Thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus patients in Ghana: A comparative cross-sectional study.

INTRODUCTION: Thyroid disorders and diabetes mellitus coexist and are prevalent endocrinopathies among adult population. Thyroid dysfunction contributes to metabolic imbalances, increase beta-cell apoptosis and glucose intolerance. There is paucity of data and contradicting findings on how thyroid dysfunction influence glycaemic control. Therefore, we evaluated thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus (T2DM) patients in Ghana. METHODS: A comparative cross-sectional study was conducted among 192 T2DM patients from Effia Nkwanta Regional Hospital. Three consecutive monthly fasting plasma glucose (FBG) and glycated haemoglobin (HbA1c) were analysed and the results were classified as, moderate hyperglycaemia (MH) (FBG = 6.1-12.0 mmol/L, HbA1c < 7%), severe hyperglycaemia (SH) (FBG ≥ 12.1 mmol/L, HbA1c > 7%) and good glycaemic controls (GC) (FBG = 4.1-6.0 mmol/L, HbA1c < 7%). Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), body mass index (BMI) and other clinical parameters were measured. Data analysis was done using R language version 4.0.2 and p < .05 was considered statistically significant. RESULTS: There were no significant differences in age (years) between patients in the various glycaemic groups (p = .9053). The overall prevalence of thyroid disorders was 7.8% among T2DM patients. The prevalence of thyroid disorders was higher in patients with SH (11.7%) followed by those with MH (7.5%) and then those with GC (5.4%). Serum levels of TSH and FT3/FT4 ratio were significantly lower in T2DM patients with SH compared to those with MH and the GC (p < .0001). However, FT4 was significantly higher in SH patients compared to the good glycaemic controls (p < .01). The first tertiles of TSH [aOR = 10.51, 95% CI (4.04-17.36), p < .0001] and FT3 [aOR = 2.77, 95% CI (1.11-6.92), p = .0290] were significantly and independently associated with increased odds of hyperglycaemia. CONCLUSION: The prevalence of thyroid dysfunction is high in T2DM and increases with hyperglycaemia. Reduced TSH and T3 may worsen glycaemic control. Periodic monitoring of thyroid function should be incorporated into management guidelines among T2DM patients in Ghana.

Assessment of intestinal and blood protozoan infections among pregnant women visiting ante-natal care at Tafo Hospital, Ghana.

Introduction: Intestinal and blood protozoans cause morbidity and mortality in both pregnant women and developing foetuses worldwide. It constitutes a major health problem in many tropical areas in Africa. This study assessed the prevalence of intestinal and blood protozoans' parasitic load and their risk factors among pregnant women visiting antenatal care at Tafo Hospital, Ghana from November 2016 to January 2017. Method: A pilot cross-sectional study was conducted among consented pregnant women who visited antenatal care at Tafo Government Hospital, Kumasi Ghana. Structured questionnaires were administered to obtain socio-demographic data, knowledge on protozoan infections, and their risk factors among study participants. A stool sample was obtained from each participant for the microscopic examination of the intestinal protozoa. Venous blood was taken from participants for the detection of Plasmodium and Toxoplasma gondii infections. Wet mount and the faecal protozoan concentrated method were done for the identification of intestinal parasites. Blood films and serological examination for malaria rapid diagnostic tests (RDT) were done for identification of Plasmodium parasites while an Enzyme-linked immunosorbent assay (ELISA) was used for detecting the antibodies of T. gondii among participants. Data were analyzed using statistical packages for the social sciences (SPSS). Results: The mean age of the study participants was 27.83, and ranges from 18 to 40 years. The majority of the participants (82.2%) had never experienced stillbirth nor spontaneous abortion. Intestinal parasites were found in 36.7% of participants. Giardia lamblia (28.1%), Cryptosporidium parvum (5.3%), and Entamoeba histolytica/dispar (3.3%) were among the intestinal protozoans detected. T. gondii antibodies were detected by high levels of immunoglobulins, resulting in IgG (48.0%) and IgM (11.3%) being found among participants, with 7.3% testing positive for both IgM and IgG. The prevalence of malaria infection among the study participants was 2.7%. The consumption of raw or cooked vegetables had significant influence on their intestinal and blood protozoan infections status (p = 0.004) (OR = 0.32, CI = 0.12-0.86). There was a significant association between Hb levels and malaria (p = 0.014) and that of intestinal protozoans (p = 0.035). Conclusion: The prevalence of intestinal protozoans and blood protozoans such as T. gondii were high and therefore effective measures should be put in place to reduce the infectivity. Environmental hygiene should be improved and education by relevant agencies should be intensified on the possible transmission of intestinal and blood parasite infections given the possible role of these infections in adverse pregnancy outcomes.

