Nutritional, immune, micronutrient and health status of HIV-infected children in care centres in Mangaung

Aim: To assess the nutritional, immune, micronutrient and health status of antiretroviral-naïve HIV-infected children.Method: A cross-sectional descriptive study was undertaken between September 2004 and March 2006 amongst HIV-infected children of which none received antiretroviral therapy, in care centres in Mangaung, Free State.Results: The study included 37 clinically stable and food-secure HIV-infected children. Their median age was 5.4 years (range 1.2–10.2 years). Fifteen children (41%) were underweight, 30 (81%) were stunted and one (3%) was wasted. The most commonly observed clinical features were lymphadenopathy (84%), skin rashes (51%), hepatomegaly (32%) and pallor (41%). Eight per cent of children had features of TB, while 19% had a lower respiratory tract infection. The median viral load of the group (n = 35) was 117 000 copies/ml, the median CD4+ cell count was 477 cells/mm3 and the median CD4 percentage was 22.5%. A significant negative correlation could be demonstrated between viral load and nutritional indicators. Children had deficient serum levels relative to normal reference values for glutathione (91% of children), albumin (78%), vitamin A (63%), vitamin D (44%), zinc (38%) and vitamin E (13%). Sixty per cent of the children were anaemic and 30% were iron deficient.Conclusion: A high prevalence of acute and chronic malnutrition and micronutrient deficiencies occurred among HIV-infected children residing in care centres. The study highlights the need to investigate early initiation of antiretroviral therapy and nutrition interventions, including aggressive supplementation, in order to improve the prognosis of these children

An epidemiological study of a patient population, triage category allocations and principal diagnosis within the emergency centres of a private healthcare group in the Emirate of Dubai, United Arab Emirates

Aim: To describe, compare and correlate the number of patients seen, their demographics, triage category allocations and principal diagnosis in four emergency centres; to better understand the patient population and triage practices in this setting. Design: An observational, cross-sectional, epidemiological study. Methods: Electronic medical records were retrospectively evaluated from patients triaged in each of the four emergency centres over six months. Descriptive statistics were used to describe the patient demographics and variance between triage category allocations. Results: A total of 56,984 patient records were captured, with an equal gender split and the workforce being the largest patient population (20–50 years). Acute upper respiratory infection was the most prolific diagnosis, and lower acuity triage categories were allocated the most. There were inconsistencies in the application of triage systems between the emergency centres, the most obvious being the variance in triage system selection and application

Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa

Rifampicin mono-resistant TB (RMR-TB, rifampicin resistance and isoniazid susceptibility) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.0001). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.0001). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 mug/ml (range 0.125-1 mug/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection

A review of the use of blood and blood products in HIV-infected patients

Despite numerous publications on the appropriate use of blood and blood products, few specifically consider the role of transfusion in the management of HIV. This review is a synthesis of conditions encountered in the management of HIV-infected patients where the transfusion of blood or blood products may be indicated. A consistent message emerging from the review is that the principles of transfusion medicine do not differ between HIV-negative and -positive patients. The aim of the review is to provide clinicians witha practical and succinct overview of the haematological abnormalities and clinical circumstances most commonly encountered in the HIV setting, while focusing on the rational and appropriate use of blood and blood products forHIV patients. Important ethical considerations in dealing with both the collection and transfusion blood and blood products in the HIV era have also been addressed

Potential contribution of HIV during first-line tuberculosis treatment to subsequent rifampicin-monoresistant tuberculosis and acquired tuberculosis drug resistance in South Africa: a retrospective molecular epidemiology study

