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Onchocerciasis, caused by Onchocerca volvulus, affects more than 37 million people worldwide. Despite the progress achieved with mass drug distribution, suitable vaccines against onchocerciasis are needed to effectively eliminate the infection. The O. volvulus cysteine protease inhibitor (onchocystatin) is an immuno-dominant antigen detected in O. volvulus infections, capable of inducing protective immunity. Here, we explore the onchocystatin for a multi-epitope subunit vaccine candidate targeted against onchocerciasis. A multi-epitope vaccine candidate composed of RS-09 as adjuvant, a CD8+ T cell peptide, a CD4+ T cell peptide and a B cell peptide concatenated with suitable linkers was computationally constructed. Immune simulation of the vaccine response predicted several aspects of antibody-dependent and cellular-mediated immunity with accompanied B cell and helper T cell immune memory development. The levels of lFN-γ and IL-2 were also predicted to be elevated. Collectively, our results suggest that the multi-epitope vaccine construct has the potential to mimic the natural immunity targeted against onchocerciasis and other related filarial infections, and should be considered for further experimental validations.

BackgroundFilarial pathologies such as lymphedema may be associated with complications such as chronic non-healing wounds. Nonetheless, the role of bacterial population colonizing the lymphedematous legs has been posited to worsen the conditions of those living with the infection. These bacteria are usually composed of staphylococcal species partly because they are commensals. Thus, this present study sought to type the methicillin-resistant Staphylococcus aureus (MRSA) prevalence among individuals presenting with filarial lymphedema, particularly as MRSA tends to affect treatments options.MethodsWe recruited individuals (n = 321) with stages I–VII of 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 later identified using Matrix-assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) mass spectrometry.ResultsA total of 192 Staphylococci species were isolated, with an overall prevalence of 39.7% (95% CI: 35%–44%; N = 483). S. hominis was the most prevalent species (23.95%), followed by S. haemolyticus (20.83%), S. epidermidis (15.10%), S. aureus (10.41%), and S. saprophyticus (9.32%). The remaining 20.34% were distributed among S. wanneri, S. sciuri, S. pasteuri, S. xylosus, S. simulans, S. cohnii, S. caprae, S. lugdunensis, and S. capitis. MRSA, containing mecA gene, was detected in 21 out of 31 Staphylococci isolates tested, with an overall prevalence of 68% (95% CI: 51%–84%). In addition, a virulent gene, Panton–Valentine leukocidin (PVL), which is usually associated with S. aureus, was detected in 20/31 (64.5%) S. aureus in the study.ConclusionThese results suggest that MRSA species may pose a challenge to the treatment of filarial lymphedema with antibiotics particularly, as doxycycline is currently being piloted in some endemic areas to treat the infection. Thus, intensive antimicrobial resistance surveillance should be conducted in endemic areas by health authorities to forestall the dilemma of multidrug resistance not only against lymphatic filariasis (LF) infection but other diseases.

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.

