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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 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 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 In sub-Saharan Africa, the use of malaria rapid diagnostic tests (mRDT) has raised awareness of alternative fever causes in children but few studies have included adults. To address this gap, we conducted a study of mRDT-negative fever aetiologies among children and adults in Tanzania. Methods A total of 1028 patients aged 3 months to 50 years with a febrile illness and negative mRDT were enrolled from a Tanzanian hospital outpatient department. All had a physical examination and cultures from blood, nasopharynx/throat and urine. Patients were followed on Days 7 and 14 and children meeting WHO criteria for pneumonia were followed on Day 2 with chest radiology. Results Respiratory symptoms were the most frequent presenting complaint, reported by 20.3% of adults and 64.0% (339/530) of children. Of 38 X-rayed children meeting WHO pneumonia criteria, 47.4% had a normal X-ray. Overall, only 1.3% of 1028 blood cultures were positive. Salmonella typhi was the most prevalent pathogen isolated (7/13, 53.8%) and S. typhi patients reported fever for a median of 7 days (range 2–14). Children with bacteraemia did not present with WHO symptoms requiring antibiotic treatment. Young children and adults had similar prevalences of positive urine cultures (24/428 and 29/498, respectively). Conclusion Few outpatient fevers are caused by blood stream bacterial infection, and most adult bacteraemia would be identified by current clinical guidelines although paediatric bacteraemia may be more difficult to diagnose. While pneumonia may be overdiagnosed, urinary tract infection was relatively common. Our results emphasise the difficulty in identifying African children in need of antibiotics among the majority who do not.

More than 350 million people worldwide are chronically infected with the hepatitis B virus (HBV), 170 million with the hepatitis C virus (HCV) [1], and 33 million with the human immunodeficiency virus (HIV) [2]. HBV and HCV are more prevalent among HIV-infected individuals due to shared routes of transmission; HIV increases the speed of liver dysfunction among those with coinfection [3, 4]; and liver disease due to chronic hepatitis is becoming an increasing cause of morbidity and mortality among HIV-infected persons, particularly in resource-limited settings. It has been previously established among HIV-negative cohorts that manifestations of HBV infection vary depending on the age of an individual at the time they acquire infection. Adults who become infected with HBV have up to 5% risk of acquiring chronic disease; in contrast to a 25%–30% risk with infection before the age of 5 years, and up to a 90% risk of developing chronic hepatitis B with perinatal infection. Furthermore, infants who develop chronic HBV have a 25% risk of dying prematurely due to cirrhosis or liver cancer [5–8]. In contrast to HBV, persistent infection with HCV occurs in 50%–60% of infected children, regardless of age [9]. The relative risk for the development of cirrhosis is doubled in patients with HIV-HCV coinfection [10]. Data on both HIV-hepatitis coinfection and hepatitis monoinfection among African populations, especially children, are limited [11–19]. Although the treatment of hepatitis C in resource-poor settings is still quite limited, there are often treatment options available for those with HBV. For HIV-HBV coinfected individuals, several nucleotide and nucleoside reverse transcriptase inhibitors are available for the treatment of both viruses, including lamivudine (3TC), tenofovir disoproxil fumarate (TDF), and emtricitabine (FTC). Lamivudine has long been a mainstay of first-line highly active antiretroviral therapy (HAART) for children in sub-Saharan Africa, and although it has potent activity against both HIV and HBV, when used as a single anti-HBV agent resistance develops rapidly [20–23]. Increasingly, TDF and combination TDF/FTC are being rolled out for the treatment of HIV in some sub-Saharan African settings. Tenofovir disoproxil fumarate has potent activity against HBV and a high barrier to resistance [24, 25]. Furthermore, TDF is now approved for use in HIV-infected children down to the age of 2 years [26]. Optimal treatment for HIV-HBV coinfected children is not established. HIV-infected pregnant women and children in Tanzania are currently not screened for hepatitis coinfection; thus, most clinicians are unaware of coinfected patients. A better understanding of the prevalence of coinfection is a necessary first step to develop optimal monitoring and treatment approaches. This study aimed to determine the prevalence of HBV and HCV among healthy, HIV-negative children, and HIV-infected children on HAART living in the Kilimanjaro Region of northern Tanzania.

