Contemporary epidemiological data of Rift Valley fever virus in humans, mosquitoes and other animal species in Africa: A systematic review and meta-analysis.

Rift Valley fever (RVF) is a severe zoonotic mosquito-borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta-analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta-analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random-effects model. Subgroup analysis and sensitivity analysis were performed, and the I2 -statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0-52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2-9.6] in humans and 9.3% [95% CI = 8.1-10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health.

Update on laboratory data of animal rabies at the Centre Pasteur of Cameroon from 2014 to 2021.

Rabies is a worldwide zoonotic disease mainly transmitted to humans by an infected dog bite. Despite the endemicity of rabies in dogs and few documented cases in Cameroon, there is still not enough data on frequency of rabies cases in animals. The present study aims to update data on the circulation of rabies in animals screened at the Centre Pasteur of Cameroon (CPC) between 2014 and 2021. The detection of rabies in animals was based on passive surveillance. Animal rabies cases were confirmed on brain biopsies using fluorescent antibody test and SYBR green based real-time RT-PCR for negative results confirmation. The total nucleoprotein (N) gene of animal-derived RABV isolated were amplified by hemi nested RT-PCR and subjected to phylogenetic analyses. From 2014 to 2021, a total of 92 animals including 86 dogs (93.5%), 3 cats, 2 pigs and 1 chiropteran were screened for rabies at the CPC. From the 86 dog sampled, 62.3% (54/86) were tested positive for rabies and 1 out of 3 cat samples was also tested positive. The PEP demand was very high (59,371) during the study period. Phylogenetic analyses assigned all 15 studied isolates successfully sequenced to the Africa-1a lineage belonging to the Cosmopolitan clade. The study highlights the frequent circulation of rabies in Cameroon and the role of dogs and cat as main reservoir and vector of rabies.

Epidemiology of yellow fever virus in humans, arthropods, and non-human primates in sub-Saharan Africa: A systematic review and meta-analysis.

Yellow fever (YF) has re-emerged in the last two decades causing several outbreaks in endemic countries and spreading to new receptive regions. This changing epidemiology of YF creates new challenges for global public health efforts. Yellow fever is caused by the yellow fever virus (YFV) that circulates between humans, the mosquito vector, and non-human primates (NHP). In this systematic review and meta-analysis, we review and analyse data on the case fatality rate (CFR) and prevalence of YFV in humans, and on the prevalence of YFV in arthropods, and NHP in sub-Saharan Africa (SSA). We performed a comprehensive literature search in PubMed, Web of Science, African Journal Online, and African Index Medicus databases. We included studies reporting data on the CFR and/or prevalence of YFV. Extracted data was verified and analysed using the random effect meta-analysis. We conducted subgroup, sensitivity analysis, and publication bias analyses using the random effect meta-analysis while I2 statistic was employed to determine heterogeneity. This review was registered with PROSPERO under the identification CRD42021242444. The final meta-analysis included 55 studies. The overall case fatality rate due to YFV was 31.1% (18.3-45.4) in humans and pooled prevalence of YFV infection was 9.4% (6.9-12.2) in humans. Only five studies in West and East Africa detected the YFV in mosquito species of the genus Aedes and in Anopheles funestus. In NHP, YFV antibodies were found only in members of the Cercopithecidae family. Our analysis provides evidence on the ongoing circulation of the YFV in humans, Aedes mosquitoes and NHP in SSA. These observations highlight the ongoing transmission of the YFV and its potential to cause large outbreaks in SSA. As such, strategies such as those proposed by the WHO's Eliminate Yellow Fever Epidemics (EYE) initiative are urgently needed to control and prevent yellow fever outbreaks in SSA.

Sustained circulation of yellow fever virus in Cameroon: an analysis of laboratory surveillance data, 2010-2020.

