Safety and efficacy of toll-like receptor agonists as therapeutic agents and vaccine adjuvants for infectious diseases in animals: a systematic review.

Introduction: Strengthening global health security relies on adequate protection against infectious diseases through vaccination and treatment. Toll-like receptor (TLR) agonists exhibit properties that can enhance immune responses, making them potential therapeutic agents or vaccine adjuvants. Methods: We conducted an extensive systematic review to assess the efficacy of TLR agonists as therapeutic agents or vaccine adjuvants for infectious diseases and their safety profile in animals, excluding rodents and cold-blooded animals. We collected qualitative and available quantitative data on the efficacy and safety outcomes of TLR agonists and employed descriptive analysis to summarize the outcomes. Results: Among 653 screened studies, 51 met the inclusion criteria. In this review, 82% (42/51) of the studies used TLR agonists as adjuvants, while 18% (9/51) applied TLR agonist as therapeutic agents. The predominant TLR agonists utilized in animals against infectious diseases was CpG ODN, acting as a TLR9 agonist in mammals, and TLR21 agonists in chickens. In 90% (46/51) of the studies, TLR agonists were found effective in stimulating specific and robust humoral and cellular immune responses, thereby enhancing the efficacy of vaccines or therapeutics against infectious diseases in animals. Safety outcomes were assessed in 8% (4/51) of the studies, with one reporting adverse effects. Discussion: Although TLR agonists are efficacious in enhancing immune responses and the protective efficacy of vaccines or therapeutic agents against infectious diseases in animals, a thorough evaluation of their safety is imperative to in-form future clinical applications in animal studies. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323122.

Ecological and subject-level drivers of interepidemic Rift Valley fever virus exposure in humans and livestock in Northern Kenya.

Nearly a century after the first reports of Rift Valley fever (RVF) were documented in Kenya, questions on the transmission dynamics of the disease remain. Specifically, data on viral maintenance in the quiescent years between epidemics is limited. We implemented a cross-sectional study in northern Kenya to determine the seroprevalence, risk factors, and ecological predictors of RVF in humans and livestock during an interepidemic period. Six hundred seventy-six human and 1,864 livestock samples were screened for anti-RVF Immunoglobulin G (IgG). Out of the 1,864 livestock samples tested for IgG, a subset of 1,103 samples was randomly selected for additional testing to detect the presence of anti-RVFV Immunoglobulin M (IgM). The anti-RVF virus (RVFV) IgG seropositivity in livestock and humans was 21.7% and 28.4%, respectively. RVFV IgM was detected in 0.4% of the livestock samples. Participation in the slaughter of livestock and age were positively associated with RVFV exposure in humans, while age was a significant factor in livestock. We detected significant interaction between rainfall and elevation's influence on livestock seropositivity, while in humans, elevation was negatively associated with RVF virus exposure. The linear increase of human and livestock exposure with age suggests an endemic transmission cycle, further corroborated by the detection of IgM antibodies in livestock.

Infectious disease modelling for SARS-CoV-2 in Africa to guide policy: A systematic review.

Applied epidemiological models have played a critical role in understanding the transmission and control of disease outbreaks. Their utility and accuracy in decision-making on appropriate responses during public health emergencies is however a factor of their calibration to local data, evidence informing model assumptions, speed of obtaining and communicating their results, ease of understanding and willingness by policymakers to use their insights. We conducted a systematic review of infectious disease models focused on SARS-CoV-2 in Africa to determine: a) spatial and temporal patterns of SARS-CoV-2 modelling in Africa, b) use of local data to calibrate the models and local expertise in modelling activities, and c) key modelling questions and policy insights. We searched PubMed, Embase, Web of Science and MedRxiv databases following the PRISMA guidelines to obtain all SARS-CoV-2 dynamic modelling papers for one or multiple African countries. We extracted data on countries studied, authors and their affiliations, modelling questions addressed, type of models used, use of local data to calibrate the models, and model insights for guiding policy decisions. A total of 74 papers met the inclusion criteria, with nearly two-thirds of these coming from 6% (3) of the African countries. Initial papers were published 2 months after the first cases were reported in Africa, with most papers published after the first wave. More than half of all papers (53, 78%) and (48, 65%) had a first and last author affiliated to an African institution respectively, and only 12% (9) used local data for model calibration. A total of 60% (46) of the papers modelled assessment of control interventions. The transmission rate parameter was found to drive the most uncertainty in the sensitivity analysis for majority of the models. The use of dynamic models to draw policy insights was crucial and therefore there is need to increase modelling capacity in the continent.

The COVID-19 pandemic and disruptions to essential health services in Kenya: a retrospective time-series analysis.

