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Whole genome sequencing-based drug resistance predictions of multidrug-resistant Mycobacterium tuberculosis isolates from Tanzania
Get PDFThis research article published by Oxford University Press, 2022Background: Rifampicin- or multidrug-resistant (RR/MDR) Mycobacterium tuberculosis complex (MTBC) strains
account for considerable morbidity and mortality globally. WGS-based prediction of drug resistance may guide
clinical decisions, especially for the design of RR/MDR-TB therapies.
Methods: We compared WGS-based drug resistance-predictive mutations for 42 MTBC isolates from MDR-TB pa tients in Tanzania with the MICs of 14 antibiotics measured in the Sensititre™ MycoTB assay. An isolate was
phenotypically categorized as resistant if it had an MIC above the epidemiological-cut-off (ECOFF) value, or as
susceptible if it had an MIC below or equal to the ECOFF.
Results: Overall, genotypically non-wild-type MTBC isolates with high-level resistance mutations (gNWT-R) cor related with isolates with MIC values above the ECOFF. For instance, the median MIC value (mg/L) for rifampicin gNWT-R strains was .4.0 (IQR 4.0–4.0) compared with 0.5 (IQR 0.38–0.50) in genotypically wild-type (gWT-S,
P,0.001); isoniazid-gNWT-R .4.0 (IQR 2.0–4.0) compared with 0.25 (IQR 0.12–1.00) among gWT-S (P=
0.001); ethionamide-gNWT-R 15.0 (IQR 10.0–20.0) compared with 2.50 (IQR; 2.50–5.00) among gWT-S (P,
0.001). WGS correctly predicted resistance in 95% (36/38) and 100% (38/38) of the rifampicin-resistant isolates
with ECOFFs .0.5 and .0.125 mg/L, respectively. No known resistance-conferring mutations were present in
genes associated with resistance to fluoroquinolones, aminoglycosides, capreomycin, bedaquiline, delamanid,
linezolid, clofazimine, cycloserine, or p-amino salicylic acid.
Conclusions: WGS-based drug resistance prediction worked well to rule-in phenotypic drug resistance and the
absence of second-line drug resistance-mediating mutations has the potential to guide the design of RR/MDR-TB
regimens in the future
Context-specific optimal dietary guidelines for managing cancer for hospitalized patients in Tanzania
Get PDFThis research article was published by Emerald Publishing Limited, 2022Purpose – The lack of food-based dietary guidelines for managing cancer among hospitalized patients
has led to an increasing economic burden on the government and families in low- and middle-economy
countries. There have been increasing medical costs due to delayed recovery, readmission and
mortality. The purpose of this study is to contribute in reducing these effects by developing context specific food-based dietary guidelines to assist health-care professionals and caregivers in planning
diets for cancer patients.
Design/methodology/approach – For seven days, the dietary intakes of 100 cancer patients in the
hospital were recorded using weighed food records. Data on the costs of commonly consumed foods during
hospitalization were obtained from hospital requisition books as well as nearby markets and shops. The
information gathered was used to create optimal food-based dietary guidelines for cancer patients.
Findings – Most patients did not meet the recommended food group and micronutrient intake according to
their weighed food records. Sugar intake from processed foods was (51 6 19.8 g), (13% 6 2%), and calories
(2585 6 544 g) exceeded recommendations. Optimized models generated three menus that met the World
Cancer Research Fund 2018 cancer prevention recommendation at a minimum cost of 2,700 Tanzanian
Shillings (TSH), 3500TSH, and 4550TSH per day. The optimal dietary pattern includes nutrient-dense foods
from all food groups in recommended portions and within calorie limits.
