Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

The disc-endplate-bone-marrow complex classification: progress in our understanding of Modic vertebral endplate changes and their clinical relevance.

BACKGROUND CONTEXT: The disc, endplate (EP), and bone marrow region of the spine form a single anatomical and functional interdependent unit; isolated degeneration of any one structure is rare. Modic changes (MC), however, are restricted to the subchondral bone alone and based on only T1 and T2 sequences of MRI. This results in poor reliability in differentiating fat from edema and hence may give a false impression of disease inactivity. PURPOSE: To study the changes in disc, endplate, and bone marrow as a whole in degeneration and propose a classification based on the activity status of this complex with the addition of STIR MRI sequences. STUDY DESIGN: Observational cohort. PATIENT SAMPLE: Patients with isolated brain, cervical, or thoracic spine injury and patients with low back pain (LBP) who underwent MRI formed the control and study groups, respectively. OUTCOME MEASURES: Demographic data, the prevalence of MC and disc-endplate-bone marrow classification (DEBC) changes, EPs undergoing reclassification based on DEBC, and comparison of the prevalence of MC, DEBC, H+modifier and DEBC with H+concordance between control and LBP group. The study determined the risk of LBP patients undergoing surgery as well as the incidence of postoperative infection based on DEBC changes. Significance was calculated by binomial test and chi-square test with the effect size of 0.3 to 0.5. Prevalence and association of outcome were calculated by Altman's odds ratio with the 95% CI and the scoring of z statistics. Logistic expression was plotted for independent variables associated with each class of both Modic and DEBC against dependent variables surgery and nonsurgery. METHODS: Lumbar segments in both groups were assessed for MC types. The DEBC classification was developed with the addition of STIR images and studying the interdependent complex as a whole: type-A: acute inflammation; type-B: chronic persistence; type-C: latent and type-D: inactive. Modifier H+ was added if there was disc herniation. The classification was compared with MC and correlated to clinical outcomes. RESULTS: A total of 3,560 EPs of 445 controls and 8,680 EPs in 1,085 patients with LBP were assessed. Four nonMC, 560 MC-II, and 22 MC-III EPs were found to have previously undetected edema in STIR (n=542) or hyperintensity in discs (n=44) needing reclassification. The formerly undescribed type-B of DEBC, representing a chronic persistent activity state was the most common (51.8%) type. The difference between the control and LBP of H+(12% vs 28.8%) and its co-occurrence with DEBC type 1.1% vs 23.3%) was significant (p<.0001). The odds ratio for the need for surgery was highest (OR=5.2) when H+ and DEBC type change co-occurred. Postoperative deep infection (as determined by CDC criteria) was 0.47% in nonDEBC, compared with 2.4% in patients with DEBC (p=.002), with maximum occurrence in type-B. CONCLUSION: Classification based on the classic MC was found to need a reclassification in 586 EPs showing the shortcomings of results of previous studies. Considering the DEBC allowed better classification and better predictability for the need for surgical intervention and incidence of postoperative infection rate than MC.

Correlation Analysis Between Computed Tomography and Magnetic Resonance Imaging for Assessing Thoracic Pedicle Morphology.

OBJECTIVE: This study aimed to determine the accuracy and reliability of using magnetic resonance imaging (MRI) to characterize thoracic pedicle morphology in the normal population. METHODS: Computed tomography (CT) and MRI datasets of 63 surgically treated patients were included in the study. Bilateral T3, T6, T9, and T12 vertebral levels were evaluated for the type of pedicle, pedicle chord length, and pedicle isthmic diameter on both MRI and CT scans. Pedicles were classified according to Sarwahi et al. into type A (normal pedicle), >4 mm cancellous channel; type B, 2-4 mm channel; type C, completely cortical channels >2 mm; and type D, <2 mm cortical bone channel. RESULTS: Of 504 pedicles, 294 were classified as type A, 173 as type B, 24 as type C, and 13 as type D based on a CT scan. MRI had an overall accuracy rate of 92.86% for detecting type A, 96.53% for type B, and 100% for type C and type D compared with CT scans. Regarding the thoracic levels, MRI had an overall concordance of 97.98% at T3 level, 94.43% at T6 level, 98.11% at T9 level, and 99.3% at T12 level with CT readings. Comparing measurements between MRI and CT studies for pedicle isthmic diameter and pedicle chord length showed moderate to good reliability at all measured levels. CONCLUSIONS: Pedicle measurements obtained by MRI may be used to estimate pedicle dimensions, allowing surgeons to preoperatively determine pedicle screw sizes based on MRI scans alone.

