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Background Antibiotic resistance is a threat to global child health. Primary healthcare workers play a key role in antibiotic stewardship in the community, but few studies in low-income countries have described their experiences of initiating antibiotic treatment in children. Thus, the present study aimed to describe primary healthcare workers’ experiences of antibiotic prescription for children under 5 years of age and their conceptions of antibiotic resistance in Northern Tanzania. Methods A qualitative study involving individual in-depth interviews with 20 prescribing primary healthcare workers in Moshi urban and rural districts, Northern Tanzania, was performed in 2019. Interviews were transcribed verbatim, translated from Kiswahili into English and analysed according to the phenomenographic approach. Findings Four conceptual themes emerged during the analysis; conceptions in relation to the prescriber, the mother and child, other healthcare actors and in relation to outcome. The healthcare workers relied mainly on clinical examination and medical history provided by the mother to determine the need for antibiotics. Confidence in giving advice concerning non-antibiotic treatment varied among the participants and expectations of antibiotic treatment were perceived to be common among the mothers. Antibiotic resistance was mainly perceived as a problem for the individual patient who was misusing the antibiotics. Conclusions To increase rational antibiotic prescription, an awareness needs to be raised among Tanzanian primary healthcare workers of the threat of antibiotic resistance, not only to a few individuals, but to public health. Guidelines on childhood illnesses should be updated with advice concerning symptomatic treatment when antibiotics are not necessary, to support rational prescribing practices and promote trust in the clinician and mother relationship.

Background:Pharmacovigilance is a means of ensuring drug safety and thus ensuring the risk of drug use does not outweigh the benefit. Antiretroviral therapy for HIV care and treatment has been reported to have reduced mortality and morbidity but has adverse drug reactions. These adverse drug reactions (ADR) lead to treatment failure. In 2015 in Tanzania 688,800 adults were taking ART. All health care providers are required to report all suspected adverse drug reactions seen or reported by their patients using the yellow forms that are available at all CTC centres in Tanzania. However the actual practice of reporting is not taking place. This study aimed to explore the patients’ knowledge and HIV/AIDS health care providers’ and reporting practices of adverse events of ART, with the specific objective to determine the knowledge of patients on ART adverse events and practices of health care providers on reporting of ART ADR at Kilimanjaro Christian Medical Centre (KCMC). Methods:A cross-sectional study using a semi-structured questionnaire was conducted between June to July 2016 within HIV, dermatology and infectious disease clinics at KCMC. All health care providers (HCPs) providing HIV services within these clinics completed a questionnaire. Mean and standard deviation were used to summarize the numerical data with normal distribution (age of patients) while undistributed numerical data (duration on ART) was summarized using median and range. Frequency and percentage was used to summarize categorical variables. Results:All 63 HCPs , agreed ADR reporting was necessary. Forty six (73%) were aware of the national ADR reporting system but only 32(50.8%) reported having received training on pharmacovigilance. Only 4(6.3%) of all HCPs reported to always fill ADR report forms, 27(42.9%) rarely filled the forms and 32(50.8%) reported to have never filled an ADR reporting form. Training on pharmacovigilance had positive influence towards ADR reporting. Lack of motivation, unsure on how to report, Lack of time, unavailability of reporting forms and ignorance were the major factors affecting reporting among HCP. Conclusion:Whilst the majority of HCPs were aware of the need and importance of ADR reporting and the national pharmacovigilance system, the study suggests, however, there exists an under reporting of ART adverse events. More effort is needed to strengthen the continuous reporting of ADRs by providing continuous education to health care providers that will lead to their active participation in pharmacovigilance.

Background Antimicrobial resistance has been named as one of the top ten threats to public health in the world. Hospital-based antimicrobial stewardship programs (ASPs) can help reduce antimicrobial resistance. The purpose of this study was to determine perceived barriers to the development and implementation of ASPs in tertiary care centers in three low- and middle-income countries (LMICs). Methods Interviews were conducted with 45 physicians at tertiary care hospitals in Sri Lanka (n = 22), Kenya (12), and Tanzania (11). Interviews assessed knowledge of antimicrobial resistance and ASPs, current antimicrobial prescribing practices, access to diagnostics that inform antimicrobial use, receptiveness to ASPs, and perceived barriers to implementing ASPs. Two independent reviewers coded the interviews using principles of applied thematic analysis, and comparisons of themes were made across the three sites. Results Barriers to improving antimicrobial prescribing included prohibitively expensive antimicrobials, limited antimicrobial availability, resistance to changing current practices regarding antimicrobial prescribing, and limited diagnostic capabilities. The most frequent of these barriers in all three locations was limited drug availability. Many physicians in all three sites had not heard of ASPs before the interviews. Improved education was a suggested component of ASPs at all three sites. The creation of guidelines was also recommended, without prompting, by interviewees at all three sites. Although most participants felt microbiological results were helpful in tailoring antibiotic courses, some expressed distrust of laboratory culture results. Biomarkers like erythrocyte sedimentation rate and c-reactive protein were not felt to be specific enough to guide antimicrobial therapy. Despite limited or no prior knowledge of ASPs, most interviewees were receptive to implementing protocols that would include documentation and consultation with ASPs regarding antimicrobial prescribing. Conclusions Our study highlighted several important barriers to implementing ASPs that were shared between three tertiary care centers in LMICs. Improving drug availability, enhancing availability of and trust in microbiologic data, creating local guidelines, and providing education to physicians regarding antimicrobial prescribing are important steps that could be taken by ASPs in these facilities.

