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BackgroundTyphoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia.MethodsConsecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012-2013.ResultsSixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (4.3.1.1), with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates.ConclusionsWe report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype 4.3.1.1, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.

ABSTRACT Knowledge on the duration of Cryptosporidium oocyst shedding, and how shedding may be affected by subtypes and clinical parameters, is limited. Reduced transmission may be a secondary benefit of cryptosporidiosis treatment in high-prevalence areas. We conducted a prospective clinical case series in children of

BackgroundCryptosporidiosis is a major cause of diarrhoea in young children in low-and-middle-income countries. New interventions should be informed by evidence pertaining to risk factors and their relative importance. Inconsistencies in the literature may to some extent be explained by choice of methodology, furthermore, most previous risk factor studies compared cryptosporidiosis cases to diarrhoea cases of other aetiologies rather than with controls without diarrhoea.Methodology/principal findingsWe investigated a broad set of factors in under-2-year-olds presenting with diarrhoea to a hospital and a health center in southwestern Ethiopia. We applied quantitative cut-offs to distinguish between cryptosporidiosis and incidental Cryptosporidium infection or carriage, a hierarchical causal framework to minimize confounding and overadjustment, and a case-case-control design, to describe risk factors for both cryptosporidiosis and non-cryptosporidiosis diarrhoea. Moderate and severe acute malnutrition were strongly associated with both cryptosporidiosis and non-cryptosporidiosis diarrhoea. Previous healthcare attendance and low maternal education were only associated with cryptosporidiosis, whereas unsafe child stool disposal, prematurity and early cessation of exclusive breastfeeding were significantly associated with non-cryptosporidiosis diarrhoea only. By estimation of population attributable fractions, socioeconomic factors-specifically low maternal education-and public tap water use, were apparently more important risk factors for cryptosporidiosis than for non-cryptosporidiosis diarrhoea.Conclusions/significanceNutritional management of moderate acute malnutrition may be an effective intervention against cryptosporidiosis, particularly if combined with targeted therapy for cryptosporidiosis which, again, may mitigate nutritional insult. Focused caregiver education in healthcare settings and follow-up of children with acute malnutrition may prevent or improve outcomes of future episodes of cryptosporidiosis.

Objectives: The aim of this study was to characterize molecular mechanisms of resistance to trimethoprim and other antibiotics in Streptococcus pneumoniae isolates from HIV-infected adults in Dar es Salaam, Tanzania. Methods: A total of 1877 nasopharyngeal swabs were collected and screened for pneumococcal colonization from 537 newly diagnosed individuals with HIV at four clinic visits during a 1-year follow-up from 2017–2018 as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov ID: NCT03087890). Results: A total of 76 pneumococcal isolates were obtained. Of the 70 isolates that could be serotyped, 42 (60.0%) were vaccine serotypes included in pneumococcal conjugate vaccine 23 (PCV23). The majority of isolates (73.7%; 56/76) were non-susceptible to penicillin (MICs of 0.06–2 μg/mL). Isolates were frequently resistant to co-trimoxazole (trimethoprim/sulfamethoxazole) (71.1%) but less so to azithromycin (22.4%), erythromycin (21.1%), chloramphenicol (18.4%), tetracycline (14.5%), clindamycin (10.5%) and levofloxacin (0%). Moreover, 26.3% were multidrug-resistant (resistant to ≥3 antibiotic classes). Vaccine-type pneumococci were resistant to more classes of antibiotics, were more frequently resistant to erythromycin, azithromycin, clindamycin and tetracycline, and had higher MICs to penicillin (median, 0.19 μg/mL; range, 0.002–1.5 μg/mL) compared with non-vaccine serotypes (median, 0.125 μg/mL; range, 0.012–0.25 μg/mL) (P = 0.003). Co-trimoxazole-resistant isolates carried from 1 to 11 different mutations in the dihydrofolate reductase (DHFR) gene, most commonly Ile100Leu (100%), Glu20Asp (91.8%), Glu94Asp (61.2%), Leu135Phe (57.1%), His26Tyr (53.1%), Asp92Ala (53.1%) and His120Gln (53.1%). Conclusion: Streptococcus pneumoniae isolated from HIV-diagnosed patients were frequently non-susceptible to penicillin and co-trimoxazole. Most isolates carried multiple mutations in DHFR.

Background. Bacterial infection remains the most common cause of morbidity and mortality in pediatric patients with burn wounds. The increase in infection and multidrug-resistant (MDR) pathogens necessitates a periodic review of antimicrobial susceptibility patterns in the burn units. The study aimed to determine the magnitude of multidrug-resistant Gram-negative (MDRGN) bacteria in children with burn wound infections and describe the resistance patterns in the tertiary and regional hospitals in Dar es Salaam, Tanzania. Materials and Methods. The study was a hospital-based cross-sectional study design conducted between May 2017 and February 2018. Bacterial isolates from 103 wound swabs of pediatric patients with burn wounds were identified using conventional methods and API 20E. The antimicrobial susceptibility pattern was determined by the Kirby–Bauer disc diffusion method. Data were analyzed using Statistical Package for Social Science (SPSS) version 23.0. Results. A total of 136 pathogenic Gram-negative organisms were isolated from burn wound infections in pediatric patients. The most isolated Gram-negative bacterium was Pseudomonas aeruginosa (39.0%), followed by Acinetobacter spp. (28.7%) and Klebsiella spp. (16.2%). MDRGN strains made up 80.1% of all Gram-negative isolates. All (100%) Klebsiella spp. and E. coli were MDR, while 69.2% and 79.2% of Acinetobacter spp. and P. aeruginosa, respectively, displayed MDR strains. We observed high levels of resistance to commonly prescribed antibiotics. Among P. aeruginosa isolates, highest resistance (81.8%) was seen toward meropenem and piperacillin, 79.5% of Acinetobacter spp. showed resistance to aztreonam, while 93–100% of Klebsiella spp and E. coli displayed resistance to amoxyclavulanic acid, ceftriaxone, and ceftazidime. The proportion of extended-spectrum beta-lactamase producers among Enterobacteriaceae was 78.6%. There was a significant higher rate of infection with MDRGN organisms in pediatric patients with a higher percentage of total burn surface area (TBSA) than patients with lower TBSA (p = 0.016). Conclusions. P. aeruginosa, Acinetobacter spp., and Klebsiella spp. are the common Gram-negative pathogens causing burn wound infections in hospitalized pediatric patients in our setting. A high proportion of these organisms were multidrug resistant. The findings appeal for regular antimicrobial resistance surveillance in burn wound infection to inform empirical therapy.