Changes in Prevalence and Seasonality of Pathogens Identified in Acute Respiratory Tract Infections in Hospitalised Individuals in Rural and Urban Settings in South Africa; 2018-2022.

Severe acute respiratory tract infections (SARIs) has been well described in South Africa with seasonal patterns described for influenza and respiratory syncytial virus (RSV), while others occur year-round (rhinovirus and adenovirus). This prospective syndromic hospital-based surveillance study describes the prevalence and impact of public interventions on the seasonality of other respiratory pathogens during the coronavirus disease-19 (COVID-19) pandemic. This occurred from August 2018 to April 2022, with 2595 patients who met the SARS case definition and 442 controls, from three sentinel urban and rural hospital sites in South Africa. Naso/oro-pharyngeal (NP/OP) swabs were tested using the FastTrack Diagnostics® Respiratory pathogens 33 (RUO) kit. Descriptive statistics, odds ratios, and univariate/multivariate analyses were used. Rhinovirus (14.80%, 228/1540) and Streptococcus pneumoniae (28.50%, 439/1540) were most frequently detected in NP/OP swabs and in children <1 years old (35%, 648/1876). Among others, pathogens associated with SARI cases causing disease were influenza A&B, HRV, RSV, hCoV 229e, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Pre-COVID-19, seasonal trends of these pathogens correlated with previous years, with RSV and influenza A seasons only resuming after the national lockdown (2021). It is evident that stringent lockdown conditions have severe impacts on the prevalence of respiratory tract infections.

Reported antibiotic use among patients in the multicenter ANDEMIA infectious diseases surveillance study in sub-saharan Africa.

BACKGROUND: Exposure to antibiotics has been shown to be one of the drivers of antimicrobial resistance (AMR) and is critical to address when planning and implementing strategies for combatting AMR. However, data on antibiotic use in sub-Saharan Africa are still limited. Using hospital-based surveillance data from the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA), we assessed self-reported antibiotic use in multiple sub-Saharan African countries. METHODS: ANDEMIA included 12 urban and rural health facilities in Côte d'Ivoire, Burkina Faso, Democratic Republic of the Congo, and Republic of South Africa. Patients with acute respiratory infection (RTI), acute gastrointestinal infection (GI) and acute febrile disease of unknown cause (AFDUC) were routinely enrolled, and clinical, demographic, socio-economic and behavioral data were collected using standardized questionnaires. An analysis of ANDEMIA data from February 2018 to May 2022 was conducted. Reported antibiotic use in the ten days prior to study enrolment were described by substance and by the WHO AWaRe classification ("Access", "Watch", "Reserve", and "Not recommended" antibiotics). Frequency of antibiotic use was stratified by location, disease syndrome and individual patient factors. RESULTS: Among 19,700 ANDEMIA patients, 7,258 (36.8%) reported antibiotic use. A total of 9,695 antibiotics were reported, including 54.7% (n = 5,299) from the WHO Access antibiotic group and 44.7% (n = 4,330) from the WHO Watch antibiotic group. The Watch antibiotic ceftriaxone was the most commonly reported antibiotic (n = 3,071, 31.7%). Watch antibiotic use ranged from 17.4% (56/322) among RTI patients in Côte d'Ivoire urban facilities to 73.7% (630/855) among AFDUC patients in Burkina Faso urban facilities. Reported antibiotic use included WHO Not recommended antibiotics but no Reserve antibiotics. CONCLUSIONS: Reported antibiotic use data from this multicenter study in sub-Saharan Africa revealed a high proportion of WHO Watch antibiotics. Differences in Watch antibiotic use were found by disease syndrome, country and health facility location, which calls for a more differentiated approach to antibiotic use interventions including further evaluation of accessibility and affordability of patient treatment.

Epidemiology and aetiology of moderate to severe diarrhoea in hospitalised patients ≥5 years old living with HIV in South Africa, 2018-2021: A case-control analysis.

