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Abstract Introduction Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. Methods We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. Findings We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4–96.7); for Isoniazid, 96.6 (95% CI, 92.1–98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8–99.7); for Amikacin, 96.6%; and (95% CI 92.1–98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. Conclusion The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Abstract Introduction Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. Objective We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. Methods A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. Results The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. Conclusion The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.

Abstract Background The standard face-to-face training for the integrated management of childhood illness (IMCI) continues to be plagued by concerns of low coverage of trainees, the prolonged absence of trainees from the health facility to attend training and the high cost of training. Consequently, the distance learning IMCI training model is increasingly being promoted to address some of these challenges in resource-limited settings. This paper examines participants’ accounts of the paper-based IMCI distance learning training programme in three district councils in Mbeya region, Tanzania. Methods A cross-sectional qualitative descriptive design was employed as part of an endline evaluation study of the management of possible serious bacterial infection in Busokelo, Kyela and Mbarali district councils of Mbeya Region in Tanzania. Key informant interviews were conducted with purposefully selected policymakers, partners, programme managers and healthcare workers, including beneficiaries and training facilitators. Results About 60 key informant interviews were conducted, of which 53% of participants were healthcare workers, including nurses, clinicians and pharmacists, and 22% were healthcare administrators, including district medical officers, reproductive and child health coordinators and programme officers. The findings indicate that the distance learning IMCI training model (DIMCI) was designed to address concerns about the standard IMCI model by enhancing efficiency, increasing outputs and reducing training costs. DIMCI included a mix of brief face-to-face orientation sessions, several weeks of self-directed learning, group discussions and brief face-to-face review sessions with facilitators. The DIMCI course covered topics related to management of sick newborns, referral decisions and reporting with nurses and clinicians as the main beneficiaries of the training. The problems with DIMCI included technological challenges related to limited access to proper learning technology (e.g., computers) and unfriendly learning materials. Personal challenges included work-study-family demands, and design and coordination challenges, including low financial incentives, which contributed to participants defaulting, and limited mentorship and follow-up due to limited funding and transport. Conclusion DIMCI was implemented successfully in rural Tanzania. It facilitated the training of many healthcare workers at low cost and resulted in improved knowledge, competence and confidence among healthcare workers in managing sick newborns. However, technological, personal, and design and coordination challenges continue to face learners in rural areas; these will need to be addressed to maximize the success of DIMCI.

Abstract Background In nature and in cultivated fields, plants encounter multiple stress factors. Nonetheless, our understanding of how plants actively respond to combinatorial stress remains limited. Among the least studied stress combination is that of flooding and herbivory, despite the growing importance of these stressors in the context of climate change. We investigated plant chemistry and gene expression changes in two heirloom tomato varieties: Cherokee Purple (CP) and Striped German (SG) in response to flooding, herbivory by Spodoptera exigua, and their combination. Results Volatile organic compounds (VOCs) identified in tomato plants subjected to flooding and/or herbivory included several mono- and sesquiterpenes. Flooding was the main factor altering VOCs emission rates, and impacting plant biomass accumulation, while different varieties had quantitative differences in their VOC emissions. At the gene expression levels, there were 335 differentially expressed genes between the two tomato plant varieties, these included genes encoding for phenylalanine ammonia-lyase (PAL), cinnamoyl-CoA-reductase-like, and phytoene synthase (Psy1). Flooding and variety effects together influenced abscisic acid (ABA) signaling genes with the SG variety showing higher levels of ABA production and ABA-dependent signaling upon flooding. Flooding downregulated genes associated with cytokinin catabolism and general defense response and upregulated genes associated with ethylene biosynthesis, anthocyanin biosynthesis, and gibberellin biosynthesis. Combining flooding and herbivory induced the upregulation of genes including chalcone synthase (CHS), PAL, and genes encoding BAHD acyltransferase and UDP-glucose iridoid glucosyltransferase-like genes in one of the tomato varieties (CP) and a disproportionate number of heat-shock proteins in SG. Only the SG variety had measurable changes in gene expression due to herbivory alone, upregulating zeatin, and O-glucosyltransferase and thioredoxin among others. Conclusion Our results suggest that both heirloom tomato plant varieties differ in their production of secondary metabolites including phenylpropanoids and terpenoids and their regulation and activation of ABA signaling upon stress associated with flooding. Herbivory and flooding together had interacting effects that were evident at the level of plant chemistry (VOCs production), gene expression and biomass markers. Results from our study highlight the complex nature of plant responses to combinatorial stresses and point at specific genes and pathways that are affected by flooding and herbivory combined.

