A Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa-Endemic Areas.

BACKGROUND: Implementation of an ivermectin-based community treatment strategy for the elimination of onchocerciasis or lymphatic filariasis has been delayed in Central Africa because of the occurrence of serious adverse events, including death, in persons with high levels of circulating Loa loa microfilariae. The LoaScope, a field-friendly diagnostic tool to quantify L. loa microfilariae in peripheral blood, enables rapid, point-of-care identification of persons at risk for serious adverse events. METHODS: A test-and-not-treat strategy was used in the approach to ivermectin treatment in the Okola health district in Cameroon, where the distribution of ivermectin was halted in 1999 after the occurrence of fatal events related to L. loa infection. The LoaScope was used to identify persons with an L. loa microfilarial density greater than 20,000 microfilariae per milliliter of blood, who were considered to be at risk for serious adverse events, and exclude them from ivermectin distribution. Active surveillance for posttreatment adverse events was performed daily for 6 days. RESULTS: From August through October 2015, a total of 16,259 of 22,842 persons 5 years of age or older (71.2% of the target population) were tested for L. loa microfilaremia. Among the participants who underwent testing, a total of 15,522 (95.5%) received ivermectin, 340 (2.1%) were excluded from ivermectin distribution because of an L. loa microfilarial density above the risk threshold, and 397 (2.4%) were excluded because of pregnancy or illness. No serious adverse events were observed. Nonserious adverse events were recorded in 934 participants, most of whom (67.5%) had no detectable L. loa microfilariae. CONCLUSIONS: The LoaScope-based test-and-not-treat strategy enabled the reimplementation of community-wide ivermectin distribution in a heretofore "off limits" health district in Cameroon and is a potentially practical approach to larger-scale ivermectin treatment for lymphatic filariasis and onchocerciasis in areas where L. loa infection is endemic. (Funded by the Bill and Melinda Gates Foundation and others.).

Loss of sensitivity of immunochromatographic test (ICT) for lymphatic filariasis diagnosis in low prevalence settings: consequence in the monitoring and evaluation procedures.

BACKGROUND: Diagnostic tools for lymphatic filariasis (LF) elimination programs are useful in mapping the distribution of the disease, delineating areas where mass drug administrations (MDA) are required, and determining when to stop MDA. The prevalence and burden of LF have been drastically reduced following mass treatments, and the evaluation of the performance of circulating filarial antigen (CFA)-based assays was acknowledged to be of high interest in areas with low residual LF endemicity rates after multiple rounds of MDA. The objective of this study was therefore to evaluate the immunochromatographic test (ICT) sensitivity in low endemicity settings and, specifically, in individuals with low intensity of lymphatic filariasis infection. METHODS: To perform this study, calibrated thick blood smears, ICT and Og4C3 enzyme-linked immunosorbent assay (ELISA) were carried out by night to identify Wuchereria bancrofti microfilarial and circulating filarial antigen carriers. A threshold determination assay regarding ICT and ELISA was performed using serial plasma dilutions from individuals with positive microfilarial counts. RESULTS: All individuals harbouring microfilariae (positive blood films) were detected by ICT and ELISA, but among individuals positive for ELISA, only 35.7 % of them were detected using ICT (Chi square: 4.57; p-value = 0.03), indicating a moderate agreement between both tests (kappa statistics = 0.49). Threshold determination analyses showed that ELISA was still positive at the last plasma dilution with negative ICT result. CONCLUSIONS: These findings suggest a loss of sensitivity for ICT in low endemicity settings, especially in people exhibiting low levels of circulating filarial antigen, raising serious concern regarding the monitoring and evaluation procedures in the framework of LF elimination program.

