Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics.

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.

Fluoroquinolone resistance among fecal extended spectrum ßeta lactamases positive Enterobacterales isolates from children in Dar es Salaam, Tanzania.

BACKGROUND: Fluoroquinolones have been, and continue to be, routinely used for treatment of many bacterial infections. In recent years, most parts of the world have reported an increasing trend of fluoroquinolone resistant (FQR) Gram-negative bacteria. METHODS: A cross-sectional study was conducted between March 2017 and July 2018 among children admitted due to fever to referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were used to screen for carriage of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). ESBL-PE isolates were tested for quinolone resistance by disk diffusion method. Randomly selected fluroquinolone resistant isolates were characterized by using whole genome sequencing. RESULTS: A total of 142 ESBL-PE archived isolates were tested for fluoroquinolone resistance. Overall phenotypic resistance to ciprofloxacin, levofloxacin and moxifloxacin was found in 68% (97/142). The highest resistance rate was seen among Citrobacter spp. (100%, 5/5), followed by Klebsiella. pneumoniae (76.1%; 35/46), Escherichia coli (65.6%; 42/64) and Enterobacter spp. (31.9%; 15/47). Whole genome sequencing (WGS) was performed on 42 fluoroquinolone resistant-ESBL producing isolates and revealed that 38/42; or 90.5%, of the isolates carried one or more plasmid mediated quinolone resistance (PMQR) genes. The most frequent PMQR genes were aac(6')-lb-cr (74%; 31/42), followed by qnrB1 (40%; 17/42), oqx, qnrB6 and qnS1. Chromosomal mutations in gyrA, parC and parE were detected among 19/42 isolates, and all were in E. coli. Most of the E. coli isolates (17/20) had high MIC values of > 32 µg/ml for fluoroquinolones. In these strains, multiple chromosomal mutations were detected, and all except three strains had additional PMQR genes. Sequence types, ST131 and ST617 predominated among E. coli isolates, while ST607 was more common out of 12 sequence types detected among the K. pneumoniae. Fluoroquinolone resistance genes were mostly associated with the IncF plasmids. CONCLUSION: The ESBL-PE isolates showed high rates of phenotypic resistance towards fluoroquinolones likely mediated by both chromosomal mutations and PMQR genes. Chromosomal mutations with or without the presence of PMQR were associated with high MIC values in these bacteria strains. We also found a diversity of PMQR genes, sequence types, virulence genes, and plasmid located antimicrobial resistance (AMR) genes towards other antimicrobial agents.

Drivers of irrational use of antibiotics among children: a mixed-method study among prescribers and dispensers in Tanzania.

BACKGROUND: Misuse of antibiotics has been associated with poor knowledge, attitude and practice (KAP). Therefore, this study aimed to assess if KAP of prescribers and dispensers could drive irrational use of antibiotics among children in Tanzania. METHODS: A convergent parallel mixed-methods study design that employed quantitative and qualitative approaches was conducted in 14 regional referral hospitals (RRHs). A total of 108 participants, prescribers [54] and dispensers [54] working with the pediatric population in the respective regions participated in a quantitative survey, by filling the standard questionnaire while 28 key informant interviews were conducted with in-charges of units from the pharmacy and pediatric departments. Two key informants (prescriber and dispenser) were selected from each RRH. RESULTS: Overall, among prescribers and dispensers, there was adequate knowledge; 81.5% and 79.6%, p = 0.53, those with positive attitudes were 31.5% and 81.5%, p < 0.001 and poor practices were among 70.4% and 48% p = 0.0312 respectively. Among prescribers, 14.8% agreed and strongly agreed that prescribing antibiotics that a patient did not need does not contribute to resistance. Moreover 19% disagreed to prescribe antibiotics according to local guidelines. Among dispensers, a-quarter of the dispensers thought individual efforts to implement antibiotic stewardship would not make a difference, 17% agreed and strongly agreed that antibiotics can treat viral infection and 7% agreed and strongly agreed antibiotics can be stopped upon resolution of symptoms. From qualitative interviews, both participants displayed an adequate understanding of multi-contributors of antibiotic resistance (AR) including polypharmacy, community self-medication, among others. Regardless, both professions declared to prescribed and dispensed antibiotics according to the antibiotics available in stock at the facility. Furthermore, prescribers perceived laboratory investigation took a long time, hence wasting their time. On the other hand, Dispensers reported not to provide adequate instruction to the patients, after dispensing antibiotics. CONCLUSIONS: Both prescribers and dispensers had adequate knowledge, few prescribers had positive attitudes and the majority had poor practices. Few dispensers had poor attitude and practice. These findings highlight the need to provide adequate training on antimicrobial stewardship and enforce regulation that foster appropriate medical practice.

Profiling of antimicrobial dispensing practices in accredited drug dispensing outlets in Tanzania: a mixed-method cross-sectional study focusing on pediatric patients.

