Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.

BACKGROUND: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. METHODS: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. RESULTS: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. CONCLUSIONS: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.

Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial.

Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit Mycobacterium tuberculosis infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology.

HIV/AIDS and rheumatoid arthritis.

The acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). It was first recognized in the United States in 1981, and the HIV/AIDS epidemic has since spread to affect all countries. The interface of HIV/AIDS with opportunistic infectious diseases is well characterized, but further research is required into the concurrence of other chronic diseases. The objective of this review was to identify possible interferences of HIV infection in the diagnosis and management of rheumatoid arthritis (RA). A review of the available evidence was conducted using the GRADE approach. Overall, the quality of evidence was low. Our main conclusions were: (1) the occurrence of rheumatoid-like arthritis in patients with HIV/AIDS is quite rare; therefore, it is not recommended that HIV infection be considered routinely as a differential diagnosis in this condition (C2); (2) HIV infection may lead to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity, but usually at low titers (C1); (3) RA might cause false-positive HIV serology and ELISA seems to be a more specific test for HIV in patients with RA (C2); (4) RA and AIDS may coexist, even in cases of severe immunosuppression (C1); (5) RA emergence may seldom occur during or after immune reconstitution (C1); and (6) there is insufficient safety data to recommend use of specific disease-modifying antirheumatic drugs (DMARDs) in RA patients with HIV/AIDS. Therefore, these drugs should be used cautiously (C1).