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Human papillomavirus (HPV) E6 and E7 oncogene expression is essential for cervical carcinogenesis. Evidence exists that E6/E7 variants may have different transforming activities while the risk of HPV-16 variants (A/D) differs by race/ethnicity. We determined the type-specific diversity of HPV infection in women with high grade cervical disease or cervical cancer in Ghana and investigated naturally occurring E6/E7 DNA variants in this population. HPV genotyping was carried out on 207 cervical swab samples collected from women referred to a gynaecology clinic at two teaching hospitals in Ghana. HPV-16, HPV-18 and HPV-45 were detected in 41.9%, 23.3% and 16.3% of cases respectively. HPV-16 E6/E7 DNA sequencing was performed in 36 samples. Thirty samples contained E6/E7 variants of the HPV-16-B/C lineage. 21/36 samples were of the HPV-16C1 sublineage variant and all contained the E7 A647G(N29S) single nucleotide polymorphism (SNP). This study reveals the diversity of E6/E7 DNA and the dominance of HPV16 B/C variants in cervicovaginal HPV infection in Ghana. Type-specific HPV diversity analysis indicates that most Ghanaian cervical disease cases are vaccine preventable. The study provides an important baseline from which for the impact of vaccine and antivirals on clinically relevant HPV infection and associated disease can be measured.
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Filarial infections are among the world's most disturbing diseases caused by 3 major parasitic worms; Onchocerca volvulus, Wuchereria bancrofti, and Brugia malayi, affecting more than 500 million people worldwide. Currently used drugs for mass drug administration (MDA) have been met with several challenges including the development of complications in individuals with filaria co-infections and parasitic drug resistance. The filarial endosymbiont, Wolbachia, has emerged as an attractive therapeutic target for filariasis elimination, due to the dependence of the filaria on this endosymbiont for survival. Here, we target an important enzyme in the Wolbachia heme biosynthetic pathway (ferrochelatase), using high-throughput virtual screening and molecular dynamics with MM-PBSA calculations. We identified four drug candidates; Nilotinib, Ledipasvir, 3-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane, and 2-(4-Amino-piperidin-1-yl)-ethanol as potential small molecules inhibitors as they could compete with the enzyme's natural substrate (Protoporphyrin IX) for active pocket binding. This prevents the worm from receiving the heme molecule from Wolbachia for their growth and survival, resulting in their death. This study which involved targeting enzymes in biosynthetic pathways of the parasitic worms' endosymbiont (Wolbachia), has proven to be an alternative therapeutic option leading to the discovery of new drugs, which will help facilitate the elimination of parasitic infections.
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Brugia Malayi , Filariasis , Wolbachia , Animales , Wolbachia/metabolismo , Ferroquelatasa/metabolismo , Ferroquelatasa/uso terapéutico , Filariasis/tratamiento farmacológico , Filariasis/parasitología , Hemo/metabolismoRESUMEN
Reactive case detection (RACD) is the screening of household members and neighbors of index cases reported in passive surveillance. This strategy seeks asymptomatic infections and provides treatment to break transmission without testing or treating the entire population. This review discusses and highlights RACD as a recommended strategy for the detection and elimination of asymptomatic malaria as it pertains in different countries. Relevant studies published between January 2010 and September 2022 were identified mainly through PubMed and Google Scholar. Search terms included "malaria and reactive case detection", "contact tracing", "focal screening", "case investigation", "focal screen and treat". MedCalc Software was used for data analysis, and the findings from the pooled studies were analyzed using a fixed-effect model. Summary outcomes were then presented using forest plots and tables. Fifty-four (54) studies were systematically reviewed. Of these studies, 7 met the eligibility criteria based on risk of malaria infection in individuals living with an index case < 5 years old, 13 met the eligibility criteria based on risk of malaria infection in an index case household member compared with a neighbor of an index case, and 29 met the eligibility criteria based on risk of malaria infection in individuals living with index cases, and were included in the meta-analysis. Individuals living in index case households with an average risk of 2.576 (2.540-2.612) were more at risk of malaria infection and showed pooled results of high variation heterogeneity chi-square = 235.600, (p < 0.0001) I2 = 98.88 [97.87-99.89]. The pooled results showed that neighbors of index cases were 0.352 [0.301-0.412] times more likely to have a malaria infection relative to index case household members, and this result was statistically significant (p < 0.001). The identification and treatment of infectious reservoirs is critical to successful malaria elimination. Evidence to support the clustering of infections in neighborhoods, which necessitates the inclusion of neighboring households as part of the RACD strategy, was presented in this review.
