Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria.

Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum-host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and/or B antigen on RBCs from AA, BB and AB genotypes compared to AO/BO genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and in vitro adhesion assays to test the hypothesis that "double dose" non-O genotypes (AA, BB, AB) are associated with increased risk of severe malaria and larger rosettes than "single dose" heterozygotes (AO, BO). In the case-control study, compared to OO, the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with AB (OR 1.93) and AO (OR 1.27) showing most marked difference (p = 0.02, Wald test). In vitro experiments with blood group A-preferring P. falciparum parasites showed that significantly larger rosettes were formed with AA and AB host RBCs compared to OO, whereas AO and BO genotypes rosettes were indistinguishable from OO. Overall, the data show that ABO genotype influences P. falciparum rosetting and support the hypothesis that double dose non-O genotypes confer a greater risk of severe malaria than AO/BO heterozygosity.

Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in three Kenyan referral hospitals: Repeated cross-sectional surveys 2020-21.

INTRODUCTION: The high proportion of SARS-CoV-2 infections that have remained undetected presents a challenge to tracking the progress of the pandemic and estimating the extent of population immunity. METHODS: We used residual blood samples from women attending antenatal care services at three hospitals in Kenya between August 2020 and October 2021and a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. We fitted a two-component mixture model as an alternative to the threshold analysis to estimate of the proportion of individuals with past SARS-CoV-2 infection. RESULTS: We estimated seroprevalence in 2,981 women; 706 in Nairobi, 567 in Busia and 1,708 in Kilifi. By October 2021, 13% of participants were vaccinated (at least one dose) in Nairobi, 2% in Busia. Adjusted seroprevalence rose in all sites; from 50% (95%CI 42-58) in August 2020, to 85% (95%CI 78-92) in October 2021 in Nairobi; from 31% (95%CI 25-37) in May 2021 to 71% (95%CI 64-77) in October 2021 in Busia; and from 1% (95% CI 0-3) in September 2020 to 63% (95% CI 56-69) in October 2021 in Kilifi. Mixture modelling, suggests adjusted cross-sectional prevalence estimates are underestimates; seroprevalence in October 2021 could be 74% in Busia and 72% in Kilifi. CONCLUSIONS: There has been substantial, unobserved transmission of SARS-CoV-2 in Nairobi, Busia and Kilifi Counties. Due to the length of time since the beginning of the pandemic, repeated cross-sectional surveys are now difficult to interpret without the use of models to account for antibody waning.

Co-administration of chloroquine and coenzyme Q10 improved treatment outcome during experimental cerebral malaria.

Development of cerebral malaria (CM) is driven by parasitemia levels, harmful inflammatory response, oxidative stress and consequent breach of the blood brain barrier. Use of adjunct therapy that utilizes an antioxidant and anti-inflammatory agent alongside chloroquine (CQ), may improve treatment outcome and shorten recovery from post-infection sequelae. Though withdrawn in some countries, CQ is still in use for prophylaxis and treatment of malaria in many countries. Current study investigated whether oral co-administration of 50 mg/kg CQ and 200 mg/kg of coenzyme Q10 (CoQ10) would improve treatment outcome against experimental cerebral malaria (ECM) and assuage the deleterious effects of oxidative stress and inflammation upon infection by Plasmodium berghei ANKA (PbA) in a C57BL/6 J mouse model. Treatment with CQ + CoQ10 resulted in an improved parasite elimination; clearing the parasite one day early, when compared to mice on CQ alone. Remarkably, treatment with CQ and CoQ10 separately or in combination, assuaged PbA induced elevation of serum levels of TNF-α and IFN-γ an indication of protection from ECM progression. Furthermore, CQ and CoQ10-administration, blocked parasite-driven elevation of aspartate transaminase (AST), alanine transaminase (ALT) and bilirubin. In the presence of CQ and CoQ10, severe PbA-induced systemic induction of oxidative stress and resultant GSH depletion was reduced in the brain, liver, spleen, and kidney. Overall, these findings demonstrate that administration of CQ and CoQ10 ameliorates harmful parasite-driven oxidative stress and inflammation, while slowing the progression to full blown ECM and may improve treatment outcome in CM.

