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Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality., (© 2022 The Author(s). Published by Elsevier Inc /Elsevier B.V./ Wiley on behalf of The International Federation of Gynecology and Obstetrics (FIGO) / John Wiley & Son Ltd. All rights reserved.)

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cardiac disease is one of the commonest causes of indirect maternal deaths globally. This brief report is a reminder that isolated maternal tachycardia at rest is a clinical alert and warrants a detailed history in relation to cardiac disorders, thorough clinical examination of all organ systems, relevant investigations such as imaging, and expert advice to avoid serious adverse events. We reflect on a belatedly investigated persistent maternal tachycardia resulting in a fatal postpartum collapse due to mitral stenosis. The lost window of opportunity for appropriate investigation and management of the tachycardia provides an insight into many similar maternal deaths in South Africa. Key clinical messages regarding persistent maternal tachycardia are presented for midwives and doctors caring for pregnant women.

Background: In 2013, a pregnancy exposure registry and birth defects surveillance (PER/BDS) system was initiated in eThekwini District, KwaZulu-Natal (KZN), to assess the impact of antiretroviral treatment (ART) on birth outcomes., Objectives: At the end of the first year, we assessed the risk of major congenital malformations (CM) and other adverse birth outcomes (ABOs) detected at birth, in children born to women exposed to ART during pregnancy., Method: Data were collected from women who delivered at Prince Mshiyeni Memorial Hospital, Durban, from 07 October 2013 to 06 October 2014, using medicine exposure histories and birth outcomes from maternal interviews, clinical records and neonatal surface examination. Singleton births exposed to only one ART regimen were included in bivariable analysis for CM risk and multivariate risk analysis for ABO risk., Results: Data were collected from 10 417 women with 10 517 birth outcomes (4013 [38.5%] HIV-infected). Congenital malformations rates in births exposed to Efavirenz during the first trimester (T1) (RR 0.87 [95% CI 0.12-6.4; p = 0.895]) were similar to births not exposed to ART during T1. However, T1 exposure to Nevirapine was associated with the increased risk of CM (RR 9.28 [95% CI 2.3-37.9; p = 0.002]) when compared to the same group. Other ABOs were more frequent in the combination of HIV/ART-exposed births compared to HIV-unexposed births (29.9% vs. 26.0%, adjusted RR 1.23 [1.14-1.31; p < 0.001])., Conclusion: No association between T1 use of EFV-based ART regimens and CM was observed. Associations between T1 NVP-based ART regimen and CM need further investigation. HIV- and ART-exposed infants had more ABOs compared to HIV-unexposed infants., Competing Interests: The authors have no conflict of interests., (© 2019. The Authors.)

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder of nucleoside metabolism that is caused by mutations in the nuclear thymidine phosphorylase gene ( TYMP ) gene, encoding for the enzyme thymidine phosphorylase. There are currently no approved treatments for MNGIE. The aim of this study was to investigate the safety, tolerability, and efficacy of an enzyme replacement therapy for the treatment of MNGIE. In this single centre study, three adult patients with MNGIE received intravenous escalating doses of erythrocyte encapsulated thymidine phosphorylase (EE-TP; dose range: 4 to 108 U/kg/4 weeks). EE-TP was well tolerated and reductions in the disease-associated plasma metabolites, thymidine, and deoxyuridine were observed in all three patients. Clinical improvements, including weight gain and improved disease scores, were observed in two patients, suggesting that EE-TP is able to reverse some aspects of the disease pathology. Transient, non-serious adverse events were observed in two of the three patients; these did not lead to therapy discontinuation and they were managed with pre-medication prior to infusion of EE-TP. To conclude, enzyme replacement therapy with EE-TP demonstrated biochemical and clinical therapeutic efficacy with an acceptable clinical safety profile.

Maternal deaths associated with caesarean deliveries (CDs) have been increasing in South Africa over the past decade. The objective of this report is to bring national attention to this increasing epidemic of maternal deaths due to bleeding associated with CD in the majority of provinces of the country. Individual chart reviews of women who died from bleeding at or after CD show that 71% had avoidable factors. Among the steps we can take are to improve surgical skills and experience, especially in rural hospitals, to improve clinical observations in the immediate postoperative period and in the postnatal wards, and to ensure that appropriate oxytocic agents are given to prevent postpartum haemorrhage. CEOs and medical managers of health facilities, district clinical specialists, heads of obstetrics and gynaecology, and midwifery training institutions must show leadership and accountability in providing an appropriate environment to ensure that women who require CD receive the procedure for the correct indications and in a safe manner to minimise risks.

