Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Rapid Malaria Screening in Children
Source: D'Acremont V, et al. Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test. Clin Inf Dis. 2010;51:506-511.
In countries endemic for malaria, young children often receive empiric antimalarial therapy for febrile illness, resulting in over treatment and expense. In addition to the fact that environmental control measures in some of these countries have reduced the risk of malaria, the introduction of a rapid diagnostic test for malaria (RDTm) provides more efficient screening of suspect cases.
One thousand children ages 6 months to < 5 years (median age, 2 years) in the Kilombero Valley, Tanzania, with fever > 37.5 within the previous 48 hours without other apparent illness, participated in this project to assess the risk of infection and the safety of RDTm screening. Children with a negative RDTm screening test did not receive antimalarials and were asked to return to the clinic for follow-up in seven days, or in the event of persistent symptoms. Children who returned to the clinic were re-evaluated, and repeat RDTm testing was performed.
Of these, 603 (60%) had a negative RDTm test result and did not receive antimalarials. At the study site in Dar es Salaam, 41/300 (14%) children tested positive and were treated with antimalarials; all but one of the other children received empiric antibiotics. At the other study site in Signal, 356/700 (51%) tested positive for malaria; 91% of the remaining children received an antibiotic. Two of the children with positive RTDm test results died of other causes. (Thirteen of the children were lost to follow-up.)
Of the remaining 591 who tested negative, 573 (97%) were doing well and considered cured at day 7 of follow-up. Of the 18 children who were not well by day seven, repeat RTDm test results were negative in all of them, 14 recovered by day 14, two were lost to follow-up, and two died (one from sepsis and one from pneumonia).
In addition, 37 children with initially negative RTDm test results re-visited the health care clinic before day seven for persistent symptoms three had newly positive malaria tests, including one at day 4 and two at day 7 (one of these was thought to possibly be a new infection). Overall, four children with persistent symptoms between study entry and day 7 required hospitalization (two others from severe diarrhea and dehydration, and the other from severe anemia); blood smears and repeat RTDm tests were negative in all four.
Withholding empiric antimalarial therapy from febrile children under the age of 5 years who have a negative rapid diagnostic test for malaria appears to be appropriate and safe, and avoids excessive use of antimalarials. The percentage of children with persistent symptoms at day 7 was similar between the treated and untreated groups (2% vs. 3%, respectively). The risk of hospitalization and death was similar between the two groups, and no child died of malaria. Only three of 591 (0.67%) children who initially tested negative subsequently had a positive rapid malaria test.
Fungal Infection in Organ Transplantation
Source: Pappas PG, et al. Invasive fungal infections among organ transplant recipients: Results of the transplant-associated infection surveillance network (TRANSNET). Clin Infect Dis. 2010;50:1091-1100.
Since 2001, the transnet surveillance network has been tracking data from 23 transplant centers around the United States for both solid-organ and hematopoietic stem-cell transplants. Between 2001 and 2006, data on invasive fungal infection (IFI) was collected for a total of 16,808 solid-organ transplant patients from 15 transplant centers (all solid organ transplant centers). Data for more than 15% of all transplant cases in the United States are captured using this network.
The median age of the patients was 50 years (0.5 to 81 years); only 5% were pediatric cases. Slightly more than half of the group were kidney transplant patients, including 33% unrelated donors and 19% living donors; the rest were liver (27%), lung (7%), pancreas (7%), heart (7%), small bowel (0.4%), or other (0.1%). Patients with multiple organ transplants were classified according to their highest risk transplant.
Only documented and probable cases of invasive fungal infection were prospectively included in the database. During this five-year period, 1,208 proven (42%) and probable (58%) cases of IFI occurred among 1,063 organ transplant recipients. The most common IFI was candidiasis, involving 53% of the group, two-thirds of which were bloodstream infections; the rest involved the urinary tract infection or peritoneum. The remaining IFI were due to invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Pneumocystis occurred infrequently (~1%).
Three-fourths of the cases of Aspergillus infection involved the lungs (78%). Of those cases with documented microbiological results, half were due to A. fumigatus; mixed aspergillus infection was observed in 12% of patients. Not surprisingly, given the difficulty in documenting Aspergillus infection, nearly three-fourths of these infections were classified as probable. In contrast, cryptococcal infection more frequently involved the nervous system (in 45%), the lungs (in 39%), and only the bloodstream (in 4%). Molds and other non-endemic fungal infections, such as fusariosis, phaeophyphomycosis, and various zygomycosis resulted in IFI in about 10% of cases. These were quite varied in their presentation, involving the lungs in 56% of cases, sinuses in 13%, skin in 13%, or resulted in disseminated infection in 9%.
