Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections.

Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30-41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman's rank correction coefficient (r) between TB-MBLA and MGIT was -0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics.

Formulation, Optimization, and Evaluation of Moringa oleifera Leaf Polyphenol-Loaded Phytosome Delivery System against Breast Cancer Cell Lines.

Moringa 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.

Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania.

Rifampin or multidrug-resistant tuberculosis (RR/MDR-TB) treatment has largely transitioned to regimens free of the injectable aminoglycoside component, despite the drug class' purported bactericidal activity early in treatment. We tested whether Mycobacterium tuberculosis killing rates measured by tuberculosis molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB regimen. Serial sputa were collected from patients with RR/MDR- and drug-sensitive TB at days 0, 3, 7, and 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable M. tuberculosis 16S rRNA in sputum for estimation of colony forming units per ml (eCFU/ml). M. tuberculosis killing rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures. Thirty-seven patients produced 296 serial sputa and received treatment as follows: 13 patients received an injectable bedaquiline-free reference regimen, 9 received an injectable bedaquiline-containing regimen, 8 received an all-oral bedaquiline-based regimen, and 7 patients were treated for drug-sensitive TB with conventional rifampin/isoniazid/pyrazinamide/ethambutol (RHZE). Compared to the adjusted M. tuberculosis killing of -0.17 (95% confidence interval [CI] -0.23 to -0.12) for the injectable bedaquiline-free reference regimen, the killing rates were -0.62 (95% CI -1.05 to -0.20) log10 eCFU/ml for the injectable bedaquiline-containing regimen (P = 0.019), -0.35 (95% CI -0.65 to -0.13) log10 eCFU/ml for the all-oral bedaquiline-based regimen (P = 0.054), and -0.29 (95% CI -0.78 to +0.22) log10 eCFU/ml for the RHZE regimen (P = 0.332). Thus, M. tuberculosis killing rates from sputa were higher among patients who received bedaquiline but were further improved with the addition of an injectable aminoglycoside.

TB or not TB? Definitive determination of species within the Mycobacterium tuberculosis complex in unprocessed sputum from adults with presumed multidrug-resistant tuberculosis.

OBJECTIVES: Differences among Mycobacterium tuberculosis complex (MTC) species may predict drug resistance or treatment success. Thus, we optimised and deployed the genotype MTBC assay (gMTBC) to identify MTC to the species level, and then performed comparative genotypic drug-susceptibility testing to anti-tuberculosis drugs from direct sputum of patients with presumed multidrug-resistant tuberculosis (MDR-TB) by the MTBDRplus/sl reference method. METHODS: Patients with positive Xpert® MTB/RIF (Xpert) results were consented to provide early-morning-sputum for testing by the gMTBC and the reference MTBDRplus/sl. Chi-square or Fisher's exact test compared proportions. Modified Poisson regression modelled detection of MTC by gMTBC. RESULTS: Among 73 patients, 53 (73%) were male and had a mean age of 43 (95% CI; 40-45) years. In total, 34 (47%), 36 (49%) and 38 (55%) had positive gMTBC, culture and MTBDR respectively. Forty patients (55%) had low quantity MTC by Xpert, including 31 (78%) with a negative culture. gMTBC was more likely to be positive in patients with chest cavity 4.18 (1.31-13.32, P = 0.016), high-quantity MTC by Xpert 3.03 (1.35-6.82, P = 0.007) and sputum smear positivity 1.93 (1.19-3.14, P = 0.008). The accuracy of gMTBC in detecting MTC was 95% (95% CI; 86-98; κ = 0.89) compared to MTBDRplus/sl. All M. tuberculosis/canettii identified by gMTB were susceptible to fluoroquinolone and aminoglycosides/capreomycin. CONCLUSIONS: The concordance between the gMTBC assay and MTBDRplus/sl in detecting MTC was high but lagged behind the yield of Xpert MTB/RIF. All M. tuberculosis/canettii were susceptible to fluoroquinolones, a core drug in MDR-TB treatment regimens.