Purpose The purpose of the study is to assess the nutritional and health status of people living with HIV/AIDS (18-60 years) in selected health facilities in the eastern region of Ghana and to determine the influence nutrition support programmes (NSP) have on the nutritional and health status of people living with HIV/AIDS. Design/methodology/approach A retrospective study design was used. Purposive and convenience sampling was used to select four hospitals and 200 beneficiaries and non-beneficiaries of the NSP. A structured questionnaire was used to collect the sociodemographic, anthropometric, biochemical and clinical history of the participants. Dietary intake was assessed with food frequency and 24-h dietary intake questionnaires. Previous data from the medical record within three to six months before the research was collected and compared with current data. Findings The prevalence of underweight (using body mass index) was 17 per cent and overweight/obesity was 37 per cent. Most respondents had adequate consumption of phosphorus (70.5 per cent); inadequate intake of calcium (95 per cent), vitamin E (77.5 per cent) and vitamin A (94 per cent); and excess intakes of sodium (93 per cent), selenium (77 per cent), copper (83.5 per cent) and manganese (76 per cent). There was no significant difference in nutrient intake of beneficiaries and non-beneficiaries of the NSP, although there were significant differences in the frequency of consumption of fruits (p < 0.001), vegetables (p < 0.001), legumes (p = 0.002), animal foods (p < 0.001) and cereals, grains and starch (p < 0.001) between beneficiaries and non-beneficiaries of NSP. About 38 and 20 per cent of respondents, respectively, had low haemoglobin (Hb < 11 g/dL) and high viral load (1,000 cp/mL). Comparing the current and previous (three to six months before the study) health and nutritional status of beneficiaries and non-beneficiaries of NSP, among the beneficiaries of NSP, monocytes increased by 40.6 per cent (p = 0.028) and mean weight decreased by 2.4 per cent (p = 0.007), Hb decreased by 7.1 per cent (p = 0.27) and viral load decreased by 4.2 per cent (p = 0.49), whereas among the non-beneficiaries, mean weight decreased by 0.05 per cent (p = 0.95) and Hb increased by 9.6 per cent (p = 0.06) and monocytes increased (p = 0.28) and viral load increased by 98.2 per cent (p = 0.34). Research limitations/implications A significant proportion of people living with HIV/AIDS had a high prevalence of underweight and overweight/obesity, inadequate nutrients intake and high viral load. The NSP for people living with HIV/AIDS in the eastern region of Ghana did not significantly influence the nutritional and health status of these people. Practical implications Knowing the nutritional status will help health institutions plan activities towards improving the health and nutritional status of people living with HIV/AIDS. This research is aimed at not only contributing to the existing body of knowledge but also making recommendations of action towards improving NSPs of people living with HIV/AIDS. Social implications Improvement in nutritional and health status of people living with HIV/AIDS will help reduce morbidity and mortality and its related cost to families, communities and the nation. Originality/value This study is first to determine the influence of NSPs on nutritional and health status of people living with HIV/AIDS in the eastern region of Ghana.

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.

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.

The transcription factor NF-κB promotes immunity by controlling the expression of genes involved in inflammation. Cytokines and pathogen-associated molecular patterns stimulate cell surface receptors, including toll-like receptors, to initiate a signalling cascade resulting in the activation of NF-κB. NF-κB drives the expression of target genes that mediate cell proliferation and release antimicrobial molecules and cytokines to activate an immune response. Filariasis is one of the most complex infections of humans. The actual causes of the heterogeneity in infection are not well understood. However, they have been attributed to differences in inflammatory processes that are immune-mediated, secondary bacterial infections, and host immune-genetics. Elevated production of angiogenic molecules (VEGFs, CEACAM and MMPs) in filarial pathology has been shown to be dependent on phosphorylation and intracellular activation of NF-κB. This review examines the role of NF-κB in filarial pathology and its potential therapeutic options for individuals with the disease.

Background Lymphatic filariasis (LF) is a neglected tropical disease with several infection phenotypes. In addition to mass drug administration, host immune response contributes to microfilariae clearance. An important influence of immunity, nutritional status, remains to be evaluated among filarial lymphedema patients. This study sought to assess the nutritional status of LF patients and its association with the pathology. Methods As cross-sectional study was conducted to determine the nutrition status of lymphedema patients in Ahanta West, Ghana. To obtain sociodemographic and nutrition data, a structured questionnaire was administered to the study participants. Anthropometry and 24-hour food recall were used to assess the nutritional status of participants. Results While all and 71 (82.6%) had adequate carbohydrate and protein intakes respectively, 83 (96.5%) had inadequate intake of fat. There were widespread inadequate nutrients intakes that were associated with stage of lymphedema: fat, r = -0.267, p = .024; carbohydrate, r = 0.305, p = .010; sodium, r = -0.259, p = .029; copper, r = -0.249, p = .036; selenium, r = -0.265, p = .025; pantothenic acid, r = -0.265, p = .025; vitamin B6, r = -0.270, p = .023; vitamin B12, r = -0.288, p = .015; and vitamin A, r = -0.276, p = .020. Conclusion The study shows widespread malnutrition among the participants. A nutritional intervention is recommended to complement current management strategies of filarial lymphedema.

