Background: Reducing the burden of malaria requires better understanding of vector populations, particularly in forested regions where the incidence remains elevated. Here, we characterized malaria vectors in a locality near the Yaoundé international airport, Cameroon, including species composition, abundance, Plasmodium infection rate, insecticide resistance profiles and underlying resistance mechanisms. Methods: Blood-fed adult mosquitoes resting indoors were aspirated from houses in April 2019 at Elende, a locality situated 2 km from the Yaoundé-Nsimalen airport. Female mosquitoes were forced to lay eggs to generate F 1 adults. Bioassays were performed to assess resistance profile to the four insecticides classes. The threshold of insecticide susceptibility was defined above 98% mortality rate and mortality rates below 90% were indicative of confirmed insecticide resistance. Furthermore, the molecular basis of resistance and Plasmodium infection rates were investigated. Results: Anopheles funestus s.s. was the most abundant species in Elende (85%) followed by Anopheles gambiae s.s. (15%) with both having similar sporozoite rate. Both species exhibited high levels of resistance to the pyrethroids, permethrin and deltamethrin (<40% mortality). An. gambiae s.s. was resistant to DDT (9.9% mortality) and bendiocarb (54% mortality) while susceptible to organophosphate. An. funestus s.s. was resistant to dieldrin (1% mortality), DDT (86% mortality) but susceptible to carbamates and organophosphates. The L119F-GSTe2 resistance allele (8%) and G119S ace-1 resistance allele (15%) were detected in An. funestus s.s. and An. gambiae s.s., respectively. Furthermore, the high pyrethroid/DDT resistances in An. gambiae corresponded with an increase frequency of 1014F kdr allele (95%). Transcriptional profiling of candidate cytochrome P450 genes reveals the over-expression of CYP6P5, CYP6P9a and CYP6P9b. Conclusion: The resistance to multiple insecticide classes observed in these vector populations alongside the significant Plasmodium sporozoite rate highlights the challenges that vector control programs encounter in sustaining the regular benefits of contemporary insecticide-based control interventions in forested areas.
Onchocerciasis is a skin and eye disease that exerts a heavy socio-economic burden, particularly in sub-Saharan Africa, a region which harbours greater than 96% of either infected or at-risk populations. The elimination plan for the disease is currently challenged by many factors including amongst others; the potential emergence of resistance to the main chemotherapeutic agent, ivermectin (IVM). Novel tools, including preventative and therapeutic vaccines, could provide additional impetus to the disease elimination tool portfolio. Several observations in both humans and animals have provided evidence for the development of both natural and artificial acquired immunity. In this study, immuno-informatics tools were applied to design a filarial-conserved multi-epitope subunit vaccine candidate, (designated Ov-DKR-2) consisting of B-and T-lymphocyte epitopes of eight immunogenic antigens previously assessed in pre-clinical studies. The high-percentage conservation of the selected proteins and epitopes predicted in related nematode parasitic species hints that the generated chimera may be instrumental for cross-protection. Bioinformatics analyses were employed for the prediction, refinement, and validation of the 3D structure of the Ov-DKR-2 chimera. In-silico immune simulation projected significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses. Preliminary immunological analyses revealed that the multi-epitope vaccine candidate reacted with antibodies in sera from both onchocerciasis-infected individuals, endemic normals as well as loiasis-infected persons but not with the control sera from European individuals. These results support the premise for further characterisation of the engineered protein as a vaccine candidate for onchocerciasis.
The public health goal of onchocerciasis in Africa has advanced from control to elimination. In this light, accurate diagnosis is necessary to determine treatment endpoints and confirm elimination, as well as to conduct surveillance for the identification of any possible recrudescence of the disease. Currently, the monitoring of onchocerciasis elimination relies on the Ov-16 test. However, this test is unable to discriminate between past and active infections. Furthermore, about 15–25% of infected persons are reported to be negative for the Ov-16 test, giving a misleading sense of security to false-negative individuals who might continue to serve as reservoirs for infections. Therefore, we opted to design and validate a more sensitive and specific chimeric antigen (OvMANE1) for onchocerciasis diagnosis, using previously reported immunodominant peptides of O. volvulus, the parasite responsible for the disease. In silico analysis of OvMANE1 predicted it to be more antigenic than its individual peptides. We observed that OvMANE1 reacts specifically and differentially with sera from O. volvulus infected and non-infected individuals, as well as with sera from communities of different levels of endemicity. Moreover, we found that total IgG, unlike IgG4 subclass, positively responded to OvMANE1, strongly suggesting its complementarity to the Ov-16 diagnostic tool, which detects Ov-16 IgG4 antibodies. Overall, OvMANE1 exhibited the potential to be utilized in the development of specific diagnostic tools—based on both antibody capture and antigen capture reactions—which are indispensable to monitor the progress of onchocerciasis elimination programs.
Onchocerciasis is a Neglected Tropical Disease that has a significant socioeconomic impact, especially in Sub-Saharan Africa. Numerous reports indicate that the Expanded Special Project for the Elimination of Neglected Tropical Diseases needs novel diagnostic tools before achieving its goal of successful elimination of onchocerciasis in Africa. The current diagnostic tests are either invasive, insensitive, or not applicable in the field and about 25% of persons infected cannot mount immune responses against the single antigen used in the only approved Ov-16 serological test. In the quest to identify novel biomarkers that can be used to certify that a patient is free from the disease, evaluate the progress of elimination programmes, and conduct post elimination surveillances, mass spectrometric analysis of Onchocerca volvulus crude extract revealed that 1392 proteins are expressed in the adult and microfilariae stages of the parasite. Computational analysis predicted six of the proteins as O. volvulus potential diagnostic targets. Linear B-epitopes were predicted from the six proteins and used to construct a multiepitope antigen (OvMCBL02). Serological analysis revealed that the OvMCBL02 test significantly differentiated between serum samples of onchocerciasis patients from the Kombone Health Area in the South West Region of Cameroon (n = 63) and control serum samples from Rwanda (n = 29) and Europe (n = 26) as well as between serum samples from the onchocerciasis hyperendemic region of Kombone Health Area (n = 63) and the hypoendemic region of Bandjoun Health District (n = 54). Interestingly, the test did not cross-react with serum samples from patients suffering from related nematode infections, thereby suggesting that further characterization of the OvMCBL02 multiepitope antigen will render it an additional member of the diagnostic toolbox for the elimination of onchocerciasis.
African swine fever (ASF) is a hemorrhagic contagious porcine disease caused by the African swine fever virus. The disease poses enormous problems to the pork industry with pig mortality ranging from 30% to 100%, depending on the virulence of the virus circulating. Cameroon, situated in Central Africa is one of the countries in which the African swine fever virus (ASFV) has been endemic since its first outbreak in 1982. The disease is a major problem to the pig industry causing huge economic losses. A clear and concise review on ASF in Cameroon relating to the entry and current genotype of the virus, epidemiology, pathogenesis and economic impact is lacking. A thorough literature search revealed: (1) The virus entered the country in 1982 and caused the death of 80% of the pigs. (2) All isolates belong to serogroup I and only Genotype I is circulating in Cameroon principally in the domestic cycle as there are neither soft ticks nor warthog in the pig production regions sampled. (3) 70% of the pig farmers are involved in the traditional system of production with local and hybrid breeds of pigs with minimal input. (4) The country is endemic to the virus with huge economic losses. (5) So far, very little research has been effected on ASFV in Cameroon. This review gives a detailed overview of the situation of African swine fever virus (ASFV) in the country along with potential avenues for future research into ASFV in Cameroon.
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