A pooled testing strategy for identifying SARS-CoV-2 at low prevalence.

Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups1-7. A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test8. Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30-48-fold dilutions described in previous studies9-11). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).

Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium-Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands.

An efficient synthetic protocol was devised for the preparation of five cationic ruthenium-arene complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands from the [RuCl2(p-cymene)]2 dimer and 2 equiv of an NHC·CS2 zwitterion. The reactions proceeded cleanly and swiftly in dichloromethane at room temperature to afford the expected [RuCl(p-cymene)(S2C·NHC)]Cl products in quantitative yields. When the [RuCl2(p-cymene)]2 dimer was reacted with only 1 equiv of a dithiolate betaine under the same experimental conditions, a set of five bimetallic compounds with the generic formula [RuCl(p-cymene)(S2C·NHC)][RuCl3(p-cymene)] was obtained in quantitative yields. These novel, dual anionic and cationic ruthenium-arene complexes were fully characterized by various analytical techniques. NMR titrations showed that the chelation of the dithiocarboxylate ligands to afford [RuCl(p-cymene)(S2C·NHC)]+ cations was quantitative and irreversible. Conversely, the formation of the [RuCl3(p-cymene)]- anion was limited by an equilibrium, and this species readily dissociated into Cl- anions and the [RuCl2(p-cymene)]2 dimer. The position of the equilibrium was strongly influenced by the nature of the solvent and was rather insensitive to the temperature. Two monometallic and two bimetallic complexes cocrystallized with water, and their molecular structures were solved by X-ray diffraction analysis. Crystallography revealed the existence of strong interactions between the azolium ring protons of the cationic complexes and neighboring donor groups from the anions or the solvent. The various compounds under investigation were highly soluble in water. They were all strongly cytotoxic against K562 cancer cells. Furthermore, with a selectivity index of 32.1, the [RuCl(p-cymene)(S2C·SIDip)]Cl complex remarkably targeted the erythroleukemic cells vs mouse splenocytes.

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae).

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC50 (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC50 (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots' crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.

The Inhibition of NLRP3 Inflammasome and IL-6 Production by Hibiscus noldeae Baker f. Derived Constituents Provides a Link to Its Anti-Inflammatory Therapeutic Potentials.

The activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and/or its components is associated with the physio-pathogenesis of many respiratory diseases including asthma, COPD (chronic obstructive pulmonary disease), SARS Cov-2 (severe acute respiratory syndrome coronavirus 2), and in several autoimmune diseases. Hibiscus noldeae Baker f. has been widely reported to be traditionally used in the treatment of different ailments, some of which are of inflammatory background such as asthma, wounds, headache, etc. However, the claims have not been supported by evidence at the molecular and functional levels. Here, we report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6). The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1ß (IL-1ß) in Lipopolysaccharide (LPS) and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages. It was observed that hexane and ethyl acetate fractions of the crude extract of the aerial parts of H. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1ß and IL-6 production. The ER2.4 and ER2.7 fractions downregulated the production of IL-1ß and IL-6, in a similar range as the caspase-1 inhibitor AC-YVAD-CHO and the drug Dexamethasone, both used as controls, respectively. Overall, our work does provide the very first scientific based evidence for Hibiscus noldeae anti-inflammatory effects and widespread use by traditional healers in Rwanda for a variety of ailments.

Zic2 mutation causes holoprosencephaly via disruption of NODAL signalling.

The ZIC2 transcription factor is one of the genes most commonly mutated in Holoprosencephaly (HPE) probands. Studies in cultured cell lines and mice have shown a loss of ZIC2 function is the pathogenic mechanism but the molecular details of this ZIC2 requirement remain elusive. HPE arises when signals that direct morphological and fate changes in the developing brain and facial primordia are not sent or received. One critical signal is sent from the prechordal plate (PrCP) which develops beneath the ventral forebrain. An intact NODAL signal transduction pathway and functional ZIC2 are both required for PrCP establishment. We now show that ZIC2 acts downstream of the NODAL signal during PrCP development. ZIC2 physically interacts with SMAD2 and SMAD3, the receptor activated proteins that control transcription in a NODAL dependent manner. Together SMAD3 and ZIC2 regulate FOXA2 transcription in cultured cells and Zic2 also controls the foxA2 expression during Xenopus development. Variant forms of the ZIC2 protein, associated with HPE in man or mouse, are deficient in their ability to influence SMAD-dependent transcription. These findings reveal a new mechanism of NODAL signal transduction in the mammalian node and provide the first molecular explanation of how ZIC2 loss-of-function precipitates HPE.