BackgroundLike all other diseases, the advent of the COVID-19 pandemic has been implicated to impact the elimination schedule and control of neglected tropical diseases such as human lymphatic filarial (LF) infections in endemic countries. However, it is unclear the extent to which delays in mass drug administration has affected people living with chronic lymphatic filarial pathology in rural Ghana as a result of the COVID-19 pandemic, and thus remain to be investigated. MethodTo address this, a cross-sectional study where 133 LF participants from 8 LF-endemic communities in the Ahanta West District of Ghana were recruited to assess the impact of MDA interruptions as a result of COVID-19 among individuals presenting with the filarial pathology. Here, the chi-square test of independence was used as a statistical tool to assess the dependency: 1) between MDA interruption and filarial attacks 2) between MDA interruption and filarial-related pains 3) between MDA interruption and a perceived increase in LF transmission.ResultsStudy participants were asked whether the MDA interruption has affected them in any way. Here, 81% of the patients indicated yes, it had. In addition, we sought to investigate whether MDA interruption has resulted in increased filarial attacks and pains. At this, 68% of the study respondents reported an increase in filarial attacks. Similarly, 65% reported an increase in filarial-related pains. The study further reported that filarial attacks (B=14.997, df=1, p-value ConclusionIn this study, MDA interruption is reported to increase filarial attacks, filarial-related pains, and a perceived LF transmission increase in the study communities. This study's findings are important and urgent, suggesting that sustained MDA interruption in LF-endemic communities could further worsen LF patients' plight as filarial attacks, pains, and transmission could increase. Therefore, the need to immediately identify alternative modes of MDA distribution in LF-endemic areas where mass treatment has been halted in the wake of COVID-19 to prevent an unwarranted surge in LF attacks, pains, and transmission.

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.

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.

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, p12 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.

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 Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019. Methods We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 site-years of vital registration data, 705 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, and 680 site-years of mortality surveillance data to estimate mortality due to tuberculosis among HIV-negative individuals. We used a population attributable fraction approach to estimate mortality related to HIV and tuberculosis coinfection. A compartmental meta-regression tool (DisMod-MR 2.1) was then used to synthesise all available data sources, including prevalence surveys, annual case notifications, population-based tuberculin surveys, and tuberculosis cause-specific mortality, to produce estimates of incidence, prevalence, and mortality that were internally consistent. We further estimated the fraction of tuberculosis mortality that is attributable to independent effects of risk factors, including smoking, alcohol use, and diabetes, for HIV-negative individuals. For individuals with HIV and tuberculosis coinfection, we assessed mortality attributable to HIV risk factors including unsafe sex, intimate partner violence (only estimated among females), and injection drug use. We present 95% uncertainty intervals for all estimates. Findings Globally, in 2019, among HIV-negative individuals, there were 1·18 million (95% uncertainty interval 1·08–1·29) deaths due to tuberculosis and 8·50 million (7·45–9·73) incident cases of tuberculosis. Among HIV-positive individuals, there were 217 000 (153 000–279 000) deaths due to tuberculosis and 1·15 million (1·01–1·32) incident cases in 2019. More deaths and incident cases occurred in males than in females among HIV-negative individuals globally in 2019, with 342 000 (234 000–425 000) more deaths and 1·01 million (0·82–1·23) more incident cases in males than in females. Among HIV-positive individuals, 6250 (1820–11 400) more deaths and 81 100 (63 300–100 000) more incident cases occurred among females than among males in 2019. Age-standardised mortality rates among HIV-negative males were more than two times greater in 105 countries and age-standardised incidence rates were more than 1·5 times greater in 74 countries than among HIV-negative females in 2019. The fraction of global tuberculosis deaths among HIV-negative individuals attributable to alcohol use, smoking, and diabetes was 4·27 (3·69–5·02), 6·17 (5·48–7·02), and 1·17 (1·07–1·28) times higher, respectively, among males than among females in 2019. Among individuals with HIV and tuberculosis coinfection, the fraction of mortality attributable to injection drug use was 2·23 (2·03–2·44) times greater among males than females, whereas the fraction due to unsafe sex was 1·06 (1·05–1·08) times greater among females than males. Interpretation As countries refine national tuberculosis programmes and strategies to end the tuberculosis epidemic, the excess burden experienced by males is important. Interventions are needed to actively communicate, especially to men, the importance of early diagnosis and treatment. These interventions should occur in parallel with efforts to minimise excess HIV burden among women in the highest HIV burden countries that are contributing to excess HIV and tuberculosis coinfection burden for females. Placing a focus on tuberculosis burden among HIV-negative males and HIV and tuberculosis coinfection among females might help to diminish the overall burden of tuberculosis. This strategy will be crucial in reaching both equity and burden targets outlined by global health milestones. Funding Bill & Melinda Gates Foundation.

