Non-typhoid Salmonella endocarditis complicated by cardiac failure and acute limb ischaemia in a person living with HIV and hepatitis C: A case report and literature review.

Salmonella infections are responsible for a large burden of disease worldwide. Non-typhoidal Salmonella (NTS) species cause a myriad of disease manifestations, particularly amongst severely immunocompromised individuals. We present a rare case of endocarditis caused by the NTS species Salmonella Enteritidis in an individual living with HIV and hepatitis C. In this case, endocarditis was complicated by embolization and acute arterial occlusion of the left arm, as well as mitral valve perforation resulting in cardiac failure. A review of the available literature shows few cases of NTS causing endocarditis in people living with HIV, with the earliest reported case in 1983. Our case demonstrates the potential complications of NTS endocarditis and highlights the importance of evaluating patients with NTS-associated blood stream infection for cardiovascular involvement. Prompt surgical intervention in addition to appropriate antimicrobial therapy is essential to reduce the high morbidity and mortality associated with NTS endocarditis.

Coronavirus Host Genomics Study: South Africa (COVIGen-SA).

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa's response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA-a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

Validation of the COVID-19 IgG/IgM Rapid Test Cassette (BNCP - 402 and BNCP402) in a South African setting.

Background: Different diagnostic tools could improve early detection of coronavirus disease 2019 (COVID-19). A number of antibody-based serological point-of-care tests have been developed to supplement real-time reverse transcriptase polymerase chain reaction (RT-PCR)-based diagnosis. This study describes the validity of an antibody test, namely the immunoglobulin G (IgG)/immunoglobulin M (IgM) Rapid Test Cassette® (BNCP - 402 and BNCP402), manufactured by Spring Healthcare Services. Methods: A prospective cohort validation study was undertaken at Chris Hani Baragwanath Academic Hospital between 16 July 2020 and 12 August 2020. A total of 101 patients admitted as COVID-19 cases under investigation were included in the study. They were divided into two categories depending on time since symptom onset: testing performed within seven days (early cohort) and after seven days (late cohort). The rapid antibody test was compared to the RT-PCR. Results: Overall, the test has a sensitivity and specificity of 85.2% and 80.0%, respectively, for a combination of IgG and IgM. Sensitivity and specificity of IgG testing alone were 81.5% and 85%. Sensitivity improved for testing with increasing time from symptom onset; however, specifity was not significantly different. Conclusion: The study data adds to the body of evidence that because of relatively low sensitivity and specificity, there is a limited role for antibody-based point-of-care testing in the acute phase of COVID-19 infection, as was the case with this IgG/IgM Rapid Test Cassette (BNCP - 402 and BNCP402). There may exist a role for such testing in patients recovered from prior COVID-19 infection or in seroprevalence studies; however, additional evaluations at later timepoints from symptom onset are required.

Tropical forests are home to over half of the world's vertebrate species.

Tropical forests are renowned for their astonishing diversity of life, but the fundamental question of how many species occur in tropical forests remains unanswered. Using geographic range maps and data on species habitat associations, we determined that tropical forests harbor 62% of global terrestrial vertebrate species, more than twice the number found in any other terrestrial biome on Earth. Up to 29% of global vertebrate species are endemic to tropical forests, with more than 20% of these species at risk of extinction. Humid tropical forests (also known as tropical rainforests) and the Neotropics dominate as centers of species diversity, harboring more than 90% and nearly half of all tropical forest vertebrates, respectively. To maintain the biodiversity that underpins the ecosystem functions and services essential for human well-being, we emphasize the critical importance of environmental policies aimed at reducing tropical deforestation and mitigating deleterious anthropogenic pressures on these imperiled ecosystems.

Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study.

BACKGROUND: Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. METHODS: In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. FINDINGS: From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010). INTERPRETATION: In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. FUNDING: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. TRANSLATION: For the Zulu translation of the abstract see Supplementary Materials section.

Vitamin D status and COVID-19 severity.