BACKGROUND: The emergency of antimicrobial resistance due to irrational antimicrobial use has put public health under threat. Accredited Drug Dispensing Outlets (ADDOs) play an important role in enhancing availability and accessibility of antimicrobials, however, there is a scarcity of studies assessing antimicrobial dispensing practices in these outlets, focusing on children in Tanzania. OBJECTIVE: This study was conducted to assess the antimicrobial dispensing practices among ADDO dispensers and explore the factors influencing the use of antimicrobials for children in Tanzania. METHODS: A community-based cross-sectional study utilizing both qualitative (interviews) and quantitative (simulated clients) methods was conducted between June and September 2020 in seven zones and 14 regions in Tanzania. RESULTS: The study found inappropriate dispensing and use of antimicrobials for children, influenced by multiple factors such as patient's and dispenser's knowledge and attitude, financial constraints, and product-related factors. Only 8% (62/773) of dispensers asked for prescriptions, while the majority (90%) were willing to dispense without prescriptions. Most dispensers, 83% (426/513), supplied incomplete doses of antimicrobials and only 60.5% (345/570) of the dispensers gave proper instructions for antimicrobial use to clients. Over 75% of ADDO dispensers displayed poor practice in taking patient history. CONCLUSION: ADDO dispensers demonstrated poor practices in dispensing and promoting rational antimicrobial use for children. Training, support, and regulatory interventions are required to improve antimicrobial dispensing practices in community drug outlets.

High fecal carriage of extended Beta Lactamase producing Enterobacteriaceae among adult patients admitted in referral hospitals in Dar es Salaam, Tanzania.

BACKGROUND: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. METHODS: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 µg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. RESULTS: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07-69.88, p = 0.01). CONCLUSIONS: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.

Seroprevalence of Brucella infection and associated factors among pregnant women receiving antenatal care around human, wildlife and livestock interface in Ngorongoro ecosystem, Northern Tanzania. A cross-sectional study.

BACKGROUND: Brucellosis is a zoonotic disease transmitted to humans through contact with infected animals, animal products or consumption of infected dairy products. Brucella infection during pregnancy is of special interest due to association with adverse pregnancy outcomes. This study determined the seroprevalence and factors associated with Brucella infection among pregnant women around the human-wildlife-livestock interface area in Ngorongoro ecosystem, Northern Tanzania. METHODS: A facility-based cross-sectional study was conducted between May and June 2018 at six health facilities that provide antenatal services. Pregnant women receiving antenatal care were invited to participate. A structured questionnaire was used to collect socio-demographic and obstetric characteristics in addition to behavior and practices related to the occurrence of human brucellosis. The presence of serum immunoglobulin against Brucella was determined using Rose Bengal Plate Test (RBPT). The positive samples were further assayed for the presence of IgG and IgM using The enzyme-linkedimmunosorbent assay. Bivariate analysis was conducted to determine the variables associated with Brucella seropositivity. Multivariable logistic regression analysis was performed to examine the factors independently associations with Brucella seropositivity after adjustment for other explanatory variables. RESULTS: A total of 313 participants were enrolled in the study. The overall seroprevalence of Brucella infection was 10.9% (34/313) determined by Rose Bengal plate test. Of 34 positive individuals, 27(79.4%) and 8(23.5%) were positive in the ELISA specific for IgG and IgM Brucella antibodies respectively. Regular contact with manure (AOR 3.16, 95%CI 1.27-7.83) and preference for animal fresh milk (AOR 3.80, 95% CI 1.23-11.69), raw meat (AOR 2.58, 95% CI 1.14-5.81) and raw animal blood (AOR 2.71, 95% CI 1.15-6.35) increased the odds of being Brucella seropositive. Contact with the animal placenta were not associated with Brucella seropositivity after adjustment. CONCLUSION: This study has found that brucellosis is an important public health problem among pregnant women in areas with interactions of humans; livestock and wildlife. The risk of infection increased with the regular contact with manure and preference of raw foodstuffs like animal blood, meat, and milk. We emphasize the need for interventional strategies to reduce the risk of exposure.

Predominance of non-Candida albicans species oral colonisation among patients on anticancer therapy: findings from a cross-sectional study in Tanzania.

OBJECTIVES: This study aimed to determine the oral carriage prevalence of Candida species and identify factors associated with the carriage of Candida species among patients with cancer on treatment. DESIGN: A hospital-based cross-sectional study. SETTING: The study was conducted at a tertiary-level cancer hospital Ocean Road Cancer Institute (ORCI), Dar es Salaam, Tanzania. PARTICIPANTS: We enrolled 196 participants who consented to join the study. Oral swabs were collected from all participants and inoculated onto Sabouraud dextrose agar supplemented with 50 mg/mL gentamicin and 50 mg/mL chloramphenicol, and chromogenic agar for phenotypic identification of Candida species. PRIMARY OUTCOME: The study reported the high prevalence of oral carriage of Candida species among patients with cancer on treatment at the tertiary-level cancer hospital in Dar es Salaam, Tanzania. RESULTS: A total of 196 participants were enrolled in the study. The overall oral carriage of Candida species was 37.8% (74/196). The prevalence was higher among patients undergoing chemotherapy and radiotherapy (44.4%) than those in monotherapy (13.3% chemotherapy, 20% radiotherapy). Candida krusei was the most common isolated species, 48.6% (36/74). Head and neck (adjusted OR (aOR) 15.09, 95% CI 3.05 to 74.59, p=0.00), gastrointestinal (aOR 14.14, 95% CI 2.25 to 88.63, p=0.00) malignancies and diabetes (aOR 3.18, 95% CI 1.03 to 9.77, p=0.04) were factors independently associated with oral carriage of Candida species. CONCLUSION: The oral carriage of Candida species among patients with cancer receiving treatment at ORCI is high, mainly due to C. krusei species. This is alarming since C. krusei has intrinsic resistance to fluconazole, a common antifungal agent used to manage adult fungal infections. Therefore, efforts should be put into conducting regular check-ups for such opportunistic pathogens as they can lead to subsequent infections. Furthermore, studies conducted to determine the antifungal profile of the causative agents are warranted since different causative agents might have different profiles.

