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Leptospirosis is a neglected zoonotic disease. In 2015, leptospirosis was diagnosed in 2 prison inmates in South Africa. Using real-time PCR and DNA sequencing, we identified Leptospira interrogans serogroup Icterohaemorrhagiae in rodents and water samples within the prison. Leptospirosis might be frequently underdiagnosed in South Africa.

BackgroundThis study investigated the value of prognostic scores to predict 90-day, 1-, 3- and 5-year survival after salvage TIPS (sTIPS) in patients with exsanguinating variceal bleeding who failed endoscopic intervention.MethodsThe Model for End-Stage Liver Disease (MELD), Model for End-Stage Liver Disease Sodium (MELD-Na), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Child-Pugh (C-P) grades and scores were calculated using Kaplan-Meier curves and Cox proportional hazards models in sTIPS patients treated between August 1991 and November 2020.ResultsThirty-four patients (29 men, 5 women), mean age 52 years, SD ± 11.6 underwent sTIPS which controlled bleeding in 32 (94%) patients. Ten (29.4%) patients died in hospital at a median of 4.8 (range 1–10) days. On bivariate analysis, C-P score ≥ 10 (p = 0.017), high C-P grade (p = 0.048), MELD ≥ 15 (p = 0.010), MELD-Na score ≥ 22 (p 10 units of blood transfused (p = 0.004), balloon tube placement (p < 0.001), endotracheal intubation (< 0.001) and inotrope support (p < 0.001).The overall 90-day, 1-, 3- and 5-year survival rates were 67.6%, 55.9%, 26.5% and 20.6% respectively. Nine patients (26.5%) were alive at a median of two years (range 1–18 years) post-TIPS. Patients with C-P grade A, C-P score < 10, MELD score < 15, MELD-Na score < 22 and APACHE II score < 15 had significantly better 90-day, 1-, 3- and 5-year survival rates.ConclusionAlthough sTIPS controlled variceal bleeding in 94% of patients after failed endoscopic therapy, in-hospital mortality was 29% and less than one quarter were alive after five years. The selected cut-off values for the nominated scoring systems accurately predicted 90-day mortality and long-term survival.

Background: Major pancreatic injuries are complex to treat, especially when combined with vascular and other critical organ injuries. This case-matched analysis assessed the influence of associated visceral vascular injuries on outcome in pancreatic injuries. Method: A registered prospective database of 461 consecutive patients with pancreatic injuries was used to identify 68 patients with a Pancreatic Injury combined with a major visceral Vascular Injury (PIVI group) and were matched one-to-one by an independent blinded reviewer using a validated individual matching method to 68 similar Pancreatic Injury patients without a vascular injury (PI group). The two groups were compared using univariate and multivariate logistic regression analysis and outcome including complication rates, length of hospital stay and 90-day mortality rate was measured. Results: The two groups were well matched according to surgical intervention. Mortality in the PIVI group was 41% (n = 28) compared to 13% (n = 9) in the PI alone group (p = 0.000, OR 4.5, CI 1.00-10.5). On univariate analysis the PIVI group was significantly more likely to (i) be shocked on admission, (ii) have a RTS < 7.8, (iii) require damage control laparotomy, (iv) require a blood transfusion, both in frequency and volume, (v) develop a major postoperative complication and (vi) die. On multivariate analysis, the need for damage control laparotomy was a significant variable (p = 0.015, OR 7.95, CI 1.50-42.0) for mortality. Mortality of AAST grade 1 and 2 pancreatic injuries combined with a vascular injury was 18.5% (5/27) compared to an increased mortality of 56.1% (23/41) of AAST grade 3, 4 and 5 pancreatic injuries with vascular injuries (p = 0.0026) Conclusion: This study confirms that pancreatic injuries associated with major visceral vascular injuries have a significantly higher complication and mortality rate than pancreatic injuries without vascular injuries and that the addition of a vascular injury with an increasing AAST grade of pancreatic injury exponentially compounds the mortality rate.