Background: Age, body mass index (BMI) and pre-existing comorbidities are known risk factors of severe coronavirus disease 2019 (COVID-19). In this study we explore the relationship between vitamin D status and COVID-19 severity. Methods: We conducted a prospective, cross-sectional descriptive study. We enrolled 100 COVID-19 positive patients admitted to a tertiary level hospital in Johannesburg, South Africa. Fifty had symptomatic disease (COVID-19 pneumonia) and 50 who were asymptomatic (incidental diagnosis). Following written informed consent, patients were interviewed regarding age, gender and sunlight exposure during the past week, disease severity, BMI, calcium, albumin, magnesium and alkaline phosphatase levels. Finally, blood was collected for vitamin D measurement. Results: We found an 82% prevalence rate of vitamin D deficiency or insufficiency among COVID-19 patients. Vitamin D levels were lower in the symptomatic group (18.1 ng/mL ± 8.1 ng/mL) than the asymptomatic group (25.9 ng/mL ± 7.1 ng/mL) with a p-value of 0.000. The relative risk of symptomatic COVID-19 was 2.5-fold higher among vitamin D deficient patients than vitamin D non-deficient patients (confidence interval [CI]: 1.14-3.26). Additional predictors of symptomatic disease were older age, hypocalcaemia and hypoalbuminaemia. Using multiple regression, the only independent predictors of COVID-19 severity were age and vitamin D levels. The patients exposed to less sunlight had a 2.39-fold increased risk for symptomatic disease compared to those with more sunlight exposure (CI: 1.32-4.33). Conclusion: We found a high prevalence of vitamin D deficiency and insufficiency among patients admitted to hospital with COVID-19 and an increased risk for symptomatic disease in vitamin D deficient patients.

Multiple opportunistic infections (pulmonary tuberculosis, Mycobacterium avium complex and parvovirus B19) in a single patient.

INTRODUCTION: HIV infection is a common disease in the South African population. The virus can lead to the development of many opportunistic infections. This case study examines co-infection with three opportunistic infections and the need for clinical suspicion of infections in our HIV population. PATIENT PRESENTATION: A 36-year-old unemployed female residing in Soweto, Johannesburg, presented at Chris Hani Baragwanath Hospital (CHBAH). She was HIV positive, defaulting treatment, with no other comorbidities. She presented to CHBAH with general body weakness, diarrhoea, cough and constitutional symptoms; clinically she appeared pale and chronically ill. A differential diagnosis was made of multiple infections co-inhabiting the patient. MANAGEMENT AND OUTCOME: The patient had blood, sputum, radiological and invasive bone marrow aspiration, and trephine biopsies completed. The investigations revealed that she was co-infected with Mycobacterium tuberculosis (MTB), Mycobacterium avium complex (MAC) and parvovirus B19. The TB and disseminated MAC infection were managed with rifampicin, isoniazid, ethambutol, pyrazinamide and azithromycin, and reinitiation of antiretroviral (ARV) treatment was planned on further follow-up of the ARV drug resistance test. The parvovirus B19 infection was managed with immunoglobulins (Polygam) and steroids (prednisone). She was discharged successfully for further follow-up. CONCLUSION: A thorough history, clinical examination and subsequent targeted investigations are vital to arriving at the correct diagnosis or diagnoses. The case presented above serves to illustrate how three life-threatening opportunistic infections (OIs), all with differing treatments, may present in a single patient. Clinicians caring for immunosuppressed patients need to remain vigilant for the presence of multiple OIs occurring simultaneously.

Clinical, radiological, and laboratory predictors of a positive urine lipoarabinomannan test in sputum-scarce and sputum-negative patients with HIV-associated tuberculosis in two Johannesburg hospitals.

