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Abstract Objectives We determined the prevalence and risk factors of hypertension among public servants of Ejisu Juaben municipality. Results The overall prevalence of hypertension was 29.3% (95%CI:22.5–36.1%) and only 8.6% of the participants were aware of their hypertensive status. Respondents who were > 40 years were twice as likely to develop hypertension compared to those who were ≤ 40 years [adjusted odds ratio (AOR) = 2.37, 95% confidence interval (CI) 1.05–5.32]. Those who were married were 2.54 times more likely to be hypertensive compared with those unmarried [AOR = 2.54, 95%CI: 1.06–6.08]. Compared to health workers, Judicial and Security service workers were almost five times more likely to be hypertensive [AOR = 4.77, 95%CI: 1.20–18.96]. Being overweight [AOR = 2.25, 95%CI: 1.06–6.41] and obese [AOR = 4.80, 95%CI: 1.82–12.91] was associated with increased odds of hypertension. The prevalence of hypertension among the participants in this study is high. Employee wellness programs are needed at workplaces and the Ghana Health Service must adopt targeted intervention programs such as regular screening for non-communicable diseases and promotion of physical activities at the workplace.

Background: Bacterial meningitis continues to be a global health problem even after introducing of meningococcal and pneumococcal vaccines. Surveillance of high-risk populations such as prisoners is necessary for timely identification of outbreaks and prophylaxis. This study assessed pharyngeal colonisation of prisoners and officers in a Ghanaian prison with meningitis-causing bacteria. Methods: A cross-sectional study was conducted from January to April 2018. Oropharyngeal swabs were collected, and microbiological and antimicrobial susceptibility analyses were performed. Results: There were 205 participants. Carriage of meningitis-causing bacterial was 102 (49.7%), 8 (3.9%) and 1(0.48%) for Neisseria species (spp.), Staphylococcus aureus (S. aureus) and Streptococcus pneumoniae (S. pneumoniae), respectively and with a total carriage of 52.2% (107/ 205). Four individuals (1.9%) carried both Neisseria spp. and S. aureus. The S. aureus isolates were resistant to ampicillin (87.5%), chloramphenicol (87.5%), and penicillin (87.5%) and sensitive to cefoxitin (100%) cotrimoxazole (87.5%), clindamycin (87.5%), ciprofloxacin (75.0%), oxacillin (75.0%), and erythromycin (62.5%). None of the S. aureus isolated was methicillin resistant. The S. pneumoniae isolated was resistant to cotrimoxazole, tetracycline, and penicillin and sensitive to chloramphenicol, erythromycin, and clindamycin. Education (OR = 1.910, 95% CI 1.029 – 3.545, p < /em> = 0.040) and years of incarceration (OR = 3.808, 95% CI 1.350 – 10.739, p < /em> = 0.011) were associated with carriage of meningitis-causing bacteria. Conclusion: This study showed carriage of potential meningitis-causing bacteria in a Ghanaian prison. Multivalent meningococcal conjugate vaccine is key to controlling meningococcal disease outbreaks.

Background: T-lymphocyte subsets CD4 and CD8 play important role in host immune responses. However, little attention has been given to the impact of time lapse and the various anticoagulant blood collection tubes on the expression frequency and activation status of CD4+ and CD8+ T cells. To this end, we explore the impact of time (t

Abstract Background Antimicrobial resistance is associated with increased morbidity in secondary infections and is a global threat owning to the ubiquitous nature of resistance genes in the environment. Recent estimate put the deaths associated with bacterial antimicrobial resistance in 2019 at 4.95 million worldwide. Lymphatic filariasis (LF), a Neglected Tropical Disease (NTD), is associated with the poor living in the tropical regions of the world. LF patients are prone to developing acute dermatolymphangioadenitis (ADLA), a condition that puts them at risk of developing secondary bacterial infections due to skin peeling. ADLA particularly worsens the prognosis of patients leading to usage of antibiotics as a therapeutic intervention. This may result in inappropriate usage of antibiotics due to self-medication and non-compliance; exacerbating antimicrobial resistance in LF patients. In this perspective, we assessed the possibilities of antimicrobial resistance in LF patients. We focused on antibiotic usage, antibiotic resistance in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa isolates and looked at genes (mecA and Extended-spectrum beta-lactamase [blaCTX-M, blaSHV and blaTEM]) coding for resistance in multi-drug resistant (MDR) bacterial isolates. Results Of the sixty (60) participants, fifty-four (n = 54, 90%) were within 31–60 years of age, twenty (n = 20, 33.33%) were unemployed and thirty-eight (n = 38, 50.67%) had wounds aged (in months) seven (7) months and above. Amoxicillin (54%) and chloramphenicol (22%) were the most frequently used antibiotics for self-medication. Staphylococcus aureus isolates (n = 26) were mostly resistant to penicillin (n = 23, 88.46%) and least resistant to erythromycin (n = 2, 7.69%). Escherichia coli isolates (n = 5) were resistant to tetracycline (n = 5, 100%) and ampicillin (n = 5, 100%) but were sensitive to meropenem (n = 5, 100%). Pseudomonas aeruginosa isolates (n = 8) were most resistant to meropenem (n = 3, 37.50%) and to a lesser ciprofloxacin (n = 2, 25%), gentamicin (n = 2, 25%) and ceftazidime (n = 2, 25%). Multi-drug resistant methicillin resistant Staphylococcus aureus (MRSA), cephalosporin resistant Escherichia coli. and carbapenem resistant Pseudomonas aeruginosa were four (n = 4, 15.38%), two (n = 2, 40%) and two (n = 2, 25%) respectively. ESBL (blaCTX-M) and mecA genes were implicated in the resistance mechanism of Escherichia coli and MRSA, respectively. Conclusion The findings show presence of MDR isolates from LF patients presenting with chronic wounds; thus, the need to prioritize resistance of MDR bacteria into treatment strategies optimizing morbidity management protocols. This could guide antibiotic selection for treating LF patients presenting with ADLA.

