Salmonella enterica serovar Typhi H58 clone has been endemic in Zimbabwe from 2012 to 2019.

BACKGROUND: Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. OBJECTIVES: To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. METHODS: A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. RESULTS: A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, ß-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs. CONCLUSIONS: This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.

The Effect of Hearing Loss on Novel Word Learning in Infant- and Adult-Directed Speech.

OBJECTIVES: Relatively little is known about how young children with hearing impairment (HI) learn novel words in infant- and adult-directed speech (ADS). Infant-directed speech (IDS) supports word learning in typically developing infants relative to ADS. This study examined how children with normal hearing (NH) and children with HI learn novel words in IDS and ADS. It was predicted that IDS would support novel word learning in both groups of children. In addition, children with HI were expected to be less proficient word learners as compared with their NH peers. DESIGN: A looking-while-listening paradigm was used to measure novel word learning in 16 children with sensorineural HI (age range 23.2 to 42.1 months) who wore either bilateral hearing aids (n = 10) or bilateral cochlear implants (n = 6) and 16 children with NH (age range 23.1 to 42.1 months) who were matched for gender, chronological age, and maternal education level. Two measures of word learning were assessed (accuracy and reaction time). Each child participated in two experiments approximately 1 week apart, one in IDS and one in ADS. RESULTS: Both groups successfully learned the novel words in both speech type conditions, as evidenced by children looking at the correct picture significantly above chance. As a group, children with NH outperformed children with HI in the novel word learning task; however, there were no significant differences between performance on IDS versus ADS. More fine-grained time course analyses revealed that children with HI, and particularly children who use hearing aids, had more difficulty learning novel words in ADS, compared with children with NH. CONCLUSIONS: The pattern of results observed in the children with HI suggests that they may need extended support from clinicians and caregivers, through the use of IDS, during novel word learning. Future research should continue to focus on understanding the factors (e.g., device type and use, age of intervention, audibility, acoustic characteristics of input, etc.) that may influence word learning in children with HI in both IDS and ADS.

Indeterminate Pulmonary Nodules in Resected Liver Metastases from Colorectal Cancer: A Comparison of Patient Outcomes.

AIMS: Hepatic metastasectomy remains the only potentially curative treatment for colorectal liver metastases (CRLM). Some of these patients develop indeterminate pulmonary nodules (IPNs). This study aimed to compare outcomes of patients with and without IPN undergoing resection of CRLM to ascertain whether their presence is clinically significant. METHODS: Cases and controls were identified from a prospectively maintained database of CRLM resections. Patients with staging radiology demonstrating IPNs were included as cases. Controls were matched to the cases by four primary factors: age, type of resection (primary or redo), clinical risk score (CRS) and chemotherapy. RESULTS: The median disease-free survival (DFS) and overall survival (OS) for the cases were 7.0 months (95% CI 4.8-9.2) and 28.6 months (95% CI 21.2-36.0), respectively, and 12.0 months (95% CI 10.7-13.2) and 30.5 months (95% CI 19.4-41.6) for the controls. The 1-, 3- and 5-year survival rates were 92.7, 39.7 and 0.0% for the IPN group, and 92.4, 32.9 and 21.9% for those without. In total, 60.7% of IPN patients progressed to lung metastases, of which 39.3% underwent pulmonary resections. DFS was significantly shorter in the IPN group (p = 0.022), but OS was not significantly different (p = 0.421). The presence of IPN was independently associated with a shortened DFS (p = 0.027), as was a CRS of 3 or greater (p = 0.007). CONCLUSION: This study suggests that IPN does not significantly affect OS, but may predict earlier disease recurrence. IPN presence alone should not preclude radical resection but could be used to prompt more careful post-operative surveillance to detect lung metastases at a potentially operable stage.

Etiology and risk factors of meningitis in patients admitted at a Central Hospital in Harare.

