Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals.

BACKGROUND: Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID­19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). OBJECTIVES: To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID­19, and the level of medical control of these chronic diseases. METHODS: We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID­19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID­19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. RESULTS: On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID­19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID­19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/µL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. CONCLUSION: The study revealed a high prevalence of comorbid conditions among individuals with COVID­19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID­19 pandemic.

First report of an imported case of haemorrhagic fever with renal syndrome in South Africa.

Haemorrhagic fever with renal syndrome (HFRS) is caused by hantavirus infection. Hantaviruses are not endemic to South Africa, and we report the first detection of an imported case of HFRS in the country. The case involved a traveller from Croatia who presented to a Johannesburg hospital with an acute febrile illness with renal dysfunction. The patient reported visiting rurally located horse stables in Croatia before falling ill, and that a worker in the stables with similar illness was diagnosed with HFRS. Given the exposure history and clinical findings of the case, a clinical diagnosis of HFRS was made and confirmed by laboratory testing.

Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves. METHODS: 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council. RESULTS: For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years. Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave. Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital. CONCLUSION: There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.

Epidemiology of human rabies in South Africa, 2008 - 2018.

BACKGROUND: Human rabies cases continue to be reported annually in South Africa (SA). Previous investigations have shown the association between the occurrence of human rabies cases and dog rabies cases in the country. OBJECTIVES: To describe the epidemiology of laboratory-confirmed human rabies cases in SA for the period 2008 - 2018. METHODS: A retrospective document review of laboratory-confirmed human rabies cases for the period 2008 - 2018 was performed using a case register and related documentation available from the National Institute for Communicable Diseases. RESULTS: A total of 105 human rabies cases were laboratory confirmed from 2008 to 2018, with cases reported from all the provinces of SA except the Western Cape. Children and adolescents were most affected by the disease during the study period. In almost half of the cases, medical intervention was not sought after exposure. When victims did seek healthcare, deviations from post-exposure prophylaxis protocols were reported in some cases. CONCLUSIONS: The epidemiological trends of human rabies cases reported in SA for the period 2008 - 2018 remained largely the same as in previous reports. Dog-mediated rabies remains the main source of human rabies in SA.

Implementing malaria control in South Africa, Eswatini and southern Mozambique during the COVID-19 pandemic.

The COVID-19 pandemic has strained healthcare delivery systems in a number of southern African countries. Despite this, it is imperative that malaria control and elimination activities continue, especially to reduce as far as possible the number and rate of hospitalisations caused by malaria. The implementation of enhanced malaria control/elimination activities in the context of COVID-19 requires measures to protect healthcare workers and the communities they serve. The aim of this review is therefore to present innovative ideas for the timely implementation of malaria control without increasing the risk of COVID-19 to healthcare workers and communities. Specific recommendations for parasite and vector surveillance, diagnosis, case management, mosquito vector control and community outreach and sensitisation are given.

Long-COVID: An evolving problem with an extensive impact.

Persistence of symptoms or development of new symptoms relating to SARS-CoV-2 infection late in the course of COVID-19 is an increasingly recognised problem facing the globally infected population and its health systems. 'Long-COVID' or 'COVID long-haulers' generally describes those persons with COVID-19 who experience symptoms for >28 days after diagnosis, whether laboratory confirmed or clinical. Symptoms are as markedly heterogeneous as seen in acute COVID-19 and may be constant, fluctuate, or appear and be replaced by symptoms relating to other systems with varying frequency. Such multisystem involvement requires a holistic approach to management of long-COVID, and descriptions of cohorts from low- and middle-income countries are eagerly awaited. Although many persons with long-COVID will be managed in primary care, others will require greater input from rehabilitation medicine experts. For both eventualities, planning is urgently required to ensure that the South African public health service is ready and able to respond.

Maintaining focus on administering effective malaria treatment during the COVID-19 pandemic.