Abstract Background Filarial infections continue to pose a great challenge in endemic countries. One of the central goals in the fight against human filarial infections is the development of strategies that will lead to the inhibition of microfilariae (mf) transmission. Keeping mf under a certain threshold within endemic populations will stop transmission and eliminate the infection. Method A narrative review was carried out to identify the possibilities and limitations of exploring the use of eosinophil responses as an anti‐filarial vaccine, and biomarker for the detection of filarial infections. An extensive literature search was performed in online scientific databases including PubMed Central, PubMed, BioMed Central, with the use of predefined search terms. Results A better understanding of the parasite‐host interactions will lead to the development of improved and better treatment or vaccine strategies that could eliminate filariasis as soon as possible. Highlighted in this review is the explorative use of eosinophil‐producing CLC/Galectin‐10 as a potential biomarker for filarial infections. Also discussed are some genes, and pathways involved in eosinophil recruitments that could be explored for anti‐filarial vaccine development. Conclusion In this short communication, we discuss how eosinophil‐regulated genes, pathways, and networks could be critical in providing more information on how reliably a front‐line immune player could be exploited for anti‐filarial vaccine development and early infection biomarker.

Abstract Despite the successes achieved so far with the Global Programme to Eliminate Lymphatic Filariasis, there is still an appreciable number of lymphatic filarial patients who need alternative treatment and morbidity management strategies. The unresponsiveness of some cohorts to the drugs used in the mass drug administration program is currently raising a lot of questions and this needs urgent attention. Natural medicinal plants have a long‐standing history of being effective against most disease conditions. Countries such as India have been able to integrate their natural plant remedies into the treatment of lymphatic filarial conditions, and the results are overwhelmingly positive. Components of Azadirachta indica A. Juss, Parkia biglobosa, Adansonia digitata, and Ocimum spp have been shown to have anti‐inflammatory, anticancerous, and antimicrobial activities in animal models. Therefore, this review calls for attention toward the use of natural plant components as an alternate treatment against lymphatic filariasis to help reduce the World Health Organization's burden of providing drugs for people in need of treatment every year.

Abstract Background and Aims Hemolysis is a fundamental feature of sickle cell disease (SCD) contributing to the vaso‐occlusive crisis of patients. The objectives of the study were to assess the link between hemolysis proteins and hematological parameters, and to validate cystatin C (CYS C) as a potent renal marker in diagnoising SCD. Method Here, a cross‐sectional study carried out at the pediatric SCD clinic of the Komfo Anokye Teaching Hospital comprised 90 SCD children (HbSC, HbSF, and HbSS). ANOVA, t‐test, and Spearman's rank correlation analysis were done. Elevated proteins levels were compared to standard values; alpha‐1 microglobulin (A1M) (1.8−65 µg/L), CYS C (0.1−4.5 µmol/L), and haemopexin (HPX) (500−1500 µg/mL). Results The mean (standard deviation) age of participants was 9.830 (±0.3217) years, and 46% of them were males. From simple descriptive analysis, we observed that all but one patient had their HPX level below the reference range (