Diarrhoea is a recognised complication of HIV-infection, yet there are limited local aetiological data in this high-risk group. These data are important for informing public health interventions and updating diagnostic and treatment guidelines. This study aimed to determine the pathogenic causes of diarrhoeal admissions in people living with HIV (PLHIV) compared to hospital controls between July 2018 and November 2021. Admitted diarrhoeal cases (n = 243) and non-diarrhoeal hospital controls (n = 101) ≥5 years of age were enrolled at Kalafong, Mapulaneng and Matikwana hospitals. Stool specimens/rectal swabs were collected and pathogen screening was performed on multiple platforms. Differences in pathogen detections between cases and controls, stratified by HIV status, were investigated. The majority (n = 164, 67.5%) of enrolled diarrhoeal cases with known HIV status were HIV-infected. Pathogens could be detected in 66.3% (n = 228) of specimens, with significantly higher detection in cases compared to controls (72.8% versus 50.5%, p<0.001). Amongst PLHIV, prevalence of Cystoisospora spp. was significantly higher in cases than controls (17.7% versus 0.0%, p = 0.028), while Schistosoma was detected more often in controls than cases (17.4% versus 2.4%, p = 0.009). Amongst the HIV-uninfected participants, prevalence of Shigella spp., Salmonella spp. and Helicobacter pylori was significantly higher in cases compared to controls (36.7% versus 12.0%, p = 0.002; 11.4% versus 0.0%, p = 0.012; 10.1% versus 0.0%, p = 0.023). Diarrhoeal aetiology differed by HIV status, with Shigella spp. (36.7%) and Salmonella spp. (11.4%) having the highest prevalence amongst HIV-uninfected cases and Shigella spp. (18.3%), Cystoisospora (17.7%), and Cryptosporidium spp. (15.9%) having the highest prevalence in cases amongst PLHIV. These differences should be considered for the development of diagnostic and treatment guidelines.

Diagnostic testing practices for diarrhoeal cases in South African public hospitals.

BACKGROUND: Stool samples submitted for diagnostic testing represent a proportion of diarrhoeal cases seeking healthcare, and an even smaller proportion of diarrhoeal cases in the community. Despite this, surveillance relies heavily on these laboratory results. This study described diarrhoeal diagnostic practices and aetiological agents of diarrhoea in patients admitted to three South African public hospitals in order to understand biases in surveillance data, and inform guidelines, diagnostic and laboratory practices to improve clinical management. METHODS: A doctors' survey was conducted to determine sample submission, diarrhoeal treatment and barriers to submitting samples for testing. Results for all samples submitted for routine diagnostics were obtained from the NHLS Central Data Warehouse. An enhanced surveillance study enrolled patients with acute diarrhoea at the same hospitals over the same period. Differences between routine culture results and molecular testing from the surveillance study were described. RESULTS: Stool samples were seldom submitted for diagnostic testing (median of 10% of admitted cases). Current diagnostic guidelines were not useful, hence most doctors (75.1%) relied on their own clinical judgement or judgement of a senior clinician. Although most doctors (90.3%) agreed that diagnostics were helpful for clinical management, they reported patients being unwilling to provide samples and long laboratory turnaround times. Routine diagnostic data represent cases with chronic diarrhoea and dysentery since doctors are most likely to submit specimens for these cases. Pathogen yield (number of pathogens detected for samples tested for specific pathogens) was significantly higher in the surveillance study, which used molecular methods, than through routine diagnostic services (73.3% versus 8.2%, p < 0.001), including for viruses (48.9% versus 2.6%, p < 0.001), bacteria (40.1% versus 2.2%, p < 0.001) and parasites (16.2% versus 3.6%, p < 0.001). Despite viruses being commonly detected in the surveillance study, viral testing was seldom requested in routine diagnostic investigations. CONCLUSIONS: Comprehensive diagnostic and treatment guidelines are required for diarrhoeal diseases. These guidelines should be informed by local epidemiological data, where diagnostic testing is reserved for cases most likely to benefit from specific treatment. Optimisation of current diagnostic processes and methods are required for these cases, specifically in terms of minimising turnaround times while maximising diagnostic acumen.

Identifying gaps in hand hygiene practice to support tailored target audience messaging in Soweto: A cross-sectional community survey.

Effective risk communication is essential for outbreak mitigation, as recently highlighted during the coronavirus disease 2019 (COVID-19) pandemic. Hand hygiene is one of the proposed public health interventions to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition and transmission along with social distancing, improved ventilation, environmental cleaning, and wearing of masks. Improving hand hygiene practices in the community requires an understanding of the socio-behavioural context. This cross-sectional community survey in Soweto identified gaps in hand hygiene, which can inform appropriate messaging at the community level. Only 42% of survey respondents practiced adequate hand hygiene. Tailored educational messaging should be targeted at young adults in particular, and the importance of soap for hand hygiene must be emphasised for all age groups. Risk communication should expand to focus on preventing multiple infectious diseases during and beyond the COVID-19 pandemic.

