Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera (Clusiaceae)

Ateba JET, Toghueo RMK, Awantu AF, et al. Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera (Clusiaceae). JOURNAL OF FUNGI. 2018;4(2): UNSP 70.There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC50 < 10 mu g.mL(-1)) with three fungi including Paecilomyces lilacinus (IC50 = 0.44 mu g.mL(-1)), Penicillium janthinellum (IC50 = 0.2 mu g.mL(-1)), and Paecilomyces sp. (IC50 = 0.55 mu g.mL(-1)) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing

High efficacy of chlorfenapyr-based net Interceptor ® G2 against pyrethroid-resistant malaria vectors from Cameroon

Background: The increasing reports of resistance to pyrethroid insecticides associated with reduced efficacy of pyrethroid-only interventions highlight the urgency of introducing new non-pyrethroid-only control tools. Here, we investigated the performance of piperonyl-butoxide (PBO)-pyrethroid [Permanet 3.0 (P3.0)] and dual active ingredients (AI) nets [Interceptor G2 (IG2): containing pyrethroids and chlorfenapyr and Royal Guard (RG): containing pyrethroids and pyriproxyfen] compared to pyrethroid-only net Royal Sentry (RS) against pyrethroid-resistant malaria vectors in Cameroon. Methods: The efficacy of these tools was firstly evaluated on Anopheles gambiae s.l. and Anopheles funestus s.l. from Gounougou, Mibellon, Mangoum, Nkolondom, and Elende using cone/tunnel assays. In addition, experimental hut trials (EHT) were performed to evaluate the performance of unwashed and 20 times washed nets in semi-field conditions. Furthermore, pyrethroid-resistant markers were genotyped in dead vs alive, blood-fed vs unfed mosquitoes after exposure to the nets to evaluate the impact of these markers on net performance. The XLSTAT software was used to calculate the various entomological outcomes and the Chi-square test was used to compare the efficacy of various nets. The odds ratio and Fisher exact test were then used to establish the statistical significance of any association between insecticide resistance markers and bed net efficacy. Results: Interceptor G2 was the most effective net against wild pyrethroid-resistant An. funestus followed by Permanet 3.0. In EHT, this net induced up to 87.8% mortality [95% confidence interval (CI): 83.5–92.1%) and 55.6% (95% CI: 48.5–62.7%) after 20 washes whilst unwashed pyrethroid-only net (Royal Sentry) killed just 18.2% (95% CI: 13.4–22.9%) of host-seeking An. funestus. The unwashed Permanet 3.0 killed up to 53.8% (95% CI: 44.3–63.4%) of field-resistant mosquitoes and 47.2% (95% CI: 37.7–56.7%) when washed 20 times, and the Royal Guard 13.2% (95% CI: 9.0–17.3%) for unwashed net and 8.5% (95% CI: 5.7–11.4%) for the 20 washed net. Interceptor G2, Permanet 3.0, and Royal Guard provided better personal protection (blood-feeding inhibition 66.2%, 77.8%, and 92.8%, respectively) compared to pyrethroid-only net Royal Sentry (8.4%). Interestingly, a negative association was found between kdrw and the chlorfenapyr-based net Interceptor G2 (χ2 = 138; P < 0.0001) with homozygote-resistant mosquitoes predominantly found in the dead ones. Conclusions: The high mortality recorded with Interceptor G2 against pyrethroid-resistant malaria vectors in this study provides first semi-field evidence of high efficacy against these major malaria vectors in Cameroon encouraging the implementation of this novel net for malaria control in the country. However, the performance of this net should be established in other locations and on other major malaria vectors before implementation at a large scale

Alarming rates of virological failure and HIV-1 drug resistance amongst adolescents living with perinatal HIV in both urban and rural settings: evidence from the EDCTP READY-study in Cameroon

Objectives: Adolescents living with perinatal HIV infection (ALPHI) experience persistently high mortality rates, particularly in resource-limited settings. It is therefore clinically important for us to understand the therapeutic response, acquired HIV drug resistance (HIVDR) and associated factors among ALPHI, according to geographical location. Methods: A study was conducted among consenting ALPHI in two urban and two rural health facilities in the Centre Region of Cameroon. World Health Organization (WHO) clinical staging, self-reported adherence, HIVDR early warning indicators (EWIs), immunological status (CD4 count) and plasma viral load (VL) were assessed. For those experiencing virological failure (VF, VL&nbsp;≥&nbsp;1000 copies/mL), HIVDR testing was performed and interpreted using the Stanford HIV Drug Resistance Database v.8.9-1. Results: Of the 270 participants, most were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (61.7% urban vs. 82.2% rural), and about one-third were poorly adherent (30.1% vs. 35.1%). Clinical failure rates (WHO-stage III/IV) in both settings were&nbsp;&lt;&nbsp;15%. In urban settings, the immunological failure (IF) rate (CD4 &nbsp;&lt;&nbsp;250 cells/μL) was 15.8%, statistically associated with late adolescence, female gender and poor adherence. The VF rate was 34.2%, statistically associated with poor adherence and NNRTI-based antiretroviral therapy. In the rural context, the IF rate was 26.9% and the VF rate was 52.7%, both statistically associated with advanced clinical stages. HIVDR rate was over 90% in both settings. EWIs were delayed drug pick-up, drug stock-outs and suboptimal viral suppression. Conclusions: Poor adherence, late adolescent age, female gender and advanced clinical staging worsen IF. The VF rate is high and consistent with the presence of HIVDR in both settings, driven by poor adherence, NNRTI-based regimen and advanced clinical staging

