Publications by authors named "Giacomo Maria Paganotti"

Malaria caused by Plasmodium falciparum is one of the deadliest and most common tropical infectious diseases. However, the emergence of artemisinin drug resistance associated with the parasite's Pfk13 gene, threatens the public health of individual countries as well as current efforts to reduce malaria burdens globally. It is of concern that artemisinin-resistant parasites may be selected or have already emerged in Africa.

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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 transmission depends on the continued effectiveness of antimicrobials and of biocides used for topical antisepsis and surface disinfection. 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.

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A simple external calibration liquid chromatography-diode array detector method was developed, validated, and applied for the determination of lumefantrine (Lum) in dried blood spot (DBS) samples collected from malaria patients in Botswana. The samples were validated in accordance with the United States Food and Drug Administration guidelines for bioanalytical methods after sample preparation using solid-liquid extraction. Separation was achieved using an XTerra C18 column (50 × 4.

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Background: The continued spread of infectious diseases by mosquitoes remains a formidable obstacle to the well-being of the people all over the world. Arboviruses are spread from one vertebrate host to another by vectors through intricate transmission cycles that involve the virus, the vertebrate host, and the vector. It is essential to acquire a better understanding of the current abundance and distribution of major vectors in order to adequately prepare for the possibility of arbovirus outbreaks.

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We report the molecular evidence of dengue virus (DENV) and chikungunya virus (CHIKV) infection in symptomatic individuals in Cameroon and Gabon, respectively. Arthropod-borne viruses (arboviruses) are distributed in the tropical or subtropical regions, with DENV having the highest burden. The morbidity and mortality related to arboviral diseases raise the concern of timely and efficient surveillance and care.

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Breast cancer is the most frequent cause of cancer death in low- and middle-income countries, in particular among sub-Saharan African women, where response to available anticancer treatment therapy is often limited by the recurrent breast tumours and metastasis, ultimately resulting in decreased overall survival rate. This can also be attributed to African genomes that contain more variation than those from other parts of the world. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to specific available treatments and the known genetic variabilities associated with metabolism and/or transport of breast cancer drugs, and treatment outcomes when possible.

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We demonstrate the suitability of a fast, green, easy-to-perform, and modified sample extraction procedure, i.e., dispersive liquid-liquid microextraction (DLLME) for the determination of efavirenz (EFV) in human plasma.

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Objectives: Plasmodium vivax malaria was thought to be rare in Africans who lack the Duffy blood group antigen expression. However, recent studies indicate that P. vivax can infect Duffy-negative individuals and has spread into areas of high Duffy negativity across Africa.

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In 2016, we reported the presence of Plasmodium vivax in Botswana through active case detection. A real-time PCR was used during a similar study in 10 districts to assess changes in the P. vivax prevalence.

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Background: In spite of the global effort to eliminate malaria, it remains the most significant vector-borne disease of humans. Plasmodium falciparum is the dominant malaria parasite in sub-Saharan Africa. However, Plasmodium vivax is becoming widely spread throughout Africa.

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The Duffy blood group is a critical receptor for Plasmodium vivax (P. vivax) invasion of red blood cells, and consequently, P. vivax infections were considered rare in sub-Saharan Africa where the prevalence of Duffy-negativity is high.

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Introduction: Cryptosporidium, Giardia and rotaviruses are amongst the leading causes of acute gastroenteritis in children ≤5 years worldwide. The purpose of this study was to determine the occurrence of Cryptosporidium parvum, Giardia intestinalis and molecular characteristics of rotaviruses after Rotarix® introduction in Botswana.

Methods: in this case study, 200 diarrheic stool specimens and 100 control samples from children under five years old were collected between March and November, 2017.

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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.

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Malaria continues to be one of the top infectious agents contributing to morbidity and mortality in sub-Saharan Africa. Annually, Botswana accounts only for a small proportion of cases (<<1%). Despite significantly reduced incidence rate, the country still experiences sporadic outbreaks that hamper the goal of malaria elimination.

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Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is commonly seen in malaria endemic areas as it is known to confer a selective advantage against malaria. Recently, we reported a high proportion of asymptomatic reservoir of Plasmodium vivax in Botswana, that calls for intervention with primaquine to achieve radical cure of vivax malaria. Considering that individuals with this enzyme deficiency are at risk of haemolysis following primaquine treatment, assessment of the population for the relative frequency of G6PD deficiency is imperative.

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Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499).

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Background: Little is known about the peopling of the Sahara during the Holocene climatic optimum, when the desert was replaced by a fertile environment.

Results: In order to investigate the role of the last Green Sahara in the peopling of Africa, we deep-sequence the whole non-repetitive portion of the Y chromosome in 104 males selected as representative of haplogroups which are currently found to the north and to the south of the Sahara. We identify 5,966 mutations, from which we extract 142 informative markers then genotyped in about 8,000 subjects from 145 African, Eurasian and African American populations.

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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.

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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.

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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.

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The burden of human immunodeficiency virus (HIV) is mainly concentrated to resources-limited countries where the response to available antiretroviral therapy is often limited by the occurrence of toxicity or by the emergence of HIV drug resistance. Efavirenz and nevirapine are the antiretroviral drugs most prescribed in resources-limited countries as part of antiretroviral combination therapy. Their metabolism and conjugation are largely influenced by enzymatic genetic polymorphisms.

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The prescription of patients' tailored anti-infectious treatments is the ultimate goal of pharmacogenetics/genomics applied to antimicrobial treatments, providing a basis for personalized medicine. Despite the efforts to screen Africans for alleles underlying defective metabolism for a panel of different drugs, still more research is necessary to clarify the interplay between host genetic variation and treatments' response. HIV is a major infectious disease in sub-Saharan African countries, and the main prescribed anti-HIV combination therapy includes efavirenz (EFV) or nevirapine (NVP).

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Study of host pharmacogenetics can improve our knowledge of mechanisms of drug resistance selection and spread. This issue has recently been addressed with respect to chloroquine and amodiaquine in malaria endemic areas of West and East Africa. Here we report, from surveys performed in two different areas of Uganda, that the human CYP2C8*3 allele, which had been reported to be strongly associated with parasite drug resistance in Zanzibar, is absent, being a marker of genetic admixture of the Zanzibari population with a Caucasoid component.

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