Qualitative healthcare worker survey: Retrospective cross-sectional case study on COVID-19 in the African context.

Background: Despite the presence of COVID-19 epidemiologic data in Africa, there are gaps in the understanding of healthcare workers' concerns and fears early in the pandemic. Methods: A retrospective cross-sectional multi-country pan-African qualitative survey case study on the perceived effects of the COVID-19 pandemic on healthcare workers in the continent focused specifically on personal safety and misinformation. The survey was distributed to 13 countries via snowball sampling of practitioners between April 22 and May 15, 2020. The survey solicited free-form answers, resulting in a large spectrum of responses. Qualitative analysis included open and axial coding methods for thematic emergence. Results: A total of 489 analyzable responses were recorded. The majority of respondents (n = 273, 57%) highlighted personal safety concerns including lack of resources and training to prevent infection (33%); fear of infection and transmission (24%); lack of public awareness and compliance with regulations (12%); governmental concerns (9%) and economic insecurity (11%) amongst others. 328 respondents (67%) reported having heard misinformation about COVID-19. Responses included misinformation regarding origin of the virus (11%), false modes of transmission (6%), differential effect for specific groups (30%), unproven cures (35%), and disbelief in existence (11%). Responses for misinformation and fears revealed categorical associations between certain countries. Conclusion: Addressing fears and concerns of frontline healthcare workers facilitates their essential role in combating community misinformation, and further understanding could provide essential insight to institutions and governments to direct resource allotment and community education.

The Road to Elimination: Current State of Schistosomiasis Research and Progress Towards the End Game.

The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches.

Performance Evaluation of Lateral Flow Assays for Coronavirus Disease-19 Serology.

The coronavirus disease of 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has undoubtedly resulted in significant morbidities, mortalities, and economic disruptions across the globe. Affordable and scalable tools to monitor the transmission dynamics of the SARS-CoV-2 virus and the longevity of induced antibodies will be paramount to monitor and control the pandemic as multiple waves continue to rage in many countries. Serologic assays detect humoral responses to the virus, to determine seroprevalence in target populations, or induction of antibodies at the individual level following either natural infection or vaccination. With multiple vaccines rolling out globally, serologic assays to detect anti-SARS-CoV-2 antibodies will be important tools to monitor the development of herd immunity. To address this need, serologic lateral flow assays (LFAs), which can be easily implemented for both population surveillance and home use, will be vital to monitor the evolution of the pandemic and inform containment measures. Such assays are particularly important for monitoring the transmission dynamics and durability of immunity generated by natural infections and vaccination, particularly in resource-limited settings. In this review, we discuss considerations for evaluating the accuracy of these LFAs, their suitability for different use cases, and implementation opportunities.

Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons.

The social environment is a major determinant of morbidity, mortality and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune-stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, while we observe pronounced rank-related differences in baseline immune gene activity, only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.

Seroprevalence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Kenya.

BACKGROUND: Few studies have assessed the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Africa. We report findings from a survey among HCWs in 3 counties in Kenya. METHODS: We recruited 684 HCWs from Kilifi (rural), Busia (rural), and Nairobi (urban) counties. The serosurvey was conducted between 30 July and 4 December 2020. We tested for immunoglobulin G antibodies to SARS-CoV-2 spike protein, using enzyme-linked immunosorbent assay. Assay sensitivity and specificity were 92.7 (95% CI, 87.9-96.1) and 99.0% (95% CI, 98.1-99.5), respectively. We adjusted prevalence estimates, using bayesian modeling to account for assay performance. RESULTS: The crude overall seroprevalence was 19.7% (135 of 684). After adjustment for assay performance, seroprevalence was 20.8% (95% credible interval, 17.5%-24.4%). Seroprevalence varied significantly (P < .001) by site: 43.8% (95% credible interval, 35.8%-52.2%) in Nairobi, 12.6% (8.8%-17.1%) in Busia and 11.5% (7.2%-17.6%) in Kilifi. In a multivariable model controlling for age, sex, and site, professional cadre was not associated with differences in seroprevalence. CONCLUSION: These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.

