected. Multivariate logistic regression was used to assess predictors of IPTp and ITN use. RESULTS: Data were collected from 7407 households containing 6985 WOCBA and 3213 recently pregnant women (women who reported a completed pregnancy in the 2 years before the survey). Most recently pregnant women (96 %) had at least one antenatal care (ANC) clinic visit; 91 % reported receiving at least one dose of IPTp, and 72 % reported receiving two or more doses of IPTp. Women in Phalombe, Rumphi, and Lilongwe were more likely to receive two doses of IPTp than those in Blantyre [adjusted odds ratio (aOR) 2.5 (95 % CI 1.5-4.5), 2.5 (95 % CI 1.5-4.3), and 2.0 (95 % CI 1.2-3.1), respectively]. Educated women were more likely to have received IPTp compared to women with no education [aOR 1.6 (95 % CI 1.0-2.6) for those who completed primary school, aOR1.9 (95 % CI 1.1-3.3) for some secondary school, and aOR 4.1 (95 % CI 1.9-8.7) for completed secondary school or above], and women in the poorest socioeconomic status quintile were less likely to receive IPTp than those in the least poor quintile [aOR 0.68 (95 % CI 0.48-0.97)]. In all, 53 % of WOCBA used an ITN the previous night. Women in Nkhotkhota and Phalombe were less likely to have slept under an ITN the previous night compared to those in Blantyre [aOR 0.52 (95 % CI 0.39-0.69) and aOR 0.67 (95 % CI 0.47-0.95), respectively]. In addition, age [aOR 0.61 (95 % CI 0.45-0.83) for women 15-19 years old], and either being currently pregnant [aOR 1.5 (95 % CI 1.2-2.0)] or having been pregnant in the previous 2 years [aOR 2.4, (95 % CI 2.1-2.8)] were associated with ITN use. CONCLUSION: In Malawi in 2009, IPTp and ITN use in WOCBA fell short of national and international goals. Adoption of new guidelines encouraging administration of IPTp at every scheduled ANC visit might increase IPTp use. Increasing health promotion activities to encourage earlier attendance at ANC clinics and create demand for IPTp and ITNs might improve overall IPTp and ITN use.
Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/epidemiologia , Malária/prevenção & controle , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/prevenção & controle , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Malaui/epidemiologia , Pessoa de Meia-Idade , Controle de Mosquitos , Gravidez , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effect of repeated mass drug administration (MDA) of azithromycin in the Gambia on the nasopharyngeal carriage of Streptococcus pneumoniae and on the emergence of antibiotic-resistant strains. METHODS: This study involved villages that participated in a cluster randomized trial comparing the effect of one versus three azithromycin MDA rounds on the prevalence of trachoma. Only villages in which most children received 7-valent pneumococcal conjugate vaccine were included. Three cross-sectional surveys were performed in two villages that received three annual MDA rounds: the first immediately before the third MDA round and the second and third, 1 and 6 months, respectively, after the third MDA round. The third survey also covered six villages that had received one MDA round 30 months previously. Pneumococcal carriage was assessed using nasopharyngeal swabs and azithromycin resistance was detected using the Etest. FINDINGS: The prevalence of pneumococcal carriage decreased from 43.4% to 19.2% between the first and second surveys (P < 0.001) but rebounded by the third survey (45.8%; P = 0.591). Being a carrier at the first survey was a risk factor for being a carrier at the second (odds ratio: 3.71; P < 0.001). At the third survey, the prevalence of carriage was similar after one and three MDA rounds (50.3% versus 45.8%, respectively; P = 0.170), as was the prevalence of azithromycin resistance (0.3% versus 0.9%, respectively; P = 0.340). CONCLUSION: Three azithromycin MDA rounds did not increase the prevalence of nasopharyngeal carriage of azithromycin-resistant S. pneumoniae strains compared with one round.
Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Nasofaringe/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Tracoma/tratamento farmacológico , Portador Sadio , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana , Feminino , Gâmbia/epidemiologia , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Vacinas Pneumocócicas/administração & dosagem , Prevalência , Fatores de Risco , População Rural , Tracoma/epidemiologiaRESUMO
OBJECTIVE: To establish haematological and biological reference values for Gambian infants. METHODS: Basic haematological and biochemical indices were analysed in blood samples obtained from healthy infants from Sukuta in the Western Division of The Gambia. The 2.5 and the 97.5 centiles for these indices were estimated. RESULTS: Reference ranges for haematological and biochemical indices were determined. Haemoglobin, total white cell count (WBC) and platelet levels decreased with age (P < 0.001), whereas most of the white cell count subsets except monocytes did not vary with age. Potassium and alkaline phosphatase fell significantly with increasing age (P < 0.001; P < 0.001), whereas urea and creatinine rose with increasing age (P = 0.002; P < 0.001, respectively). CONCLUSION: Our set of haematological and biochemical reference values for healthy infants in The Gambia differs from values in other settings, thus underscoring the importance of establishing region-specific paediatric reference ranges to ensure optimal patient management and evaluate the impact of interventions in clinical research.