Abstract This study examined the perceived effects of examination special centres on teaching and learning of English language and the quality of education in Nsukka Local Government Area, Enugu State, Nigeria. The study employed a descriptive survey design. All the 123 English language teachers (PPMB Statistics, 2020) from 31 secondary schools, five secondary school principals, three religious priests and three traditional leaders in Nsukka Local Government Area of Enugu State, Nigeria were sampled for the study. The researchers developed a 15-item-structured questionnaire for data collection from the 31 teachers; while 3 structured interview questions were used to elicit responses from the principals, religious priests and traditional leaders. Mean and standard deviation were used to analyse the data collected with questionnaire; while the oral interview was analysed qualitatively through thematic analysis. The study revealed that examination special centres have detrimental effect on the teaching and learning of English language in secondary schools and the quality of education in Nsukka Local Government Area, Enugu State, Nigeria. It was recommended among others that private and public secondary schools, and tutorial centres that have been turned into examination special centres should be closed down by Enugu State Ministry of Education.

Abstract Background Stigma and masculinity represent persistent barriers in delivering successful HIV interventions to men. Our study examined community perceptions of HIV and anti-retroviral therapy (ART) and their implications for men on ART across the life course in Blantyre, Malawi. Methods Our qualitative study is based on 72 face-to-face semi-structured interviews. Participants were selected purposively and included men on ART (with suppressed and unsuppressed viral loads), adult male community members irrespective of HIV status and other HIV stakeholders such as health personnel and program implementers. Interviews were conducted in Chichewa and English, transcribed verbatim and analyzed thematically in NVivo 12. We applied the socio-ecological model as our theoretical framework as well as a “life-course” perspective. Results Our findings highlight lingering negative perceptions towards ART in general and towards PLHIV irrespective of viral load suppression. With intersecting notions of masculinity and stigma, men’s descriptions of anticipated stigma in their relationships and when visiting health facilities dominated. Stigma was experienced at the personal, interpersonal, facility and community level. Yet, men living with HIV were perceived differently throughout the life-course, with young sexually active men seen as the most stigmatized group and older men seen as drawing resilience from a greater range of masculine norms. Some men of all ages displayed “transformative” masculinities independent of stigma and community expectations. Conclusions We propose the “life-course” as a useful concept for studies on masculinity, HIV and stigma. Considering gendered constructions of “respectable” midlife-older age vis-à-vis younger age, and how they influence stigma as well as uptake and adherence to ART might lead to more targeted services for men that build on “transformative masculinities”.

Abstract Background The potential shift of major causes of febrile illnesses from malaria to non-malarial febrile illnesses, including arboviral diseases such as chikungunya and dengue, is of concern. The last outbreaks of these infections were reported in 2018 and 2019 for chikungunya in Zanzibar and dengue in Dar es Salaam. We conducted a cross-sectional study that involved serological testing of stored blood samples from the blood banks in Temeke Referral Hospital in Dar es Salaam and the National Blood Bank Unit in Zanzibar. The samples were collected from Zanzibar and Dar es Salaam donors in May and June 2020, respectively. A total of 281 samples were included in the study, and their demographic information extracted from the registers. The samples were then transported to Muhimbili University of Health and Allied Sciences at the Microbiology Laboratory. They were subjected to an indirect ELISA to detect IgG and IgM against dengue and chikungunya viruses. Results Seropositive IgM samples from Dar es Salaam were 3/101 (2.97%) for chikungunya and 1/101 (0.9%) for dengue, while samples from Zanzibar were all IgM negative for both viruses. Chikungunya IgG seropositivity was significantly higher (p ≤ 0.05) in Dar es Salaam 21/101 (21.2%) than Zanzibar 22/180 (12.2%). There was no difference in dengue IgG seropositivity between Dar es Salaam 44/101 (43.5%) and Zanzibar 68/180 (37.8%). Similarly, dual IgG seropositivity for both dengue and chikungunya viruses were not different between Dar es Salaam 13/101 (12.9%) and Zanzibar 11/180 (6.1%). Conclusion Detection of IgM for dengue and chikungunya in Dar es Salaam indicates recent or ongoing transmission of the two viruses in the absence of a reported outbreak. These findings suggest the possibility of transmission of the two infections through blood transfusion. Detection of IgG antibodies for dengue and chikungunya viruses might be contributed by both; the ongoing infections and residual responses caused by preceding infections in the country. Results from blood banks may represent the tip of the iceberg. Further studies are needed to gain insight into the actual burden of the two diseases in Tanzania.