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BACKGROUND: Haemoglobinopathies such as sickle cell disorder and glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as differences in ABO blood groups have been shown to influence the risk of malaria and/or anaemia in malaria-endemic areas. This study assessed the effect of adding MNP containing iron to home-made weaning meals on anaemia and the risk of malaria in Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups. METHODS: This study was a double-blind, randomly clustered trial conducted within six months among infants and young children aged 6 to 35 months in rural Ghana (775 clusters, n = 860). Participants were randomly selected into clusters to receive daily semiliquid home-prepared meals mixed with either micronutrient powder without iron (noniron group) or with iron (iron group; 12.5 mg of iron daily) for 5 months. Malaria infection was detected by microscopy, blood haemoglobin (Hb) levels were measured with a HemoCue Hb analyzer, the reversed ABO blood grouping microtube assay was performed, and genotyping was performed by PCR-RFLP analysis. RESULTS: The prevalence of G6PD deficiency among the study participants was 11.2%. However, the prevalence of G6PD deficiency in hemizygous males (8.5%) was significantly higher than that in homozygous females (2.7%) (p = 0.005). The prevalence rates of sickle cell traits (HbAS and HbSC) and sickle cell disorder (HbSS) were 17.5% and 0.5%, respectively. Blood group O was dominant (41.4%), followed by blood group A (29.6%) and blood group B (23.3%), while blood group AB (5.7%) had the least frequency among the study participants. We observed that children on an iron supplement with HbAS had significantly moderate anaemia at the endline (EL) compared to the baseline level (BL) (p = 0.004). However, subjects with HbAS and HbAC and blood groups A and O in the iron group had a significantly increased number of malaria episodes at EL than at BL (p < 0.05). Furthermore, children in the iron group with HbSS (p < 0.001) and the noniron group with HbCC (p = 0.010) were significantly less likely to develop malaria. CONCLUSIONS: Iron supplementation increased anaemia in children with HbAS genotypes and provided less protection against malaria in children with HbAC and AS and blood groups A and O. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01001871 . Registered 27/10/2009. REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/record/NCT01001871 .
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Immune-based diagnosis of Buruli ulcer disease (BUD) in children is difficult due to cross-reactivity between mycobacteria. We found that T-cell IFNγ/TNFαresponses against Mycobacterium (M.) ulcerans and M. tuberculosis (PPDMulc, PPDMtub) were different between children with BUD (n=27) and TB (n=20) but only ratios (PPDMtub/PPDMulc) discriminated the study groups efficiently.
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BACKGROUND: Doxycycline is used for treatment of Mansonella (M.) perstans infection. Immune modulatory effects of both, M. perstans and doxycycline, have been described but long-term implications on host immune response are not defined. Here we determined multiple immune parameters of M. perstans infected individuals prior to and after doxycycline treatment to characterize doxycycline effects on host T-cell immunity. METHODS: Immune characterization of doxycycline-treated M. perstans infected individuals was performed as part of an open-label randomized clinical trial. Immune cell population phenotyping by flow cytometry and functional in vitro T-cell assays were performed at baseline, six months, and 'long-term' (18-24 months) after treatment start. Treatment efficacy, based on peripheral blood microfiliaria burden, was correlated with immune parameters and effects on immune response against concomitant Mycobacterium tuberculosis infection were determined. RESULTS: Immune population phenotyping indicated changes in functional T-cell responses after doxycycline treatment. Constitutive and superantigen induced T-cell activation and polarization towards T helper type (TH)1 phenotype at baseline declined after doxycycline treatment whereas low proportions of TH17 and TH1* cells at baseline increased significantly at follow-up. In accordance, long-term decline in antigen-specific TH1 responses against concomitant Mycobacterium tuberculosis infection was seen. Notably, only TH17 and TH1* changes after six months and TH17 at baseline were negatively correlated with M. perstans microfilaria burden or reduction whereas long-term changes were not associated with treatment efficacy. CONCLUSIONS: We found long-term immune modulatory effects of doxycycline treatment leading to decreased constitutive T-cell activation, polarization towards TH17/TH1*, and impaired immune response against concomitant Mycobacterium tuberculosis infection.