Lymphatic Filariasis (LF), a parasitic nematode infection, often resulting in disability poses huge economic burden to affected countries. To meet eradication deadlines in line with the global Neglected Tropical Diseases elimination and health system strengthening goals, novel strategies are needed to complement existing approaches. LF endemicity is localized and prevalence, spatially heterogeneous. Species distribution models (SDMs) can help identify subtle differences in risk factors that influences the transmission of LF in geographically distinct regions. Thus in this contribution, presence absence records of microfilaria (m)f in Ghana were stratified into Northern and Southern Zones and used to run SDMs, whilst climate, socioeconomic and land coverage variables provided explanation information. GLM (Generalized Linear model), GBM (Generalized Boosted Model), ANN (Artificial Neural Network), SRE (Surface Range Envelope), MARS (Multivariate Adaptive Regression Splines) and RF (Random Forests) algorithms were run for both study zones and also for the entire country for the purpose of comparison. Best model quality was obtained with RF and GBM algorithms with highest AUC between 0.98 and 0.95, respectively. The models predicted high suitable environments for LF transmission in the short grass savanna areas in the northern and along the coastal southern parts of Ghana. Mainly, land cover and socioeconomic variables such as, proximity to inland waterbodies and population density uniquely influenced LF transmission in the South while poor housing was a distinctive risk factors in the North. Precipitation, temperature, slope and poverty were common risk factors but with subtle variations in response values, which was confirmed by the countrywide model. This study has demonstrated that, an understanding of the geographic distinctness in risk factors is required to inform the development of area-specific transmission control systems towards LF elimination in Ghana and internationally.

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 r = 0.71, p-value Conclusion Our findings support previous works on the reduced quality of life among lymphatic filariasis patients with pathology. In this study, our results reveal a depressing financial condition among people presenting with late stages of LF pathologies, which eventually reduces their well-being.

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. ctDNA was readily detected in 15 blood samples collected in Ghana at the time of suspected breast cancer. Genomic alterations previously associated with unfavorable prognostic outcomes were observed in the majority of patients. This supports the use of liquid biopsies for diagnosis, surveillance and clinical management of breast cancer in Ghana.

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.

Graphical abstract, Highlights • 404SKQLQQSMSSADS416 and 92RRIRGGDGKMKDL104 sequences of N-protein are predicted to induce B-cell memory response . • 79SSPDDQIGY87 and 305AQFAPSASAFFGMSR319 are predicted to elicit T-cell-mediated immune response with accompanied memory. • 305AQFAPSASAFFGMSR319 is predicted to cross-react with SARS-CoV1, MERS-CoV and hCoV−OC43. • Zidovudine triphosphate is a potential inhibitor of the N-terminal domain of SARS-CoV2 N-protein., 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.

BackgroundHuman lymphatic filarial pathology is the main 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 morbidity associated with the disease with the purpose of improving the quality of life of the patients. Consequently, the current study assessed the overall quality of life of lymphatic filariasis (LF) pathology patients in some selected endemic communities in rural Ghana. MethodIn the present study, the Lymphatic Filariasis Quality of Life Questionnaires (LFSQQ) was used to evaluate the effect of lymphatic filariasis on the quality of life of people with the disease in ten (10) communities in the Ahanta West District of the Western Region of Ghana where, mass drug administration is being implemented for the past twenty years. ResultsOf 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) lymphedema while only 2 patients had stage seven (7) lymphedema. 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 < 0.0001) between the stage of lymphedema (severity of the disease) and the quality of life of the LF patients. In addition, a clear pattern of positive correlation (r = 0.71, p-value < 0.001) was observed between the disease burden and pain/discomfort domains of the study participants. Whereas, the highest domain specific score (85.03) was observed in the domain of self-care, we noted that the environmental domain, which consist of the financial status was the lowest (45.94) among the study participants. ConclusionOur findings support previous works on the reduced quality of life among lymphatic filariasis patients with pathology. In this study, our results reveal a depressing financial condition among people presenting with late stages of LF pathologies, which eventually reduces their wellbeing.

