HIV viral suppression and risk of viral rebound in patients on antiretroviral therapy: a two- year retrospective cohort study in Northern Tanzania.

BACKGROUND: The world is moving towards the third target of the Joint United Nations Programme on HIV/AIDS to ensure most people receiving antiretroviral therapy (ART) are virologically suppressed. Little is known about viral suppression at an undetectable level and the risk of viral rebound phenomenon in sub-Saharan Africa which covers 67% of the global HIV burden.This study aimed to investigate the proportion of viral suppression at an undetectable level and the risk of viral rebound among people living with HIV receiving ART in northern Tanzania. METHODOLOGY: A hospital based-retrospective study recruited people living with HIV who were on ART for at least two years at Kibong'oto Infectious Disease Hospital and Mawenzi Regional Referral Hospital in Kilimanjaro Region, Tanzania. Participants' two-year plasma HIV were captured at months 6, 12, and 24 of ART. Undetectable viral load was defined by plasma HIV of viral load (VL) less than 20copies/ml and viral rebound (VR) was considered to anyone having VL of more than 50 copies/ml after having history of undetectable level of the VL less than 20copies/ml. A multivariable log-binomial generalized linear model was used to determine factors for undetectable VL and viral VR. RESULTS: Among 416 PLHIV recruited, 226 (54.3%) were female. The mean (standard deviation) age was 43.7 (13.3) years. The overall proportion of undetectable VL was 68% (95% CI: 63.3-72.3) and 40.0% had viral rebound (95% CI: 34.7-45.6). Participants who had at least 3 clinic visits were 1.3 times more likely to have undetectable VL compared to those who had 1 to 2 clinic visits in a year (p = 0.029). Similarly, participants with many clinical visits ( > = 3 visits) per year were less likely to have VR compared to those with fewer visits ( = 2 visits) [adjusted relative risk (aRR) = 0.64; 95% CI: 0.44-0.93]. CONCLUSION: Participants who had fewer clinic visits per year(ART refills) were less likely to achieve viral suppression and more likely to experience viral rebound. Enhanced health education and close follow-up of PLHIV on antiretroviral therapy are crucial to reinforce adherence and maintain an undetectable viral load.

Effectiveness of Point of Entry Health Screening Measures among Travelers in the Detection and Containment of the International Spread of COVID-19: A Review of the Evidence.

COVID-19 remains a communicable disease with the capacity to cause substantial damage to health and health systems. Enhanced health screening at points of entry (POEs) is a public health measure implemented to support early detection, prevention and response to communicable diseases, such as COVID-19. The purpose of this study was to review the available evidence on the effectiveness of POE health screening in the detection and containment of the COVID-19 pandemic. This study was registered under PROSPERO and followed PRISMA guidelines in which the literature between 2019 and 2022 was retrieved from Scopus, PubMed, Web of Science, Global Health, CINAHL, Embase, Google Scholar and international organizations. A total of 33,744 articles were screened for eligibility, from which 43 met the inclusion criteria. The modeling studies predicted POE screening able to detect COVID-19 in a range of 8.8% to 99.6%, while observational studies indicated a detection rate of 2% to 77.9%, including variants of concern depending on the screening method employed. The literature also indicated these measures can delay onset of the epidemic by 7 to 32 days. Based on our review findings, if POE screening measures are implemented in combination with other public health interventions such as rapid tests, they may help detect and reduce the spread of COVID-19.

Correlating food and nutritional patterns with cancers in the pediatric oncology population at two specialized hospitals in Tanzania.