As September marks the start of the malaria season in South Africa (SA), it is essential that healthcare professionals consider both COVID- 19 and malaria when a patient who lives in or has recently travelled to a malaria area presents with acute febrile illness. Early diagnosis of malaria by either a rapid diagnostic test or microscopy enables prompt treatment with the effective antimalarial, artemether-lumefantrine, preventing progression to severe disease and death. Intravenous artesunate is the preferred treatment for severe malaria in both children and adults. Adding single low-dose primaquine to standard treatment is recommended in endemic areas to block onward transmission. Use of the highly effective artemisinin-based therapies should be limited to the treatment of confirmed malaria infections, as there is no clinical evidence that these antimalarials can prevent or treat COVID-19. Routine malaria case management services must be sustained, in spite of COVID-19, to treat malaria effectively and support SA's malaria elimination efforts.

Implementing malaria control in South Africa, Eswatini and southern Mozambique during the COVID-19 pandemic

The COVID-19 global pandemic reached South Africa (SA), Mozambique and Eswatini in March 2020.[1] Since then an exponential increase in SARS-CoV-2 infections has severely stretched SA's healthcare system, especially in terms of in-hospital treatment of severe cases. The impact of COVID-19 in Mozambique and Eswatini at the time of writing has been comparatively mild, but is increasing. It is therefore imperative to reduce as far as possible the number and rate of hospitalisations caused by trauma and other diseases, including malaria. Malaria incidence in SA is seasonal and peaks in the wetter summer months, especially during January to April.[2] Although malaria incidence in SA is currently low, the risk of outbreaks is always present, with the most recent having occurred in 2017 and, at a more localised level in Limpopo Province, in 2019. The reasons for these latest outbreaks are varied and include unusually high rainfall and cross-border movement of migrant populations, fuelling local transmission. These issues are particularly pertinent to COVID-19 in SA's malaria-affected districts. They highlight the importance of mitigating factors contributing to high malaria incidence and consequent hospitalisations, which may be further exacerbated by COVID-19/malaria coinfections and the re-opening of SA's borders with those neighbouring countries with higher malaria transmission intensities.

Atypical presentation of Crimean-Congo haemorrhagic fever: Lessons learned.

An atypical case of Crimean-Congo haemorrhagic fever is presented. The diagnosis of the case in the presence of several comorbidities was complicated and illustrates the importance of maintaining a high index of suspicion for viral haemorrhagic fever in cases presenting with multisystem disease and an epidemiological history that could present opportunities for exposure to a haemorrhagic fever virus.

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

Risk factors for pertussis among hospitalized children in a high HIV prevalence setting, South Africa.

BACKGROUND: In low- and middle-income countries, including South Africa, the epidemiology of pertussis in relation to immunization, nutritional, and HIV status is poorly described. This article reports on risk factors in South African children hospitalized with pertussis. METHODS: A prospective, hospital-based, sentinel surveillance programme for pertussis was conducted in Gauteng Province, South Africa. Hospitalized children (≤10 years) meeting the surveillance criteria for clinically suspected pertussis were screened and enrolled. Nasopharyngeal specimens were collected for real-time multiplex PCR and culture of Bordetella species. RESULTS: Bordetella pertussis was detected in 6.2% (61/992) of children. Pertussis was significantly more prevalent in infants younger than 3 months (9.8%; 38/392) and in young children between the ages of 5 and 9 years (12%; 4/34) (p=0.0013). Of the 61 confirmed pertussis cases, 17 were too young for vaccination. Of the remaining 44 infants, vaccination DTP1 was administered in 73% (32/44) of pertussis-confirmed patients who were eligible, DTP2 in 50% (16/32), DTP3 in 54% (14/26), and DTP4 in 56% (5/9) of vaccine-eligible cases at 18 months of age. B. pertussis infection was less likely in children immunized at least once (5%, 32/692) than in unvaccinated children (10%, 24/230) (p=0.0001). HIV exposure and infection status were determined in 978 (99%) patients: 69% (678/978) were HIV-unexposed and uninfected and 31% (300/978) were HIV-exposed. Of these HIV-exposed patients, 218 (22%) were proven HIV-exposed and uninfected and 82 patients were HIV-infected (8.4%, 82/978). HIV prevalence was similar in pertussis-positive (6%, 5/82) and pertussis-negative (6%, 55/896) children (p=0.90). B. pertussis infection was unrelated to poor nutritional status. CONCLUSIONS: In South Africa, B. pertussis poses a greater risk to infants who are too young for the first vaccine dose, those who are not vaccinated in a timely manner, and those who do not receive all three primary doses. HIV infection and HIV exposure were not associated with pertussis infection.