Diarrhoeal diseases in Soweto, South Africa, 2020: a cross-sectional community survey.

BACKGROUND: In South Africa, there are limited data on the burden of diarrhoea at a community level, specifically in older children and adults. This community survey estimated rates of and factors associated with diarrhoea across all ages and determined the proportion of cases presenting to healthcare facilities. METHODS: Households were enrolled from an existing urban health and demographic surveillance site. A household representative was interviewed to determine associated factors and occurrence of diarrhoea in the household, for all household members, in the past 2 weeks (including symptoms and health seeking behaviour). Diarrhoeal rate of any severity was calculated for < 5 years, 5-15 years and > 15 years age groups. Factors associated with diarrhoea and health seeking behaviour were investigated using binomial logistic regression. RESULTS: Diarrhoeal rate among respondents (2.5 episodes/person-year (95% CI, 1.8-3.5)) was significantly higher than for other household members (1.0 episodes/person-year (95% CI, 0.8-1.4); IRR = 2.4 (95% CI, 1.5-3.7) p < 0.001). Diarrhoeal rates were similar between age groups, however younger children (< 5 years) were more likely to present to healthcare facilities than adults (OR = 5.9 (95% CI, 1.1-31.4), p = 0.039). Oral rehydration solution was used in 44.8% of cases. Having a child between 5 and 15 years in the household was associated with diarrhoea (OR = 2.3 (95% CI, 1.3-3.9), p = 0.003) and, while 26.4% of cases sought healthcare, only 4.6% were hospitalised and only 3.4% of cases had a stool specimen collected. While the majority of cases were mild, 13.8% of cases felt they required healthcare but were unable to access it. CONCLUSION: Diarrhoeal rate was high across all age groups in this community; however, older children and adults were less likely to present to healthcare, and are therefore underrepresented through facility-based clinical surveillance. Current diarrhoeal surveillance represents a fraction of the overall cases occurring in the community.

The African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents.

BACKGROUND: In sub-Saharan Africa, acute respiratory infections (ARI), acute gastrointestinal infections (GI) and acute febrile disease of unknown cause (AFDUC) have a large disease burden, especially among children, while respective aetiologies often remain unresolved. The need for robust infectious disease surveillance to detect emerging pathogens along with common human pathogens has been highlighted by the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. The African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA) is a sentinel surveillance study on the aetiology and clinical characteristics of ARI, GI and AFDUC in sub-Saharan Africa. METHODS: ANDEMIA includes 12 urban and rural health care facilities in four African countries (Côte d'Ivoire, Burkina Faso, Democratic Republic of the Congo and Republic of South Africa). It was piloted in 2018 in Côte d'Ivoire and the initial phase will run from 2019 to 2021. Case definitions for ARI, GI and AFDUC were established, as well as syndrome-specific sampling algorithms including the collection of blood, naso- and oropharyngeal swabs and stool. Samples are tested using comprehensive diagnostic protocols, ranging from classic bacteriology and antimicrobial resistance screening to multiplex real-time polymerase chain reaction (PCR) systems and High Throughput Sequencing. In March 2020, PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and analysis of full genomic information was included in the study. Standardised questionnaires collect relevant clinical, demographic, socio-economic and behavioural data for epidemiologic analyses. Controls are enrolled over a 12-month period for a nested case-control study. Data will be assessed descriptively and aetiologies will be evaluated using a latent class analysis among cases. Among cases and controls, an integrated analytic approach using logistic regression and Bayesian estimation will be employed to improve the assessment of aetiology and associated risk factors. DISCUSSION: ANDEMIA aims to expand our understanding of ARI, GI and AFDUC aetiologies in sub-Saharan Africa using a comprehensive laboratory diagnostics strategy. It will foster early detection of emerging threats and continued monitoring of important common pathogens. The network collaboration will be strengthened and site diagnostic capacities will be reinforced to improve quality management and patient care.

Epidemiology of invasive bacterial infections in pneumococcal conjugate vaccine-vaccinated and -unvaccinated children under 5 years of age in Soweto, South Africa: a cohort study from a high-HIV burden setting.