The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis.

The zinc finger of the cerebellum gene (ZIC) discovered in Drosophila melanogaster (odd-paired) has five homologs in Xenopus, chicken, mice, and humans, and seven in zebrafish. This pattern of gene copy expansion is accompanied by a divergence in gene and protein structure, suggesting that Zic family members share some, but not all, functions. ZIC genes are implicated in neuroectodermal development and neural crest cell induction. All share conserved regions encoding zinc finger domains, however their heterogeneity and specification remain unexplained. In this review, the evolution, structure, and expression patterns of the ZIC homologs are described; specific functions attributable to individual family members are supported. A review of data from functional studies in Xenopus and murine models suggest that ZIC genes encode multifunctional proteins operating in a context-specific manner to drive critical events during embryogenesis. The identification of ZIC mutations in congenital syndromes highlights the relevance of these genes in human development.

Correction: Suh Nchang et al. Knowledge about Asymptomatic Malaria and Acceptability of Using Artemisia afra Tea among Health Care Workers (HCWs) in Yaoundé, Cameroon: A Cross-Sectional Survey. Int. J. Environ. Res. Public Health 2023, 20, 6309.

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AKAP8 promotes ovarian cancer progression and antagonizes PARP inhibitor sensitivity through regulating hnRNPUL1 transcription.

Ovarian cancer (OC) is the highest worldwide cancer mortality cause among gynecologic tumors, but its underlying molecular mechanism remains largely unknown. Here, we report that the RNA binding protein A-kinase anchoring protein 8 (AKAP8) is highly expressed in ovarian cancer and predicts poor prognosis for ovarian cancer patients. AKAP8 promotes ovarian cancer progression through regulating cell proliferation and metastasis. Mechanically, AKAP8 is enriched at chromatin and regulates the transcription of the specific hnRNPUL1 isoform. Moreover, AKAP8 phase separation modulates the hnRNPUL1 short isoform transcription. Ectopic expression of the hnRNPUL1 short isoform could partially rescue the growth inhibition effect of AKAP8-knockdown in ovarian cancer cells. In addition, AKAP8 modulates PARP1 expression through hnRNPUL1, and AKAP8 inhibition enhances PAPR inhibitor cytotoxicity in ovarian cancer. Together, our study uncovers the crucial function of AKAP8 condensation-mediated transcription regulation, and targeting AKAP8 could be potential for improvement of ovarian cancer therapy.

The RNA-binding protein XSeb4R regulates maternal Sox3 at the posttranscriptional level during maternal-zygotic transition in Xenopus.

The maternal-zygotic transition (MZT) is an embryonic event that overlaps with and plays key roles in primary germ layer specification in vertebrates. During MZT, maternally supplied mRNAs are degraded while zygotic transcripts are synthesized to either reinforce the already specified cell fate or to trigger new cell identity. Here, we show that forced expression of the RNA-binding protein, XSeb4R, in animal pole blastomeres of Xenopus embryos, inappropriately stabilizes transcripts there, including maternal Sox3. This leads to the impaired ability of the ectodermal progenitors to respond to factors regulating brain patterning and their eventual loss by apoptosis. XSeb4R protein binds specifically to the 3'UTR of Sox3 mRNA. XSeb4R gain-of-function in ectodermal explants reveals increased stability of the maternal Sox3 transcripts, associated with a robust Sox3 protein production. Conversely, whereas XSeb4R depletion abolishes VegT expression, the amount of the maternal Sox3 mRNA is rather increased but without augmentation in the amount of Sox3 protein. Moreover, XSeb4R protein knockdown leads to the modification of the ectoderm-mesoderm boundary, marked by expanded/shifted expression of the mesodermal marker genes such as Xbra and Apod, followed by an expression inhibition of Epi. K., an ectodermal marker. Overall, our data suggest XSeb4R as a novel player in gene expression regulation, acting at the posttranscriptional level during ectoderm specification in Xenopus.