Pesticide exposure and genotoxic effects as measured by DNA damage and human monitoring biomarkers.

Occupational pesticides exposure rises health concern due to genotoxicity and accumulation of pesticides in human biological matrices. Continuous and sublethal exposure to pesticides had been associated with oxidative stress, mutagenic and cell death. Exposure to pesticides exhibits increased level of DNA damage even if no detectable amounts of pesticides are seen in biological matrices by binding specific areas in the DNA. This interferes normal body systems and mutation in gene encoding specific activities which may lead to a wide range of cancer. Presence of pesticides compounds in human biological matrices had been evident from various studies. However, detection methods are complex and inconsistent, making it difficult to compare and generalize findings. This article provides insight into genotoxic effects, presence of pesticides and their metabolites in human biological matrices and the resultant health effects as measured by DNA damage, acetylcholinesterase (AChE) activity inhibition and other biomarkers of pesticides exposure.

Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.

BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015. METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values ≤10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value ≤5%. All patients' notes were kept confidential as per the Helsinki declaration. RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/µl). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p < 0.009). Increased age, above 35 years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p < 0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p < 0.010). CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.

Genomic characterization of methicillin-resistant Staphylococcus aureus isolated from patients attending regional referral hospitals in Tanzania.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of subsequent infection by MRSA strain complex interlinking between hospital and community-acquired MRSA which increases the chance of drug resistance and severity of the disease. OBJECTIVE: Genomic characterization of Staphylococcus aures strains isolated from patients attending regional referral hospitals in Tanzania. METHODOLOGY: A laboratory-based cross-sectional study using short read-based sequencing technology, (Nextseq550,Illumina, Inc. San diego, California, USA). The samples used were collected from patients attending selected regional referral hospitals in Tanzania under the SeqAfrica project. Sequences were analyzed using tools available in the center for genomic and epidemiology server, and visualization of the phylogenetic tree was performed in ITOL 6.0. SPSS 28.0 was used for statistical analysis. RESULTS: Among 103 sequences of S. aureus, 48.5% (50/103) carry the mecA gene for MRSA. High proportions of MRSA were observed among participants aged between 18 and 34 years (52.4%), in females (54.3%), and among outpatients (60.5%). The majority of observed MRSA carried plasmids rep5a (92.0%), rep16 (90.0%), rep7c (90.0%), rep15 (82.0%), rep19 (80.0%) and rep10 (72.0%). Among all plasmids observed rep5a, rep16, rep20, and repUS70 carried the blaZ gene, rep10 carried the erm(C) gene and rep7a carried the tet(K) gene. MLST and phylogeny analysis reveal high diversity among MRSA. Six different clones were observed circulating at selected regional hospitals and MRSA with ST8 was dominant. CONCLUSION: The study reveals a significant presence of MRSA in Staphylococcus aureus strains from Tanzanian regional hospitals, with nearly half carrying the mecA gene. MRSA is notably prevalent among young adults, females, and outpatients, showing high genetic diversity and dominance of ST8. Various plasmids carrying resistance genes indicate a complex resistance profile, highlighting the need for targeted interventions to manage MRSA infections in Tanzania.

Digital Technologies to Enhance Infectious Disease Surveillance in Tanzania: A Scoping Review.

Mobile phones and computer-based applications can speed up disease outbreak detection and control. Hence, it is not surprising that stakeholders in the health sector are becoming more interested in funding these technologies in Tanzania, Africa, where outbreaks occur frequently. The objective of this situational review is, therefore, to summarize available literature on the application of mobile phones and computer-based technologies for infectious disease surveillance in Tanzania and to inform on existing gaps. Four databases were searched-Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (Embase), PubMed, and Scopus-yielding a total of 145 publications. In addition, 26 publications were obtained from the Google search engine. Inclusion and exclusion criteria were met by 35 papers: they described mobile phone-based and computer-based systems designed for infectious disease surveillance in Tanzania, were published in English between 2012 and 2022, and had full texts that could be read online. The publications discussed 13 technologies, of which 8 were for community-based surveillance, 2 were for facility-based surveillance, and 3 combined both forms of surveillance. Most of them were designed for reporting purposes and lacked interoperability features. While undoubtedly useful, the stand-alone character limits their impact on public health surveillance.

