ABSTRACT
BACKGROUND: Typhoid 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. METHODS: Consecutively, 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. RESULTS: Sixty-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. CONCLUSIONS: We 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.
Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Drug Resistance, Multiple, Bacterial , Genotype , Microbial Sensitivity Tests , Salmonella typhi , Typhoid Fever , Humans , Salmonella typhi/genetics , Salmonella typhi/drug effects , Salmonella typhi/isolation & purification , Salmonella typhi/classification , Ciprofloxacin/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Typhoid Fever/microbiology , Typhoid Fever/epidemiology , Tanzania/epidemiology , Adolescent , Male , Child , Adult , Young Adult , Female , Child, Preschool , Whole Genome Sequencing , Middle Aged , Infant , AgedABSTRACT
BACKGROUND: Control efforts in Zanzibar reduced the burden of malaria substantially from 2000 to 2015, but re-emergence of falciparum malaria has been observed lately. This study evaluated the prevalence of malaria and performance of routine diagnostic tests among hospitalized fever patients in a 1.5 years period in 2015 and 2016. METHODS: From March 2015 to October 2016, paediatric and adult patients hospitalized with acute undifferentiated fever at Mnazi Mmoja Hospital, Zanzibar were included. The malaria prevalence, and performance of rapid diagnostic test (RDT) and microscopy, were assessed using polymerase chain reaction (PCR) as gold standard. RESULTS: The malaria prevalence was 9% (63/731). Children under 5 years old had lower malaria prevalence (5%, 14/260) than older children (15%, 20/131, p = 0.001) and persons aged 16 to 30 years (13%, 15/119, p = 0.02), but not different from persons over 30 years old (6%, 14/217, p = 0.7). All cases had Plasmodium falciparum infection, except for one case of Plasmodium ovale. Ten malaria patients had no history of visiting mainland Tanzania. The RDT had a sensitivity of 64% (36/56) and a specificity of 98% (561/575), and microscopy had a sensitivity of 50% (18/36) and a specificity of 99% (251/254), compared to PCR. The malaria parasitaemia was lower in patients with false negative results on RDT (median 7 × 103 copies/µL, interquartile range [IQR] 2 × 103 - 8 × 104, p = 0.002) and microscopy (median 9 × 103 copies/µL, IQR 8 × 102 - 7 × 104, p = 0.006) compared to those with true positive RDT (median 2 × 105 copies/µL, IQR 3 × 104 - 5 × 105) and microscopy (median 2 × 105 copies/µL, IQR 6 × 104 - 5 × 105). CONCLUSIONS: The study emphasizes that malaria was a frequent cause of febrile illness in hospitalized patients in Zanzibar in the years 2015-2016, particularly among school age children and young adults. We found evidence of autochthonous malaria transmission in Zanzibar. Compared to PCR, both RDT and microscopy had low sensitivity, and false negative results were associated with low parasitaemia. While low parasitaemia identified only by PCR in a semi-immune individual could be coincidental and without clinical relevance, clinicians should be aware of the risk of false negative results on routine tests.
Subject(s)
Malaria, Falciparum , Malaria , Adolescent , Adult , Child , Child, Preschool , Diagnostic Tests, Routine/methods , Humans , Malaria/diagnosis , Malaria/epidemiology , Malaria, Falciparum/diagnosis , Malaria, Falciparum/epidemiology , Plasmodium falciparum , Prevalence , Sensitivity and Specificity , Tanzania/epidemiology , Young AdultABSTRACT
BACKGROUND: The number of drugs prescribed for old people has been rising in recent decades. With increasing age and multiple medications, the risk of complications and drug prescription complexity increases. Multiple changes to prescriptions could be a factor that improves treatment quality. OBJECTIVES: Our objective was to investigate trends in drug prescriptions and factors that contribute to prescription changes. Specific objectives were to find out whether high numbers of prescription changes are significantly correlated with age, sex, comorbidity, length of care episode, and number of drugs. METHODS: Data were extracted from geriatric clinic records in Stockholm in 2005, 2010, and 2015. Indicators for good drug therapy were used to assess the effects of prescription changes on quality, using an index of inappropriate drug use (IDU). Data were analyzed with Student's t-test, PR test, Wilcoxon's rank sum test, and linear regression. RESULTS: Patients had more comorbidities and used more drugs but had shorter hospital stays and significantly fewer prescription changes in 2015 than in 2005. Length of care episode was significantly associated with prevalence of prescription changes. Our model showed that, for each day by which the length of care episode decreased, the number of prescription changes decreased by 8%. The number of prescription changes was negatively correlated to the IDU index score. CONCLUSIONS: The study showed that more prescription changes were associated with longer care episodes and improved drug prescribing quality as per the IDU index. Given prescription changes are regarded as a quality factor in geriatric care, quality may have decreased along with the length of care episodes between 2005 and 2015.