Training programmes to improve health worker skills in managing obstetric emergencies have been introduced in various countries with the aim of reducing maternal mortality through these interventions. In South Africa, based on an ongoing confidential enquiry system started in 1997, detailed information about maternal deaths is published in the form of regular 'Saving Mothers' reports. This article tracks the recommendations made in successive Saving Mothers reports with regard to emergency obstetric training, and it assesses the impact of these recommendations on reducing maternal mortality. Since 2009, South Africa has had its own training package, Essential Steps in the Management of Obstetric Emergencies (ESMOE), which the last three Saving Mothers reports have specifically recommended for all doctors and midwives working in maternity units. A special emphasis has been placed on the need for the simulation training component of ESMOE, also called obstetric 'fire drills', to be integrated into the clinical routines of all maternity units. The latest Saving Mothers report (2011-2013) suggests there has been little progress so far in improving emergency obstetric skills, indicating a need for further scale-up of ESMOE training in the country. The example of the KwaZulu-Natal province of South Africa is used to illustrate the process of scale-up and factors likely to facilitate that scale-up, including the introduction of ESMOE into the undergraduate medical training curriculum. Additional factors in the health system that are required to convert improved skills levels into improved quality of care and a reduction in maternal mortality are discussed. These include intelligent government health policies, formulated with input from clinical experts; strong clinical leadership to ensure that doctors and nurses apply the skills they have learnt appropriately, and work professionally and ethically; and a culture of clinical governance., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Unlabelled: Intracranial hypertension (IH) has been associated with hypocortisolism caused by either primary adrenocortical insufficiency or corticosteroid withdrawal., Method: The authors describe a case of IH in association with Sheehan syndrome (SS) in a postpartum 29-year-old woman., Results: The clinical manifestations of IH resolved with corticosteroid replacement., Conclusions: This case supports a causal role of hypocortisolism in IH. The authors are unaware of previous reports of hypocortisolism caused by SS leading to IH.

The effect of HIV infection on maternal mortality is best documented in South Africa, where HIV prevalence rates in pregnancy are among the highest in the world. Since 1998, detailed data on maternal deaths in South Africa have been available in the form of Confidential Enquiries reports. The latest report (Saving Mothers Report, 2005-2007) suggests that the maternal mortality ratio in HIV-infected women was about 10 times higher than in uninfected women. This was in a context where only a small minority of HIV-positive pregnant women were receiving HAART. The most common causes of maternal death among HIV-positive women were nonpregnancy-related infections, including AIDS, pneumonia, tuberculosis, and meningitis. HIV-infected pregnant women were also at greater risk of dying from pregnancy-related sepsis and complications of abortion than their uninfected counterparts. Reduction of HIV-related maternal deaths must be seen as a worldwide priority in maternal health care., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Refractory status epilepticus (RSE) is associated with high mortality. We report a potential treatment alternative., Hypothesis: Deep brain stimulation (DBS) of the centromedian thalamic nuclei (CMN) can be effective in the treatment of RSE., Methods: Report of the evolution of RSE after DBS of the CMN in a 27-year-old man., Results: In the course of an encephalopathy of unknown origin, and after a cardiac arrest, the patient developed RSE with myoclonic jerks and generalized tonic-clonic seizures. The EEG showed continuous generalized periodic epileptiform discharges (GPEDS). Five weeks after RSE onset, bilateral DBS of the CMN was started. This treatment was immediately followed by disappearance of tonic-clonic seizures and GPEDS, suggesting a resolution of RSE. The patient continued having multifocal myoclonic jerks, probably subcortical in origin, which resolved after 4 weeks. The patient remained clinically stable for 2 months in a persistent vegetative state., Conclusions: The remission of RSE, the abolition of GPEDS, and the patient survival suggest that DBS of the CMN may be efficacious in the treatment of refractory, generalized status epilepticus., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Our objective was to estimate the effect of various childbirth care packages on neonatal mortality due to intrapartum-related events ("birth asphyxia") in term babies for use in the Lives Saved Tool (LiST)., Methods: We conducted a systematic literature review to identify studies or reviews of childbirth care packages as defined by United Nations norms (basic and comprehensive emergency obstetric care, skilled care at birth). We also reviewed Traditional Birth Attendant (TBA) training. Data were abstracted into standard tables and quality assessed by adapted GRADE criteria. For interventions with low quality evidence, but strong GRADE recommendation for implementation, an expert Delphi consensus process was conducted to estimate cause-specific mortality effects., Results: We identified evidence for the effect on perinatal/neonatal mortality of emergency obstetric care packages: 9 studies (8 observational, 1 quasi-experimental), and for skilled childbirth care: 10 studies (8 observational, 2 quasi-experimental). Studies were of low quality, but the GRADE recommendation for implementation is strong. Our Delphi process included 21 experts representing all WHO regions and achieved consensus on the reduction of intrapartum-related neonatal deaths by comprehensive emergency obstetric care (85%), basic emergency obstetric care (40%), and skilled birth care (25%). For TBA training we identified 2 meta-analyses and 9 studies reporting mortality effects (3 cRCT, 1 quasi-experimental, 5 observational). There was substantial between-study heterogeneity and the overall quality of evidence was low. Because the GRADE recommendation for TBA training is conditional on the context and region, the effect was not estimated through a Delphi or included in the LiST tool., Conclusion: Evidence quality is rated low, partly because of challenges in undertaking RCTs for obstetric interventions, which are considered standard of care. Additional challenges for evidence interpretation include varying definitions of obstetric packages and inconsistent measurement of mortality outcomes. Thus, the LiST effect estimates for skilled birth and emergency obstetric care were based on expert opinion. Using LiST modelling, universal coverage of comprehensive obstetric care could avert 591,000 intrapartum-related neonatal deaths each year. Investment in childbirth care packages should be a priority and accompanied by implementation research and further evaluation of intervention impact and cost., Funding: This work was supported by the Bill and Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US.