Background Antimicrobial stewardship programs (ASPs) are being developed internationally to mitigate the misuse of antimicrobials. An understanding of current practices and prescribing patterns is necessary to determine targets to develop context-specific ASPs in low- and middle-income country (LMIC) hospitals. Methods We conducted a prospective study of patients admitted to the adult medical wards at three LMIC tertiary care centers in 2018- 2019: a 1,800-bed public hospital in Galle, Sri Lanka; a 991-bed public hospital in Eldoret, Kenya; and a 630-bed private hospital in Moshi, Tanzania. Information regarding antimicrobial therapy received during hospitalization, indications for antimicrobial therapy, and duration of antimicrobial use were extracted from the medical record. Results In total, 3150 patients were enrolled: 1297 in Sri Lanka, 750 in Kenya, and 1103 in Tanzania. Antimicrobial use prevalence varied between the three sites, with 56.0% of patients receiving antimicrobials during hospitalization in Sri Lanka, 56.5% in Kenya, and 35.4% in Tanzania. Third-generation cephalosporins were used most frequently in Kenya (70.0%) and Tanzania (73.1%), whereas amoxicillin/ clavulanic acid was used most frequently in Sri Lanka (48.4%). Lower respiratory tract infection was the most common indication for antimicrobial use in all three locations: 37.4% in Sri Lanka, 27.8% in Kenya, and 49.2% in Tanzania. No clear indication for antimicrobial use was documented among 11.6% patients receiving antimicrobials in Sri Lanka, 32.8% in Kenya, and 10.5% in Tanzania. In Tanzania, 8.6% of the patients had documentation of input from the microbiology or infectious diseases teams compared to less than 1% in either Sri Lanka or Kenya. Pertinent culture data related to the primary indication for antimicrobials was present in 16.1% (Sri Lanka), 6.1% (Kenya), and 7.4% (Tanzania). Conclusion Unclear documentation for antimicrobial use was common in all three sites and most patients on antimicrobial therapy did not have pertinent culture data. Improving documentation and the capacity of the local microbiology laboratories could be initial targets for ASPs in these LMIC hospitals. Disclosures All Authors: No reported disclosures

Background Pneumonia is among the leading causes of avoidable deaths for young children globally. The main burden of mortality falls on children from poor and rural families who are less likely to obtain the treatment they need, highlighting inequities in access to effective care and treatment. Caretakers’ illness perceptions and care-seeking practices are of major importance for children with pneumonia to receive adequate care. This study qualitatively explores the caretaker concepts of childhood pneumonia in relation to treatment seeking behaviour and health worker management in Moshi urban district, Tanzania. Methods In May - July 2013 data was gathered through different qualitative data collection techniques including five focus group discussions (FGDs) with mothers of children under-five years of age. The FGDs involved free listing of pneumonia symptoms and video presentations of children with respiratory symptoms done, these were triangulated with ten case narratives with mothers of children admitted with pneumonia and eleven in-depth interviews with hospital health workers. Transcripts were coded and analysed using qualitative content analysis. Results Mothers demonstrated good awareness of common childhood illnesses including pneumonia, which was often associated with symptoms such as cough, flu, chest tightness, fever, and difficulty in breathing. Mothers had mixed views on causative factors and treatments options but generally preferred modern medicine for persisting and severe symptoms. However, all respondent reported access to health facilities as a barrier to care, associated with transport, personal safety and economic constraints. Conclusion Local illness concepts and traditional treatment options did not constitute barriers to care for pneumonia symptoms. Poor access to health facilities was the main barrier. Decentralisation of care through community health workers may improve access to care but needs to be combined with strengthened referral systems and accessible hospital care for those in need.