BACKGROUND: The re-emergence of yellow fever poses a serious public health risk to unimmunized communities in the tropical regions of Africa and South America and unvaccinated travelers visiting these regions. This risk is further accentuated by the likely spread of the virus to areas with potential for yellow fever transmission such as in Asia, Europe, and North America. To mitigate this risk, surveillance of yellow fever is pivotal. We performed an analysis of laboratory-based surveillance of yellow fever suspected cases in Cameroon during 2010-2020 to characterize the epidemiology of yellow fever cases and define health districts at high risk. METHOD: We reviewed IgM capture ELISA and plaque reduction neutralization test (PRNT) test results of all suspected yellow fever patients analyzed at Centre Pasteur of Cameroon, the national yellow fever testing laboratory, during 2010-2020. RESULTS: Of the 20,261 yellow fever suspected patient's samples that were tested, yellow fever IgM antibodies were detected in 360 patients representing an annual average of 33 cases/year. A major increase in YF IgM positive cases was observed in 2015 and in 2016 followed by a decrease in cases to below pre-2015 levels. The majority of the 2015 cases occurred during the latter part of the year while those in 2016, occurred between February and May. This trend may be due to an increase in transmission that began in late 2015 and continued to early 2016 or due to two separate transmission events. In 2016, where the highest number of cases were detected, 60 health districts in the 10 regions of Cameroon were affected with the Littoral, Northwest and, Far North regions being the most affected. After 2016, the number of detected yellow fever IgM positive cases dropped. CONCLUSION: Our study shows that yellow fever transmission continues to persist and seems to be occurring all over Cameroon with all 10 regions under surveillance reporting a case. Preventive measures such as mass vaccination campaigns and routine childhood immunizations are urgently needed to increase population immunity. The diagnostic limitations in our analysis highlight the need to strengthen laboratory capacity and improve case investigations.

Molecular characterization of chikungunya virus from the first cluster of patients during the 2020 outbreak in Chad.

We sequenced a portion of the E1 envelope protein gene of two of four CHIKV RT-PCR-positive samples from the first cluster of chikungunya patients during the 2020 Chad outbreak. Phylogenetic analysis revealed that the viruses belonged to the East/Central/South/African genotype but lacked the E1 A226V and K211E mutations associated with viral adaptability and transmission, suggesting an autochthonous transmission. These sequences are a useful basis for tracking viral evolution in subsequent outbreaks in Chad.

A cost-benefit algorithm for rapid diagnosis of tuberculosis and rifampicin resistance detection during mass screening campaigns.

BACKGROUND: Active tuberculosis (TB) case finding is important as it helps detect pulmonary TB cases missed by the other active screening methods. It requires periodic mass screening in risk population groups such as prisoners and refugees. Unfortunately, in these risk population groups periodic mass screening can be challenging due to lengthy turnaround time (TAT), cost and implementation constraints. The aim of this study was to evaluate a diagnostic algorithm that can reduce the TAT and cost for TB and Rifampicin resistance (RR) detection. The algorithm involves testing with TB-LAMP followed by Xpert MTB/RIF for positive TB-LAMP cases to diagnose TB during mass campaigns in prisons and refugee camps. METHODS: The National Tuberculosis Control Program (NTCP) organized routine TB mass-screening campaigns in 34 prisons and 3 villages with refugees camps in Cameroon in 2019. TB LAMP was used for initial TB diagnosis and all TB-LAMP positive cases tested with the Xpert MTB/RIF assay to determine RR. TAT and cost benefits analysis of the combined use of TB-LAMP and Xpert MTB/RIF assays was determined and compared to the Xpert MTB/RIF assay when used only. RESULTS: A total of 4075 sputum samples were collected from TB presumptive, 3672 cases in 34 prisons and 403 samples in 3 villages. Of the 4,075 samples screened with TB-LAMP, 135 were TB positive (3.31%) and run on the Xpert MTB/RIF. Of the 135 positives cases, Xpert MTB/RIF revealed 3 were RR (2.22%). The use of TB-LAMP followed by testing with Xpert MTB/RIF for TB and RR detection reduced the TAT by 73.23% in prisons and 74.92% in villages. In addition to a reduced TAT, the two molecular tests used in synergy is cost benefit from year 2 onwards. CONCLUSION: This study demonstrates the advantages of a diagnostic algorithm based on an initial testing with TB-LAMP followed by testing with Xpert MTB/RIF for TB diagnosis. This approach improved early and rapid TB detection with an added advantage of providing RR status. The proposed algorithm is effective and less costly from the second year of implementation and should be used by TB control programs.