Assessing the variability and the role of inflammatory cytokines and monocyte chemoattractant protein-1 (MCP-1) in predicting stroke among hypertensives: A case-control study.

Background: Atherosclerosis is a complex lipid-driven inflammatory disease in which numerous cell types and inflammatory mediators are involved in the progression of hypertension to stroke. Mediators' markers that could predict the progression of hypertension to stroke are of research importance. We assessed the predictive value of individual and combined cytokines and monocyte chemoattractant protein-1 (MCP-1) among hypertensives with or without stroke. Methods: In a case-control study, we enrolled 63 cases with stroke and hypertension (HPT-S), 59 stroke-free hypertensives (HPT), and 53 stroke free normotensives as controls (CS). Sociodemographic data and blood samples were collected for the estimation of Interleukin-10 (IL-10), IL-6, IL-8, IL-1ß and monocyte chemoattractant protein-1 (MCP-1) using commercially available ELISA kits from Biobase Biotech, Shanghai, China. The Receiver Operator Characteristics (ROC) analysis was used to calculate diagnostic accuracy for cytokines in predicting stroke among hypertensives. A combined bioscore model of IL-10 and MCP-1 was generated to predict stroke among hypertensives. The multiple logistic regression analysis was used to assess the chances of IL-10 and MCP-1 in predicting stroke among hypertensives. Statistical analyses were performed using R-language. Results: The HPT-S group had significantly higher levels of MCP-1 and IL-10 compared to the HPT and CS groups (p < 0.05). There was no significant difference in IL-1ß, IL-8 and IL-6 amongst the three study groups. MCP-1 and IL-10 were predictive of stroke occurrence among hypertensives and were used to develop a bioscore model. An elevated MCP-1 and IL-10 with a bioscore 2 had a predictive accuracy of 0.81, a sensitivity of 0.77 and specificity of 0.84. At a bioscore of 1, the sensitivity and specificity for predicting stroke among hypertensives was 97.0% and 61.0% respectively. In a binary logistic regression, having a bioscore of 1 [aOR = 20.43, 95% CI (2.17-192.62), p = 0.008] or 2 [aOR = 26.00, 95% CI (2.92-231.31), p = 0.003] were significantly associated with stroke occurrence among hypertensives. Conclusion: Higher levels of IL-10 with a concomitant level of MCP-1 could serve as a good predictor of stroke among hypertensives. Subsequently, MCP-1 may prove useful as a therapeutic target for atherosclerosis in hypertensives. Combined bioscore of MCP-1 and IL-10 could serve as a good predictor of stroke among hypertensives.

Profiling immuno-metabolic mediators of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in Ghana.

