Objectives To assess the performance of WHO’s “Guidelines for care at the first-referral level in developing countries” in an area of intense malaria transmission and identify bacterial infections in children with and without malaria.Design Prospective study.Setting District hospital in Muheza, northeast Tanzania. Participants Children aged 2 months to 13 years admitted to hospital for febrile illness.Main outcome measures Sensitivity and specificity of WHO guidelines in diagnosing invasive bacterial disease; susceptibility of isolated organisms to recommended antimicrobials.Results Over one year, 3639 children were enrolled and 184 (5.1%) died; 2195 (60.3%) were blood slide positive for Plasmodium falciparum, 341 (9.4%) had invasive bacterial disease, and 142 (3.9%) were seropositive for HIV. The prevalence of invasive bacterial disease was lower in slide positive children (100/2195, 4.6%) than in slide negative children (241/1444, 16.7%). Non-typhi Salmonella was the most frequently isolated organism (52/100 (52%) of organisms in slide positive children and 108/241 (45%) in slide negative children). Mortality among children with invasive bacterial disease was significantly higher (58/341, 17%) than in children without invasive bacterial disease (126/3298, 3.8%) (P<0.001), and this was true regardless of the presence of P falciparum parasitaemia. The sensitivity and specificity of WHO criteria in identifying invasive bacterial disease in slide positive children were 60.0% (95% confidence interval 58.0% to 62.1%) and 53.5% (51.4% to 55.6%), compared with 70.5% (68.2% to 72.9%) and 48.1% (45.6% to 50.7%) in slide negative children. In children with WHO criteria for invasive bacterial disease, only 99/211(47%) of isolated organisms were susceptible to the first recommended antimicrobial agent.Conclusions In an area exposed to high transmission of malaria, current WHO guidelines failed to identify almost a third of children with invasive bacterial disease, and more than half of the organisms isolated were not susceptible to currently recommended antimicrobials. Improved diagnosis and treatment of invasive bacterial disease are needed to reduce childhood mortality.

Arjen Dondorp and colleagues investigate whether the plasma level of Plasmodium falciparum histidine-rich protein 2 can be used to distinguish between severe malaria and other severe febrile illness in African children with malaria.

BackgroundThe importance of invasive salmonellosis in African children is well recognized but there is inadequate information on these infections. We conducted a fever surveillance study in a Tanzanian rural hospital to estimate the case fraction of invasive salmonellosis among pediatric admissions, examine associations with common co-morbidities and describe its clinical features. We compared our main findings with those from previous studies among children in sub-Saharan Africa.Methodology/Principal FindingsFrom 1 March 2008 to 28 Feb 2009, 1,502 children were enrolled into the study. We collected clinical information and blood for point of care tests, culture, and diagnosis of malaria and HIV. We analyzed the clinical features on admission and outcome by laboratory-confirmed diagnosis. Pathogenic bacteria were isolated from the blood of 156 (10%) children, of which 14 (9%) were S. typhi, 45 (29%) were NTS and 97 (62%) were other pathogenic bacteria. Invasive salmonellosis accounted for 59/156 (38%) bacteremic children. Children with typhoid fever were significantly older and presented with a longer duration of fever. NTS infections were significantly associated with prior antimalarial treatment, malarial complications and with a high risk for death.Conclusions/SignificanceInvasive salmonellosis, particularly NTS infection, is an important cause of febrile disease among hospitalized children in our rural Tanzanian setting. Previous studies showed considerable variation in the case fraction of S. typhi and NTS infections. Certain suggestive clinical features (such as older age and long duration of fever for typhoid whereas concomitant malaria, anemia, jaundice and hypoglycemia for NTS infection) may be used to distinguish invasive salmonellosis from other severe febrile illness.

Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research.

Objective-To assess technical and operational performance of a dried blood spot (DBS)-based HIV-1 RNA service for remote healthcare facilities in a low-income country.Design-A method comparison and operational evaluation of DBS RNA against conventional tests for early infant diagnosis of HIV and HIV RNA quantitation under field conditions in Tanzania.Methods-DBS were prepared and plasma was frozen at −80°C. DBS were mailed and plasma couriered to a central laboratory for testing using the Abbott m2000 system. Infant diagnosis DBS were also tested for HIV-1 DNA by ROCHE COBAS AmpliPrep/COBAS TaqMan System. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults of DBS RNA were compared with conventional tests; program performance was described.Results-Among 176 infant diagnosis participants, using a threshold of ≥1,000 copies/mL, sensitivity and specificity of DBS versus plasma RNA were 1.00 and 0.99, and of DBS RNA versus DBS DNA were 0.97 and 1.00. Among 137 viral load monitoring participants, when plasma and DBS RNA were compared R was 0.9709; R was 0.9675 ≥5,000 copies/mL but was 0.7301 <5,000 copies/mL. The highest plasma RNA value at which DBS RNA was not detected was 2,084 copies/mL. Median (range) turnaround time from sample collection to result receipt at sites was 23 (4-69) days. The Tanzania mail service successfully transmitted all DBS and results between sites and the central laboratory.Conclusion-Under program conditions in Tanzania, DBS provided HIV-1 RNA results comparable to conventional methods to remote healthcare facilities. DBS RNA testing is an alternative to liquid plasma for HIV-1 RNA services in remote areas.