In vitro, in vivo and in silico antiplasmodial profiling of the aqueous extract of Hibiscus asper HOOK F. Leaf (Malvaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Plasmodium resistance to antimalarial drugs raises the urgent need to seek for alternative treatments. Aqueous extract of Hibiscus asper leaves is currently used in malaria management but remains less documented. AIM OF THE STUDY: The study aims to evaluate antimalarial effects of the aqueous extract of Hibiscus asper. UHPLC/MS, was used to identify some likely compounds present in the plant that were thereafter docked to some malaria parasite proteins. STUDY DESIGN: In vitro anti-plasmodium and antioxidant, UHPLC/Ms analysis, in vivo antimalarial of the plant extract, and in silico molecular docking prediction of some identified compounds were performed to investigate the pharmacological effects of H. asper. MATERIAL AND METHODS: The in vitro antiplasmodial activity of the extract was carried out on Plasmodium falciparum strains using SYBR-green dye; then, the curative antimalarial activity was conducted on Plasmodium berghei NK65-infected male Wistar rats. The UHPLC/MS analysis was used to identify plant compounds, followed by interactions (docking affinity) between some compounds and parasitic enzymes such as P. falciparum purine nucleoside phosphorylase (2BSX) and 6-phosphogluconate dehydrogenase (6FQY) to explore potential mechanisms of action at the molecular level. RESULTS: No hemolysis effect of the extract was observed at concentrations up to 100 mg/mL. In vitro test of the aqueous leaves extract of H. asper showed inhibitory activity against P. falciparum Dd2 and 3D7 strains with IC50 values of 19.75 and 21.97 µg/mL, respectively. The curative antimalarial test of the H. asper extract in infected rats exhibited significant inhibition of the parasite growth (p < 0.001) with inhibition percentage of 95.11%, 97.68% and 95.59% at all the doses (50, 100 and 200 mg/kg) respectively. The extract corrected major physiological alterations such as liver and kidney impairments, oxidative stress and architectural disorganization in liver, spleen and kidneys tissues. The UHPLC/MS analysis identified 7 compounds, namely chlorogenic acid, azulene, quercetin, rhodine, 1-ethyl-2,4-dimethyl benzene and phthalan. Out of seven compounds identified in the extract quercetin and phthalan showed higher in silico inhibitory activity against P. falciparum purine nucleoside phosphorylase and Plasmodium falciparum 6-phosphosgluconate dehydrogenase parasite enzymes. CONCLUSION: These findings indicate that H. asper could be a promising complementary medicine to manage malaria. Meanwhile, the affinity of annoted compounds with these enzymes should be further confirmed.

Antibacterial and antishigellosis activity of Xylopia staudtii (engl. & diels), Annonaceae.

ETHNOPHARMACOLOGICAL RELEVANCE: Xylopia staudtii is a medicinal plant which fruits are traditionally used in western Cameroon as a spice in the preparation of soups known for their abdominal cramp relieving properties. Often identified as Xylopia africana, its bark is used in the treatment of dysentery in Mont Cameroun localities. This plant could therefore contain active ingredients against intestinal pathogens, including Shigella spp, which are responsible of the deathly dysenteric diarrhoea. AIM OF THE STUDY: This study aims to assess the efficacy of the hydroethanolic extract from Xylopia staudtii bark in immunodepressed mice infected with Shigella flexneri. MATERIALS AND METHODS: Qualitative detection of compounds in the crude extract was done using UPLC-DAD-(HR) ESI-MS analysis in an attempt to link the activity to the chemical composition. The MIC and the MBC of the extract was determined using broth dilution method. Shigellosis was induced by intraperitoneal administration of Shigella flexneri to immunodepressed mice pretreated with streptomycin. These infected mice were then treated with the extract (100, 200 and 400 mg/kg), and reference substances (ciprofloxacin and saline). During the 9 days of treatment, animal morphology, fecal pathology and deaths were recorded. At the end of the treatment period, blood and organs were collected from any surviving animals for hematological, biochemical and histopathological analyses. RESULTS: The extract was found to be significantly active, with a bactericidal effect against Shigella and a bacteriostatic effect against Escherichia coli. It was able to reduce and stop the faecal pathology caused by the infection in mice, as well as the rate of deaths which was brought to zero (0) in animal treated at 400 mg/kg. The bacteria load in faeces was reduced by 100% in animal treated at 400 mg/kg. Xylopia staudtii extract elicited anti-inflammatory properties by reducing MPO activity and Lcn2 intestinal level. It also prevents damages in the intestinal tissue and the shortening of colon which characterise Shigella infection. The serum level of ASAT, ALAT, bilirubin, urea and creatinine in animals treated with the extract was similar to those of normal animal used in the study. These activities of the plant may be due at least in part to the presence of ent-kauran type diterpens such as kaurenoic acid identified in the extract. CONCLUSION: These findings support the usage of Xylopia staudtii as an antimicrobial against bacillary dysentery, making this plant a potential candidate for the formulation of an improved standardized traditional medicine.

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei.

BACKGROUND: Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. OBJECTIVES: The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. MATERIALS AND METHODS: Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. RESULTS: Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 µg/mL to 5.886 µg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50 = 0.809 µg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. CONCLUSION: The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity.