BACKGROUND: This study of nutritional patterns in relation to cancers among pediatric oncology population in Tanzania was motivated by the lack of up-to-date information about the nutritional practices, the controversy around the importance of nutritional support and the lack of consistent nutritional criteria among pediatric oncology populations. METHODS: A survey study in two cancer referral hospitals of children diagnosed with any cancers, aged between 1 and 17 years inclusive and being eligible for enteral feeding included 131 children. Their demographic, nutritional, feeding and cancer profiles were analyzed descriptively through mapping and other approaches as well as inferentially using multinomial regression models to understand different aspects of nutrition for children suffering from cancers. RESULTS: The majority (15% or higher) of pediatric oncology population originated from the lake zone. Between 7 and 12% of pediatric oncology population originated from the Western zone. The top-three cancers with their percentages in the brackets were: Wilms Tumor (32%), Acute Lymphoblastic Leukemia (26%) and Retinoblastoma (13%). About 69% of the pediatric oncology population ate foods that are rich in energy but poor in protein such as rice (21.5%), porridge (19.3%), banana (11.7%) and potatoes (10.2%). On the other hand, only 17.5% ate foods that are generally protein-rich such as meat (8.0%), fish (5.3%) and chicken (4.2%); and 12.7% ate milk (4.2%), beans (3.4%), vegetables (2.7%), eggs (1.9%) and fruits (1.5%). Cancers impacted food intake in about 60% of all children with cancers and affected appetite in 18.3% of them. Cancers caused vomiting in 16% and diarrhea in 6.1% of children. The majority of children with cancers (61.8%) took at least one meal while 34.4% took just snacks (p < 0.001). CONCLUSIONS: The majority of pediatric oncology population had erratic nutritional patterns and took foods high in energy and poor in proteins. There is a two-way interaction between cancers and nutrition in which cancers affect general nutritional intake which could affect the cancer treatment outcomes in return. Therefore, it is important to consider these interactions while managing pediatric oncology populations in this and similar settings.

Integrating a community-based continuous mass dog vaccination delivery strategy into the veterinary system of Tanzania: A process evaluation using normalization process theory.

Abstract: Sustained vaccination coverage of domestic dog populations can interrupt rabies transmission. However, challenges remain including low dog owner participation, high operational costs associated with current (centralized and annually delivered (pulse)) approaches and high dog population turnover. To address these challenges an alternative (community-based continuous mass dog vaccination (CBC-MDV)) approach was designed. We investigated the potential for successful normalization of CBC-MDV into routine practice within the context of local communities and the veterinary system of Tanzania. Methods: In a process evaluation of a pilot implementation of CBC-MDV, we conducted in-depth interviews with implementers and community leaders (n = 24), focus group discussion with implementers and community members (n = 12), and non-participant observation (n = 157 h) of delivery of the intervention components. We analyzed these data thematically drawing on the normalization process theory, to assess factors affecting implementation and integration. Main findings: Implementers and community members clearly understood the values and benefits of the CBC-MDV, regarding it as an improvement over the pulse strategy. They had a clear understanding of what was required to enact CBC-MDV and considered their own involvement to be legitimate. The approach fitted well into routine schedules of implementers and the context (infrastructure, skill sets and policy). Implementers and community members positively appraised CBC-MDV in terms of its perceived impact on rabies and recommended its use across the country. Implementers and community members further believed that vaccinating dogs free of charge was critical and made community mobilization easier. However, providing feedback to communities and involving them in evaluating outcomes of vaccination campaigns were reported to have not been done. Local politics was cited as a barrier to collaboration between implementers and community leaders. Conclusion: This work suggests that CBC-MDV has the potential to be integrated and sustained in the context of Tanzania. Involving communities in design, delivery and monitoring of CBC-MDV activities could contribute to improving and sustaining its outcomes.

Prevalence and risk factors of brain atrophy and associated confusion state among adults from three hospitals in northern Tanzania.

