Infections In Early Life Research Articles

Maternal COVID-19 during pregnancy results in altered immune status at birth and increases the risk for early life infections

Maternal COVID-19 during pregnancy results in altered immune status at birth and increases the risk for early life infections

Pregnancy-induced transfer of pathogen-specific Tcells from mother to fetus in mice.

Neonatal health is determined by the transfer of maternal antibodies from the mother to the fetus. Besides antibodies, maternal cells cross the placental barrier and seed into fetal organs. Contrary to maternal antibodies, maternal microchimeric cells (MMc) show a high longevity, as they can persist in the offspring until adulthood. Recent evidence highlights that MMc leukocytes promote neonatal immunity against early-life infections in mice and humans. As shown in mice, this promotion of immunity was attributable to an improved fetal immune development. Besides this indirect effect, MMc may be pathogen-specific and thus, directly clear pathogen threats in the offspring postnatally. By using ovalbumin recombinant Listeria monocytogenes (LmOVA), we here provide evidence that OVA-specific T cells are transferred from the mother to the fetus, which is associated with increased activation of T cells and a milder course of postnatal infection in the offspring. Our data highlight that maternally-derived passive immunity of the neonate is not limited to antibodies, as MMc have the potential to transfer immune memory between generations.

Early-life respiratory infections and developmental immunity determine lifelong lung health.

Respiratory infections are common in infants and young children. However, the immune system develops and matures as the child grows, thus the effects of infection during this time of dynamic change may have long-term consequences. The infant immune system develops in conjunction with the seeding of the microbiome at the respiratory mucosal surface, at a time that the lungs themselves are maturing. We are now recognizing that any disturbance of this developmental trajectory can have implications for lifelong lung health. Here, we outline our current understanding of the molecular mechanisms underlying relationships between immune and structural cells in the lung with the local microorganisms. We highlight the importance of gaining greater clarity as to what constitutes a healthy respiratory ecosystem and how environmental exposures influencing this network will aid efforts to mitigate harmful effects and restore lung immune health.

Clinical predictors of wheeze trajectories and associations with allergy in Asian children

BackgroundChildhood wheezing is a highly heterogeneous condition with an incomplete understanding of the characteristics of wheeze trajectories, particularly for persistent wheeze. ObjectiveTo characterize predictors and allergic comorbidities of distinct wheeze trajectories in a multiethnic Asian cohort. MethodsA total of 974 mother-child pairs from the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were included in this study. Wheeze and allergic comorbidities in the first 8 years of life were assessed using the modified International Study of Asthma and Allergies in Childhood questionnaires and skin prick tests. Group-based trajectory modeling was used to derive wheeze trajectories and regression was used to assess associations with predictive risk factors and allergic comorbidities. ResultsThere were 4 wheeze trajectories derived, including the following: (1) early-onset with rapid remission from age 3 years (4.5%); (2) late-onset peaking at age 3 years and rapidly remitting from 4 years (8.1%); (3) persistent with a steady increase to age 5 years and high wheeze occurrence until 8 years (4.0%); and (4) no or low wheeze (83.4%). Early-onset wheezing was associated with respiratory infections during infancy and linked to subsequent nonallergic rhinitis throughout childhood. Late-onset and persistent wheeze shared similar origins characterized by parent-reported viral infections in later childhood. However, persistent wheezing was generally more strongly associated with a family history of allergy, parent-reported viral infections in later childhood, and allergic comorbidities as compared with late-onset wheezing. ConclusionThe timing of viral infection occurrence may determine the type of wheeze trajectory development in children. Children with a family history of allergy and viral infections in early life may be predisposed to persistent wheeze development and the associated comorbidities of early allergic sensitization and eczema.

Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes

This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon respiratory syncytial virus (RSV) infection of 7-day-old mice, a significantly altered phenotype of BMDC at 4 weeks post-infection is observed in a sex-dependent manner. The alterations include heightened Ifnb/ interleukin (Il12a) and enhanced IFNAR1+ expression in BMDC from early-life RSV-infected female mice that leads to increased IFN-γ production by T cells. Phenotypic differences were verified upon pulmonary sensitization whereby EL-RSV male-derived BMDC promoted enhanced T helper 2/17 responses and exacerbated disease upon RSV infection while EL-RSV/F BMDC sensitization was relatively protective. Assay for transposase-accessible chromatin using sequencing analysis (ATAC-seq) demonstrated that EL-RSV/F BMDC had enhanced chromatin accessibility near type-I immune genes with JUN, STAT1/2, and IRF1/8 transcription factors predicted to have binding sites in accessible regions. Importantly, ATAC-seq of human cord blood-derived monocytes displayed a similar sex-associated chromatin landscape with female-derived monocytes having more accessibility in type-I immune genes. These studies enhance our understanding of sex-associated differences in innate immunity by epigenetically controlled transcriptional programs amplified by early-life infection in females via type-I immunity.