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População Negra , Desenvolvimento Infantil/fisiologia , Testes Hematológicos/normas , Distribuição por Idade , Fosfatase Alcalina/sangue , Estatura/fisiologia , Peso Corporal/fisiologia , Creatinina/sangue , Feminino , Gâmbia , Testes Hematológicos/métodos , Testes Hematológicos/estatística & dados numéricos , Hemoglobinas/análise , Humanos , Lactente , Modelos Lineares , Masculino , Desnutrição/sangue , Estado Nutricional/fisiologia , Potássio/sangue , Valores de Referência , Distribuição por Sexo , Estatística como Assunto , População Urbana/estatística & dados numéricos , Ureia/sangueRESUMO
BACKGROUND: Malaria is commonly associated with poverty. Macro-level estimates show strong links between malaria and poverty, and increasing evidence suggests that the causal link between malaria and poverty runs in both directions. However, micro-level (household and population) analyses on the linkages between malaria and poverty have often produced mixed results. METHODS: The Gambia Malaria Indicator Survey (MIS) 2010/11 was carried out between November 2010 and January 2011. Laboratory-confirmed malaria and wealth quintiles were used to assess the association of socio-economic status and malaria infection in children and the general population. Simple and multiple logistic regressions and survey data analysis procedures, including linearized standard errors to account for cluster sampling and unequal selection probabilities were applied. RESULTS: Children (six to 59 months) from the second, third, fourth and richest quintiles were significantly less likely to have malaria compared to children from the poorest quintiles. Children (five to 14 years) from the fourth and richest quintiles were also significantly less likely to have malaria compared to those from the poorest quintiles. The malaria burden has shifted from the under-five children (six to 59 months) to children aged five to 14 years. Malaria prevalence was significantly higher in the Central River Region compared to the Upper River Region; and males bear the malaria brunt more than females. Children (six to 59 months) and children (five to 14 years) living in houses with poor walls, floors, roofs and windows were significant associated with higher prevalence of malaria. However, in the general population, only poor wall housing materials were associated with higher prevalence of malaria. CONCLUSIONS: Investments in strategies that address socio-economic disparities and improvements in the quality of housing could, in the long term, significantly reduce the malaria burden in the poorest communities.
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Malária/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Gâmbia/epidemiologia , Habitação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Gravidez , Prevalência , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Awareness of various aspects of Diabetes Mellitus (DM) is essential for the prevention, management and control of the disease. However, several studies have consistently shown that awareness of DM in the general population is low. None of these studies, however, was conducted in The Gambia, even though the condition constitutes a major public health problem in the country. In this paper, we assessed the awareness of DM among diabetic patients attending the Medical Out-Patient Department (MOPD) of Royal Victoria Teaching Hospital (RVTH), Banjul. METHODS: We interviewed 200 patients attending the MOPD of RVTH. We used a tool containing questions on patient's demographic characteristics and awareness of various aspects of DM including general knowledge on DM, causes, complications, management and prevention. RESULTS: Of the 199 patients who were aware of their condition, only 47% said they knew what DM is. Similarly, 53% of the study participants had no knowledge of the causes of DM and about 50% were not aware of the methods of prevention. 67% knew that DM can result to loss of sight while 46.5% knew that DM can cause poor wound healing. Few respondents knew that DM can lead to kidney failure (13.5%), skin sepsis (12.0%), heart failure (5.5%) and stroke (4.5%). Close to 50% of the respondent did not know how DM can be prevented. Level of education, duration of illness and knowledge of a family member with diabetes were important predictors of knowledge in our study. CONCLUSION: Our study shows that the majority of patients attending the MOPD have poor knowledge on several aspects of DM. Hence, there is need for conscious efforts towards improving the level of awareness through health education and promotion, not limited to the hospital but also within the general population, as part of strategies to prevent, manage and control DM.
Assuntos
Diabetes Mellitus/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/epidemiologia , Feminino , Gâmbia/epidemiologia , Educação em Saúde , Promoção da Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
Early identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa.