Objective: To determine etiology and risk factors of meningitis in patients admitted a tertiary referral Hospital in Harare. Design: Cross-Sectional Study. Setting: Urban Referral Health Facility. Subjects: Patients suspected of having Meningitis admitted at Parirenyatwa Hospital were consecutively consented and recruited into the study until sample size accrual. Main Outcome Measures: Prevalence of pathogens associated with Meningitis. Risk factors of meningitis. Results: Two Hundred and Ninety Six (296) clinically suspected meningitis patients were recruited into the study, 51.7 %( n=115) were male. Meningitis was confirmed in 20.6% (n=61) cases with the following pathogen proportions, C. neoformans - 45.9 %( n=28), S. pneumoniae ­ 27.9 % (n=17), TBM ­ 4.9 %( n=3), probable viral meningitis ­ 6.6% (n=4 and other bacteria- 14.8% (n=9). Patients from crowded households were also more likely to suffer from meningitis than those from sparsely populated households (p<0.001). Conclusion: The use of Latex agglutination increases the proportion of detected pathogens both fungal and bacterial when used in conjunction with CSF gram stain and culture. Cryptococcus neoformans and S. pneumoniae are the leading causes of meningitis in patients admitted at Parirenyatwa Hospital.

Cryptococcus gattii: A dilemma in diagnosis and treatment in sub-Saharan Africa an area with high HIV prevalence.

Sub-Saharan Africa contributes at least 70% of the global cryptococcal meningoencephalitis cases each year and the majority of cases are caused by the Cryptococcus neoformans species. We present a case of meningoencephalitis due to Cryptococcus gattii in an 18 year old apparently immunocompetent male patient from Zimbabwe.

Auditing use of antibiotics in Zimbabwean neonates.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in low-income settings. As signs of sepsis are non-specific and deterioration precipitous, antibiotics are often used profusely in these settings where diagnostics may not be readily available. Harare Central Hospital, Zimbabwe, delivers 12000 babies per annum admitting ∼4800 to the neonatal unit. Overcrowding, understaffing and rapid staff turnover are consistent problems. Suspected sepsis is highly prevalent, and antibiotics widely used. We audited the impact of training and benchmarking intervention on rationalizing antibiotic prescription using local, World Health Organization-derived, guidelines as the standard. METHODS: An initial audit of admission diagnosis and antibiotic use was performed between 8th May - 6th June 2018 as per the audit cycle. An intern training programme, focusing on antimicrobial stewardship and differentiating between babies 'at risk of' versus 'with' clinically-suspected sepsis was instituted post-primary audit. Re-audit was conducted after 5 months. RESULTS: Sepsis was the most common admitting diagnosis by interns at both time points but reduced at repeat audit (81% versus 59%, P<0.0001). Re-audit after 5 months demonstrated a decrease in antibiotic prescribing at admission and discharge. Babies prescribed antibiotics at admission decreased from 449 (98%) to 96 (51%), P<0.0001. Inpatient days of therapy (DOT) reduced from 1243 to 1110/1000 patient-days. Oral amoxicillin prescription at discharge reduced from 349/354 (99%) to 1% 1/161 (P<0.0001). CONCLUSION: A substantial decrease in antibiotic use was achieved by performance feedback, training and leadership, although ongoing performance review will be key to ensuring safety and sustainability.

The three-dimensional structural characterization of hexachlorocyclopentenyl-dibromocyclooctane (HCDBCO).

The 1H NMR spectrum and the crystal structure of HCDBCO [(1R,2R,5R,6R,9S,10S)-5,6-dibromo-1,10,11,12,13,13-hexachlorotricyclo[8,2,1,0(2,9)]-tridec-11-ene)] are reported. The measured dihedral angles from the X-ray structure correlate very well with those calculated from the proton-proton coupling constants indicating that the conformations in solution and in the solid state are probably very similar. Attempts at calculating the 3D model structure of HCDBCO only produced a very poor match between the measured dihedral angles between vicinal protons and the observed proton-proton coupling constants from the 1H NMR spectrum. GC/MS analysis with an injector temperature of 250 degrees C produced minor amounts of debrominated HCDBCO. Reducing the temperature to 200 degrees C eliminated this problem.

Formation Constants and Conformational Analysis of Carbamates in Aqueous Solutions of 2-Methylpiperidine and CO2 from 283 to 313 K by NMR Spectroscopy.