Knowledge about Asymptomatic Malaria and Acceptability of Using Artemisia afra Tea among Health Care Workers (HCWs) in Yaoundé, Cameroon: A Cross-Sectional Survey.

Malaria is the most widespread endemic disease in Cameroon, and asymptomatic Plasmodium (gametocyte) carriers (APCs) constitute more than 95% of infectious human reservoirs in malaria endemic settings. This study assesses the knowledge of asymptomatic malaria (ASM) among health care workers (HCWs) in health facilities (HFs) in the Centre Region of Cameroon and the acceptability of using Artemisia afra tea to treat APCs. A cross-sectional descriptive survey was conducted among 100 HCWs, in four randomly selected HFs in the Centre Region, in the period of 1-20 April 2022, using semi-structured self-administered questionnaires. Logistic regression analyses were performed to determine factors associated with knowledge. More than seven in eight (88%) respondents were aware of the existence of ASM, 83% defined ASM correctly, 75% knew how it was diagnosed, 70% prescribe ACTs for APCs, and 51.1% were informed about ASM transmission. The professional category of HCWs was significantly associated with their knowledge of the existence and transmission of ASM, and longevity of service was associated with knowledge of transmission (p < 0.05). Two-thirds (67%) of respondents knew about Artemisia afra tea, 53.7% believed that it was effective in treating ASM, and 79% were willing to prescribe it if authorized. There was a fair level of knowledge of ASM among HCWs in the study settings.

A cross-sectional survey on the use of herbal tea among Cameroonian adults (18-65 years).

BACKGROUND: In respect of the WHO's commendation to incorporate traditional medicine (TM) in health care, the Cameroon government wants to promote the use of the traditional medicine and is resolute on encouraging the treatment of patients with alternative medicine from traditional sources. This study explores the use of herbal tea by Cameroonian adults to prevent or treat diseases and the socio-demographic determinants of tea use among participants. METHODS: A cross-sectional survey was conducted among 307 Cameroonian adults (18-65 years) randomly selected within 4 hospitals and 4 communities in the Centre and Southwest regions of Cameroon between 04/01-20/04/2022, using interviewer administered semi-structured questionnaires. Binary logistic regression analysis was conducted to determine the association between variables. RESULTS: Over four-fifth (89.3%) of participants had taken herbal teas at least once within the last 2 years prior to the survey, and most participants used the teas for the prevention and treatment of Covid-19 (67.9%), malaria (59.7%) and typhoid fever (35%). Most respondents took the teas warm (75%), and the treatment dosage used by most respondents (51%) was "one glass in the morning and evening for one to two weeks". The teas taken by 70% of users had bad or bitter taste and 52.2% of them were uncomfortable with the bad taste. However, the majority of users completed their treatment dosage (72%), 90.5% of them were willing to use teas for treatment if prescribed in health facilities in future, and 90.1% were in support that herbal teas should be prescribed in hospitals. There was no significant association (p ≥ 0.05) between sociodemographic characteristics of participants and herbal tea use. However, the major motivating factor for acceptability of herbal tea use was treatment effectiveness (52.7%). CONCLUSION: There is high prevalence of herbal tea use among adults Cameroonians in the studied settings in the Centre and Southwest regions of Cameroon, with a positive opinion and willingness to use teas if prescribed in health facilities. Authorities must ensure the effectiveness and safety of traditional medicine served in health facilities, to enhance compliance and adequate use.

Secondary Metabolites Isolated from Artemisia afra and Artemisia annua and Their Anti-Malarial, Anti-Inflammatory and Immunomodulating Properties-Pharmacokinetics and Pharmacodynamics: A Review.

There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components.

Effects of the suspension of mass drug administration during the COVID-19 pandemic on onchocerciasis prevalence in the Bandjoun and Massangam health districts, West Region of Cameroon.