BACKGROUND: The association between prolong metformin usage and B12 deficiency has been documented. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency. Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum. Lack of intrinsic factor due to the presence of auto-antibodies to parietal cells (IFA) could lead to vitamin B12 deficiency and subsequently cause peripheral neuropathy. We investigated the prevalence of vitamin B12 deficiency using more sensitive, combined markers of vitamin B12 status (4cB12) and the immuno-biochemical mediators of vitamin B12 deficiency. METHODS: In this observational study, 200 consecutive consenting metformin-treated T2DM patients, aged 35 and above, attending the diabetic clinic at KATH were recruited. Vitamin B12 deficiency was classified based on the Fedosov age-normalized wellness quotient. Anthropometric measurement was taken as well as blood samples for immunological and biochemical mediators. Peripheral neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Statistical analysis was performed using the R Language for Statistical Computing. RESULTS: Using the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 32.5% and 6.5% respectively. Participants with vitamin B12 deficiency had significantly higher levels of IFA, GPA, TNF-α, TC, LDL and albumin compared to those with normal vitamin B12 levels (p < 0.05). Correlation analysis revealed a statistically significant negative association between 4cB12 and the immunological markers [IFA (rs = -0.301, p<0.0001), GPA (rs = -0.244, p = 0.001), TNF-α (rs = -0.242, p = 0.001) and IL-6 (rs = -0.145, p = 0.041)]. Likewise, 4cB12 was negatively associated with TC (rs = -0.203, p = 0.004) and LDL (rs = -0.222, p = 0.002) but positively correlated with HDL (rs = 0.196, p = 0.005). CONCLUSION: Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-α and cardiometabolic risk factors (higher LDL and TC and lower HDL). Upon verification of these findings in a prospective case-control study, it may be beneficial to include periodic measurement of Vitamin B12 using the more sensitive combined indicators (4cB 12) in the management of patients with T2DM treated with metformin in Ghana.

Increased metformin dosage suppresses pro-inflammatory cytokine levels in systemic circulation and might contribute to its beneficial effects.

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder, characterized by persistent elevation of blood glucose either due to insulin resistance or insulin insufficiency. Metformin is the recommended first choice of drug for the management of T2DM and is known to improve insulin sensitivity and prevents hyperglycemia by reducing chronic inflammation. T-helper type 1 (Th1) and type 17 (Th17) cells, are important pro-inflammatory CD4+ T cell subsets secreting TNF-α, and INF-γ (Th1), and interleukin 17 (Th17). These cytokines have been shown to play a crucial role in inflammation, insulin resistance, and the development of T2DM. Here, we explore the effect of different metformin dosages on pro-inflammatory cytokine (TNF-α, INF-γ, GM-CSF and IL-17) levels in systemic circulation among T2DM patients in Ghana, since inflammatory responses and cytokines play significant roles in the pathogenesis and progression of T2DM patients on metformin. Two hundred and nine (209) consenting T2DM patients receiving treatment at the Diabetic unit of the Komfo Anokye Teaching Hospital (KATH) in the Ashanti region of Ghana were recruited in a hospital-based cross-sectional study design. Blood samples were collected and serum obtained from each participant were analyzed for the concentrations of TNF-α, INF-γ, GM-CSF and IL-17 cytokine levels by solid-phase sandwich ELISA. We observed that participants on 3000 mg/day dose of metformin had significantly lower levels of TNF-α (p < .001) and IFN-γ (p = .014) compared to those on other dosages (1000 mg and 2000 mg/day). However, GM-CSF and IL-17 levels were not affected by increased metformin dosages. After adjusting for age, gender, dose and duration of metformin use, we observed that participants who took higher doses of metformin had significantly reduced levels of TNF-α (ß = -0.0297, 95% CI = (-0.005 to -0.002) p < .001. Metformin dosage independently predicted reduced TNF-α levels with 14.4% variations in the metformin dosage levels. Increased metformin dosage suppresses TNF-α levels in systemic circulation and hence might contribute to its beneficial effects.

Individual and combined bioscore model of presepsin, procalcitonin, and high sensitive C - reactive protein as biomarkers for early diagnosis of paediatric sepsis.

