Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla(CTX-M-15) in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla(CTX-M-15) gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla(CTX-M-15) on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92-98.8%. The data describe an outbreak of a novel bla(CTX-M-15)-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum β-lactamases as well as improvements in hygiene measures in developing countries.

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BackgroundDrug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs.MethodsA prospective single cohort study was conducted at Igombe health centre using artemether-lumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously.ResultsA total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/μl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites.ConclusionThe efficacy of artemether-lumefantrine for treatment of uncomplicated malaria is still high in the study area although the rate of re-infection is higher than previously reported. Parasite clearance after 48 hours was lower compared to previous studies. The prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study area while markers for SP resistance is still high. Artemether-lumefantrine may be selecting for wild type alleles on both positions (437 and 540) of pfdhps.

Objectives: The WHO recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high-burden TB/HIV countries. Design: Retrospective longitudinal cohort. Methods: We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted. Results: Twenty thousand seven hundred and six patients collectively had 316 740 clinic visits, of which 240 161 (75.8%) had documented TB symptom screens. There were 35 701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4--64.0) and 88.8% (95% CI 88.7--88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7--17. Conclusion: Although specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.

Malaria remains common in sub-Saharan Africa, but it is frequently over-diagnosed and over-treated in hospitalized children. HIV is prevalent in many malaria endemic areas and may delay parasite clearance and increase mortality among children with malaria. This prospective cohort study enrolled children with suspected malaria between 3 months and 12 years of age hospitalized at two referral hospitals in Tanzania. Both a thick blood smear (BS) and a malaria rapid diagnostic test (mRDT) were performed. If discordant results were obtained, PCR was performed for P. falciparum. Malaria was confirmed if two out of three tests were positive. Malaria parasite densities were determined for two consecutive days after diagnosis and treatment of malaria. All participants were tested for HIV. Among 1492 hospitalized children, 400 (26.8%) were enrolled with suspected malaria infection. There were 196/400 (49.0%) males, and the median age was 18 [9–36] months. BS was positive in 95/400 (23.8%), and mRDT was positive in 70/400 (17.5%), with moderate agreement (Kappa = 0.598). Concordant results excluded malaria in 291/400 (72.8%) and confirmed malaria in 56/400 (14.0%). PCR performed on 53 discordant results confirmed malaria in 1/39 of the BS-positive/mRDT-negative cases, and 6/14 of the BS-negative/mRDT-positive cases. The prevalence of confirmed malaria was 63/400 (15.8%). In multivariable logistic regression, malaria was associated with HIV (OR 3.45 [1.65–7.20], p=0.001). Current breastfeeding (OR 0.25 [0.11–0.56], p=0.001) and higher hemoglobin (OR 0.70 [0.60–0.81], p<0.001 per 1g/dL) were associated with decreased odds of malaria. Malaria parasite clearance was delayed in HIV-infected participants (p<0.001). Malaria is over-diagnosed even at referral centers in high transmission areas. Hospitalized HIV-infected children are more likely to have malaria and exhibit delayed clearance of parasites. Hospitals should consider using mRDTs as a first step for malaria testing among hospitalized children in sub-Saharan Africa.