Michaëla A. M. Huson

Community-Acquired Bacterial Bloodstream Infections in HIV-Infected Patients: A Systematic Review

Information on community-acquired bacterial bloodstream infections (BSIs) in individuals infected with human immunodeficiency virus (HIV) is limited. We conducted a systematic literature review. The case fraction of community-acquired bacterial BSIs in hospitalized patients is 20% and 30% in adults and children, respectively, compared to 9% in HIV-negative adults and children. Worldwide, the main pathogens of community-acquired BSI are nontyphoid salmonellae (NTS), Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, but regional differences are apparent, especially for S. pneumoniae. Compared to HIV-negative populations, HIV patients are particularly at risk to develop NTS bacteremia. Bacteremia incidence is related to immunosuppression, and antiretroviral therapy reduces the incidence of BSI in HIV patients (rate ratios, 0.63-0.02). Mortality rates varied between 7% and 46%. These results suggest that bacterial BSI is more likely to be found in HIV-positive than in HIV-negative patients upon hospitalization, and that causative pathogens vary by region.

The effect of HIV infection on the host response to bacterial sepsis

Bacterial sepsis is an important cause of morbidity and mortality in patients with HIV. HIV causes increased susceptibility to invasive infections and affects sepsis pathogenesis caused by pre-existing activation and exhaustion of the immune system. We review the effect of HIV on different components of immune responses implicated in bacterial sepsis, and possible mechanisms underlying the increased risk of invasive bacterial infections. We focus on pattern recognition receptors and innate cellular responses, cytokines, lymphocytes, coagulation, and the complement system. A combination of factors causes increased susceptibility to infection and can contribute to a disturbed immune response during a septic event in patients with HIV. HIV-induced perturbations of the immune system depend on stage of infection and are only in part restored by combination antiretroviral therapy. Immunomodulatory treatments currently under development for sepsis might be particularly beneficial to patients with HIV co-infection because many pathogenic mechanisms in HIV and sepsis overlap.

Clinical, environmental, and serologic surveillance studies of melioidosis in Gabon, 2012-2013.

Burkholderia pseudomallei and B. thailandensis are in the soil; a novel B. pseudomallei sequence type causes lethal septic shock.

Methicillin-resistant Staphylococcus aureus as a cause of invasive infections in Central Africa: a case report and review of the literature.

IntroductionCommunity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) colonization and infection are increasingly being reported worldwide and are associated with severe illness. The vast majority of MRSA infections are skin and soft tissue infections, while invasive disease remains rare. In Western countries, the epidemiology of MRSA is well documented, but from Central Africa, reports on MRSA are very limited.MethodsCase presentation and review of the literature. The clinical features, epidemiology, and characteristics of MRSA in Central Africa, as well as the treatment options, are discussed. We present a case of severe invasive CA-MRSA infection with pneumonia, pericarditis, and bacteremia in a previously healthy young woman in Gabon. Several virulence factors, like Panton–Valentine leukocidin and type I arginine catabolic mobile element, may play a role in the ability of CA-MRSA to cause severe invasive infections. Based on studies from Gabon and Cameroon (no reports were available from other countries), we find that the prevalence of MRSA is relatively low in this region. Treatment depends primarily on local prevalence and resistance profile of MRSA combined with clinical characteristics.ConclusionSevere invasive infection with CA-MRSA is a rare disease presentation in Central Africa, where this pathogen is still relatively uncommon. However, cases of MRSA may be complicated by the human immunodeficiency virus (HIV) and tuberculosis epidemics, and also the limited availability of effective antibiotics.

Monoclonal antibodies for the treatment of Ebola virus disease

ABSTRACT Introduction: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp™ and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.

HIV Coinfection Enhances Complement Activation During Sepsis

BACKGROUNDnHuman immunodeficiency virus (HIV)-induced complement activation may play a role in chronic immune activation in patients with HIV infection and influence the complement system during acute illness. We determined the impact of HIV infection on the complement system in patients with asymptomatic HIV infection and HIV-infected patients with sepsis or malaria.nnnMETHODSnWe performed a prospective observational study of 268 subjects with or without HIV infection who were asymptomatic, were septic, or had malaria. We measured complement activation products (C3bc and C4bc) and native complement proteins (C3 and C4). levels of mannose-binding lectin and C1q-C4 were measured to examine activation of the lectin and classical pathways, respectively.nnnRESULTSnAsymptomatic HIV infection was associated with increased C4 activation, especially in patients with high HIV loads, and was accompanied by elevated C1q-C4 levels. Similarly, sepsis and malaria resulted in increased C4 activation and elevated C1q-C4 concentrations. HIV coinfection enhanced C4 activation and consumption in patients with sepsis; this effect was not detected in patients with malaria. Mannose-binding lectin deficiency (defined as a mannose-binding lectin level of <500 ng/mL) did not influence complement activation in any group.nnnCONCLUSIONSnHIV activates the complement system, predominantly via the classical pathway, and causes increased C4 activation and consumption during sepsis. HIV-induced complement activation may contribute to tissue injury during chronic infection and acute intercurrent bacterial infections.

