Distal sensory polyneuropathy in South Africans infected with human immunodeficiency virus : a cross-sectional analysis of a community cohort

Includes bibliographical references (leaves 93-107).Introduction: Distal sensory polyneuropathy (DSP), the most common neurological complication of HIV infection, is related to either HIV or antiretroviral therapy (ART). Dideoxynucleoside reverse transcriptase inhibitors such as stavudine are widely used in resource-poor countries and often associated with neuropathy. The prevalence of DSP in developed countries range from 21% to 63%; little data is available from Africa. We aimed to estimate the prevalence of DSP in a South African community clinic-based population and to investigate associated risk factors. Methods: In a cross-sectional study, DSP status was determined in 598 HIV-infected adults using validated tools (Brief Peripheral Neuropathy Screen and a modified version of the Total Neuropathy Score) to categorize subjects. Symptomatic DSP required the presence of at least two neuropathic signs together with at least one symptom. Asymptomatic DSP required the presence of two neuropathic signs. Clinical, anthropometric, quality of life and laboratory evaluations were prospectively performed. Information about CD4 counts, antiretroviral therapy (ART) and questionnaires regarding previous tuberculosis (TB) and alcohol exposure was retrospectively collected Results: Approximately half (49%) of the study population were diagnosed with DSP (30% symptomatic DSP). In the ART-naïve group 37% had evidence of neuropathy (23% symptomatic) compared to 63% of the ART-exposed subjects (39% symptomatic). Overall, subjects with DSP were older (p<0.001) and had lower CD4 counts (p<0.001) compared to those without neuropathy. Previously treated TB infection (p<0.001) and ART use (p<0.001) showed strong associations with DSP. In multivariate analyses the odds (95% confidence interval) of developing DSP was independently associated with ART use (OR 1.7, 1.0-2.9), age (per 10 year increments) (OR 1.7, 1.4-2.2) and previously treated TB infection (OR 2.0, 1.3-3.0). Although stavudine significantly associated with DSP, the duration of exposure was similar irrespective of neuropathy status. Pain or paresthesia was reported by 69% of those with symptomatic DSP and rated as at least moderate to severe. ART-exposed subjects had a tendency towards lower pain scores compared to ART-naïves (p=0.032). Conclusions: DSP is a clinically significant problem in urban HIV-infected Africans. The findings of this study raise the possibility that with avoidance of stavudine-containing regimens in older subjects, especially those with a history of previously treated TB infection, the prevalence of DSP may be reduced

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Indeterminate HIV PCR results represent missed diagnostic opportunities within South Africa’s early infant diagnosis programme. These results not only delay diagnosis and appropriate management but are also a source of confusion and apprehension amongst clinicians and caregivers. We describe the extent of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme and provide recommendations for the management of these cases, both in terms of laboratory practice and the clinical care of the infants.They also thank the United Nations Children’s Emergency Fund (UNICEF) for partial funding of this work. A.H.M. acknowledges the Discovery Foundation for financial support.http://www.sajhivmed.org.zaam2016Medical Virolog

Effects of postnatal environmental tobacco smoke on non-nutritive swallowing-breathing coordination in newborn lambs

While prenatal environmental tobacco smoke (ETS) exposure is a well-known risk factor for sudden infant death syndrome, the effect of postnatal ETS exposure is less clear. The objective of this study was to investigate the effect of postnatal ETS exposure on non-nutritive swallowing (NNS) and NNS-breathing coordination, which are crucial to prevent aspiration related-cardiorespiratory events. Eighteen newborn lambs (6 per group) were randomly exposed to either 10 cigarettes/day, 20 cigarettes/day or room air for 15 days. Lambs were instrumented for recording states of alertness, swallowing, electrocardiogram and breathing; recordings were performed in non-sedated lambs at the end of ETS exposure. Urinary cotinine/creatinine ratio confirmed relevant real-life exposure. Postnatal ETS exposure had no effect on NNS frequency but tended to decrease inspiratory NNS (p=0.07) during quiet sleep. No effect on respiratory or heart rate (p>0.6), apnea index (p=0.2) or sleep states (p=0.3) was observed. In conclusion, postnatal ETS exposure in lambs had only mild effects on NNS-breathing coordination

An analysis of the HIV testing cascade of a group of HIV-exposed infants from birth to 18 months in peri-urban Khayelitsha, South Africa