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AIM: Rheumatoid arthritis (RA) is an autoimmune disease which affects millions of lives globally characterized by chronic inflammation in the joints of the body. There is no known cause for RA; however, genetic predisposition has been associated with its occurrence. The association between genetic predisposition and RA has been reported largely among Caucasians and Asians. However, few studies with limited data have reported genome-wide association studies of RA in Africa, especially in Ghana. In addition, there is genetic heterogeneity that exists geographically among different populations. This study therefore investigated the association of protein arginine deiminase type 4 (PAD4) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) single nucleotide polymorphisms with susceptibility of RA among Ghanaians. METHODS: This case-control study included 75 RA patients and 75 healthy controls from the Komfo Anokye Teaching Hospital in Ghana. Validated questionnaires were used to obtain demographic data, and blood samples were collected and processed for DNA and polymerase chain reaction analysis. Statistical analysis was done using SPSS version 25.0. RESULTS: PTPN22 demonstrated a 100% minor allele frequency (GG) in both cases and healthy controls; however, an association could not be made for PTPN22 polymorphism with susceptibility of RA when comparing cases to controls. The homozygous minor allele (GG) of PAD4 was absent in the population. CONCLUSION: PAD4 polymorphism was absent, while PTPN22 was present in the Ghanaian population. The association between PTPN22 (rs2476601) and PAD4 (rs2240340) with RA susceptibility could not be established, thus may not contribute as risk factors for RA in the Ghanaian population.
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Artritis Reumatoide , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Arginina Deiminasa Proteína-Tipo 4 , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Ghana/epidemiología , Humanos , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Arginina Deiminasa Proteína-Tipo 4/genéticaRESUMEN
BACKGROUND: Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective Antiretroviral Therapy (ART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on ART in Kumasi, Ghana. METHODS: This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on ART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. p < 0.05 was considered statistically significant. RESULTS: Proportions of patients with viral suppression and viral rebound were 76.1% and 21.0% respectively. Being diagnosed at WHO stage I [aOR = 11.40, 95% CI (3.54-36.74), p < 0.0001], having good adherence to ART [aOR = 5.09, 95% CI (2.67-9.73), p < 0.0001], taking Nevirapine-based regimen [aOR = 4.66, 95% CI (1.20-18.04), p = 0.0260] and increasing duration of treatment (p < 0.0001) were independently associated with higher odds of viral suppression. However, being diagnosed at WHO stage II (aOR = 7.39, 95% CI 2.67-20.51; p < 0.0001) and stage III (aOR = 8.62, 95% CI 3.16-23.50; p < 0.0001), having poor adherence (aOR = 175.48, 95% CI 44.30-695.07; p < 0.0001), recording baseline suppression value of 20-49 copies/mL (aOR = 6.43, 95% CI 2.72-15.17; p < 0.0001) and being treated with Zidovudine/Lamivudine/Efavirenz (aOR = 6.49, 95% CI 1.85-22.79; p = 0.004) and Zidovudine/Lamivudine/Nevirapine (aOR = 18.68, 95% CI 1.58-220.90; p = 0.02) were independently associated with higher odds of viral rebound. CONCLUSION: Approximately 76% viral suppression rate among HIV patients on ART in Kumasi falls below the WHO 95% target by the year 2030. Choice of ART combination, drug adherence, WHO clinical staging and baseline viral load are factors associated with suppression or rebound. These clinical characteristics of HIV patients must be monitored concurrently with the viral load.