Investigating the role of relationship satisfaction and paternal psychological distress during pregnancy on offspring health in early life.

The research on the role of father in the foetal programming of health and behaviour has received increasing attention. However, the influences of paternal depressive symptoms and couple relationship satisfaction during pregnancy - potentially mediated via maternal well-being - on the offspring's risk of infections in early life is still seldom assessed. The aim was to investigate if paternal psychological distress during pregnancy is associated with elevated risk of recurrent respiratory infections (RRIs) for offspring at 12 months of age, and whether maternal distress mediates the association between paternal distress and offspring RRIs. The study population was drawn from the nested case-control cohort of the FinnBrain Birth Cohort Study. Children with RRIs (n = 50) were identified by maternal reports at the age of 12 months, whereas mothers did not report RRIs for the comparison group (n = 716). Parental depressive symptoms were measured with the Edinburgh Postnatal Depression Scale and couple relationship satisfaction was measured with the Revised Dyadic Adjustment Scale. The association between paternal depressive symptoms during pregnancy and offspring RRIs was mediated by maternal prenatal depressive symptoms. Additionally, paternal poorer relationship satisfaction was associated with child RRIs independently of maternal distress. The results suggest different pathways through which paternal distress during pregnancy may contribute to elevated risk of offspring RRIs, and more research is needed to study their underlying mechanisms. Paternal distress and couple relationship satisfaction during pregnancy should be assessed and screened as a contributor to offspring health.

Infection, nutritional status, and body composition: Associations at birth and 6 months postnatally in Soweto, South Africa.

The impact of infection on infant nutritional status, body size, and growth is well documented. However, research into the impact of infection on infant body composition is limited. Greater understanding is, therefore, needed on the effects of infection in early life. Associations between a composite morbidity index consisting of the sum of the cumulative tallies for a range of symptoms representing infection and morbidity in the infants and nutritional status (height-for-age (HAZ), and weight-for-height (WHZ)), and body composition (fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI)) at 6 months of age were investigated using hierarchical regression analysis. The sample comprised data between birth and 6 months postnatally, of 156 infants who were a priori born healthy in Soweto, South Africa. Morbidity, over the cumulative period of birth to 6 months, was associated with lower FMI (β = -1.77) and lower FM (β = -0.61), and conversely with higher FFM (β = 0.94), in infants at 6 months. No associations were found between the morbidity index and FFMI, HAZ, and WHZ. Increased birthweight was associated with a higher FFM (β = 0.66), HAZ (β = 1.14), and WHZ (β = 0.87). Finally, safely managed sanitation facilities, representative of reduced environmental exposure to fecal-oral transmission pathways were associated with a higher HAZ (β = 1.21). Reduction in FMI and FM and exposure to inflammatory cytokines associated with mounting an immune response could alter phenotypic trajectories during to this period of plasticity. From a public health perspective, these results imply that it is important to intensify efforts to prevent infection in infants in the first 6 months postnatally, and that these efforts should concentrate on access to safely managed sanitation facilities.

Micro-CT Features of Lung Consolidation, Collagen Deposition and Inflammation in Experimental RSV Infection Are Aggravated in the Absence of Nrf2.

Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV triggers the production of reactive oxygen species (ROS), which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an important redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2-deficient BALB/c mice (Nrf2-/-; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild-type Nrf2+/+ competent mice (WT). These events that occur at very early time points lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes in the lung architecture, mice were scanned weekly via high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV-infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. The results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury, not only in the acute pathogenesis of RSV infection but also in the long-term consequences of chronic airway injury.

Age-associated features of norovirus infection analysed in mice.