Use of a trauma registry to drive improvement in the regional trauma network systems in Hawassa, Ethiopia.

AIM: Our aim is to establish and analyse the first year of trauma registry data from Hawassa University Comprehensive Specialised Hospital (HUCSH)-an Ethiopian tertiary referral centre. We plan to identify possible trends in injury patterns, access to health care and referral pathways and establish if our observations are in keeping with data published from other sub-Saharan LMIC's. METHODS: Prospective data collection using the WHO trauma registry dataset. All trauma patients presenting to HUCSH between November 2019 and November 2020 were included. Military patients were excluded. DATASET: Age, sex, region of residence, mode of transport to hospital, referral centre, time from injury to arrival in HUCSH, arrival triage category, Kampala Trauma Score (KTS), mechanism of injury, injury type, closed/open fracture and 24 h outcomes. Data statistical analysis was performed to calculate frequencies of the above variables. RESULTS: There were a total of 1919 cases. Fifty-three per cent were caused by road traffic collision and 49% were fracture/dislocations. Public transport was the most common mode to hospital-40%. Seventy-seven per cent of all trauma admissions were referred from other centres, 69% had a mild KTS. A total of 376 patients presented with an open fracture-76% had a low KTS and 67% remained in ED for > 24 h. Sixty-five per cent of ambulances were utilised for mild KTS patients, only 25% of ambulances transported moderate and severe injuries. CONCLUSION: We have shown that a 'one size fits all approach' should not be adopted for LMIC's as trends vary between regions and countries. Improvements are needed in ambulance utilisation, the use of appropriate triaging tools to facilitate initial basic trauma care and appropriate, timely referrals and the management of open fractures.

Systematic review of complications associated with treatment by traditional bone setters for musculoskeletal injury.

In order to synthesise the existing evidence of Traditional Bone Setters' (TBS) treatment and its associated complications in Low and Middle Income Countries (LMICs), we conducted a literature search following PRISMA guidelines. The keywords "traditional bone setter", "traditional bone healer", "traditional bone setting", "fracture", "complication", "low income country"," low to middle income country", "poor outcome" and "death" were searched in PubMed. Articles included in the review demonstrated complications associated with treatment by TBS for Musculoskeletal injury in LMICs. Out of 878 papers screened, twelve studies were finally included for review. Seven were prospective, and five retrospective studies. All were observational studies with all but one hospital based, the remaining being community based, and investigated the outcomes of treatment of fractures by traditional bonesetters published between 1999 and 2020 in LMICs. In total, this review covers 833 participants with 691 complications of TBS treatment. We identify a significant number of limb and life-threatening complications including mortality associated with the treatment by TBS. However, recent studies have shown that TBS are willing and keen to engage with local orthodox services and training courses. As shown in many countries, this can lead to a reduction in complications including mortality and can form a favourable environment where TBS and orthodox services can work side by side.

Increased TGFß1 and SMAD3 Contribute to Age-Related Aortic Valve Calcification.