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Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/uso terapéutico , Ghana/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Lamivudine/uso terapéutico , Nevirapina/uso terapéutico , Estudios Retrospectivos , Carga Viral , Zidovudina/uso terapéuticoRESUMEN
OBJECTIVE: The study evaluated the socio-demographic characteristics, obstetric variables and foeto-maternal complications associated with low birth weight (LBW) in order to provide better treatment and management options. METHODS: The prospective study conducted from February, 2019 to June, 2020 recruited 312 primigravid pregnant women who reported for antenatal care in three tertiary referral hospitals in northern Ghana. Their socio-demographic, obstetric and adverse foeto-maternal outcome information were obtained with a well-structured questionnaire according to the World Health Organisation (WHO) guidelines. Participants' blood samples were collected for haematological tests. Odds ratio [OR, 95% confidence interval (CI)] for the association between socio-demographic, obstetric characteristics, foeto-maternal complications and haematological tests in relation to LBW were assessed using logistic regression model. RESULTS: This study reported a LBW prevalence of 13.5%. Increasing maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 1st visit, before and after delivery significantly increased the odds of LBW. Preterm delivery (PTD<37 weeks) (COR = 9.92, 95% CI (4.87-2020), p<0.001), preeclampsia (PE) (COR = 5.94, 95% CI (2.96-11.94), p<0.001), blood transfusion (COR = 14.11, 95% CI (2.50-79.65), p = 0.003), caesarian delivery (COR = 3.86, 95% CI (1.96-7.58), p<0.001) and male sex neonates (COR = 2.25, 95%CI (1.14-4.47), P = 0.020) presented with increased odds of LBW. Increasing gestational age at delivery presented with 28% reduced odds of LBW (COR = 0.72, 95% CI (1.12-4.40), P = 0.023). Upon controlling for potential confounders in multivariate logistic regression, only gestational age at delivery (AOR = 0.67, 95% CI (0.47-0.96), P = 0.030) remained significantly associated with reduced odds of LBW. CONCLUSION: This study found that high blood pressure at 1st visit, before and after delivery results in increased chances of delivering a baby with LBW. Furthermore, PTD<37 weeks, having PE in current pregnancy, and male sex potentiate the risk of LBW. On the other hand, increasing gestational age reduces the risk of LBW. Thus, we recommend that midwives should intensify education to pregnant women on the benefits of regular ANC visits to aid in the early detection of adverse foeto-maternal complications. We also recommend proper clinical management of pregnancies associated with an elevated blood pressure at registration. Also, maternal intrapartum blood pressure measurement could be used to predict LBW in low resourced settings.
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Hipertensión , Preeclampsia , Nacimiento Prematuro , Peso al Nacer , Femenino , Ghana/epidemiología , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Embarazo , Nacimiento Prematuro/epidemiología , Atención Prenatal , Estudios Prospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: COVID-19 pandemic has had a greater psychological impact on patients with chronic ailments such as diabetes mellitus, tuberculosis, and HIV/AIDS compared to those without chronic conditions. We explored the psychological impacts of COVID-19 among people living with diabetes mellitus in Ghana. METHODS: this study employed a hospital-based cross-sectional design involving 157 diabetes mellitus patients aged 20 years and above. We assessed diabetes distress by the seventeen-item diabetes stress (DDS17) scale and COVID-19 worries by 3 specific benchmarks: "worry about overly affected due to diabetes if infected with COVID-19", "worry about people with diabetes characterized as a risk group" and "worry about not able to manage diabetes if infected with COVID-19". A close-ended questionnaire was used in data collection. RESULTS: of 157 diabetic patients interviewed, the majority had type 2 diabetes mellitus with known complications and only 42.7% were managing COVID-19 symptoms. The participants showed moderate to high level of COVID-19 specific worry, moderate fear of isolation, and low level of diabetes-associated distress. About 33.8% of the study population expressed a sense of worry towards the pandemic. The logistic regression showed that age, employment status, and presence of other chronic diseases were significantly associated with worries about being overly affected if infected with COVID-19 due to their diabetes status. Age and sex were associated with worries about people with diabetes being characterized as a risk group and age, sex and employment status were associated with participants who were worried about not being able to manage diabetes if infected with COVID-19. CONCLUSION: the general trend indicates a sense of worry among diabetes patients during the COVID-19 pandemic which is associated with poorer psychological health. Clients' education and counseling on COVID-19 are necessary to address some of their concerns to minimize the level of anxiety and emotional stress in these individuals.
