Epidemiology of hepatitis E virus infection in animals in Africa: a systematic review and meta-analysis.

BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute hepatitis in humans worldwide and have high burden in the resource-limited countries. Better knowledge of the epidemiology of hepatitis in animals in Africa can help to understand the epidemiology among humans. The objective of this study was to summarize the prevalence of HEV infection and distribution of HEV genotypes among animals in Africa. METHODS: In this systematic review and meta-analysis, we comprehensively searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to March 22th, 2020 without any language restriction. We considered cross-sectional studies of HEV infection in animals in Africa. Study selection, data extraction, and methodological quality of included studies were done independently by two investigators. Prevalence data were pooled using the random-effects meta-analysis. This review was registered in PROSPERO, CRD42018087684. RESULTS: Twenty-five studies (13 species and 6983 animals) were included. The prevalence (antibodies or ribonucleic acid [RNA]) of HEV infection in animals varied widely depending on biological markers of HEV infection measured: 23.4% (95% confidence interval; 12.0-37.2) for anti-HEV immunoglobulins G, 13.1% (3.1-28.3) for anti-HEV immunoglobulins M, and 1.8% (0.2-4.3) for RNA; with substantial heterogeneity. In subgroup analysis, the immunoglobulins G seroprevalence was higher among pigs 37.8% (13.9-65.4). The following HEV genotypes were reported in animals: Rat-HEV genotype 1 (rats and horses), HEV-3 (pigs), HEV-7 (dromedaries), and Bat hepeviruses (bats). CONCLUSIONS: We found a high prevalence of HEV infection in animals in Africa and HEV genotypes close to that of humans. Some animals in Africa could be the reservoir of HEV, highlighting the need of molecular epidemiological studies for investigating zoonotic transmission.

Dengue virus infection in people residing in Africa: a systematic review and meta-analysis of prevalence studies.

Better knowledge of the face of the current dengue virus (DENV) epidemiology in Africa can help to implement efficient strategies to curb the burden of dengue fever. We conducted this systematic review and meta-analysis to determine the prevalence of DENV infection in Africa. We searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to June 10th, 2019 without any language restriction. We used a random-effects model to pool studies. A total of 76 studies (80,977 participants; 24 countries) were included. No study had high risk of bias. Twenty-two (29%) had moderate and 54 (71%) had low risk of bias. In apparently healthy individuals, the pooled prevalence of DENV was 15.6% (95% confidence interval 9.9-22.2), 3.5% (0.8-7.8), and 0.0% (0.0-0.5) respectively for immunoglobulins (Ig) G, IgM, and for ribonucleic acid (RNA) in apparently healthy populations. In populations presenting with fever, the prevalence was 24.8% (13.8-37.8), 10.8% (3.8-20.6k) and 8.4% (3.7-14.4) for IgG, IgM, and for RNA respectively. There was heterogeneity in the distribution between different regions of Africa. The prevalence of DENV infection is high in the African continent. Dengue fever therefore deserves more attention from healthcare workers, researchers, and health policy makers.

Case fatality rate and viral aetiologies of acute respiratory tract infections in HIV positive and negative people in Africa: The VARIAFRICA-HIV systematic review and meta-analysis.

BACKGROUND: To set priorities for efficient control of acute respiratory tract infection (ARTI) in Africa, it is necessary to have accurate estimate of its burden, especially among HIV-infected populations. OBJECTIVES: To compare case fatality rate (CFR) and viral aetiologies of ARTI between HIV-positive and HIV-negative populations in Africa. STUDY DESIGN: We searched PubMed, EMBASE, Web of Knowledge, Africa Journal Online, and Global Index Medicus to identify studies published from January 2000 to April 2018. Random-effect meta-analysis method was used to assess association (pooled weighted odds ratios (OR) with 95% confidence interval (CI)). RESULTS: A total of 36 studies (126,526 participants) were included. CFR was significantly higher in patients with HIV than in HIV-negative controls (OR 4.10, 95%CI: 2.63-6.27, I²: 93.7%). The risk was significantly higher among children ≤5 years (OR 5.51, 95%CI 2.83-10.74) compared to people aged >5 years (OR 1.48, 95%CI 1.17-1.89); p = 0.0002. There was no difference between children (15 years) and adults and between regions of Africa. There was no difference for viral respiratory aetiologies (Enterovirus, Adenovirus, Bocavirus, Coronavirus, Metapneumovirus, Parainfluenza, Influenza, and Respiratory Syncytial Virus) of ARTI between HIV-positive and HIV-negative people, except for Rhinovirus where being HIV-negative was associated with Rhinovirus (OR 0.70; 95%CI 0.51-0.97, I²: 63.4%). CONCLUSIONS: This study shows an increased risk of deaths among HIV-infected individuals with ARTI, however with no difference in viral aetiologies compared to HIV-negative individuals in Africa. ARTI deserves more attention from HIV health-care providers for efficient control. Specific strategies are needed for HIV-positive children under 5.

