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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.
Neonatal Yellow Fever Vaccine Strain
Source: MMWR. Transmission of Yellow Fever Vaccine Virus through Breast-Feeding Brazil, 2009. MMWR. 2010;59:130-132.
Yellow fever vaccine (YFV) is a live, attenuated viral vaccine that is manufactured using a variety of strains of YF virus. Milder side effects of YFV occur in 2%-10% of people (headache, muscle aches, and fever) within 3 to 9 days of vaccination. More severe and life-threatening YFV-related side effects are rare; the incidence of vaccine-related encephalitis in adults is 0.4 in 100,000 cases, although it is more frequent in infants (0.5-4.0/1,000 cases). It is for this reason that YFV is contraindicated in infants < 6 months of age. In addition, based on a theoretical risk of transmission from mother to infant, YFV is contraindicated in nursing women. Limited data suggest that flaviviruses, such as West Nile Virus, may be transmitted in breast milk during periods of viremia, although the data for YF virus in breast milk is even more limited.
This unusual case report describes a 23-day-old infant who presented with one day of fever and irritability and progressive seizures requiring hospitalization. An initial lumbar puncture was unremarkable, with 1 WBC/mm3 and a slightly elevated protein level and diminished glucose; all cultures and serologic studies were negative. Despite empiric treatment for meningoencephalitis, the baby continued to do poorly, with progressive seizures (every 10 minutes), requiring intensive care. A repeat CSF examination on the third day of hospitalization showed lymphocytosis, with 128 WBC/mm3 and a protein level of 106 mg/dL.
Mom reported receiving 17DD YFV 15 days post-partum when she presented for postpartum care. About five days after vaccination, she developed headache and low grade fever for two days. An epidemic of yellow fever was occurring near her home.
Remarkably, YF vaccine virus RNA was detected by PCR in the baby's CSF which was identical to 17DD vaccine strain received by mom. Serological studies demonstrated YF virus IgM in both sera and CSF, consistent with intrathecal antibody production. The onset of the infant's symptoms coincided within a day or two of the period of mom's presumed vaccine-related viremia. Fortunately, the baby gradually improved and was eventually discharged from hospital with no evident sequelae. Further data on the duration of excretion of vaccine-strain virus in breast milk would be useful.
TB in Haiti
Source: ProMED-mail post, February 5, 2010; www.promedmail.org
Haiti is one of the poorer countries in the world, with the highest per-capita rate of tuberculosis in Latin America and the Caribbean. According to the WHO 2009 Global TB Control Report, 29,333 new cases of tuberculosis were diagnosed in Haiti in 2007 (approximate incidence, 300 cases per 100,000 population). Of these, 53% were sputum smear positive, and 1.8% were multi-drug resistant. An estimated 6,814 people died from TB in Haiti in 2007 alone.
Since 1998, the Ministry of Health stepped up TB control efforts in the country, increasing detection efforts and initiating a DOT program. Attempts at DOT therapy have varied from region to region, but it was used for as many as 91% of cases in 2006, although that number declined somewhat to 70% in 2007. The situation is compounded by the high rate of HIV and TB co-infection, which is as much as 30% of TB cases in some areas.
The recent earthquake not only demolished buildings and infrastructure in Haiti, but also has devastated TB control efforts. The only TB hospital/sanitorium in the country, which housed several hundred of the sickest patients, was critically damaged, and The New York Times reports that patients have fled and are now living in tent cities, where TB transmission seems likely. "Hundreds" still report daily to pick up their medications, but the efforts of trained personnel have been diverted, or they have died in the quake. The obvious concern is the potential for increasing drug resistance and widespread infection.
If Only Mr. Oster Knew
Source: Silverman MS, et al. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroentero Hepatol. 2010;
Increasingly, my partner and I are seeing patients with recurrent Clostridium difficile enterocolitis (CDI) who are "vancomycin-dependent." Whenever they attempt to taper or stop their orally administered vancomycin, their symptoms recur. We've tried prolonged vancomycin tapers for 6-12 weeks, "terminal" treatment with rifaximine, intermittent courses of nitazoxanide, and IVIg infusions without success (the latter seemed to work in one person). These patients are incredibly frustrated by their infection and hamstrung by the financial burden, which can cost anywhere from $1,200-$3,000 per month (depending on the dosage and formulation of oral vancomycin).
Fecal transplants have been proposed for such patients, with preliminary reports from Europe and Canada of success in small numbers of patients, but the procedure has not gained acceptance in the United States. A family member as donor is considered best, perhaps because they may share fecal flora.