Massive hemoptysis during pregnancy has been infrequently reported. The management of massive hemoptysis in an immunocompromised 22-year-old woman positive for human immunodeficiency virus undergoing treatment for cavitating pulmonary tuberculosis in the last trimester of pregnancy is reported. The difficulties encountered in applying our standard protocol for massive hemoptysis in this instance are described. The patient was managed by emergency cesarean section and lobectomy.

Objectives: To describe the clinical characteristics of epilepsy in a representative sample of the UK population, including seizure frequency and severity; overall severity of epilepsy; patterns of anti-epileptic drug (AED) use; and the impact of epilepsy on patients' lives. Secondly, to determine if these characteristics differ according to age., Method: A large, geographically comprehensive survey of people with epilepsy by means of a postal questionnaire distributed by general practitioners to 3455 unselected patients receiving AEDs for epilepsy, regardless of age or type of epilepsy and including all regions of the UK. Data were collected on age and gender; age of onset of seizures; seizure frequency and severity; AED use and adverse effect levels; and impact on life of epilepsy. Sub-analyses were performed with stratification by epilepsy severity and age-group., Results: There were 1652 completed replies. The mean age was 44.2 years; there were 47.2% males, 48.5% females (4.4% not recorded). The mean age at first seizure, 25.1 years, and the mean duration of epilepsy, 19.7 years, were comparable with previous studies. In the preceding one year, 51.7% of patients had no seizures; 7.9% one seizure, 17.2% 2-9 seizures and 23.2% 10 or more. Sixty-four percent of patients had epilepsy classified as mild and 32% severe. There was a marked and significant decrement of seizure frequency with increasing age. The most commonly used AEDs were carbamazepine (37.4%), valproate (35.7%), phenytoin (29.4%), phenobarbitone or primidone (14.2%) and lamotrigine (10.3%). Monotherapy was used in 68% of patients. Patients taking multiple AEDs reported significantly higher levels of adverse effects and worse seizure control. The major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life. The impacts listed varied with the epilepsy severity and age., Conclusions: Seizures remain uncontrolled in up to half of all people with epilepsy in the UK with significant impact on work, family and social life. Previously, there has been a deficiency of data on the characteristics of epilepsy in older people, although it is recognized that the condition is of increasing epidemiological importance in this age group. We have found clear differences in the clinical characteristics of epilepsy in older people, particularly that seizure frequency appears to decline with increasing age., (Copyright 2003 BEA Treading Ltd.)