Background:The clients’ level of satisfaction is an important measure in assessing the quality of health care services provided in health facilities, and is important in enhancing the utilisation of health care services.Objectives:This study aimed to determine pregnant women’s level of satisfaction on the quality of care in the Reproductive and Child Health (RCH) clinic at Huruma Designated District Hospital, Rombo Kilimanjaro.Methodology:A cross-sectional study was conducted from May to June 2018 using the Donabediean model. Using systematic sampling, 270 pregnant women were selected to participate in the study. Data was collected using a pre-tested Service Quality(SERVQUAL) questionnaire. Descriptive statistics were performed using univariate and bivariate analysis, and one sample t-test to compare mean gap scores. The principal component analysis was employed to identify key items that measure the quality of care. A p-value of

Background The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. Methods Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440–600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. Results Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. Conclusion The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631

Background Antimicrobial stewardship programs (ASPs) have been shown to improve the appropriate use of antimicrobials, especially in high-income countries. However, ASPs are relatively less well implemented in low-or-middle income countries. To improve the effectiveness of ASPs in these settings, it is important to determine the core actions and targets for improving antimicrobial use. We sought to describe the prevalence and patterns of antibiotic use at a tertiary care hospital in Tanzania. Methods Consecutive patients admitted to an adult medical ward at a tertiary care hospital, Kilimanjaro Christian Medical Centre, in Moshi, Tanzania were enrolled from June 2018 to March 2019. The medical record was reviewed for data regarding the type of antibiotics prescribed, indications for use, and microbiologic testing ordered. Results A total of 1103 patients were enrolled during the study period. The majority of patients were males (663, 60.1%), with the median age being 54 years (IQR 39–70). About one-third (390, 35.4%) of the admitted patients received antimicrobials during hospitalization, with pneumonia being the leading indication for antimicrobial use (158, 40.5%). The most commonly used antibiotics included ceftriaxone in 285 (73.1%), metronidazole in 155 (39.7%), and amoxicillin/ ampicillin in 46 (11.8%) patients. The median duration of antimicrobial use was 5 days (IQR 3–7). Few patients on antimicrobials (27, 6.9%) had culture results, of which half (15, 55.6%) were positive for an organism and a minority (8, 29.6%) were susceptible to the antibiotics being used. Overall, mortality in the cohort was 22.7% and the median duration of hospitalization was 5 days (IQR 3–8). Conclusion Antibiotics were used in a substantial proportion of admitted patients. However, in most cases, treatment was empirical with limited use of culture results. Future ASP efforts can target the improved use of microbiologic cultures to target antimicrobial use. Disclosures All authors: No reported disclosures.

Objective Measurement of respiratory rate is an important clinical sign in the diagnosis of pneumonia but suffers from interobserver variation. Here, we assess the use of video recordings as a quality assurance tool that could be useful both in research and in training of staff. Methods Respiratory rates (RR) were recorded in children aged 2–59 months presenting with cough or difficulty breathing at two busy outpatient clinics in Tanzania. Measurements were repeated at 10‐min intervals in a quiet environment with simultaneous video recordings that were independently reviewed by two paediatricians. Results Eight hundred and fifty‐nine videos were sent to two paediatricians; 148 (17.2%) were considered unreadable by one or both. For the 711 (82.8%) videos that were readable by both paediatricians, there was perfect agreement for the presence of raised RR with a kappa value (κ) of 0.85 (P < 0.001); and in 476 (66.9%) cases, both paediatricians agreed on the RR within 2 breaths per minute (±2 bpm). A reported illness of 5 days or more was associated with unreadable video recordings (OR = 3.44, CI: 1.5–6.08; P < 0.001). The multilevel model showed that differences between observers accounted for only 13% of the variability in RR. Conclusion Video recordings are reliable tools for quality assurance of RR measurements in children with suspected pneumonia. Videos with a clear view of respiratory movements may also be useful in training primary healthcare staff.

Background WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT). However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. Methods Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. Results Over the course of one year, 965 children were enrolled; 158 (16.4%) were RDT-positive and treated with artemether-lumefantrine and 807 (83.4%) were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6%) children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2%) children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9%) children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7) and specificity of 96.3% (95%CI 96.3-98.4). Conclusions Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive bacterial disease is uncommon in children with non-severe illness and most cases occurred in infants with a current fever.