Aims: Calcific aortic valve disease (CAVD) is a progressive heart disease that is particularly prevalent in elderly patients. The current treatment of CAVD is surgical valve replacement, but this is not a permanent solution, and it is very challenging for elderly patients. Thus, a pharmacological intervention for CAVD may be beneficial. In this study, we intended to rescue aortic valve (AV) calcification through inhibition of TGFß1 and SMAD3 signaling pathways. Methods and Results: The klotho gene, which was discovered as an aging-suppressor gene, has been observed to play a crucial role in AV calcification. The klotho knockout (Kl -/-) mice have shorter life span (8-12 weeks) and develop severe AV calcification. Here, we showed that increased TGFß1 and TGFß-dependent SMAD3 signaling were associated with AV calcification in Kl -/- mice. Next, we generated Tgfb1- and Smad3-haploinsufficient Kl -/- mice to determine the contribution of TGFß1 and SMAD3 to the AV calcification in Kl -/- mice. The histological and morphometric evaluation suggested a significant reduction of AV calcification in Kl -/-; Tgfb1 ± mice compared to Kl -/- mice. Smad3 heterozygous deletion was observed to be more potent in reducing AV calcification in Kl -/- mice compared to the Kl -/-; Tgfb1 ± mice. We observed significant inhibition of Tgfb1, Pai1, Bmp2, Alk2, Spp1, and Runx2 mRNA expression in Kl -/-; Tgfb1 ± and Kl -/-; Smad3 ± mice compared to Kl -/- mice. Western blot analysis confirmed that the inhibition of TGFß canonical and non-canonical signaling pathways were associated with the rescue of AV calcification of both Kl -/-; Tgfb1 ± and Kl -/-; Smad3 ± mice. Conclusion: Overall, inhibition of the TGFß1-dependent SMAD3 signaling pathway significantly blocks the development of AV calcification in Kl -/- mice. This information is useful in understanding the signaling mechanisms involved in CAVD.

Coaching for impact: successful implementation of a multi-national, multi-institutional synchronous research course in Ethiopia.

Purpose: Under the American College of Surgeons' Operation Giving Back, several US institutions collaborated with a teaching and regional referral hospital in Ethiopia to develop a surgical research curriculum. Methods: A virtual, interactive, introductory research course which utilized a web-based classroom platform and live educational sessions via an online teleconferencing application was implemented. Surgical and public health faculty from the US and Ethiopia taught webinars and led breakout coaching sessions to facilitate participants' project development. Both a pre-course needs assessment survey and a post-course participation survey were used to examine the impact of the course. Results: Twenty participants were invited to participate in the course. Despite the majority of participants having connection issues (88%), 11 participants completed the course with an 83% average attendance rate. Ten participants successfully developed structured research proposals based on their local clinical needs. Conclusion: This novel multi-institutional and multi-national research course design was successfully implemented and could serve as a template for greater development of research capacity building in the low- and middle-income country (LMIC) setting.

Myocardial TGFß2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development.

Among the three transforming growth factor beta (TGFß) ligands, TGFß2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGFß2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2flox mice with Tgfb2+/-; cTntCre mice. Tgfb2flox/- embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG+/- mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5-E18.5) were used to determine the role of myocardium-derived TGFß2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFß signaling, was "paradoxically" increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGFß2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development.

Case series of hyena bite injuries and their surgical management in a resource-limited setup: 1-year experience.

Animal bites are a significant cause of morbidity and mortality and pose a major public health problem worldwide. Children are reportedly the most common victims of animal bites. Bites may be limited to superficial tissues or lead to extensive disfiguring injuries, fractures, infections and rarely result in death. Recently, human injuries caused by non-domesticated animals are increasingly common as ecosystems change and humans encroach on previously wild land. Wild animals like hyenas have been reported to prey on humans and cattle in parts of Africa. Discussed here are four children out of 11 patients that presented with hyena bites-the children had severe bites to the face and head with extensive soft tissue loss, fractures and concomitant severe infections that led to high mortality, indicating the necessity for advanced intensive care and multidisciplinary treatment needed in such situations.

Transforming Growth Factor Beta3 is Required for Cardiovascular Development.