Phytochemical Profile and Antimicrobial Activities of Edible Mushroom Termitomyces striatus.

The mushroom Termitomyces striatus is an edible mushroom that grows wildly and belongs to the family Lyophyllaceae. Studies in the last few decades have demonstrated that mushrooms and their active components have beneficial effects on a variety of biological systems. Some mushrooms do exhibit antibacterial properties. Qualitative phytochemical profile was done on the mushroom Termitomyces striatus to establish the presence of compounds responsible for important biological activities. This study also investigated the effect of Termitomyces striatus extracts on certain bacterial strains that included Escherichia coli and Pseudomonas aeruginosa representing the Gram-negative bacteria and Bacillus subtilis and Staphylococcus aureus representing Gram-positive bacteria. The fungi were represented by Candida albicans and Saccharomyces cerevisiae. The mushroom was collected in western Kenya, air-dried, and crushed into powder, followed by extraction using water, methanol, and dichloromethane (DCM) solvents. Antibacterial and antifungal activities were evaluated using the disc-diffusion method. Qualitative phytochemical screening of the aqueous extract revealed the presence of alkaloids, flavonoids, steroids, sterols, saponins, phenols, carbohydrates, and proteins. The three extracts exhibited antibacterial against tested bacterial strains. The DCM extract revealed higher effects among the bacterial strains tested. The three extracts showed antifungal effects against C. albicans. However, both methanol and aqueous extracts did not inhibit growth of S. cerevisiae. In conclusion, T. striatus extracts are a promising source of novel antimicrobial and antifungal agents.

Mental health symptoms and inflammatory markers among HIV infected patients in Tanzania.

BACKGROUND: HIV and mental disorders are predicted to be the leading causes of illness worldwide by the year 2030. HIV-infected patients are at increased risk of developing mental disorders which are significantly associated with negative clinical outcomes and propagation of new HIV infections. There is little evidence that links inflammation to development of mental disorders among HIV patients. Therefore, the main objective of this study was to evaluate if mental health symptoms were associated with biomarkers of inflammation in HIV infected subjects. METHODS: A cross-sectional study was conducted in Dar es Salam, Tanzania from March to May 2018. Standardized tools were used to collect data based on the World Health Organisation's (WHO) stepwise approach for non-communicable diseases (NCD) surveillance. A total of 407 HIV+ patients on antiretroviral therapy were recruited. The WHO stepwise approach for NCD surveillance was used to collect data together with anthropometric measurements. Mental health symptoms were determined based on self-reported thoughts of helplessness, suicide ideation, depression, despair, discouragement, and feelings of isolation. Enzyme-linked immunosorbent assay was used to test for inflammatory markers:- C-reactive protein (CRP), Iinterleukin-6 (IL-6), interleukin-18 (IL-18), soluble tumour necrosis factor receptor-I (sTNFR-I), and soluble tumour necrosis factor receptor-II (sTNFR-II). Bivariate and multi-variate analysis was conducted to examine the association between biomarkers and mental health symptoms. RESULTS: The prevalence of self-reported mental health symptoms was 42% (n = 169). Participants with self-reported symptoms of mental health had elevated CRP, were less likely to walk or use a bicycle for at least 10 minutes, were less likely to participate in moderate-intensity sports or fitness activities, and had poor adherence to HIV treatment (p < 0.005). CRP remained significant in the sex adjusted, age-sex adjusted, and age-sex-moderate exercise adjusted models. In the fully adjusted logistic regression model, self-reported mental health symptoms were significantly associated with a higher quartile of elevated CRP (OR 4.4; 95% CI 1.3-5.9) and sTNFR-II (OR 2.6; 95% CI 1.4-6.6) and the third quartile of IL-18 (OR 5.1;95% CI 1.5-17.5) as compared with those reporting no mental health symptoms. The significance of sTNFR-II and IL-18 in the fully adjusted model is confounded by viral load suppression rates at the sixth month. CONCLUSION: High CRP and sTNFR II were important contributors to the prevalence of mental health symptoms. This study is among the minimal studies that have examined mental health issues in HIV, and therefore, the findings may offer significant knowledge despite the potential reverse causality. Regardless of the nature of these associations, efforts should be directed toward screening, referral, and follow-up of HIV patients who are at-risk for mental health disorders.

