Establishing Ghanaian adult reference intervals for hematological parameters controlling for latent anemia and inflammation

CITATION: Bawua, A. et al. 2020. Establishing Ghanaian adult reference intervals for hematological parameters controlling for latent anemia and inflammation. International journal of laboratory hematology, 42(6):705–717. doi:10.1111/ijlh.13296The original publication is available at https://onlinelibrary.wiley.com/journal/1751553xBackground: In Ghana, diagnostic laboratories rely on reference intervals (RIs) provided by manufacturers of laboratory analyzers which may not be appropriate. This study aimed to establish RIs for hematological parameters in adult Ghanaian population. Methods: This cross-sectional study recruited 501 apparently healthy adults from two major urban areas in Ghana based on the protocol by IFCC Committee for Reference Intervals and Decision Limits. Whole blood was tested for complete blood count (CBC) by Sysmex XN-1000 analyzer, sera were tested for iron and ferritin by Beckman-Coulter/AU480, for transferrin, vitamin-B12, and folate was measured by Centaur-XP/Siemen. Partitioning of reference values by sex and age was guided by “effect size” of between-subgroup differences defined as standard deviation ratio (SDR) based on ANOVA. RIs were derived using parametric method with application of latent abnormal values exclusion method (LAVE), a multifaceted method of detecting subjects with abnormal results in related parameters. Results: Using SDR ≥ 0.4 as a threshold, RIs were partitioned by sex for platelet, erythrocyte parameters except mean corpuscular constants, and iron markers. Application of LAVE had prominent effect on RIs for majority of erythrocyte and iron parameters. Global comparison of Ghanaian RIs revealed lower-side shift of RIs for leukocyte and neutrophil counts, female hemoglobin and male platelet count, especially compared to non-African countries. Conclusion: The LAVE effect on many hematological RIs indicates the need for de-liberate secondary exclusion for proper derivation of RIs. Obvious differences in Ghanaian RIs compared to other countries underscore the importance of country-specific RIs for improved clinical decision-making.https://onlinelibrary.wiley.com/doi/10.1111/ijlh.13296Publishers versio

Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential

Autophagy is a conserved homeostatic process active in all human cells and affecting a spectrum of diseases. Here we use a pharmaceutical screen to discover new mechanisms for activation of autophagy. We identify a subset of pharmaceuticals inducing autophagic flux with effects in diverse cellular systems modelling specific stages of several human diseases such as HIV transmission and hyperphosphorylated tau accumulation in Alzheimer’s disease. One drug, flubendazole, is a potent inducer of autophagy initiation and flux by affecting acetylated and dynamic microtubules in a reciprocal way. Disruption of dynamic microtubules by flubendazole results in mTOR deactivation and dissociation from lysosomes leading to TFEB (transcription factor EB) nuclear translocation and activation of autophagy. By inducing microtubule acetylation, flubendazole activates JNK1 leading to Bcl-2 phosphorylation, causing release of Beclin1 from Bcl-2-Beclin1 complexes for autophagy induction, thus uncovering a new approach to inducing autophagic flux that may be applicable in disease treatment

Mycobacterial infection: Immune evasion, host susceptibility and immunological markers of diagnostic importance

IIn the first study, we investigated the functional implications of prolonged TLR signalling on IFN-γ mediated killing of mycobacteria by murine macrophages in vitro. TLR2, but not TLR4 ligation interfered with IFN-γ mediated killing of mycobacteria in macrophages. In terms of mechanisms, neither TNF nor nitric oxide (NO) production was significantly affected, and the refractoriness induced could be reversed with increasing amounts of IFN-γ In the second study, we aimed to identify immunological markers of diagnostic importance in both the respiratory tract and serum during pulmonary mycobacterial infection in mice. We found that increased levels of immunological markers in the respiratory tract, but not serum, correlated better with active mycobacterial infection in the lungs, suggesting that the immune response in the respiratory tract is more reflective of the infection status and pathology than the systemic response. Finally, we investigated the level and nature of immune responses to pulmonary mycobacterial infection in BALB/c and C57BL/6 mice, two mouse strains known to exhibit different susceptibilities to infection with several intracellular pathogens, including mycobacteria. We showed that increased susceptibility of BALB/c mice to early mycobacterial infection was associated with reduced Th1 immune responses, and increased sTNFR secretion in the lung. Moreover, BALB/c mice recruited fewer monocytes/macrophages to the lung, and although IFN-γ stimulation of infected bone marrow derived macrophages in both mouse strains resulted in induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The work presented in this thesis provide further insight into the mechanisms involved in the host-pathogen interaction; from persistence, to the immunological processes induced by the pathogen, to susceptibility of the host to infection

