The Tuberculin Skin Test (TST) Is Affected by Recent BCG Vaccination but Not by Exposure to Non-Tuberculosis Mycobacteria (NTM) during Early Life

The tuberculin skin test (TST) is widely used in TB clinics to aid Mycobacterium tuberculosis (M.tb) diagnosis, but the definition and the significance of a positive test in very young children is still unclear. This study compared the TST in Gambian children at 4½ months of age who either received BCG vaccination at birth (Group 1) or were BCG naïve (Group 2) in order to examine the role of BCG vaccination and/or exposure to environmental mycobacteria in TST reactivity at this age. Nearly half of the BCG vaccinated children had a positive TST (≥5 mm) whereas all the BCG naïve children were non-reactive, confirming that recent BCG vaccination affects TST reactivity. The BCG naïve children demonstrated in vitro PPD responses in peripheral blood in the absence of TST reactivity, supporting exposure to and priming by environmental mycobacterial antigens. Group 2 were then vaccinated at 4½ months of age and a repeat TST was performed at 20–28 months of age. Positive reactivity (≥5 mm) was evident in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that the timing of BCG vaccination had little effect by this age. We further assessed for immune correlates in peripheral blood at 4½ months of age. Mycobacterial specific IFNγ responses were greater in TST responders than in non-responders, although the size of induration did not correlate with IFNγ. However the IFNγ: IL-10 ratio positively correlated with TST induration suggesting that the relationship between PPD induced IFNγ and IL-10 in the peripheral blood may be important in controlling TST reactivity. Collectively these data provide further insights into how the TST is regulated in early life, and how a positive response might be interpreted

Maintenance of Large Subpopulations of Differentiated CD8 T-Cells Two Years after Cytomegalovirus Infection in Gambian Infants

BACKGROUND: In a previously published study, we found that large differentiated subpopulations of CD8 T-cells emerged rapidly after CMV infection in young infants and persisted throughout the following year. Here we describe a follow-up study conducted on the same infants to establish whether the differentiated subpopulations continued through the second year post-infection. METHODOLOGY / PRINCIPAL FINDINGS: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population. The large subpopulation of differentiated cytotoxic (CD28(-)CD62L(-)Bcl-2(low)CD95(+)perforin(+)) cells that emerged rapidly after infection remained stable after two years. No similar subpopulation was found in CMV-uninfected infants indicating that two years after infection, CMV remained a major factor in driving CD8 T-cell differentiation. Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly. The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially. CONCLUSIONS / SIGNIFICANCE: The large differentiated subpopulations of CD8 T-cells that had emerged immediately after CMV infection persisted through the second year post-infection, while levels of activation and functional capacity remained fairly constant.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants

The global burden of neonatal and infant mortality due to infection is staggering, particularly in resource-poor settings. Early childhood vaccination is one of the major interventions that can reduce this burden, but there are specific limitations to inducing effective immunity in early life, including impaired neonatal leukocyte production of Th1-polarizing cytokines to many stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate immune responses in infants may shed light on susceptibility to infection in this vulnerable age group, and provide insights into TLR agonists as candidate adjuvants for improved neonatal vaccines. As little is known about the leukocyte responses of infants in resource-poor settings, we characterized production of Th1-, Th2-, and anti-inflammatory- cytokines in response to agonists of TLRs 1-9 in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12 months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5, and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that also uniquely induced cord blood IFNγ production. For most agonists, TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of age. TLR8 agonists also induced the greatest production of the Th1-polarizing cytokines TNFα and IFNγ throughout the first year of life, although the relative responses to the single TLR8 agonist and the combined TLR7/8 agonist changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most agonists were robust at birth and remained stable through 12 months of age. These observations provide fresh insights into the ontogeny of innate immunity in African children, and may inform development of age-specific adjuvanted vaccine formulations important for global health

Placental Malaria is associated with reduced early life weight development of affected children independent of low birth weight