Women with epilepsy have different needs from men, particularly associated with childbearing. Despite clinical guidelines, the care of women with epilepsy remains suboptimal. The aim of this study was to establish whether women with epilepsy recall being given information on topics relating to childbearing. Design of study and methods included a postal questionnaire study of 795 women with epilepsy and of childbearing age. The respondents were identified through both general practices and hospital clinics as part of the Clinical Standards Advisory Group study into Epilepsy Services. Of those women who considered the questions personally relevant, 38-48% recalled receiving information about contraception, pre-pregnancy planning, folic acid and teratogenicity, with lower overall proportions among adolescent women. The proportions that recalled receiving information about vitamin K, safety in child-care and breast-feeding were lower at 12, 24 and 24%, respectively. While it is recognised that information provided may not be recalled, our results suggest that further measures are required to improve the effectiveness of information provision in the UK in relation to women of childbearing age with epilepsy.

Background: Drawing a distinction between cortical and subcortical dementias seems both useful and justified. Recent research has, however, cast doubt on the clinical, neuropsychological, neuroimaging and neuroanatomical basis of the distinction., Aims: To arrive at a reasoned conclusion about the relationship between the two types of dementia and the validity of distinguishing between them., Method: The historical and recent clinical and scientific literature on subcortical dementia was reviewed., Results: The traditional claim that subcortical dementia has distinct clinical manifestations, neuroimaging findings and a neuropathological profile is not altogether borne out by the literature. Some studies show that frontal executive dysfunction and the profile of memory deficits are not significantly different from those seen in Alzheimer's disease. Neuropathological findings also overlap., Conclusions: The category of subcortical dementia may be clinically useful in highlighting the likelihood that an individual with dementia is more likely to suffer from bradyphrenia and motor difficulties. As neuroscience advances a preoccupation with the distinction may hinder the assessment and treatment of individual cases.

Visual inspection and volumetric analysis of MRIs allow mesial temporal sclerosis (MTS) to be reliably identified in patients with temporal lobe epilepsy. The presence of unilateral MTS ipsilateral to the side of habitual seizure onset is an indicator for the prognosis of good outcome after temporal lobe resection. There is evidence to suggest that widespread temporal lobe pathology, leading to atrophy, may be associated with MTS and such abnormal tissue may play an important role in epileptogenesis. We have analysed quantitatively the volumes of the mesial and lateral temporal lobe substructures in MRIs from 62 patients with intractable mesial temporal lobe epilepsy and in 20 normal controls. We found significant atrophy in these structures in patients, ranging from 8.3 to 18.4% compared with controls. The degree of atrophy in the extrahippocampal structures correlated with the degree of hippocampal atrophy, suggesting that a common process may be responsible. There was no correlation between the degree of atrophy in the extrahippocampal structures and the duration of epilepsy, a history of febrile convulsions or of generalized seizures. These findings suggest that there may be widespread pathological abnormalities in the temporal lobe associated with MTS. The importance of extrahippocampal atrophy to surgical outcome and whether it occurs in temporal lobe epilepsy not associated with MTS remain to be investigated.

Studies of post-operative imaging data have mainly concentrated on brain atrophy following radiotherapy and/or chemotherapy. We have investigated the effect of conventional surgery on the unresected brain tissue based on the comparison of magnetic resonance images acquired pre- and post-operatively in 13 subjects with a history of mesio-temporal epilepsy. The pre- and post-operative scans were co-registered prior to volumetric analysis. The total brain volume (TBV) was calculated by semi-automated segmentation, and the total volume loss was the difference between the post-operative and pre-operative TBV. The total volume of resection was determined by manual delineation in the post-operative scan. The atrophy volume in the post-operative scan was calculated as the difference between the total volume loss and the resection volume. In 6 cases, there was generalised cerebral atrophy of the order 4-5% of the total brain volume. In addition to the automated volumetric technique, the images were assessed by two expert neuroradiologists. There was complete correspondence between their assessment and the automated technique. The causes and significance of this phenomenon are unknown but it requires further investigation as it may be related to seizure control and neuropsychological changes following epilepsy surgery.