Quantitative 13C nuclear magnetic resonance (NMR) spectroscopy was used to investigate the speciation in (2-methylpiperidine + H2O + CO2) systems at 283.2-313.2 K. The carbamate of 2-methylpiperidine(2-methylpiperidine- N-carboxylate) was shown for the first time to be a stable species in aqueous solutions. The spectroscopic results were used to obtain temperature-dependant formation constants for the carbamate using a simplified model for the activity coefficients from which the standard molar enthalpy of reaction was estimated. The results were incorporated into a self-consistent chemical equilibrium model, which includes vapor-liquid equilibria and all aqueous species, including the formation of carbamate. The predominant conformation of the sterically hindered carbamate, which was determined using two-dimensional exchange spectroscopy NMR, has the methyl group in the axial orientation and is in agreement with the density functional theory quantum chemical calculations.

Theoretical studies of the conformations and 19F NMR spectra of linear and a branched perfluorooctanesulfonamide (PFOSAmide).

Technical perfluorooctanesulfonate (PFOS) and its derivatives, such as perfluorooctanesulfonamide (PFOSA), are not clean compounds but, instead, complex mixtures of linear and branched isomers, and other compounds including sulfonate homologues. Questions have been raised as to whether the linear and the branched isomers behave differently in the environment. However, little is known about the physical properties or the finer details of the structures of the individual branched isomers. This study sought an effective computational method to model the preferred conformations of PFOS derivatives, and the energy differences between them and to determine if these results can be used to explain the temperature dependence of their NMR spectra. Good predictions of the 19F chemical shifts were obtained for some PFOSA-type molecules with a computational approach [B3LYP-GIAO/6-31++G(d,p)//B3LYP/6-31G(d,p)] that is relatively inexpensive. Large 5JFF couplings found in one of the branched isomers could be rationalized on the basis of the relevant F-F distances in the optimized structure. At low temperatures, the splitting observed in the NMR spectrum at C-1 for these sulfonamides can be explained by the existence of the two conformers predicted by the computations.

Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients.

OBJECTIVE: To determine the causative organisms and characteristics of patients presenting with features of meningitis. DESIGN: A prospective cross-sectional study. SETTING: Two tertiary university-affiliated hospitals in Harare, Zimbabwe. PATIENTS: Four-hundred and six patients clinically suspected to have meningitis. MAIN OUTCOME MEASURES: Causative organisms of meningitis; clinical and cerebrospinal fluid characteristics. RESULTS: Four-hundred and six predominantly adult (95% were aged > or = 18 years) patients were suspected to have meningitis. Of the 200 patients confirmed to have meningitis, 89 (45%) had cryptococcal meningitis (CM), 54 (27%) had mononuclear meningitis (MM), 31 (16%) had pyogenic meningitis (PM), 24 (12%) had tuberculous meningitis (TBM) and 2 (1%) had undefined meningitis. HIV seropositivity was 100% in CM, 83% in MM, 81% in PM and 88% in TBM patients. In-hospital mortality rate was 38.8% for CM, 34.9% for MM, 68% for PM and 66.7% for TBM. HIV seropositivity was 80% in the 206 patients not found to have meningitis. CONCLUSIONS: All patients suspected to have meningitis had a high HIV sero positivity irrespective of whether they were later confirmed to have meningitis or not. CM was the most common type of meningitis seen. In-hospital mortality was high irrespective of the cause of meningitis.

A prospective study of infants of human immunodeficiency virus seropositive and seronegative women with a history of intravenous drug use or of intravenous drug-using sex partners, in the Bronx, New York City.

A prospective study was conducted in the Bronx, New York, of 70 infants of human immunodeficiency virus (HIV)-infected (n = 33) and uninfected (n = 37) mothers who had a history of intravenous drug use or of intravenous drug-using sex partners. Infants were observed from birth to a median age of 23 months (range 3 to 54 months). HIV infection was confirmed in seven infants (21%) of seropositive mothers; six developed HIV disease, with symptoms observed in the first year. Of these, three died (3, 9, and 36 months) of HIV-related causes; 3 of 4 survivors were greater than 25 months of age. HIV symptoms preceded or were concurrent with abnormalities in T-lymphocyte subsets; postneonatal polymerase chain reaction confirmed HIV infection in five infants with symptoms and one without symptoms. Among infants of seropositive mothers, seven without laboratory evidence of HIV (including polymerase chain reaction) had findings suggestive of HIV infection, including persistent generalized lymphadenopathy, hepatosplenomegaly, oral candidiasis, parotitis, and inverted T-lymphocyte ratios. These findings were not observed in infants of seronegative mothers. Although the presence of HIV proviral sequences was associated with HIV disease, the observation of indeterminate symptoms in at-risk infants indicates the importance of long-term clinical follow-up to exclude HIV infection. Disease manifestations in comparable infants of seronegative mothers are important for assessment of the impact of maternal drug use, development of specific clinical criteria for early diagnosis of HIV and eligibility for antiretroviral therapy.