Prevalence and intensity of human soil transmitted helminth infections in the Akonolinga health district (Centre Region, Cameroon): Are adult hosts contributing in the persistence of the transmission?

BACKGROUND: Soil-transmitted helminthiases (STHs) are among the most prevalent afflictions of the developing world, with approximately 2 billion people infected worldwide. Heavily infected individuals suffer from severe morbidity that can result in death. These parasitic diseases also impair physical and mental growth in childhood, thwart educational advancement, and hinder economic development. Periodic deworming with Albendazole or Mebendazole of high-risk groups (school-age children, preschool children, and pregnant women) can significantly lower the levels of infections below the threshold associated with morbidity. However, an important proportion of the population (adults) is excluded from this high-risk group treatment based-strategy, and might lead to the persistence of these diseases in endemic areas despite the repeated treatments. The main objective of this study was to evaluate the contribution of this neglected at-risk group in the spread and persistence of STH in Cameroon. METHODS: A cross sectional survey was conducted in the Akonolinga health district (Centre Region, Cameroon) to assess the prevalence and intensity of these helminth infections. Stool samples were collected from males and females, aged 18 years and over, and analyzed using the Kato-Katz technique. RESULTS: A total of 334 patients, among which 181 (54.2%) females and 153 (45.8%) males, were examined. The STH of major concern was found in this group of individuals, with overall prevalence equal to 18.0% (95% CI: 14.2-22.4) for Ascaris lumbricoides, 43.7% (95% CI: 38.5-49.1) for Trichuris trichiura, and 7.5% (95% CI: 5.1-10.8) for Necator americanus. CONCLUSION: This study reveals that STH infections are prevalent in adults in the Akonolinga health district, with moderate to high risk and light intensity of infection. These infected adults might constitute a potential parasite reservoir and a source of dissemination and persistence of these infections, highlighting the need to really take into account this neglected group of individuals in the mass treatment policy.

Acute and sub-acute toxicity of a lyophilised aqueous extract of the aerial part of Spilanthes africana Delile in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Spilanthes africana is a plant used in several countries for the treatment of toothache, malaria, fracture, pneumonia, and dysentery. In order to establish the safety of aerial part of the plant extract, the acute and sub-acute toxicity of the aqueous extract of this plant has been evaluated in male and female young rats. MATERIAL AND METHODS: In acute toxicity, the effects of a single oral dose (2,000 mg/kg and 5,000 mg/kg) of the lyophilised aqueous extract have been determined. General behaviour, adverse effects and mortality were determined for up to 14 days. In sub-acute treatment, the effects of the extract in daily single oral administration at the doses of 250, 500 and 1,000 mg/kg during 28 days were evaluated. One group treated at the dose of 1,000 mg/kg for 28 days was let without treatment during 14 days to assess the possible reversibility of the harmful effects of the extract. Body weight, food and water intakes, biochemical and haematological parameters were recorded. Histopathological examination of liver, kidney and lungs were assessed. RESULTS: In acute study, a single administration of the aqueous extract at the doses of 2,000 mg/kg or 5,000 mg/kg did not induce mortality. Thus, the LD50 of the aqueous extract of S. africana has been estimated higher than 5,000 mg/kg. Four hours after administration of the extract, a reduction of the mobility, sensitivity to the noise and to touch has been observed. In sub-acute study, the administration of the extract during 28 days at all doses did not significantly modify the body weight. On the haematological analysis, a decrease of the rate of monocytes and a rise of lymphocytes counts were observed among the male group. In both sexes, it appeared a decrease of the rate of granulocytes two weeks after stopping the treatment. It has also been observed in different groups among the females, an increase of the mean corpuscular content and the mean concentration in haemoglobin as well as an increase of platelets. A significant decrease of transaminases, alkaline phosphatase, triglycerides, and a significant increase of total bilirubin compared to the normal group has been observed. There was a significant decrease in renal catalase in both sexes compared with different control groups. Besides, a significant increase of the kidney rates of glutathione and malondialdehyde have also been observed in the female treated at the doses of 1,000 mg/kg. Histopathological analysis has shown vascular congestion and leucocyte infiltrations in the liver of animals treated at the dose of 1,000 mg/kg. This congestion has been marked in satellite group. In the kidney female satellite group, tubular clarifications have been observed and disappear when stopping the treatment. CONCLUSION: These results show that the aqueous extract of S. africana given by the oral route is slightly toxic. However in sub-acute treatment, higher doses could provoke functional and structural changes in the organism which could in part reversible. Thus the extract should be used with caution.