Abstract Background Vaccine hesitancy has been recognized as an important barrier to timely vaccinations around the world, including in sub-Saharan Africa. In Tanzania, 1 in 4 children is not fully vaccinated. The objective of this mixed methods study was to describe and contextualize parental concerns towards vaccines in Tanzania. Methods Between 2016 and 2017, we conducted a cross-sectional survey (n = 134) and four focus group discussions (FGDs, n = 38) with mothers of children under 2 years of age residing in Mtwara region in Southern Tanzania. The survey and FGDs assessed vaccination knowledge and concerns and barriers to timely vaccinations. Vaccination information was obtained from government-issued vaccination cards. Results In the cross-sectional survey, 72% of mothers reported missed or delayed receipt of vaccines for their child. Although vaccine coverage was high, timeliness of vaccinations was lower and varied by vaccine. Rural mothers reported more vaccine-related concerns compared to urban mothers; literacy and access to information were identified as key drivers of the difference. Mothers participating in FGDs indicated high perceived risk of vaccine-preventable illnesses, but expressed concerns related to poor geographic accessibility, unreliability of services, and missed opportunities for vaccinations resulting from provider efforts to minimize vaccine wastage. Conclusions Findings from our cross-sectional survey indicate the presence of vaccination delays and maternal concerns related to childhood vaccines in Tanzania. In FGDs, mothers raised issues related to convenience more often than issues related to vaccine confidence or complacency. Further research is necessary to understand how these issues may contribute to the emergence and persistence of vaccine hesitancy and to identify effective mitigation strategies.

Abstract Background The first yaws eradication campaign reduced the prevalence of yaws by 95%. In recent years, however, yaws has reemerged and is currently subject to a second, ongoing eradication campaign. Yet, the epidemiological status of Tanzania and 75 other countries with a known history of human yaws is currently unknown. Contrary to the situation in humans in Tanzania, recent infection of nonhuman primates (NHPs) with the yaws bacterium Treponema pallidum subsp. pertenue (TPE) have been reported. In this study, we consider a One Health approach to investigate yaws and describe skin ulcers and corresponding T. pallidum serology results among children living in the Tarangire-Manyara ecosystem, an area with increasing wildlife-human interaction in northern Tanzania. Methods To investigate human yaws in Tanzania, we conducted a cross-sectional study to screen and interview skin-ulcerated children aged 6 to 15 years, who live in close proximity to two national parks with high numbers of naturally TPE-infected monkeys. Serum samples from children with skin ulcers were tested for antibodies against the bacterium using a treponemal (Treponema pallidum Particle Agglutination assay) and a non-treponemal (Rapid Plasma Reagin) test. Results A total of 186 children aged between 6 and 15 years (boys: 10.7 ± 2.1 (mean ± SD), N = 132; girls: 10.9 ± 2.0 (mean ± SD), N = 54) were enrolled. Seven children were sampled at health care facilities and 179 at primary schools. 38 children (20.4%) reported active participation in bushmeat hunting and consumption and 26 (13.9%) reported at least one physical contact with a NHP. None of the lesions seen were pathognomonic for yaws. Two children tested positive for treponemal antibodies (1.2%) in the treponemal test, but remained negative in the non-treponemal test. Conclusions We found no serological evidence of yaws among children in the Tarangire-Manyara ecosystem. Nevertheless, the close genetic relationship of human and NHPs infecting TPE strains should lead to contact prevention with infected NHPs. Further research investigations are warranted to study the causes and possible prevention measures of spontaneous chronic ulcers among children in rural Tanzania and to certify that the country is free from human yaws.

