Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases

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.

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Recrudescence ofPlasmodium malariaeafter Quinine

Case Reports in Medicine ◽

10.1155/2014/590265 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Irfanali R. Kugasia ◽

Farhana K. Polara ◽

Hussein Assallum

Keyword(s):

Case Reports ◽

Plasmodium Malariae ◽

Sub Saharan Africa ◽

Case Patient ◽

Liver Stage ◽

Literature Research ◽

Development Of Resistance ◽

Sub Saharan ◽

Emergence Of Resistance

Plasmodium malariaecauses uncommon benign malaria found in the malaria endemic regions mostly of Sub-Saharan Africa. AsPlasmodium malariaedoes not have a continued liver stage in humans the only way to have reinfection without reexposure is through recrudescence. However, reports of its recrudescence after antimalarials are rare with only a handful of case reports in the literature. Research in this field to date has not been able to establish definitively an emergence of resistance inPlasmodium malariaeto commonly used antimalarials. In the presented case, patient had a recrudescence ofP. malariaeafter full treatment with quinine and clindamycin. This recrudescence was treated with full course of chloroquine with clearance of parasite from blood immediately after treatment and at two months’ follow up. The recrudescence in this case cannot be explained by mechanisms explained in prior articles. We propose that the indolence of some of thePlasmodium malariaetrophozoites in the blood can shield them from the effect of the toxic effects of antimalarials and enable them to produce recrudescence later. However, when recrudescence happens, this should not be considered a case of development of resistance and a course of chloroquine should be considered.

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Malaria in developing countries

The Journal of Infection in Developing Countries ◽

10.3855/jidc.4610 ◽

2014 ◽

Vol 8 (01) ◽

pp. 001-004 ◽

Cited By ~ 15

Author(s):

Gema Ruiz Lopez del Prado ◽

Cristina Hernán García ◽

Lourdes Moreno Cea ◽

Virginia Fernández Espinilla ◽

Mari Fe Muñoz Moreno ◽

...

Keyword(s):

Developing Countries ◽

Length Of Stay ◽

Pregnant Women ◽

Papua New Guinea ◽

Pacific Islands ◽

Vaccine Candidate ◽

Sub Saharan Africa ◽

Transmission Rates ◽

Sub Saharan ◽

South Pacific Islands

Malaria still poses a real threat to travellers, particularly in areas with high transmission rates such as sub-Saharan Africa, Papua New Guinea, and the South Pacific islands. Malaria causes an estimated 660,000 deaths each year from 219 million cases of illness. It is a preventable and curable disease. Malaria symptoms appear after a period of seven days or longer, and without treatment, the disease can lead to death. Mosquito bite prevention is the main way to reduce malaria transmission. Chemoprophylaxis recommendations depend on travelers’ age, destination, type of travelling, or length of stay. Pregnant women, children, and immunosuppressed travelers are the most susceptible. There are currently no licensed vaccines against malaria. Results about a research vaccine candidate known as RTS,S/AS01 are expected in 2015.

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Methylene blue inhibits lumefantrine-resistant Plasmodium berghei

The Journal of Infection in Developing Countries ◽

10.3855/jidc.7556 ◽

2016 ◽

Vol 10 (06) ◽

pp. 635-642 ◽

Cited By ~ 4

Author(s):

Victor Irungu Mwangi ◽

Ruth Mwende Mumo ◽

Daniel Muthui Kiboi ◽

Sabah Ahmed Omar ◽

Zipporah Waithera Ng'ang'a ◽

...

Keyword(s):

Methylene Blue ◽

Combination Therapy ◽

Large Scale ◽

Public Health Problem ◽

Drug Repurposing ◽

Sub Saharan Africa ◽

Major Public Health Problem ◽

Resistant Strains ◽

Sub Saharan ◽

Emergence Of Resistance

Introduction: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei. Methodology: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. Results: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. Conclusions: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine-resistant parasites.

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Baseline Evaluation of Bioinformatics Capacity in Tanzania

10.21203/rs.3.rs-112131/v1 ◽

2020 ◽

Author(s):

Raphael Zozimus Sangeda ◽

Aneth David Mwakilili ◽

Upendo Masamu ◽

Siana Nkya ◽

Liberata Alexander Mwita ◽

...