The impact of HIV on presentation and outcome of bacterial sepsis and other causes of acute febrile illness in Gabon

PurposeHIV, bacterial sepsis, malaria, and tuberculosis are important causes of disease in Africa. We aimed to determine the impact of HIV on the presentation, causes and outcome of bacterial sepsis and other acute febrile illnesses in Gabon, Central Africa.MethodsWe performed a prospective observational study in new adult admissions with fever or hypothermia (≥38 or <36xa0°C). Blood cultures, as well as HIV and malaria testing were performed in all patients.ResultsWe enrolled 382 patients, including 77 (20.2xa0%) with HIV infection. Malaria was the most frequent diagnosis (nxa0=xa0130, 34xa0%), and was associated with a more severe presentation in HIV patients. Sepsis was also common (nxa0=xa0107, 28xa0%), including 29 (7.6xa0%) patients with culture confirmed bacterial bloodstream infection. Bacterial bloodstream infections were more frequent in HIV patients, in particular with S. pneumoniae. Tuberculosis was observed in 29 (7.6xa0%) patients, and was also more common in HIV patients. The majority of HIV patients was newly diagnosed, and only 15 (19.5xa0%) were using combination antiretroviral therapy.ConclusionsOur findings illustrate the impact of HIV co-infection on the burden of sepsis, malaria and tuberculosis in Gabon, as well as the need to scale up HIV counseling, testing and treatment.

Application of the qSOFA score to predict mortality in patients with suspected infection in a resource-limited setting in Malawi

PurposeTo determine the predictive value of qSOFA (quick Sequential Organ Failure Assessment) in Malawian patients with suspected infection.MethodsProspective observational study in a tertiary referral hospital in Malawi.ResultsPredictive ability of qSOFA was reasonable [AUROC 0.73 (95% CI 0.68–0.78)], increasing to 0.77 (95% CI 0.72–0.82) when classifying all patients with altered mental status as high risk. Adding HIV status as a variable to the qSOFA score did not improve predictive value.ConclusionqSOFA is a simple tool that can aid risk stratification in resource-limited settings.

TB and HIV in the Central African region: current knowledge and knowledge gaps

PurposeReliable and comprehensive data on the HIV/AIDS and TB co-pandemics from Central Africa remain scarce. This systematic review provides a comprehensive overview on current and past research activities in the region and provides a basis for future research work to close knowledge gaps.MethodsThe scientific literature was searched for publications meeting the following search terms: “tuberculosis” or “HIV” or “acquired immunodeficiency syndrome”, combined with “Central Africa”, or the names of individual countries within the region. Original studies, reviews and case series were included, and a selection of relevant articles was made.ResultsMost research in the field of HIV and TB has been conducted in Cameroon, where the epidemics have been described fairly well. The Democratic Republic of Congo ranked second on the amount of publications, despite the civil wars over the past several decades. Very little has been published on HIV and TB in the other countries, possibly due to the poor infrastructure of health care systems, lack of scientific capacity building or shortage of laboratory equipment.ConclusionsDespite the relatively high burden of HIV and TB in the Central African region, the amount of research activities on these topics is limited. A better understanding of the co-epidemics in this region is urgently needed. The occurrence of opportunistic infections, treatment complications and drug resistance in TB and HIV need to be better described; the failure of public health systems needs to be understood, and research infrastructure needs to be developed. Only then will it be possible to turn the tide against the HIV and TB epidemics in this region.

Tuberculosis patients hospitalized in the Albert Schweitzer Hospital, Lambaréné, Gabon-a retrospective observational study.

Epidemiological data on tuberculosis in Central Africa are limited. We performed a retrospective observational study on clinical characteristics of 719 hospitalized tuberculosis patients in Lambaréné, Gabon. Human immunodeficiency virus (HIV) co-infection rate was high (34%) and in-hospital mortality was significantly higher in HIV-positive patients (10% versus 2%). Long-term information on patient outcome was limited; however, from 2008 to 2011, loss to follow up was noted in 28% of cases. Our data illustrate the high burden of TB in Gabon, where loss to follow up and emerging drug resistance are important problems for which comprehensive data are still lacking.