Abstract Background The uptake of sickle cell trait (SCT) test is challenged by several factors. A community of healthcare professionals educating the public to undergo screening is critical in reducing the disease burden. We investigated knowledge and attitude towards premarital SCT screening among healthcare trainee students who are the next generation of healthcare practitioners. Methods A cross‐sectional design was employed, and quantitative data were collected from 451 female students pursuing healthcare programs at a tertiary institution in Ghana. Descriptive, bivariate, and multivariate logistic regression analysis was performed. Results More than half of the participants were 20–24 years (54.55%) and had good knowledge (71.18%) about sickle cell disease (SCD). Age and school or social media as sources of information were significantly associated with good knowledge about SCD. Students between the age 20–24 (adjusted odds ratio [AOR] = 2.54, confidence interval [CI] = 1.30–4.97) and knowledge (AOR = 2.19, CI = 1.41–3.39) were 3 times and 2 times more likely to have a positive perception about SCD severity. Students who have SCT (AOR = 5.16, CI = 2.46–10.82), whose source of information was family member/friends (AOR = 2.83, CI = 1.44–5.59) and social media (AOR = 4.59, CI = 2.09–10.12) were 5 times, 2 times and 5 times likely to have a positive perception about the susceptibility of SCD. Students whose source of information is school (AOR = 2.06, CI = 1.11–3.81) and who have good knowledge of SCD (AOR = 2.25, CI = 1.44–3.52) were 2 times more likely to have a positive perception about the benefits of testing. Students with SCT (AOR = 2.64, CI = 1.36–5.13) and source of information was social media (AOR = 3.01, CI = 1.36–6.64) were about 3 times more likely to have a positive perception about the barriers to testing. Conclusion Our data shows that high level of SCD knowledge influences positive perceptions about the severity of SCD, the benefits and relatively low barriers to SCT or SCD testing and genetic counseling. Dissemination of SCT, SCD and premarital genetic counseling education should be intensified especially in schools.

Abstract Background and Aim Filarial infections affect over 150 million people in the tropics. One of the major forms of filarial pathologies is lymphedema; a condition where the immune response is significantly altered, resulting in changes in the normal flora. Staphylococcus hominis, a human skin commensal, can also be pathogenic in immunocompromised individuals. Therefore, there is the possibility that S. hominis could assume a different behavior in filarial lymphedema patients. To this end, we investigated the levels of antibiotic resistance and extent of mecA gene carriage in S. hominis among individuals presenting with filarial lymphedema in rural Ghana. Method We recruited 160 individuals with stages I–VII lymphedema, in a cross‐sectional study in the Ahanta West District of the Western Region of Ghana. Swabs from lymphedematous limb ulcers, pus, and cutaneous surfaces were cultured using standard culture‐based techniques. The culture isolates were subjected to Matrix‐Assisted Laser Desorption/Ionization Time of Flight (MALDI‐TOF) mass spectrometry for bacterial identification. Antimicrobial susceptibility testing (AST) was performed using the Kirby–Bauer method. mecA genes were targeted by polymerase chain reaction for strains that were cefoxitin resistant. Results In all, 112 S. hominis were isolated. The AST results showed resistance to chloramphenicol (87.5%), tetracycline (83.3%), penicillin (79.2%), and trimethoprim/sulphamethoxazole (45.8%). Of the 112 strains of S. hominis, 51 (45.5%) were resistant to cefoxitin, and 37 (72.5%) of the cefoxitin‐resistant S. hominis haboured the mecA gene. Conclusion This study indicates a heightened level of methicillin‐resistant S. hominis isolated among filarial lymphedema patients. As a result, opportunistic infections of S. hominis among the already burdened filarial lymphedema patients in rural Ghana may have reduced treatment success with antibiotics.

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease that is one of the leading global causes of permanent disability. To date, LF interventions have been largely biomedical, focusing on drug treatments to disrupt parasite transmission and manage disease morbidity. Although important, these Mass Drug Administration (MDA) programs neglect the significance of socio-economic burden to the health of LF patients, which are compounded by social stigmatization, discrimination and associated depressive illnesses. The MDA program also typically fails to engage with local community beliefs and perceptions of LF, which may differ markedly from biomedical explanations and may have fueled non-compliance to treatments which is one of the major challenges of the Mass Drug Administration program. LF is not only a biomedical issue but also a social issue and LF interventions need to understand people's world views and the contexts through which they interpret bodily maladies. Hence, an effective LF intervention must bring together both the biomedical and the social components. The goal of this exploratory study was to assist in refining a large qualitative study (currently underway) that seeks to integrate culturally appropriate LF interventions into current LF control programs in Ghana. In this paper, we discuss the findings of a pre-intervention, exploratory study aimed at gaining a baseline grasp of a local culturally informed understanding of lymphatic filariasis and the knowledge gaps looking at three endemic Ghanaian communities in the Ahanta West District. A structured questionnaire was employed to assess the wellbeing, social inclusion, and cultural understanding of LF with a geographic focus within LF-endemic areas in Ghana. Interestingly, 45.8% of the 72 participants reported to have received information about LF from health care providers and the MDA program but only 5 out of the 72 (6.9%) respondents believed that LF was transmitted by mosquitos. This baseline study revealed several alternative interpretations and misconceptions about the disease, as well as the social and economic impacts, and importantly, the need to integrate qualitative research to develop culturally appropriate interventions and increase engagement with existing control programs.