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COVID-19/psicología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 2/psicología , Adulto , Factores de Edad , Ansiedad/epidemiología , Estudios Transversales , Miedo , Femenino , Ghana , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Iron fortification and micronutrient initiatives, specifically, vitamin A, and zinc supplementation are the most cost-effective developmental strategies against malnutrition and health emergencies in pre-school children. Iron-deficiency among pre-school children have been documented, however, studies evaluating the impact of immunoglobulin G (IgG) isotype responses among iron-fortified pre-school children in malaria endemic communities has not been assessed. We evaluated the impact of iron fortification on the IgG responses to GLURP R0, GLURP R2 and MSP3 FVO malaria-specific antigens among pre-school children in malaria endemic areas. METHODS: This community-based, placebo-controlled, double-blinded, cluster-randomized trial study was conducted in Wenchi Municipal and Tain District of Bono Region. The trial was registered at ClinicalTrials.gov-registered trial (Identifier: NCT01001871). Ethical approval was obtained and informed consent were sought from each participant parents/guardian. For the current objective, 871 children aged 6-35 months were screened, from which 435 children received semi-liquid home-made meals mixed with 12.5 mg of iron daily (intervention group), and 436 received micronutrient powder without iron (placebo group) for 5 months. Standardized clinical and epidemiological questionnaires were administered and blood samples taken to measure IgG responses to GLURP R0, GLURP R2 and MSP3 FVO recombinant antigens using the Afro Immunoassay (AIA) protocol. RESULTS: Baseline anthropometry, malaria diagnosis, anaemia and iron status, demographic features and dietary intake were identical among the groups (p > 0.05). After the intervention, there was no significant difference in the IgG response against GLUP R0, GLUP R2 and MSP3 FVO between the iron-containing micronutrient and placebo groups (p > 0.05). The iron-containing micronutrient powder group who were iron-sufficient or iron replete had significantly higher IgG response to GLURP R0 and GLURP R2 compared to iron-deficient and iron-deficiency anaemia in the same group (p < 0.05). The IgG responses to all the three malaria specific antigens were low among children without malaria episode but high among those with two and four episodes due to exposure differences. CONCLUSION: Iron fortification did not influence antibody response against endogenous malaria specific antigens among pre-school children in malaria endemic areas, however, IgG response to malaria specific antigens were high among children with sufficient iron status.
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Antígenos de Protozoos/inmunología , Suplementos Dietéticos , Inmunoglobulina G/inmunología , Hierro/uso terapéutico , Malaria/inmunología , Preescolar , Método Doble Ciego , Femenino , Ghana/epidemiología , Humanos , Lactante , Masculino , Proteínas Protozoarias/inmunologíaRESUMEN
BACKGROUND: Vitamin D is a steroid hormone important for the normal functioning of the body. It is produced through skin exposure to sunlight and from the diet. Although Ghana is located in the tropics where sunlight is abundant, factors like culture, diet, skin pigmentation, variation in the ozone layer, and geographical area influence the optimization of vitamin D concentration. It is imperative to evaluate the interplay between sunshine exposure, proinflammatory cytokines, and mediators of vitamin D metabolism and their relationship to vitamin D status in three geographical sections among apparent healthy Ghanaians. METHODS AND RESULTS: In a cross-sectional study, a total of five hundred (500) healthy blood donors from three geographical areas in Ghana were enrolled. Their age ranged from 17 to 55 years with a mean age of 27.97 ± 8.87 years. The overall prevalence rate of vitamin D deficiency was 43.6% (218/500), with 41.2% (91/221), 45.3% (63/139), and 45.7% (64/140) of vitamin D deficiency being recorded in participants from the Northern Sector (NS), Middle Belt (MB), and Southern Sector (SS), respectively. However, there were no significant differences in the proportions of vitamin D deficiency across various geographical sectors. The median 25-hydroxyvitamin D serum levels were compared among geographical areas (NS, MB, and SS) and there were no significant differences (P=0.275) after adjusting for confounding factors. 25-Hydroxyvitamin D correlated positively with corrected ionized calcium (rs = 0.622, P ≤ 0.001) and phosphorus (rs = 0.299, P ≤ 0.001) and negatively correlated with SBP (rs = -0.092, P=0.039), vitamin D binding protein (VDBP) (rs = -0.421, P ≤ 0.001), intact parathyroid hormone (iPTH) (rs = -0.0568, rs ≤ 0.001), IFN-gamma (rs = -0.684, P ≤ 0.001), and TNF-alpha (rs = -0.600, P ≤ 0.001). After adjusting for possible confounders, not having knowledge about vitamin D foods, taking fewer vitamin D foods, and higher levels of IF-γ and IL-10 were associated with a higher risk of having vitamin D deficiency. CONCLUSION: The prevalence of 25-hydroxyvitamin D deficiency is high among the general adult population in Ghana despite the abundance of sunlight. Increasing knowledge on vitamin D diet coupled with a daily intake of vitamin D dietary supplements is likely to reduce the risk of developing 25-hydroxyvitamin D deficiency.