BACKGROUND: Public health emergencies can disrupt the provision of and access to essential health-care services, exacerbating health crises. We aimed to assess the effect of the COVID-19 pandemic on essential health-care services in Kenya. METHODS: Using county-level data routinely collected from the health information system from health facilities across the country, we used a robust mixed-effect model to examine changes in 17 indicators of essential health services across four periods: the pre-pandemic period (from January, 2018 to February, 2020), two pandemic periods (from March to November 2020, and February to October, 2021), and the period during the COVID-19-associated health-care workers' strike (from December, 2020 to January, 2021). FINDINGS: In the pre-pandemic period, we observed a positive trend for multiple indicators. The onset of the pandemic was associated with statistically significant decreases in multiple indicators, including outpatient visits (28·7%; 95% CI 16·0-43·5%), cervical cancer screening (49·8%; 20·6-57·9%), number of HIV tests conducted (45·3%; 23·9-63·0%), patients tested for malaria (31·9%; 16·7-46·7%), number of notified tuberculosis cases (26·6%; 14·7-45·1%), hypertension cases (10·4%; 6·0-39·4%), vitamin A supplements (8·7%; 7·9-10·5%), and three doses of the diphtheria, tetanus toxoid, and pertussis vaccine administered (0·9%; 0·5-1·3%). Pneumonia cases reduced by 50·6% (31·3-67·3%), diarrhoea by 39·7% (24·8-62·7%), and children attending welfare clinics by 39·6% (23·5-47·1%). Cases of sexual violence increased by 8·0% (4·3-25·0%). Skilled deliveries, antenatal care, people with HIV infection newly started on antiretroviral therapy, confirmed cases of malaria, and diabetes cases detected were not significantly affected negatively. Although most of the health indicators began to recover during the pandemic, the health-care workers' strike resulted in nearly all indicators falling to numbers lower than those observed at the onset or during the pre-strike pandemic period. INTERPRETATION: The COVID-19 pandemic and the associated health-care workers' strike in Kenya have been associated with a substantial disruption of essential health services, with the use of outpatient visits, screening and diagnostic services, and child immunisation adversely affected. Efforts to maintain the provision of these essential health services during a health-care crisis should target the susceptible services to prevent the exacerbation of associated disease burdens during such health crises. FUNDING: Bill & Melinda Gates Foundation.

Endemicity of Coxiella burnetii infection among people and their livestock in pastoral communities in northern Kenya.

Background: Coxiella burnetti can be transmitted to humans primarily through inhaling contaminated droplets released from infected animals or consumption of contaminated dairy products. Despite its zoonotic nature and the close association pastoralist communities have with their livestock, studies reporting simultaneous assessment of C. burnetti exposure and risk-factors among people and their livestock are scarce. Objective: This study therefore estimated the seroprevalence of Q-fever and associated risk factors of exposure in people and their livestock. Materials and methods: We conducted a cross-sectional study in pastoralist communities in Marsabit County in northern Kenya. A total of 1,074 women and 225 children were enrolled and provided blood samples for Q-fever testing. Additionally, 1,876 goats, 322 sheep and 189 camels from the same households were sampled. A structured questionnaire was administered to collect individual- and household/herd-level data. Indirect IgG ELISA kits were used to test the samples. Results: Household-level seropositivity was 13.2% [95% CI: 11.2-15.3]; differences in seropositivity levels among women and children were statistically insignificant (p = 0.8531). Lactating women had higher odds of exposure, odds ratio (OR) = 2.4 [1.3-5.3], while the odds of exposure among children increased with age OR = 1.1 [1.0-1.1]. Herd-level seroprevalence was 83.7% [81.7-85.6]. Seropositivity among goats was 74.7% [72.7-76.7], while that among sheep and camels was 56.8% [51.2-62.3] and 38.6% [31.6-45.9], respectively. Goats and sheep had a higher risk of exposure OR = 5.4 [3.7-7.3] and 2.6 [1.8-3.4], respectively relative to camels. There was no statistically significant association between Q-fever seropositivity and nutrition status in women, p = 0.900 and children, p = 1.000. We found no significant association between exposure in people and their livestock at household level (p = 0.724) despite high animal exposure levels, suggesting that Q-fever exposure in humans may be occurring at a scale larger than households. Conclusion: The one health approach used in this study revealed that Q-fever is endemic in this setting. Longitudinal studies of Q-fever burden and risk factors simultaneously assessed in human and animal populations as well as the socioeconomic impacts of the disease and further explore the role of environmental factors in Q-fever epidemiology are required. Such evidence may form the basis for designing Q-fever prevention and control strategies.