Originality/value – Findings show that optimal dietary guidelines that are context-specific for managing
cancer in hospitalized patients can be formulated using culturally acceptable food ingredients at minimum cost
Formulation, Optimization, and Evaluation of Moringa oleifera Leaf Polyphenol-Loaded Phytosome Delivery System against Breast Cancer Cell Lines
Get PDFThis research article was published by MDPI, 2022Moringa oleifera leaf polyphenols (Mopp) were encapsulated with phytosomes to enhance their efficacy on 4T1 cancer cell lines. The Mopp were extracted via microwave-assisted extraction. Moringa oleifera polyphenol-loaded phytosomes (MoP) were prepared with the nanoprecipitation method and characterized using the dynamic light scattering and dialysis membrane techniques. The in vitro cytotoxic and antiproliferative activity were investigated with the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazole) MTT assay. Acute toxicity was assessed using Swiss albino mice. An MoP particle size of 296 ± 0.29 nm, −40.1 ± 1.19 mV zeta potential, and polydispersity index of 0.106 ± 0.002 were obtained. The total phenolic content was 50.81 ± 0.02 mg GAE/g, while encapsulation efficiency was 90.32 ± 0.11%. The drug release profiles demonstrated biphasic and prolonged subsequent sustained release. In vitro assays indicated MoP had a low cytotoxicity effect of 98.84 ± 0.53 μg/mL, doxorubicin was 68.35 ± 3.508, and Mopp was 212.9 ± 1.30 μg/mL. Moreover, MoP exhibited the highest antiproliferative effect on 4T1 cancer cells with an inhibitory concentration of 7.73 ± 2.87 μg/mL and selectivity index > 3. The results indicated a significant difference (p ≤ 0.001) in MoP when compared to Mopp and doxorubicin. The in vivo investigation showed the safety of MoP at a dose below 2000 mg/kg. The present findings suggest that MoP may serve as an effective and promising formulation for breast cancer drug delivery and therapy
Evaluation of autodissemination technique using novaluron against anopheles arabiensis under semi-field conditions in south-eastern Tanzania
Get PDFA Dissertation Submitted in Partial Fulfilment of the Requirements for the Degree of Master of Science in Public Health Research of the Nelson Mandela African Institution of Science and TechnologyThis study assessed the susceptibility of immature stages of An. arabiensis, An. gambiae and An.
funestus to novaluron and the autodissemination technique using An. arabiensis. Susceptibility
bioassays using technical grade novaluron (98% active ingredient) were performed inside the
semi-field system using first instar larvae of the mosquito test species. A total of 1500 larvae were
exposed to novaluron within three replicates of control and treatment assays. Concentration ranges
of 0.01 mg/l to 2 mg/l of novaluron were tested to establish lethal concentration (LC) sufficient to
kills 50%, 90% and 99% of the exposed larvae (LC50, LC90 and LC99) by using log-dose response
analysis. The autodissemination experiment exposed 2500 mated female blood fed An. arabiensis
mosquitoes (aged 6-7 days) to both contaminated and uncontaminated clay pots. In two each
chambers in the semi-field tunnel cage; an artificial breeding habitats were provided in each
chamber to assess the autodissemination. The successful autodissemination and contamination was
assessed by comparing larval mortality from treated and untreated chambers. An. gambiae were
highly susceptible to novaluron followed by An. arabiensis and then An. funestus. Lethal
concentrations, LC50, LC90 and LC99 (95%CI) in mg/l for An. gambiae were 0.018 (0.016-0.020),
0.546 (0.374-0.719) and 2.001 (1.986-3.206) respectively. For An. arabiensis were 0.032 (0.027-
0.038), 0.332 (0.168-0.496) and 2.013 (1.997-4.491); and for An. funestus were 0.02561 (0.02140-
0.0299), 1 (0.4657-1.5347) and 5.580 (4.687-8.496). High larval mortality was recorded at high
concentration (2mg/L) for all species, with 80% mortality within 3 days post exposure. Similarly,
low larval mortality was observed at low concentration (0.1 mg/L) (for all species) with 80%
mortality within 9 days post exposure. There were no evidence of autodissemination following
adults’ exposure to novaluron. The results showed no significant difference between treatment and
control cups when An. arabiensis larvae were exposed to the water samples from the breeding