Mixed erythrocyte chimerism: implications for tolerance of the donor immune system to recipient non-ABO system red cell antigens.

We report a case of a minor degree of ABO incompatibility in a BMT recipient, demonstrating mixed RBC chimerism, who, late in the post-transplant period, developed a warm autoimmune hemolytic anemia and subsequently developed antibodies with donor-anti-recipient specificities for non-ABO system RBC antigens. While this implies a lack of tolerance of the donor immune system for recipient non-ABO system RBC antigens, other factors may be operating and should be evaluated before such a conclusion is reached. Underscored is the importance of obtaining pretransplant RBC antigen phenotypes on both the recipient and donor.

Setting safe and effective suction pressure: the effect of using a manometer in the suction circuit.

OBJECTIVES: To establish the levels of pressure used to perform tracheal suction (TS) and if they are affected by having a manometer visible in the suction circuit. DESIGN: A bench test evaluation of simulated tracheal suction. SETTING: Physiotherapy department of a major teaching hospital in Melbourne, Australia. PARTICIPANTS: Sixty-four nurses and physiotherapists who regularly apply TS to patients in the intensive care units of this hospital. INTERVENTIONS: All subjects used both circuit A (without a visible manometer) and B (with a visible manometer) in a predetermined random order. For both, subjects adjusted the suction control tap to where they said a safe and effective pressure (set pressure) was delivered and then occluded the suction catheter as though suctioning (applied pressure). Subjects then completed a questionnaire on their current TS practise. MEASUREMENTS AND RESULTS: All set pressures (mean = 228.57 mmHg) and all applied pressures (mean = 359. 52 mmHg) were significantly higher (P <.001) when compared to the expected pressures (mean = 135 mmHg). Pressures set without a visible manometer (circuit A) were significantly higher (P <.05) than those using a visible manometer (circuit B) but the applied pressures were not significantly different (P =.166). Neither the investigator (P =.618) or the test order (P =.167) had a significant effect on the outcome. Questionnaire results showed 31 % of subjects considered 100-170 mmHg a safe and effective suction pressure whilst none reported using an objective means of measuring pressure. CONCLUSION: All pressures in both circuits were significantly higher than those recommended as safe in the literature. In addition, pressures were unaffected by the inclusion of a visible manometer in the suction circuit.

Clinicopathological features of cutaneous histoplasmosis in human immunodeficiency virus-infected patients in Zimbabwe.

Reports of disseminated Histoplasma infection in African AIDS patients are scanty. In Zimbabwe, 12 patients presented in 1994-2000 with facial nodular/papular cutaneous lesions, which became umbilicated and finally ulcerated. Histology revealed non-granulomatous inflammation and macrophages stuffed with Histoplasma. Recognition of these clinical features may lead to more rapid diagnosis of disseminated histoplasmosis in Africa.

Pulmonary diseases in patients infected with the human immunodeficiency virus in Zimbabwe, Central Africa.