BACKGROUND: Despite the reduction of HIV mother-to-child transmission, there are concerns regarding transmission rate in the breastfeeding period. We describe the routine uptake of 6 or 10 (6/10) weeks, 9 months and 18 months testing, with and without tracing, in a cohort of infants who received HIV PCR testing at birth (birth PCR) (with and without point of care (POC) testing) in a peri-urban primary health care setting in Khayelitsha, South Africa. METHODS: In this cohort study conducted between November 2014 and February 2018, HIV-positive mothers and their HIV-exposed babies were recruited at birth and all babies were tested with birth PCR. Results of routine 6/10 weeks PCR, 9 months and 18 months testing were followed up by a patient tracer. We compared testing at 6/10 weeks with a subgroup from historical cohort who was not tested with birth PCR. RESULTS: We found that the uptake of 6/10 weeks testing was 77%, compared to 82% with tracing. When including all infants in the cascade and comparing to a historical cohort without birth testing, we found that infants who tested a birth were 22% more likely to have a 6/10 weeks test compared to those not tested at birth. There was no significant difference between the uptake of 6/10 weeks testing after birth PCR POC versus birth PCR testing without POC. Uptake of 9 months and 18 months testing was 39% and 24% respectively. With intense tracing efforts, uptake increased to 45% and 34% respectively. CONCLUSION: Uptake of HIV testing for HIV-exposed uninfected infants in the first 18 months of life shows good completion of the 6/10 weeks PCR but suboptimal uptake of HIV testing at 9 months and 18 months, despite tracing efforts. Birth PCR testing did not negatively affect uptake of the 6/10 weeks HIV test compared to no birth PCR testing

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Irreproducible positive results on the Cobas AmpliPrep/Cobas TaqMan HIV-1 Qual test are qualitatively different from confirmed positive results

The original publication is available at http://onlinelibrary.wiley.com/doi/10.1002/jmv.23811/fullCriteria that define low positive results on the COBAS® AmpliPrep/COBAS® TaqMan (CAP/CTM) HIV- 1 Qual test as inconclusive have been adopted by all academic centres in South Africa that conduct infant HIV PCR, following previous investigations that showed poor specificity of these results. Retesting all these specimens has considerable cost implications. It was therefore attempted to better characterise such inconclusive results, by comparing those that prove to be either negative or positive on follow-up testing. This retrospective, laboratory-based study found that 193 of 211 (91.5%) patients with with previous inconclusive results (defined as reported positive by CAP/CTM but with cycle threshold [Ct] values of >32 and/or fluorescence intensity [FI] values of <5) tested negative and only 18 (8.5%) positive using independently obtained follow-up samples after a median of 28 days). The only significant independent predictor of a later positive result was a higher FI value (3.326 vs. 0.495, p<0.0001), whereas Ct values were not independently predictive. Specimens from patients negative on follow-up testing were qualitatively different from specimens that proved to be true positive. As the lower FI values in false-positive compared to true-positive results are probably indicative of a non-specific signal, the incorporation of stringent amplification slope criteria in the assay’s test definition file may improve correct classification and thus reduce the need for repeat testing of a large number of inconclusive specimens

The impact of cerebrospinal fluid viral analysis on empiric antibiotic use in children admitted to Tygerberg Children’s hospital with suspected meningitis

CITATION: Kruger, I., Maritz, J. & Finlayson, H. 2018. The impact of cerebrospinal fluid viral analysis on empiric antibiotic use in children admitted to Tygerberg Children’s hospital with suspected meningitis. Southern African Journal of Infectious Diseases, 33(4):101-105, doi:10.4102/sajid.v33i4.157.The original publication is available at https://sajid.co.zaBackground: Viral meningitis is the most common form of aseptic meningitis and requires minimal investigation and treatment. Polymerase chain reaction (PCR) has become the ‘gold standard’ for identifying viruses in cerebrospinal fluid and can provide rapid results. The objective of the study was to describe the aetiology and epidemiology of viral meningitis at Tygerberg Children’s Hospital, as well as the impact of a positive cerebral spinal fluid (CSF) viral panel on the duration of empiric antibiotic treatment. Methods: This was a retrospective folder review of all children aged between 29 days and 13 years who had a CSF specimen on which a viral analysis was performed from January 1, 2010 to December 31, 2014. Results: A total of 288 specimens were identified from the laboratory database. Seventy-nine specimens were presented for data analysis. Thirty-seven specimens had a positive viral analysis. The median age was 11.3 months (IQR 3.7–49.16 months). The microscopy and chemistry results were similar for the two groups except for the CSF lymphocyte count, which was significantly higher in the group with a positive CSF viral analysis compared to those with a negative CSF viral analysis (median 52 vs. 12 × 106/l, p = 0.005). The most common identified virus was Epstein–Barr virus (EBV) (23%), followed by enterovirus (17%). Children with a positive viral analysis tended to receive antibiotics for longer than those who had negative results (p = 0.223). Conclusion: The addition of CSF viral analysis could be helpful in the management of children with meningitis, but at present appears to have little impact on the length of antibiotic use.https://sajid.co.za/index.php/sajid/article/view/157Publisher's versio

Pandemic influenza A (H1N1) 2009 : the experience of the first six months

Includes bibliographyAfter a break of 41 years, 2009 saw the first influenza pandemic of the 21st century caused by a triple-reassortant influenza A (H1N1) virus. The current estimated case fatality rate is lower than that of previous influenza pandemics, but this may change as the pandemic evolves. Illness frequently occurs in previously healthy, young adults with a wide range of clinical presentations. The majority of circulating pandemic viruses remain susceptible to neuraminidase inhibitors, although all strains are intrinsically resistant to the adamantanes. Monovalent vaccines against the pandemic strain are available in both live attenuated and inactivated forms. This review aims to summarise important virological, epidemiological and clinical aspects of the pandemic influenza A (H1N1) virus for physicians and other clinical personnel

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