A Comparative Study of Asymptomatic Malaria in a Forest Rural and Depleted Forest Urban Setting during a Low Malaria Transmission and COVID-19 Pandemic Period.

The global malaria morbidity and mortality witnessed an increase from 2019 to 2020 partly due to disruptions in control programs' activities imposed by the COVID-19 pandemic. Therefore, there is still a significant burden of malaria in Cameroon which needs attention from all fronts to attain elimination goals. It is normally expected that a typical forest ecology that has undergone urbanization and subjected to high rates of ecological instabilities should also have a shift from characteristic perennial malaria transmission and a shift in the type of malaria endemicity plaguing such distorted forest ecology. In this observational comparative study, we randomly enrolled participants from rural and urban settings of a forest zone during a low malaria transmission period, which coincided with the onset of COVID-19 pandemic. An optimized structured questionnaire was employed, to collect socio-demographic data and associated risk factors. The CareStart™ Malaria HRP2 antigen test was performed on participants from both settings to determine the prevalence of community asymptomatic malaria. Of 307 participants, 188 (61.0%) were from the rural, while 119 (38.8%) from the urban community. The overall prevalence of asymptomatic malaria (27.0%) detected Plasmodium falciparum antigen in 83 participants. The urban community's prevalence was 4.2% (5 positives) while the rural community's was 41.5% (78 positives). In simple logistic regression models, rural forest community and farm around the house were statistically significant predictors of testing positive (coefficient 2.8, 95% CI 1.8-3.7, p value<0.001) and (coefficient 3.1, 95% CI 1.1-5.1, p value =0.003), respectively. In the multivariate model, the strongest predictor of testing positive was living in a rural community, with p < 0.001 and odds ratio of 10.9 (95% CI, 3.8-31.8). These results indicate that during a low transmission period, the prevalence of asymptomatic malaria differs between depleted urban and rural forested settings, suggesting a need for strategic target intervention for the control of asymptomatic malaria.

Onchocerciasis drug development: from preclinical models to humans.

Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of NTDs is embedded within the Sustainable Development Goals for 2030, under target 3.3. Onchocerciasis afflicts approximately 20.9 million people worldwide with > 90% of those infected residing in Africa. Control programs have made tremendous efforts in the management of onchocerciasis by mass drug administration and aerial larviciding; however, disease elimination is not yet achieved. In the new WHO roadmap, it is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate the achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. The high cost and slow pace of discovery and development of new drugs has led to the repurposing of "old" drugs, as this is more cost-effective and allows development timelines to be shortened. However, even if a drug is marketed for a human or veterinary indication, the safety margin and dosing regimen will need to be re-evaluated to determine the risk in humans. Drug repurposing is a promising approach to enlarging the pool of active molecules in the drug development pipeline. Another consideration when providing new treatment options is the use of combinations, which is not addressed in this review. We here summarize recent advances in the late preclinical or early clinical stage in the search for a potent macrofilaricide, including drugs against the nematode and against its endosymbiont, Wolbachia pipientis.

Knowledge, attitudes, practices of/towards COVID 19 preventive measures and symptoms: A cross-sectional study during the exponential rise of the outbreak in Cameroon.

Severe Acute Respiratory Syndrome Coronavirus 2 (COVID 19) has plagued the world with about 7,8 million confirmed cases and over 430,000 deaths as of June 13th, 2020. The knowledge, attitude, and practices (KAP) people hold towards this new disease could play a major role in the way they accept measures put in place to curb its spread and their willingness to seek and adhere to care. We sought to understand if: a) demographic variables of Cameroonian residents could influence KAP and symptomatology, and b) KAP could influence the risk of having COVID19.A cross-sectional KAP/symptomatology online survey was conducted between April 20 to May 20. All analyses were performed using SPSS version 23. Of all respondents (1006), 53.1% were female, 26.6% were students, 26.9% interacted face to face and 62.8% were residents in Yaoundé with a median age of 33. The overall high score was 84.19% for knowledge, 69% for attitude, and 60.8% for practice towards COVID 19. Age > 20 years was associated with a high knowledge of COVID 19. Women had lower practice scores compared to men (OR = 0.72; 95%CI 0.56-0.92). 41 respondents had ≥3 symptoms and only 9 (22.95%) of them had called 1510 (emergency number). There was no significant difference between KAP and symptomatology. The presence of ≥ 3 symptoms in 4% of respondents (with 56% of them having co-morbidities) supports the current trend in the number of confirmed cases (8681) in Cameroon. The continuous increase in the number of cases and the overall good KAP warrants further investigation to assess the effectiveness of the measures put in place to curb the spread of the disease. Sensitization is paramount to preclude negative health-seeking behaviors and encourage positive preventive and therapeutic practices, for fear of an increase in mortality.

Antioxidant activity of dichloromethane fraction of Dichrocephala integrifolia in Salmonella typhi-infected rats.

