Date Published: April 19, 2019
Publisher: Public Library of Science
Author(s): Nsoh Godwin Anabire, Paul Armah Aryee, Abass Abdul-Karim, Osbourne Quaye, Gordon Akanzuwine Awandare, Gideon Kofi Helegbe, Jason Blackard.
The overlap of malaria and chronic hepatitis B (CHB) is common in endemic regions, however, it is not known if this co-infection could adversely influence clinical and immunological responses. This study investigated these interactions in pregnant women reporting to antenatal clinics in Ghana.
Clinical parameters (hemoglobin, liver function biomarker, peripheral malaria parasitemia, and hepatitis B viremia) and cytokine profiles were assayed and compared across four categories of pregnant women: un-infected, mono-infected with Plasmodium falciparum (Malaria group), mono-infected with chronic hepatitis B virus (CHB group) and co-infected (Malaria+CHB group).
Women with Malaria+CHB maintained appreciably normal hemoglobin levels (mean±SEM = 10.3±0.3 g/dL). That notwithstanding, Liver function test showed significantly elevated levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin [P<0.001 for all comparisons]. Similarly, the Malaria+CHB group had significantly elevated pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 [P<0.05 for all comparisons]. In women with Malaria+CHB, correlation analysis showed significant negative association of the pro-inflammatory cytokines responses with malaria parasitemia [IL-1β (P<0.001; r = -0.645), IL-6 (P = 0.046; r = -0.394) and IL-12 (P = 0.011; r = -0.49)]. On the other hand, the pro-inflammatory cytokine levels positively correlated with HBV viremia [TNF-α (P = 0.004; r = 0.549), IL-1β (P<0.001; r = 0.920), IL-6 (P<0.001; r = 0.777), IFN-γ (P = 0.002; r = 0.579), IL-2 (P = 0.008; r = 0.512) and IL-12 (P<0.001; r = 0.655)]. Also, for women in the Malaria+CHB group, parasitemia was observed to diminish HBV viremia [P = 0.003, r = -0.489]. Put together the findings suggests that Malaria+CHB could exacerbate inflammatory cytokine responses and increase susceptibility to liver injury among pregnant women in endemic settings.
Coinfections are increasingly being recognized as common risk factors that may contribute to the increased burden of morbidity in pregnancy. In many endemic setting, the overlap of chronic hepatitis virus (HBV) and P. falciparum infections is common, and an increased prevalence, from 0.7% to 1.7%, of this co-infection has been reported among pregnant women in Ghana [1, 2]. The disease causing pathogens share a common intra-hepatic niche, and each may independently cause liver function test abnormalities [3–9]. Immunologically, both pathogen may also overlap, as each is observed to mainly trigger T helper type 1 (Th1) cytokine responses [10–14]. P. falciparum causes anemia by reducing red cell counts, while HBV is postulated to increase hemoglobin (Hb) levels by increasing the release of erythropoietin from regenerating hepatic tissues [15–17]. Thus, it may be logical to postulate that HBV could compensate for the effect of P. falciparum on Hb levels in co-infection state.
Maternal anemia is an issue of important public health relevance. During pregnancy, women with Hb <11g/dL are diagnosed as anemic while those with Hb ≥ 11g/dL are considered to have normal level . P. falciparum causes anemia by reducing red cell counts, HBV on the other hand is postulated to increase Hb levels by increasing the release of erythropoietin from regenerating hepatic tissues [15–17]. It is therefore logical that pregnant women with Malaria+CHB maintained intermediate levels of hemoglobin (above the Malaria group and un-infected, and below CHB group). This observation may suggest that in women with Malaria+CHB, activities of the plasmodium parasites in reducing red cell count may be compensated for by the activities of the virus, thus maintaining an appreciable hemoglobin concentration. The significant association of CHB with Hb ≥11g/dL further justifies the possible impact of HBV in increasing hemoglobin levels among the pregnant women. However, this might not necessarily translate into improved pregnancy outcomes, since cases of gestational diabetes, antepartum hemorrhage and preterm delivery are observed to be more frequent in pregnant women with CHB [30–32]. A longitudinal approach on changes of Hb levels in the co-infected cohorts after clearance of P. falciparum would have been paramount in substantiating the compensatory effect of the viral infection. Again such an approach would have enabled us to see the kinetics of Malaria+CHB co-infection and to identify times when the markers of liver injury and inflammatory responses are enhanced. In addition, such an approach would have enabled us to substantiate our findings by profiling placental cytokines responses, malaria parasitemia and HBV viremia, and associating the results with pregnancy complications. Also profiling of innate immune cells and T-cell populations would have given a better insight of the effect of the co-infection on the immune response. Nonetheless, the current study provides evidence on the need to take into cognizance the possible deleterious impact of Malaria+CHB on pregnant women. In this regard, liver functions test which is important in guiding diagnosis and treatment of liver diseases in pregnancy must be readily accessible to pregnant women on ANC clinics. Put together the findings suggests that Malaria+CHB could exacerbate inflammatory cytokine responses and increase susceptibility to liver injury among pregnant women in endemic settings. Source: http://doi.org/10.1371/journal.pone.0215550