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População Negra , Predisposição Genética para Doença , Humanos , Fatores de Risco , Medição de Risco , População Negra/genética , África , Estudo de Associação Genômica AmplaRESUMO
BACKGROUND: In 2007, Malawi replaced the first-line medication for uncomplicated malaria, sulfadoxine-pyrimethamine-a single-dose regimen-with artemether-lumefantrine (AL)-a 6-dose, 3-day regimen. Because of concerns about the complex dosing schedule, we assessed patient adherence to AL 2 years after routine implementation. METHODS: Adults and children with uncomplicated malaria were recruited at 3 health centers. We conducted both pill counts and in-home interviews on medication consumption 72 hours after patients received AL. Complete adherence was defined as correctly taking all 6 AL doses, as assessed by pill count and dose recall. We used logistic regression to identify factors associated with complete adherence. RESULTS: Of 386 patients, 65% were completely adherent. Patients were significantly more likely to be completely adherent if they received their first dose of AL as directly observed therapy at the health center (odds ratio [OR], 2.4; P < .01), received instructions using the medication package as a visual aid (OR, 2.5; P = .02), and preferred AL over other antimalarials (OR, 2.7; P < .001). In contrast, children <5 years of age were significantly less likely to be adherent (OR, 0.5; P = .05). CONCLUSIONS: Adherence to AL treatment for uncomplicated malaria was moderate, and children, who are the most likely to die of malaria, were less adherent than adults. Efforts to improve adherence should be focused on this vulnerable group. Interventions including the introduction of child-friendly antimalarial formulations, direct observation of the first dose, use of the AL package as a visual aid for instructions, and enhancing patient preference for AL could potentially increase AL adherence and overall effectiveness.
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Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Malária/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Plasmodium/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação Arteméter e Lumefantrina , Criança , Pré-Escolar , Estudos Transversais , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Lactente , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Pirimetamina/administração & dosagem , População Rural , Sulfadoxina/administração & dosagem , Adulto JovemRESUMO
Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.
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COVID-19/imunologia , Adulto , África Subsaariana/epidemiologia , Antibacterianos/administração & dosagem , Anticorpos/sangue , COVID-19/sangue , COVID-19/epidemiologia , Coinfecção/imunologia , Citocinas/sangue , Dexametasona/administração & dosagem , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/isolamento & purificação , Tratamento Farmacológico da COVID-19RESUMO
Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1) and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1) roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity differences. These findings support a set-point control mechanism rather than immaturity for explaining not only neonatal susceptibility but also resilience to infection. In summary, our findings show that neonatal HCMV infection leads to a highly plastic and functional robust programming of dendritic cells in vivo and in vitro. In comparison with adults, a minimal number of subtle quantitative and temporal differences may contribute to variability in host susceptibility and resilience, in a context dependent manner.
RESUMO
BACKGROUND: We conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage. METHODS: 636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected. RESULTS: Prevalence of pneumococcal nasopharyngeal carriage in the study subjects (median age 11 years) was 55.0%; this prevalence decreased linearly with increasing age (p = 0.001). Prevalence of carriage was significantly higher during the dry than the rainy season for any pneumococcal carriage [57.6% versus 47.8% (p<0.001)], pneumococcal vaccine serotype carriage [10.3% versus 6.5% (p< 0.001)] and non-vaccine serotype carriage [49.7% versus 42.7% (p<0.001)]. Differences remained significant in the adjusted analysis. CONCLUSIONS: In areas of Africa with marked variation in rainfall, seasonality of pneumococcal carriage needs to be considered when interpreting carriage data.
Assuntos
Portador Sadio , Nasofaringe/microbiologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Estações do Ano , Streptococcus pneumoniae/imunologia , Adolescente , Portador Sadio/epidemiologia , Criança , Pré-Escolar , Feminino , Gâmbia/epidemiologia , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Humanos , Estudos Longitudinais , Masculino , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , VacinaçãoRESUMO
OBJECTIVE: To measure mortality and its risk factors among children discharged from a health centre in rural Gambia. METHODS: We conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2-59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors. FINDINGS: One hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2-11 and 12-59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid-upper arm circumference (MUAC) of 11.5-13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5-11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non-medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality. CONCLUSION: Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children.
Assuntos
Mortalidade da Criança , Meningite/mortalidade , Pneumonia/mortalidade , Sepse/mortalidade , Criança , Transtornos da Nutrição Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Gâmbia , Hospitalização , Humanos , Lactente , Masculino , Meningite/fisiopatologia , Alta do Paciente , Pneumonia/fisiopatologia , População Rural , Sepse/fisiopatologiaRESUMO
BACKGROUND: Rotavirus is the leading cause of diarrhea in children <5 years of age. In light of the implementation of rotavirus vaccines of limited valency, it is important to characterize the genotypic diversity of circulating rotavirus in sub-Saharan Africa. METHODS: We collected stool samples from children 0-59 months of age who presented at the health centres as cases with moderate-to-severe diarrhea in the Upper River Region of The Gambia. Stool samples were also collected from age, sex and area-matched healthy controls. All stool samples were assayed for rotavirus antigens by enzyme-linked immunosorbent assay and genotyping was done using reverse transcriptase polymerase chain reaction. RESULTS: We enrolled 1029 cases and 1569 controls during the 3-year study period (2008-2010). The detection rate of rotavirus among the cases was 20% (204/1029) and 3% (42/1569) among controls. At least 18 genotypes were found and the predominant genotypes were G2P[6] (28%), G1P[8] (26%) and G1P[10] (10%). The rare identified genotypes (<1%) were G2P[14], G8P[6], G9P[6] and G4P[10]. There was also a strong positive association between rotavirus infection and the dry season (odds ratio: 9.83, 95% confidence interval: 6.18-15.63, P < 0.001). A significant increase in the odds of rotavirus and G1P[8] detection with the use of untreated water and the presence of cats, rodents and cows in the child's residence was also found. CONCLUSION: This study provides important baseline data for the genotypes circulating before vaccine implementation. The wide diversity of genotypes circulating in The Gambia implies the need for vigilant effectiveness surveillance following the implementation of RotaTeq in August 2013.