BACKGROUND: Tuberculosis (TB) is a major cause of mortality in persons living with HIV (PLWH). Sputum-based diagnosis of TB in patients with low CD4 counts is hampered by paucibacillary disease and consequent sputum scarcity or negative sputum results. Urine lipoarabinomannan (LAM) has shown promise in the point-of-care detection of TB in this patient subset but lacks sensitivity, and its exact role in a diagnostic algorithm for TB in South Africa remains to be clarified. OBJECTIVES: The objective of this study was to better define the patient profile and the TB characteristics associated with a positive urine LAM (LAM+ve) test. METHOD: This multicentre retrospective record review examined the clinical, radiological, and laboratory characteristics of hospitalised PLWH receiving urine LAM testing with sputum-scarce and/or negative sputum GeneXpert ® (mycobacterium tuberculosis/resistance to rifampicin [MTB/RIF]) results. RESULTS: More than a third of patients, 121/342 (35%), were LAM+ve. The positive yield was greater in the sputum-scarce than the sputum-negative group, 66/156 (42%) versus 55/186 (30%), P = 0.0141, respectively. Patients who were LAM+ve were more likely to be confused (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.2-3.7, P = 0.0045), have a higher median heart rate (P = 0.0135) and an elevated quick sepsis-related organ failure assessment score (≥ 2), OR = 3.5, 95% CI = 1.6-7.6, P = 0.0014. A LAM+ve test was significantly associated with disseminated TB (dTB), P < 0.0001, TB-related immune reconstitution inflammatory syndrome (IRIS), P = 0.0035, and abdominal TB, P < 0.0001. Laboratory predictors of a LAM+ve status included renal dysfunction, P = 0.044, severe anaemia, P = 0.0116, and an elevated C-reactive protein, P = 0.0131. Of the 12 PLWH with disseminated non-TB mycobacteria cultured from the blood and/or bone marrow, n = 9 (75%) had a LAM+ve result (OR = 5.8, 95% CI = 1.6-20.8, P = 0.0053). CONCLUSION: Urine LAM testing of hospitalised PLWH with suspected active TB had significant diagnostic utility in those that were sputum-scarce or sputum-negative. A LAM+ve result was associated with dTB, clinical and laboratory markers of severe illness, and TB-IRIS. Disseminated non-tuberculous mycobacterial infection of hospitalised PLWH may also yield urine LAM+ve results, and mycobacterial cultures must be checked in those non-responsive to conventional TB treatment. Selective use of the LAM test in the critically ill is likely to maximise the diagnostic yield, improve the test's predictive value, and reduce the time to TB diagnosis and initiation of treatment.

Multisystem inflammatory syndrome (MIS): a multicentre retrospective review of adults and adolescents in South Africa.

OBJECTIVES: The aim of this study was to add to the descriptive data pertaining to the epidemiology, presentation, and clinical course of multisystem inflammatory syndrome (MIS) temporally associated with coronavirus disease 2019 in adults and adolescents from low- and middle-income countries. METHODS: Patients presenting to the adult wards (14 years and older) of three academic hospitals in South Africa, who were diagnosed with MIS between August 1, 2020 and May 31, 2021, were reviewed retrospectively. The presentation, laboratory and radiographic findings, and clinical course are described. RESULTS: Eleven cases of MIS were reported, four in adolescents (14-19 years) and seven in adults (≥19 years). Fever was universal. Gastrointestinal symptoms (90.9%), cardiorespiratory abnormalities (90.9%), and mucocutaneous findings (72.7%) were prominent. Echocardiography in 10/11 patients (90.9%) showed a median left ventricular ejection fraction of 26.3% (interquartile range 21.9-33.6%). All patients required high care admission and 72.7% required inotropic support. Glucocorticoids were initiated in all cases and 72.7% received intravenous immunoglobulin. CONCLUSIONS: This constitutes the largest multicentre review of adults and adolescents with MIS in Africa. MIS may be overlooked in resource-limited settings, and heightened suspicion is needed in patients with multi-organ dysfunction, especially where repeated investigations for other aetiologies are negative.

Optimal climate for large trees at high elevations drives patterns of biomass in remote forests of Papua New Guinea.

Our ability to model global carbon fluxes depends on understanding how terrestrial carbon stocks respond to varying environmental conditions. Tropical forests contain the bulk of the biosphere's carbon. However, there is a lack of consensus as to how gradients in environmental conditions affect tropical forest carbon. Papua New Guinea (PNG) lies within one of the largest areas of contiguous tropical forest and is characterized by environmental gradients driven by altitude; yet, the region has been grossly understudied. Here, we present the first field assessment of aboveground biomass (AGB) across three main forest types of PNG using 193 plots stratified across 3,100-m elevation gradient. Unexpectedly, AGB had no direct relationship to rainfall, temperature, soil, or topography. Instead, natural disturbances explained most variation in AGB. While large trees (diameter at breast height > 50 cm) drove altitudinal patterns of AGB, resulting in a major peak in AGB (2,200-3,100 m) and some of the most carbon-rich forests at these altitudes anywhere. Large trees were correlated to a set of climatic variables following a hump-shaped curve. The set of "optimal" climatic conditions found in montane cloud forests is similar to that of maritime temperate areas that harbor the largest trees in the world: high ratio of precipitation to evapotranspiration (2.8), moderate mean annual temperature (13.7°C), and low intra-annual temperature range (7.5°C). At extreme altitudes (2,800-3,100 m), where tree diversity elsewhere is usually low and large trees are generally rare or absent, specimens from 18 families had girths >70 cm diameter and maximum heights 20-41 m. These findings indicate that simple AGB-climate-edaphic models may not be suitable for estimating carbon storage in forests where optimal climate niches exist. Our study, conducted in a very remote area, suggests that tropical montane forests may contain greater AGB than previously thought and the importance of securing their future under a changing climate is therefore enhanced.