Norovirus (NoV) is the leading global cause of viral gastroenteritis. Young children bear the highest burden of disease and play a key role in viral transmission throughout the population. However, which host factors contribute to age-associated variability in NoV severity and shedding are not well-defined. The murine NoV (MNoV) strain CR6 causes persistent infection in adult mice and targets intestinal tuft cells. Here we find that natural transmission of CR6 from infected dams occurred only in juvenile mice. Direct oral CR6 inoculation of wild-type neonatal mice led to accumulation of viral RNA in the ileum and prolonged shedding in the stool that was replication-independent. This viral exposure induced both innate and adaptive immune responses including interferon-stimulated gene expression and MNoV-specific antibody responses. Interestingly, viral uptake depended on passive ileal absorption of luminal virus, a process blocked by cortisone acetate administration, which prevented ileal viral RNA accumulation. Neonates lacking interferon signalling in haematopoietic cells were susceptible to productive infection, viral dissemination and lethality, which depended on the canonical MNoV receptor CD300LF. Together, our findings reveal developmentally associated aspects of persistent MNoV infection, including distinct tissue and cellular tropism, mechanisms of interferon regulation and severity of infection in the absence of interferon signalling. These emphasize the importance of defining viral pathogenesis phenotypes across the developmental spectrum and highlight passive viral uptake as an important contributor to enteric infections in early life.

Adverse birth outcomes and early-life infections after in utero exposure to corticosteroids for inflammatory bowel disease: a Danish nationwide cohort study

BackgroundSystemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring.MethodsWe used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment.ResultsAfter in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82–2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91–3.13), 1.21 (95% CI: 0.76–1.90), and 0.91 (95% CI: 0.33–2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94–1.39).ConclusionsThis nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased.

Changes in the Global Epidemiology of Type 1 Diabetes in an Evolving Landscape of Environmental Factors: Causes, Challenges, and Opportunities.

The worldwide incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades. The reasons behind this phenomenon are not yet fully understood. Early life infections, prenatal and perinatal factors, and diet composition have been associated with the triggering of autoimmunity and the risk of presentation of T1DM. However, the rapid increase in new cases of the disease raises the hypothesis that lifestyle factors, which have traditionally been associated with type 2 diabetes, such as obesity and unhealthy eating patterns could also play a role in the genesis of autoimmune diabetes. This article aims to highlight the changing epidemiology of T1DM and the importance of properly recognizing the environmental factors behind it, as well as the connections with the pathogenesis of the disorder and the need to prevent or delay T1DM and its long-term complications.

Antibody Immunity to Zika Virus among Young Children in a Flavivirus-Endemic Area in Nicaragua.

Objective: To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas. Methods: We performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied. Results: Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6-9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection. Conclusions: These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings.

An Intersectional Approach to Hepatitis B

Hepatitis B is a chronic condition, primarily associated with hepatitis B viral infection in early life. The failure of prevention and appropriate management can lead to subsequent liver cirrhosis and cancer. Hepatitis B most commonly affects people born in Asia and Sub-Saharan Africa and their global diasporas. The physical, psychological, and social impacts of hepatitis B are strongly influenced by sex and gender. Inequities in access to timely, sensitive diagnosis and effective management arise from interactions between structural inequalities related to race, ethnicity, Indigenous/settler status, class, and geography. The biomedical response to hepatitis B has led to advances in prevention, diagnosis, and treatment, but many affected communities have explanatory health belief models that differ from that of biomedicine. We argue that an intersectional approach, led by affected people and communities, can integrate biomedicine with the lived experience and social context that give purpose to and shape all personal, communal, clinical, and public health responses to hepatitis B. This approach has the potential to enable a consciously equitable, effective response to the biopsychosocial complexities of hepatitis B, improve the health and wellbeing of people living with hepatitis B, and reduce hepatitis B-associated mortality.

The myxozoan parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) infection dynamics and host specificity in hybrid tilapia aquaculture.

Nile × blue tilapia hybrid (Oreochromis niloticus × O. aureus) has become an important food fish in intensive freshwater aquaculture. Recently, the parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) was found to infect hybrid tilapia gills at high prevalence, causing immune suppression and high mortality. Here, we explored additional characteristics of M. bejeranoi–tilapia interaction, which enable efficient proliferation of this parasite inside its specific host. Highly sensitive quantitative polymerase chain reaction (qPCR) and in situ hybridization analyses of fry collected from fertilization ponds provided evidence to an early-life infection of fish by a myxozoan parasite, occurring less than 3 weeks post-fertilization. Because Myxobolus species are highly host-specific, we next compared infection rates in hybrid tilapia and in both its parental species following a 1-week exposure to infectious pond water. Analysis by qPCR and histological sections showed that while blue tilapia was as susceptible to M. bejeranoi as the hybrid, Nile tilapia appeared to be resistant. This is the first report of differential susceptibility of a hybrid fish vs its parental purebreds to a myxozoan parasite. These findings advance our understanding of the relationship between M. bejeranoi and tilapia fish and raise important questions regarding the mechanisms that allow the parasite to distinguish between very closely related species and to infect a specific organ at very early-life stages.

Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life.

Pathological neovascularization in age-related macular degeneration (nvAMD) drives the principal cause of blindness in the elderly. While there is a robust genetic association between genes of innate immunity and AMD, genome-to-phenome relationships are low, suggesting a critical contribution of environmental triggers of disease. Possible insight comes from the observation that a past history of infection with pathogens such as Chlamydia pneumoniae, or other systemic inflammation, can predispose to nvAMD in later life. Using a mouse model of nvAMD with prior C. pneumoniae infection, endotoxin exposure, and genetic ablation of distinct immune cell populations, we demonstrated that peripheral infections elicited epigenetic reprogramming that led to a persistent memory state in retinal CX3CR1+ mononuclear phagocytes (MNPs). The immune imprinting persisted long after the initial inflammation had subsided and ultimately exacerbated choroidal neovascularization in a model of nvAMD. Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identified activating transcription factor 3 (ATF3) as a central mediator of retina-resident MNP reprogramming following peripheral inflammation. ATF3 polarized MNPs toward a reparative phenotype biased toward production of proangiogenic factors in response to subsequent injury. Therefore, a past history of bacterial endotoxin-induced inflammation can lead to immunological reprograming within CNS-resident MNPs and aggravate pathological angiogenesis in the aging retina.

Silent neonatal influenza A virus infection primes systemic antimicrobial immunity.

Infections with influenza A viruses (IAV) cause seasonal epidemics and global pandemics. The majority of these infections remain asymptomatic, especially among children below five years of age. Importantly, this is a time, when immunological imprinting takes place. Whether early-life infections with IAV affect the development of antimicrobial immunity is unknown. Using a preclinical mouse model, we demonstrate here that silent neonatal influenza infections have a remote beneficial impact on the later control of systemic juvenile-onset and adult-onset infections with an unrelated pathogen, Staphylococcus aureus, due to improved pathogen clearance and clinical resolution. Strategic vaccination with a live attenuated IAV vaccine elicited a similar protection phenotype. Mechanistically, the IAV priming effect primarily targets antimicrobial functions of the developing innate immune system including increased antimicrobial plasma activity and enhanced phagocyte functions and antigen-presenting properties at mucosal sites. Our results suggest a long-term benefit from an exposure to IAV during the neonatal phase, which might be exploited by strategic vaccination against influenza early in life to enforce the host's resistance to later bacterial infections.

Assessment of the role and mechanism of Bifidobacterium animalis subsp. lactis isolated from neonates' feces in protecting neonatal rats from Salmonella infection.

It is now well known that Bifidobacterium animalis subsp. lactis (B. lactis), an important early-life colonizer of the gut, provides immune-related benefits to infants. The aim of the work is to explore the intraspecific resistance to Salmonella infection of B. lactis isolated from neonatal feces, and to learn more insights into how B. lactis mediates beneficial roles in early-life infection resistance. Five strains of B. lactis (NFBAL11/NFBAL23/NFBAL44/NFBAL63/NFBAL92) were screened from fecal samples of neonates born within fifteen days and pretreated neonatal rats prior to infection with Salmonella typhimurium (S. typhimurium) SL1344. The survival rate, fecal occult blood, diarrhea and hepatosplenomegaly were detected to assess the ability of B. lactis to prevent S. typhimurium infection. Furthermore, the structure of mucus layer, gene expression, cytokine levels, antioxidant levels and intestinal microflora composition were detected to explore the mechanism. All strains showed activity against S. typhimurium, with B. lactis NFBAL23 being the most active, followed by NFBAL63 and NFBAL92. And these advantages weren't attained by enhancing physical growth and development. Mechanistically, the neonatal rats treated with B. lactis (NFBAL23/NFBAL63/NFBAL92) had improved intestinal barrier function involving physical, chemical, immune and biological barriers in the face of challenges posed by S. typhimurium. These findings revealed the intraspecific difference, beneficial roles and mechanisms of action of B. lactis against Salmonella infection early in life, which highlighted the necessity of supplementing appropriate B. lactis, and provided several potential B. lactis candidates for Salmonella infection treatment.

Synergistic effects of high early-life stress exposure and HIV infection on reaction time variability.