<p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium falciparum </it>during pregnancy contributes substantially to the disease burden in both mothers and offspring. Placental malaria may lead to intrauterine growth restriction or preterm delivery resulting in low birth weight (LBW), which, in general, is associated with increased infant morbidity and mortality. However, little is known about the possible direct impact of the specific disease processes occurring in PM on longer term outcomes such as subsequent retarded growth development independent of LBW.</p> <p>Methods</p> <p>In an existing West-African cohort, 783 healthy infants with a birth weight of at least 2,000 g were followed up during their first year of life. The aim of the study was to investigate if <it>Plasmodium falciparum </it>infection of the placenta, assessed by placental histology, has an impact on several anthropometric parameters, measured at birth and after three, six and 12 months using generalized estimating equations models adjusting for moderate low birth weight.</p> <p>Results</p> <p>Independent of LBW, first to third born infants who were exposed to either past, chronic or acute placental malaria during pregnancy had significantly lower weight-for-age (-0.43, 95% CI: -0.80;-0.07), weight-for-length (-0.47, 95% CI: -0.84; -0.10) and BMI-for-age z-scores (-0.57, 95% CI: -0.84; -0.10) compared to infants born to mothers who were not diagnosed with placental malaria (p = 0.019, 0.013, and 0.012, respectively). Interestingly, the longitudinal data on histology-based diagnosis of PM also document a sharp decline of PM prevalence in the Sukuta cohort from 16.5% in 2002 to 5.4% in 2004.</p> <p>Conclusions</p> <p>It was demonstrated that PM has a negative impact on the infant's subsequent weight development that is independent of LBW, suggesting that the longer term effects of PM have been underestimated, even in areas where malaria transmission is declining.</p

Maternal and Child Health Services in Rural Settings of The Gambia: Contextual Determinants of Postnatal Care from Mothers’ Perspectives—A Community-Based Analytical Cross-Sectional Study

Background. Maternal and child health in The Gambia is a trending public health burden. The postnatal period is critical and vital to the lives and health of the maternal mothers and their newborns, and pieces of evidence deduced that a majority of maternal and newborn deaths occur during this period. Hence, this research aimed to assess the prevalence and determinants of postnatal care utilization across women in rural Gambia. Methods. A community-based cross-sectional design was conducted in January 2020, with 265 women of childbearing age were recruited from the selected households in rural communities across the Upper River Region (URR), Gambia, using multistage sampling technique. A structured-interview questionnaire was developed to elicit contextual sociodemographic characteristics regarding the use of postnatal care. Percentages, chi-square/Fisher’s exact test for variables with p value ≤0.15 were considered for inclusion into the logistic regression model. The significance level was set at p<0.05. The adjusted odds ratios (aOR) with 95% confidence interval (CI) were computed to declare significance. Results. The study revealed that 90% of women utilize postnatal care (PNC) services in the rural settings of URR, Gambia. Factors such as women’s occupation, location, number of pregnancies, attending in last pregnancy, current uptake of family planning, and complication(s) in last labor were found to be associated with PNC utilization. Women who attended antenatal care (ANC) services in their last pregnancy were 10.8 times (aOR = 10.795, 95% CI: 1.025–113.694), current users of FP were 10.7 times (aOR = 10.708, 95% CI: 1.379–83.152), women’s number of pregnancies increases by a factor of 4.6 times (aOR = 4.649, 95% CI: 1.518–14.243) more likely to utilize PNC while women’s number of children alive were less likely by 76.1% (aOR = 0.239, 95% CI: 0.071–0.810) as compared to those who were not utilizing PNC services. Conclusion. The findings showed that attending ANC services, current uptake of FP, women’s number of pregnancies, and number of children alive were associated with PNC. Strengthening women empowerment and designing responsive ANC programs especially for rural women to improve PNC services are required

Exploring rural households’ knowledge and perception of acute kidney injury in the southern region of The Gambia: a mixed-method community-based cross-sectional study design