Feasibility of Early Infant Diagnosis of HIV in Resource-Limited Settings: The ANRS 12140-PEDIACAM Study in Cameroon

BACKGROUND: Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon. METHODS/FINDINGS: The ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8(th) day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001). CONCLUSIONS: In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery

Eruptive and earthquake activities related to the 2000 eruption of Mount Cameroon volcano (West Africa)

Mount Cameroon is an active volcano located in the Gulf of Guinea, west of Central Africa. After the March-April 1999 eruption on the SW flank, another eruption of the volcano occurred in 2000. It took place from three sites on the southwest flank and near the summit. The first eruptive site was located 500 m to the southwest of the summit, at 3900 m altitude. Activity on this site was mainly explosive with no lava flow. The second site was located between 3220 and 3470 m altitude. Lava was emitted along NNE-SSE fissures from this site and flew towards Buea, the main city of the area, stopping similar to 4 km from the first houses. The last site was located in the south western flank at 2750 m altitude. The lava ejected from an old cone near the first 1999 eruptive site was divided into two branches, for a total length of around 1 km. The location of active volcanic cones in 1999 and 2000 seems to be linked to the local tectonics. The pre-eruptive period was characterized by a seismic swarm which may be a precursor recorded in March 2000 by an analogue seismic station. The main shock was a magnitude 3.2 event, and was felt by the population in Ekona town located on the eastern flank. It had a Modified Mercalli intensity of III-IV. When the eruption started, a temporary network of short period 3-component seismic stations was set up around the volcano to improve the monitoring of seismic activity. The co-eruptive period from late May to September was characterized by sequences of earthquake swarms, volcanic tremor and a family of earthquakes having similar waveform and appearing regularly in August and early September. Some of the earthquakes were felt by the population in Buea and its environments. The largest seismic event recorded had a magnitude of 4. During the post-eruptive period from mid-September to December, seismicity returned to its background level of 1-3 earthquakes per 3 days. Hypocenter locations reveal a linear narrow structure under the summit zone which could represent the magmatic conduit of the volcano. The frequency/magnitude relationship revealed a b-value of 1.43 higher than those previously determined, but more representative of volcanic media. Seismic energy release was gradual after the 2000 eruption started

Oxidized palm oil impairs reproductive functions and architectures in female rats

Objective: To evaluate the effects of three oxidized palm oil diets (OPD) on female rat reproductive function. Methods: Forty-four female Wistar rats presenting five consecutive and regular estrous cycles were divided into 4 groups. The rats were fed with: a standard diet, 70% of standard diet+30% oxidized palm oil diet (OPD1), OPD1+5 g of boiled yolk egg (OPD2) and OPD1+10% sucrose (OPD3) for 125 days, respectively. During the feeding period, morphometric, estrous cycle, sexual behavior, gestation, biochemical and histomorphometric parameters were evaluated. Results: All OPDs significantly increased abdominal circumference, body mass index and Lee index coupled to an irregularity and lengthening of the estrous cycle. They significantly decreased appetite and consumption behaviours, quantic pregnancy index, fertility rate, implantation sites and index, serum progesterone and high-density lipoprotein levels, increased pre-implantation losses, anti-implantation activities, serum estradiol, triglycerides, total and low-density lipoprotein-cholesterol levels, and impaired brain and ovaries oxidative status. Histomorphometric examinations revealed increases in the number of atresic and primary follicles and decreases in secondary, tertiary, Degraaf, total and corpus luteum follicles in ovaries coupled to a neurodegeneration of hypothalamic anteroventral periventricular neurons in the OPD groups compared to the standard diet group. Conclusions: The three OPDs induce obesity and impair the female reproductive function, especially OPD2 and OPD3. These findings contribute to a better understanding of the adverse effects of palm oil bleaching on the reproductive function in female rats, which could be useful in the management of women with obesity-related sexual dysfunction