Keyword(s):

Sequence Alignment ◽

Early Career ◽

Sub Saharan Africa ◽

Infrastructure Development ◽

Bioinformatics Analyses ◽

Cross Sectional ◽

Public And Private ◽

Poor Access ◽

Baseline Evaluation ◽

Sub Saharan

Abstract BackgroundEven though the genomics technologies have grown to a large extent, Sub Saharan Africa countries have not entirely reaped the benefits due to the lack of enough capacity to use these technologies. The lack of documentation on existing bioinformatics capacity in these countries hinders the guidance on leveraging the resources and in the identification of areas for improvement. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related research in Tanzania. Our findings identify critical areas for skills and infrastructure development for bioinformatics research. The study is a cross-sectional, explorative, descriptive study, among Tanzanian researchers in public and private academic and research institutionsResultsOut of 84 respondents, 50 (59.5%) were males. More than half of these 44 (52.4%) were in the age between 26-32 years. The majority 41 (48.8%) were master's degree holders with at least one publication related to bioinformatics. Eighty (95.2%) were willing to join the bioinformatics network and initiative in Tanzania. The major challenge faced by 22 (26.2%) of respondents was the lack of training and skills. The most used resources for bioinformatics analyses were the BLAST, PubMed and GenBank. Most performed analyses include sequence alignment and phylogenetic, which was reported by 57 (67.9%) and 42 (50%) of respondents, respectively. The most frequently used statistical software packages were SPSS and R. A quarter of the respondents were conversant with computer programming.ConclusionEarly career and young scientists were the largest group of responders engaged in bioinformatics research and activities across surveyed institutions in Tanzania. The use of bioinformatics tools for analysis is still low, including basic analysis tools such as BLAST, GenBank, sequence alignment software, Swiss-prot and TrEMBL. There is also poor access to resources and tools for bioinformatics analyses. As a way to address the skills and resources gaps, we recommend various modes of training and capacity building of relevant bioinformatics skills and provision of infrastructure so as to improve bioinformatics capacity in Tanzania.

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Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

Plants ◽

10.3390/plants11010047 ◽

2021 ◽

Vol 11 (1) ◽

pp. 47

Author(s):

Douglas O. Ochora ◽

Esezah K. Kakudidi ◽

Jane Namukobe ◽

Perpetua Ipulet ◽

Dancan M. Wakoli ◽

...

Keyword(s):

Drug Combination ◽

Ex Vivo ◽

Malaria Prevalence ◽

Sub Saharan Africa ◽

Cross Resistance ◽

Field Isolates ◽

Malaria Burden ◽

Inhibition Concentration ◽

Sub Saharan ◽

Emergence Of Resistance

Malaria is the most lethal parasitic disease in the world. The frequent emergence of resistance by malaria parasites to any drug is the hallmark of sustained malaria burden. Since the deployment of artemisinin-based combination therapies (ACTs) it is clear that for a sustained fight against malaria, drug combination is one of the strategies toward malaria elimination. In Sub-Saharan Africa where malaria prevalence is the highest, the identification of plants with a novel mechanism of action that is devoid of cross-resistance is a feasible strategy in drug combination therapy. Thus, artemether and lumefantrine were separately combined and tested with extracts of Securidaca longipedunculata, a plant widely used to treat malaria, at fixed extract–drug ratios of 4:1, 3:1, 1:1, 1:2, 1:3, and 1:4. These combinations were tested for antiplasmodial activity against three strains of Plasmodium falciparum (W2, D6, and DD2), and seven field isolates that were characterized for molecular and ex vivo drug resistance profiles. The mean sum of fifty-percent fractional inhibition concentration (FIC50) of each combination and singly was determined. Synergism was observed across all fixed doses when roots extracts were combined with artemether against D6 strain (FIC50 0.403 ± 0.068) and stems extract combined with lumefantrine against DD2 strain (FIC50 0.376 ± 0.096) as well as field isolates (FIC50 0.656 ± 0.067). Similarly, synergism was observed in all ratios when leaves extract were combined with lumefantrine against W2 strain (FIC50 0.456 ± 0.165). Synergism was observed in most combinations indicating the potential use of S. longipedunculata in combination with artemether and lumefantrine in combating resistance.

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Chloroquine and Sulfadoxine–Pyrimethamine Resistance in Sub-Saharan Africa—A Review

Frontiers in Genetics ◽

10.3389/fgene.2021.668574 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alexandra T. Roux ◽

Leah Maharaj ◽

Olukunle Oyegoke ◽

Oluwasegun P. Akoniyon ◽

Matthew Adekunle Adeleke ◽

...

Keyword(s):

Drug Resistance ◽

Antimalarial Drug ◽

Indoor Residual Spraying ◽

Sub Saharan Africa ◽

Bed Nets ◽

African Countries ◽

Antimalarial Drug Resistance ◽

Sub Saharan ◽

Insecticide Treated Bed Nets ◽

Emergence Of Resistance

Malaria is a great concern for global health and accounts for a large amount of morbidity and mortality, particularly in Africa, with sub-Saharan Africa carrying the greatest burden of the disease. Malaria control tools such as insecticide-treated bed nets, indoor residual spraying, and antimalarial drugs have been relatively successful in reducing the burden of malaria; however, sub-Saharan African countries encounter great challenges, the greatest being antimalarial drug resistance. Chloroquine (CQ) was the first-line drug in the 20th century until it was replaced by sulfadoxine–pyrimethamine (SP) as a consequence of resistance. The extensive use of these antimalarials intensified the spread of resistance throughout sub-Saharan Africa, thus resulting in a loss of efficacy for the treatment of malaria. SP was replaced by artemisinin-based combination therapy (ACT) after the emergence of resistance toward SP; however, the use of ACTs is now threatened by the emergence of resistant parasites. The decreased selective pressure on CQ and SP allowed for the reintroduction of sensitivity toward those antimalarials in regions of sub-Saharan Africa where they were not the primary drug for treatment. Therefore, the emergence and spread of antimalarial drug resistance should be tracked to prevent further spread of the resistant parasites, and the re-emergence of sensitivity should be monitored to detect the possible reappearance of sensitivity in sub-Saharan Africa.