Endemic fungal infection (histoplasmosis, coccidioidomycosis, and blastomycosis) occurred in just 5% of the cases, and often resulted in widespread infection with multi-organ system involvement. Three-fourths of these cases were due to histoplasmosis, with seven cases of coccidioidomycosis and nine cases of blastomycosis.
While each of these infections occurred to varying degree in all transplant groups, candidal infections tended to dominate in patients with small bowel, liver, and pancreas transplants, whereas aspergillosis and non-aspergillus molds tended to dominate in lung transplants. Cryptococcus occurred more commonly in kidney and heart transplants. Generally, most episodes of candidemia and disseminated candidal infection occurred within the immediate transplant period (< 3 months). The median time to developing IFI was 103, 184, and 575 days post-transplantation, respectively, for candida, aspergillus, and cryptococcal infection. Endemic fungal infection also commonly occurred within the first six months of transplantation, generally as the result of reactivation of latent infection or, in 2 of 7 cases of cocci, as the result of donor reactivation of infection. The cumulative incidence of fungal infection for the first 12 months post-transplantation was greatest for patients with either small-bowel transplantation (11.6%) or lung (8.6%), followed by 4.7%, 4%, 3.4%, and 1.3% for liver, heart, pancreas, and kidney transplant.
Following a diagnosis of invasive fungal infection, the 12-month survival was best for Cryptococcus (73%), followed by 66% of candidiasis, 61% for non-Aspergillus molds, and 59% for aspergillosis. These figures are depressing when one considers them against the backdrop of much more aggressive and frequent use of antifungal chemoprophylaxis and an improved antifungal armamentarium.
Fungal infection in Stem-Cell Transplantation
Source: Kontoyiannis DP, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: Overview of the transplant-associated infection surveillance network (TRANSNET) database. Clin Infect Dis. 2010; 50:1091-1100.
Data similar to that above was collected for IFI in hematopoietic stem-cell transplant recipients (HSCT). Between 2001 and 2006, data on invasive fungal infection (IFI) was collected for a total of 16,200 hematopoietic stem-cell transplant patients from 22 transplant centers. The median age was 50 years (range, 0.1-85 years), and 9% of the patients were pediatric. More than half (59%) of the cases were autologous stem-cell transplants, and the rest were allogeneic matched-related (22%), allogeneic unrelated (16%), allogeneic mismatched-related (3%), and synogeneic (0.2%). During the 12 months following transplantation, 13% of transplant recipients had recurrence of their underlying disease and 15% died.
During the five-year period of surveillance, 983 proven (56%) and probable (44%) IFI cases among 875 HSCT were observed. Unlike the solid organ cases, more than half of the infections were due to aspergillosis (43%) and zygomycosis (8%), or unspecified molds (6%), and fewer were due to invasive candidiasis (28%), reflecting the differing immune system dysfunction. The overall cumulative incidence of fungal infection for the first 12 months post-transplantation was 3.4% (range by transplant site, 0.3% to 13.2%). The 12-month incidence of IFI was higher for mismatched-related donor recipients (8.1%), unrelated-donor recipients (7.7%), matched-donor recipients (5.8%), and lower among autologous HSCT recipients (1.2%).
The median time to developing IFI was 61, 99, 123, and 135 days post-transplantation, respectively, for candida, aspergillus, fusariosis, and zygomycosis infection. Within 60 days of onset of neutropenia (< 500 cells/mm3), 57% developed IFI; 61% of the cases occurred within 60 days of onset of graft-versus-host disease. In autologous transplant recipients, 66% of the cases of invasive candidiasis occurred within one month of transplantation, and 74% occurred within four months. Similarly, nearly half (45%) of aspergillus infections in matched-related HSCT recipients, and 61% in unmatched-related cases, occurred within four months of transplantation. More than half of these cases (57%) had received myeloablative "conditioning" prior to transplantation.
Overall one-year survival among the entire group of HSCT recipients was best for patients with candidiasis (34%), followed by zygomycosis (28%) and aspergillus infection (25%), and was worst for those with fusarium infection (6%).
Interestingly, the risk for aspergillus infection appeared to increase over the study period, especially at a subset of sites, where the risk for aspergillus infection was highest, for reasons that are not clear. In contrast, the risk for candidiasis remained steady. Importantly, the risk of IFI did not appear to decrease despite the more aggressive and frequent use of fungal chemoprophylaxis in these patients.
In countries endemic for malaria, young children often receive empiric antimalarial therapy for febrile illness, resulting in over treatment and expense.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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