Plasma parasitemia as assessed by quantitative PCR in relation to clinical disease severity in African adults with falciparum malaria with and without HIV co-infection

Abstract

Purpose When considering malaria disease severity, estimation of parasitemia in erythrocytes is important, but sometimes misleading, since the infected erythrocytes may be sequestered in peripheral capillaries. In African children and Asian adults with falciparum malaria, parasitemia as assessed by quantitative PCR (qPCR) in plasma seems to be a valuable indicator of disease severity, but data on African adults as well as the impact of co-infection with HIV is lacking. Methods In 131 patients with falciparum malaria in a public tertiary teaching hospital in Mozambique, plasma malaria parasitemia as assessed by qPCR, compared to qualitative malaria PCR in blood cell fraction, was related to malaria disease severity and HIV co-infection. Results Of the 131 patients with falciparum malaria, based on positive qualitative PCR in the blood cell fraction, 93 patients (72%) had positive malaria qPCR in plasma. Patients with severe malaria as defined by the WHO criteria had higher malaria quantitative plasma parasitemia (median 143 genomes/µL) compared to those with uncomplicated malaria (median 55 genomes/µL, p = 0.037) in univariate analysis, but this difference was attenuated after adjusting for age, sex and HIV coinfection (p = 0.055). A quarter of the patients with severe malaria had negative qPCR in plasma. Conclusions This study of adult African in-patients with falciparum malaria with and without HIV co-infection, neither confirms nor rejects previous studies of malaria qPCR in plasma as an indicator of disease severity in patients with falciparum malaria. There is a need for further and larger studies to clarify if parasitemia as assessed malaria qPCR in plasma could be a surrogate marker of disease severity in falciparum malaria.

A meta-analysis on the prevalence and characteristics of severe malaria in patients with Plasmodium spp. and HIV co-infection

“… Berg et al (2008) 23 NA NA NA NA NA NA NA NA 5. Berg et al (2020) 24 NA NA NA NA NA NA NA NA 6. Berkley et al (2009) 25 37,500 (2680–172,150) (n = 133) 22,352 (2213–142,590) (n = 938) NA NA NA NA NA NA 7.…”

“…and HIV co-infection were analysed in the present study (Table 1 ). Of the 29 included studies, 28 (96.6%) were conducted in African countries: 6 (20.7%) in Malawi 27 , 31 , 34 , 35 , 37 , 44 ; 5 (17.2%) in Mozambique 2 , 23 , 24 , 30 , 40 ; 3 (10.30%) in Kenya 25 , 29 , 46 ; 2 (6.90%) each in Ghana 17 , 41 , Cameroon 38 , 39 , South Africa 15 , 42 and Ethiopia 21 , 26 and 1 (3.40%) each in Nigeria 22 , Zambia 28 , Gabon 32 , Uganda 43 , Congo 33 and Burundi 45 . The other study involved patients in France 36 .…”

“…Most of the included studies were cross-sectional studies (20/29, 69%) 2 , 17 , 21 – 27 , 29 , 30 , 33 , 35 , 37 – 42 , 45 , whereas two were prospective cohort studies 15 , 46 , four were case–control studies 28 , 31 , 34 , 43 , and one was retrospective study 36 . Most of the studies had included adults aged > 15 years 2 , 15 , 21 , 23 , 24 , 28 , 32 , 37 , 38 , 40 – 42 , 45 , children aged < 15 years (10/29, 34.5%) 22 , 25 , 27 , 29 , 31 , 34 , 35 , 43 , 44 , 46 and any age group 17 , 26 , 30 , 33 , 36 , 39 , respectively. Most participants at enrolment reflected patients with malaria (16/29, 55.2%) 15 , 21 , 24 , 25 , 27 – 31 , 33 – 37 , 43 , 45 , patients with HIV/AIDS 17 , 22 , 26 , 32 , 39 , 41 , with undefined 23 ...…”

“…Most of the studies had included adults aged > 15 years 2 , 15 , 21 , 23 , 24 , 28 , 32 , 37 , 38 , 40 – 42 , 45 , children aged < 15 years (10/29, 34.5%) 22 , 25 , 27 , 29 , 31 , 34 , 35 , 43 , 44 , 46 and any age group 17 , 26 , 30 , 33 , 36 , 39 , respectively. Most participants at enrolment reflected patients with malaria (16/29, 55.2%) 15 , 21 , 24 , 25 , 27 – 31 , 33 – 37 , 43 , 45 , patients with HIV/AIDS 17 , 22 , 26 , 32 , 39 , 41 , with undefined 23 , 38 , 40 , 46 febrile 2 , 42 and other conditions/diseases 44 . The most common diagnostic method for the detection of Plasmodium spp.…”

“… Berg et al (2008) 23 Mozambique (2006) Cross-sectional study 16–92 Male (167), Female (166) 333 adult patients Immunosuppressed 8 ( P. falciparum ) Microscopy Severe malaria 4 Jaundice 1, Renal failure 2, fatal 1 NA RDT 12 ( P. falciparum ) Severe malaria 9 ( P. falciparum ) Jaundice 2, Renal failure 6, Fatal 1 5. Berg et al (2020) 24 Mozambique (2011–2012) Cross-sectional study ≥ 18 years Male (71), Female (60) 131 P. falciparum Undertreated 61 ( P. falciparum ) Microscopy, RDT Severe malaria 28 Bleeding disturbances and/or haemolysis 1, Fatal 1 NA PCR 70 ( P. falciparum ) Severe malaria 57 ( P. falciparum ) Bleeding disturbances and/or hemolysis 9, Fetal 9 6. Berkley et al (2009) 25 Kenya (1998–2002) Cross-sectional study Children aged ≥ 60 days NA 3,068 severe P. falciparum , 592 healthy control Recently diagnosed P. falciparum Microscopy Severe malaria 938/1071 119/684 10/592 ELISA Severe malaria 133/1071 ( P. falciparum ) 7.…”