Assuntos
Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Pré-Escolar , Diarreia/epidemiologia , Diarreia/microbiologia , Diarreia/virologia , Fezes/virologia , Feminino , Gâmbia/epidemiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores SocioeconômicosRESUMO
Little is known about the impact of indoor residual spraying (IRS) in areas with intense malaria transmission such as sub-Saharan Africa. In Malawi, IRS with lambda-cyhalothrin has been applied annually in an area of intense year-long transmission since 2007. We evaluated the impact of IRS on parasitemia and anemia prevalence in children less than five years of age by using a cross-sectional household survey conducted in 2009, six months after the second IRS spray round. We measured malaria parasitemia and anemia (hemoglobin level < 11 g/dL) in 899 children less than five years of age and used binomial regression to assess the impact of IRS by comparing children living in a household sprayed with IRS (direct IRS) with those in a household not sprayed with IRS, but in an IRS area (indirect IRS) and those living in a household not sprayed with IRS and not in an IRS area (no IRS). In the IRS area, 77% of households reported receiving IRS. Adjusting for bed net use, house construction, and socioeconomic status, we found that receiving direct IRS and indirect IRS were significantly associated with a 33% (95% confidence interval [CI] = 1-54%) and 46% (95% CI = 20-64%) reduction in parasitemia and a 21% (95% CI = 4-34%) and 30% (95% CI = 12-45%) reduction in anemia prevalence, respectively.
Assuntos
Anemia/epidemiologia , Inseticidas/farmacologia , Malária/epidemiologia , Nitrilas/farmacologia , Parasitemia/epidemiologia , Piretrinas/farmacologia , Anemia/prevenção & controle , Pré-Escolar , Estudos Transversais , Características da Família , Humanos , Malária/transmissão , Malaui/epidemiologia , Controle de Mosquitos/métodos , Parasitemia/prevenção & controle , Parasitemia/transmissão , PrevalênciaRESUMO
BACKGROUND: High levels of insecticide treated bednet (ITN) use reduce malaria burden in countries with intense transmission such as Malawi. Since 2007 Malawi has implemented free health facility-based ITN distribution for pregnant women and children <5 years old (under-5s). We evaluated the progress of this targeted approach toward achieving universal ITN coverage. METHODS: We conducted a cross-sectional household survey in eight districts in April 2009. We assessed household ITN possession, ITN use by all household members, and P. falciparum asexual parasitemia and anemia (hemoglobin <11 grams/deciliter) in under-5s. RESULTS: We surveyed 7,407 households containing 29,806 persons. Fifty-nine percent of all households (95% confidence interval [95% CI]: 56-62), 67% (95% CI: 64-70) of eligible households (i.e., households with pregnant women or under-5s), and 40% (95% CI: 36-45) of ineligible households owned an ITN. In households with at least one ITN, 76% (95% CI: 74-78) of all household members, 88% (95% CI: 87-90) of under-5s and 90% (95% CI: 85-94) of pregnant women used an ITN the previous night. Of 6,677 ITNs, 92% (95% CI: 90-94) were used the previous night with a mean of 2.4 persons sleeping under each ITN. In multivariable models adjusting for district, socioeconomic status and indoor residual spraying use, ITN use by under-5s was associated with a significant reduction in asexual parasitemia (adjusted odds ratio (aOR) 0.79; 95% CI: 0.64-0.98; p-value 0.03) and anemia (aOR 0.79; 95% CI 0.62-0.99; p-value 0.04). Of potential targeted and non-targeted mass distribution strategies, a campaign distributing 1 ITN per household might increase coverage to 2.1 household members per ITN, and thus achieve near universal coverage often defined as 2 household members per ITN. CONCLUSIONS: Malawi has substantially increased ITN coverage using health facility-based distribution targeting pregnant women and under-5s, but needs to supplement these activities with non-targeted mass distribution campaigns to achieve universal coverage and maximum public health impact.