Background and Aim. RNA extraction is a commonly used technique in molecular biology. In recent years, commercially available RNA extraction kits have largely replaced conventional approaches. However, these commercial kits are expensive and are not readily available in many resource-constrained institutions and laboratories. This study therefore compared the performance of the conventional acid guanidinium thiocyanate-phenol-chloroform (AGPC) extraction method to QIAamp® Viral RNA Mini Kit (QIAGEN, Cat. No. 52906) and OxGEn RNA Kit (OxGEn Molecular Solutions, GE-009) to build an in-house RNA extraction technique from blood and oral swab samples. Method. In a comparative experimental cross-sectional study, RNA was extracted from oral swabs and blood samples from 25 healthy individuals at the Department of Molecular Medicine, KNUST. RNA was extracted by the manual AGPC extraction method and commercial RNA extraction kits. The quantity (ng/μl) and purities (260/280 nm) of the extracted RNA were measured spectrophotometrically using the IMPLEN NanoPhotometer® N60. The presence of RNA in the extracts was confirmed using 2% agarose gel electrophoresis. Statistical analyses were conducted using R language. Results. The yield of RNA extracted from blood and oral swab samples using modified AGPC was significantly higher compared to the commercial methods (p

BackgroundThe use of motor tricycles in transporting municipal solid waste (MSW) within urban and peri-urban towns in Ghana is on the increase. This activity often leads to the introduction of pathogen-containing bioaerosols into the environment, as well as to the tricycle operators. We sought to investigate the prevalence and associated risk factors of respiratory pathogens among solid waste tricycle operators.MethodsA cross-sectional study was conducted among 155 solid waste transporters who use motor tricycles using semi-structured interviews. Nasopharyngeal swabs were obtained from participants and screened for respiratory pathogens using Polymerase Chain Reaction (PCR).ResultsPathogens detected in participants were SARS-CoV-2 (n = 10, 6.5%) and Streptococcus pneumoniae (n = 10, 6.5%), constituting an overall prevalence of 12.9% and co-infection rate of 1.3%. The most common self-reported symptoms were cough (n = 67, 43.2%), sore throat (n = 44, 28.4%) and difficulty in breathing (n = 22, 14.2%). Adherence to the use of gloves (n = 117, 75.5%) and nose mask (n = 110, 71.0%) was high. There was a significant association between the detection of respiratory pathogens and the use of gloves, use of more than one PPE and exposure to other pollutants (p < 0.05). Individuals who were exposed to "other pollutants" significantly had lower odds of becoming infected with respiratory pathogens (Adj. OR (95% CI): 0.119(0.015,0.938).ConclusionAlthough prevalence of respiratory pathogens is generally low, strict adherence to PPE use could further reduce its rates to even lower levels. Governmental health institutions and informal solid waste transporters should address challenges related to exposure to pollutants, use of gloves, and multiple PPE.

Background The use of motor tricycles in transporting municipal solid waste (MSW) within urban and peri-urban towns in Ghana is on the increase. This activity often leads to the introduction of pathogen-containing bioaerosols into the environment, as well as to the tricycle operators. We sought to investigate the prevalence and associated risk factors of respiratory pathogens among solid waste tricycle operators. Methods A cross-sectional study was conducted among 155 solid waste transporters who use motor tricycles using semi-structured interviews. Nasopharyngeal swabs were obtained from participants and screened for respiratory pathogens using Polymerase Chain Reaction (PCR). Results Pathogens detected in participants were SARS-CoV-2 (n = 10, 6.5%) and Streptococcus pneumoniae (n = 10, 6.5%), constituting an overall prevalence of 12.9% and co-infection rate of 1.3%. The most common self-reported symptoms were cough (n = 67, 43.2%), sore throat (n = 44, 28.4%) and difficulty in breathing (n = 22, 14.2%). Adherence to the use of gloves (n = 117, 75.5%) and nose mask (n = 110, 71.0%) was high. There was a significant association between the detection of respiratory pathogens and the use of gloves, use of more than one PPE and exposure to other pollutants (p < 0.05). Individuals who were exposed to “other pollutants” significantly had lower odds of becoming infected with respiratory pathogens (Adj. OR (95% CI): 0.119(0.015,0.938). Conclusion Although prevalence of respiratory pathogens is generally low, strict adherence to PPE use could further reduce its rates to even lower levels. Governmental health institutions and informal solid waste transporters should address challenges related to exposure to pollutants, use of gloves, and multiple PPE.

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-1β 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-1β, 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.

Abstract Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients.

Abstract Background and Aims Children with sickle cell disease (SCD) have an increased risk of multiple hemotransfusions and this can predispose them to elevated iron stores. The objectives of the study were to determine the extent of elevated iron stores and the associated risk factors in a population of steady‐state SCD children in Ghana. Methods This cross‐sectional study was conducted at the pediatric sickle cell clinic at the Komfo Anokye Teaching Hospital. Complete blood count and serum ferritin assay were performed for (n = 178) steady‐state SCD children. Descriptive and multivariate logistic regression analysis were performed. Elevated iron stores were defined as serum ferritin levels >300 ng/ml. Statistical significance was considered at p

Filarial infections caused by nematodes are one of the major neglected tropical diseases with public health concern. Although there is significant decrease in microfilariae (mf) prevalence following mass drug administration (IVM/DEC/ALB administration), this is transient, in that there is reported microfilaria repopulation 6-12 months after treatment. Wolbachia bacteria have been recommended as a novel target presenting antibiotic-based treatment for filarial disease. Potency of antibiotics against filarial diseases is undoubtful, however, the duration for treatment remains a hurdle yet to be overcome in filarial disease treatment.