In this pilot study, donors were excluded if they had a history of hospitalization within the previous three months, a history of malignancy, or a history of bowel disorders, such as irritable or inflammatory bowel disease. Seven patients with recalcitrant CDI agreed to participate; all of them had had repeated episodes of CDI whenever they attempted to taper or stop their vancomycin. Stool cultures for CD were positive in one of the seven (during treatment with oral vanco); studies demonstrated this isolate was consistent with the epidemic hypervirulent NAP1 strain.
The procedure is somewhat more complicated than you would imagine, and begins with formal laboratory screening of the donor, much the same as in transplantation of body parts (including cell counts, chemistries, serologies for HIV, HTLV I/II, RPR, Hepatitis A IgM, Hepatitis Bs antigen, HCV antibody, H. pylori Ab, and stool for culture, O&P x 3, and C. difficile assay). Stools were prepared in a kitchen blender at home, mixed with 200 mL of saline, and administered at home using a standard enema kit. (An earlier procedure recommended straining the stool, presumably to remove any of the residual peas and carrots, but this adds to the complexity and mess.) The recipient lay down for as long as possible, but if he or she passed the transplant within an hour, the procedure was repeated.
All seven patients recovered without recurrence of their CDI and remained disease-free for 4-14 months. Three patients received antibiotics in the post-transplantation period (two for UTI and one for perioperative prophylaxis for hip replacement), and none developed recurrent symptoms. One patient developed symptoms of intermittent constipation and diarrhea, but colonoscopy and studies for CD were negative. These data lend added support for the idea of home-stool transplants for patients with recalcitrant CDI. One hopes that Mr. Oster would approve.
C. difficile Ubiquitous Following Treatment
Source: Sethi AK, et al. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidemiol. 2010;31:21-26.
CD is fast becoming one of the most significant and stubborn infections in the hospital setting. Questions remain whether asymptomatic patients with positive CD PCR tests require isolation in the hospital, what patient hygiene and environmental measures are necessary and effective, and how long patients require contact isolation following resolution of symptoms. To assess the frequency of persistent skin and environmental colonization, these authors from the Cleveland Clinic prospectively collected stool, skin, and environmental samples from 52 patients with active CDI every 2-3 days during treatment, and weekly following resolution of symptoms, as long as they remained hospitalized or resided at a long-term care facility. Of these, 34 received oral metronidazole and 18 received oral vancomycin; ten (29%) were switched to oral vancomycin for persistent symptoms.
Samples were cultured for CD, and cytotoxic assays and molecular ribotyping using PCR were performed on a subset of isolates. Environmental samples were taken using premoistened cotton gauze pads, applied to the call button, bedrails, telephone, and bedside table, immediately following which, the areas would be cleansed with a bleach solution. At baseline, before initiation of therapy, 100% of stool specimens and approximately 88% of skin specimens were culture-positive for CD. Nearly two-thirds of the isolates were the epidemic NAP 1 strain, and produced binary toxin.
By the time diarrheal symptoms resolved (an average of 4.2 days), stool cultures were negative (on therapy) in 82% of patients, and only two (7%) patients had positive stool cultures at the end of therapy. However, more than half (56%) of patients who had successfully completed treatment and remained asymptomatic had one or more positive stool cultures 1-6 weeks following discontinuation of treatment; six patients (12%) eventually relapsed.
Furthermore, despite the inability to demonstrate CD in stool specimens at the end of therapy, skin contamination remained common at the end of treatment. During the first 1-4 weeks following completion of treatment, 58% of patients had positive skin cultures. And, despite ongoing environmental measures, shedding of CD organisms during this period was common, resulting in positive cultures in 50% of environmental specimens. Persistent skin and environmental colonization was more common in patients who received antibiotics for other indications compared with those who did not (80% vs. 36%, p = .04). The investigators also donned gloves, and examined the frequency of glove contamination with CD organisms following skin contact with 18 of the patients (groin, chest and abdomen, and arms and hands). Three to 22 days following resolution of diarrhea, 50% of the gloves were positive.
These data support aggressive environmental measures to combat environmental colonization with CD, for at least 4-6 weeks after resolution of CDI symptoms. Further study should also focus on measures to improve patient hygiene in reducing environmental colonization. Based on these data, contact isolation should be extended for at least six weeks post-CD treatment, either during hospitalization or if the patient requires readmission.