Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study

Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established. We assessed the incidence of bloodstream infection and risk factors for fatal outcome in a prospective cohort study of 1828 consecutive admissions of children aged zero to seven years with signs of systemic infection. Blood was obtained for culture, malaria microscopy, HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical features, underlying diseases, antimicrobial drug use and patients' outcome. The incidence of laboratory-confirmed bloodstream infection was 13.9% (255/1828) of admissions, despite two thirds of the study population having received antimicrobial therapy prior to blood culture. The most frequent isolates were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9%) of the children with laboratory-confirmed bloodstream infection died. The mortality rate from Gram-negative bloodstream infection (43.5%) was more than double that of malaria (20.2%) and Gram-positive bloodstream infection (16.7%). Significant risk factors for death by logistic regression modeling were inappropriate treatment due to antimicrobial resistance, HIV infection, other underlying infectious diseases, malnutrition and bloodstream infection caused by Enterobacteriaceae, other Gram-negatives and candida. Bloodstream infection was less common than malaria, but caused more deaths. The frequent use of antimicrobials prior to blood culture may have hampered the detection of organisms susceptible to commonly used antimicrobials, including pneumococci, and thus the study probably underestimates the incidence of bloodstream infection. The finding that antimicrobial resistance, HIV-infection and malnutrition predict fatal outcome calls for renewed efforts to curb the further emergence of resistance, improve HIV care and nutrition for children

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria

Background The immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating. Here we examined T-cell, monocyte/macrophage and neutrophil activation during P. falciparum infection by using soluble activation markers for these leukocyte subsets. Methods In a prospective cross-sectional study clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) co-infection with HIV-1, as well as HIV-infected patients with similar symptoms but without malaria (n = 58) and healthy controls (n = 52). Soluble (s)CD25, sCD14, sCD163 and myeloperoxidase (MPO) as markers for T-cell, monocyte/macrophage and neutrophil activation, respectively as well as CX3CL1, granzyme B and TIM-3 as markers of T-cell subsets and T-cell exhaustion, were analyzed. Results All patient groups had raised levels of activation markers compared with healthy controls. Levels of sCD25 and MPO increased gradually from patient with HIV only to patient with malaria only, with the highest levels in the HIV/malaria group. In the malaria group as a whole, MPO, sCD14 and in particular sCD25 were correlated with disease severity. sCD163, sCD25 and in particular MPO correlated with the degree of parasitemia as assessed by qPCR. Patients with falciparum malaria also had signs of T-cell subset activation (i.e. increased granzyme B and CX3CL1) and T-cell exhaustion as assessed by high levels of TIM-3 particularly in patients co-infected with HIV. Conclusion Our data support a marked immune activation in falciparum malaria involving all major leukocyte subsets with particular enhanced activation of neutrophils and T-cells in patients co-infected with HIV. Our findings also support a link between immune activation and immune exhaustion during falciparum malaria, particularly in relation to T-cell responses in patients co-infected with HIV

Prevalence of ESBL carriage in different age groups.

<p>The graph shows the prevalence (%) of ESBL carriage among the study participants when categorized into five different age groups.</p

Prevalence of ESBL screening positive children in the different study groups.

<p>Prevalence of ESBL screening positive children in the different study groups.</p

Characteristics of faecal carriage of ESBL screening positive bacteria among children in Dar es Salaam, Tanzania.

<p>Characteristics of faecal carriage of ESBL screening positive bacteria among children in Dar es Salaam, Tanzania.</p

Prevalence of ESBL carriage among children admitted at each of the study hospitals.

<p>Prevalence of ESBL carriage among children admitted at each of the study hospitals.</p

Primers and probes used in this study.

<p>¹Oligo, Name of the oligonucleotide</p><p>²Probe labelled with different fluorophore than used in the reference</p><p>³Primers and probe for detection of <i>Giardia lamblia</i></p><p>⁴Primers for typing of <i>Giardia lamblia</i></p><p>Primers and probes used in this study.</p

Prevalence of <i>Cryptosporidium</i> and <i>G</i>. <i>lamblia</i> for the different age groups.

<p>The graph shows the prevalence of (A) <i>Cryptosporidium</i> infection and (B) <i>G</i>. <i>lamblia</i> infection for the different age groups.</p