Epidemiology of hepatitis E virus infection in animals in Africa: a systematic review and meta-analysis protocol.

BACKGROUND: Hepatitis E virus (HEV) is one of the major causes of acute hepatitis in humans worldwide with a case-fatality rate of 1-4% in the general population that might reach 30% in pregnant women. In the past decade in Africa, studies have shown that HEV infects not only humans but also animals. A systematic review summarizing the epidemiological data of HEV has been only performed in humans residing in Africa. We will perform this systematic review and meta-analysis to assess the prevalence of HEV infection in animal species in Africa. METHODS: This review will include cross-sectional studies among different animal species that reported the prevalence of HEV in Africa. We will consider published and unpublished studies from January 1, 2000 to present. A comprehensive search of PubMed, Excerpta Medica, African Journals Online, and Africa Index Medicus will be conducted to identify all relevant articles. Reference lists of eligible items and relevant articles will be reviewed. The funnel plots and the Egger test will be used to assess the publication bias. Study-specific estimates will be aggregated using a DerSimonian and Laird random-effects meta-analysis model to obtain an overall summary estimate of HEV prevalence across studies. The heterogeneity of the studies will be evaluated by the χ2 test on the Cochran's Q test. The results will be presented by animal species. DISCUSSION: HEV-infected animals are likely to transmit this virus to humans in Africa, as studies have already shown in developed countries. This systematic review and meta-analysis will provide a clear picture of the epidemiology of HEV in animals in Africa, to better understand this infection and to respond adequately to the epidemic challenges that often afflict Africa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018087684 .

Epidemiology of respiratory viral infections in people with acute respiratory tract infections in Africa: the VARIAFRICA systematic review and meta-analysis protocol.

INTRODUCTION: Better characterisation of the epidemiological data on respiratory viral infections among people with acute respiratory tract infection (ARTI) can help to implement efficient strategies to curb the burden of ARTI in Africa. We will conduct a systematic review and meta-analysis to determine the prevalence and factors associated with respiratory viral infection in people of all ages with ARTI residing in Africa. METHODS: This work will include cross-sectional studies published between January 1, 2000 and December 31, 2017, without any language restriction, on populations residing in African countries. We will consider studies that reported the prevalence of respiratory viruses in people with ARTI confirmed by a polymerase chain reaction technique. We will be searching PubMed, Embase, African Journals Online, Web of Science, and Global Index Medicus. The selection of relevant studies, extraction of data, and evaluation of the quality of the articles will be carried out independently by two review authors, and the discrepancies will be resolved by consensus or intervention of a third author. The heterogeneity of the studies will be assessed using the χ2 test on Cochrane's Q statistic. Publication bias will be assessed by the Egger test. Studies will be pooled using a random-effect meta-analysis model. Results will be presented by age group and sub-region of Africa. Using meta-regression models, we will identify factors associated with viral infections in people with ARTI. DISCUSSION: This systematic review and meta-analysis is based on published data and therefore does not require ethical approval. This work will serve as a basis for the development of strategies for prevention and control ARTI in Africa and will also serve to identify data gaps and guide future investigations. The final report will be published in peer-reviewed journals as a scientific article and presented in workshops, conferences, and scientific conferences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018088261 .

Case fatality rate and risk factors for Nipah virus encephalitis: A systematic review and meta-analysis.