Purpose: The nature of the resection in surgery for intractable medial temporal lobe epilepsy is likely to be a principal factor determining seizure and neuropsychological outcome. However, there is no universally accepted system for describing the characteristics of individual resections to allow comparison between patients and patient groups treated at different institutions. We therefore developed a technique of volumetric analysis of temporal lobe resections., Methods: With comparison of coregistered pre- and postoperative, volumetric magnetic resonance imaging (MRI) scans in 10 subjects, the volumes of six temporal lobe substructures were determined by manual delineation in the pre- and post-operative images for each case, allowing the extent of resection to be determined., Results: The substructures and their extent of resection were measured with acceptable repeatability in each case., Conclusions: We developed a reliable method for the quantitative description of temporal lobe resections. This will be of application in determining the relation between the anatomic nature of the resection in intractable epilepsy and the seizure and neuropsychological outcome.

Objectives: To characterise the clinical features and response to treatment of supratentorial cavernomas associated with epilepsy., Methods: A systematic review of the literature was carried out and a retrospective case series of patients with cavernoma diagnosed by MRI and/or histology was compiled. Patient selection biases in the literature review were reduced as far as possible by selection of unbiased publications., Results: In the literature, cavernomas were relatively less common in the frontal lobes. There were multiple cavernomas in 23% of cases. The main clinical manifestations were seizures (79%) and haemorrhage (16%). The annual haemorrhage rate was 0.7%. The outcome after excision was good with improvement in seizures in 92% of patients. In the case series the surgical outcome was less favourable, reflecting inclusion of a higher proportion of patients with intractable epilepsy. In both the literature review and the case series, outcome was poorer in cases with a longer duration of seizures at the time of surgery., Conclusions: The good surgical results, particularly in cases treated earlier, and the significant cumulative haemorrhage rate, suggest that excision is the optimum treatment. However, these factors have not been examined prospectively and, despite the availability of several retrospective studies, the optimum treatment, particularly for non-intractable cases, will only be determined by a prospective study.

A 25-year-old man with a long history of temporal lobe epilepsy developed right occipital lobe seizures and a progressive right homonymous hemianopia. MRI showed diffuse enhancement of the left temporoparieto-occipital white matter and cortical thickening of the left medial temporal lobe. The resected temporal lobe revealed cortical dysplasia and angiodysplasia with foci of more recent ischemic necrosis and chronic inflammation as an explanation for the clinical deterioration.

The purpose of this work is to detect and assess the significance of subtle signal changes in mixed-signal lesions based on serial MRI scan matching. Pairs of serially acquired T1-weighted volume MR images from 20 normal controls and seven patients with epilepsy were matched and difference images obtained. The precision and consistency of the registration were evaluated. The Gaussian noise level in the difference images was determined automatically. A structured difference filter was then used to segment structured (changed) voxels from the Gaussian noise. In the controls, the structured difference images were normalized into Talairach space, resulting in a structured noise map. The significance of changes in patients was assessed by spatial normalization and comparison with the structured noise map. The precision and consistency of the co-registration were < or = 0.06 mm with a registration success rate of 100%. The Gaussian noise level in the difference images was in the range 3.0-6.9. In the controls, an average of 1.6% of the brain voxels were classified as structured. Sine-based registration resulted in a reduction of < 1% in the amount of structure compared to linear interpolation. The structured noise map in controls showed high noise density in areas affected by image artefacts. We show examples of significant changes found in lesions which had been reported as unchanged on visual inspection. A novel quantitative approach has been presented for the detection and quantification of subtle signal changes in lesions. This method is of potential clinical value in the non-invasive characterization of signal change and biological behaviour of neoplastic lesions.

During a prospective study of 147 patients with snakebite presenting to a rural South African hospital, 13 of 17 patients (76%) treated with South African Institute for Medical Research (SAIMR) polyvalent antivenom experienced potentially severe early (anaphylactoid) reactions. The most common reaction was generalized urticaria (12; 71%), but 3 cases of angio-oedema (18%), 2 of bronchospasm (12%), and 2 of hypotension (12%) were also observed. Reactions were controlled with adrenaline, antihistamines, and resuscitation. All patients fully recovered from envenoming although the full dose of antivenom was not given to most. Indications for the use of this antivenom should be reconsidered and patients should be given antivenom in a high care setting if possible. Use of antivenom by lay people outside hospital should be discouraged and antivenom manufacturing processes could usefully be reviewed.