Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the di erences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with di erent ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516G>T (rs3745274), 785A>G (rs2279343) and 983T>C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed di erent haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic pro le. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a di erent haplotype structure due to the di erent genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence

Molecular evidence of Plasmodium vivax infection in Duffy negative symptomatic individuals from Dschang, West Cameroon

Background: Plasmodium vivax infection is known to be rare in West/Central Africa, the most accepted explanation being the lack of expression of erythroid Duffy antigen in the local human populations. Duffy negativity prevents the parasite to exploit the entry mechanism on the red blood cell surface. However, there are a growing number of reported vivax infections in Duffy-negative individuals. Data on P. vivax circulation in Cameroon are limited. The aim of the study was to evaluate the P. vivax presence, and its association with the Duffy genotype in West Cameroon. Results: Overall, 484 blood samples were collected consecutively from febrile outpatients attending the Dschang’s Hospital (West Cameroon) during a 3-months period. Plasmodium vivax infection was detected by PCR in 5.6% (n = 27/484) of the cases, representing 38.6% (n = 27/70) of all Plasmodium infections detected. All P. vivax infected individuals showed a Duffy-negative genotype, and the frequency of Duffy-positive individuals in the whole tested population was 1.7%. Conclusions: The results of this study confirm the circulation of P. vivax in Cameroon, as well as that the lack of expression of Duffy-antigen does not confer full protection against vivax malaria acquisition

Preliminary survey on Anopheles species distribution in Botswana shows the presence of Anopheles gambiae and Anopheles funestus complexes

Background: Botswana is one of the four front line malaria elimination countries in Southern Africa, with malaria control activities that include routine vector control. Past and recent studies have shown that Anopheles arabiensis is the only known vector of Plasmodium parasites in the country. This report presents a preliminary evaluation on Anopheles species composition in seven districts of Botswana with some inferences on their vectorial role. Results: Overall, 404 Anopheles mosquito females were collected, of which 196 were larvae collected from several breeding sites, and 208 were adults obtained from indoor pyrethrum spray catches (PSC). Anopheles arabiensis (58.9%) accounted for the highest relative frequency in 5 out of 7 districts sampled. The other species collected, among those identified, were barely represented: Anopheles longipalpis type C (16.3%), Anopheles parensis (8.9%), Anopheles quadriannulatus (5.4%), and Anopheles leesoni (0.2%). PCR test for human β-globin on mosquitoes collected by PSC showed that An. arabiensis and An. parensis had bitten human hosts. Moreover, An. arabiensis showed a non-negligible Plasmodium falciparum infection rate in two sites (3.0% and 2.5% in Chobe and Kweneng West districts, respectively). Conclusions: This work provides first time evidence of Anopheles diversity in several areas of Botswana. Anopheles arabiensis is confirmed to be widespread in all the sampled districts and to be vector of P. falciparum. Moreover, the presence of Anopheles funestus group in Botswana has been assessed. Further research, entomological surveillance activities and possibly vector control programmes need to be better developed and implemented as well as targeting outdoors resting vectors

Osservazioni sui fattori di rischio coinvolti nell'infezione da Human herpes Virus (HHV-8) associati alla malaria da Plasmodium falciparum in Uganda

Background. Human herpes virus 8 (HHV-8) is the causal agent of Kaposi’s Sarcoma (KS) and it is most prevalent in sub-Saharan Africa, and also in Uganda, where Plasmodium falciparum malaria is a priority in public health and represents one of the most important parasitic diseases (1). Following primary infection HHV-8, as all the herpesviridae, establishes a long life persistent infection also in a latent stage that bring to a delicate equilibrium between viral replication and the host immune responses. We investigated how is prevalent the malaria infection in children and if could have an impact on HHV-8 reactivation and also an influence in the transmission of Kaposi Sarcoma Associated Herpes Virus (KSHV) in endemic areas (2,3). Material/methods. Children were enrolled during cross-sectional surveys performed in two different zones of Uganda: Kampala suburbs (Central-Southern Uganda) and in rural sites of Karamoja region (North-Eastern Uganda). Fingerpick blood samples and saliva samples were spotted on Whatman grade 1 filter papers at the time of the field survey and then air-dried before being separately stored in sealed plastic containers. From each sample, the presence of P. falciparum DNA was investigated by nested PCR and the presence of HHV8 DNA was detected by Real Time PCR. Statistical analysis was performed with the application of descriptive methods (means, SD, and percentage) and 95% confidence interval. Results. We analyzed a sample of 259 children (46.0% male and 49.8% female) with mean age of 7.1 (1<13) years. P. falciparum DNA was detected in 36.7% (95% C. I. 31.0 – 42.7) of samples, while HHV8-DNA in 5.8 % (95% C.I. 9.8 – 24.4). The coinfection was detected in 8.3% showing that a decrease in host immune response due to coinfection, affecting the host, in this case malaria, could represent a possible risk factor for infection or reactivation of latent HHV-8. Conclusions. So far our results show some initial evidence that the immune response due to malaria infection, could represent a possible risk factor for the infection or reactivation of latent HHV-8. Anyway further studies are needed investigating other Africa sub-Saharan countries where the diseases are endemic