OBJECTIVE: Infectious diseases such as typhoid fever lead to the formation of free radicals which can damage the body. Many medicinal plants have antioxidant molecules that neutralize free radicals. The present work evaluated the antioxidant activity and histopathological effects of the dichloromethane fraction of Dichrocephala integrifolia in Salmonella typhi-infected rats. METHODS: The S. typhi-infected rats concurrently received daily doses of D. integrifolia extract at doses of 25, 50 and 100 mg/kg body weight or ciprofloxacin (5 mg/kg body weight) for 15 days. Body temperature was measured daily during infection and treatment periods. At the end of treatment period, the animals were sacrificed and biological responses including hematological parameters, superoxide dismutase and catalase activities, and glutathione, malondialdehyde and nitric oxide concentrations were evaluated. RESULTS: The elevated body temperature induced by infection was significantly decreased in animals treated with 25, 50 or 100 mg/kg of the extract. Platelet levels decreased slightly in infected rats, while treatment with the dichloromethane fraction of D. integrifolia significantly increased platelet levels; this response was greater than that elicited by ciprofloxacin. The doses of 50 and 100 mg/kg of the dichloromethane fraction of D. integrifolia notably decreased monocyte and neutrophil values. Activity of superoxide dismutase and catalase and levels of glutathione in the tissues of treated animals were increased significantly (P < 0.01), while malondialdehyde and nitric oxide levels were significantly decreased (P < 0.01), following treatment with the dichloromethane fraction of D. integrifolia. CONCLUSION: The results of this study show that the dichloromethane fraction of D. integrifolia has protective effects against a series of pathological conditions initiated by oxidation and tissue damage in the course of a S. typhi infection.

Macro and microfilaricidal activities of extracts of Annona senegalensis and Milletia comosa against Onchocerca ochengi and Loa loa.

Despite the efforts employed for the control of onchocerciasis, the latter has remained a significant public health problem, due mainly to the lack of safe and effective adult worm drugs and/or microfilaricides that do not kill Loa loa microfilariae (mf). Serious adverse events have been encountered after administering ivermectin to some onchocerciasis patients coinfected with Loa loa. There is therefore, an urgent need for a macro and/or microfilaricidal drug which kills Onchocerca but not L. loa microfilariae. A total of 12 crude extracts from Milletia comosa and Annona senegalensis were prepared and screened in vitro against the bovine species of Onchocerca, O. ochengi, and L. loa mf from humans. Mf and male worm viabilities were determined by motility scoring using microscopy at 120 h of incubation with drug, while adult female worm viability and cytotoxicity were determined biochemically by MTT/formazan colorimetry after 120 h of incubation with drug. Out of the 12 extracts, all 6 from M. comosa and 4 from A. senegalensis were active against male, female and mf of O. ochengi. The hexane extract from M. comosa leaves (MCL hex) was the most active with IC50 values of 1.38, 0.86 and 17.74 µg/mL for O. ochengi adult males, adult female and the mf, respectively. About 58% of the extracts were more active against O. ochengi than L. loa mf. These results demonstrate that these extracts contain active principles that kill Onchocerca parasite and to a lesser extent L. loa, and suggest that they can be fractionated for isolation of lead molecules for the safe treatment of onchocerciasis.

Filaricidal properties of Lantana camara and Tamarindus indica extracts, and Lantadene A from L. camara against Onchocerca ochengi and Loa loa.

BACKGROUND: Ivermectin is the only drug currently recommended for the treatment of onchocerciasis, the second leading infectious cause of blindness in the world. This drug kills only the first stage larvae-microfilariae (mf) of Onchocerca volvulus and is to be used cautiously in areas where Loa loa is prevalent because of severe adverse events observed with coinfected patients. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated the anti-filarial activities of two Cameroonian medicinal plants, Lantana camara and Tamarindus indica locally used to treat onchocerciasis. Twelve (12) extracts were prepared and tested in vitro on the bovine model parasite, O. ochengi as well as L. loa mf. Both mf and adult male worm viabilities were assessed by motility scoring, while adult female worm viability was determined biochemically by standard MTT/formazan colorimetry. Cytotoxicity and acute toxicity were determined respectively, in monkey kidney epithelial cells and in BALB/c mice. Pure compounds were isolated by LC/MS using a bio-assay guided strategy. All the extracts showed 100% activity at 500 µg/mL against O. ochengi adult worms and mf. The highest activity against O. ochengi was observed with the hexane extract of L. camara leaves (LCLhex), with IC50 of 35.1 µg/mL for adult females and 3.8 µg/mL for the mf. Interestingly, this extract was more active against O. ochengi mf than L. loa mf. Further studies on the extracts led to the isolation of lantadene A from the methylene chloride extract of L. camara leaves, with IC50s of 7.85 µg/mL for adult males, 10.38 µg/mL for adult females, 10.84 µg/mL for O. ochengi mf and 20.13 µg/mL for L. loa mf. CONCLUSIONS/SIGNIFICANCE: We report for the first time the anti-onchocercal activities of these locally consumed medicinal plants and lantadene A, a potential lead for further development as an onchocerciasis cure.