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BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens. METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment. RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment. CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.
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Antihelmínticos/uso terapéutico , Anticuerpos Antiprotozoarios/inmunología , Infecciones por Uncinaria/tratamiento farmacológico , Vacunas contra la Malaria/inmunología , Malaria Falciparum/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Albendazol/uso terapéutico , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Infecciones por Uncinaria/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Estudios Longitudinales , Vacunas contra la Malaria/genética , Malaria Falciparum/parasitología , Masculino , Persona de Mediana Edad , Parasitemia/parasitología , Proteínas Protozoarias/inmunología , Adulto JovenRESUMEN
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.
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Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/farmacología , Deficiencia de Vitamina B 12/complicaciones , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Ghana , Humanos , Masculino , Metformina/uso terapéutico , Persona de Mediana EdadRESUMEN
The D614G variant of SARS-CoV-2 S-protein emerged in early 2020 and quickly became the dominant circulating strain in Europe and its environs. The variant was characterized by the higher viral load, which is not associated with disease severity, higher incorporation into the virion, and high cell entry via ACE-2 and TMPRSS2. Previous strains of the coronavirus and the current SARS-CoV-2 have demonstrated the selection of mutations as a mechanism of escaping immune responses. In this study, we used molecular dynamics simulation and MM-PBSA binding energy analysis to provide insights into the behaviour of the D614G S-protein at the molecular level and describe the neutralization mechanism of this variant. Our results show that the D614G S-protein adopts distinct conformational dynamics which is skewed towards the open-state conformation more than the closed-state conformation of the wild-type S-protein. Residue-specific variation of amino acid flexibility and domain-specific RMSD suggest that the mutation causes an allosteric conformational change in the RBD. Evaluation of the interaction energies between the S-protein and neutralizing antibodies show that the mutation may enhance, reduce or not affect the neutralizing interactions depending on the neutralizing antibody, especially if it targets the RBD. The results of this study have shed insights into the behaviour of the D614G S-protein at the molecular level and provided a glimpse of the neutralization mechanism of this variant.
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Enzima Convertidora de Angiotensina 2/química , Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Receptores Virales/química , SARS-CoV-2/genética , Serina Endopeptidasas/química , Glicoproteína de la Espiga del Coronavirus/química , Sustitución de Aminoácidos , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/metabolismo , Sitios de Unión , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/transmisión , COVID-19/virología , Evolución Molecular , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Humanos , Simulación de Dinámica Molecular , Mutación , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Estructura Secundaria de Proteína , Receptores Virales/genética , Receptores Virales/metabolismo , SARS-CoV-2/inmunología , Selección Genética , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , TermodinámicaRESUMEN
Anaemia in young sub-Saharan African children may be due to the double burden of malaria and iron deficiency. Primary analysis of a double-blind, cluster randomized trial of iron containing micronutrient powder supplementation in Ghanaian children aged 6 to 35 months found no difference in malaria risk between intervention and placebo groups. Here, we performed a secondary analysis of the trial data to assess the impact of long-term prophylactic iron fortificant on the risk of iron deficiency and anaemia in trial subjects. This population-based randomized-cluster trial involved 1958 children aged between 6 to 35 months, identified at home and able to eat semi-solid foods. The intervention group (n = 967) received a daily dose containing 12.5 mg elemental iron (as ferrous fumarate), vitamin A (400 µg), ascorbic acid (30 mg) and zinc (5 mg). The placebo group (n = 991) received a similar micronutrient powder but without iron. Micronutrient powder was provided daily to both groups for 5 months. At baseline and endline, health assessment questionnaires were administered and blood samples collected for analysis. The two groups had similar baseline anthropometry, anaemia, iron status, demographic characteristics, and dietary intakes (p > 0.05). Of the 1904 (97.2%) children who remained at the end of the intervention, the intervention group had significantly higher haemoglobin (p = 0.0001) and serum ferritin (p = 0.0002) levels than the placebo group. Soluble transferrin receptor levels were more saturated among children from the iron group compared to non-iron group (p = 0.012). Anaemia status in the iron group improved compared to the placebo group (p = 0.03). Continued long-term routine use of micronutrient powder containing prophylactic iron reduced anaemia, iron deficiency and iron deficiency anaemia among pre-school children living in rural Ghana's malaria endemic area.