Introduction: brain atrophy is the reduction of brain volume often accompanied with cognitive changes. Despite the availability of computerized-tomography (CT) scanners in Tanzania, little is known about the magnitude of brain atrophy, its associated confusion state and the risk factors in adults. This study aimed to fill those knowledge gaps. Methods: a retrospective cross-sectional hospital-based survey was conducted in northern Tanzania using a sample size of 384 CT images of adults who underwent brain CT scans in three referral hospitals. CT images were evaluated using a diagonal brain fraction (DBF) method to determine the presence of brain atrophy. Data for other covariates were also collected. Results: we report a prevalence of 60.67% for brain atrophy and 35% for the associated confusion state. Association between confusion state and brain atrophy was statistically significant (χ2 = 21.954, p<0.001). Brain atrophy was prognosticated by: age (adjusted OR: 1.11; 95% CI [1.05, 1.20], p<0.001), smoking (adjusted OR: 6.97; 95% CI [2.12, 26.19], p<0.001), alcohol-consumption (adjusted OR: 11.87; 95% CI [3.44, 40.81], p<0.001), hypertension (adjusted OR: 61.21; 95 CI [15.20, 349.43], p<0.001), type-2 diabetes mellitus (adjusted OR: 15.67; 95% CI [5.32, 52.77], p<0.001) and white matter demyelination (adjusted OR: 13.45; 95% CI [4.66, 44.25], p<0.001). Conclusion: there is high prevalence of brain atrophy and associated confusion state among hospitalized adults in northern Tanzania. Reported prognostic factors for brain atrophy such as age, smoking, alcohol consumption, hypertension, type-2 diabetes mellitus and white matter demyelination could help focus interventions in this area.

Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: An observational and genomic study.

Background: Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle. Methods: We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon. Results: We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island. Conclusions: A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere. Funding: Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa's Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421.

A case-control study on the driving factors of childhood brain volume loss: What pediatricians must explore.

BACKGROUND: The brain volume loss also known as brain atrophy is increasingly observed among children in the course of performing neuroimaging using CT scan and MRI brains. While severe forms of brain volume loss are frequently associated with neurocognitive changes due to effects on thought processing speed, reasoning and memory of children that eventually alter their general personality, most clinicians embark themselves in managing the neurological manifestations of brain atrophy in childhood and less is known regarding the offending factors responsible for developing pre-senile brain atrophy. It was therefore the goal of this study to explore the factors that drive the occurrence of childhood brain volume under the guidance of brain CT scan quantitative evaluation. METHODS: This study was a case-control study involving 168 subjects with brain atrophy who were compared with 168 age and gender matched control subjects with normal brains on CT scan under the age of 18 years. All the children with brain CT scan were subjected to an intense review of their birth and medical history including laboratory investigation reports. RESULTS: Results showed significant and influential risk factors for brain atrophy in varying trends among children including age between 14-17(OR = 1.1), male gender (OR = 1.9), birth outside facility (OR = 0.99), immaturity (OR = 1.04), malnutrition (OR = 0.97), head trauma (OR = 1.02), maternal alcoholism (OR = 1.0), antiepileptic drugs & convulsive disorders (OR = 1.0), radiation injury (OR = 1.06), space occupying lesions and ICP (OR = 1.01) and birth injury/asphyxia (OR = 1.02). CONCLUSIONS: Pathological reduction of brain volume in childhood exhibits a steady trend with the increase in pediatric age, with space occupying lesions & intracranial pressure being the most profound causes of brain atrophy.

Participatory development of practical, affordable, insecticide-treated mosquito proofing for a range of housing designs in rural southern Tanzania.

BACKGROUND: Insecticidal mosquito-proof netting screens could combine the best features of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), the two most important front line vector control interventions in Africa today, and also overcome the most important limitations of these methods. This study engaged members of a rural Tanzanian community in developing and evaluating simple, affordable and scalable procedures for installing readily available screening materials on eave gaps and windows of their own houses, and then treating those screens with a widely used IRS formulation of the organophosphate insecticide pirimiphos-methyl (PM). METHODS: A cohort of 54 households recruited upon consent, following which the structural features and occupant demographics of their houses were surveyed. Indoor mosquito densities were surveyed longitudinally, for approximately 3 months before and over 5 months after participatory house modification and screening using locally available materials. Each house was randomly assigned to one of three study arms: (1) No screens installed until the end of the study (negative control), (2) untreated screens installed, and (3) screened installed and then treated with PM, the insecticidal activity of which was subsequently assessed using standard cone assays. RESULTS: Almost all (52) recruited households participated until the end, at which point all houses had been successfully screened. In most cases, screening was only installed after making enabling structural modifications that were accepted by the enrolled households. Compared to unscreened houses, houses with either treated or untreated screens both almost entirely excluded Anopheles arabiensis (Relative reduction (RR) ≥ 98%, P < < 0.0001), the most abundant local malaria vector. However, screens were far less effective against Culex quinquefasciatus (RR ≤ 46%, P < < 0.0001), a non-malaria vector causing considerable biting nuisance, regardless of their treatment status. While PM did not augment household level protection by screens against either mosquito species (P = 0.676 and 0.831, respectively), 8 months after treatment it still caused 73% and 89% mortality among susceptible insectary-reared Anopheles gambiae following exposures of 3 and 30 min, respectively. CONCLUSIONS: Participatory approaches to mosquito proofing houses may be acceptable and effective, and installed screens may be suitable targets for residual insecticide treatments.