Background The Acute Kidney Injury (AKI) outbreak in The Gambia is a national tragedy attracting international concern, linked to nearly 100 deaths in children. This situation arose due to the use of contaminated medical products by children in the country.Method We used a mixed-method, cross-sectional study design to assess households’ knowledge and perceptions of AKI in the southern region of The Gambia. A total of 2174 respondents from 123 rural communities were recruited via multistage sampling and were interviewed face-to-face using a questionnaire. Qualitatively, focus group discussions and key informant interviews were conducted. The collected data were analysed as categorical and continuous variables, and thematic areas using SPSS V.26 and NVivo software.Results The mean age was 36 years (SD±14.17) and 70% of the respondents were women. Most respondents had no formal education (45.6%), lived in extended family households (55%) and 91.6% earned a monthly income of less than GMD5000 (Gambian dalasi) (&lt;US$100). Although 80% of the respondents were aware of the AKI outbreak in The Gambia, 90% showed poor knowledge about the disease. Half of the respondents correctly identified contaminated medical products as the cause of AKI. Interestingly, 97.1% of the participants held a moderate perception of AKI in The Gambia and firmly rejected the notion that the outbreak was politically motivated. The AKI outbreak was viewed as a stern lesson and a wake-up call for the Ministry of Health to take the necessary actions.Conclusion A significant deficiency in AKI knowledge exists among rural households, even though their perceptions of health services remain positive and unwavering. AKI is viewed as a widespread health concern rather than a political issue. To maintain this view and enhance trust, a national dialogue involving the Ministry of Health and the population is recommended

Knowledge, Attitude, and Practice of Provincial Dwellers on Prevention and Control of Schistosomiasis: Evidence from a Community-Based Cross-Sectional Study in the Gambia

Background. Socioeconomically disadvantaged and neglected communities were found to be the most affected groups for schistosomiasis as a result of inadequate safe water and sanitation facilities. In order to inform policies and practices, the present study examined the influence of sociodemographic factors and attitudes on the knowledge and practice in the prevention and control of schistosomiasis in eighteen endemic rural communities in the Gambia. Methods. In January 2019, a community-based cross-sectional study was conducted in which 383 household heads in rural communities across Kuntaur and Janjanbureh Local Government Areas (LGAs) in Central River Region were recruited. A structured interview questionnaire was developed to elicit information regarding residents’ knowledge, attitude, and practice on schistosomiasis prevention and control measures. Percentages, chi-square test, and binary and multiple logistic regression models were used to identify sociodemographic factors associated with the KAP variables. The significance level was set at p<0.05. Results. Among the 383 participants, only 14.9% had good knowledge, while 54.3% had poor knowledge, 96.9% had positive attitude, and 57.7% had good practice towards prevention and control of schistosomiasis. Older age (≥40 years), compared with residents aged 30–39 years (AOR = 0.331; 95% CI: 0.133, 0.825); ever heard of bilharziasis (AOR = 11.911; 95% CI: 3.452, 41.099); and risks of contact with the polluted river (AOR = 0.101; 95% CI: 0.042, 0.242) were more likely to have good knowledge on schistosomiasis prevention and control in the rural Gambia. Conversely, young people (≤30 years), compared with residents aged ≥40 years (AOR = 2.503; 95% CI = 1.539, 4.071); residents aged 30–39 years (AOR = 2.880; 95% CI = 1.559, 5.320); and male residents (AOR = 2.631; 95% CI = 1.703, 4.067) were more likely to have good practice towards schistosomiasis prevention and control in the rural Gambia. Conclusion. Despite the low knowledge, rural dwellers’ attitudes were found to be positive with slightly good practice towards schistosomiasis prevention and control measures. Thus, while maintaining health system improvement strategies, disease control efforts should focus on these factors as they may influence the knowledge and practices of rural dwellers in a given setting. The findings could prompt appropriate policy responses towards improving the knowledge and practices on schistosomiasis prevention and control in the Gambia

Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

Abstract Background Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge. Methods We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry. We measured the length, weight and head circumference at birth and 12 months. Results IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates. At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants. Conclusions Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.</p