While M1 macrophages initiate wound healing by inducing the inflammation phase, M2 macrophages are crucial in the proliferation phase by producing growth factors that accelerate new tissue formation. Turmeric (Curcuma longa L.) is known to accelerate wound closure; however, mechanisms underlying the wound healing properties of C. longa L. remain to be documented. Therefore, this study investigated the mechanisms by which C. longa L. accelerates wound healing. Here, an experimental study was conducted using 30 male Swiss Webster mice. Curcuma longa L. extract was applied on the wound bed tissue starting on day 3 after wound induction. The Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) (M1 and M2 markers) gene expressions from wound skin tissue were analyzed, while collagenesis during tissue repair was observed by histopathology analysis of excised skin on day 6 after wound induction. Upregulation of Arg-1 in the treated group was observed on day 6 after wound induction compared to the positive control (p = 0.0394) and the negative control groups (p = 0.0313). In addition, the Arg-1/iNOS ratio revealed a significant increase of M2 polarization in the C. longa L.-treated wound compared to negative controls (p < 0.0001), but not significant when compared with positive controls (p = 0.0535). Similarly, collagen density was significantly higher in the C. longa L.-treated wound than the negative control (p = 0.0418) and the positive control (p < 0.0001). These results suggest that administration of C. longa L. extract gel improved wound tissue repair on skin excision by inducing M2 polarization on wound tissue during healing.

Purpose: Analysis of cell free DNA could provide a rapid and non-invasive approach to detect cancer and provide new molecular insights in many African countries where expert pathology is lacking. Hence, we tested whether whole-genome sequencing of cfDNA (WGS-cfDNA) could identify somatic alterations that drive breast cancer. Methods: We conducted a pilot on 15 Ghanaian women (median age 49.5 years) recruited as part of the Ghana Breast Health Study. cfDNA was extracted and subjected to WGS at 30x and 0.1x. ichorCNA software was used to predict copy number alterations and ctDNA fractions. Results: We found extensive amplification and deletion of multiple chromosomal regions including those with oncogenes and tumor suppressor genes associated with breast cancer. Similar copy number alterations for selected breast cancer genes were observed with 0.1x and 30x cfDNA-WGS with increasing concordance between the two instruments as the ctDNA fraction increases. We observed a high frequency (>50%) of copy number gain in 3/5 regions and potential target genes for the amplification (chr8p11-12 [ZNF703] n=8, 53.3%; chr8q24.2 [MYC] n=9, 60%; chr19q12 [CCNE1] n=9, 60%), which were in agreement to previous observations among African-American (AA) ancestry compared to European-American (EA) ancestry in TCGA datasets. Conclusion: Our data provided evidence that ctDNA-based genomic studies are possible and ctDNA analysis could be a tool for future molecular oncology studies in Africa for cancer etiology, surveillance and clinical trials. Citation Format: Samuel Ahuno, Anna-Lisa Doebley, Thomas Ahearn, Joel Yarney, Nicholas Titiloye, Nancy Hamel, Ernest Adjei, Joe-Nat Clegg-Lamptey, Lawrence Edusei, Baffour Awuah, Xiaoyu Song, Verne Vanderpuye, Mustapha Abubakar, Maire Duggan, Daniel Stover, Kofi Nyarko, John Bartlet, Francis Aitpillah, Daniel Ansong, Kevin Gardner, Anne Bowcock, Carlos Caldas, William Foulkes, Seth Wiafe, Wiafe-Addai, Montserrat Garcia-Closas, Alexander Kwarteng, Gavin Ha, Jonine Figueroa, Paz Polak, On Behalf Of Ghana Breast Health Study Team. Studying Ghanian Cancer Genomes Using Cell-free DNA [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 81.

Background:Hepatitis B is a liver infection caused by the hepatitis B virus (HBV). It affects all women and men irrespective of age. Although sub-Saharan Africa is an area of high prevalence of this disease, data on the prevalence of acute and chronic HBV infections in this region remain to be widely documented.Objective:This study aimed to investigate the prevalence of HBV in relation to age in Centre Hospitalier Universitaire Campus (CHU-C), one of the two teaching hospitals of Lome, Togo.Method:The present study is a cross-sectional study about the prevalence of hepatitis B surface antigen (HBsAg) carriage from 2009 to 2011. All study participants were screened for HBsAg at the Immunology laboratory of CHU Campus of Lome.Results:One thousand two hundred individuals were screened for HBsAg from 2009-2011. The overall prevalence of HBV infection was 19.08%. This prevalence was significantly higher in men (25.00%) than women (14.80%). The highest prevalence of HBV was observed in age range of 20-29 years and 30-39 years with respectively 26.33% and 21.67%. The lowest prevalence was 6.08%, found in people over 50 years. Concerning the clinical indication of the test, the prevalence during the clinical abnormalities related to liver (CARL) was the highest (26.21%), followed by the systematic screening (SS) with 20.25% while the pre-operative assessment (POA) showed the lowest prevalence with 5.56%.Conclusion:The study shows the high prevalence of HBsAg carriage in young people. This could be used to enhance prevention and treatment of HBV infection in Togo.