Transforming growth factor beta3 (TGFB3) gene mutations in patients of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5)/Rienhoff syndrome are associated with cardiomyopathy, cardiac arrhythmia, cardiac fibrosis, cleft palate, aortic aneurysms, and valvular heart disease. Although the developing heart of embryos express Tgfb3, its overarching role remains unclear in cardiovascular development and disease. We used histological, immunohistochemical, and molecular analyses of Tgfb3-/- fetuses and compared them to wildtype littermate controls. The cardiovascular phenotypes were diverse with approximately two thirds of the Tgfb3-/- fetuses having one or more cardiovascular malformations, including abnormal ventricular myocardium (particularly of the right ventricle), outflow tract septal and alignment defects, abnormal aortic and pulmonary trunk walls, and thickening of semilunar and/or atrioventricular valves. Ventricular septal defects (VSD) including the perimembranous VSDs were observed in Tgfb3-/- fetuses with myocardial defects often accompanied by the muscular type VSD. In vitro studies using TGFß3-deficient fibroblasts in 3-D collagen lattice formation assays indicated that TGFß3 was required for collagen matrix reorganization. Biochemical studies indicated the 'paradoxically' increased activation of canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) pathways. TGFß3 is required for cardiovascular development to maintain a balance of canonical and noncanonical TGFß signaling pathways.

The in vitro anthelmintic properties of browse plant species against Haemonchus contortus is determined by the polyphenol content and composition.

The aims of the present study were to (a) evaluate the anthelmintic activity of 10 East African browse plant extracts, (b) examine their role in inhibition of Haemonchus contortus larval exsheathment, (c) establish relationship between inhibition of larval exsheathment and browse plant extract polyphenol composition. Acetone/water (70/30%) extracts of air dried leaves of Acacia etbaica, Cadaba farinosa, Capparis tomentosa, Dichrostachys cinerea, Dodonaea angustifolia, Euclea racemosa, Maerua angolensis, Maytenus senegalensis, Rhus natalensis and Senna singueana were used. The larval exsheathment inhibition assay (LEIA) was applied using H. contortus third stage larvae (L3) and browse plant extract concentrations of 0, 150, 300, 600, 1200µg/ml in phosphate buffered saline (PBS). Data were analysed using the PROC MIXED procedure of SAS. Polyvinylpolypyrrolidone (PVPP) was used to evaluate whether polyphenols were involved in L3 exsheathment inhibition. All browse plant extracts significantly (P≤0.001) inhibited larval exsheathment in a dose dependent manner. The dose required to inhibit 50% of the larvae (EC50) was highest in C. farinosa and lowest in E. racemosa and M. senegalensis. Significant differences (P<0.001) between the control and PVPP treated A. etbaica, C. tomentosa, M. angolensis, R. natalensis and D. cinerea indicates that larval inhibition was largely due to non-phenol compounds. For E. racemosa, M. senegalensis, D. angustifolia and S. singueana, PVPP treatment reversed inhibition activity and in these extracts, inhibition was mostly attributable to tannin and other polyphenols (kaempferol, quercetin and myricetin based glycosides). Overall, the browse plant extracts have anthelmintic property against H. contortus and larval inhibition resulting from the presence of phenolic and non-phenolic compounds.

Preference of goats (Capra hircus L.) for tanniniferous browse species available in semi-arid areas in Ethiopia.

The objectives were to determine browse species preference of goats using dry matter intake (DMI) as a proxy, to compare preference when offered in combination with polyethylene glycol (PEG) and to establish relationships between browse species intake and chemical compositional data. Air-dried leaves of Acacia etbaica, Cadaba farinosa, Capparis tomentosa, Dichrostachys cinerea, Dodonaea angustifolia, Euclea racemosa, Maerua angolensis, Maytenus senegalensis, Rhus natalensis and Senna singueana were used. Two cafeteria trials, each lasting 10 days, were conducted using four local mature male goats of 2-2.5 years receiving a daily ration of grass hay (4% of body weight) and 200 g wheat bran. In trial 1, goats were offered 25 g of each browse species for a total of 30 min with intake, time spent on consumption and the number of visits to specific browse species recorded at 10-min intervals. In trial 2, the same procedure was followed except that 25 g of PEG 4000 was added to the daily wheat bran ration. Crude protein and neutral detergent fibre in browse species ranged from 69.0-245.5 to 159.8-560.6 g/kg dry matter (DM) respectively. Total phenols and total tannins contents ranged between 3.7-70.6 and 2.5-68.1 mg tannic acid equivalent/g DM, respectively, and condensed tannins 1.7-18.4 Abs550 nm /g DM. Preference indicators measured in the first 10 min of browse species intake differed significantly among browse species and with PEG (p < 0.0001). Principal components explained 69.9% of the total variation in browse species DMI. Despite the high tannin levels, D. cinerea, R. natalensis and A. etbaica were the most preferred species regardless of PEG presence. Tannin levels at the observed browse species DMI did not determine preference, instead, preference appeared to be based on hemicellulose. Determining browse species preference is essential to exploit them to improve nutrient utilization and control parasites in goats.