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Compuestos Ferrosos/uso terapéutico , Oligoelementos/uso terapéutico , Anemia Ferropénica/sangre , Anemia Ferropénica/epidemiología , Ácido Ascórbico/uso terapéutico , Preescolar , Suplementos Dietéticos , Femenino , Ghana/epidemiología , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Efecto Placebo , Vitamina A/uso terapéutico , Vitaminas/uso terapéutico , Zinc/uso terapéuticoRESUMEN
BACKGROUND: Acute kidney injury (AKI) is routinely diagnosed by creatinine-based guidelines, which is sub-optimal marker after injury due to renal and non-renal factors. This has necessitated the need for more specific and sensitive biomarkers for early detection of AKI in at risk patients. This prospective cross-sectional study used the biomarkers of cell cycle arrest and Neutrophil Gelatinase Associated Lipocalin (NGAL) to assess AKI among hospitalized patients. METHODS: We conveniently enrolled 151 in-patients at the Trauma and Specialist Hospital, Winneba in Ghana. Socio-demographic and clinical information were collected using structured questionnaires. Blood samples were collected for the estimation of serum creatinine, and AKI diagnosed and staged using the KDIGO guideline. Fresh urine samples were collected and urinary NGAL, TIMP-2 (tissue inhibitor metalloproteinase 2) and IGFBP-7 (insulin-like growth factor binding protein 7) were estimated using ELISA kits. RESULTS: The cell cycle arrest biomarkers and NGAL were significantly (P < 0.001) higher among participants with AKI than those without AKI. [TIMP-2]∗[IGFBP-7] showed the best diagnostic performance (AUC = 0.94, CI = 0.90-0.98) followed by [IGFBP-7]∗NGAL] (AUC = 0.93, CI = 0.87-0.99), with NGAL having the least (AUC = 0.62, CI = 0.46-0.78). The cut-off for [TIMP-2]∗[IGFBP-7] showed the best predictive ability (95.8% sensitivity, 77.2% specificity, 44.2% PPV and 99% NPV). The cut-off for NGAL, on the other hand, showed the least predictive ability (62.5% sensitivity, 42.5% specificity, 17.0% PPV and 85.7% NPV). CONCLUSION: Tissue inhibitor metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) best predicts the development of AKI, and can be used in high risk patients for early diagnosis of AKI.
RESUMEN
Highly active antiretroviral therapy (HAART) is known to cause lipid abnormalities such as dyslipidaemia in HIV-infected individuals. Yet, dyslipidaemia may not independently occur as it may be worsened by single nucleotide polymorphisms (SNPs) in lecithin cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). This case-control study was conducted in three-selected hospitals in the Northern part of Ghana. The study constituted a total of 118 HIV-infected participants aged 19-71 years, who had been on HAART for 6-24 months. Dyslipidaemia was defined based on the NCEP-ATP III criteria. HIV-infected individuals on HAART with dyslipidaemia were classified as cases while those without dyslipidaemia were grouped as controls. Lipid profile was measured using an automatic clinical chemistry analyzer and genomic DNA was extracted for PCR (GeneAmp PCR System 2700). Overall, the prevalence of dyslipidaemia was 39.0% (46/118). High levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and reduced levels of high-density lipoprotein cholesterol (HDL-C) were observed in all cases. A total of 256 selected PCR amplicons comprising 137 LPL (exons 3, 5 and 6) and 119 LCAT (exons 1, 4, and 6) were sequenced in 46 samples (Inqaba Biotech). Six (6) clinically significant SNPs were identified in exons 1 and 4 for LCAT whereas 25 non-clinically significant SNPs were identified for LPL in exons 5 and 6. At position 97 for LCAT exon 1, there was a deletion of the nucleotide, 'A' in 32.5% (13/40) of the sampled population while 67.5% (27/40) of the sample population retained the nucleotide, 'A' which was significantly associated with dyslipidaemic outcomes in the study population (p = 0.0004). A total of 25 SNPs were identified in exons 5 and 6 of LPL; 22 were substitutions, and 3 were insertions. However, none of the 25 SNPs identified in LPL exon 5 and 6 were statistically significant. SNPs in LCAT may independently contribute to dyslipidaemia among Ghanaian HIV-infected individuals on HAART, thus, allowing genetic and/or functional differential diagnosis of dyslipidaemia and creating an opportunity for potentially preventive options.