Respiratory viral infections are important causes of morbidity and mortality worldwide. Information on circulating respiratory viruses among prisoners is lacking, although this is of public health importance and knowledge would assist in putting in place preventive measures to forestall disease outbreaks. The aim of this study therefore was to get the footprint of such diseases that have epidemic potential to be described and quantified for control. Prisoners on remand numbering 203 in a prison in Kumasi, the Ashanti Regional capital, were interviewed using prevalidated questionnaire, nasopharyngeal samples taken and screened by real-time PCR for common respiratory viruses in February, 2018. Of the total number of 203 participants enrolled, majority were males (n = 198, 97.54%). The modal age unsurprisingly was in the active working class of 18 to 35 years (n = 155, 76.36%) with 48 (23.65%) of participants older than 35 years. Inmates reported nasal congestion (n = 83, 40.89%), cough with or without pharyngitis (n =108, 53.20%) and fever (n = 74, 39.48%). Viruses detected in throat samples were Influenza A (n = 1, 0.49%) and Rhinovirus (n = 8, 3.94%). There was no statistically significant association between respiratory virus positivity and age (p = 0.118), gender (p > 0.900), duration of incarceration (p = 0.239) and reported symptoms (p = 0.724). The prison population may have a lower prevalence of respiratory viruses circulating in them. This may be dominated by those with high antigenic diversity.

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. Electronic supplementary material The online version of this article (10.1186/s12879-019-4084-2) contains supplementary material, which is available to authorized users.

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., Author summary Regulation of the host`s immune system by filarial nematodes is crucial for the fertility and survival of the nematode. Indeed, the majority of W. bancrofti-infected individuals are characterized by a regulated state including increased regulatory T cells (Treg), IL-10, TGF-β and filarial-specific IgG4 and suppressed Th2 cytokine responses. However, the functional role of Treg populations and regulatory B cells (Breg) during filarial infection remains unknown. Thus, in this study we investigated whether W. bancrofti-infected individuals from Ghana harbored distinct Breg and Treg populations which might be important for filarial-specific immunomodulation. Overall, this study shows that W. bancrofti induces distinct Breg populations, especially in patently (microfilaremic) infected individuals who presented significantly increased frequencies of IL-10-producing CD19+CD24highCD38dhigh Breg. Furthermore, clearance of the infection, due to anti-filarial treatment, returned these regulatory immune cells to homeostatic levels showing that an ongoing filarial infection is important for the activation of distinct Breg and Treg subsets. Those regulatory immune cell subsets are a part of a complex system which are induced by filarial nematodes to modulate the host`s immune system and maintain long-term survival.

Cancer incidence is rising and mortality rates are high in Africa, where access to molecular pathology is limited. Analysis of cancer-related mutations in circulating tumor DNA (ctDNA) from cell-free DNA (cfDNA) that is shed into the bloodstream by tumor cells could be transformative to the African continent and provide new molecular insights. Using samples collected from the Ghana Breast Health Study we tested whether whole-genome sequencing (WGS) of cfDNA could detect ctDNA and identify somatic alterations that drive breast cancer. We selected 15 breast cancer patients (median age 49.5 years) with duplicated plasma samples. Pathologic grade, age, and immunohistochemical (IHC) stains for estrogen receptor (ER), progesterone receptor (PR) and HER2 were available for the majority of patients (>80%). cfDNA extraction and WGS at 30x and 0.1x was performed. ichorCNA software was used on Next Generation Sequencing (NGS) read counts to estimate the ctDNA fraction and predict copy number alteration profiles. High depth 30x cfDNA-WGS analysis showed that all 15 breast cancer patients had 1% ctDNA or greater (median[IQR] 3.96%[2.22%-8.13%]). There was high concordance between estimated ctDNA fraction using 0.1x and 30x WGS (Pearson r = 0.9). Copy number profiling showed extensive amplification and deletion of multiple chromosomal regions containing important cancer genes (such as MYC, PIK3CA, TERT, and GATA3). Of the four patients classified as HER2 positive based on IHC, two had increased ERBB2 copy number (50 and 3 copies, respectively). Our data provide evidence that ctDNA-based genomic studies are possible and ctDNA analysis could be a tool for future molecular oncology studies in Africa for cancer etiology, surveillance and clinical trials. Citation Format: Samuel T. Ahuno, Lawrence Edusei, Nicolas Titiloye, Ernest Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Verne Vanderpuye, Maire Duggan, Seth Wiafe, Kofi Nyarko, Francis Aitpillah, Daniel Ansong, Thomas Ahearn, Alexander Kwarteng, Mustapha Abubakar, Montserrat Garcia-Closas, Gavin Ha, Jonine D. Figueroa, Paz Polak, on behalf of the Ghana Breast Health Study Team. Circulating tumor DNA (ctDNA) from peripheral blood is detectable among Ghanaian breast cancer patients [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-093.