BACKGROUND: A wide range of Nipah virus (NiV) encephalitis case fatality rates (CFR) have been reported. Data on the involvement of several potential risk factors in Nipah virus transmission remain controversial. We performed a systematic review and meta-analysis to estimate the pooled CFR of NiV encephalitis and to assess the risk factors for NiV infection. METHODS: Articles published up to the 27thof November 2018 in MedLine, Embase and Web of knowledge databases were considered for this study. We included cross-sectional, cohort, and case-control studies that have reported NiV CFR and/or risk factors. Data were pooled with random-effects model. This review was registered in the PROSPERO, CRD42018116242. FINDINGS: This global review included 22 citations (25 studies) including 2156, 1682, and 474 suspected, probable, and confirmed cases of NiV encephalitis, respectively. We determined a pooled CFR for NiV encephalitis at 61.0% (95% CI, 45.7-75.4; I² = 96.8%). Climbing trees (OR = 1.4; 95% CI; 1.0-1.9), male gender (OR = 1.5; 95% CI; 1.1-2.0), travel outside their own sub-district (OR = 2.0; 95% CI; 1.4-2.9), and exposure to date palm sap (DPS) (OR = 5.7; 95% CI; 3.8-8.6) or pigs (OR = 7.6; 95% CI; 1.2-45.4) were significantly associated with NiV infection. CONCLUSION: Findings from this study suggest that NiV Encephalitis is associated with a high CFR and that male gender, travel outside their sub-district, climbing trees, and exposure to pigs and DPS are associated with an increased risk of NiV encephalitis.

Contemporaneous data on the prevalence of Human Respiratory Syncytial Virus infection in people with acute respiratory tract infections in Africa (2000-2017).

Availability of accurate data on the burden of the Human Respiratory Syncytial Virus (HRSV) can help to implement better strategies to curb this burden in Africa continent among people with acute respiratory tract infections (ARTI). We summarize here available contemporaneous data published from January 1, 2000 to August 31, 2017 on the prevalence of HSRV infection among people with ARTI in the continent.

Prevalence of human respiratory syncytial virus infection in people with acute respiratory tract infections in Africa: A systematic review and meta-analysis.

AIM: The epidemiology of human respiratory syncytial virus (HRSV) infection has not yet been systematically investigated in Africa. This systematic review and meta-analysis are to estimate the prevalence of HRSV infections in people with acute respiratory tract infections (ARTI) in Africa. METHOD: We searched PubMed, EMBASE, Africa Journal Online, and Global Index Medicus to identify observational studies published from January 1, 2000, to August 1, 2017. We used a random-effects model to estimate the prevalence across studies. Heterogeneity (I2 ) was assessed via the chi-square test on Cochran's Q statistic. Review registration: PROSPERO CRD42017076352. RESULTS: A total of 67 studies (154 000 participants) were included. Sixty (90%), seven (10%), and no studies had low, moderate, and high risk of bias, respectively. The prevalence of HRSV infection varied widely (range 0.4%-60.4%). The pooled prevalence was 14.6% (95% CI 13.0-16.4, I2  = 98.8%). The prevalence was higher in children (18.5%; 95% CI 15.8-21.5) compared to adults (4.0%; 95% CI 2.2-6.1) and in people with severe respiratory tract infections (17.9%; 95% CI 15.8-20.1) compared to those with benign forms (9.4%; 95% CI 7.4-11.5); P-values <0.0001. The HRSV prevalence was not associated with sex, subregion in Africa, setting, altitude, latitude, longitude, and seasonality. CONCLUSION: This study suggests a high prevalence of HRSV in people with ARTI in Africa, particularly among children and people with severe clinical form. All innovative strategies to curb the burden should first focus on children which present the highest HRSV-related burden.

Acute blindness as a presenting sign of childhood endemic Burkitt's lymphoma in Cameroon: a case report.

