Methods We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. Results The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P = 0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P = 0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P = 0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P = 0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P = 0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P = 0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albuminbolus group and 56% (9 of 16) in the saline-bolus group died (P = 0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. Conclusions Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.)

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Mortality after Fluid Bolus in African Children with Severe Infection

Biomedical engineers have traditionally developed technologies in response to the needs of the developed world's medical community. As a result, the diagnostic systems on which they have worked have met the requirements of well-funded laboratories in highly regulated and quality-assessed environments. However, such approaches do not address the needs of the majority of the world's people afflicted with infectious diseases, who have, at best, access to poorly resourced health care facilities with almost no supporting clinical laboratory infrastructure. A major challenge for the biomedical engineering community is to develop diagnostic tests to meet the needs of these people, the majority of whom are in the developing world. We here review the context in which the diagnostics must operate, some of the appropriate diagnostic technologies already in distribution, and some emerging technologies that promise to address this challenge. However, there is much room for innovation, adaptation, and cost reduction be...

https://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.10.061807.160524

Point-of-care diagnostics for global health.

Providing health care in sub-Saharan Africa is a complex problem. Recent reports call for more resources to assist in the prevention and treatment of infectious diseases that affect this population, but policy makers, clinicians, and the public frequently fail to understand that diagnosis is essential to the prevention and treatment of disease. Access to reliable diagnostic testing is severely limited in this region, and misdiagnosis commonly occurs. Understandably, allocation of resources to diagnostic laboratory testing has not been a priority for resource-limited health care systems, but unreliable and inaccurate laboratory diagnostic testing leads to unnecessary expenditures in a region already plagued by resource shortages, promotes the perception that laboratory testing is unhelpful, and compromises patient care. We explore the barriers to implementing consistent testing within this region and illustrate the need for a more comprehensive approach to the diagnosis of infectious diseases, with an emphasis on making laboratory testing a higher priority.

https://www.jstor.org/stable/pdfplus/4484608.pdf

Laboratory medicine in Africa: a barrier to effective health care.

Summary Data on the prevalence and causes of community-acquired bloodstream infections in Africa are scarce. We searched three databases for studies that prospectively studied patients admitted to hospital with at least a blood culture, and found 22 eligible studies describing 58 296 patients, of whom 2051 (13·5%) of 15 166 adults and 3527 (8·2%) of 43 130 children had bloodstream infections. 1643 (29·1%) non-malaria bloodstream infections were due to Salmonella enterica (58·4% of these non-typhoidal Salmonella ), the most prevalent isolate overall and in adults, and 1031 (18·3% overall) were due to Streptococcus pneumoniae , the most common isolate in children. Other common isolates included Staphylococcus aureus (531 infections; 9·5%) and Escherichia coli (412; 7·3%). Mycobacterium tuberculosis complex accounted for 166 (30·7%) of 539 isolates in seven studies that used mycobacterial culture techniques. HIV infection was associated with any bloodstream infection, particularly with S enterica and M tuberculosis complex bacteraemia. Where recorded, patients with bloodstream infections had an in-hospital case fatality of 18·1%. Our results show that bloodstream infections are common and associated with high mortality. Improved clinical microbiology services and reassessment of empirical treatment guidelines that account for the epidemiology of bloodstream infections might contribute to better outcomes.

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Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis

Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species. This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking clinical examination and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e. clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits or coma or respiratory distress or anaemia [haemoglobin < 5 g/dl]). Out of 17201 presumptive malaria cases 9537 (55%) had a confirmed Plasmodium parasitaemia. Among those 6.2% (95% confidence interval [CI] 5.7%-6.8%) fulfilled the case definition of SM most of them in children < 5 y. In this age group the proportion of SM was 11.7% (10.4%-13.2%) for P. falciparum 8.8% (7.1%-10.7%) for P. vivax and 17.3% (11.7%-24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41% p = 0.002) but less often with anaemia (19% versus 41% p = 0.0001). P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM. There is no indication that mixed infections protected against SM. Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden and especially severe disease in areas where P. falciparum and P. vivax coexist. (authors)

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Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea.

Background:  Early recognition of children at highest risk of dying and the targeting of appropriate drug therapy are vital to the improvement of paediatric care in developing countries. This will rely upon the development of simple clinically-based algorithms and treatment guidelines.

Aim:  To determine the role of bacteraemia in children presenting with clinical signs and symptoms of severe malaria.

Design:  Retrospective analysis of blood culture results following prospective data collection.

Methods:  We studied 251 children presenting with symptoms and signs of severe malaria to a tertiary referral centre in Ghana. Blood was taken for malaria blood films, bacterial culture and haemograms.

Results:  On the basis of clinical signs alone, malaria-film-positive ( n = 182) and -negative ( n = 69) patients were indistinguishable. Some 40% of film-negative patients were bacteraemic, vs. 12% of film-positive patients. Severe malaria and bacteraemia were not positively associated. Film-negative bacteraemic patients had a mortality of 39%, primarily affecting the age group <30 months.

Discussion:  Infants presenting with symptoms and signs of severe malaria but a negative malaria film require immediate antibiotic treatment.

/pdf/high-mortality-of-infant-bacteraemia-clinically-1seo89bsqu.pdf

E. Frimpong

Papers

High mortality of infant bacteraemia clinically indistinguishable from severe malaria