Diagnostic accuracy and usefulness of the Genotype MTBDRplus assay in diagnosing multidrug-resistant tuberculosis in Cameroon? a cross-sectional study.

BACKGROUND: Drug-resistant tuberculosis, especially multidrug-resistant tuberculosis (MDR-TB), is a major public health problem. Effective management of MDR-TB relies on accurate and rapid diagnosis. In this study, we assessed the diagnostic accuracy of the Genotype MTBDRplus assay in diagnosing MDR-TB in Cameroon, and then discuss on its utility within the diagnostic algorithm for MDR-TB. METHODS: In this cross-sectional study, 225 isolates of Mycobacterium tuberculosis cultured from sputum samples collected from new and previously treated pulmonary tuberculosis patients in Cameroon were used to determine the accuracy of the Genotype MTBDRplus assay. We compared the results of the Genotype MTBDRplus assay with those from the automated liquid culture BACTEC MGIT 960 SIRE system for sensitivity, specificity, and degree of agreement. The pattern of mutations associated with resistance to RIF and INH were also analyzed. RESULTS: The Genotype MTBDRplus assay correctly identified Rifampicin (RIF) resistance in 48/49 isolates (sensitivity, 98% [CI, 89%-100%]), Isoniazid (INH) resistance in 55/60 isolates (sensitivity 92% [CI, 82%-96%]), and MDR-TB in 46/49 (sensitivity, 94% [CI, 83%-98%]). The specificity for the detection of RIF-resistant and MDR-TB cases was 100% (CI, 98%-100%), while that of INH resistance was 99% (CI, 97%-100%). The agreement between the two tests for the detection of MDR-TB was very good (Kappa = 0.96 [CI, 0.92-1.00]). Among the 3 missed MDR-TB cases, the Genotype MTBDRplus assay classified two samples as RIF-monoresistant and one as INH monoresistant. The most frequent mutations detected by the Genotype MTBDRplus assay was the rpoB S531 L MUT3 41/49 (84%) in RIF-resistant isolates, and the KatG S315 T1 (MUT1) 35/55 (64%) and inhA C15T (MUT1) 20/55 (36%) mutations in INH-resistant isolates. CONCLUSION: The Genotype MTBDRplus assay had good accuracy and could be used for the diagnosis of MDR-TB in Cameroon. For routine MDR-TB diagnosis, this assay could be used for Mycobacterium tuberculosis cultures containing contaminants, to complement culture-based drug susceptibility testing or to determine drug resistant mutations.

Lobular Distribution and Variability in Hepatic ATP Binding Cassette Protein B1 (ABCB1, P-gp): Ontogenetic Differences and Potential for Toxicity.

The ATP Binding Cassette B1 (ABCB1) transporter has critical roles in endo- and xenobiotic efficacy and toxicity. To understand population variability in hepatic transport we determined ABCB1 mRNA and protein levels in total liver lysates sampled from 8 pre-defined sites (n = 24, 18-69 years), and in S9 from randomly acquired samples (n = 87, 7 days-87 years). ABCB1 levels did not differ significantly throughout individual livers and showed 4.4-fold protein variation between subjects. Neither mRNA nor protein levels varied with sex, ethnicity, obesity or triglycerides in lysates or S9 (that showed the same relationships), but protein levels were lower in pediatric S9 (p < 0.0001), with 76% of adult ABCB1 present at birth and predicted to mature in 5 years. Pediatric total liver lysates were not available. In summary, opportunistic collection for studying human hepatic ABCB1 is acceptable. Additionally, ABCB1 may be lower in children, indicating differential potential for toxicity and response to therapy in this special population.