Participation in mass dog vaccination campaigns in Tanzania: Benefits of community engagement.

Background: Canine rabies causes about 59,000 human deaths each year globally but the disease can be eliminated by sustaining sufficient dog vaccination coverage over several consecutive years. A challenge to achieving high coverage is low participation of dog owners in vaccination campaigns. We explored whether and how previously identified contributory factors to low participation can be addressed through community engagement activities. Methods: We engaged communities in two wards in Tanzania on dog behavior and handling, safe ways of interacting with dogs, and their perceptions of dog vaccination. We shared and elicited information from them through village meetings, video screenings, posters and leaflets and involved the leadership of one of the wards in planning and implementing a dog vaccination exercise to explore the feasibility of their participation. We assessed the impact of engagement activities with household surveys, meeting reports, observations and focus group discussions. We used a generalized linear mixed-effects model to identify predictors of knowledge and perceptions and compared knowledge amongst respondents before and after engagement activities. Qualitative data was analyzed inductively to explore perceptions of dog handling and vaccination and feasibility, opportunities and barriers to community leadership participation in organizing mass dog vaccination. Main findings: Knowledge of dog behavior, dog handling, and safe ways of interacting with dogs was positively associated with age (p < 0.0001), dog ownership (p = 0.0203), training (p = 0.0010) and previous experience of a dog bite (p = 0.0002); and was negatively associated with being afraid of dogs (p = 0.0061) and participation in a recent dog vaccination campaign (p = 0.0077). Knowledge was low before and significantly improved after engagement activities. The majority (92%) of respondents believed dog vaccination has no negative effects on dogs. Respondents perceived lack of bonding with their dog as a limitation to the ability to restrain a dog for vaccination. The community performed most roles assigned to them in the dog vaccination exercise, but barriers such as lack of motivation for volunteering exist. Conclusion: Engaging communities regularly on dog vaccination can improve their knowledge of dog behavior and dog handling techniques, and may help improve owner participation in dog vaccination campaigns.

Development, feasibility and potential effectiveness of community-based continuous mass dog vaccination delivery strategies: Lessons for optimization and replication.

OBJECTIVES: Dog vaccination can eliminate rabies in dogs, but annual delivery strategies do not sustain vaccination coverage between campaigns. We describe the development of a community-based continuous mass dog vaccination (CBC-MDV) approach designed to improve and maintain vaccination coverage in Tanzania and examine the feasibility of delivering this approach as well as lessons for its optimization. METHODS: We developed three delivery strategies of CBC-MDV and tested them against the current annual vaccination strategy following the UK Medical Research Council's guidance: i) developing an evidence-based theoretical framework of intervention pathways and ii) piloting to test feasibility and inform optimization. For our process evaluation of CBC-MDV we collected data using non-participant observations, meeting reports and implementation audits and in-depth interviews, as well as household surveys of vaccination coverage to assess potential effectiveness. We analyzed qualitative data thematically and quantitative data descriptively. RESULTS: The final design included delivery by veterinary teams supported by village-level one health champions. In terms of feasibility, we found that less than half of CBC-MDV's components were implemented as planned. Fidelity of delivery was influenced by the strategy design, implementer availability and appreciation of value intervention components, and local environmental and socioeconomic events (e.g. elections, funerals, school cycles). CBC-MDV activities decreased sharply after initial campaigns, partly due to lack of supervision. Community engagement and involvement was not strong. Nonetheless, the CBC-MDV approaches achieved vaccination coverage above the critical threshold (40%) all-year-round. CBC-MDV components such as identifying vaccinated dogs, which village members work as one health champions and how provision of continuous vaccination is implemented need further optimization prior to scale up. INTERPRETATION: CBC-MDV is feasible to deliver and can achieve good vaccination coverage. Community involvement in the development of CBC-MDV, to better tailor components to contextual situations, and improved supervision of activities are likely to improve vaccination coverage in future.

Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania.

OBJECTIVE: Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. METHODS: A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. RESULTS: Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p > 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p = 0.870), respectively. Age ≥ 40 years (p = 0.038), bacteriological positive (p = 0.039), HIV (p = 0.009), or recurrent TB (p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. CONCLUSION: IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.

Prevalence and Predictors of Antibiotic Prescriptions at Primary Healthcare Facilities in the Dodoma Region, Central Tanzania: A Retrospective, Cross-Sectional Study.

Background: Accelerated by the misuse or overuse of antibiotics, antibiotic resistance remains a global public health threat. We report the prevalence and predictors of antibiotic prescriptions in primary healthcare facilities in Dodoma, Tanzania. Methods: This retrospective cross-sectional study by medical records review was conducted in the Dodoma region, Central Tanzania. Results: In this study, children < 5 years accounted for over 45% (474/1021) of the patients consulted. The majority, 76.3% (779/1021), of consultations had an antibiotic prescribed; amoxicillin and cotrimoxazole were the most prescribed. Over 98% (766/779) of the antibiotics prescribed were on the National Essential Medicines List, but only 45% (429/779) of the antibiotic prescriptions adhered to the Standard Treatment Guidelines. The prescribing of antibiotics by clinical officers was almost 2.55 times higher than that among medical doctors (Odds Ratio (OR) = 2.546; 95% Confidence Interval (CI): 1.359, 4.769; p = 0.0035). Patients with pneumonia and upper respiratory tract infection were 15.9 (OR = 15.928; 95% CI: 2.151, 17.973; p = 0.0067) and 2 (OR = 2.064; 95% CI: 1.184, 3.600; p = 0.0106) times more likely to be prescribed antibiotics, respectively. Conclusions: We, therefore, report high rates of antibiotic prescriptions, poor adherence to standard treatment guidelines and high levels of antibiotic prescribing practices among prescribers with a diploma in clinical medicine.

Comparison of cone bioassay estimates at two laboratories with different Anopheles mosquitoes for quality assurance of pyrethroid insecticide-treated nets.

BACKGROUND: Quality assurance (QA) of insecticide-treated nets (ITNs) delivered to malaria-endemic countries is conducted by measuring physiochemical parameters, but not bioefficacy against malaria mosquitoes. This study explored utility of cone bioassays for pre-delivery QA of pyrethroid ITNs to test the assumption that cone bioassays are consistent across locations, mosquito strains, and laboratories. METHODS: Double-blinded bioassays were conducted on twenty unused pyrethroid ITNs of 4 brands (100 nets, 5 subsamples per net) that had been delivered for mass distribution in Papua New Guinea (PNG) having passed predelivery inspections. Cone bioassays were performed on the same net pieces following World Health Organization (WHO) guidelines at the PNG Institute of Medical Research (PNGIMR) using pyrethroid susceptible Anopheles farauti sensu stricto (s.s.) and at Ifakara Health Institute (IHI), Tanzania using pyrethroid susceptible Anopheles gambiae s.s. Additionally, WHO tunnel tests were conducted at IHI on ITNs that did not meet cone bioefficacy thresholds. Results from IHI and PNGIMR were compared using Spearman's Rank correlation, Bland-Altman (BA) analysis and analysis of agreement. Literature review on the use of cone bioassays for unused pyrethroid ITNs testing was conducted. RESULTS: In cone bioassays, 13/20 nets (65%) at IHI and 8/20 (40%) at PNGIMR met WHO bioefficacy criteria. All nets met WHO bioefficacy criteria on combined cone/tunnel tests at IHI. Results from IHI and PNGIMR correlated on 60-min knockdown (KD60) (rs = 0.6,p = 0.002,n = 20) and 24-h mortality (M24) (rs = 0.9,p < 0.0001,n = 20) but BA showed systematic bias between the results. Of the 5 nets with discrepant result between IHI and PNGIMR, three had confidence intervals overlapping the 80% mortality threshold, with averages within 1-3% of the threshold. Including these as a pass, the agreement between the results to predict ITN failure was good with kappa = 0.79 (0.53-1.00) and 90% accuracy. CONCLUSIONS: Based on these study findings, the WHO cone bioassay is a reproducible bioassay for ITNs with > 80% M24, and for all ITNs provided inherent stochastic variation and systematic bias are accounted for. The literature review confirms that WHO cone bioassay bioefficacy criteria have been previously achieved by all pyrethroid ITNs (unwashed), without the need for additional tunnel tests. The 80% M24 threshold remains the most reliable indicator of pyrethroid ITN quality using pyrethroid susceptible mosquitoes. In the absence of alternative tests, cone bioassays could be used as part of pre-delivery QA.