Abstract Background Vaccination is a cost-effective strategy for reducing morbidity and mortality among children under 5 years old. To be fully protected from diseases such as tuberculosis, diphtheria, pertussis, and polio, children must receive all recommended vaccinations in a timely manner. In many countries, including Tanzania, high overall vaccination rates mask substantial regional variation in vaccination coverage and low rates of vaccination timeliness. This study evaluates the efficacy of mobile phone-based (mHealth) reminders and incentives for improving vaccination timeliness in the first year of life. Methods The study, conducted in Mtwara Region in Tanzania, includes 400 late-stage pregnant women enrolled from rural and urban health facilities and surrounding communities. The primary outcome is timeliness of vaccinations among their children at 6, 10, and 14 weeks after birth. Timeliness is defined as vaccination receipt within 28 days after the vaccination due date. The quasi-randomized controlled trial includes three arms: (1) standard of care (no reminders or incentives), (2) mobile phone-based reminders, and (3) mobile phone-based reminders and incentives in the form of conditional financial transfers. Assignment into study arms is based on scheduled vaccination dates. Reminder messages are sent to arms 2 and 3 participants via mobile phones 1 week and 1 day prior to each scheduled vaccination. For arm 3 participants, reminder messages offer an incentive that is provided in the form of a mobile phone airtime recharge voucher code for each timely vaccination. Vaccination dates are recorded via participant contact with an mHealth system, phone calls with mothers, and a review of government-issued vaccination cards during an end-line survey. Random effects logistic regression models will be used to estimate the effects of reminders and incentives on the timeliness of vaccinations. Discussion The results will inform implementation science research on the effectiveness of reminders and incentives as a means of improving vaccination timeliness. Trial registration ClinicalTrials.gov, NCT03252288. Registered on 17 August 2017 (retrospectively registered).

Abstract Background Uterine fibroids are the most common uterine tumours in females of reproductive age. During pregnancy, uterine fibroids may be complicated by aseptic necrobiosis. We herein report an ambiguous clinical presentation of uterine fibroids in pregnancy and discuss the diagnostic challenges encountered in our resource-constraint setting. Case presentation A term pregnant Cameroonian woman was admitted to our maternity unit with clinical findings suggestive of a strangulated umbilical hernia. She underwent an emergency caesarean section which fortuitously revealed aseptic necrobiosis of a uterine fibroid, managed within the same surgical intervention by myomectomy. Her post-operative course was uneventful. Conclusion The authors highlight the need for a high index of suspicion by healthcare providers, as well as the need for a multidisciplinary approach for a favourable maternal and foetal outcome.

Abstract Background Artemether–lumefantrine (AL) is the recommended first-line artemisinin-based combination therapy (ACT) for the treatment of uncomplicated falciparum malaria in most of the malaria-endemic countries, including Tanzania. Recently, dihydroartemisinin–piperaquine (DP) has been recommended as the alternative anti-malarial to ensure effective case management in Tanzania. This study assessed the parasite clearance rate and efficacy of AL and DP among patients aged 6 months to 10 years with uncomplicated falciparum malaria in two sites with different malaria transmission intensity. Methods This was an open-label, randomized trial that was conducted at two sites of Muheza Designated District Hospital and Ujiji Health Centre in Tanga and Kigoma regions, respectively. Patients meeting inclusion criteria were enrolled, treated with either AL or DP and followed up for 28 (extended to 42) and 42 (63) days for AL and DP, respectively. Parasite clearance time was monitored in the first 72 h post treatment and the clearance rate constant and half-life were calculated using an established parasite clearance estimator. The primary outcome was parasitological cure on days 28 and 42 for AL and DP, respectively, while secondary outcome was extended parasitological cure on days 42 and 63 for AL and DP, respectively. Results Of the 509 children enrolled (192 at Muheza and 317 at Ujiji), there was no early treatment failure and PCR uncorrected cure rates on day 28 in the AL group were 77.2 and 71.2% at Muheza and Ujiji, respectively. In the DP arm, the PCR uncorrected cure rate on day 42 was 73.6% at Muheza and 72.5% at Ujiji. With extended follow-up (to day 42 for AL and 63 for DP) cure rates were lower at Ujiji compared to Muheza (AL: 60.2 and 46.1%, p = 0.063; DP: 57.6 and 40.3% in Muheza and Ujiji, respectively, p = 0.021). The PCR corrected cure rate ranged from 94.6 to 100% for all the treatment groups at both sites. Parasite clearance rate constant was similar in the two groups and at both sites (