Seroprevalence and risk factors of Toxoplasmosis among HIV infected women of child-bearing age attending care and treatment clinics in Dar es Salaam, Tanzania

Background: Toxoplasmosis in HIV-infected women of child-bearing age (HIV-WCB) increases the risk for congenital toxoplasmosis, leading to many complications. However, its magnitude is unknown in this population. Objectives: The study aimed to determine the prevalence and factors associated with toxoplasmosis among HIV-WCB. Methods: This was a cross-sectional study conducted from July to August 2020 among HIV- WCB attending care and treatment clinic (CTC) at Muhimbili National Hospital and Mnazi Mmoja hospital. Questionnaire and TORCH rapid test were used to obtain data and serological testing respectively. Data analysis was done using statistical package for social sciences (SPSS) version 20. Results: Overall, 29.7% of the study participants were positive for anti-T. gondii IgG, whereas none tested positive for IgM. Multivariate analysis showed that the probability of being infected with T. gondii increased by 57.1% for participants who consumed raw vegetables (p=0.005, aOR=0.43, 95%CI = 1.24-8.77). Other common risk factors such as undercooked meat consumption, source of drinking water, and cat ownership at home showed no association. Conclusion: A high number of HIV-WCB have not developed immunity to T. gondii in the study area. Introduction of routine screening during antenatal visits for pregnant women and further epidemiological studies are warranted in the country. Keywords: T. gondii; HIV women

Antimicrobial resistance profile of Enterococcus species and molecular characterization of Vancomycin resistant Enterococcus faecium from the fecal samples of newly diagnosed adult HIV patients in Dar es Salaam, Tanzania

Background: Enterococci are becoming clinically more important especially among immunocompromised patients. Of concern are vancomycin resistant enterococci (VRE) which have both intrinsic and acquired forms of resistance. This work aimed to determine the antimicrobial resistance patterns of Enterococcus spp. and characterize VRE isolate obtained from HIV-infected patient using whole genome sequencing (WGS). Methods: Antimicrobial susceptibility testing was done on 57 enterococci isolates by both the disk diffusion method and Epsilometer test (E-Test). WGS was performed on VRE isolate determined by E-test. Results: Out of the 57 enterococci isolates; 58% (33/57) were E. faecalis, 39% (22/57) E. faecium and 4% (2/57) were E. gallinarum. The highest antimicrobial resistance was observed in E. faecalis isolates. The most prevalent antimicrobial resistance was observed towards quinupristin-dalfopristin (56%, 32/57), followed by ciprofloxacin (28%), tigecycline (18%), daptomycin (16%), chloramphenicol (14%), ampicillin and teicoplanin (2%). Multidrug resistance (MDR) was detected in 11% (6/57) of the isolates. Vancomycin resistance and high-level gentamycin resistance (HLGR) were observed in one E. faecium and one E. faecalis isolates respectively. The VRE was typed as ST80, carried vanA and other resistance genes for aminoglycosides, tetracyclines, quinolones and ampicillin. Furthermore, the isolate had chromosomal mutations responsible for quinolone (gyrA (p.S83I) and parC (p.S80I) and ampicillin (pbp5) resistance. Conclusions: The detection of VRE, HLGR and MDR in the study settings underscores the sustained surveillance of VRE in high-risk groups and institution of infection control measures for prompt identification and isolation of carriers to prevent the spread of VRE in the community and hospital settings

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings A Randomized Clinical Trial

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.publishedVersionPeer reviewe

Gastrointestinal colonization of extended-spectrum beta-lactamase-producing bacteria among children below five years of age hospitalized with fever in Dar es Salaam, Tanzania

Objectives: Gastrointestinal colonization of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) is of concern because prior colonization increases risk for subsequent infections. To date, the link between ESBL-PE faecal carriage and the risk of subsequent ESBL-PE infection has not been well established, and information on carriage of such pathogens among children with invasive infections such as bloodstream infections (BSI) remains to be explored worldwide. Methods: This cross-sectional study was conducted among children under the age of 5 years admitted for febrile illness in Dar es Salaam, Tanzania, between March 2017 and July 2018. We used rectal swabs to screen for ESBL-PE using selective media, ChromID ESBL. Bacterial isolates were identified by MALDI-TOF. Blood cultures were drawn from all children. Antimicrobial susceptibility testing was done using a disk diffusion method. ESBL alleles were identified by real-time PCR and sequencing. Results: The overall prevalence of ESBL-PE carriage was 56% (112/200) and was highest among children 4 to 6 months old (17/21, 81%) (P = 0.05). Children with BSI had high ESBL-PE carriage (78.4%) compared to those without BSI (53.1%) (P = 0.02; aOR 3.4, 95% confidence interval 1.20–9.58). The most common isolate was E. coli (64/112, 45%). Sixteen pairs of ESBL-PE isolates (from the gut and from blood) had a similar antimicrobial susceptibility profile. We detected blaCTX-M gene in 97% of all phenotypically detected ESBL-PE; among those, blaCTX-M-15 was dominant (99%). Conclusion: We report a high prevalence of ESBL-PE faecal carriage among children with BSI in Tanzania. Colonization of ESBL-PE was a risk factor for ESBL-BSI.publishedVersio

Fluoroquinolone resistance among fecal extended spectrum βeta 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 β-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 Citrobacterspp. (100%, 5/5), followed by Klebsiella.pneumoniae (76.1%; 35/46), Escherichiacoli (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

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

BackgroundBacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera.MethodsAntiBiotics 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.ResultsAmong 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.ConclusionsAcute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment.Clinical trials registrationNCT03130114