BACKGROUND: Paediatric sepsis remains a major public health problem with significant morbidity and mortality especially in developing countries. Clinical symptoms associated with sepsis are unreliable and laboratory parameters unspecific, making an early diagnosis of paediatric sepsis difficult. The lack of definitive biomarker(s) for early diagnosis of sepsis further leads to the misuse of antibiotics. Diagnosis based on a single biomarker does not provide adequate accuracy. Subsequently, combining multiple biomarkers into a single score will help clinicians make a better diagnostic judgment. AIMS: This study for the first time evaluated the individual and combined diagnostic accuracy of procalcitonin (PCT), presepsin (sCD14-ST) and high sensitive C-reactive protein (hs-CRP) using a Bioscore model. MATERIALS AND METHODS: In a case control study conducted at the Paediatric Emergency Unit (PEU) and the Mother and Baby Unit (MBU) of Komfo Anokye Teaching Hospital (KATH), sixty (60) paediatric subjects aged zero to six (0-6) years, were diagnosed with sepsis using case-definition by the national neonatal bloodstream infection surveillance and Pediatric Sepsis Consensus Congress. Thirty (30) other paediatric subjects, aged and sex matched without sepsis or inflammatory conditions were used as controls. One-time blood sample was taken at the time of admission for blood culture and measurement of PCT, hs-CRP, and presepsin by ELISA. The Statistical Package for Social Sciences (SPSS release 20.0, Copyright ©SPSS Inc.) was used for analysis. RESULTS: Out of the sixty septic paediatric subjects, 14 patients (23.3%) had positive blood cultures (LCS) and 46 (76%) had negative for blood cultures (CS). Klebsiella spp. recorded the highest median levels of PCT, and hs-CRP while Pseudo. Aeruginasa recorded the highest of sCD14-ST levels. Significant elevations in PCT, sCD14-ST and hs-CRP levels were observed among septic cases in comparison to controls (p < 0.0001). Individually, PCT showed better accuracy (AUC = 78.7%) followed by hs-CRP (AUC = 78.4%) and sCD14-ST (AUC = 74.8%). Combination of PCT + hs-CRP had the highest accuracy (AUC = 80.1%) followed by hs-CRP + sCD14-ST (AUC = 77.2%), PCT + sCD14-ST + hs-CRP (AUC = 77.0%) and PCT + sCD14-ST (AUC = 75.9%).Conclusion: hs-CRP, PCT, and sCD14-ST are independent predictors of paediatric sepsis due to their high prognostic values. Moreover, Bioscore combination of these biomarkers was significantly associated with increased odds for sepsis. The incorporation of these biomarkers into routine diagnostic tests will aid in prompt diagnosis of paediatric sepsis.

Evaluation of red blood cell count as an ancillary index to hemoglobin level in defining the severe falciparum malarial anemia among Ghanaian children in low-resource communities.

Our study evaluated red blood cell count as supporting hematological index to hematocrit level in predicting severe malarial anemia instead of the hemoglobin levels among malaria-infected children in Ghana. This case-control study was conducted at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. The study recruited 139 children, of which 45 were Controls (C), 43 with severe malaria (SM), and 51 with mild malaria (MM). Validated questionnaires were administered to obtain the socio-demographic data from each respondent. Venous blood was obtained for parasitemia count and to determine the hematological profile of each participant. With point of observation, data analysis was done. The mean age of the children was 4.22 ± 2.65 years. Median levels of hemoglobin (Hb) decreased in the order; C > MM > SM (P < 0.0001). There was a reduction in median levels of hematocrit (HCT) (P < 0.0001), RBC (red blood cells count) (<0.0001), from the MM to the SM. Among patients with severe malaria, there were a positive significant spearmen's co-efficient correlations between median levels of RBC (r = 0.652, P = 0.005) and HB (r = 0.640, P = 0.006) individually against HCT. However among the mild malaria patients only RBC (r = 0.884, P < 0.001) was positively correlated against HCT. At a cut-off of <4.0×106/uL for RBC and <8.8 g/dL for Hb, RBC (90.4%) recorded a slightly high accuracy in predicting severe falciparum malarial anemia than Hb (86.9%) among the cases. Red blood cell count may be a promising indicator to support hematocrit (<15%) in defining severe malarial anemia than hemoglobin level (<5 g/dL) among malaria-infected children from endemic areas in Ghana.