Background There is compelling evidence that not only do anti-filarials significantly reduce larval forms, but that host immune responses also contribute to the clearance of filarial parasites; however, the underlying mechanisms have not been fully elucidated. Main text Filarial infections caused by Wuchereria bancrofti and Brugia species (lymphatic filariasis) and Onchocerca volvulus (onchocerciasis) affect almost 200 million individuals worldwide and pose major public health challenges in endemic regions. Indeed, the collective disability-adjusted life years for both infections is 3.3 million. Infections with these thread-like nematodes are chronic and, although most individuals develop a regulated state, a portion develop severe forms of pathology. Mass drug administration (MDA) programmes on endemic populations focus on reducing prevalence of people with microfilariae, the worm's offspring in the blood, to less than 1 %. Although this has been successful in some areas, studies show that MDA will be required for longer than initially conceived. Conclusion This paper highlights the mode of action of the various antifilarial treatment strategies and role of host immune response. Electronic supplementary material The online version of this article (doi:10.1186/s40249-016-0183-0) contains supplementary material, which is available to authorized users.

Bacterial meningitis continues to be one of the most dreaded infections in sub-Saharan Africa and other countries that fall in the "meningitis belt" due to recurrent nature of the infection and the sequel of deliberating effects among survivors even after treatment. Ghana has had recurrent epidemics in the past but has been free from high mortality levels. Whereas reasons for the low reported number of deaths in the past are unclear, we hypothesize that it may be due to increased vaccination from expanded program on immunization (EPI) and consequent herd immunity of the general population. As at the end of February, 2016, 100 individuals were reported to have died out of 500 recorded cases. The infection may cause severe brain damage and kills at least 1 out of 10 individuals if quick interventions are not provided. The Ghana Health Service (GHS) and the Ministry of Health (MoH), together with other local and international stakeholders are working intensely to control the spread of the infection in affected communities with treatment and other health management programmes. This review presents a quick overview of meningitis in Ghana with emphasis on S. pneumoniae (responsible for about 70% of cases in the recent epidemic) together with some recommendations aimed at ensuring a "meningitis-free Ghana".

Treatment with doxycycline leads to improvement of filarial lymphedema independent of active infection (ie, patients positive or negative for circulating filarial antigen). Therefore, doxycycline (200 mg/d for 6 weeks) should be considered for patients with stage 1–3 lymphedema to improve morbidity management., Background. The aim of this study was to determine whether improvement of filarial lymphedema (LE) by doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity. Methods. One hundred sixty-two Ghanaian participants with LE stage 1–5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) doxycycline (200 mg/d), or (3) placebo matching doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months. Results. Doxycycline-treated patients with LE stage 2–3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks. Conclusions. Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1–3 should benefit from a 6-week course of doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE. Clinical Trials Registration. ISRCTN 90861344.