During the 11 month period up to 30 September 1987, 37 patients (26 male, 11 female, mean age 27 years) with respiratory symptoms who were human immunodeficiency virus (HIV) positive, were studied prospectively on 40 occasions to determine the cause of any pulmonary complications. HIV was heterosexually transmitted. Predominant symptoms were cough (89%), fever (89%), weight loss (83%), and dyspnoea (60%). Transnasal fibre-optic bronchoscopy (with bronchoalveolar lavage, bronchial brushings and transbronchial lung biopsies) was performed on 35 patients, twice on 3 patients. 'Tru-cut' lung biopsies were obtained from 2 patients who died before bronchoscopy. Pulmonary tuberculosis was the commonest disease, being found in one-third of the patients (12 of 37). Mycobacterium tuberculosis was cultured from 4; the remainder of the plates were contaminated. Pneumocystis carinii was present in 8 patients: as the sole pathogen in 3, with Streptococcus pneumoniae in 4, Staphylococcus aureus in 2, and one also had tuberculous lymphadenitis. Endobronchial Kaposi's sarcoma was seen in 6 of 7 patients with skin nodules. Bacterial pathogens isolated included Staph. aureus (5), S. pneumoniae (5), Klebsiella pneumoniae (2), Haemophilus influenzae (2), H. parainfluenzae (1) and Pseudomonas aeruginosa (1). Invading Aspergillus fumigatus was diagnosed by lung biopsy in one. No diagnosis was reached for 8 patients. It is concluded that in Central Africa pulmonary complications in AIDS patients are similar to those in Europe and North America but the incidence of different pathogens depends on the prevalence of pathogens in the community. M. tuberculosis is probably the commonest pathogen. This study has confirmed that P. carinii pneumonia does occur, but occurs less frequently.

Research and the cumulation of knowledge in Physical Therapy.

BACKGROUND AND PURPOSE: Published research contributes to the knowledge base that distinguishes one discipline from another. More research is now published in the physical therapy journals, but concerns with the profession's knowledge base continue. SUBJECTS: The study examined citations from 78 clinical articles published and indexed on three thematic areas in Physical Therapy between 1951 and 1990. METHODS: Unique items and multiple-cited items were identified and counted and their sources ascertained. Linkages among multiple-cited items in each thematic area were identified and described. RESULTS: Most cited items were unique and not from the physical therapy literature. Few linkages were identified among the clinical articles. CONCLUSION AND DISCUSSION: The lack of evidence of cumulation or of coherence among the articles examined and the extent of reliance on non-physical therapy sources suggest that concerns with the knowledge base of the profession are well founded.

A quantitative analysis of research in Physical Therapy.

BACKGROUND AND PURPOSE: Some physical therapists argue that research will justify and improve practice in the discipline. Whether these outcomes can be realized is partly a function of the nature of the research, the research methods used, and the extent to which clinical treatments are investigated. SUBJECTS AND METHODS: This study analyzed aspects of a sample of 272 articles published in Physical Therapy during 1954 through 1993. Each article was read and categorized according to the method used and to whether it investigated clinical treatments. RESULTS: An increasing percentage of the articles sampled described studies that used group designs, and most of the studies did not investigate clinical treatments. CONCLUSION AND DISCUSSION: These findings are paradoxical given existing criticisms of group designs and expectations in physical therapy of research. More discussions and evaluations of current research practices in physical therapy are needed.

A review of therapeutic ultrasound: effectiveness studies.

BACKGROUND AND PURPOSE: Therapeutic ultrasound is one of the most widely and frequently used electrophysical agents. Despite over 60 years of clinical use, the effectiveness of ultrasound for treating people with pain, musculoskeletal injuries, and soft tissue lesions remains questionable. This article presents a systematic review of randomized controlled trials (RCTs) in which ultrasound was used to treat people with those conditions. Each trial was designed to investigate the contributions of active and placebo ultrasound to the patient outcomes measured. Depending on the condition, ultrasound (active and placebo) was used alone or in conjunction with other interventions in a manner designed to identify its contribution and distinguish it from those of other interventions. METHODS: Thirty-five English-language RCTs were published between 1975 and 1999. Each RCT identified was scrutinized for patient outcomes and methodological adequacy. RESULTS: Ten of the 35 RCTs were judged to have acceptable methods using criteria based on those developed by Sackett et al. Of these RCTs, the results of 2 trials suggest that therapeutic ultrasound is more effective in treating some clinical problems (carpal tunnel syndrome and calcific tendinitis of the shoulder) than placebo ultrasound, and the results of 8 trials suggest that it is not. DISCUSSION AND CONCLUSION: There was little evidence that active therapeutic ultrasound is more effective than placebo ultrasound for treating people with pain or a range of musculoskeletal injuries or for promoting soft tissue healing. The few studies deemed to have adequate methods examined a wide range of patient problems. The dosages used in these studies varied considerably, often for no discernable reason.