COVID-19 in Africa: Survey Analysis of Impact on Health-Care Workers.

As coronavirus disease 2019 (COVID-19) spreads across Africa, little is known about the impact of the pandemic on health-care workers (HCWs) in the region. We designed an anonymous survey distributed via e-mail and phone messaging to 13 countries through the African Hepatitis B Network. We obtained 489 analyzable responses. We used risk ratio analysis to quantify the relationship between binary variables and χ2 testing to quantify the statistical significance of these relationships. Median age of respondents was 30 years (interquartile range, 26-36 years) and 63% were physicians. The top three sources of information used by HCWs for COVID-19 management included the Ministry of Health of each country, the WHO, and social media. Forty-nine percent reported a decrease in income since the start of the pandemic, with the majority experiencing between a 1% and a 25% salary reduction. Sixty-six percent reported some access to personal protective equipment; only 14% reported appropriate access. Moreover, one third of respondents reported no availability of ventilators at their facility. Strikingly, the percentage of HCWs reporting never feeling depressed changed from 61% before the pandemic to 31% during the pandemic, with a corresponding increase in daily depressive symptoms from 2% to 20%. Most respondents (> 97%) correctly answered survey questions about COVID-19 symptoms, virus transmission, and prevention. Our survey revealed African HCWs face a variety of personal and professional context-dependent challenges. Ongoing support of HCWs through and after the COVID-19 pandemic is essential.

Risk of Healthcare Worker Burnout in Africa during the COVID-19 Pandemic.

COVID-19 is now impacting every country in Africa and healthcare workers (HCWs) across the continent remain susceptible to professional burnout. We designed a 43-question survey addressing multiple aspects of the COVID-19 pandemic. The survey was anonymous, distributed via email and phone messaging to 13 countries in Africa. We obtained 489 analyzable responses. 49% off HCWs reported a decrease in income, with the majority experiencing between 1-25% salary reduction. Sixty-six percent reported some access to personal protective equipment (PPE), 20% had no access to PPE and only 14% reported proper access. Strikingly, the percentage reporting never feeling depressed changed from 61% before the pandemic to 31% during the pandemic, with an increase in daily depression from 2% to 20%. We found no association between depression and change in income, household size, availability of PPE or lockdown. Safety concerns related to stigma from being HCWs affected 56% of respondents.

Hepatitis B Awareness and Vaccination Patterns among Healthcare Workers in Africa.

Hepatitis B virus (HBV) vaccination patterns and the understanding of its risks among healthcare workers (HCWs) is a critical step to decrease transmission. However, the depth of this understanding is understudied. We distributed surveys to HCWs in 12 countries in Africa. Surveys had nine multiple-choice questions that assessed HCWs' awareness and understanding of HBV. Participants included consultants, medical trainees, nurses, students, laboratory personnel, and other hospital workers. Surveys were completed anonymously. Fisher's exact test was used for analysis, with a P-value of < 0.05 considered significant; 1,044 surveys were collected from Kenya, Egypt, Sudan, Tanzania, Ethiopia, Uganda, Malawi, Madagascar, Nigeria, Cameroon, Ghana, and Sierra Leone. Hepatitis B virus serostatus awareness, vaccination rate, and vaccination of HCWs' children were 65%, 61%, and 48%, respectively. Medical trainees had higher serostatus awareness, vaccination rate, and vaccination of their children than HCWs in other occupations (79% versus 62%, P < 0.001; 74% versus 58%, P < 0.001; and 62% versus 45%, P = 0.006, respectively). Cost was cited as the most frequent reason for non-vaccination. West African countries were more aware of their serostatus but less often vaccinated than East African countries (79% versus 59%, P < 0.0001 and 52% versus 60%, P = 0.03, respectively). West African countries cited cost as the reason for non-vaccination more than East African countries (59% versus 40%, P = 0.0003). Our study shows low HBV serostatus awareness and vaccination rate among HCWs in Africa, and reveals gaps in the perception and understanding of HBV prevention that should be addressed to protect HCWs and improve their capacity to control HBV infection.