(i) To determine the frequencies of urogenital pathologies in men infected with bancroftian filariasis, and (ii) to evaluate the role of ultrasonography (USG) as a diagnostic tool to differentiate between diverse pathologies with different clinical implications. To date, all types of scrotal enlargement resulting from lymphatic filariasis (LF) have been summarized under one term: "filaricele".Data were compiled from recruitment phases for field trials in an endemic area for LF in Ghana. 1453 men aged 18 years and above underwent ultrasound examinations of the scrotum. Observation parameters were: Filaria Dance Sign (FDS), dilation of supratesticular lymphatic vessels, thickness of scrotal skin, occurrence and amount of fluid accumulation, echogenicity of the fluid between the layers of the tunica vaginalis, as well as position and homogenicity of testis, epididymis and spermatic cord. In 1132 men, blood samples were taken for parasitological analysis.In 56% of examined patients, fluid accumulation around the testis was detected (38% subclinical-, 18% clinical stages). Differentiation of the echogenicity of the fluid revealed echo-free hydrocele (EFH) in 47% and echo-dense hydrocele (EDH) in 9%. Patients without hydrocele and subclinical stages had a thinner scrotal skin than those in clinical stages or with lymphscrotum (P0.001). In the EDH group the scrotal skin was thicker than in the EFH group (P0.001). 1.4% had a lymphscrotum. FDS was detected in 24% of all 1453 volunteers who underwent USG. The number of worm nests correlated with microfilarial load and levels of circulating filarial antigen (P0.001; 20% microfilaremic, 48% antigen positive).In an unexpected high number of men (56%) fluid accumulation around the testis was detected by USG of which more than one third (38%) presented with subclinical stages. The study showed that echo-dense and echo-free fluid could be differentiated and that a considerable number of cases had EDH (9%) posing a risk to develop necrotic testis and infertility and therefore requiring immediate surgical intervention. USG thus turned out to be a useful diagnostic technique to differentiate between those cases requiring immediate surgical intervention from those that can be treated with (anti-wolbachial and hyperpermeability reducing) drugs that ameliorate or halt progression of the disease.

Sub-optimal responses to ivermectin (IVM) have emerged. Targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline is effective in clearing microfilariae in onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment., Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839.

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., Author Summary Onchocerciasis affects over 37 million people in poor communities. Infected individuals usually present a generalized form which is characterized by low inflammation, tightly-controlled immune responses and high parasite burden. In contrast, patients with chronic dermatitis (sowda) have reduced parasite loads and severe pathology. Current disease control is based on mass drug administration (MDA) with ivermectin (IVM) which mainly eliminates microfilariae (MF), the transmission life-stage. In hyperendemic areas, 95% of individuals are MF+, whereas in hypoendemic areas the rate is

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., Author Summary The tropical helminth infection lymphatic filariasis affects more than 120 million people worldwide and is considered a major public health concern. Over 90% of infections are elicited by Wucheria bancrofti and adult worms reside in the lymphatic system releasing millions of microfilariae (MF), which periodically circulate in the blood. New diagnostic tools have provided a method to determine asymptomatic patients that are amicrofilaremic: a subset of individuals that have so far been neglected but are of special interest since these patients represent a dead end in terms of parasite transmission. Therefore, we were interested in determining whether the absence of MF was associated with distinct immunological profiles and observed that indeed responses in MF+ patients were dampened. From the viewpoint of the helminth such overall suppression of immune responses may facilitate MF transmission. Latent individuals however, presented elevated filarial specific responses and extrapolating these findings to the host provides novel insight into possible protective mechanisms which either actively hinders the release of MF from worms or their travel to the periphery. Further research into these aspects may broaden the range of strategies currently employed to reduce transmission and in turn eliminate bancroftian filariasis.

The diversity, relative importance, canopy height and cover of plant species in the Kwame Nkrumah University of Science and Technology (KNUST) Botanic Garden were evaluated in five 1-ha plots using a stratified random sampling technique in order to build an understanding of its floristic composition and structure in two distinct parts of the garden (cultivated and uncultivated). We recorded 184 species which belonged to 146 genera, 51 families and six growth forms. The most dominant tree species in the garden were Elaeis guineensis Jacq., Hevea brasiliensis (Willd.) Muell.-Arg. and Parkia biglobosa (Jacq.) G. Don. with a combined importance index of 60.09 (20 % relative importance). The differences in importance value indices of species between the cultivated and uncultivated areas of the garden were statistically insignificant (p > 0.05), suggesting the presence of conducive growth environments for plants in both areas. The most dominant families were Fabaceae, Moraceae, Arecaceae and Euphorbiaceae whilst trees were the most predominant growth forms (62.5 %). Average crown height and percentage canopy were 28.8 ± 8.81 m and 66.4 ± 8.26 % respectively. These results show the floristic richness of the KNUST botanic garden and underscore the garden\'s potential as a centre for ex-situ conservation beside its traditional roles in education, research and recreation. Keywords: Floristic composition, structure, botanic garden, KNUST Journal of Science & Technology (Ghana) Vol. 28 (3) 2008: pp. 103-122

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold