Insecticide susceptibility status of Anopheles gambiae mosquitoes and the effect of pre-exposure to a piperonyl butoxide (PBO) synergist on resistance to deltamethrin in northern Namibia.

Background: Pyrethroid-based indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) have been employed as key vector control measures against malaria in Namibia. However, pyrethroid resistance in Anopheles mosquitoes may compromise the efficacy of these interventions. To address this challenge, the World Health Organization (WHO) recommends the use of piperonyl butoxide (PBO) LLINs in areas where pyrethroid resistance is confirmed to be mediated by mixed function oxidase (MFO).

Human and vector behaviors determine exposure to Anopheles in Namibia.

Background: Although the Republic of Namibia has significantly reduced malaria transmission, regular outbreaks and persistent transmission impede progress towards elimination. Towards an understanding of the protective efficacy, as well as gaps in protection, associated with long-lasting insecticidal nets (LLINs), human and Anopheles behaviors were evaluated in parallel in three malaria endemic regions, Kavango East, Ohangwena and Zambezi, using the Entomological Surveillance Planning Tool to answer the question: where and when are humans being exposed to bites of Anopheles mosquitoes?

Methods: Surveillance activities were conducted during the malaria transmission season in March 2018 for eight consecutive nights. Four sentinel structures per site were selected, and human landing catches and human behavior observations were consented to for a total of 32 collection nights per site.

The in-vivo dynamics of Plasmodium falciparum HRP2: implications for the use of rapid diagnostic tests in malaria elimination.

Background: Rapid diagnostic tests (RDTs) that rely on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) have become key tools for diagnosing P. falciparum infection. The utility of RDTs can be limited by PfHRP2 persistence, however it can be a potential benefit in low transmission settings where detection of persistent PfHRP2 using newer ultra-sensitive PfHRP2 based RDTs can serve as a surveillance tool to identify recent exposure.

FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences.

The growing prevalence of deadly microbes with resistance to previously life-saving drug therapies is a dire threat to human health. Detection of low abundance pathogen sequences remains a challenge for metagenomic Next Generation Sequencing (NGS). We introduce FLASH (Finding Low Abundance Sequences by Hybridization), a next-generation CRISPR/Cas9 diagnostic method that takes advantage of the efficiency, specificity and flexibility of Cas9 to enrich for a programmed set of sequences.

Using parasite genetic and human mobility data to infer local and cross-border malaria connectivity in Southern Africa.

Local and cross-border importation remain major challenges to malaria elimination and are difficult to measure using traditional surveillance data. To address this challenge, we systematically collected parasite genetic data and travel history from thousands of malaria cases across northeastern Namibia and estimated human mobility from mobile phone data. We observed strong fine-scale spatial structure in local parasite populations, providing positive evidence that the majority of cases were due to local transmission.

Loop-mediated isothermal amplification (LAMP) and Polymerase Chain Reaction (PCR) as quality assurance tools for Rapid Diagnostic Test (RDT) malaria diagnosis in Northern Namibia.

Malaria cases sometimes go undetected using RDTs due to their inaccurate use, poor storage conditions and failure to detect low parasitaemia (<50parasites/μL). This could result in continuous transmission of malaria and sustenance of parasite reservoirs. Molecular diagnostic tools are more sensitive and specific than RDTs in the detection of plasmodium parasites.

Evaluation of loop-mediated isothermal amplification as a surveillance tool for malaria in reactive case detection moving towards elimination.

Background: As malaria transmission decreases, the proportion of infections that are asymptomatic at any given time increases. This poses a challenge for diagnosis as routinely used rapid diagnostic tests (RDTs) miss asymptomatic malaria cases with low parasite densities due to poor sensitivity. Yet, asymptomatic infections can contribute to onward transmission of malaria and therefore act as infectious reservoirs and perpetuate malaria transmission.

RANDOMIZED ANTICANCER AND CYTOTOXICITY ACTIVITIES OF AND .

Background: Plants have consistently proven to be a reliable and yet not fully explored source of medicines. In light of this, there is a constant demand for new treatment regimens for cancer. Namibia has a rich diversity of plant species of over 4300 with 17 % of them being endemic to Namibia.

Phytochemical Analysis and Anti-Inflammatory Activity of the Extracts of the African Medicinal Plant Ximenia caffra.

A method was developed for identification and quantification of polyphenols in the leaves of Ximenia caffra using HPLC/UV/MS. Based on analyzing the MS and UV data and in comparison to the authentic standards, a total of 10 polyphenols were identified and quantified, including gallic acid, catechin, quercetin, kaempferol, and their derivatives. The total content of these compounds was found to be approximately 19.

Evidence for a superoxide permeability pathway in endosomal membranes.

The compartmentalized production of superoxide (*O(2)(-)) by endosomal NADPH oxidase is important in the redox-dependent activation of NF-kappaB following interleukin 1beta (IL-1beta) stimulation. It remains unclear how *O(2)(-) produced within endosomes facilitates redox-dependent signaling events in the cytoplasm. We evaluated *O(2)(-) movement out of IL-1beta-stimulated endosomes and whether SOD1 at the endosomal surface mediates redox-signaling events required for NF-kappaB activation.

Increase of therapeutic effects by treating melanoma with targeted combinations of c-myc antisense and doxorubicin.

Patients with advanced or metastatic melanoma have a very poor prognosis, due to the resistance of melanoma cells to conventional chemotherapy. We previously reported that coated cationic liposomes targeted with a monoclonal antibody against the disialoganglioside GD(2) and containing c-myc antisense oligodeoxynucleotides (alpha GD(2)-CCL[c-myc-as]) induced partial tumor growth arrest in melanoma xenografts. Here we addressed the role of c-myc-asODN treatment in the susceptibility to doxorubicin (DXR) in human melanoma cells.

Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates.

Some formulations of liposomal doxorubicin with intermediate rates of drug release have shown increased levels of toxicity in mice. Because antibody-mediated targeting of liposomal drugs influences the pharmacokinetics, mechanism of uptake, and selectivity of the associated drugs, we hypothesized that anti-CD19-mediated targeting of liposomal doxorubicin might moderate the toxicity of the problem formulations. Phosphatidylcholine/cholesterol liposomal formulations of doxorubicin having faster, intermediate, and slower drug release rates were prepared by altering the fatty acyl chain length or degree of saturation of the phosphatidylcholine component.