Epstein-Barr Virus Coinfection in Cerebrospinal Fluid Is Associated With Increased Mortality in Malawian Adults With Bacterial Meningitis

Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that—particularly in individuals infected with human immunodeficiency virus (HIV)—herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation

Epidemiology of Severe Acute Respiratory Illness and Risk Factors for Influenza Infection and Clinical Severity among Adults in Malawi, 2011-2013

Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged ≥ 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7-16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83-6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57-5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35-4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43-0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36-0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35-2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17-7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings

Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults:A Prospective Cohort and Parallel Case-Control Study

The impact of HIV infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings, but is rarely implemented in Africa.We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized lower respiratory tract infection (LRTI)), and mild influenza (influenza-like illness (ILI)).The cohort study enrolled 608 adults (360 (59%) HIV-infected). Between April 2013 and March 2015, 24/229 (10.5%) ILI episodes in HIV-infected and 5/119 (4.2%) in HIV-uninfected adults were influenza PCR positive (incidence rates 46.0 vs. 14.5 per 1000 person years, incidence rate ratio 2.75; 95% confidence interval [CI] 1.02-7.44; p=0.03, adjusted for age, gender, household crowding and food security). In the case control study, influenza was identified in 56/518 (10.8%) patients with hospitalized LRTI, and 88/642 (13.7%) with ILI. HIV prevalence among influenza-positive cases and controls were 69.6% and 29.6% respectively. HIV was a significant risk factor for severe influenza (odds ratio 4.98, 95%CI 2.09-11.88, p<0.001; population attributable fraction 57%, adjusted for season, sanitation facility and food security).HIV is an important risk factor for influenza-associated ILI and severe presentation in this high HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be re-evaluated and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined

Respiratory virus-associated severe acute respiratory illness (SARI) and viral clustering in Malawian children in a setting with a high prevalence of HIV, malaria and malnutrition

Background We used four years of paediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi to identify factors associated with clinical severity and co-viral clustering. Methods From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with co-viral detection. Results Hospital-attended influenza-positive SARI incidence was 2.0 cases per 10,000 children annually; it was highest children aged under 1 year (6.3 cases per 10,000), and HIV-infected children aged 5 to 9 years (6.0 cases per 10,000). 605 (26.8%) SARI cases had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR]: 2.4, 95% CI: 1.4, 3.9), RSV infection (aRR: 1.9, 95% CI: 1.3, 3.0) and rainy season (aRR: 2.4, 95% CI: 1.6, 3.8). We identified six co-viral clusters; one cluster was associated with SARI with warning signs. Conclusions Influenza vaccination may benefit young children and HIV infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance

A comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study

Background: Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome. Methods: We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinION™ in Blantyre. Results: We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p &lt; 0.001) and steroids (38.7% [29/75] vs. 70.3% [167/239], p &lt; 0.001) in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0–25.0 p = 0.05) compared to the first wave of infection. Conclusions: Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave

Prevalence of endemic respiratory viruses during the COVID-19 pandemic in urban and rural Malawi

Background Non-pharmaceutical interventions (NPI) during the COVID-19 pandemic disrupted respiratory virus circulation. Malawi employed multiple NPI but did not impose a “lockdown”. We aimed to investigate endemic respiratory virus circulation patterns in urban and rural Malawi during this period. Methods Within a prospective cohort of randomly selected households in an urban and rural community in Malawi, adult participants provided upper respiratory tract samples at four timepoints, between February 2021 and April 2022. PCR for SARS-CoV-2, influenza and other endemic respiratory viruses was performed. Results 1626 URT samples from 945 participants in 542 households were included. Overall, 7.6% (n = 123) of samples were PCR-positive for 1 respiratory virus; SARS-CoV-2 (4.4%) and rhinovirus (2.0%) were most frequently detected. No influenza A virus was detected. Influenza B and RSV were rare. Significantly higher levels of virus positivity were detected in the rural setting, and at earlier timepoints. Co-infections were infrequent (0.2%; n = 3). Conclusion Endemic respiratory viruses circulated in the community in Malawi during the pandemic, although influenza and RSV were rarely detected. Distinct differences in virus positivity and demographics were observed between urban and rural cohorts. Ongoing surveillance is needed to monitor the impact of continuing co-circulation of SARS-CoV-2 with endemic respiratory viruses