Metformin's effectiveness in preventing prednisone-induced hyperglycemia in hematological cancers.

BACKGROUND: Research has established the development of steroid-induced hyperglycemia as a glucometabolic side effect of high-dose prednisone therapy. Few studies, however, have demonstrated preventative measures that could effectively curtail this side effect in susceptible patients undergoing high-dose prednisone treatment. OBJECTIVE: To assess metformin's prophylactic effectiveness of prednisone-induced hyperglycemia among hematological cancer patients. SETTING: Prospective randomized controlled trial conducted at the Kenyatta National Hospital Oncology Clinic and Wards, Nairobi, Kenya. METHOD: Non-hyperglycemic hematological cancer patients on current or newly initiated high-dose prednisone-based chemotherapy were randomized to receive metformin 850 mg once then 850 mg twice daily for two successive weeks each or to the control group receiving the standard care. Patients were subjected to once weekly fasting and 2-h postprandial glucose measurements for four weeks. MAIN OUTCOME MEASURE: The primary outcome of measure was the development of hyperglycemia defined by fasting capillary blood glucose values >5.6 mmol/L or 2-h postprandial capillary blood glucose values >7.8 mmol/L. RESULTS: Eighteen of 24 randomized patients completed the study (11 control and 7 treatment). The proportion of the control subjects that developed prediabetes was 72.7% (95% confidence interval 45.5-90.9%) using fasting glucose and 54.5% (95% confidence interval 27.3-81.8%) using 2-h postprandial glucose. One treatment group participant developed prediabetes using fasting glucose, representing 14.3% (95% confidence interval 0-42.9%). No prediabetes was detected using the 2-h postprandial glucose. Analysis of mean fasting glucose between the two arms found no significant difference. However, significant differences in mean 2-h postprandial glucose were noted in week 2 (p = 0.0144), week 3 (p = 0.0095), and week 4 (p = 0.0074) of the study. Double dose (1700 mg) metformin was more effective in lowering blood glucose than single dose (850 mg) (p = 1.0000 (fasting), p = 0.4531(2-h postprandial). CONCLUSION: Metformin's prophylactic effectiveness was demonstrated in this randomized study on new and previously exposed non-diabetic cancer patients on high-dose prednisone-based chemotherapy.

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses.

BACKGROUND: Schistosoma mansoni is one of the most common helminth infections affecting a large population of people in sub-Saharan Africa. This helminth infection is known to cause immunomodulation which has affected the efficacy of a number of vaccines. This study examined whether a chronic schistosoma infection has an effect on the immunogenicity of HPV vaccine which is currently administered to girls and women aged 9 to 24. Little is known about the immune responses of the HPV vaccine in individuals with chronic schistosomiasis. METHODS: This study was carried out at the Institute of Primate Research (IPR) and involved an Olive baboon model. The experimental animals were randomly placed into three groups (n = 3-4); Two groups were infected with S. mansoni cercaria, and allowed to reach chronic stage (week 12 onwards), at week 13 and 14 post-infection, one group was treated with 80mg/kg of praziquantel (PZQ). Sixty four weeks post schistosoma infection, all groups received 2 doses of the Cervarix HPV vaccine a month apart. Specific immune responses to the HPV and parasite specific antigens were evaluated. RESULTS: Animals with chronic S. mansoni infection elicited significantly reduced levels of HPV specific IgG antibodies 8 weeks after vaccination compared the PZQ treated and uninfected groups. There was no significant difference in cellular proliferation nor IL-4 and IFN-γ production in all groups. CONCLUSION: Chronic S. mansoni infection results in reduction of protective HPV specific IgG antibodies in a Nonhuman Primate model, suggesting a compromised effect of the vaccine. Treatment of schistosomiasis infection with PZQ prior to HPV vaccination, however, reversed this effect supporting anti-helminthic treatment before vaccination.