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A Baseline Evaluation of Bioinformatics Capacity in Tanzania Reveals Areas for Training

Frontiers in Education ◽

10.3389/feduc.2021.665313 ◽

2021 ◽

Vol 6 ◽

Author(s):

Raphael Zozimus Sangeda ◽

Aneth David Mwakilili ◽

Upendo Masamu ◽

Siana Nkya ◽

Liberata Alexander Mwita ◽

...

Keyword(s):

Community Of Practice ◽

Sequence Alignment ◽

Early Career ◽

Sub Saharan Africa ◽

Language Experience ◽

Bioinformatics Analyses ◽

Bioinformatics Tools ◽

Baseline Evaluation ◽

Sub Saharan ◽

Number Of Publications

Due to the insufficient human and infrastructure capacity to use novel genomics and bioinformatics technologies, Sub-Saharan Africa countries have not entirely ripped the benefits of these technologies in health and other sectors. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related research in Tanzania. The survey collected demographic information like age group, experience, seniority level, gender, number of respondents per institution, number of publications, and willingness to join the community of practice. The survey also investigated the capacity of individuals and institutions about computing infrastructure, operating system use, statistical packages in use, the basic Microsoft packages experience, programming language experience, bioinformatics tools and resources usage, and type of analyses performed. Moreover, respondents were surveyed about the challenges they faced in implementing bioinformatics and their willingness to join the bioinformatics community of practice in Tanzania. Out of 84 respondents, 50 (59.5%) were males. More than half of these 44 (52.4%) were between 26–32 years. The majority, 41 (48.8%), were master’s degree holders with at least one publication related to bioinformatics. Eighty (95.2%) were willing to join the bioinformatics network and initiative in Tanzania. The major challenge faced by 22 (26.2%) respondents was the lack of training and skills. The most used resources for bioinformatics analyses were BLAST, PubMed, and GenBank. Most respondents who performed analyses included sequence alignment and phylogenetics, which was reported by 57 (67.9%) and 42 (50%) of the respondents, respectively. The most frequently used statistical software packages were SPSS and R. A quarter of the respondents were conversant with computer programming. Early career and young scientists were the largest groups of responders engaged in bioinformatics research and activities across surveyed institutions in Tanzania. The use of bioinformatics tools for analysis is still low, including basic analysis tools such as BLAST, GenBank, sequence alignment software, Swiss-prot and TrEMBL. There is also poor access to resources and tools for bioinformatics analyses. To address the skills and resources gaps, we recommend various modes of training and capacity building of relevant bioinformatics skills and infrastructure to improve bioinformatics capacity in Tanzania.

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RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum

Emerging Topics in Life Sciences ◽

10.1042/etls20170101 ◽

2017 ◽

Vol 1 (6) ◽

pp. 533-537

Author(s):

Lorenz von Seidlein ◽

Borimas Hanboonkunupakarn ◽

Podjanee Jittmala ◽

Sasithon Pukrittayakamee

Keyword(s):

Protective Efficacy ◽

Age Groups ◽

Sub Saharan Africa ◽

Phase Iii ◽

European Medicines Agency ◽

Older Children ◽

Pivotal Phase ◽

Malaria Epidemiology ◽

Maximum Benefit ◽

Sub Saharan

RTS,S/AS01 is the most advanced vaccine to prevent malaria. It is safe and moderately effective. A large pivotal phase III trial in over 15 000 young children in sub-Saharan Africa completed in 2014 showed that the vaccine could protect around one-third of children (aged 5–17 months) and one-fourth of infants (aged 6–12 weeks) from uncomplicated falciparum malaria. The European Medicines Agency approved licensing and programmatic roll-out of the RTSS vaccine in malaria endemic countries in sub-Saharan Africa. WHO is planning further studies in a large Malaria Vaccine Implementation Programme, in more than 400 000 young African children. With the changing malaria epidemiology in Africa resulting in older children at risk, alternative modes of employment are under evaluation, for example the use of RTS,S/AS01 in older children as part of seasonal malaria prophylaxis. Another strategy is combining mass drug administrations with mass vaccine campaigns for all age groups in regional malaria elimination campaigns. A phase II trial is ongoing to evaluate the safety and immunogenicity of the RTSS in combination with antimalarial drugs in Thailand. Such novel approaches aim to extract the maximum benefit from the well-documented, short-lasting protective efficacy of RTS,S/AS01.

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