Intestinal parasitic infections and predisposing factors among prison inmates in Southern Ghana: A cross‐sectional study

Abstract Background and Aims The environment within prisons, such as overcrowding, lack of access to portable water, poor sanitation, and hygiene predisposes inmates to infections, including intestinal parasitic infections (IPIs). This study therefore determined the prevalence and associated factors of IPIs among prison inmates in Southern Ghana. Methods A cross‐sectional study using the stratified sampling technique was employed. The study recruited 461 prison inmates across three notable prisons, with 50 inmates from Ho Central, 357 inmates from Nsawam Medium Security, and 54 inmates from Sekondi Central Prisons all in Southern Ghana. A structured closed‐ended questionnaire was administered to collect data on sociodemographics, lifestyle/behavioral characteristics, and signs and symptoms of IPIs. In addition, stool samples were collected and analyzed for the presence of various stages of intestinal parasites (trophozoites, cysts, ova, and larva) using formol‐ether concentration, and the modified Ziehl–Neelsen techniques. Results The prevalence of IPIs among inmates of the three selected prisons was 38.2% (95% confidence interval [CI]: 33.72%–42.79%). The prevalence of IPIs among inmates of the three prisons, the Ho Central, Nsawam Medium Security, and Sekondi Central were 46% (95% CI: 31.82%–60.68%), 37.5% (95% CI: 32.49%–42.79%), and 35.2% (95% CI: 22.68%–49.38%), respectively. After adjusting for confounders, the following factors; handwashing after defecation (adjusted odds ratio [AOR]: 0.05 [0.00–0.67]; p = 0.024), trimmed fingernails (AOR: 0.32 [0.13–0.76]; p = 0.011), itchy skin (AOR [95% CI]: 5.99 [3.43–10.43]; p < 0.001), anal itching (AOR [95% CI]: 0.35 [0.19–0.62]; p < 0.001), nausea (AOR [95% CI]: 5.57 [3.22–9.65]; p < 0.001), and worm expulsion (AOR [95% CI]: 3.80 [1.42–10.18]; p = 0.008) were found to be associated with intestinal parasitic infections. Conclusion The study revealed that the prevalence of intestinal parasitic infections among prisons in Southern Ghana is high and is therefore an important public health concern. The Public Health Department of Ghana Health Service should therefore embark on health promotion and deworming exercise in all prisons in Ghana

Health Risks Associated with Informal Electronic Waste Recycling in Africa: A Systematic Review

Informal electronic waste (e-waste) recycling in Africa has become a major public health concern. This review examined studies that report on the association between e-waste exposure and adverse human health outcomes in Africa. The review was conducted following the updated version of the Preferred Items for Systematic Review and Meta-analysis (PRISMA 2020) statement checklist. We included papers that were original peer-reviewed epidemiological studies and conference papers, written in English, and reported on e-waste exposure among human populations and any health-related outcome in the context of Africa. Our results from the evaluation of 17 studies found an association between informal e-waste recycling methods and musculoskeletal disease (MSD) symptoms and physical injuries such as back pains, lacerations, eye problems, skin burns, and noise-induced hearing loss (NIHL). In addition, the generation and release of particulate matter (PM) of various sizes, and toxic and essential metals such as cadmium (Cd), lead (Pb), zinc (Zn), etc., during the recycling process are associated with adverse systemic intermediate health outcomes including cardiopulmonary function and DNA damage. This systematic review concludes that the methods used by e-waste recyclers in Africa expose them to increased risk of adverse health outcomes. However, there is a need for more rigorous research that moves past single pollutant analysis

Air Quality Impacts at an E- Waste Site in Ghana Using Flexible, Moderate- Cost and Quality- Assured Measurements