Validating Community-Led Forest Biomass Assessments.

The lack of capacity to monitor forest carbon stocks in developing countries is undermining global efforts to reduce carbon emissions. Involving local people in monitoring forest carbon stocks could potentially address this capacity gap. This study conducts a complete expert remeasurement of community-led biomass inventories in remote tropical forests of Papua New Guinea. By fully remeasuring and isolating the effects of 4,481 field measurements, we demonstrate that programmes employing local people (non-experts) can produce forest monitoring data as reliable as those produced by scientists (experts). Overall, non-experts reported lower biomass estimates by an average of 9.1%, equivalent to 55.2 fewer tonnes of biomass ha(-1), which could have important financial implications for communities. However, there were no significant differences between forest biomass estimates of expert and non-expert, nor were there significant differences in some of the components used to calculate these estimates, such as tree diameter at breast height (DBH), tree counts and plot surface area, but were significant differences between tree heights. At the landscape level, the greatest biomass discrepancies resulted from height measurements (41%) and, unexpectedly, a few large missing trees contributing to a third of the overall discrepancies. We show that 85% of the biomass discrepancies at the tree level were caused by measurement taken on large trees (DBH ≥50 cm), even though they consisted of only 14% of the stems. We demonstrate that programmes that engage local people can provide high-quality forest carbon data that could help overcome barriers to reducing forest carbon emissions in developing countries. Nonetheless, community-based monitoring programmes should prioritise reducing errors in the field that lead to the most important discrepancies, notably; overcoming challenges to accurately measure large trees.

Targeting global protected area expansion for imperiled biodiversity.

Governments have agreed to expand the global protected area network from 13% to 17% of the world's land surface by 2020 (Aichi target 11) and to prevent the further loss of known threatened species (Aichi target 12). These targets are interdependent, as protected areas can stem biodiversity loss when strategically located and effectively managed. However, the global protected area estate is currently biased toward locations that are cheap to protect and away from important areas for biodiversity. Here we use data on the distribution of protected areas and threatened terrestrial birds, mammals, and amphibians to assess current and possible future coverage of these species under the convention. We discover that 17% of the 4,118 threatened vertebrates are not found in a single protected area and that fully 85% are not adequately covered (i.e., to a level consistent with their likely persistence). Using systematic conservation planning, we show that expanding protected areas to reach 17% coverage by protecting the cheapest land, even if ecoregionally representative, would increase the number of threatened vertebrates covered by only 6%. However, the nonlinear relationship between the cost of acquiring land and species coverage means that fivefold more threatened vertebrates could be adequately covered for only 1.5 times the cost of the cheapest solution, if cost efficiency and threatened vertebrates are both incorporated into protected area decision making. These results are robust to known errors in the vertebrate range maps. The Convention on Biological Diversity targets may stimulate major expansion of the global protected area estate. If this expansion is to secure a future for imperiled species, new protected areas must be sited more strategically than is presently the case.

Ten principles for a landscape approach to reconciling agriculture, conservation, and other competing land uses.

"Landscape approaches" seek to provide tools and concepts for allocating and managing land to achieve social, economic, and environmental objectives in areas where agriculture, mining, and other productive land uses compete with environmental and biodiversity goals. Here we synthesize the current consensus on landscape approaches. This is based on published literature and a consensus-building process to define good practice and is validated by a survey of practitioners. We find the landscape approach has been refined in response to increasing societal concerns about environment and development tradeoffs. Notably, there has been a shift from conservation-orientated perspectives toward increasing integration of poverty alleviation goals. We provide 10 summary principles to support implementation of a landscape approach as it is currently interpreted. These principles emphasize adaptive management, stakeholder involvement, and multiple objectives. Various constraints are recognized, with institutional and governance concerns identified as the most severe obstacles to implementation. We discuss how these principles differ from more traditional sectoral and project-based approaches. Although no panacea, we see few alternatives that are likely to address landscape challenges more effectively than an approach circumscribed by the principles outlined here.