Medical certification of death in South Africa – moving forward

Despite improvements to the Death Notification Form (DNF) used in South Africa (SA), the quality of cause-of-death information remains suboptimal. To address these inadequacies, the government ran a train-the-trainer programme on completion of the DNF, targeting doctors in public sector hospitals. Training materials were developed and workshops were held in all provinces. This article reflects on the lessons learnt from the training and highlights issues that need to be addressed to improve medical certification and cause-of-death data in SA. The DNF should be completed truthfully and accurately, and confidentiality of the information on the form should be maintained. The underlying cause of death should be entered on the lowest completed line in the cause-of-death section, and if appropriate, HIV should be entered here. Exclusion clauses for HIV in life insurance policies with Association of Savings and Investments South Africa companies were scrapped in 2005. Interactive workshops provide a good learning environment, but are logistically challenging. More use should be made of online training resources, particularly with continuing professional development accreditation and helpline support. In addition, training in the completion of the DNF should become part of the curriculum in all medical schools, and part of the orientation of interns and community service doctors in all facilities

Mortality trends and diff erentials in South Africa from 1997 to 2012: second National Burden of Disease Study

Background The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997–2012 and develop national, population group, and provincial estimates of the levels and causes of mortality. Method We used underlying cause of death data from death notifi cations for 1997–2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassifi ed HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison. Findings All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29·1%) followed by cerebrovascular disease (7·5%) and lower respiratory infections (4·9%). All-cause age-standardised death rates were 1·7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2·2 times higher in black Africans compared to whites, and 1·4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial diff erences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence. Interpretation This study shows the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality diff erentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Diff erences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

Background: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry

Evidence that the Human Pathogenic Fungus Cryptococcus neoformans var. grubii May Have Evolved in Africa

Most of the species of fungi that cause disease in mammals, including Cryptococcus neoformans var. grubii (serotype A), are exogenous and non-contagious. Cryptococcus neoformans var. grubii is associated worldwide with avian and arboreal habitats. This airborne, opportunistic pathogen is profoundly neurotropic and the leading cause of fungal meningitis. Patients with HIV/AIDS have been ravaged by cryptococcosis – an estimated one million new cases occur each year, and mortality approaches 50%. Using phylogenetic and population genetic analyses, we present evidence that C. neoformans var. grubii may have evolved from a diverse population in southern Africa. Our ecological studies support the hypothesis that a few of these strains acquired a new environmental reservoir, the excreta of feral pigeons (Columba livia), and were globally dispersed by the migration of birds and humans. This investigation also discovered a novel arboreal reservoir for highly diverse strains of C. neoformans var. grubii that are restricted to southern Africa, the mopane tree (Colophospermum mopane). This finding may have significant public health implications because these primal strains have optimal potential for evolution and because mopane trees contribute to the local economy as a source of timber, folkloric remedies and the edible mopane worm

Medical certification of death in South Africa – moving forward

CITATION: Burger, E. H., et al. 2015. Medical certification of death in South Africa – moving forward. South African Medical Journal, 105(1):27-30, doi:10.7196/SAMJ.8578.The original publication is available at http://www.samj.org.zaDespite improvements to the Death Notification Form (DNF) used in South Africa (SA), the quality of cause-of-death information remains suboptimal. To address these inadequacies, the government ran a train-the-trainer programme on completion of the DNF, targeting doctors in public sector hospitals. Training materials were developed and workshops were held in all provinces. This article reflects on the lessons learnt from the training and highlights issues that need to be addressed to improve medical certification and cause-of-death data in SA. The DNF should be completed truthfully and accurately, and confidentiality of the information on the form should be maintained. The underlying cause of death should be entered on the lowest completed line in the cause-of-death section, and if appropriate, HIV should be entered here. Exclusion clauses for HIV in life insurance policies with Association of Savings and Investments South Africa companies were scrapped in 2005. Interactive workshops provide a good learning environment, but are logistically challenging. More use should be made of online training resources, particularly with continuing professional development accreditation and helpline support. In addition, training in the completion of the DNF should become part of the curriculum in all medical schools, and part of the orientation of interns and community service doctors in all facilities.http://www.samj.org.za/index.php/samj/article/view/8578Publisher's versio

Leptospirosis in South Africa

Leptospirosis is a common zoonosis worldwide. It has a ubiquitous distribution and causes a wide spectrum of disease. Leptospirosis therefore has a broad reservoir host range, and many infected species of animals excrete leptospires in their urine, which leads to contamination of soil and water. Typical descriptions of the disease include a biphasic (anicteric form) and fulminant disease in the icterohaemorrhagic form. Only a few local case reports of human leptospirosis have been published, the most recent one being in 1974. A rodent-related zoonosis study (RatZooMan) was conducted from 2003 until 2006 in three provinces (Limpopo, KwaZulu-Natal and the Eastern Cape). Of the people sampled in Cato Crest (Durban, KwaZulu-Natal Province), 43/217 (19.8%) were seropositive for leptospirosis. Of the clinical samples sent to the Special Bacterial Pathogens Reference Unit from all over the country for testing in 2009, 16/176 (9%) were IgM positive; in 2010 and January 2011 to May 2011, 14/215 (6.5%) and 12/96 (12.5%), respectively, were IgM positive. The apparent incidence of leptospirosis in the South African population is moderately high based on the detected positives in suspected cases; it is thought that the circulating infection rate may be even higher when looking at the RatZooMan results. This may be due to underreporting and undiagnosed cases. Communities in informal settlements in urban areas are especially at risk as infected rodent populations are a continuous source of transmission