Five-year cross-sectional study to determine the burden of Candida spp. infections of the urinary tract system among patients attending tertiary hospital in Northwestern Tanzania.

OBJECTIVE: Urinary tract infections (UTIs) stand as a prominent global health concern. This study entails a 5-year retrospective analysis, using a cross-sectional study design to examine microbiology laboratory data of individuals clinically diagnosed with UTIs at Bugando Medical Centre to gain insights into the prevalence and factors linked to candiduria. METHODOLOGY: Data extracted were meticulously cleaned and coded in an MS Excel sheet, subsequently transferred to STATA V.15 for analysis. Binary logistic regression analysis was used to identify factors associated with candiduria. A probability value below 0.05 at a 95% CI was considered statistically significant. RESULTS: Urine samples for culture and sensitivity comprised 33.4% (20755) of the total biological samples (62335). The median age of the patients stood at 19 years. A slight majority were female, accounting for 52.8% (10051), and two-thirds sought treatment at outpatient departments (67.5%, 12843). Among patients with significant pathogenic growth, the prevalence of candiduria was 4.6% (221 out of 4772). Notably, inpatients exhibited a higher incidence of candiduria compared with outpatients, with rates of 9.4% (1882) versus 1.6% (2890), p value of 0.000. Non-albicans Candida spp. (NAC) remained the most prevalent pathogen. Factors significantly associated with candiduria included being female (OR=1.7, 95% CI 1.3 to 2.3) and hospital admission (OR=6.6, 95% CI 4.7 to 9.2). In conclusion, candiduria affect 5 out of every 100 UTI-diagnosed patients, predominantly among females and those admitted to the hospital. Clinicians at tertiary hospitals should consider urinary candidiasis as a potential diagnosis for patients at risk who present with UTI-like symptoms.

Implementation research for promoting access and rational use of antibiotics for children: lessons learnt from Tanzania.

Implementation research (IR) has proved to be a potential catalyst in facilitating the uptake of evidence-based innovations into routine practices and thereby maximizing public health outcomes. IR not only focuses on the effectiveness of the innovations but also identifies and addresses the barriers and facilitators to maximize their uptake into routine practices. This article describes the processes undertaken to implement a research project aimed at promoting access and rational use of antibiotics for children (PARAC). It also provides an overview of the lessons learnt during its implementation in Tanzanian hospital and community settings.

Aetiology of ear infection and antimicrobial susceptibility pattern among patients attending otorhinolaryngology clinic at a tertiary hospital in Dar es Salaam, Tanzania: a hospital-based cross-sectional study.

OBJECTIVES: To determine the aetiological pathogens causing ear infections and their antimicrobial susceptibility patterns among patients with ear complaints at a tertiary hospital in Dar es Salaam. DESIGN: Hospital-based cross-sectional study. SETTINGS: Otorhinolaryngology clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania. PARTICIPANTS: Patients presenting with signs and symptoms of ear infection. MAIN OUTCOME MEASURE: Bacteria and fungi isolated from ear swab specimens of patients presenting with signs and symptoms of ear infection; and antimicrobial susceptibility patterns of isolated bacteria. RESULTS: Two hundred and fifty-five participants were enrolled, with a median age of 31 years and an IQR of 15-49. Otitis externa was the predominant type of ear infection, accounting for 45.1%. We observed positive bacteria culture in 53.3% of study participants, in which 41% of isolates were obtained from patients with chronic suppurative otitis media. Moreover, Staphylococcus aureus (27.3%) and Pseudomonas aeruginosa (24.2%) were the most frequently isolated bacteria, while Candida spp, 12 (63.8%) and Aspergillus spp, 9 (36.2%) were the only isolated fungi. Furthermore, we report that 93% of isolated Enterobacterales were resistant to amoxicillin/clavulanic acid, and 73% were resistant to ceftazidime. In addition, we detected 34.4% extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and 44.4% methicillin-resistance S. aureus (MRSA). We also found that 22% of the bacteria isolates were resistant to ciprofloxacin, a primary topical antibiotic used in managing ear infections. CONCLUSIONS: The findings from this study reveal that the leading aetiological agent of ear infection is bacteria. Furthermore, our findings show a significant proportion of ESBL-PE and MRSA-causing ear infections. Hence, detecting multidrug-resistant bacteria is crucial to improving ear infection management.