Abstract Introduction The active form of vitamin D has immunomodulatory and anti‐inflammatory effect. Vitamin D is implicated in pathogenesis of rheumatoid arthritis (RA) and its deficiency leads to increased inflammation. Moreover, its production is dependent on concentration of calcium, phosphorus, and parathyroid hormone (PTH). Cytokines mediates inflammation in RA synovium. This study evaluated vitamin D, its mediators and proinflammatory cytokines among RA patients. Methods In a case–control study, 78 RA patients from Komfo Anokye Teaching Hospital rheumatology clinic and 60 healthy blood donors were recruited. Chemistry analyzer and enzyme‐linked immunosorbent assay kits were used to measure biochemical parameters and cytokines. Results We found significantly higher levels of interleukin (IL)‐1β, interferon gamma (IFN‐γ), and tumor necrosis factor‐α (TNF‐α) in RA patients compared with controls (p .05), IL‐1β (r = −0.25, p > .05), TNF‐α (r = −0.26, p > .05), IFN‐γ (r = −0.24, p > .05), and iPTH. There was a significant negative correlation between IL‐1β (r = −0.33, p

Abstract Background Lymphatic Filariasis (LF), a neglected tropical disease, has been speculated to be complicated by secondary bacteria, yet a systematic documentation of these bacterial populations is lacking. Thus, the primary focus of this study was to profile bacteria diversity in the progression of filarial lymphedema among LF individuals with or without wounds. Methods A cross‐sectional study design recruited 132 LF individuals presenting with lymphedema with or without wounds from eight communities in the Ahanta West District in the Western Region, Ghana. Swabs from the lymphedematous limbs, ulcers, pus, and cutaneous surfaces were cultured using standard culture‐based techniques. The culture isolates were subsequently profiled using Matrix‐assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry. Results Of the 132 LF participants recruited, 65% (85) had filarial lymphedema with no wounds. In total, 84% (235) of the bacterial isolates were identified. The remaining 16% (46) could not be identified with the method employed. Additionally, 129(55%) of the strains belonged to the phylum Firmicutes, while 61 (26%) and 45 (19%) represented Proteobacteria and Actinobacteria, respectively. Generally, irrespective of the samples type (i.e., wound sample and non‐wound samples), there was a sharp increase of bacteria diversity from Stages 1 to 3 and a drastic decrease in these numbers by Stage 4, followed by another surge and a gradual decline in the advanced stages of the disease. The Shannon Diversity Index and Equitability for participants with and without wounds were (3.482, 0.94) and (3.023, 0.75), respectively. Further, Staphylococcus haemolyticus and Escherichia coli showed resistance to tetracycline, chloramphenicol, and penicillin. Conclusion The present study reveals a sharp decline in bacterial load at the late stages of filarial lymphedema patients. In addition, we report an emerging antimicrobial resistance trend of S. haemolyticus and E. coli against commonly used antibiotics such as tetracycline, chloramphenicol, and penicillin in communities endemic for LF in the Ahanta West District, Ghana. This could pose a huge challenge to the management of the disease; particularly as current treatments are not quite effective against the infection.

Background: Lymphatic filariasis (LF) is a debilitating neglected tropical disease that remains a major public challenge in endemic countries. In addition to providing mass drugs administration (ivermectin, albendazole and diethylcarbamazine) to reduce parasite burden in endemic communities, there is also a need to mitigate the challenges associated with lymphedema progression. Filarial lymphedema is known to be complicated by secondary bacterial infections; however, this is yet to receive considerable attention in LF-endemic communities in rural Ghana. Thus, the focus of this study was to understand the skin microbiome of individuals presenting with filarial lymphedema over a period. Methods: This longitudinal study employed culture and Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) to characterize the microbiota of filarial lymphedema lesions over 24 months follow-ups and considered how different it is from the skin bacterial composition of non-filarial individuals described previously in literature. Results: The result reveals that filarial lymphedema lesions had four main phyla: Firmicutes (69.7%), Proteobacteria (16.6%), Actinobacteria (13.3%), and Bacteroidetes (0.3%). Firmicutes presented the highest abundance. There were observable differences in the distribution of Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria, with the Firmicutes and Proteobacteria phyla enriched while the Bacteroidetes and Actinobacteria were markedly diminished in the filarial lymphedema lesions, relative to healthy skin. Propionibacterium and Corynebacterium, which are usually resident and abundant in healthy skin, were underrepresented in the skin from lymphedema lesions. Most of the taxa found in the skin from lymphedema lesions are not the typical organisms in human skin instead they were potentially pathogenic, with the Streptococcus, Acinetobacter, Klebsiella, Pseudomonas, Bacillus, Corynebacterium, Micrococcus, Enterococcus, Proteus and Staphylococcus genera being topmost isolates. Conclusion: Our data revealed a significant shift of the bacterial population with the introduction of potentially pathogenic bacteria to compete with the healthy skin resident microbiota during LF infection.