habitats. The study demonstrates the efficacy of novaluron against immature stages of susceptible
and resistant Anopheles mosquito species. The findings present a promising candidate IGR for
rotation to counteract the insecticide resistance development. Moreover, these results warrant
further evaluation of novaluron for autodissemination by vector species for its inclusion in rotation
to prevent evolution of resistance in both chemistries
Modified World Health Organization (WHO) Tunnel Test for Higher Throughput Evaluation of Insecticide-Treated Nets (ITNs) Considering the Effect of Alternative Hosts, Exposure Time, and Mosquito Density
Get PDFThis research article was published by MDPI, 2022The standard World Health Organization (WHO) tunnel test is a reliable laboratory bioassay used for “free-flying” testing of insecticide-treated nets (ITNs) bio-efficacy where mosquitoes pass through a ITN sample to reach a live animal bait. Multiple parameters (i.e., bait, exposure time, and mosquito density) may affect the outcomes measured in tunnel tests. Therefore, a comparison was conducted of alternative hosts, exposure time, and lower mosquito density against the current gold standard test (100 mosquitoes, animal bait, and 12-h exposure) as outlined in the WHO ITN evaluation guideline. This was done with the aim to make the tunnel test cheaper and with higher throughput to meet the large sample sizes needed for bio-efficacy durability monitoring of chlorfenapyr ITNs that must be evaluated in “free-flying” bioassays. Methods: A series of experiments were conducted in the WHO tunnel test to evaluate the impact of the following factors on bio-efficacy endpoints of mosquito mortality at 24-h (M24) and 72-h (M72) and blood-feeding success (BFS): (1) baits (rabbit, membrane, human arm); (2) exposure time in the tunnel (1 h vs. 12 h); and (3) mosquito density (50 vs. 100). Finally, an alternative bioassay using a membrane with 50 mosquitoes (membrane-50) was compared to the gold standard bioassay (rabbit with 100 mosquitoes, rabbit-100). Pyrethroid-resistant Anopheles arabiensis and pyrethroid susceptible Anopheles gambiae were used to evaluate Interceptor® and Interceptor® G2 ITNs. Results: Using a human arm as bait gave a very different BFS, which impacted measurements of M24 and M72. The same trends in M24, M72 and BFS were observed for both Interceptor® ITN and Interceptor® G2 unwashed and washed 20 times measured using the gold standard WHO tunnel test (rabbit-100) or rabbit with 50 mosquitoes (rabbit-50). M24, M72 and BFS were not statistically different when either 50 or 100 mosquitoes were used with rabbit bait in the tunnel bioassay for either the susceptible or resistant strains. No systematic difference was observed between rabbit-50 and rabbit-100 in the agreement by the Bland and Altman method (B&A). The mean difference was 4.54% (−22.54–31.62) in BFS and 1.71% (−28.71–32.12) in M72 for rabbit-50 versus rabbit-100. Similar M24, M72 and lower BFS was measured by membrane-50 compared to rabbit-100. No systematic difference was observed in the agreement between membrane-50 and rabbit-100, by B&A. The mean difference was 9.06% (−11.42–29.64) for BSF and −5.44% (−50.3–39.45) for M72. Both membrane-50, rabbit-50 and rabbit-100 predicted the superiority of Interceptor® G2 over Interceptor® ITN for the resistant strain on M72. Conclusion: These results demonstrate that WHO tunnel tests using rabbit bait may be run with 50 mosquitoes to increase sample sizes needed for bio-efficacy durability monitoring of ITNs in “free-flying” bioassays. Using a membrane feeder with 50 mosquitoes is a potential replacement for the WHO tunnel bioassay with animal bait if control blood feeding rates can be improved to 50% because blood feeding impacts mosquito survival after exposure to insecticides
Perceived facilitators and barriers to enrolment in health insurance among people working in the informal sector in Morogoro, Tanzania
Get PDFA Dissertation Submitted in Partial Fulfilment of the Requirements for the Degree of Master of Science in Public Health Research of the Nelson Mandela African Institution of Science and TechnologyHealth financing is an important pathway towards universal health coverage (UHC). In Tanzania,
despite an improved Community Health Fund (iCHF) rollout, people in the informal sector haven’t
