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Severe anaemia complicating HIV in Malawi; multiple co-existing aetiologies are associated with high mortality

PLOS ONE, 2020-02-25

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Background: Severe anaemia is a major cause of morbidity and mortality in HIV-infected adults living in resource-limited countries. Comprehensive data on the aetiology is lacking and needed to improve outcomes. Methods: HIV-infected adults with severe (haemoglobin ≤70g/l) or very severe anaemia (haemoglobin ≤50 g/l) were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Fifteen potential causes of severe anaemia of anaemia and associations with anaemia severity and mortality were explored. Results: 199 patients were enrolled: 42.2% had very severe anaemia and 45.7% were on ART. Over two potential causes for anaemia were present in 94% of the patients; including iron deficiency (55.3%), underweight (BMI<20: 49.7%), TB-infection (41.2%) and unsuppressed HIV-infection (viral load >1000 copies/ml) (73.9%). EBV/CMV co-infection (16.5%) was associated with very severe anaemia (OR 2.8 95% CI 1.1-6.9). Overall mortality was high (53%; 100/199) with a median time to death of 16 days. Death was associated with folate deficiency (HR 2.2; 95% CI 1.2-3.8) and end stage renal disease (HR 3.2; 95% CI 1.6-6.2). Conclusion: Mortality among severely anaemic HIV-infected adults is strikingly high. Clinicians must be aware of the urgent need for a multifactorial approach, including starting or optimising HIV treatment; considering TB treatment, nutritional support and attention to potential renal impairment.

High SARS-CoV-2 seroprevalence in Health Care Workers but relatively low numbers of deaths in urban Malawi

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Background In low-income countries, like Malawi, important public health measures including social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of the true burden of infection and death. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection in urban Malawi. Methods Five hundred otherwise asymptomatic HCWs were recruited from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples were collected all participants. A commercial ELISA was used to measure SARS-CoV-2 IgG antibodies in serum. We run local negative samples (2018 - 2019) to verify the specificity of the assay. To estimate the seroprevalence of SARS CoV-2 antibodies, we adjusted the proportion of positive results based on local specificity of the assay. Results Eighty-four participants tested positive for SARS-CoV-2 antibodies. The HCW with a positive SARS-CoV-2 antibody result came from different parts of the city. The adjusted seroprevalence of SARS-CoV-2 antibodies was 12.3% [CI 9.0-15.7]. Using age-stratified infection fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence, the number of predicted deaths was 8 times the number of reported deaths. Conclusion The high seroprevalence of SARS-CoV-2 antibodies among HCW and the discrepancy in the predicted versus reported deaths, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

Hepcidin and conventional markers to detect iron deficiency in severely anaemic HIV-infected patients in Malawi

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Introduction: Iron deficiency is a treatable cause of severe anaemia in low-and-middle-income-countries (LMIC). Diagnosing it remains challenging as peripheral blood markers poorly reflect bone-marrow iron deficiency (BM-ID), especially in the context of HIV-infection. Methods: Severe anaemic (haemoglobin ≤70g/l) HIV-infected adults were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. BM-ID was evaluated. Accuracy of blood markers including hepcidin alongside mean corpuscular volume, mean cellular haemoglobin concentration, serum iron, serum ferritin, soluble transferrin receptor (sTfR), sTfR -index, sTfR –ratio to detect BM-ID was valued by ROC area under the curve (AUCROC ). Results: Seventy-three patients were enrolled and 35 (48.0%) had BM-ID. Hepcidin and MCV performed best; AUCROC of 0.593 and 0.545. Other markers performed poorly (ROC<0.5). The AUCROC of hepcidin in males was 0.767 (sensitivity 80%, specificity 78%) and in women 0.490 (sensitivity 60%, specificity 61%). Conclusion: BM-ID deficiency was common in severely anaemic HIV-infected patients and is an important and potential treatable contributor to severe anaemia. Hepcidin was the best, though still suboptimal, marker of BM-ID. Hepcidin, which is directly linked to iron absorption, is a very promising marker to guide curative iron supplementation policies in severely anaemic HIV-infected patients.