Impact of livestock interventions on maternal and child nutrition outcomes in Africa: A systematic review and meta-analysis protocol.

The challenge of undernutrition (stunting and wasting) still remains a major health concern in children below 5 years of age in Africa, with the continent accounting for more than one third of all stunted children and more than one quarter of all wasted children globally. Despite the growing evidence on the role of agriculture interventions in improving nutrition, empirical evidence on the impact of livestock intervention on nutrition in Africa is scant. This review is aimed at determining whether livestock interventions are effective in reducing undernutrition in children below five years of age and in pregnant and lactating women in Africa. The review will be conducted according to PRISMA guidelines. Major electronic databases will be searched and complemented with grey and non-indexed literature from google and google scholar, and expert consultation for additional articles and reports. PICO criteria will be used while employing search strategies including MeSH, Boolean search operators and truncation/wildcard symbol to narrow or broaden the search. Articles on effect of livestock interventions on maternal and child nutrition conducted in Africa that meet the set inclusion criteria will be included in the review after critical appraisal by two independent reviewers. A standardized form will be used to extract data from included studies. The extracted data will be summarized and synthesized both qualitatively and quantitatively and key outcomes presented. Evidence generated from the systematic review and meta-analysis will be important for guiding nutrition sensitive livestock interventions and policies on nutrition programming, specifically on how to leverage on livestock interventions to reduce the burden of undernutrition.

Serological evidence of single and mixed infections of Rift Valley fever virus, Brucella spp. and Coxiella burnetii in dromedary camels in Kenya.

Camels are increasingly becoming the livestock of choice for pastoralists reeling from effects of climate change in semi-arid and arid parts of Kenya. As the population of camels rises, better understanding of their role in the epidemiology of zoonotic diseases in Kenya is a public health priority. Rift Valley fever (RVF), brucellosis and Q fever are three of the top priority diseases in the country but the involvement of camels in the transmission dynamics of these diseases is poorly understood. We analyzed 120 camel serum samples from northern Kenya to establish seropositivity rates of the three pathogens and to characterize the infecting Brucella species using molecular assays. We found seropositivity of 24.2% (95% confidence interval [CI]: 16.5-31.8%) for Brucella, 20.8% (95% CI: 13.6-28.1%) and 14.2% (95% CI: 7.9-20.4%) for Coxiella burnetii and Rift valley fever virus respectively. We found 27.5% (95% CI: 19.5-35.5%) of the animals were seropositive for at least one pathogen and 13.3% (95% CI: 7.2-19.4%) were seropositive for at least two pathogens. B. melitensis was the only Brucella spp. detected. The high sero-positivity rates are indicative of the endemicity of these pathogens among camel populations and the possible role the species has in the epidemiology of zoonotic diseases. Considering the strong association between human infection and contact with livestock for most zoonotic infections in Kenya, there is immediate need to conduct further research to determine the role of camels in transmission of these zoonoses to other livestock species and humans. This information will be useful for designing more effective surveillance systems and intervention measures.

One Health education in Kakuma refugee camp (Kenya): From a MOOC to projects on real world challenges.

Today, the world counts millions of refugees but only a fraction of them have access to higher education. Despite the multiple public health problems in refugee camps and the need to build local capacities to prevent and combat them, University level courses in public health are largely unavailable for refugees. This paper describes the development, implementation and evaluation of an innovative two-module blended-learning programme on One Health in Kakuma refugee camp (Kenya). This programme combines: (I) Interdisciplinary and multi-expert MOOC on "Global Health at the Human-Animal-Ecosystem interface"; (II) peer-to-peer learning involving students from University of Geneva Master of science in Global Health and research collaborations around specific and locally-relevant problems; (III) online mentoring and lecturing by experts from the Institute of Global Health of the University of Geneva in Kakuma. A total of 67 refugees applied to Module 1; 15 started the Module 1 in October 2017, of these 14 completed it and 6 passed the exams, finally five students started the Module 2 in October 2018 which they all passed in February 2019. Five student-led collaborative projects were developed focusing on the conception of a community-based monitoring system for prevalent diseases in the camp. With such a pedagogic approach, the programme provides an overview on Global Health challenges at the human-animal-ecosystem interface and the importance of the One Health approach, and introduces students to scientific research through interdisciplinary and international collaborations and innovation. The high number of applicants and positive feedback from students in Kakuma show the interest in One Health education in the camp. This learning experience ultimately aims at building local knowledge and capacity fostering "One Health" champions to reinforce local and national health system. This framework for One Health education could be potentially scaled up to other camps in Africa and the world.