Renal abnormalities among children with sickle cell conditions in highly resource-limited setting in Ghana.

Sickle cell disease (SCD) is associated with progressive multi-organ failure especially, the brain and kidney and leads to high morbidity and mortality rate. The aim of this study was to determine the prevalence of renal abnormalities among children with SCD. This cross-sectional study recruited 212 sickling positive patients comprising of 96 Hb AS, 48 Hb SC, and 68 Hb SS phenotypes from the Pediatric Unit of Wassa Akropong Government Hospital, Wassa Akropong, Ghana. Early morning urine and venous blood samples were collected from each participant. Urinalysis was conducted and serum urea and creatinine levels were estimated. Estimate glomerular filtration rate (eGFR) was calculated using the Swartz equation. Classification of chronic kidney disease (CKD) was based on 'The Kidney Disease: Improving Global Outcomes (KIDIGO)' criteria. The mean age of the children were 7.90 years. Serum creatinine (p = 0.0310) and urea (p<0.0001) levels were significantly higher among Hb AS participants compared with Hb SS phenotype. The prevalent indicators of renal abnormalities were proteinuria (26.4%), urine granular cast (5.6%) and CKD (39.6%). Proteinuria, urine granular cast and CKD were most prevalent among Hb SS (47.1%, 11.8% and 73.5% respectively) compared with Hb SC (41.7%, 8.3%, and 45.8% respectively) and Hb AS (4.2%, 0.0%, and 14.5%) phenotypes, respectively. Sickle cell conditions were significantly associated with proteinuria (p<0.0001) and CKD (p = 0.0378). Children with Hb SS [aOR = 5.04, 95% CI (2.47-10.3); p<0.0001] and Hb SC [aOR = 3.14 95% CI (1.39-7.01); p = 0.0174] were at increased odds of developing CKD after adjusting for age, BMI and gender. Proteinuria and CKD are associated with sickle cell disease (Hb SC and Hb SS). Renal function should be routinely monitored for children with SCD.

Prevalence of metabolic syndrome and the comparison of fasting plasma glucose and HbA1c as the glycemic criterion for MetS definition in non-diabetic population in Ghana.

BACKGROUND: Glycated hemoglobin (HbA1c), owing to its ability to reflect glycemia over a relatively longer time span, is still been investigated as an adjunct test for fasting plasma glucose (FPG) to identify subjects at risk of metabolic syndrome (MetS) in some Caucasian populations. However, whether or not HbA1c can serve as an adjunct to FPG in the definition of MetS in the Ghanaian population remains unknown. This study determined the prevalence of MetS and evaluated HbA1c ≥ 5.6% and FPG ≥ 5.6 mmol/l as the glycemic component of MetS among non-diabetic population in Ghana. METHODS: This was a case-control study conducted at St Francis Xavier Hospital, Assin Fosu, Central Region, Ghana. A total of 264 non-diabetic Ghanaian adults consisting of 158 newly diagnosed hypertensives and 106 normotensives, were recruited for the study. Fasting plasma insulin and glucose, HbA1c, and lipid profile was performed for each respondent. RESULTS: Using the FPG as glycemic criterion, the overall MetS prevalence was 46.6%, 37.1%, and 12.5% according by the IDF, NCEP ATP III, and WHO criteria, respectively. The prevalence of MetS using the HbA1c criterion was 54.2%, 52.7%, and 42.4% by the IDF, NCEP ATP III and WHO criteria, respectively. The HbA1c criterion identified more participants with MetS compared to the FPG criterion with a good agreement between HbA1c and FPG using the IDF and NCEP ATP III criteria (κ = 0.484 to 0.899) respectively. However, the overlap between HbA1c and FPG based diagnosis of MetS was limited for the WHO criterion. CONCLUSION: The prevalence of metabolic syndrome is high among non-diabetics in Ghana. Introduction of HbA1c in addition to FPG in the screening of MetS improves identification of more people with MetS who would otherwise have been missed when only FPG-based diagnosis of MetS is used; with a substantial agreement with FPG, except when using the WHO criteria.