Addressing comorbidities contributing to cognitive impairment in people living with HIV (PLWH) remains imperative. Prior studies utilizing reaction time intra-individual variability (RT-IIV), a robust behavioral marker of cognitive dysfunction, demonstrate increased cognitive impairment in adults living with HIV who have high early life stress (ELS) exposure relative to those with low-ELS exposure. Yet, it is unknown whether RT-IIV elevations are due to high-ELS alone or both HIV-status and high-ELS. In the current study, we explore the potential additive effects of HIV and high-ELS exposure on RT-IIV to better characterize the independent and combined effects of these factors on RT-IIV among PLWH. We assessed 59 PLWH and 69 HIV-negative healthy control (HC) participants with either low or high ELS on RT-IIV during a working memory task (1-back). We observed a significant interaction between HIV status and ELS exposure on RT-IIV, PLWH who had experienced high ELS demonstrating RT-IIV elevations relative to all other groups. In addition, RT-IIV was significantly associated with ELS exposure in PLWH, but not in the HC group. We also observed associations between RT-IIV and measures of HIV-disease severity (plasma HIV viral load, nadir CD4) among PLWH. Taken as a whole, these findings provide novel evidence of the combined effects of HIV and high-ELS exposure on RT-IIV, and thus suggest HIV-related and ELS-related neural abnormalities may act in an additive or synergistic manner to affect cognition. Such data warrant further investigation into the neurobiological mechanisms associated with HIV and high-ELS exposure that contribute to increased neurocognitive dysfunction among PLWH.

The adaptive immune system in early life: The shift makes it count.

Respiratory infectious diseases encountered early in life may result in life-threatening disease in neonates, which is primarily explained by the relatively naive neonatal immune system. Whereas vaccines are not readily available for all infectious diseases, vaccinations have greatly reduced childhood mortality. However, repeated vaccinations are required to reach protective immunity in infants and not all vaccinations are effective at young age. Moreover, protective adaptive immunity elicited by vaccination wanes more rapidly at young age compared to adulthood. The infant adaptive immune system has previously been considered immature but this paradigm has changed during the past years. Recent evidence shows that the early life adaptive immune system is equipped with a strong innate-like effector function to eliminate acute pathogenic threats. These strong innate-like effector capacities are in turn kept in check by a tolerogenic counterpart of the adaptive system that may have evolved to maintain balance and to reduce collateral damage. In this review, we provide insight into these aspects of the early life's adaptive immune system by addressing recent literature. Moreover, we speculate that this shift from innate-like and tolerogenic adaptive immune features towards formation of immune memory may underlie different efficacy of infant vaccination in these different phases of immune development. Therefore, presence of innate-like and tolerogenic features of the adaptive immune system may be used as a biomarker to improve vaccination strategies against respiratory and other infections in early life.

Caregiver’s perspectives on the Central Nervous System infection illness trajectory among older persons with dementia in Northern Uganda—a qualitative community-based study

BackgroundFew studies have explored the Central Nervous System (CNS) infection illness trajectory among older persons with dementia in sub-Saharan African (SSA) settings. This study explored the Caregiver’s perspectives on the Central Nervous System infection illness trajectory among the older persons with dementia in Northern Uganda.MethodsThis was a qualitative study conducted in Lira District northern Uganda in March 2022 amongst purposively selected 20 caregivers of the older persons aged 50 + years with a positive history of CNS infection and later life dementia. Data were collected using an in-depth interview guide. Audio recordings and field notes of the interviews were undertaken. The interviews generated data on the CNS infection illness trajectory from onset to the current demented state of the older persons. The audio-recorded interviews were transcribed verbatim before manual reflective thematic analysis.ResultsOlder persons with a positive history of CNS infection illness and later life dementia in rural northern Uganda presented with symptoms of early life CNS infection illness ranging from neck pain, back pain, chronic headache, and fatigue. There were also manifestations of comorbidities particularly road traffic accidents involving traumatic injury to the head, neck, and spine, high blood pressure, chronic headache, and or their medications in the older person’s trajectory to later life dementia. A plurality of healthcare which included both formal and informal healthcare medicines was sought and utilized for the treatment and care of the CNS infection illness and dementia by the older persons amidst improper diagnosis and mismanagement.Conclusions and recommendationsOlder persons with early-life CNS infections illness and later-life dementia were reported to present with symptoms including neck pain, back pain, chronic headache, high blood pressure, and fatigue. The reported symptoms of CNS infection illness may be intertwined with co-morbidities particularly traumatic injury involving the head, neck, and spine, high blood pressure, and chronic headache. Healthcare professionals should integrate routine screening of older persons for the history of CNS infections, chronic headache, high blood pressure, trauma to the head, neck, and spine, and dementia and early treatment.