Wild Bird Surveillance in the Gauteng Province of South Africa during the High-Risk Period for Highly Pathogenic Avian Influenza Virus Introduction

Migratory birds carried clade 2.3.4.4B H5Nx highly pathogenic avian influenza (HPAI) viruses to South Africa in 2017, 2018 and 2021, where the Gauteng Province is a high-risk zone for virus introduction. Here, we combined environmental faecal sampling with sensitive rRT-PCR methods and direct Ion Torrent sequencing to survey wild populations between February and May 2022. An overall IAV incidence of 42.92% (100/231) in water bird faecal swab pools or swabs from moribund or dead European White Storks (Ciconia ciconia) was detected. In total, 7% of the IAV-positive pools tested H5-positive, with clade 2.3.4.4B H5N1 HPAI confirmed in the storks; 10% of the IAV-positive samples were identified as H9N2, and five complete H9N2 genomes were phylogenetically closely related to a local 2021 wild duck H9N2 virus, recent Eurasian LPAI viruses or those detected in commercial ostriches in the Western and Eastern Cape Provinces since 2018. H3N1, H4N2, H5N2 and H8Nx subtypes were also identified. Targeted surveillance of wild birds using environmental faecal sampling can thus be effectively applied under sub-Saharan African conditions, but region-specific studies should first be used to identify peak prevalence times which, in southern Africa, is linked to the peak rainfall period, when ducks are reproductively active.     

Prevalence and indicators of HIV and AIDS among adults admitted to medical and surgical wards in Blantyre,Malawi

Despite high seroprevalence there are few recent studies of the effect of HIV on hospitals in sub-Saharan Africa. We examined 1226 consecutive patients admitted during two 2-week periods in October 1999 and January 2000. 70% medical patients were HIV positive, and 45% had AIDS. 36% surgical patients were HIV positive and 8% had AIDS. Seroprevalence rose to a peak among 30–40 year olds; 91% medical, 56% surgical and 80% all patients in this age group were HIV positive. Seropositive women were younger than seropositive men (median age 29 v 35, p<0.0001). Symptoms strongly indicative of HIV were history of shingles, chronic diarrhoea or fever or cough, history of tuberculosis, weight loss, and persistent itchy rash (adjusted odds ratios all over 5). Clinical signs strongly indicative of HIV were oral hairy leukoplakia, shingles scar, Kaposi''s sarcoma, oral thrush, and hair loss (adjusted odds ratios all over 10). Of surgical patients with ‘deep infections’ (breast abscess, pyomyositis, osteomyelitis, septic arthritis, and multiple abscesses), 52% were HIV positive (OR compared with other surgical patients 2.4). Severe bacterial infections, tuberculosis, and AIDS caused 68% deaths. HIV dominates adult medicine, is a major part of adult surgery, is the main cause of death in hospital, and affects the economically active age group of the population.     

Insights into the preclinical treatment of blood-stage malaria by the antibiotic borrelidin

Background and Purpose

Blood-stage Plasmodium parasites cause morbidity and mortality from malaria. Parasite resistance to drugs makes development of new chemotherapies an urgency. Aminoacyl-tRNA synthetases have been validated as antimalarial drug targets. We explored long-term effects of borrelidin and mupirocin in lethal P. yoelii murine malaria.

Experimental Approach

Long-term (up to 340 days) immunological responses to borrelidin or mupirocin were measured after an initial 4 day suppressive test. Prophylaxis and cure were evaluated and the inhibitory effect on the parasites analysed.

Key Results

Borrelidin protected against lethal malaria at 0.25 mg·kg⁻¹·day⁻¹. Antimalarial activity of borrelidin correlated with accumulation of trophozoites in peripheral blood. All infected mice treated with borrelidin survived and subsequently developed immunity protecting them from re-infection on further challenges, 75 and 340 days after the initial infection. This long-term immunity in borrelidin-treated mice resulted in negligible parasitaemia after re-infections and marked increases in total serum levels of antiparasite IgGs with augmented avidity. Long-term memory IgGs mainly reacted against high and low molecular weight parasite antigens. Immunofluorescence microscopy showed that circulating IgGs bound predominantly to late intracellular stage parasites, mainly schizonts.

Conclusions and Implications

Low borrelidin doses protected mice from lethal malaria infections and induced protective immune responses after treatment. Development of combination therapies with borrelidin and selective modifications of the borrelidin molecule to specifically inhibit plasmodial threonyl tRNA synthetase should improve therapeutic strategies for malaria.     

The impact of CT colonography for colorectal cancer screening on the UK NHS

Background

Biennial faecal occult blood testing (FOBT) for individuals aged 60–69 years is the primary screening tool for colorectal cancer (CRC) in the UK NHS, despite a large number of patients undergoing an unnecessary optical colonoscopy (OC) and evidence from modelling studies to suggest that more cost-effective technologies exist. CT colonography (CTC) is an emerging CRC screening technology with the potential to prevent CRC by detecting pre-cancerous polyps and to detect cancer at an earlier stage.

Objective

To assess the impact of introducing CTC into the UK NHS screening programme for CRC on key health outcomes as well as the NHS budget and healthcare resource capacity.

Methods

A discrete Markov model was used to reflect the natural history of CRC and the impact of three screening scenarios (biennial FOBT with and without CTC triage of patients referred to OC, and CTC every 5 years) on a range of health outcomes, including the incidence and prevalence of CRC, in a hypothetical cohort of individuals. The yearly costs, health outcomes and healthcare resource capacity requirements were estimated over a 10-year period (2009–18).

Results

Using CTC to follow up FOBT-positive patients (scenario 2) was less costly than directing all FOBT-positive patients to OC (scenario 1); saving d776 283 over 10 years for 100 000 individuals invited for screening (year 2007 values), primarily by avoiding approximately 1700 OCs, but was estimated to require 2200 additional CT scans. Implementing a programme of 5-yearly CTC as a primary screen is expected to be more expensive than FOBT screening over the short term (driven by high screening and diagnosis costs), despite substantial savings in treatment costs for CRC over the 10-year time horizon of the model and improved health outcomes.

Conclusions

Adding CTC into the existing NHS Bowel Cancer Screening Programme as part of a preventive screening strategy could be less costly to the NHS over the longer term when used to triage FOBT-positive patients to appropriate follow-up. Increased demand for radiology services may be compensated for by reduced demand in endoscopy units.