Effect of in vitro docosahexaenoic acid supplementation to marine algae-adapted and unadapted rumen inoculum on the biohydrogenation of unsaturated fatty acids in freeze-dried grass.

The objective of this study was to examine the ruminal biohydrogenation of linoleic (18:2n-6) and linolenic (18:3n-3) acid during in vitro incubations with rumen inoculum from dairy cattle adapted or not to marine algae and with or without additional in vitro docosahexaenoic acid (DHA, 22:6n-3) supplementation. Treatments were incubated in 100-mL flasks containing 400 mg of freeze-dried grass, 5 mL of strained ruminal fluid, and 20 mL of phosphate buffer. Ruminal fluid was collected just before the morning feeding from 3 cows receiving a control diet (49% ryegrass silage, 39% corn silage, 1% straw, and 11% concentrate, fresh-weight basis) supplemented with marine algae for 21 d (adapted rumen fluid, aRF) or from the same cows receiving the control diet only for 14 d after marine algae supplementation was stopped (unadapted rumen fluid, uRF). In half of the incubation flasks, pure DHA (5 mg) was added as an oil-ethanol solution (100 mL). Incubations were carried out during 0, 0.5, 1, 2, 4, 6, and 24 h. After 24 h, in vitro addition of DHA resulted in greater amounts (mg/incubation) of 18:3n-3 (0.23, 0.43, 0.26, and 0.34 for aRF, aRF+DHA, uRF, and uRF+DHA), 18:2n-6 (0.14, 0.22, 0.15, and 0.20 for aRF, aRF+DHA, uRF, and uRF+DHA) and trans-11, cis-15-18:2 (0.27, 2.40, 0.06, and 2.21 for aRF, aRF+DHA, uRF, and uRF+DHA), whereas no effect of inoculum source was observed. Trans-11-18:1 accumulated after 24 h when aRF was incubated irrespective of in vitro DHA supplementation, whereas in incubations with uRF, accumulation of trans-11-18:1 only occurred when DHA was added (6.40, 4.35, 1.06, and 3.91 for aRF, aRF+DHA, uRF, and uRF+DHA). The increased amounts of trans-11-18:1 were due to the strong inhibition of the reduction to 18:0 because no 18:0 was formed when trans-11-18:1 accumulated after 24 h. The results of the current experiment shows hydrogenation of trans-11, cis-15-18:2 occurred in the absence of in vitro DHA only, whereas substantial hydrogenation of trans-11-18:1 to 18:0 only took place in incubations without DHA and with unadapted rumen inoculum, confirming the higher sensitivity of the latter process to DHA.

Serum IgE levels of tuberculosis patients in a tropical setup with high prevalence of HIV and intestinal parasitoses.

Tuberculosis remains a major health problem worldwide in the era of HIV/AIDS. Co-infection with intestinal parasites has been suggested to worsen the outcome of infection by polarizing the immune response towards Th2. This study investigated serum IgE levels of 241 tuberculosis patients and compared the IgE profiles in the tuberculosis patients either with or without intestinal helminthic infection and/or HIV infection. The serum levels of IgE in tuberculosis patients before initiation of antimycobacterial chemotherapy were found to be 1722 +/- 1290 IU/ml (Mean +/- SD) in HIV seronegatives and 2366 +/- 1849 IU/ml in HIV seropositives. Further, the IgE level was significantly higher in patients coinfected with intestinal helminthes and HIV compared to those infected with helminthes or without coinfection (P < 0.05). Anti-tuberculosis chemotherapy significantly reduced serum IgE levels in HIV seronegative tuberculosis patients (P < 0.05). These findings might indicate an active role of therapy in shifting the immune response towards Th1 which is crucial for prognosis in tuberculosis patients.