Background This study evaluated factors influencing mortality in a large cohort of patients who sustained pancreatic injuries and underwent DCS. Methods A prospective database of consecutive patients with pancreatic injuries treated at a Level 1 academic trauma centre was reviewed to identify those who underwent DCS between 1995 and 2014. Results Seventy-nine (71 men, median age: 26 years, range 16–73 years, gunshot wounds = 62, blunt = 14, stab = 3) patients with pancreatic injuries (35 proximal, 44 distal) had DCS. Fifty-nine (74.7 %) patients had AAST grade 3, 4 or 5 pancreatic injuries. The 79 patients had a total of 327 associated injuries (mean: 3 per patient, range 0–6) and underwent a total of 187 (range 1–7) operations. Vascular injuries (60/327, 18.3 %) occurred in 41 patients. Twenty-seven (34.2 %) patients died without having a second operation. The remaining 52 patients had two or more laparotomies (range 2–7). Overall 28 (35 %) patients underwent a pancreatic resection either during DCS ( n  = 18) or subsequently as a secondary procedure ( n  = 10) including a Whipple ( n  = 6) when stable. Overall 43 (54.4 %) patients died. Mortality was related to associated vascular injuries overall ( p  < 0.01), major visceral venous injuries ( p  < 0.01) and combined vascular and total number of associated organs injured ( p  < 0.04). Conclusions Despite the magnitude of their combined injuries and the degree of physiological insult, DCS salvaged 45 % of critically injured patients who later underwent definitive pancreatic surgery. Mortality correlated with associated vascular injuries overall, major visceral venous injuries and the combination of vascular plus the total number of associated organs injured.

Rationale The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. Methods South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (∼10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. Results 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. Conclusions MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Background Orthopaedic surgery is rated among the most painful of surgeries, leaving patients at risk of experiencing moderate to severe postoperative pain. A multimodal analgesic approach helps reduce opioid requirements, with nonsteroidal anti-inflammatory drugs (NSAIDs) playing a key role in this strategy, provided they are not contraindicated. However, only limited guidance exists for safe perioperative NSAID use in orthopaedic patients with comorbidities. The objective of the study was to achieve consensus on safe, short course (≤ 1 week) administration of NSAIDs in adult orthopaedic patients with comorbidities, and to convert the results into a decision tool to aid clinicians in safe perioperative NSAID administration. Methods A Delphi panel of 18 experienced orthopaedic surgeons, physicians and anaesthetists participated in a three-round Delphi process. The panel assessed 42 patient characteristics using a nine-point Likert scale in the first two rounds. After the second round, consensus was defined as ≥ 75% either ‘disagreeing’ (Likert scale 1–3) or ‘agreeing’ (Likert scale 7–9) that NSAIDs ± proton pump inhibitors (PPIs) could or could not be administered safely. Characteristics without consensus by round 2 moved to round 3, where subspecialty experts conducted a rapid review of the literature. Consensus in this round required ≥ 75% support for expert recommendations. Results All panel members participated in the first and third rounds, with 16 in the second. After the second round, consensus was achieved for 24 of 42 patient characteristics. However, in preparation for the third round, three characteristics which had achieved consensus after round 2 were added to the pool of characteristics to be considered by subspeciality experts, resulting in 21 proceeding to the third round. In round 3, consensus for all remaining subspeciality expert recommendations was achieved and an NSAID decision tool with guidance in safe perioperative NSAIDs use ± PPIs was subsequently developed for the 42 patient characteristics. Conclusion This study establishes a consensus on short-term NSAID administration in adult orthopaedic patients with comorbidities, offering a decision tool to guide clinicians in safely incorporating NSAIDs into perioperative pain management strategies.

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, there was a reduction in access to prevention of mother-to-child transmission (PMTCT) of human Immunodeficiency virus (HIV) services globally, yet this programme is critical for reducing paediatric HIV incidence. To minimise the impact of COVID-19 and prevent disruptions to the PMTCT service provision, innovative strategies had to be developed and implemented.AimThe study aimed to describe the approaches that were developed and utilised during the COVID-19 pandemic in enhancing PMTCT services in Tshwane primary healthcare facilities.SettingsThree primary healthcare facilities that were providing PMTCT services during the COVID-19 pandemic located in the Tshwane district, Gauteng province, South Africa.MethodsThe study is part of a larger study that focused on the experiences of healthcare workers who were rendering PMTCT services during the COVID-19 pandemic. An interpretative phenomenological analysis (IPA) design was employed to gain insight into the experiences of 16 purposively sampled healthcare workers who were providing PMTCT services during the pandemic in Tshwane district facilities. In-depth individual audio-recorded interviews were conducted with study participants, following a semi-structured interview guide. Data analysis was performed using an IPA framework.ResultsThree superordinate themes emerged: strategies utilised for providing care, community-based initiatives, and support systems to enhance the PMTCT service access.ConclusionStrengthening community-based initiatives and support systems is important for the enhancement of the PMTCT programme during and beyond the pandemic.ContributionCommunity-based initiatives are critical in continuity of PMTCT services, reducing HIV incidence, under-five child morbidity and mortality particularly during emergency situations.