Onchocerciasis is an infectious disease of public health and socio-economic importance in most parts of Sub-Saharan Africa. The objective of this study was to evaluate the effects of the suspension of implementation activities towards combating onchocerciasis in the Bandjoun and Massangam health districts in the West Region of Cameroon as a consequence of the COVID-19 pandemic. Data on socio-demographic and clinical characteristics were obtained using a structured questionnaire. All participants in both health districts were examined for the presence of clinical manifestations of onchocerciasis. In addition, two skin snips were obtained from the knee of each participant and examined for the presence of microfilaria. All data were categorized, coded, entered in a database, and analysed using SPSS version 23.0. A total of 229 participants in the Bandjoun health district and 378 in the Massangam health district were recruited for the study. In both health districts, there was no significant difference between male and female participants in terms of the clinical manifestations of onchocerciasis. The prevalence of nodules was 8.7% in the Bandjoun health district and 20.6% in the Massangam health district while the prevalence of microfilaria carriers in Bandjoun and Massangam health districts was 3.5% and 3.7%, respectively. Except for the Tsesse and Lemgo communities in the Bandjoun health district, there was a reduction in the prevalence of microfilaria in the communities that were studied when compared to previous data obtained before the disruption of control programmes activities. Overall, in both health districts, elderly individuals bear the largest burden of onchocerciasis. Based on the results obtained, we conclude that the temporary suspension of Neglected Tropical Disease control programme activities by the World Head Organization as a result of COVID-19 may have resulted to recrudescence of O. volvulus transmission in hypoendemic communities in the Bandjoun health district.

Immunoinformatics Design and Assessment of a Multiepitope Antigen (OvMCBL02) for Onchocerciasis Diagnosis and Monitoring.

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.

Community engagement in epigenomic and neurocognitive research on post-traumatic stress disorder in Rwandans exposed to the 1994 genocide against the Tutsi: lessons learned.

Epigenomic and neurocognitive studies have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article outlines the lessons learned from community engagement (CE) in such research on Rwandan genocide survivors. A strong trauma-related response was observed within the research project-targeted community (genocide survivors) during explanation of the project. CE also revealed privacy concerns, as community members worried that any leakage of genetic/(epi)genomic data could affect not only themselves but also their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of targeted community needs and interests. Furthermore, CE has stimulated the development of mental healthcare interventions, which married couples can apply to protect their offspring and thus truly break the cycle of inherited vulnerability.

Studies of how human genes are affected by the environment (epigenomic studies) have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article describes the lessons learned from community engagement (CE) in this type of research in a Rwandan genocide-exposed population. A strong trauma-related response was observed within the community while explaining the project. CE also revealed the participants' privacy concerns related to leakage of genetic/(epi)genomic data that could also affect their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of community needs and interests. CE has furthermore stimulated the development of preventive interventions for married couples to protect their offspring and thus truly break the cycle of inherited vulnerability.

A lipid transfer protein ensures nematode cuticular impermeability.

The cuticle of C. elegans is impermeable to chemicals, toxins, and pathogens. However, increased permeability is a desirable phenotype because it facilitates chemical uptake. Surface lipids contribute to the permeability barrier. Here, we identify the lipid transfer protein GMAP-1 as a critical element setting the permeability of the C. elegans cuticle. A gmap-1 deletion mutant increases cuticular permeability to sodium azide, levamisole, Hoechst, and DiI. Expressing GMAP-1 in the hypodermis or transiently in the adults is sufficient to rescue this gmap-1 permeability phenotype. GMAP-1 protein is secreted from the hypodermis to the aqueous fluid filling the space between collagen fibers of the cuticle. In vitro, GMAP-1 protein binds phosphatidylserine and phosphatidylcholine while in vivo, GMAP-1 sets the surface lipid composition and organization. Altogether, our results suggest GMAP-1 secreted by hypodermis shuttles lipids to the surface to form the permeability barrier of C. elegans.

Accuracy of malaria diagnostic tests performed on non-invasively collected samples: a systematic review and meta-analysis.