Asymptomatic Bacteriuria and Anti-Microbial Susceptibility Patterns among Women of Reproductive Age. A Cross-Sectional Study in Primary Care, Ghana.

Background: Asymptomatic bacteriuria (ASB) poses serious future clinical repercussions for reproductive women. The study determined the prevalence of asymptomatic bacteriuria along with anti-microbial susceptibility patterns among women of reproductive age in a primary care facility. Method: The study recruited a total of 300 women of reproductive age attending the Tetteh Quarshie Memorial Hospital at Akuapem-Mampong, Ghana, between January and March 2018. Questionnaires were administered to obtain demographic data and predisposing risk factors of ASB. An early-morning midstream urine sample was collected from participants. Urinalysis, urine culture, and anti-microbial susceptibility testing were performed. Results: The mean age of participants was 25.43 years. The overall prevalence rate of ASB was 40.3%. The prevalence was higher among pregnant women compared to non-pregnant women (33.3% vs 7.0%). The most common bacterial isolate was E. coli (47.0%) followed by Proteus spp. (36.4%), Klebsiella spp. (8.3%), and E. faecalis (8.3%). Leukocyturia (35.0%) followed by nitrate (30.0%) were the most common urine abnormalities identified on dipstick urinalysis. Most bacteria isolates showed increased resistance to ampicillin (95.04%) and tetracycline (95.04%) while most of the bacterial isolates were sensitive to levofloxacin (94.35%). Demographic characteristics including age (p < 0.001), educational level (p < 0.001), residency (p = 0.001), and marital status (p = 0.005) were significantly associated with ASB. Lifestyle characteristics such as sexual status (p = 0.001) and frequency of washing of intimate parts after sexual intercourse (p < 0.001) were also significantly associated with ASB. Conclusion: Asymptomatic bacteriuria, particularly E. coli and Proteus spp. are prevalent in the urine of pregnant women living in Akuapem-Mampong municipality. Hence public education along with early screening of ASB is essential to reducing future risk of reproductive health complications. Future studies are required to assess the impact of public health on the rate of bacterial infections.

Evaluation of Individual and Combined Markers of Urine Dipstick Parameters and Total Lymphocyte Count as a Substitute for CD4 Count in Low-Resource Communities in Ghana.

We evaluated the individual and combined levels of urine dipstick and total lymphocyte count (TLC) as surrogate markers for CD4 count in a low-resource community in Ghana. This cross-sectional study recruited 200 HIV-infected patients from the Saint Francis Xavier Hospital, Assin Fosu, Ghana. Complete blood count, CD4 count, and urine dipstick analysis were measured for participants. The threshold values were determined as <350 cells/µl for CD4, <1200 cells/µl for TLC, and ≥+ on urine dipstick analysis. The mean age of participants was 43.09 years. Proteinuria ≥ + [aOR = 4.30 (3.0-18.5)], leukocyturia ≥ + [aOR = 2.91 (1.33-12.5)], hematuria ≥ + [aOR = 2.30 (1.08-9.64)], and TLC < 1200 cells/µl [aOR = 3.26 (3.94-15.29)] were significantly associated with increased risk of CD4 count < 350 cells/µl. Using the individual markers, the best substitute marker for predicting CD4 count < 350 cells/µl was proteinuria at a cutoff point ≥ 2++, AUC of 0.973, sensitivity of 97.6%, specificity of 100.0%, PPV of 100.0%, and NPV of 89.1%. A combination of ≤ 1200 TLC + ≥ 2++ (leukocyturia + proteinuria + hematuria) yielded an AUC of 0.980, sensitivity (72.8%), specificity (100.0%), PPV (100.0%), and NPV (97.9%). Proteinuria could serve as a noninvasive screening tool, but the combination of proteinuria, leukocyturia, hematuria, and TLC serves as a better substitute marker for CD4 count in monitoring the disease progression among HIV patients in low-resource communities.