BackgroundThere are limited data on the outcomes of rechallenge with anti-tuberculosis therapy (ATT) following anti-tuberculosis drug-induced liver injury (AT-DILI) in a high HIV prevalence setting.ObjectivesTo describe the outcomes of rechallenge with first-line ATT.MethodHospitalised participants with AT-DILI who were enrolled into a randomised controlled trial of N-acetylcysteine in Cape Town, South Africa, were followed up until completion of ATT rechallenge. We described rechallenge outcomes, and identified associations with recurrence of liver injury on rechallenge (positive rechallenge).ResultsSeventy-nine participants were rechallenged of whom 41 (52%) were female. Mean age was 37 years (standard deviation [s.d.] ±10). Sixty-eight (86%) were HIV-positive, of whom 34 (50%) were on antiretroviral therapy (ART) at time of AT-DILI presentation. Five participants had serious adverse reactions to an aminoglycoside included in the alternate ATT regimen given after first-line ATT interruption: acute kidney injury in three and hearing loss in two. The median time from first-line ATT interruption to start of first-line ATT rechallenge was 13 days (interquartile range [IQR]: 8–18 days). Antiretroviral therapy was interrupted for a median of 32 days (IQR: 17–58) among HIV-positive participants on ART before AT-DILI. Fourteen participants had positive rechallenge (18%). Positive rechallenge was associated with pyrazinamide rechallenge (P = 0.005), female sex (P = 0.039) and first episode of tuberculosis (TB) (P = 0.032).ConclusionRechallenge was successful in most of our cohort. Pyrazinamide rechallenge should be carefully considered.

Background Helicobacter pylori resistance to antibiotics commonly used in eradication regimens is increasing dramatically in many locations; new strategies are needed to manage this infectious disease.ObjectiveThis study’s aim was to collect and update information on antibiotic resistance (AR) rates in H. pylori as well as current strategies for H. pylori management, including public health issues, from a global perspective.DesignAn international survey was conducted in 31 countries on 6 continents to address key issues concerning the management of H. pylori-related AR. Individual aspects included the prevalence of AR for specific antibiotics, antibiotic susceptibility testing (AST) in different healthcare systems, availability of drugs, reimbursement issues and strategies for H. pylori AR surveillance.ResultsResistance to the most effective antibiotics used in H. pylori eradication regimens is increasing globally, with clarithromycin and levofloxacin resistance exceeding 15% in 24/31 and 18/31 countries, respectively. Amoxicillin remains an exception, with resistance rates under 2% in 14/31 countries; though African countries have reported amoxicillin resistance rates of over 90%. Bismuth-based treatment regimens are the most effective and are recommended as first-line treatment in several countries. However, more than 1 billion inhabitants worldwide have no access to bismuth-based regimens. PCR-based tests for AR are used in 16/26 countries but are reimbursed in only 4, while next generation sequencing-based tests are available, but not reimbursed, in 3 countries. In 22/26 countries only culture-based methods are available (reimbursed in 9/26 countries). AR surveillance programmes have only been established in 4/26 countries. Therefore, in most countries, empirical therapy with the most effective local regimen available locally is practiced.ConclusionThe dramatic global rise in H. pylori antibiotic resistance requires an urgent revision of current management strategies. Possible solutions include AST-based selection of effective treatment regimens, identification of novel combinations of existing drugs and exploration of novel drugs.

Kinetoplastids are a group of flagellated protozoans including medically important parasites of the genus Trypanosoma and Leishmania . The corresponding diseases have afflicted humans for centuries. In an effort to combat kinetoplastid infections, a set of 21 chalcones was synthesized and evaluated for their in vitro anti-protozoal efficacy against Trypanosoma brucei , Trypanosoma brucei rhodesiense , Trypanosoma cruzi , and Leishmania infantum . To ensure safety, these compounds underwent a selectivity evaluation by assessing toxicity against a human lung fibroblast cell line. Compound K4 exhibited remarkable and selective trypanocidal activity against T. b. brucei with IC 50 value of 0.31 ± 0.27 µM and T. b. rhodesiense with IC 50 value of 0.96 ± 0.86 µM. Compound K9 also showed significant trypanocidal activity against T. b. brucei (IC 50 : 0.45 ± 0.14 µM) and T. b. rhodesiense (IC 50 : 0.93 ± 0.51 µM). In both compounds, electron withdrawing groups are appended to the styrenyl moiety.