Drug Resistance in Mycobacterium Tuberculosis: An Investigation of Drug Transporter P-glycoprotein and an Evaluation of Improved Diagnosis of Drug Resistant Tuber- culosis in Cameroonian Pulmonary Tuberculosis Patients.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017

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.Pharmaceutical Sciences, Faculty ofNon UBCReviewedFacult

Hepatitis E virus infections among patients with acute febrile jaundice in two regions of Cameroon: First molecular characterization of hepatitis E virus genotype 4.

BackgroundFebrile jaundice is a common indicator of certain infectious diseases, including hepatitis E. In Cameroon, the yellow fever virus is the only pathogen that is monitored in patients who present with this symptom. However, more than 90% of the samples received as part of this surveillance are negative for yellow fever. This study aimed to describe the prevalence and hepatitis E virus (HEV) genotype among yellow fever-negative patients in the Far North and West regions of Cameroon.MethodsIn a cross-sectional study, yellow fever surveillance-negative samples collected between January 2021 and January 2023 were retrospectively analyzed. Anti-HEV IgM and IgG antibodies were tested using commercially available ELISA kits. Anti-HEV IgM and/or IgG positive samples were tested for HEV RNA by real-time RT-PCR, followed by nested RT-PCR, sequencing and phylogenetic analysis.ResultsOverall, 121 of the 543 samples (22.3%, 95% CI: 19.0% - 26.0%) were positive for at least one anti-HEV marker. Amongst these, 8.1% (44/543) were positive for anti-HEV IgM, 5.9% (32/543) for anti-HEV IgG, and 8.3% (45/544) for both markers. A total of 15.2% (12/79) samples were positive for HEV RNA real-time RT-PCR and 8 samples were positive for HEV RNA by nested RT-PCR. Phylogenetic analysis showed that the retrieved sequences clustered within HEV genotypes/subtypes 1/1e, 3/3f and 4/4b.ConclusionOur results showed that HEV is one of the causes of acute febrile jaundice in patients enrolled in the yellow fever surveillance program in two regions of Cameroon. We described the circulation of three HEV genotypes, including two zoonotic genotypes. Further studies will be important to elucidate the transmission routes of these zoonotic HEV genotypes to humans in Cameroon

S1 Dataset -

BackgroundFebrile jaundice is a common indicator of certain infectious diseases, including hepatitis E. In Cameroon, the yellow fever virus is the only pathogen that is monitored in patients who present with this symptom. However, more than 90% of the samples received as part of this surveillance are negative for yellow fever. This study aimed to describe the prevalence and hepatitis E virus (HEV) genotype among yellow fever-negative patients in the Far North and West regions of Cameroon.MethodsIn a cross-sectional study, yellow fever surveillance-negative samples collected between January 2021 and January 2023 were retrospectively analyzed. Anti-HEV IgM and IgG antibodies were tested using commercially available ELISA kits. Anti-HEV IgM and/or IgG positive samples were tested for HEV RNA by real-time RT-PCR, followed by nested RT-PCR, sequencing and phylogenetic analysis.ResultsOverall, 121 of the 543 samples (22.3%, 95% CI: 19.0% - 26.0%) were positive for at least one anti-HEV marker. Amongst these, 8.1% (44/543) were positive for anti-HEV IgM, 5.9% (32/543) for anti-HEV IgG, and 8.3% (45/544) for both markers. A total of 15.2% (12/79) samples were positive for HEV RNA real-time RT-PCR and 8 samples were positive for HEV RNA by nested RT-PCR. Phylogenetic analysis showed that the retrieved sequences clustered within HEV genotypes/subtypes 1/1e, 3/3f and 4/4b.ConclusionOur results showed that HEV is one of the causes of acute febrile jaundice in patients enrolled in the yellow fever surveillance program in two regions of Cameroon. We described the circulation of three HEV genotypes, including two zoonotic genotypes. Further studies will be important to elucidate the transmission routes of these zoonotic HEV genotypes to humans in Cameroon.</div

'As a clinician, you are not managing lab results, you are managing the patient': how the enactment of malaria at health facilities in Cameroon compares with new WHO guidelines for the use of malaria tests.

In response to widespread overuse of antimalarial drugs, the World Health Organisation changed guidelines in 2010 to restrict the use of antimalarials to parasitologically confirmed malaria cases. Malaria rapid diagnostic tests (RDTs) have been presented as a means to realize the new guidelines, and National Malaria Control Programmes, including that of Cameroon, are developing plans to introduce the tests to replace microscopy or clinical diagnosis at public health facilities across the country. We aimed to understand how malaria tests and antimalarial drugs are currently used as part of social interactions between health workers and patients at public and mission health facilities in Yaoundé and Bamenda and surrounding districts in the Northwest region of Cameroon. In May to June 2010, we held 17 focus group discussions with 146 health workers involved in clinical care from 49 health facilities. Clinicians enacted malaria as a 'juggling' exercise, involving attention to pathophysiology of the patient as well as their desires and medical reputations, utilising tests and medicines for their therapeutic effects as symbols in the process of care. Parasites were rarely mentioned in describing diagnostic decisions. These enactments of malaria contrast with evidence-based guidelines emanating from WHO, which assume the parasite is the central driver of practice. If RDTs are to be taken up in practice, public health practitioners need to pay careful attention to the values and priorities of health workers and patients if they are to work with them to improve diagnosis and treatment of febrile illnesses

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

Abstract 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