been fully enrolled. This study explored the perspectives of local-women food vendors (LWFV)
and Bodaboda (motorcycle taxi) drivers on factors that facilitate and challenge their enrolment in
iCHF. A phenomenological study was conducted in Morogoro Municipality. Fifty in-depth
interviews and two focus group discussions were conducted. Participants were purposively
selected based on being LWFV or Bodaboda drivers. The Theory of Planned Behaviour (TPB)
provided a framework for the inquiry and categorization of findings. Views from LWFV and
Bodaboda drivers regarding enrolment in iCHF converged. Enrolment facilitators on attitude:
value for money; and increased access to affordable health care. Subjective norms: encouragement
from already-enrolled friends and relatives. Perceived control: belief that enrolment premiums are
affordable; and improved health care. Barriers on attitude: limited knowledge of how the iCHF
works; and no health promotion activities. Subjective norms: negative views from friends and
family. Perceived control: the iCHF is not accepted in non-government facilities; limited time to
go for enrolment; and uncertainty about coverage of non-communicable diseases. Results suggest
that a positive attitude towards iCHF, supported by perceived benefits and encouragement from
significant others, can motivate LWFV and Bodaboda drivers to enroll. However, more
awareness of iCHF is needed among individuals in the informal sector. There is also a need to
make quality health care services available to iCHF members, including extending their
coverage
Plasmid characterization in bacterial isolates of public health relevance in a tertiary healthcare facility in Kilimanjaro region, Tanzania
Get PDFThis research article was published by Elsevier, 2022Objectives
Plasmids are infectious double stranded DNA molecules that are found within bacteria. Horizontal gene transfer promotes successful spread of different types of plasmids within or among bacteria species, making their detection an important task for guiding clinical treatment. We used whole genome sequenced data to determine the prevalence of plasmid replicon types in clinical bacterial isolates, the presence of resistance and virulence genes in plasmid replicon types, and the relationship between resistance and virulence genes within each plasmid replicon.
Methods
All bacterial sequences were de novo assembled using Unicycler before extraction of plasmids. Assembly graphs were submitted to Gplas+plasflow for plasmid contigs prediction. The predicted plasmid contigs were validated using PlasmidFinder.
Results
A total of 159 (56.2%) out of 283 bacterial isolates were found to carry plasmid replicons, with Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus being the most prevalent plasmid carriers. A total of 26 (86.7%) multiple-replicon types were found to carry both resistance and virulence genes compared to 4 (13.3%) single plasmid replicons. No statistically significant correlation was found between the number of antibiotic resistance and virulence genes in multiple-replicon types (r = - 0.14, P > 0.05).
Conclusion
Our findings show a relatively high proportion of plasmid replicon-carrying isolates suggesting selection pressure due to antibiotic use in the hospital. Co-occurrence of antibiotic resistance and virulence genes in clinical isolates is a public health problem warranting attention
In vitro antiproliferative effects of crude extracts of carica papaya linn (caricaceae family) black seeds against prostate cancer cell lines
Get PDFA Dissertation Submitted in Partial Fulfilment of the Requirements for the Degree of Master’s in Life Sciences of the Nelson Mandela African Institution of Science and TechnologyBlack seeds from papaya plants are utilized as traditional medicine in African and Asian
cultures to improve the functioning of the male reproductive system and management of
prostate cancer. This study analyzed the phytochemical composition, cytotoxicity and
antiproliferative activity of C. papaya black seeds against the Prostate cancer cells and Vero
cells. The phytochemical screening was performed by means of standard procedures. Methyl
tetrazolium bromide (MTT) cell viability assay was employed in the evaluation of the
cytotoxicity and antiproliferative activity of papaya crude extracts in the selected cell lines.