Background: There are limited data on paediatric invasive bacterial infections (IBI) and the impact of pneumococcal conjugate vaccine (PCV) on the spectrum of IBI pathogens, specifically in African countries with a high prevalence of HIV infection.Aim: To describe the epidemiology of IBI in a cohort of children <5 years of age in Soweto, South Africa.Methods: A cohort of children enrolled into a PCV9 efficacy trial conducted from 1998 until 2005 was used for secondary data analysis. Surveillance data were collected from admission wards at Chris Hani Baragwanath Academic Hospital. The incidence of IBI was calculated using person-time, stratified by age group, gender, PCV9 vaccination status and HIV infection status. Risk factors for IBI were investigated using binomial logistic regression.Results: A total of 395 cases of laboratory-confirmed IBI were identified. HIV infection and not receiving PCV9 vaccination were risk factors for IBI hospitalisation. PCV9 vaccination was associated with reductions in IBI hospitalisation (IRR 0.76, p = 0.006) solely owing to reductions in the incidence of Streptococcus pneumoniae (IRR 0.56, p < 0.001). PCV9 vaccination had no effect on the incidence of Haemophilus influenza type b or Salmonella species IBI. There was an increase in Klebsiella species IBI (IRR 3.50, p = 0.019) and a trend towards a higher incidence of Staphylococcus aureus IBI (IRR 1.90, p = 0.099) in PCV9-vaccinated children.Conclusions: PCV9 vaccination was effective in reducing the incidence of IBI hospitalisation in children through reductions in the incidence of S. pneumoniae. The results show that trends in other IBI causative pathogens (specifically S. aureus and Klebsiella species) should be monitored in the era of PCV vaccination.Abbreviations: ART, antiretroviral therapy; CI, confidence interval; Hib, Haemophilus influenza type b; HIV, human immunodeficiency virus; HIV+PCV-, HIV-infected, placebo-vaccinated group; HIV+PCV+, HIV-infected, PCV9-vaccinated group; HIV-PCV-, HIV-uninfected, placebo-vaccinated group; HIV+PCV+, HIV-infected, PCV9-vaccinated group; IBI, invasive bacterial infection; IPD, invasive pneumococcal disease; IRR, incidence rate ratio; IQR, interquartile range; OR, odds ratio; PCV, pneumococcal conjugate vaccine; PCV7, 7-valent pneumococcal conjugate vaccine; PCV9, 9-valent pneumococcal conjugate vaccine; PY, person-years; RCT, randomised control trial.

An Observational Pilot Study Evaluating the Utility of Minimally Invasive Tissue Sampling to Determine the Cause of Stillbirths in South African Women.

BACKGROUND: Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. METHODS: This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization's International Classification of Diseases, Tenth Revision application to perinatal deaths. RESULTS: A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). CONCLUSIONS: In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause.

Overview and Development of the Child Health and Mortality Prevention Surveillance Determination of Cause of Death (DeCoDe) Process and DeCoDe Diagnosis Standards.

Mortality surveillance and cause of death data are instrumental in improving health, identifying diseases and conditions that cause a high burden of preventable deaths, and allocating resources to prevent these deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) network uses a standardized process to define, assign, and code causes of stillbirth and child death (<5 years of age) across the CHAMPS network. A Determination of Cause of Death (DeCoDe) panel composed of experts from a local CHAMPS site analyzes all available individual information, including laboratory, histopathology, abstracted clinical records, and verbal autopsy findings for each case and, if applicable, also for the mother. Using this information, the site panel ascertains the underlying cause (event that precipitated the fatal sequence of events) and other antecedent, immediate, and maternal causes of death in accordance with the International Classification of Diseases, Tenth Revision and the World Health Organization death certificate. Development and use of the CHAMPS diagnosis standards-a framework of required evidence to support cause of death determination-assures a homogenized procedure leading to a more consistent interpretation of complex data across the CHAMPS network. This and other standardizations ensures future comparability with other sources of mortality data produced externally to this project. Early lessons learned from implementation of DeCoDe in 5 CHAMPS sites in sub-Saharan Africa and Bangladesh have been incorporated into the DeCoDe process, and the implementation of DeCoDe has the potential to spur health systems improvements and local public health action.