Antibiotic sensitivities of common bacterial pathogens in urinary tract infections at Gondar Hospital, Ethiopia.

OBJECTIVE: To determine the prevalence and sensitivity trends of urinary bacterial isolates. DESIGN: A cross-sectional study. SETTING: Gondar College of Medical Sciences (GCMS) Teaching and Referral Hospital, north west Ethiopia. SUBJECTS AND METHODS: Four hundred and twenty urine specimens from 70 in-patient and 350 out-patient cases were studied by quantitative culture method and anti-microbial sensitivity test was done by disc diffusion technique. RESULTS: One hundred and seventy two pathogenic organisms were isolated from 166 patients; the isolation rate was 39.5 %. Among the isolates E. coli, S. aureus, Klebsiella species, coagulase negative Staphylococcus species and Citrobacter species were common accounting for 46.0%, 18.0%, 10.0%, 8.0% and 6.0%, respectively. Of the total isolates 71.5% were Gram negatives. Sensitivity tested against ten antibiotics showed that resistance was common, and the effectiveness of tetracycline, ampicillin, co-trimoxazole, chloramphenicol and penicillin was under 50.0%. The resistance rate was 71.5%, 62.2%, and 62.2%, 54.7% and 40.8%, respectively. Polymixin B, cefoxitin, gentamycin and erythromycin controlled over 76.0% of the common infective agents. Ciprofloxacin did control 98.3% of the organisms. CONCLUSION: Resistance was found to be very high to the commonly used antibiotics. The sensitivity rate for the recently introduced ciprofloxacin was above 98%. Therefore, this antibiotic may be used for empirical therapy of urinary tract infection (UTI) when culture and sensitivity testing is impossible. Strict control on the use of antibiotics and appropriate measures against over the counter availability and self-medication is recommended.

Relapsing fever in Gondar, Ethiopia.

OBJECTIVE: To determine the magnitude of relapsing fever, the rate of Jarisch-Herxheimer reaction (JHR) and its outcome and compare these parameters between adults and children in the same setting, time period and more or less similar management. DESIGN: A retrospective descriptive record analysis. SETTING: Gondar College of Medical Sciences (GCMS) hospital, paediatric ward and medical wards, northwest Ethiopia. SUBJECTS: Clinical records of 262 patients discharged with confirmed diagnosis of primary relapsing fever admitted between September 1995 and August 2000. RESULTS: Of the 13,177 patients admitted during the study period, 262 (1.99%) had a primary diagnosis of relapsing fever of which 70.6% were males. Children below 14 years of age comprised 41.2%. Of the total admissions, 83.6% were from Gondar town and the rest from outside. JHR was observed in 31.7% of the patients. The overall case fatality rate was 4.6%. Bad outcome was observed more frequently in adult patients. CONCLUSIONS AND RECOMMENDATIONS: Relapsing fever is still a public health problem. Because of the potential danger of the epidemic and its outcome it should not be neglected. Preventive programmes must be integrated with other services. Though the JHR is the most feared part of the management of relapsing fever, if health personnel are trained and competent, the management of relapsing fever can be delegated to the peripheral health workers, especially when it occurs in children. Moreover, the reason for bad outcome in adult patients than in children needs to be established.

Multiple drug resistance in urinary pathogens at Gondar College of Medical Sciences Hospital, Ethiopia.

OBJECTIVE: To determine multiple drug resistance and its associated factors of urinary pathogens. DESIGN: Cross-sectional study. SETTING: Gondar College of Medical Sciences teaching and Referral Hospital, Northwest Ethiopia, between January and October 2000. SUBJECTS AND METHODS: Mid stream urine samples from 420 subjects were studied by quantitative culture method. Designed Questionnaires were used for data collection on the previous use of antimicrobials, catheterisation and hospitalisation. MAIN OUTCOME MEASURES: Rates of multiple drug resistance and the associated factors. RESULTS: Multiple drug resistance was common in the isolates tested against ten antibiotics showing more than 68% of the isolates being resistant to two or more antimicrobials. Significant variables associated with this were found to be urinary catheterisation, hospitalisation and previous use of antibiotics for urinary tract infection. CONCLUSION: The rate of multiple drug resistance was very high in this study. Probable contributing factors were found to be previous antibiotic exposure, urinary catheterisation and hospitalisation. Reduction of hospital stays and catheterisation, aseptic care of catheterised patients and selective use of antibiotics and strict follow up of hospital disease controls are recommended.