Abstract Filarial infections affect millions of individuals and are responsible for some notorious disabilities. Current treatment options involve repeated mass drug administrations, which have been met with several challenges despite some successes. Administration of doxycycline, an anti-Wolbachia agent, has shown clinical effectiveness but has several limitations, including long treatment durations and contraindications. We describe the use of an in silico drug repurposing approach to screening a library of over 3200 FDA-approved medications against the filarial endosymbiont, Wolbachia. We target the enzyme which catalyzes the first step of heme biosynthesis in the Wolbachia. This presents an opportunity to inhibit heme synthesis, which leads to depriving the filarial worm of heme, resulting in a subsequent macrofilaricidal effect. High throughput virtual screening, molecular docking and molecular simulations with binding energy calculations led to the identification of paritaprevir and nilotinib as potential anti-Wolbachia agents. Having higher binding affinities to the catalytic pocket than the natural substrate, these drugs have the structural potential to bind and engage active site residues of the wolbachia 5′-Aminolevulinic Acid Synthase. We hereby propose paritaprevir and nilotinib for experimental validations as anti-Wolbachia agents.

Abstract Background Human lymphatic filarial pathology is the leading cause of disability and poverty among people living with the infection. The second goal of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) is to manage the disease’s morbidity to improve patients’ quality of life. Consequently, the current study assessed the overall quality of life of lymphatic filariasis (LF) pathology patients in some selected endemic communities in rural Ghana. Method In the present study, the Lymphatic Filariasis Quality of Life Questionnaire (LFSQQ) was used to evaluate the effect of lymphatic filariasis on the quality of life of people, with the disease in nine (9) communities in the Ahanta West District of the Western Region of Ghana where mass drug administration is being implemented for the past twenty years. Pearson’s correlation, linear regression, and one-way analysis of variance (ANOVA) analyses were used to assess the associations between the LFSQQ instrument domains. Results Of the 155 study participants recruited, 115 (74.19%) were females, and 40 (25.81%) males. A greater proportion of the study participants (40, 25.8%) were presented with stage two (2) lymphoedema, while only two patients had stage seven (7) lymphoedema. The average of the overall quality of life scores of study participants was 68.24. There was a negative Pearson correlation (r = − 0.504, p-value

Abstract Background Lymphatic Filariasis (LF), a parasitic nematode infection, poses a huge economic burden to affected countries. LF endemicity is localized and its prevalence is spatially heterogeneous. In Ghana, there exists differences in LF prevalence and multiplicity of symptoms in the country’s northern and southern parts. Species distribution models (SDMs) have been utilized to explore the suite of risk factors that influence the transmission of LF in these geographically distinct regions. Methods Presence-absence records of microfilaria (mf) cases were stratified into northern and southern zones and used to run SDMs, while climate, socioeconomic, and land cover variables provided explanatory information. Generalized Linear Model (GLM), Generalized Boosted Model (GBM), Artificial Neural Network (ANN), Surface Range Envelope (SRE), Multivariate Adaptive Regression Splines (MARS), and Random Forests (RF) algorithms were run for both study zones and also for the entire country for comparison. Results Best model quality was obtained with RF and GBM algorithms with the highest Area under the Curve (AUC) of 0.98 and 0.95, respectively. The models predicted high suitable environments for LF transmission in the short grass savanna (northern) and coastal (southern) areas of Ghana. Mainly, land cover and socioeconomic variables such as proximity to inland water bodies and population density uniquely influenced LF transmission in the south. At the same time, poor housing was a distinctive risk factor in the north. Precipitation, temperature, slope, and poverty were common risk factors but with subtle variations in response values, which were confirmed by the countrywide model. Conclusions This study has demonstrated that different variable combinations influence the occurrence of lymphatic filariasis in northern and southern Ghana. Thus, an understanding of the geographic distinctness in risk factors is required to inform on the development of area-specific transmission control systems towards LF elimination in Ghana and internationally.

The outbreak of the deadly novel coronavirus disease (COVID-19) has disrupted life worldwide in an unprecedented manner. Over the period, scientific breakthroughs have resulted in the rollout of many vaccination programmes to protect against the disease, reduce the fear and ease public health restrictions for lives to return to some normalcy. The aim of this study was to identify the factors responsible for COVID-19 vaccine acceptance or vaccine hesitancy and to develop a framework to improve vaccine uptake in the Ghanaian-Dutch, Afro and Hindustani Surinamese-Dutch communities in Amsterdam. Using a mixed method approach, this community-based cross-sectional survey recruited 160 respondents consisting of 57 Ghanaian-Dutch, 54 Afro Surinamese-Dutch and 49 Hindustani-Dutch residents in Amsterdam. Our findings showed that the choice of a vaccine as well as the likelihood of self-reported willingness to receive a vaccine is highly dependent on vaccine efficacy and safety. Available evidence of high vaccine effectiveness and safety could encourage about 41.3% of the respondents to accept the vaccine. Additionally, 69.6% of the respondents indicated their willingness to accept the vaccine when vaccine passports are made mandatory by the government. Other major factors that could drive the likelihood of accepting the COVID-19 vaccine include travel requirement for vaccination (28.3%), the safety/probability of only minor side effects (26.1%) and recommendation by family and friends (15.2%). The study therefore provides systematic evidence of factors associated with individual preferences toward COVID-19 vaccination. It demonstrates that the needs of each community are unique and specific interventional efforts are urgently needed to address concerns likely to be associated with vaccine hesitancy.