Prevalence and predictors of self-medication with antibiotics in selected urban and rural districts of the Dodoma region, Central Tanzania: a cross-sectional study.

BACKGROUND: Antibiotic resistance is a global health threat driven partly by self-medication with antibiotics (SMA). This study aims to assess the prevalence and predictors of SMA in selected rural and urban communities of the Dodoma region, Central Tanzania. METHODS: This cross-sectional study was conducted in Chemba District Council (rural) and Dodoma City Council (urban) from August to November 2019 using multistage stratified random sampling. Data were collected through face-to-face interviews using structured questionnaires. RESULTS: A total of 430 respondents were interviewed in Chemba District Council (rural) (161/430) and Dodoma City Council (urban) (269/430). The prevalence of SMA was 23.6% (38/161) among rural respondents and 23.4% (63/269) among urban respondents. The median amount of SMA in both settings was 2, while the maximum amounts were 4 and 5, respectively. SMA among rural and urban participants was associated mostly with perceived cough (76.3%/82%), body pain (71.1%/41.5%) and fever (63.2%/39.7%), and amoxicillin was the most commonly used antibiotic in both settings (47.3%/41%). Rural participants who reported a shorter perceived distance to a health care facility than to a drug outlet were 58.9% less likely to practise SMA (adjusted OR: 0.421; 95% CI: 0.388, 0.458; p < 0.001), whereas SMA decreased by 16.3% among urban participants who reported a shorter perceived distance to a health care facility than to a drug outlet (adjusted OR: 0.837; 95% CI: 0.755, 0.929; p < 0.001). SMA was 17.3% lower among farmers than among nonfarmers in the urban area (adjusted OR: 0.827; 95% CI: 0.716, 0.955; p = 0.01), while farming had no effect in the rural area. CONCLUSIONS: The prevalence of SMA is similar among participants in rural and urban districts. In both localities, a shorter perceived distance to a drug outlet is an independent risk factor for SMA, while having health insurance reduces the risk. Equally weighted interventions to reduce SMA are required in rural and urban communities.

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.

Genomics of Adaptations in Ungulates.

Ungulates are a group of hoofed animals that have long interacted with humans as essential sources of food, labor, clothing, and transportation. These consist of domesticated, feral, and wild species raised in a wide range of habitats and biomes. Given the diverse and extreme environments inhabited by ungulates, unique adaptive traits are fundamental for fitness. The documentation of genes that underlie their genomic signatures of selection is crucial in this regard. The increasing availability of advanced sequencing technologies has seen the rapid growth of ungulate genomic resources, which offers an exceptional opportunity to understand their adaptive evolution. Here, we summarize the current knowledge on evolutionary genetic signatures underlying the adaptations of ungulates to different habitats.

Genome Scan for Variable Genes Involved in Environmental Adaptations of Nubian Ibex.