Electrocardiographic findings in Ethiopians on pentavalent antimony therapy for visceral leishmaniasis.

BACKGROUND: The old short course regimens of pentavalent antimonial (sb(v)) therapy of visceral leishmaniasis (VL) have largely been abandoned worldwide as they are associated with increasing problems of relapse and unresponsiveness. In Ethiopia, some hospitals still use the old interrupted and short course regimen partly because of fear of drug toxicity. OBJECTIVE: To evaluate the safety of the WHO recommended uninterrupted therapy at a dose of 20 mg sb(v)/kg for up to thirty days. DESIGN: A prospective study. SETTING: Patients were recruited from Addis Ababa hospitals and from Konso VL endemic area in southern Ethiopia. SUBJECTS: Forty nine patients who included, ten HIV-positive and 39 HIV-negative, were enrolled for the study. RESULTS: Twenty three HIV-negative patients got treatment for 20 days and the rest, 16 HIV-negative and 10 HIV-positive, were treated for 28 to 30 days. Among HIV-seronegatives, the mean QT interval corrected for heart rate (QTc) at the end of therapy in patients treated for 20 days and 28-30 days was comparable (0.419 +/- 0.031 seconds versus 0.424 +/- 0.027 seconds, respectively). Among patients treated for 28-30 days, the mean QTc in HIV co-infected patients was comparable to that of HIV-negatives (0.416 +/- 0.018 seconds versus 0.424 +/- 0.027). Comparable rates of new ECG changes involving the T waves were observed in two HIV-positive (20%) and two HIV-negative (12.5%) patients treated for 28-30 days, and in seven (30.4%) HIV-negative patients treated for 20 days. Overall, only two (4.1%) patients (all HIV-negative males) had QTc interval > or = 0.50 seconds at the end of therapy. In one patient, the prolonged QTc was noted on the twentieth day with bradycardia of 44/minute. CONCLUSIONS: In Ethiopian VL patients with normal renal function, sb(v) therapy at a daily dose of 20 mg/kg for up to 30 days is safe and only rarely associated with clinically significant bradycardia which resolves after temporary cessation of therapy. Furthermore, in areas with limited facilities, monitoring the pulse rate during antimonial therapy may help detect impending cardiotoxicity.

Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection.

BACKGROUND: A third of the world's population has latent infection with Mycobacterium tuberculosis, and in areas of low endemicity, most cases of active tuberculosis arise as a result of reactivation of latent bacilli. We sought to establish the cellular location of these latent organisms to facilitate their elimination. METHODS: We applied in-situ PCR to sections of macroscopically normal lung tissue from 13 individuals from Ethiopia and 34 from Mexico who had died from causes other than tuberculosis. Sections of lung tissue from six Norwegian individuals (ie, individuals from a non-endemic population) acted as negative controls, and six Ethiopian tuberculosis cases acted as positive controls. FINDINGS: Control necropsy samples from the Norwegian individuals were all negative by in-situ PCR and conventional PCR, whereas all samples from known Ethiopian tuberculosis cases were positive by both methods. However, in macroscopically normal lung tissue from Ethiopian and Mexican individuals without tuberculous lesions, the in-situ PCR revealed five of 13 and ten of 34 positive individuals, respectively. These results were confirmed by conventional PCR with extracted DNA. Positive cells included alveolar and interstitial macrophages, type II pneumocytes, endothelial cells, and fibroblasts. INTERPRETATION: M. tuberculosis can persist intracellularly in lung tissue without histological evidence of tuberculous lesions. M. tuberculosis DNA is situated not only in macrophages but also in other non-professional phagocytic cells. These findings contradict the dominant view that latent organisms exist in old classic tuberculous lesions, and have important implications for strategies aimed at the elimination of latent and persistent bacilli.