Oral administration of Coenzyme Q10 protects mice against oxidative stress and neuro-inflammation during experimental cerebral malaria.

In animal model of experimental cerebral malaria (ECM), the genesis of neuropathology is associated with oxidative stress and inflammatory mediators. There is limited progress in the development of new approaches to the treatment of cerebral malaria. Here, we tested whether oral supplementation of Coenzyme Q10 (CoQ10) would offer protection against oxidative stress and brain associated inflammation following Plasmodium berghei ANKA (PbA) infection in C57BL/6 J mouse model. For this purpose, one group of C57BL/6 mice was used as control; second group of mice were orally supplemented with 200 mg/kg CoQ10 and then infected with PbA and the third group was PbA infected alone. Clinical, biochemical, immunoblot and immunological features of ECM was monitored. We observed that oral administration of CoQ10 for 1 month and after PbA infection was able to improve survival, significantly reduced oedema, TNF-α and MIP-1ß gene expression in brain samples in PbA infected mice. The result also shows the ability of CoQ10 to reduce cholesterol and triglycerides lipids, levels of matrix metalloproteinases-9, angiopoietin-2 and angiopoietin-1 in the brain. In addition, CoQ10 was very effective in decreasing NF-κB phosphorylation. Furthermore, CoQ10 supplementation abrogated Malondialdehyde, and 8-OHDG and restored cellular glutathione. These results constitute the first demonstration that oral supplementation of CoQ10 can protect mice against PbA induced oxidative stress and neuro-inflammation usually observed in ECM. Thus, the need to study CoQ10 as a candidate of antioxidant and immunomodulatory molecule in ECM and testing it in clinical studies either alone or in combination with antimalaria regimens to provide insight into a potential translatable therapy.

The protein DIIIC-2, aggregated with a specific oligodeoxynucleotide and adjuvanted in alum, protects mice and monkeys against DENV-2.

Previously, we reported the ability of the chimeric protein DIIIC-2 (domain III of the dengue envelope protein fused to the capsid protein of dengue-2 virus), to induce immunity and protection in mice, when it is highly aggregated with a non-defined oligodeoxynucleotide (ODN) and adjuvanted in alum. In this work, three different defined ODNs were studied as aggregating agents. Our results suggest that the nature of the ODN influences the capacity of protein DIIIC-2 to activate cell-mediated immunity in mice. Consequently, the ODN 39M was selected to perform further experiments in mice and nonhuman primates. Mice receiving the preparation 39M-DIIIC-2 were solidly protected against dengue virus (DENV) challenge. Moreover, monkeys immunized with the same preparation developed neutralizing antibodies, as measured by four different neutralization tests varying the virus strains and the cell lines used. Two of the immunized monkeys were completely protected against challenge, whereas the third animal had a single day of low-titer viremia. This is the first work describing the induction of short-term protection in monkeys by a formulation that is suitable for human use combining a recombinant protein from DENV with alum.

Capsid protein: evidences about the partial protective role of neutralizing antibody-independent immunity against dengue in monkeys.

The role of cellular immune response in dengue virus infection is not yet fully understood. Only few studies in murine models propose that CD8(+) T-cells are associated with protection from infection and disease. At the light of recent reports about the protective role of CD8(+) T-cells in humans and the no correlation between neutralizing antibodies and protection observed in several studies, a vaccine based on cell-mediated immunity constitute an attractive approach. Our group has developed a capsid-based vaccine as nucleocpasid-like particles from dengue-2 virus, which induced a protective CD4(+) and CD8(+) cell-mediated immunity in mice, without the contribution of neutralizing antibodies. Herein we evaluated the immunogenicity and protective efficacy of this molecule in monkeys. Neither IgG antibodies against the whole virus nor neutralizing antibodies were elicited after the antigen inoculation. However, animals developed a cell-mediated immunity, measured by gamma interferon secretion and cytotoxic capacity. Although only one out of three vaccinated animals was fully protected against viral challenge, a viral load reduction was observed in this group compared with the placebo one, suggesting that capsid could be the base on an attractive vaccine against dengue.