BACKGROUND: Lactic acidosis is a consistent predictor of mortality owing to severe infectious disease, but its detection in low-income settings is limited to the clinical sign of "deep breathing" because of the lack of accessible technology for its measurement. We evaluated the use of a point-of-care (POC) diagnostic device for blood lactate measurement to assess the severity of illness in children admitted to a district hospital in Tanzania. METHODS: Children between the ages of 2 months and 13 years with a history of fever were enrolled in the study during a period of 1 year. A full clinical history and examination were undertaken, and blood was collected for culture, microscopy, complete blood cell count, and POC measurement of blood lactate and glucose. RESULTS: The study included 3248 children, of whom 164 (5.0%) died; 45 (27.4%) of these had raised levels of blood lactate (>5 mmol/L) but no deep breathing. Compared with mortality in children with lactate levels of ≤ 3 mmol/L, the unadjusted odds of dying were 1.6 (95% confidence interval [CI].8-3.0), 3.4 (95% CI, 1.5-7.5), and 8.9 (95% CI, 4.7-16.8) in children with blood lactate levels of 3.1-5.0, 5.1-8.0, or >8.0 mmol/L, respectively. The prevalence of raised lactate levels (>5 mmol/L) was greater in children with malaria than in children with nonmalarial febrile illness (P < .001) although the associated mortality was greater in slide-negative children. CONCLUSIONS: POC lactate measurement can contribute to the assessment of children admitted to hospital with febrile illness and can also create an opportunity for more hospitals in resource-poor settings to participate in clinical trials of interventions to reduce mortality associated with hyperlactatemia.

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.

The replacement of “presumptive treatment for malaria” by “test before treat” strategies for the management of febrile illness is raising awareness of the importance of knowing more about the causes of illness in children who are suspected to have malaria but return a negative parasitological test. The most common cause of non-malarial febrile illness (NMFI) in African children is respiratory tract infection. Whilst the bacterial causes of NMFI are well known, the increasing use of sensitive techniques such as polymerase chain reaction (PCR) tests is revealing large numbers of viruses that are potential respiratory pathogens. However, many of these organisms are commonly present in the respiratory tract of healthy children so causality and risk factors for pneumonia remain poorly understood. Infection with a combination of viral and bacterial pathogens is increasingly recognised as important in the pathogenesis of pneumonia. Similarly, blood stream infections with organisms typically grown by aerobic culture are well known but a growing number of organisms that can be identified only by PCR, viral culture, or serology are now recognised to be common pathogens in African children. The high mortality of hospitalised children on the first or second day of admission suggests that, unless results are rapidly available, diagnostic tests to identify specific causes of illness will still be of limited use in guiding the potentially life‑saving decisions relating to initial treatment of children admitted to district hospitals in Africa with severe febrile illness and a negative test for malaria. Malaria control and the introduction of vaccines against Haemophilus influenzae type b and pneumococcal disease are contributing to improved child survival in Africa. However, increased parasitological testing for malaria is associated with increased use of antibiotics to which resistance is already high.

Background Injuries represent a significant and growing public health concern in the developing world, yet their impact on patients and the emergency health-care system in the countries of East Africa has received limited attention. This study evaluates the magnitude and scope of injury related disorders in the population presenting to a referral hospital emergency department in northern Tanzania. Methods A retrospective chart review of patients presenting to the emergency department at Kilimanjaro Christian Medical Centre was performed. A standardized data collection form was used for data abstraction from the emergency department logbook and the complete medical record for all injured patients. Patient demographics, mechanism of injury, location, type and outcomes were recorded. Results Ten thousand six hundred twenty-two patients presented to the emergency department for evaluation and treatment during the 7-month study period. One thousand two hundred twenty-four patients (11.5%) had injuries. Males and individuals aged 15 to 44 years were most frequently injured, representing 73.4% and 57.8%, respectively. Road traffic injuries were the most common mechanism of injury, representing 43.9% of injuries. Head injuries (36.5%) and extremity injuries (59.5%) were the most common location of injury. The majority of injured patients, 59.3%, were admitted from the emergency department to the hospital wards, and 5.6%, required admission to an intensive care unit. Death occurred in 5.4% of injured patients. Conclusions These data give a detailed and more robust picture of the patient demographics, mechanisms of injury, types of injury and patient outcomes from similar resource-limited settings.