Epidemiology of Ocular Toxoplasmosis in Three Community Surveys in the Central Region of Ghana,West Africa

Purpose: To conduct the first ever population-based survey on ocular toxoplasmosis in the Central Region of Ghana.

Methods: A cross-sectional population-based study was conducted in three randomly selected communities in the Central Region, Ghana. Visual acuity (VA) measurement, dilated fundus examination by indirect ophthalmoscopy and serology testing were performed on all participants. Ocular toxoplasmosis was diagnosed based on characteristic retinal lesions and supported by positive serologic testing using commercial enzyme-linked immunosorbent assay (ELISA) kits.

Results: A total of 390 subjects aged 10–100 years (mean age 47 years) were examined; 118 (30.3%) were male and 272 (69.7%) female. Ten subjects (6 females and 4 males) had toxoplasmic ocular lesions (prevalence 2.6%). Of these, two had bilateral lesions and eight had unilateral lesions. Subjects with toxoplasmic ocular lesions were older than those without lesions (p = 0.028). The development of ocular toxoplasmosis was not associated with rural dwelling, sex, keeping cats, or consumption of meat.

Conclusion: The prevalence of ocular toxoplasmosis in our Ghanaian study population was lower than findings from Southern Brazil, where there is a similar prevalence of infection in the general population.     

Amyloid-β(1-15/16) as a marker for γ-secretase inhibition in Alzheimer's disease

Amyloid-β (Aβ) producing enzymes are key targets for disease-modifying Alzheimer's disease (AD) therapies since Aβ trafficking is at the core of AD pathogenesis. Development of such drugs might benefit from the identification of markers indicating in vivo drug effects in the central nervous system. We have previously shown that Aβ(1-15) is produced by concerted β-and α-secretase cleavage of amyloid-β protein precursor (AβPP). Here, we test the hypothesis that this pathway is more engaged upon γ-secretase inhibition in humans, and cerebrospinal fluid (CSF) levels of Aβ(1-15/16) represent a biomarker for this effect. Twenty healthy men were treated with placebo (n = 5) or the γ-secretase inhibitor semagacestat (100 mg [n = 5], 140 mg [n = 5], or 280 mg [n = 5]). CSF samples were collected hourly over 36 hours and 10 time points were analyzed by immunoassay for Aβ(1-15/16), Aβ(x-38), Aβ(x-40), Aβ(x-42), sAβPPα, and sAβPPβ. The CSF concentration of Aβ(1-15/16) showed a dose-dependent response over 36 hours. In the 280 mg treatment group, a transient increase was seen with a maximum of 180% relative to baseline at 9 hours post administration of semagacestat. The concentrations of Aβ(x-38), Aβ(x-40), and Aβ(x-42) decreased the first 9 hours followed by increased concentrations after 36 hours relative to baseline. No significant changes were detected for CSF sAβPPα and sAβPPβ. Our data shows that CSF levels of Aβ(1-15/16) increase during treatment with semagacestat supporting its feasibility as a pharmacodynamic biomarker for drug candidates aimed at inhibiting γ-secretase-mediated AβPP-processing.     

Associations between Polymorphisms within Interferon Gamma and Tumor Necrosis Factor Genes and Toxoplasma Retinochoroiditis in Ghanaian Patients

Purpose: To evaluate associations between IFN-γ +874T/A and TNF-α-308G/A polymorphism with the development of Toxoplasma retinochoroiditis.

Methods: By ARMS–PCR, a cross-sectional genetic study involving 30 patients with Toxoplasma retinochoroiditis and 87 controls was carried out.

Results: IFN-γ +874: by comparing with the AA genotype, individuals with the TT genotype had a 3.4 odds ratio (OR); AT had a 1.6 OR; and the T allele had a higher OR (1.6), indicating a likely susceptibility of IFN-γ +874T to the infection, though the overall distribution was not significant (p = 0.259). For TNF-α-308G/A, individuals with both GA and AA genotypes had lower ORs when compared with the GG genotype, implying the A allele could confer protection against Toxoplasma ocular lesions.

Conclusions: IFN-γ +874T allele may increase the risk of ocular lesions in Toxoplasma infection. The principle of natural selection seems to also play a role. The less common TNF-308A allelic form could be protective against the development of Toxoplasma ocular infection.     

