Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response.

Rationale: Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function.

Objectives: To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity.

Contribution of Xpert® MTB/RIF to the diagnosis of pulmonary tuberculosis among TB-exposed children in The Gambia.

Setting: Greater Banjul Area, The Gambia.

Objective: To conduct a pragmatic evaluation of the Xpert(®) MTB/RIF assay in the diagnosis of tuberculosis (TB) among child contacts.

Design: In this prospective study, one induced sputum sample was obtained from TB contacts aged <15 years and tested using fluorescent microscopy, culture and Xpert.

A multimedia consent tool for research participants in the Gambia: a randomized controlled trial.

Objective: To assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial in the Gambia.

Methods: Adults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants' comprehension of informed consent.

Neonatal admissions, quality of care and outcome: 4 years of inpatient audit data from The Gambia's teaching hospital.

Background: National facility-based neonatal mortality audits are an important source of data to identify areas for improvement of service delivery and outcome of care.

Objectives: To examine admissions to the neonatal unit, Edward Francis Small Teaching Hospital, Banjul, The Gambia and make recommendations for programme action to reduce mortality through improvements in the quality of care, particularly with respect to suspected neonatal infections.

Methods: Case notes were reviewed for all neonates admitted to the neonatal unit during a 5-year period (1 January 2009 to 31 December 2013) to assess outcome and quality of care.

Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy.

Factors influencing innate immunity and vaccine responses in infancy.

Despite significant progress in reducing the burden of mortality in children under the age of five, reducing mortality in newborns remains a major challenge. Infection plays a significant role in infant deaths and interventions such as early vaccination or antenatal immunization could make a significant contribution to prevention of such deaths. In the last few years, we have gained new insights into immune ontogeny and are now beginning to understand the impact of vaccines, nutrition and environmental factors on 'training' of the immune response in early life.

Biological challenges to effective vaccines in the developing world.

The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy.

Dysregulation of Apoptosis Is a Risk Factor for Tuberculosis Disease Progression.

Background: A major barrier to effective tuberculosis control is our limited understanding of risk factors for tuberculosis disease progression. This study examined the role of apoptosis in immunity to tuberculosis.

Methods: Cell subsets from tuberculosis cases and tuberculin skin test-positive (TST(+)) and TST-negative (TST(-)) household contacts (HHCs) were analyzed for expression of annexin-V and propidium iodide by flow cytometry.

Increased disease due to Haemophilus influenzae type b: population-based surveillance in eastern Gambia, 2008-2013.

Background: In 1997, The Gambia became the first African country to introduce conjugate Haemophilus influenzae type b (Hib) vaccine with good disease control through to 2010.

Methods: Culture-based surveillance for invasive bacterial disease in eastern Gambia, specifically the Basse Health and Demographic Surveillance System (BHDSS) area, was conducted from 12 May 2008 and in Fuladu West district from 12 September 2011 until 31 December 2013. In 2011, Hib serology was measured in 5-34-year-olds.

Ebola: a holistic approach is required to achieve effective management and control.

The current Ebola outbreak in West Africa has already caused substantial mortality and dire human and economic consequences. It continues to represent an alarming public health threat in the region and beyond and jeopardizes the provision of health care and other services in the affected countries. The scale of the epidemic has accelerated research efforts for diagnostics, treatment, and prevention galvanized through increased availability of funding.

Non-tuberculous mycobacteria in children: muddying the waters of tuberculosis diagnosis.

Non-tuberculous mycobacteria (NTM) are a large family of acid-fast bacteria, widespread in the environment. In children, NTM cause lymphadenitis, skin and soft tissue infections, and occasionally also lung disease and disseminated infections. These manifestations can be indistinguishable from tuberculosis on the basis of clinical and radiological findings and tuberculin skin testing.

Seroprevalence of pertussis in the Gambia: evidence for continued circulation of bordetella pertussis despite high vaccination rates.

Background: Bordetella pertussis can cause severe respiratory disease and death in children. In recent years, large outbreaks have occurred in high-income countries; however, little is known about pertussis incidence in sub-Saharan Africa.

Methods: We evaluated antibody responses to pertussis toxin (Ptx) from individuals aged between 2 and 90 years in rural Gambia.

The influence of paediatric HIV infection on circulating B cell subsets and CXCR5(+) T helper cells.

Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART.

The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study.

Background: There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx.

Methods: A cohort of children from rural Gambia was recruited at birth and followed up for one year.

Anti-group B Streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection.

Background: HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS.

Methods: We quantified antibodies that bind to the surface of whole Group B Streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants.

The impact of HIV exposure and maternal Mycobacterium tuberculosis infection on infant immune responses to bacille Calmette-Guérin vaccination.

Objective: The objective of this study is to assess the effect of maternal HIV and Mycobacterium tuberculosis (Mtb) infection on cellular responses to bacille Calmette-Guérin (BCG) immunization.

Design: A mother-infant cohort study.

Methods: Samples were collected from mother-infant pairs at delivery.

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M.

Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection.

Background: Children with perinatally acquired HIV (paHIV) remain at an increased risk of pneumococcal infection despite highly active antiretroviral therapy (HAART). Beyond infancy, responses to pneumococcal conjugate vaccine (PCV) remain under-investigated. There are currently no published data on serological response to 13-valent PCV (PCV13) in the HIV-infected populations.

Management of paediatric tuberculosis in leading UK centres: unveiling consensus and discrepancies.

Setting: Large specialist paediatric TB clinics in the UK.

Objective: To evaluate clinical practice and compare with national and international guidelines.

Design: A survey based on an electronic questionnaire on the management of latent tuberculous infection (LTBI) and tuberculosis (TB) disease was conducted in 13 specialist paediatric TB clinics.

Modeling the impact of novel diagnostic tests on pediatric and extrapulmonary tuberculosis.

Background: Extrapulmonary tuberculosis (EPTB) and most pediatric TB cannot be diagnosed using sputum-based assays. The epidemiological impact of different strategies to diagnose EPTB and pediatric TB is unclear.

Methods: We developed a dynamic epidemic model of TB in a hypothetical population with epidemiological characteristics similar to India.

Antibodies against Haemophilus influenzae type b in The Gambia: investigating the extent of protection across age groups.

Following a landmark clinical trial, the vaccine against Haemophilus influenzae type b (Hib) was introduced in The Gambia in 1997. Whilst the immunogenicity of this vaccine is well established subsequent to the doses administered under the EPI schedule, little data exists assessing longevity of protection, using serology. Such data are needed however to predict the susceptibility to Hib at the population level.

Availability and use of molecular microbiological and immunological tests for the diagnosis of tuberculosis in europe.

Introduction: Currently only limited data exist regarding the availability and clinical use of molecular and immunological tests for tuberculosis (TB) in the European setting.

Methods: Web-based survey of Paediatric-Tuberculosis-Network-European-Trialsgroup (ptbnet) and Tuberculosis-Network-European-Trialsgroup (TBnet) members conducted June to December 2013. Both networks comprise clinicians, microbiologists, epidemiologists and researchers predominately based in Europe.