Health professionals' knowledge on dengue and health facility preparedness for case detection: A cross-sectional study in Dar es Salaam, Tanzania.

Dengue presents a growing public health concern in the Dar es Salaam region of Tanzania, marked by the recurring incidence of outbreaks. Unfortunately, there is little information available on the region's preparedness in terms of health care workers' knowledge on dengue as well as the availability of reagents and equipment essential for diagnosing and monitoring of dengue infections. To elucidate this, 78 health facilities were visited in Temeke district and structured questionnaires were distributed to 324 health care workers. The aim was to evaluate health care workers' knowledge on dengue and to assess the availability of reagents and equipment essential for diagnosing and monitoring of dengue infections. Content validity of the questionnaire was achieved through extensive literature review and it exhibited high reliability (Cronbach Alpha coefficient = 0.813). Cumulative scores for responses on knowledge questions by health care workers were computed. Characteristics such as level of education, place of work and gender were tested for association with these scores using chi-square tests and logistics regression. Almost all health care workers (99.7%) were aware of dengue disease. However, less than half (46.9%) had knowledge scores of or over 40%. Clinicians had approximately four times higher knowledge scores than other cadres (AOR, 3.637; p-value≤ 0.0001), and those who worked in private facilities had twice the knowledge score than those working in government institutions (AOR, 2.071; p-value = 0.007). Only 8.6%, 35.6% and 14.7% of respondents reported the availability of dengue rapid tests, medical guidelines and refresher training respectively, showing a lack of health facilities readiness for the detection of dengue infections. Based on findings from this study, we recommend government authorities to build capacity of health care workers, to improve their understanding of dengue. We also urge the government and stakeholders to work together to ensure availability of diagnostic tests and other tools needed for diagnosis and surveillance of dengue.

Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients-A Systematic Review.

Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH) neutralizes ROS, although it is consumed. NAC is a precursor of GSH synthesis, and administering an appropriate dose of NAC to patients with respiratory conditions may enhance lung recovery and replenish GSH. The present review searched for articles reporting on the effects of NAC in TB treatment from 1960 to 31 May 2022. The PICO search strategy was used in Google Scholar, PubMed, SciFinder, and Wiley online library databases. The COVIDENCE tool was used to delete inappropriate content. We eventually discovered five clinical trials, one case report, seven reviews, in vitro research, and four experimental animal studies from the twenty-four accepted articles. The use of NAC resulted in increased GSH levels, decreased treatment time, and was safe with minimal adverse events. However, the evidence is currently insufficient to estimate the overall effects of NAC, thus the study warrants more NAC clinical trials to demonstrate its effects in TB treatment.

Plasmid characterization in bacterial isolates of public health relevance in a tertiary healthcare facility in Kilimanjaro region, Tanzania.

OBJECTIVES: 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.

Whole genome sequencing-based drug resistance predictions of multidrug-resistant Mycobacterium tuberculosis isolates from Tanzania.

Background: 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 patients 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) correlated 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.

Development and Validation of a Mobile Game for Culturally Sensitive Child Sexual Abuse Prevention Education in Tanzania: Mixed Methods Study.