The Nubian ibex (Capra nubiana) is a wild goat species that inhabits the Sahara and Arabian deserts and is adapted to extreme ambient temperatures, intense solar radiation, and scarcity of food and water resources. To investigate desert adaptation, we explored the possible role of copy number variations (CNVs) in the evolution of Capra species with a specific focus on the environment of Capra nubiana. CNVs are structural genomic variations that have been implicated in phenotypic differences between species and could play a role in species adaptation. CNVs were inferred from Capra nubiana sequence data relative to the domestic goat reference genome using read-depth approach. We identified 191 CNVs overlapping with protein-coding genes mainly involved in biological processes such as innate immune response, xenobiotic metabolisms, and energy metabolisms. We found copy number variable genes involved in defense response to viral infections (Cluster of Differentiation 48, UL16 binding protein 3, Natural Killer Group 2D ligand 1-like, and Interferon-induced transmembrane protein 3), possibly suggesting their roles in Nubian ibex adaptations to viral infections. Additionally, we found copy number variable xenobiotic metabolism genes (carboxylesterase 1, Cytochrome P450 2D6, Glutathione S-transferase Mu 4, and UDP Glucuronosyltransferase-2B7), which are probably an adaptation of Nubian ibex to desert diets that are rich in plant secondary metabolites. Collectively, this study's results advance our understanding of CNVs and their possible roles in the adaptation of Nubian ibex to its environment. The copy number variable genes identified in Nubian ibex could be considered as subjects for further functional characterizations.

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.

Patterns of multimorbidity and their association with hospitalisation: a population-based study of older adults in urban Tanzania.

BACKGROUND: while the HIV epidemic remains a considerable challenge in sub-Saharan Africa, a dramatic reduction in the associated mortality has led to a fundamental shift in the public health priorities aimed at tackling multimorbidity. Against the unprecedented level of urbanisation taking place in Tanzania, the burden of multimorbidity and its consequences among ageing adults, in the form of costly inpatient hospitalisation, remain unquantified. METHODS: we used data from one of Africa's largest urban population cohort, the Dar es Salaam Health and the Demographic Surveillance System, to quantity the extent of multimorbidity (occurrence of 2 ≥ health conditions) and discordant multimorbidity (occurrence of conditions in 2 ≥ domains in mental health, non-communicable and communicable health) among 2,299 adults aged ≥40 years in Dar es Salaam, Tanzania. We fitted logistic regression models to investigate the association between multimorbidity and inpatient hospitalisation. RESULTS: the prevalence of multimorbidity and discordant multimorbidity were 25.3 and 2.5%, respectively. Although the severe forms of multimorbidity (2.0% with ≥4 health conditions) and discordancy were low, hospitalisation was significantly higher based on the regression analyses. Household food insecurity was the only socio-economic variable that was significantly and consistently associated with a greater hospitalisation. CONCLUSION: we found an alarmingly high degree of multimorbidity among this ageing urban population where hospitalisation was driven by multimorbidity. As public health resources remain scarce, reducing costly inpatient hospitalisation requires multilevel interventions that address clinical- and structural-level challenges (e.g. food insecurity) to mitigate multimorbidity and promote long-term healthy independent living among older adults in Tanzania.

Estimating the risk of aflatoxin-induced liver cancer in Tanzania based on biomarker data.

Evidence about the magnitude of the aflatoxin menace can help policy makers appreciate the importance of the problem and strengthen policies to support aflatoxin mitigation measures. In this study, we estimated aflatoxin-induced liver cancer risk in 2016 for Tanzania and used the information to estimate the health burden due to the aflatoxin exposure in the country. The burden of aflatoxin-induced liver cancer was assessed based on available aflatoxin biomarker data from a previous epidemiology study, hepatitis B virus infection prevalence and population size of Tanzania in 2016. The health burden due to aflatoxin-induced liver cancer was estimated using disability adjusted life years (DALYs). The aflatoxin exposures ranged from 15.0-10,926.0 ng/kg bw/day (median, 105.5 ng/kg bw/day). We estimated that in 2016 there were about 1,480 (2.95 per 100,000 persons) new cases of aflatoxin-induced liver cancer in Tanzania and assumed all of them would die within a year. These morbidity and mortality rates led to a total loss of about 56,247.63 DALYs. These results show, quantitatively, the cases of liver cancer and related deaths that could be avoided, and the healthy life years that could be saved, annually, by strengthening measures to control aflatoxin contamination in Tanzania.