The T cell immune responses in filarial infections are primarily mediated by CD4+ T cells and type 2-associated cytokines. Emerging evidence indicates that CD8+ T cell responses are important for anti-filarial immunity, however, could be suppressed in co-infections. This review summarizes what we know so far about the activities of CD8+ T cell responses in filarial infections, co-infections, and the associations with the development of filarial pathologies.

The burden of infectious disease in developing countries is substantially higher than in developed nations. Reasons include poor health care infrastructure and deficiencies in public understanding of infectious disease mechanisms and disease prevention. While immunology education and research have an enviable role in understanding host-pathogen interactions, training programs in immunology remain fully integrated into the curricula of higher institutions, and by extension, to high schools of developing nations. Therefore, we discussed the need to make major investments in immunology research and research training into all natural sciences teaching curricula, particularly in developing countries.

Abstract Background Lymphatic Filariasis (LF) is a vector-borne neglected tropical disease caused by the filarial nematode parasites that can lead to the disfiguring swelling of the limbs (lymphedema or elephantiasis for late stage) and/or genitalia (hydrocele) in men. Growing evidence suggests that not only are filarial lymphedema patients confronted with huge societal stigma and discrimination, but also experience acute filarial attacks accompanied by swelling of the affected part(s), fever, wounds and peeling of the skin of affected limbs(s). However, the extent to which seasonal variation influence filarial attacks among people with lymphedema was highly speculated without empirical evidence and was thus investigated. Methods In light of this, a cross-sectional study where 142 (70.4% females and 29.6% males) lymphedema patients were recruited from 8 established Wuchereria bancrofti endemic communities in the Ahanta West District, Ghana was carried out to investigate the prevalence and seasonal variation (rainy/wet and dry seasons) of acute filarial attacks. Chi-square test was used to test for association between frequency of attacks and seasonality. The STROBE guidelines for reporting cross-sectional studies was adopted. Results The average lymphedema leg stage was 2.37 and 2.33 for left and right legs, respectively, while mossy lesions, sores and ulcers were observed among 33.1% of patients with late stage disease (elephantiasis). It was found that 97 (68.3%) of the study participants experience filarial attacks during the wet season and 36 (25.4%) reported the incidence of filarial attacks during both seasons (wet and dry) while 9 (6.3%) of the study participants did not experience any attack at all. Conclusions Findings from the present study show compelling evidence that the frequency and the prevalence of filarial attacks is significantly increased during wet seasons compared to the dry season.

Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high prevalence in developing countries, filarial infections are responsible for some of the most debilitating morbidities and a vicious cycle of poverty and disease. Global initiatives set to eradicate these infections include community mass treatments, vector control, provision of care for morbidity, and search for vaccines. However, there are growing challenges associated with mass treatments, vector control, and antifilarial vaccine development. With the emergence of genome editing tools and successful applications in other infectious diseases, the integration of genetic editing techniques in future control strategies for filarial infections would offer the best option for eliminating filarial infections. In this review, we briefly discuss the mechanisms of the three main genetic editing techniques and explore the potential applications of these powerful tools to control filarial infections.

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8–28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9–4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5–2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6–39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75–14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69–17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance.

BackgroundThe 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.MethodsIn 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.ResultsUsing 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, pConclusionVitamin 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.

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8-28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9-4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5-2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6-39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75-14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69-17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance.

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.

The occurrence of the SARS-CoV2 infection has become a worldwide threat and the urgent need to discover therapeutic interventions remains paramount. The primary roles of the coronavirus nucleocapsid (N) protein are to interact with the viral genome and pack them into ribonucleoprotein complex. It also plays critical roles at many stages of the viral life cycle. Herein, we explore the N protein of SARS-CoV2 to identify promising epitope-based vaccine candidates and target the N-terminal domain of SARS-CoV2 N-protein for potential inhibitors using an integrative bioinformatics approach. We identified B-cell epitopes and T-cell epitopes that are non-toxic, non-allergenic, capable of inducing IFN-γ and structurally stable with high global population coverage of response. The 404SKQLQQSMSSADS416 and 92RRIRGGDGKMKDL104 sequences of N-protein were identified to induce B-cell immunity. We also identified 79SSPDDQIGY87 and 305AQFAPSASAFFGMSR319 as potential T-cell epitopes that form stable structures with human leucocyte antigens. We have also identified zidovudine triphosphate, an anti-HIV agent, as a potential inhibitor of the N-terminal domain of SARS-CoV2 N-protein based on docking and simulation analysis and should be considered for experimental validations. The findings of this study can help fast-track the discovery of therapeutic options to combat COVID-19.