BACKGROUND: During the last decade, many studies have assessed the performance of malaria tests on non-invasively collected specimens, but no systematic review has hitherto estimated the overall performance of these tests. We report here the first meta-analysis estimating the diagnostic performance of malaria diagnostic tests performed on saliva, urine, faeces, skin odour ('sniff and tell') and hair, using either microscopy or PCR on blood sample as reference test. METHODS: We searched on PubMed, EMBASE, African Journals Online and Cochrane Infectious Diseases from inception until 19 January 2021 for relevant primary studies. A random effects model was used to estimate the overall performance of various diagnostic methods on different types of specimen. RESULTS: Eighteen studies providing 30 data sets were included in the meta-analysis. The overall sensitivity, specificity and diagnostic OR (DOR) of PCR were 84.5% (95% CI 79.3% to 88.6%), 97.3% (95% CI 95.3% to 98.5%) and 184.9 (95% CI 95.8 to 356.9) in saliva, respectively; 57.4% (95% CI 41.4% to 72.1%), 98.6% (95% CI 97.3% to 99.3%) and 47.2 (95% CI 22.1 to 101.1) in urine, respectively. The overall sensitivity, specificity and DOR of rapid diagnostic test for malaria in urine was 59.8% (95% CI 40.0% to 76.9%), 96.9% (95% CI 91.0% to 99.0%) and 30.8 (95% CI:23.5 to 40.4). CONCLUSION: In settings where PCR is available, saliva and urine samples should be considered for PCR-based malaria diagnosis only if blood samples cannot be collected. The performance of rapid diagnostic testing in the urine is limited, especially its sensitivity. Malaria testing on non-invasively collected specimen still needs substantial improvement.

Fine scale analysis of malaria incidence in under-5: hierarchical Bayesian spatio-temporal modelling of routinely collected malaria data between 2012-2018 in Cameroon.

The current study aims to provide a fine-scale spatiotemporal estimate of malaria incidence among Cameroonian under-5, and to determine its associated environmental factors, to set up preventive interventions that are adapted to each health district of Cameroon. Routine data on symptomatic malaria in children under-5 collected in health facilities, between 2012 and 2018 were used. The trend of malaria cases was assessed by the Mann-Kendall (M-K) test. A time series decomposition was applied to malaria incidence to extract the seasonal component. Malaria risk was estimated by the standardised incidence ratio (SIR) and smoothed by a hierarchical Bayesian spatiotemporal model. In total, 4,052,216 cases of malaria were diagnosed between 2012 and 2018. There was a gradual increase per year, from 369,178 in 2012 to 652,661 in 2018. After adjusting the data for completeness, the national incidence ranged from 489‰ in 2012 to 603‰ in 2018, with an upward trend (M-K test p-value < 0.001). At the regional level, an upward trend was observed in Adamaoua, Centre without Yaoundé, East, and South regions. There was a positive spatial autocorrelation of the number of malaria incident-cases per district per year as suggested by the Moran's I test (statistic range between 0.11 and 0.53). The crude SIR showed a heterogeneous malaria risk with values ranging from 0.00 to 8.90, meaning that some health districts have a risk 8.9 times higher than the national annual level. The incidence and risk of malaria among under-5 in Cameroon are heterogeneous and vary significantly across health districts and seasons. It is crucial to adapt malaria prevention measures to the specificities of each health district, in order to reduce its burden in health districts where the trend is upward.

Onchocerciasis Fingerprints in the Geriatric Population: Does Host Immunity Play a Role?

One of the most debilitating consequences of aging is the progressive decline in immune function, known as immunosenescence. This phenomenon is characterized by a shift in T-cell phenotypes, with a manifest decrease of naive T-cells-dealing with newly encountered antigens-and a concomitant accumulation of senescent and regulatory T-cells, leading to a greater risk of morbidity and mortality in older subjects. Additionally, with aging, several studies have unequivocally revealed an increase in the prevalence of onchocerciasis infection. Most lymphatic complications, skin and eye lesions due to onchocerciasis are more frequent among the elderly population. While the reasons for increased susceptibility to onchocerciasis with age are likely to be multi-factorial, age-associated immune dysfunction could play a key role in the onset and progression of the disease. On the other hand, there is a growing consensus that infection with onchocerciasis may evoke deleterious effects on the host's immunity and exacerbate immune dysfunction. Indeed, Onchocerca volvulus has been reported to counteract the immune responses of the host through molecular mimicry by impairing T-cell activation and interfering with the processing of antigens. Moreover, reports indicate impaired cellular and humoral immune responses even to non-parasite antigens in onchocerciasis patients. This diminished protective response may intensify the immunosenescence outcomes, with a consequent vulnerability of those affected to additional diseases. Taken together, this review is aimed at contributing to a better understanding of the immunological and potential pathological mechanisms of onchocerciasis in the older population.