BACKGROUND: Endemic Burkitt's lymphoma is found predominantly in malaria holoendemic zones, typically in the tropical rain forest of Africa. It usually presents as an extra-nodal tumour in children and young adults with predilection for jaws and soft tissues of the abdomen. Clinical features depend on the primary tumour site, extent of the disease and histologic subtype. Acute blindness as a presentation sign is rare. CASE PRESENTATION: A 13 year old African female presented to our facility with a 3 week history of painful abdominal distention, and loss of vision of the left eye. On examination, there was a huge abdominopelvic mass, left breast mass and complete blindness of the left eye associated with mydriatic pupils non-responsive to light. An abdominal ultrasound showed a huge hypoechoic mass arising from the pelvis and protruding into the abdomen. The jaws, teeth and maxilla were all normal. A fine needle aspiration done was negative for malignant cells. A presumptive diagnosis of Burkitt's lymphoma was made on clinical grounds and abdominal ultrasound findings. The patient was immediately placed on chemotherapy and responded well to treatment with remission of the tumour but persistence of left eye blindness. CONCLUSION: Acute blindness can be the presenting sign of Burkitt's lymphoma in a patient with neither jaw nor maxillary swelling. Primary healthcare providers in low income settings require a high index of suspicion when faced with such atypical presentations. This emphasizes the need for thorough physical examination, and when possible, the clinical utility of ultrasonography for suspicious abdominal masses in the absence of state-of the art diagnostic tools for early diagnosis and treatment, which is critical for survival and to improve quality of life.

Juvenile idiopathic arthritis­an update on its diagnosis and management.

Juvenile idiopathic arthritis (JIA) is the most common form of chronic arthritis in children and the most common cause of musculoskeletal disability in children. Early diagnosis may be challenging, but it is essential to ensure good outcomes. This review proposes an approach to the investigation and diagnosis of JIA. It also gives a summary of the latest available evidence-based treatment for this disease.

Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties.

AIM: In contrast to extensive reports on the roles of Na(v)1.5 alpha-subunits, there have been few studies associating the beta-subunits with cardiac arrhythmogenesis. We investigated the sino-atrial and conduction properties in the hearts of Scn3b(-/-) mice. METHODS: The following properties were compared in the hearts of wild-type (WT) and Scn3b(-/-) mice: (1) mRNA expression levels of Scn3b, Scn1b and Scn5a in atrial tissue. (2) Expression of the beta(3) protein in isolated cardiac myocytes. (3) Electrocardiographic recordings in intact anaesthetized preparations. (4) Bipolar electrogram recordings from the atria of spontaneously beating and electrically stimulated Langendorff-perfused hearts. RESULTS: Scn3b mRNA was expressed in the atria of WT but not Scn3b(-/-) hearts. This was in contrast to similar expression levels of Scn1b and Scn5a mRNA. Immunofluorescence experiments confirmed that the beta(3) protein was expressed in WT and absent in Scn3b(-/-) cardiac myocytes. Lead I electrocardiograms from Scn3b(-/-) mice showed slower heart rates, longer P wave durations and prolonged PR intervals than WT hearts. Spontaneously beating Langendorff-perfused Scn3b(-/-) hearts demonstrated both abnormal atrial electrophysiological properties and evidence of partial or complete dissociation of atrial and ventricular activity. Atrial burst pacing protocols induced atrial tachycardia and fibrillation in all Scn3b(-/-) but hardly any WT hearts. Scn3b(-/-) hearts also demonstrated significantly longer sinus node recovery times than WT hearts. CONCLUSION: These findings demonstrate, for the first time, that a deficiency in Scn3b results in significant atrial electrophysiological and intracardiac conduction abnormalities, complementing the changes in ventricular electrophysiology reported on an earlier occasion.

Metabotropic glutamate and GABA(B) receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells.

AIMS/HYPOTHESIS: The neurotransmitters glutamate and gamma-aminobutyric acid (GABA) could participate in the regulation of the endocrine functions of islets of Langerhans. We investigated the role of the metabotropic glutamate (mGluRs) and GABA(B) (GABA(B)Rs) receptors in this process. METHODS: We studied the expression of mGluRs and GABA(B)Rs in rat and human islets of Langerhans and in pancreatic alpha-cell and beta-cell lines using RT-PCR and immunoblot analysis. Effects of mGluR and GABA(B) R agonists on insulin secretion were determined by radioimmunoassays and enzyme-linked immunoadsorbent assays (ELISAs). RESULTS: We detected mGluR3 and mGluR5 (but not mGluR1, 6 and 7) mRNAs in all of the samples examined. Trace amount of mGluR2 was found in MIN6 beta cells; mGluR4 was identified in rat islets; and mGluR8 expression was detected in rat islets, RINm5F and MIN6 cells. GABA(B)R1 a/b and 2 mRNAs were identified in islets of Langerhans and MIN6 cells. The expression of mGluR3, mGluR5, GABA(B)R1 a/b and GABA(B)R2 proteins was confirmed using specific antibodies. Group I (mGluR1/5) and group II (mGluR2/3) specific mGluR agonists increased the release of insulin in the presence of 3 to 10 mmol/l or 3 to 25 mmol/l glucose, respectively, whereas a group III (mGluR4/6-8) specific agonist inhibited insulin release at high (10-25 mmol/l) glucose concentrations. Baclofen, a GABA(B)R agonist, also inhibited the release of insulin but only in the presence of 25 mmol/l glucose. CONCLUSION/INTERPRETATION: These data suggest that mGluRs and GABA(B)Rs play a role in the regulation of the endocrine pancreas with mechanisms probably involving direct activation or inhibition of voltage dependent Ca(2+)-channels, cAMP generation and G-protein-mediated modulation of K(ATP) channels.