BACKGROUND: Globally, 3 out of 20 children experience sexual abuse before the age of 18 years. Educating children about sexual abuse and prevention is an evidence-based strategy that is recommended for ending child sexual abuse. Digital games are increasingly being used to influence healthy behaviors in children and could be an efficient and friendly approach to educating children about sexual abuse prevention. However, little is known on the best way to develop a culturally sensitive game that targets children in Africa-where sexual education is still taboo-that would be engaging, effective, and acceptable to parents and caretakers. OBJECTIVE: This study aimed to develop a socioculturally appropriate, mobile-based game for educating young children (<5 years) and parents and caretakers in Tanzania on sexual abuse prevention. METHODS:  HappyToto children's game was co-designed with 111 parents and caretakers (females: n=58, 52.3%; male: n=53, 47.7%) of children below 18 years of age and 24 child experts in Tanzania through surveys and focus group discussions conducted from March 2020 to April 2020. From these, we derived an overview of topics, sociocultural practices, social environment, and game interface designs that should be considered when designing child sexual abuse prevention (CSAP) education interventions. We also conducted paper prototyping and storyboarding sessions for the game's interface, storylines, and options. To validate the application's prototype, 32 parents (females: n=18, 56%; males: n=14, 44%) of children aged 3-5 years and 5 children (females: n=2, 40%; males: n=3, 60%) of the same age group played the game for half an hour on average. The parents undertook a pre-post intervention assessment on confidence and ability to engage in CSAP education conversations, as well as exit surveys on the usability and sociocultural acceptability of the game, while children were quizzed on the topics covered and their enjoyment of the game. RESULTS: Parents and caregivers showed interest in the developed game during the conducted surveys, and each parent on average navigated through all the parts of the game. The confidence level of parents in talking about CSAP increased from an average of 3.56 (neutral) before using the game to 4.9 (confident) after using the game. The ability scores, calculated based on a range of topics included in CSAP education talks with children, also increased from 5.67 (out of 10) to 8.8 (out of 10) after the game was played. Both confidence level and ability scores were statistically significant (P<.001). All 5 children were interested in the game and enjoyed the game-provided activities. CONCLUSIONS: The HappyToto game can thus be an effective technology-based intervention for improving the knowledge and skills of parents and children in CSAP education.

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania.

INTRODUCTION: Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. METHODS: This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. RESULTS: A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). CONCLUSION: Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.

Co-exposure risks of pesticides residues and bacterial contamination in fresh fruits and vegetables under smallholder horticultural production systems in Tanzania.

This study was carried out to investigate the risks of simultaneous exposure to pesticide residues and bacteria contaminants in locally produced fresh vegetables and vegetables in Tanzania. A total of 613 samples were analyzed for pesticide residues, out of which 250 were also analyzed for bacterial contamination. Overall, 47.5% had pesticide residues, 74.2% exceeded Maximum Residue Levels (MRLs). Organophosphorus (95.2%), organochlorines (24.0%), pyrethroids (17.3%), and carbamates (9.2%) residues dominated. MRL values were mostly exceeded in tomatoes, onions, watermelons, cucumbers, Chinese cabbage, and sweet paper. Tetramethrin (0.0329-1.3733 mg/kg), pirimiphos-methyl (0.0003-1.4093 mg/kg), permethrin (0.0009-2.4537 mg/kg), endosulfan (beta) (0.0008-2.3416 mg/kg), carbaryl (0.0215-1.5068 mg/kg), profenofos (0.0176-2.1377 mg/kg), chlorpyrifos (0.0004-1.2549 mg/kg) and dieldrin (0.0011-0.5271 mg/kg) exceeded MRLs. The prevalence of bacteria contamination was high (63.2%). Enterobacter (55.6%) Pseudomonas aeruginosa (32.4%), E. coli (28.2%), Citrobacter (26.8%), Klebsiella oxytoca (14.8%), and Salmonella (7.7%) were isolated. Furthermore, 46.4% tested positive for both pesticide residues and bacterial contaminants. Vegetables from farms (60.7%) contained more dual contaminants than market-based vegetables (41.8%). This may have resulted from excessive pesticide use and unhygienic handling of fresh fruits and vegetables at production level. Binary logistic regression showed that fresh fruits and vegetables with pesticide residues were 2.231 times more likely to have bacteria contaminants (OR: 2.231; 95% CI: 0.501, 8.802). The contamination levels of pesticide residues and bacterial contaminants could be perceived as a serious problem as most fresh fruits and vegetables recorded values of pesticide residues far above the MRLs with pathogenic bacteria isolated in higher proportions. MRLs was higher in most vegetables consumed raw or semi-cooked such as watermelons, carrots, cucumber, tomatoes, onion and sweet paper. There is an urgent need to develop pesticide monitoring and surveillance systems at farmer level, educating farmers and promoting the use of greener pesticides to mitigate the health effects of pesticides and bacterial contaminants.