Biocide resistance in Klebsiella pneumoniae: a narrative review

Summary: Klebsiella pneumoniae is among the World Health Organization's list of priority pathogens, notorious for its role in causing healthcare-associated infections and neonatal sepsis globally. Containment of K. pneumoniae transmission depends on the continued effectiveness of antimicrobials and of biocides used for topical antisepsis and surface disinfection. Klebsiella pneumoniae is known to disseminate antimicrobial resistance (AMR) through a large auxiliary genome made up of plasmids, transposons and integrons, enabling it to evade antimicrobial killing through the use of efflux systems and biofilm development. Because AMR mechanisms are also known to impart tolerance to biocides, AMR is frequently linked with biocide resistance (BR). However, despite extensive research on AMR, there is a gap in knowledge about BR and the extent to which AMR and BR mechanisms overlap remains debatable. The aim of this paper is to review and summarise the current knowledge on the determinants of BR in K. pneumoniae and highlight content areas that require further inquiry

Evaluation of Plasmodium falciparum malaria as a risk factor involved in human herpes virus 8 (HHV8) infection in Uganda

Background. Human herpes virus 8 (HHV-8) is the causal agent of Kaposi’s Sarcoma (KS) and it is most prevalent in sub-Saharan Africa, mainly in Uganda, where Plasmodium falciparum malaria is a priority in public health and represents one of the most important parasitic diseases. Following primary infection HHV-8 establishes a long life persistent infection and this reflects a delicate equilibrium between viral replication and the host immune responses. The malaria infection could have an impact on HHV-8 reactivation and this suggests that may influence the transmission of Kaposi Sarcoma Associated Herpes Virus (KSHV) in endemic areas. Material/methods. Children and their mothers were enrolled during cross-sectional surveys performed in two different zones of Uganda: Kampala suburbs (Central-Southern Uganda) and in rural sites of Karamoja region (North-Eastern Uganda). Fingerpick blood samples and saliva samples were spotted on Whatman grade 1 filter papers at the time of the field survey and then air dried before being separately stored in sealed plastic containers. From each sample, the presence of P. falciparum DNA was investigated by nested PCR-RFLP and the presence of HHV8 DNA was detected by Real Time PCR. Statistical analysis was performed with the application of descriptive methods (means, SD, and percentage) and 95% confidence interval; the association between categorical variables was evaluated through chi-square Pearson test; results were considered significance if p< 0.05. Results. We analyzed a sample of 259 children (46.0% male and 49.8% female) with mean age 7.1 (1<13). Positivity for malaria was 36.7% (95% C. I. 31.0 – 42.7), while positivity for HHV-8 was 15.8 % (95% C.I. 9.8 – 24.4). The association between the two infection diseases (chi-square Pearson test) resulted close to the level of statistical significance (p = 0.085). Conclusions. So far our results show some initial evidence that the lower immune response due to malaria infection, affecting the host immune system, could represent a possible risk factor for infection or reactivation of latent HHV-8. Anyway further studies are needed investigating other Africa sub- Saharan countries

Improving the reading skills of children with neurodevelopmental disabilities: Preliminary study from Botswana

In Botswana, Special Needs Education has been implemented for 25 years with some success but there is still a need for evidence-based methods like Frequency Building, behavioural fluency, and Precision Teaching to be used to measure and improve school performance and learning. We explored the impact of these behavioural technologies on reading performances of four children with learning disorders (ADHD, speech impairment and acquired brain disorder) in a special school in Gaborone. At the assessment, two children were unable to read letter sounds and two could not read sight words. Reading performances were measured with frequency and displayed on a standard celeration chart. During the intervention, the length of the tasks was reduced and then augmented. Findings revealed that after 3 months of intervention children significantly increased their score stimulating self-confidence and enthusiasm during activities. This work demonstrates that behavioural technologies can be applied in Africa without using expensive or time-consuming resources

Cytochrome P450 2C8*2 allele in Botswana: human genetic diversity and public health implications

Human cytochrome P450 2C8 is a highly polymorphic gene and shows variation according to ethnicity. The CYP2C8*2 is a slow drug metabolism allele and shows 10–24% frequency in Black populations. The objective of this study was to assess the prevalence of CYP2C8*2 allele in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu-related ethnic groups (17.5% and 8.5% for San and Bantu, respectively; P = 0.00002). These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of longer drug clearance or poor level of activation of pro-drugs among the San group

Cytochrome P450 2C8*2 allele in Botswana: human genetic diversity and public health implications

Human cytochrome P450 2C8 is a highly polymorphic gene and shows variation according to ethnicity. The CYP2C8*2 is a slow drug metabolism allele and shows 10–24% frequency in Black populations. The objective of this study was to assess the prevalence of CYP2C8*2 allele in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu-related ethnic groups (17.5% and 8.5% for San and Bantu, respectively; P = 0.00002). These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of longer drug clearance or poor level of activation of pro-drugs among the San group