Isolation of Mycoplasma bovis from bovine clinical samples in the Republic of Ireland.

Mycoplasma bovis was detected in 134 (18 per cent) of 736 samples of bovine lung tissue collected from fatal pneumonia cases in the Republic of Ireland between April 1995 and December 1998. The cases occurred in 95 herds and recurred in four of them. Other respiratory pathogens were identified in 66 per cent of the M bovis-positive cases, with Pasteurella species, infectious bovine rhinotracheitis and parainfluenza 3 virus being most frequently detected. Mastitis and arthritis were less common clinical signs associated with M bovis infection; 22 cases of M bovis mastitis and five cases of M bovis arthritis were diagnosed in five herds.

Application of an indirect ELISA to milk samples to identify cows with Mycoplasma bovis mastitis.

An indirect ELISA was used to detect antibodies to Mycoplasma bovis in milk samples collected from a herd with M bovis mastitis. Antibodies were detected in samples from nine cows which had developed clinical M bovis mastitis. Milk from only three consistently antigen-negative cows tested positive for M bovis antibodies. These results indicate the potential value of the indirect ELISA for the detection of cows which have recently developed M bovis mastitis during the early stages of an outbreak.

Acidic motif responsible for plasma membrane association of the voltage-dependent calcium channel beta1b subunit.

Voltage-dependent calcium channels consist of a pore-forming transmembrane alpha1-subunit, which is known to associate with a number of accessory subunits, including alpha2-delta- and beta-subunits. The beta-subunits, of which four have been identified (beta1-4), are intracellular proteins that have marked effects on calcium channel trafficking and function. In a previous study, we observed that the beta1b-subunit showed selective plasma membrane association when expressed alone in COS7 cells, whereas beta3 and beta4 did not. In this study, we have examined the basis for this, and have identified, by making chimeric beta-subunits, that the C-terminal region, which shows most diversity between beta-subunits, of beta1b is responsible for its plasma membrane association. Furthermore we have identified, by deletion mutations, an 11-amino acid motif present in the C terminus of beta1b but not in beta3 (amino acids 547-556 of beta1b, WEEEEDYEEE), which when deleted, reduces membrane association of beta1b. Future research aims to identify what is binding to this sequence in beta1b to promote membrane association of this calcium channel subunit. It is possible that such membrane association is important for the selective localization or clustering of particular calcium channels with which beta1b is associated.

Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line.

1. Voltage-dependent calcium channels (VDCCs) show a highly non-uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin-Darby canine kidney), which has been used extensively to study the targeting of proteins. 2. We expressed the VDCC alpha1A, alpha1B or alpha1C subunits either alone or in combination with accessory subunits alpha2-delta and the different beta subunits, and examined their localization immunocytochemically. An alpha1 subunit was only targeted to the plasma membrane if co-expressed with the accessory subunits. 3. The combination alpha1C/alpha2-delta and all beta subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons. 4. In contrast, the alpha1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons. 5. The alpha1A subunit was consistently observed at the apical membrane in the combinations alpha1A/alpha2-delta/beta1b or beta4. In contrast, when co-expressed with alpha2-delta/beta2a, alpha1A was clearly targeted to the basolateral membrane. 6. In conclusion, the VDCC alpha1 subunit appears to be the primary determinant for targeting the VDCC complex, but the beta subunit can modify this destination, particularly for alpha1A.