The neuroimaging magnitude of pediatric brain atrophy in northern Tanzania.

INTRODUCTION: The loss of parenchymal brain volume per normative age comparison is a distinctive feature of brain atrophy. While the condition is the most prevalent to elderly, it has also been observed in pediatric ages. Various causes such as trauma, infection, and malnutrition have been reported to trigger the loss of brain tissues volume. Despite this literature based knowledge of risk factors, the magnitude of brain atrophy in pediatric age group is scantly addressed in most developing countries including Tanzania. The current study aims to understand the magnitude of brain atrophy in children residing in Northern Zone, Tanzania. METHODS: A cross-sectional hospital survey was performed in which 455 children who were presented with various brain pathologies from the year 2013 to 2019 and whose brains examined by Computerized tomography (CT)-Scanners were recruited in the study. The brain statuses were examined using three linear radiological methods including the measure of sulcal-width, Evans index, and lateral ventricular body width. RESULTS: Results showed a significant number of atrophied brains among children in Northern Tanzania and that the condition was observed to have a 1:1 male to female ratio. The prevalence of pediatric brain atrophy was found to be 16.04%. CONCLUSION: The cortical subtype of brain atrophy presented as the most prevalent type of brain volume loss. The findings of this study suggest existence of considerable trends of brain atrophy in children which need special attention and mitigation plans.

Insulin-delivery methods for children and adolescents with type 1 diabetes.

Efforts directed toward restoring normal metabolic levels by mimicking the physiological insulin secretion, thereby ensuring safety, efficacy, minimal invasiveness and conveniences, are of great significance in the management of type 1 diabetes among children and adolescents. Regardless of the various technologies being discovered in addressing invasiveness and enhancing medication adherence in the management of type 1 diabetes, yet limited success had been observed among children and adolescents. The multiple daily subcutaneous insulin injections route using vial and syringe, and occasionally insulin pens, remain the most predictable route for insulin administration among children and adolescents. However, this route has been associated with compromised patient compliance, fear of injections and unacceptability, resulting in poor glycemic control, which promote the demand for alternative routes of insulin administration. Alternative routes for delivering insulin are being investigated in children and adolescents with type 1 diabetes; these include the hybrid closed-loop 'artificial pancreas' system, oral, inhalation, intranasal routes, and others. This review article explores the current advances in insulin-delivery methods that address the needs of children and adolescents in the treatment of type 1 diabetes.

Biomonitoring of Acetylcholinesterase (AChE) Activity among Smallholder Horticultural Farmers Occupationally Exposed to Mixtures of Pesticides in Tanzania.

Biomonitoring of pesticides exposure has currently become a matter of great public concern due to the potential health effects of pesticides. This study assessed levels of acetylcholinesterase (AChE) inhibition and associated health effects in uncontrolled smallholder farming systems in rural Tanzania. A cross-sectional study was conducted of 90 exposed farmers and 61 nonexposed controls from horticultural zones. A structured questionnaire was administered, and a capillary blood sample of 10 µl was used to measure AChE activity using an Erythrocyte Acetylcholinesterase Test Mate Photometric Analyzer kit (Model 400). A multiple logistic regression model was used to investigate determinants of pesticide exposure. The study revealed that smallholder farmers are occupationally exposed to pesticides. Exposed farmers had significantly lower AChE levels. The use of personal protective equipment (PPE) did not significantly reduce the likelihood of AChE inhibition. Women, younger and older farmers, and underweight, overweight, and obese farmers were at increased risk of AChE inhibition. Increase in age (10 years) increased likelihood of AChE inhibition by 6.7%, while decrease in BMI increased likelihood of AChE inhibition by 86.7% while increased pesticides contact hours increased risk of having lower AChE at about 3 times. The number of exposure symptoms (14.10 ± 7.70) was higher in exposed farmers than unexposed. Self-reported symptoms are confirmed to correlate to lower AChE. Prevalence of tiredness (71.6% against 15.5%), fatigue (64.8% against 27.6%), soreness in joints (59.1% against 20.7%), thirst (52.3% against 12.1%), skin irritation (52.1% against 17.2%), salivation and abdominal pain (50% against 8.6% and 31.0%, respectively), muscle weakness (47.7% against 24.1%), and memory loss (47.7% against and 29.3%) differed significantly between exposed and control. This study provides useful information regarding the level of occupational and environmental exposure to pesticides in smallholder horticultural production systems. Pesticides use needs to be controlled at farm level by developing pesticides monitoring and surveillance systems.