Background: South Africa has a high burden of rifampicin-resistant tuberculosis (including multidrug-resistant [MDR] tuberculosis), with increasing rifampicin-monoresistant (RMR) tuberculosis over time. Resistance acquisition during first-line tuberculosis treatment could be a key contributor to this burden, and HIV might increase the risk of acquiring rifampicin resistance. We assessed whether HIV during previous treatment was associated with RMR tuberculosis and resistance acquisition among a retrospective cohort of patients with MDR or rifampicin-resistant tuberculosis. Methods: In this retrospective cohort study, we included all patients routinely diagnosed with MDR or rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa, between Jan 1, 2008, and Dec 31, 2017. Patient-level data were obtained from a prospective database, complemented by data on previous tuberculosis treatment and HIV from a provincial health data exchange. Stored MDR or rifampicin-resistant tuberculosis isolates from patients underwent whole-genome sequencing (WGS). WGS data were used to infer resistance acquisition versus transmission, by identifying genomically unique isolates (single nucleotide polymorphism threshold of five). Logistic regression analyses were used to assess factors associated with RMR tuberculosis and genomic uniqueness. Findings: The cohort included 2041 patients diagnosed with MDR or rifampicin-resistant tuberculosis between Jan 1, 2008, and Dec 31, 2017; of those, 463 (22.7%) with RMR tuberculosis and 1354 (66.3%) with previous tuberculosis treatment. In previously treated patients, HIV positivity during previous tuberculosis treatment versus HIV negativity (adjusted odds ratio [OR] 2.07, 95% CI 1.35-3.18), and three or more previous tuberculosis treatment episodes versus one (1.96, 1.21-3.17) were associated with RMR tuberculosis. WGS data showing MDR or rifampicin-resistant tuberculosis were available for 1169 patients; 360 (30.8%) isolates were identified as unique. In previously treated patients, RMR tuberculosis versus MDR tuberculosis (adjusted OR 4.96, 3.40-7.23), HIV positivity during previous tuberculosis treatment (1.71, 1.03-2.84), and diagnosis in 2013-17 (1.42, 1.02-1.99) versus 2008-12, were associated with uniqueness. In previously treated patients with RMR tuberculosis, HIV positivity during previous treatment (adjusted OR 5.13, 1.61-16.32) was associated with uniqueness as was female sex (2.50 [1.18-5.26]). Interpretation: These data suggest that HIV contributes to rifampicin-resistance acquisition during first-line tuberculosis treatment and that this might be driving increasing RMR tuberculosis over time. Large-scale prospective cohort studies are required to further quantify this risk. Funding: Swiss National Science Foundation, South African National Research Foundation, and Wellcome Trust

Transmission, distribution and drug resistance-conferring mutations of extensively drug-resistant tuberculosis in the Western Cape Province, South Africa

Extensively drug-resistant tuberculosis (XDR-TB), defined as resistance to at least isoniazid (INH), rifampicin (RIF), a fluoroqui-nolone (FQ) and a second-line injectable drug (SLID), is difficult to treat and poses a major threat to TB control. The transmission dynamics and distribution of XDR Mycobacterium tuberculosis (Mtb) strains have not been thoroughly investigated. Using whole genome sequencing data on 461 XDR-Mtb strains, we aimed to investigate the geographical distribution of XDR-Mtb strains in the Western Cape Province of South Africa over a 10 year period (2006-2017) and assess the association between Mtb sub-lineage, age, gender, geographical patient location and membership or size of XDR-TB clusters. First, we identified transmission clusters by excluding drug resistance-conferring mutations and using the 5 SNP cutoff, followed by merging clusters based on their most recent common ancestor. We then consecutively included variants conferring resistance to INH, RIF, ethambutol (EMB), pyrazinamide (PZA), SLIDs and FQs in the cluster definition. Cluster sizes were classified as small (2-4 isolates), medium (5-20 isolates), large (21-100 isolates) or very large (>100 isolates) to reflect the success of individual strains. We found that most XDR-TB strains were clustered and that including variants conferring resistance to INH, RIF, EMB, PZA and SLIDs in the cluster definition did not significantly reduce the proportion of clustered isolates (85.5-82.2 %) but increased the number of patients belonging to small clusters (4.3-12.4 %, P=0.56). Inclusion of FQ resistance-conferring variants had the greatest effect, with 11 clustered isolates reclassified as unique while the number of clusters increased from 17 to 37. Lineage 2 strains (lineage 2.2.1 typical Beijing or lineage 2.2.2 atypical Beijing) showed the large clusters which were spread across all health districts of the Western Cape Province. We identified a significant association between residence in the Cape Town metropole and cluster membership (P=0.016) but no association between gender, age and cluster membership or cluster size (P=0.39). Our data suggest that the XDR-TB epidemic in South Africa probably has its origin in the endemic spread of MDR Mtb and pre-XDR Mtb strains followed by acquisition of FQ resistance, with more limited transmission of XDR Mtb strains. This only became apparent with the inclusion of drug resistance-conferring variants in the definition of a cluster. In addition to the prevention of amplification of resistance, rapid diagnosis of MDR, pre-XDR and XDR-TB and timely initiation of appropriate treatment is needed to reduce transmission of difficult-to-treat TB