Asunto(s)
Dislipidemias/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Estudios de Casos y Controles , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/sangre , Dislipidemias/etiología , Exones/genética , Ghana , Infecciones por VIH/sangre , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Triglicéridos/sangre , Adulto JovenRESUMEN
BACKGROUND: T cell cytokines play important roles in the development and progression of rheumatoid arthritis (RA). Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. However, their role in RA within hitherto rare Ghanaian context has not been explored. Here, we evaluated the intracytoplasmic CD4+ T cell cytokine patterns in rheumatoid arthritis patients in Ghana and determined their relationship with disease activity. METHODS: This case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from two major hospitals in Ghana. Validated structured questionnaires were administered to obtain demographic data; blood samples were collected and processed for flow cytometric analysis. RESULTS: IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, IL-6/IL-4, and IL-17/IL-10 expressions were significantly higher in RA cases compared to the healthy controls. The expression of IL-6 (0.00 (0.00-0.98) vs. 0.82 (0.34-1.10) vs. 1.56 (1.39-1.68), p < 0.0001), IL-17A (0.00 (0.00-0.02) vs. 0.19 (0.09-0.30) vs. 0.99 (0.64-1.25), p < 0.0001), and IL-17A/IL-10 (0.00 (0.00-0.39) vs. 0.15 (0.09-0.26) vs. 0.88 (0.41-1.47), p < 0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (ß = 0.681, r 2 = 0.527, p < 0.0001), IL-17A (ß = 0.770, r 2 = 0.593, p < 0.0001), and IL-17A/IL-10 (ß = 0.677, r 2 = 0.452, p < 0.0001) expressions were significantly directly associated with DAS28 scores. IL-6 (cutoff = 1.32, sensitivity = 100.0%, specificity = 100.0%, accuracy = 100.0%, and AUC = 1.000) and IL-17A (cutoff = 0.58, sensitivity = 100.0%, specificity = 100.0%, accuracy = 100.0%, and AUC = 1.000) presented with the best discriminatory power in predicting moderate DAS scores from low DAS scores. CONCLUSION: Th1- and Th17-related cytokines predominate in the pathophysiology of RA, with IL-6 and IL-17 being principally and differentially expressed based on the severity of the disease. IL-6 and IL-17A could serve as useful prognostic and disease-monitoring markers in RA in the African context.
RESUMEN
BACKGROUND: This prospective cohort study evaluated the usefulness of conventional PCR in genotyping fetal Rhesus D (RhD) and sex from the maternal plasma of RhD-negative (RhD-) antenatal population in resource-limited settings. METHODS: Thirty apparently healthy RhD- pregnant women with RhD positive (RhD+) partners were included. Blood samples were collected from each participant (in the third trimester of pregnancy) for DNA extraction/purification and fetal RhD genotyping. RESULTS: Out of the 30 samples, 26 (86.7%) were found to be RhD+ while 4 (13.3%) were RhD-. The RhD+ comprised 24 (80.0%) RhD+ based on exons 5, 7, and 10 combined. Exons 5 and 7 were detected in two additional samples but not exon 10. Serological phenotyping of neonatal blood confirmed 26 RhD+ and 4 RhD-. There was a perfect agreement between the fetal RhD genotype and neonatal RhD phenotyping after delivery for exons 5 and 7 (concordance = 100%, κ = 100.0%, diagnostic accuracy = 100%, p < 0.0001) while exon 10 presented with an almost perfect agreement (concordance = 93.3%, κ = 76.2%, diagnostic accuracy = 93.3%, p < 0.0001). Regarding the prenatal test for the SRY gene, 9 (30.0%) were predicted to be males and the remaining 21 (60.0%) were females. All the 9 and 21 anticipated males and females, respectively, were confirmed after delivery (concordance = 100%, κ = 100.0%, diagnostic accuracy = 100%). CONCLUSION: Our study suggests that conventional PCR using the SRY, RhD exons 5 and 7 could be useful for predicting fetal sex and RhD from maternal peripheral blood in resource-limited settings.