Blood cytokine responses to early secreted protein antigen-6/culture filtrate protein-10 tuberculosis antigens 2 months after antituberculosis treatment among patients with drug-susceptible pulmonary tuberculosis.

BACKGROUND: Human tuberculosis is a chronic inflammatory disease caused by mycobacterium tuberculosis. Pulmonary tuberculosis is the result of the failure of host immune system to control mycobacterium tuberculosis. The aim of the study was to asses the changes of the cytokines in active pulmonary tuberculosis patients before and after the use of anti-TB therapy. METHODS: Multiple cytokine responses in active tuberculosis (TB) patients were investigated in this study following anti-TB drug therapy after 2 months. Ninety-six participants with pulmonary TB were engaged in the study between May 2018 and October 2018. Samples of blood were taken early before treatment at 0 and 2 months after using anti-TB therapy. The levels of interferon-gamma (IFN)-γ, interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor (TNF)-α in whole blood plasma collected from the QuantiFERON-TB Gold Plus were measured. RESULTS: Compared with baseline levels, TNF-α, IL6 and IL10 were significantly lower following treatment whereas the IFN-γ and IL-4 increased significantly after treatment. The responses of five cytokines varied significantly after treatment (P < 0.0001) where IFN-γ was highest compared to other cytokines with 123.6%, AUC=0.757 and P < 0001, TNF-α AUC: 0.529 and P = 0.743, IL-4 AUC:0.557 and P = 0.514, IL-6 AUC:0.629 and P = 0.047, IL-10 AUC:0.549 and P = 0.581. CONCLUSION: It is concluded that changes of cytokines that observed during the treatment of TB patients play a very important role in monitoring pulmonary TB and can be suitable biomarkers to assess the effectiveness of anti-TB therapy in patients with TB.

Ki-67, p53 and BCL-2 Expressions and their Association with Clinical Histopathology of Breast Cancer among Women in Tanzania.

This study associated Ki-67, p53, and BCL-2 markers with clinical histopathological (CH) features using currently available limited data on these markers in Tanzania. Retrospective chart review study was conducted among females with confirmed breast cancer (BC) at Muhimbili National Hospital in Tanzania between 2016 and 2017. Inclusion criteria were met by 76 patients with a mean age of 51.32 ± 14.28 years. Of these, 86.4% were stage III and IV, whereas 83.5% cases had grade 2 and grade 3. Upon immunostaining, 85.5% and 57.9% were Ki-67 and BCL-2 positive respectively. Log-linear analysis showed no statistically significant association among biomarkers expression and CH features. However, multinomial linear regression showed higher possibility for association between high expression of Ki-67, low expression of p53 and high expression of BCL-2 with age, grade, stage and tumor (T) stage. BCL-2 was positively correlated with Ki-67 expression contrary to p53, which was negatively correlated with BCL-2. Conclusively, there is evidence of correlation between the studied markers with CH features. However, studies with larger sample sizes will likely reveal significant associations that will validate the role of these markers as tools for evaluating treatment response in individualized therapeutic schemes in Tanzania.