Cryptic speciation and chromosomal repatterning in the South African climbing mice Dendromus (Rodentia, Nesomyidae)

We evaluate the intra- and interspecific diversity in the four South African rodent species of the genus Dendromus. The molecular phylogenetic analysis on twenty-three individuals have been conducted on a combined dataset of nuclear and mitochondrial markers. Moreover, the extent and processes underlying chromosomal variation, have been investigated on three species by mean of G-, C-bands, NORs and Zoo-FISH analysis. The molecular analysis shows the presence of six monophyletic lineages corresponding to D. mesomelas, D. mystacalis and four lineages within D. cfr. melanotis with high divergence values (ranges: 10.6% – 18.3%) that raises the question of the possible presence of cryptic species. The first description of the karyotype for D. mesomelas and D. mystacalis and C- and G- banding for one lineage of D. cfr. melanotis are reported highlighting an extended karyotype reorganization in the genus. Furthermore, the G-banding and Zoo-FISH evidenced an autosome-sex chromosome translocation characterizing all the species and our timing estimates this mutation date back 7.4 mya (Late Miocene). Finally, the molecular clock suggests that cladogenesis took place since the end of Miocene to Plio-Pleistocene, probably due to ecological factors, isolation in refugia followed by differential adaptation to the mesic or dry habitat

Prescribing indicators at primary health care centers within the WHO African region: a systematic analysis (1995-2015)

Abstract Background Rational medicine use is essential to optimize quality of healthcare delivery and resource utilization. We aim to conduct a systematic review of changes in prescribing patterns in the WHO African region and comparison with WHO indicators in two time periods 1995–2005 and 2006–2015. Methods Systematic searches were conducted in PubMed, Scopus, Web of science, Africa-Wide Nipad, Africa Journals Online (AJOL), Google scholar and International Network for Rational Use of Drugs (INRUD) Bibliography databases to identify primary studies reporting prescribing indicators at primary healthcare centres (PHCs) in Africa. This was supplemented by a manual search of retrieved references. We assessed the quality of studies using a 14-point scoring system modified from the Downs and Black checklist with inclusions of recommendations in the WHO guidelines. Results Forty-three studies conducted in 11 African countries were included in the overall analysis. These studies presented prescribing indicators based on a total 141,323 patient encounters across 572 primary care facilities. The results of prescribing indicators were determined as follows; average number of medicines prescribed per patient encounter = 3.1 (IQR 2.3–4.8), percentage of medicines prescribed by generic name =68.0 % (IQR 55.4–80.3), Percentage of encounters with antibiotic prescribed =46.8 % (IQR 33.7–62.8), percentage of encounters with injection prescribed =25.0 % (IQR 18.7–39.5) and the percentage of medicines prescribed from essential medicines list =88.0 % (IQR 76.3–94.1). Prescribing indicators were generally worse in private compared with public facilities. Analysis of prescribing across two time points 1995–2005 and 2006–2015 showed no consistent trends. Conclusions Prescribing indicators for the African region deviate significantly from the WHO reference targets. Increased collaborative efforts are urgently needed to improve medicine prescribing practices in Africa with the aim of enhancing the optimal utilization of scarce resources and averting negative health consequences