Air quality information is scarce in low- and middle- income countries. This study describes the application of moderate cost approaches that can provide spatial and temporal information on concentrations of particulate matter (PM) needed to assess community and occupational exposures. We evaluated PM levels at the Agbogbloshie e- waste and scrap yard site in Accra, Ghana, and at upwind and downwind locations, obtaining both optical and gravimetric measurements, local meteorological data and satellite aerosol optical depth. Due to overload issues, the gravimetric 24- hr samplers were modified for periodic sampling and some optical data were screened for quality assurance. Exceptionally high concentrations (e.g., 1- hr average PM10 exceeding 2000 μg/m3) were sometimes encountered near combustion sources, including open fires at the e- waste site and spoil piles. 24- hr PM2.5 levels averaged 31, 88 and 57 μg/m3 at upwind, e- waste and downwind sites, respectively, and PM10 averaged 145, 214 and 190 μg/m3, considerably exceeding air quality standards. Upwind levels likely reflected biomass burning that is prevalent in the surrounding informal settlements; levels at the e- waste and downwind sites also reflected contributions from biomass combustion and traffic. The highest PM levels occurred in evenings, influenced by diurnal changes in emission rates, atmospheric dispersion and wind direction shifts. We demonstrate that moderate cost instrumentation, with some modifications, appropriate data cleaning protocols, and attention to understanding local sources and background levels, can be used to characterize spatial and temporal variation in PM levels in urban and industrial areas.Key PointsAmbient particulate matter was monitored onsite, upwind and downwind of an e- waste site in Ghana using gravimetric and optical measurementsE- waste site emissions increased 24- hr PM2.5 levels by 57 μg/m3 over upwind levels of 31 μg/m3, and some exceptionally high levels were measuredModerate cost methods can measure air quality and source impacts given attention to study design, sampler performance and local influencesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156419/3/gh2178_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156419/2/gh2178.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156419/1/gh2178-sup-0001-2020GH000247-Text_SI-S01.pd

Prevalence and Determinants of Intestinal Parasitic Infections among Pregnant Women Receiving Antenatal Care in Kasoa Polyclinic, Ghana

Background. Intestinal parasitic infections affect pregnant women worldwide. The infection has been implicated in causing life-threatening conditions in both gravid women and their developing foetus. Sub-Saharan Africa is known to harbor the greatest proportion of intestinal parasitic infections largely due to socioeconomic and environmental factors. In Kasoa, Southern Ghana, there is paucity of data on the prevalence and associated factors of intestinal parasitic infections among pregnant women. Objective. The aim of the study was to determine the prevalence of intestinal parasitic infections and associated factors among pregnant women attending antenatal care in Kasoa Polyclinic. Methods. A hospital based analytical cross-sectional study was carried out among three hundred (300) conveniently sampled pregnant women receiving antenatal care services at the Kasoa Polyclinic. Structured questionnaires were administered to the study participants to assess sociodemographic and other possible factors. Stool samples were collected from each pregnant woman and examined for the presence of intestinal parasites by microscopy using direct wet mount as well as formol-ether sedimentation techniques. Results. Overall prevalence of intestinal parasites was 14.3% (95% CI 11–19%). Entamoeba histolytica (5.0%) was the most predominant parasite species identified followed by Ascaris lumbricoides (4.3%), Giardia lamblia (2.3%), Trichuris trichiura (1.3%), Schistosoma mansoni (0.3%), Hookworm (0.3%), Hymenolepis nana (0.3%), and Isospora belli (0.3%). Age > 30 years (AOR = 0.17, 95% CI = 0.06–0.48; p=0.001), multigravidity (AOR = 0.43, 95% CI = 0.19–0.97; p=0.043), and 2nd and 3rd trimesters (AOR = 4.73, 95% CI = 1.36–16.49; p=0.015) were independently associated with intestinal parasitic infections among pregnant women. Conclusions. A prevalence of 14.3% pregnant women compared to previous studies in Ghana is relatively low. It however suggests that intestinal parasitic infection is still a problem. The major factors noted were age, gravidity, and gestational age. Routine stool examination and provision of public health education are recommended to prevent infection of pregnant mothers and their unborn babies

Resistance to mycobacterial infection: a pattern of early immune responses leads to a better control of pulmonary infection in C57BL/6 compared with BALB/c mice

In this study, we have compared the immunological responses associated with early pulmonary mycobacterial infection in two mouse strains, BALB/c and C57BL/6 known to exhibit distinct differences in susceptibility to infection with several pathogens. We infected mice via the intranasal route. We have demonstrated that BALB/c was less able to control mycobacterial growth in the lungs during the early phase of pulmonary infection. Our results showed that during the early phase (day 3 to week 1), BALB/c mice exhibited a delay in the production of TNF and IFN-gamma in the lungs compared to C57BL/6 mice. Levels of IL-12 and soluble TNF receptors (sTNFR) were comparable between the mouse strains. The cellular subset distribution in these mice before and after infection showed a higher increase in CD11b+ cells in the lungs of C57BL/6, compared to BALB/c as early as day 3 postinfection. At early time points, higher levels of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein 1 (MIP)-alpha were detected in C57BL/6 than BALB/c mice. In vitro, BCG-infected bone marrow derived macrophages (BMM) from both mouse strains displayed similar capacities to either phagocytose bacteria or produce soluble mediators such as TNF, IL-12 and nitric oxide (NO). Although IFN-gamma stimulation of infected BMM in both mouse strains resulted in the induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The above observations indicate that the chain of early, possibly innate immunological events occurring during pulmonary mycobacterial infection may directly impact on increased susceptibility or resistance to infection