<i>Bartonella</i> spp. in human and animal populations in Gauteng, South Africa, from 2007 to 2009

Bartonellae are highly adaptive organisms that have the ability to evade the host immune system and cause persistent bacteraemia by occupying the host’s erythrocytes. Bartonella spp. is under-studied and health care professionals often misdiagnose Bartonella-related infections. The aim of this study was to investigate the carriage of Bartonella spp. circulating in human and animal populations in Gauteng using culturing and polymerase chain reaction (PCR) detection. A total of 424 human, 98 cat, 179 dog, and 124 wild rodent blood samples were plated onto specialised media and incubated for 7–21 days at 37 ºC in CO2. Culture isolates morphologically similar to Bartonella control strains were confirmed by PCR and sequenced to determine species. Deoxyribonucleic acid (DNA) was extracted from all blood samples and tested by nested PCR. Bartonella could only be cultured from the cat and rodent specimens. Cat isolates were > 99% similar to Bartonella henselae URBHLIE 9, previously isolated from an endocarditis patient, and rat isolates were > 98% similar to either RN24BJ (candidus ‘Bartonella thailandensis’) or RN28BJ, previously isolated from rodents in China. The PCR prevalences were 22.5% in HIV-positive patients, 9.5% in clinically healthy volunteers, 23.5% in cats, 9% in dogs and 25% in rodents. Findings of this study have important implications for HIV-positive patients

<i>Bartonella henselae</i> and <i>Bartonella quintana</i> seroprevalence in HIV-positive, HIV-negative and clinically healthy volunteers in Gauteng, South Africa

Bartonella is a genus of opportunistic, Gram-negative bacilli transmitted from animals to human hosts. Bartonellae are newly emerging pathogens that can cause a variety of clinical manifestations in both immunocompromised and healthy persons. The aims were to determine the IgG and IgM seroprevalences of Bartonella henselae and Bartonella quintana in immunocompromised and immunocompetent individuals using an immunofluorescence assay (IFA). A total of 382 HIV-positive outpatients of the Chris Hani Baragwanth HIV-clinic, 382 retrospective residual samples from HIV-negative antenatal patients, and 42 clinically healthy volunteers were tested using a commercially available IFA kit to determine the prevalence of IgG and IgM antibodies to B. henselae and B. quintana. The IgM and IgG seroprevalences for the HIV-positive patients were 14% (53/382) and 32% (121/382), respectively, compared to 18% for both IgM (62/342) and IgG (63/342) in the HIV- negative antenatal patients. Similarly, the prevalence for IgM was 17% (7/42) and IgG was 19% (8/42) for the clinically healthy volunteers. HIV-positivity appears to be a significant risk factor for Bartonella infection, compared with healthy subjects. Although IFAs have a high sensitivity for Bartonella antibody detection, they have various limitations including cross-reactivity with other closely-related human pathogens

Screening of the glucocerebrosidase (GBA) gene in South Africans of African ancestry with Parkinson's disease

Sequence variants in glucocerebrosidase (GBA) are a major genetic risk factor for Parkinson's disease (PD), and display ethnic-dependent frequencies, for example, variants such as p.N370S and 84insGG are common in Ashkenazi Jewish patients. Notably, there are limited studies on black patients from the African continent; hence, we conducted a study on 30 South African black PD patients. All 11 exons of GBA were screened using a nested PCR approach to avoid pseudogene contamination. We identified previously described Gaucher's disease–associated variants, p.R120W in one patient [age at onset (AAO) of 35 years], and p.R131L in another patient (AAO 30 years) and in her affected sibling (AAO 45 years). In addition, we found 3 previously identified [p.K(-27)R, p.T36del, and p.Q497*] and 2 novel (p.F216L and p.G478R) variants. Screening of ethnic-matched controls for the novel variants revealed that the allele frequency of p.F216L was 9.9%, whereas p.G478R was not found in the controls. Studies such as these are important and necessary to reveal the genetic architecture underlying PD in the understudied patients of African ancestry.The National Research Foundation of South Africa (Grant Number: 106052), the South African Medical Research Council (Self-Initiated Research Grant), and Stellenbosch University.http://www.elsevier.com/locate/neuaging2021-04-01hj2020Neurolog

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

CITATION: Oluwole, O. G., et al. 2020. Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients. BMC Medical Genetics, 21:23, doi:10.1186/s12881-020-0953-1.The original publication is available at https://bmcmedgenet.biomedcentral.comBackground: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-020-0953-1Publisher's versio