Summary objective To compare the performance of the Paracheck rapid diagnostic test (RDT) withmicroscopy for diagnosing malaria in hospitalised children.methods Children aged between 2 months and 13 years with fever were enrolled in the study over1 year. A standard clinical history and examination were recorded and blood drawn for culture,complete blood count, Paracheck RDT and double-read blood slide.results Of 3639 children enrolled, 2195 (60.3%) were slide positive. The sensitivity and specificityof Paracheck were 97.5% (95% CI 96.9–98.0) and 65.3% (95% CI 63.8–66.9), respectively. There wasan inverse relationship between age-specific prevalence of parasitaemia and Paracheck specificity. Inlogistic regression model, false-positive Paracheck results were significantly associated with pre-admission use of antimalarial drug (OR 1.44, 95% CI 1.16–1.78), absence of current fever (OR 0.64,95% CI 0.52–0.79) and non-typhi Salmonella bacteraemia (OR 3.89. 95% CI 2.27–6.63). In spite ofhigh sensitivity, 56⁄2195 (2.6%) of true infections were Paracheck negative and 8⁄56 (14.3%) were inpatients with >50 000 parasites⁄ll.conclusions Paracheck had poor specificity in diagnosing malaria in severely ill children; this waslikely to be due to HRP2 persistence following recent parasite clearance. The combination of positiveParacheck and negative blood slide results identified a group of children at high risk of non-typhiSalmonella infection. While Paracheck was highly sensitive, some high-density infections were missed.For children with severe febrile illness, at least two reliable negative parasitological test results should beavailable to justify withholding antimalarial treatment; the optimal choice of these has yet to beidentified.keywords malaria, severe, rapid diagnostic test, hospitalIntroductionThe use of rapid immunochromatographic tests for malaria(RDTs) in primary care facilities has been studied over anumber of years, and these tests are now being rolled outon a large scale in Africa as a means to restrict antimalarialdrug use to parasitologically confirmed cases, a policy nowsupported by WHO (WHO 2010). However, the WHOcriteria for malaria diagnosis apply irrespective of severity,and it is therefore surprising that as far as we are aware,only one small study has so far been published on the use ofRDTs in patients admitted to hospital (Birku et al. 1999).The wider use of RDTs in patients hospitalised withsevere febrile illness seems inevitable given the increasingavailability of RDTs. Given current evidence of the lowaccuracy of routinely read slide results, this may representan improvement over current practice (Reyburn et al.2004; Zurovac et al. 2006). However, the performance ofHRP2-based RDTs may differ when used for severely illchildren compared to use in non-severe illness. First,specificity may be reduced by the persistence of HRP2 forup to 5 weeks following clearance of parasites and this

OBJECTIVE To determine the normal haematological and immunological reference intervals for healthy Tanzanian children. METHODS We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents. RESULTS Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians. CONCLUSIONS Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.

Background The increasing investment in malaria rapid diagnostic tests (RDTs) to differentiate malarial and non-malarial fevers, and an awareness of the need to improve case management of non-malarial fever, indicates an urgent need for high quality evidence on how best to improve prescribers’ practices. Methods A three-arm stratified cluster-randomised trial was conducted in 36 primary healthcare facilities from September 2010 to March 2012 within two rural districts in northeast Tanzania where malaria transmission has been declining. Interventions were guided by formative mixed-methods research and were introduced in phases. Prescribing staff from all facilities received standard Ministry of Health RDT training. Prescribers from facilities in the health worker (HW) and health worker-patient (HWP) arms further participated in small interactive peer-group training sessions with the HWP additionally receiving clinic posters and patient leaflets. Performance feedback and motivational mobile-phone text messaging (SMS) were added to the HW and HWP arms in later phases. The primary outcome was the proportion of patients with a non-severe, non-malarial illness incorrectly prescribed a (recommended) antimalarial. Secondary outcomes investigated RDT uptake, adherence to results, and antibiotic prescribing. Results Standard RDT training reduced pre-trial levels of antimalarial prescribing, which was sustained throughout the trial. Both interventions significantly lowered incorrect prescribing of recommended antimalarials from 8% (749/8,942) in the standard training arm to 2% (250/10,118) in the HW arm (adjusted RD (aRD) 4%; 95% confidence interval (CI) 1% to 6%; P = 0.008) and 2% (184/10,163) in the HWP arm (aRD 4%; 95% CI 1% to 6%; P = 0.005). Small group training and SMS were incrementally effective. There was also a significant reduction in the prescribing of antimalarials to RDT-negatives but no effect on RDT-positives receiving an ACT. Antibiotic prescribing was significantly lower in the HWP arm but had increased in all arms compared with pre-trial levels. Conclusions Small group training with SMS was associated with an incremental and sustained improvement in prescriber adherence to RDT results and reducing over-prescribing of antimalarials to close to zero. These interventions may become increasingly important to cope with the wider range of diagnostic and treatment options for patients with acute febrile illness in Africa. Trial registration ClinicalTrials.gov (#NCT01292707) 29 January 2011. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0346-z) contains supplementary material, which is available to authorized users.