Glycosides, alkaloids, terpenoids tannins, flavonoids and saponins were found in papaya
seeds’ crude extracts. The crude extracts were not toxic to Vero cells. All papaya seeds’
extracts had antiproliferative activity towards prostate cancer cells. Ethyl acetate extract was
found with higher antiproliferative activity, with inhibitory concentration (IC50) of 3.64
µg/mL. Further scientific studies focusing on the isolation and characterization of active
phytocompounds from crude extracts of papaya seeds are needed
Formulation, Optimization, and Evaluation of Moringa oleifera leaf polyphenol-loaded phytosome delivery system against breast cancer cell lines
Get PDFA Dissertation Submitted in Partial Fulfilment of Requirements for Award of a Degree of Master’s in Life Sciences of The Nelson Mandela African Institution of Science and TechnologyActive plant molecules like polyphenols have been repositioned increasingly utilized for
managing breast cancer traditionally. However, polyphenols possess poor lipid miscibility, that
results in poor bioavailability and decreased efficacy. ‘Phytosome’ is a plant based nanocarrier
that improves the bioavailability of the polyphenols. The purpose of this study was to improve
the bioavailability of Moringa oleifera Lam leaf polyphenols (Mopp) through encapsulation
with phytosomes to enhance their activity on 4T1 cancer cell lines. The Mopp phytosomes
were extracted by microwave-assisted extraction. Moringa oleifera polyphenols-loaded
phytosomes (MoP) were prepared by the nanoprecipitation method and characterized by a
dynamic light scattering technique. The ultraviolet-visible spectroscopy determined the
percentage entrapment efficiency (EE%). Fourier-transform infrared (FTIR) spectroscopy
assessed MoP formation. The dialysis membrane technique investigated in vitro drug release
while storage stability test analysis identified MoP stability. The in vitro cytotoxic activity of
MoP on E6 Vero cell lines and anti-proliferative activity on 4T1 cancer cell lines were
investigated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay,
while female Swiss albino mice were used to assess acute toxicity. Results showed that MoP
average particle size was 296±0.29 nm, a zeta-potential of -40.1±1.19 mV, and polydispersity
index of 0.106±0.002. The Mopp total phenolic content was 50.81±0.02 mg GAE/g, EE% was
90.32±0.11%, while FTIR spectra demonstrated successful formation of phytosomes. The drug
release profiles demonstrated biphasic behavior of immediate burst release and subsequent
prolonged sustained release. The in vitro cytotoxicity assays indicated that the MoP had low
cytotoxic effect of 98.84±0.53 μg/mL on E6 Vero cells; while doxorubicin had
68.35±3.51while Mopp was 212.9±1.30 μg/mL. Moreover, MoP exhibited the highest
antiproliferative effect on 4T1 cancer cells with an inhibitory concentration of 7.73±2.87
μg/mL and selectivity index >3. The results indicated a significant difference (p≤ 0.001) in
MoP when compared to Mopp and doxorubicin. In vivo investigation confirmed the safety of
MoP on mice at a dose below 2000 mg/kg. The present findings suggest that the MoP can serve
as an effective and promising formulation for breast cancer drug delivery in cancer therapy
Rheological and Physicochemical Analysis of Nonedible Oils Used for Biodiesel Production
Get PDFThis research article was published by ACS Omega, 2022Rheological and physicochemical characteristics of edible oils used for biodiesel production are well established; nonetheless, the rheological and physicochemical characteristics of nonedible oils are yet to be established. The present study therefore focuses on rheological and physicochemical characterization of nonedible vegetable oils that can be used as biodiesel feedstock. The selected vegetable oils studied include cashew nut shell liquid (CNSL), castor oil (CO), Croton megalocarpus oil (CMO), Podocarpus usambarensis oil (PUO), and Thevetia peruviana oil (TPO). Physicochemical parameters analyzed were free fatty acids, acid value, saponification value, peroxide value, iodine value, specific gravity, and moisture content using methods by the Association of Official Analytical Chemists (AOAC). Rheological properties were analyzed using a VT-550 Thermo Haake Viscotester operated by the Rheowin 3 Job Manager software. The preset parameters in the Viscotester were shear rate and temperature. The shear rate increased uniformly from 5 to 100 s–1 at the temperature range of 30–60 °C. The experimental data were fitted into rheological models of Newton, Bingham, Ostwald–de Waele (power-law), and Herschel–Bulkley using Rheowin 3 Data Manager. The oil yield was 29–65%, highlighting the feedstock’s potential for commercial biodiesel production. At a constant temperature, all oil samples exhibited a Newtonian flow behavior. In contrast to edible oils, nonedible oils exhibited high shear stress, emphasizing the reconstruction of new appropriate designs of production systems. The rheological models appropriate to represent the flow behavior of the samples were the Newton and Ostwald–de Waele models, with a fit of R2 = 0.990–1.000