Abstract Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR–Cas9) are transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost of protein engineering. However, the newly developed CRISPR–Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models, generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based HIV-1 treatment and research in addition to providing perspectives for refining these techniques.

Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical symptoms and present a tightly regulated immune system characterized by higher frequencies of regulatory T cells (Treg), suppressed proliferation and Th2 cytokine responses accompanied with increased secretion of IL-10, TGF-β and infection-specific IgG4. Nevertheless, the filarial-induced modulation of the host`s immune system and especially the role of regulatory immune cells like regulatory B (Breg) and Treg during an ongoing LF infection remains unknown. Thus, we analysed Breg and Treg frequencies in peripheral blood from Ghanaian uninfected endemic normals (EN), lymphedema (LE), asymptomatic patent (CFA+MF+) and latent (CFA+MF-) W. bancrofti-infected individuals as well as individuals who were previously infected with W. bancrofti (PI) but had cleared the infection due to the administration of ivermectin (IVM) and albendazole (ALB). In summary, we observed that IL-10-producing CD19+CD24highCD38dhigh Breg were specifically increased in patently infected (CFA+MF+) individuals. In addition, CD19+CD24highCD5+CD1dhigh and CD19+CD5+CD1dhighIL-10+ Breg as well as CD4+CD127-FOXP3+ Treg frequencies were significantly increased in both W. bancrofti-infected cohorts (CFA+MF+ and CFA+MF-). Interestingly, the PI cohort presented frequency levels of all studied regulatory immune cell populations comparable with the EN group. In conclusion, the results from this study show that an ongoing W. bancrofti infection induces distinct Breg and Treg populations in peripheral blood from Ghanaian volunteers. Those regulatory immune cell populations might contribute to the regulated state of the host immune system and are probably important for the survival and fertility (microfilaria release) of the helminth.

Immunology is increasingly becoming a core biomedical discipline in recent times. Students’ interest in Science, Technology, Engineering and Mathematics programs is essential for better academic performances and outcomes in a University of Science Technology. To this end, we assessed the factors that influence students’ interest in immunology among a group of 32 graduate students in a tertiary institution in Ghana. The study was conducted using quantitative instruments (questionnaires) after which principal component analysis (PCA) was used to reveal the underlying factors affecting students’ interest in the course. In all, six components were found including students’ perception, instructor quality, student’s interest/motivation, teaching methods, teaching materials and teaching facilities. Students’ interest in immunology correlated negatively but significantly with perception; however, interest correlated positively with teaching methods (p

Interest and motivation significantly influence achievement; however, interest in immunology remains to be determined. Using a structured questionnaire, the current study assessed for the first time interest in immunology among biomedical graduate students in Ghana after a one-week introduction to immunology course. Our results revealed that approximately 80% of study participants expressed an interest in immunology. In addition, we showed that interest in immunology was independent of age and gender of the study participants. More interestingly, we observed that interest in immunology was primarily influenced by career choice. The findings from the present study have implications on immunology education and calls for investment in building capacity in immunology especially in developing countries.

Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4+ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4+CD25hiFoxp3+ regulatory T cells. These profiles included increased IL-17A+, IL-4+, RORC2+ and GATA3+CD4+ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.

Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes.

In order to guarantee the fulfillment of their complex lifecycle, adult filarial nematodes release millions of microfilariae (MF), which are taken up by mosquito vectors. The current strategy to eliminate lymphatic filariasis as a public health problem focuses upon interrupting this transmission through annual mass drug administration (MDA). It remains unclear however, how many rounds of MDA are required to achieve low enough levels of MF to cease transmission. Interestingly, with the development of further diagnostic tools a relatively neglected cohort of asymptomatic (non-lymphedema) amicrofilaremic (latent) individuals has become apparent. Indeed, epidemiological studies have suggested that there are equal numbers of patent (MF(+)) and latent individuals. Since the latter represent a roadblock for transmission, we studied differences in immune responses of infected asymptomatic male individuals (n = 159) presenting either patent (n = 92 MF(+)) or latent (n = 67 MF(-)) manifestations of Wuchereria bancrofti. These individuals were selected on the basis of MF, circulating filarial antigen in plasma and detectable worm nests. Immunological profiles of either Th1/Th17, Th2, regulatory or innate responses were determined after stimulation of freshly isolated PBMCs with either filarial-specific extract or bystander stimuli. In addition, levels of total and filarial-specific antibodies, both IgG subclasses and IgE, were ascertained from plasma. Results from these individuals were compared with those from 22 healthy volunteers from the same endemic area. Interestingly, we observed that in contrast to MF(+) patients, latent infected individuals had lower numbers of worm nests and increased adaptive immune responses including antigen-specific IL-5. These data highlight the immunosuppressive status of MF(+) individuals, regardless of age or clinical hydrocele and reveal immunological profiles associated with latency and immune-mediated suppression of parasite transmission.