Pharmacogenetic considerations in the treatment of co-infections with HIV/AIDS, tuberculosis and malaria in Congolese populations of Central Africa.

BACKGROUND: HIV-infection, tuberculosis and malaria are the big three communicable diseases that plague sub-Saharan Africa. If these diseases occur as co-morbidities they require polypharmacy, which may lead to severe drug-drug-gene interactions and variation in adverse drug reactions, but also in treatment outcomes. Polymorphisms in genes encoding drug-metabolizing enzymes are the major cause of these variations, but such polymorphisms may support the prediction of drug efficacy and toxicity. There is little information on allele frequencies of pharmacogenetic variants of enzymes involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in the Republic of Congo (ROC). The aim of this study was therefore to investigate the occurrence and allele frequencies of 32 pharmacogenetic variants localized in absorption distribution, metabolism and excretion (ADME) and non-ADME genes and to compare the frequencies with population data of Africans and non-Africans derived from the 1000 Genomes Project. RESULTS: We found significant differences in the allele frequencies of many of the variants when comparing the findings from ROC with those of non-African populations. On the other hand, only a few variants showed significant differences in their allele frequencies when comparing ROC with other African populations. In addition, considerable differences in the allele frequencies of the pharmacogenetic variants among the African populations were observed. CONCLUSIONS: The findings contribute to the understanding of pharmacogenetic variants involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in ROC and their diversity in different populations. Such knowledge helps to predict drug efficacy, toxicity and ADRs and to inform individual and population-based decisions.

First COVID-19 case in Zambia - Comparative phylogenomic analyses of SARS-CoV-2 detected in African countries.

Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. While African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 h of the individual entering the country by air travel from a trip to France. Contact tracing showed that SARS-CoV-2 infection was contained within the patient's household, with no further spread to attending health care workers or community members. Phylogenomic analysis of the patient's SARS-CoV-2 strain showed that it belonged to lineage B.1.1., sharing the last common ancestor with SARS-CoV-2 strains recovered from South Africa. At the African continental level, our analysis showed that B.1 and B.1.1 lineages appear to be predominant in Africa. Whole genome sequence analysis should be part of all surveillance and case detection activities in order to monitor the origin and evolution of SARS-CoV-2 lineages across Africa.

Use of stochastic multi-criteria decision analysis to support sustainable management of contaminated sediments.

Sustainable management of contaminated sediments requires careful prioritization of available resources and focuses on efforts to optimize decisions that consider environmental, economic, and societal aspects simultaneously. This may be achieved by combining different analytical approaches such as risk analysis (RA), life cycle analysis (LCA), multicriteria decision analysis (MCDA), and economic valuation methods. We propose the use of stochastic MCDA based on outranking algorithms to implement integrative sustainability strategies for sediment management. In this paper we use the method to select the best sediment management alternatives for the dibenzo-p-dioxin and -furan (PCDD/F) contaminated Grenland fjord in Norway. In the analysis, the benefits of health risk reductions and socio-economic benefits from removing seafood health advisories are evaluated against the detriments of remedial costs and life cycle environmental impacts. A value-plural based weighing of criteria is compared to criteria weights mimicking traditional cost-effectiveness (CEA) and cost-benefit (CBA) analyses. Capping highly contaminated areas in the inner or outer fjord is identified as the most preferable remediation alternative under all criteria schemes and the results are confirmed by a probabilistic sensitivity analysis. The proposed methodology can serve as a flexible framework for future decision support and can be a step toward more sustainable decision making for contaminated sediment management. It may be applicable to the broader field of ecosystem restoration for trade-off analysis between ecosystem services and restoration costs.

Trends of Zambia's tuberculosis burden over the past two decades.

OBJECTIVES: To study trends in Zambia's TB notification rates between 1990 and 2010 and to ascertain progress made towards TB control. METHODS: Retrospective review of TB notification returns and TB programme reports for the period from 1990 to 2010. RESULTS: Two distinct TB trend periods were identified: a period of rising trends up to a peak between 1990 and 2004 and a period of moderately declining trends between 2004 and 2010. Treatment outcomes improved over the two decades. Data on trends in paediatric TB, TB in prisoners and TB in pregnant women remain scanty and unreliable owing to poor diagnostic capability. There were no data available on trends on drug-resistant TB because of the lack of laboratory services to perform drug sensitivity testing. CONCLUSIONS: The period of increasing TB between 1990 and 2000 coincided with an increase in HIV/AIDS. The period of slightly decreasing TB between 2004 and 2010 can be attributed to improved TB care, sustained DOTS implementation and improvement in TB diagnostic services. Newer diagnostics technologies for the rapid diagnosis of active TB cases and for drug-resistant testing, recently endorsed by the WHO, need to be implemented into the national TB programmes to detect more cases and to provide epidemiological and surveillance data from which to obtain an evidence base for guided investments for TB control. Alignment of TB and HIV services is required to achieve improved management outcomes.