In vitro activity of extract and fractions of natural cocoa powder on Plasmodium falciparum

Several flavonoids isolated from certain plants have demonstrated antiplasmodial activity, after their initial indigenous use in malaria treatment. Cocoa has been found to be a rich food source of flavonoids in comparison with many common foods and beverages. The aim of this work was to investigate the in vitro activity of natural cocoa powder on the growth of Plasmodium falciparum. Prepared crude methanol extract was partitioned successively with petroleum ether, ethyl acetate, chloroform, and butanol. Total flavonoid concentration in the crude methanol extract and fractions was measured by the AlCl(3) colorimetric assay. Direct inhibitory activity of the natural cocoa powder was assessed by culturing extract and fractions with P. falciparum in vitro. Greater antiplasmodial activity was observed in nonpolar solvent fractions (chloroform, ethyl acetate, and petroleum ether) compared with polar solvents. The chloroform fraction was most active, with mean±SEM 50% and 90% inhibition concentrations of 48.3±0.9 and 417±7.8 μg/mL, respectively. The study showed a weak association between total flavonoid concentration and antiplasmodial activity. Early trophozoite (ring-stage) synchronized cultures treated with the chloroform fraction of natural cocoa powder showed a decline in growth. Further reduction in parasitemia was also observed for other erythrocytic stages. These results suggest that natural cocoa powder has measurable direct in vitro inhibitory effect on P. falciparum and support the anecdotal reports of its ability to prevent malaria as a result of regular intake as a beverage.     

Excluding pregnancy among women initiating antiretroviral therapy: efficacy of a family planning job aid

Background  

Guidelines for initiating ART recommend pregnancy testing, typically a urine test, as part of the basic laboratory package. The principal reason for this recommendation is that Efavirenz, a first-line antiretroviral medication, has the potential of causing birth defects when used in the first trimester of pregnancy and is therefore contraindicated for use by pregnant women. Unfortunately, in many African countries pregnancy tests are not routinely provided or available in ART clinics, and, when available outside clinics, are often not affordable for clients.     

Understanding factors influencing home delivery in the context of user‐fee abolition in Northern Ghana: Evidence from 2014 DHS

User‐fee exemption for skilled delivery services has been implemented in Ghana since 2003 as a way to address financial barriers to access. However, many women still deliver at home. Based on data from the 2014 Ghana Demographic and Health Survey, we estimated the prevalence of home delivery and determined the factors contributing to homebirths among a total of 622 women in the Northern region in the context of the user‐fee exemption policy in Ghana. Binary and multivariate logistic regression analyses were employed. Results suggest home delivery prevalence of 59% (365/622). Traditional birth attendants attended majority of home deliveries (93.4%). After adjusting for potential confounders, making less than four antenatal care visits (aOR = 2.42; CI = 1.91‐6.45; p = 0.001), being a practitioner of traditional African religion (aOR = 16.40; CI = 3.10‐25.40; p = 0.000), being a Muslim (aOR 2.10; CI = 1.46‐5.30; p = 0.042), not having a health insurance (aOR = 1.85; CI = 1.773‐4.72; p = 0.016), living in a male‐headed household (aOR = 2.07; CI = 1.02‐4.53; p < 0.01), and being unexposed to media (aOR = 3.10; CI = 1.12‐5.38; p = 0.021) significantly predicted home delivery. Our results suggest that unless interventions are implemented to address other health system factors like insurance coverage, and socio‐cultural and religious beliefs that hinder uptake of skilled care, the full benefits of user‐fee exemption may not be realized in Ghana.     

Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis.

The antiprotozoal compound 1,5-di(4-amidinophenoxy)pentane (pentamidine) and 36 of its analogs were screened for in vitro activity against Leishmania mexicana amazonensis clone 669 C4S (MHOM/BR/73/M2269) and Plasmodium falciparum clones W2 (Indochina III/CDC) and D6 (Sierra Leone I/CDC). Pentamidine and each of the analogs tested exhibited activity in vitro against L. m. amazonensis and P. falciparum. The pentamidine analogs were more effective against the P. falciparum clones than against L. m. amazonensis. P. falciparum was extremely susceptible to these compounds, with 50% inhibitory concentrations as low as 0.03 microM. While none of the analogs exhibited marked improvement in antileishmanial activity compared with pentamidine, 12 of the pentamidine analogs showed activity approximately equal to or greater than that of the parent compound. From the promising activity exhibited by the pentamidine analogs in this in vitro study and their potential for reduced toxicity relative to the parent drug, pentamidine-related compounds hold promise as new agents for the treatment of protozoal infections.