Oseltamivir resistance during treatment of influenza A (H5N1) infection

Influenza A (H5N1) virus with an amino acid substitution in neuraminidase conferring high-level resistance to oseltamivir was isolated from two of eight Vietnamese patients during oseltamivir treatment. Both patients died of influenza A (H5N1) virus infection, despite early initiation of treatment in one patient. Surviving patients had rapid declines in the viral load to undetectable levels during treatment. These observations suggest that resistance can emerge during the currently recommended regimen of oseltamivir therapy and may be associated with clinical deterioration and that the strategy for the treatment of influenza A (H5N1) virus infection should include additional antiviral agents. Copyright © 2005 Massachusetts Medical Society.published_or_final_versio

A successful antimicrobial regime for Chromobacterium violaceum induced bacteremia.

BACKGROUND: Chromobacterium violaceum is a proteobacterium found in soil and water in tropical regions. The organism rarely causes infection in humans, yet can cause a severe systemic infection by entering the bloodstream via an open wound. CASE PRESENTATION: We recently identified a case of severe bacteremia caused by Chromobacterium violaceum at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Here, we describe how rapid microbiological identification and a combination of antimicrobials was used to successfully treat this life threatening infection in a four-year-old child. CONCLUSIONS: This case shows the need for rapid diagnosis when there is the suspicion of a puncture wound contaminated with water and soil in tropical regions. We suggest that the aggressive antimicrobial combination used here is considered when this infection is suspected

Long-term outcome in survivors of neonatal tetanus following specialist intensive care in Vietnam

Background: Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities. Methods: We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children. Results: The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged p = 0.05) with a significantly lower cognitive domain score (3 (IQR 2–6) severe disease vs 7 (IQR 7–8) mild disease, p = 0.02). Conclusions: Neonatal tetanus is associated with long-term sequelae in those with severe disease. In view of these findings, prevention of neonatal tetanus should remain a priority.</p

Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants.

OBJECTIVES: Most data regarding prognosis in neonatal tetanus originates from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low and middle income countries have affected indicators of poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcome in a Vietnamese hospital with neonatal intensive care facilities. METHODS: Data was collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of 'death or prolonged hospital stay'. RESULTS: Multivariable analysis showed that only younger age (OR for mortality 0.69, 95% CI 0.48 to 0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01 to 0.54) were significantly associated with both the combined end point and death. Shorter period of onset (OR 0.94 95% CI 0.9 to 0.97), raised white cell count (OR 1.17, 95% CI 1.02 to 1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14 to1 2.51) were also indicators of mortality. CONCLUSIONS: Risk factors for poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission and leukocytosis

Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants.

OBJECTIVES: Most data regarding prognosis in neonatal tetanus originates from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low and middle income countries have affected indicators of poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcome in a Vietnamese hospital with neonatal intensive care facilities. METHODS: Data was collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of 'death or prolonged hospital stay'. RESULTS: Multivariable analysis showed that only younger age (OR for mortality 0.69, 95% CI 0.48 to 0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01 to 0.54) were significantly associated with both the combined end point and death. Shorter period of onset (OR 0.94 95% CI 0.9 to 0.97), raised white cell count (OR 1.17, 95% CI 1.02 to 1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14 to1 2.51) were also indicators of mortality. CONCLUSIONS: Risk factors for poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission and leukocytosis

Skin dendritic cell and T cell activation associated with dengue shock syndrome

The pathogenesis of severe dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells. We obtained skin biopsies and contemporaneous blood samples from patients within 24 hours of onset of dengue shock syndrome (DSS), and from healthy controls. We analyzed cell subsets by flow cytometry, and soluble mediators and antibodies by ELISA; the percentage of migratory CD1a+ dermal DCs was significantly decreased in the DSS patients, and skin CD8+ T cells were activated, but there was no accumulation of dengue-specific antibodies. Inflammatory monocytic cells were not observed infiltrating the skin of DSS cases on whole-mount histology, although CD14dim cells disappeared from blood

Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial

Over the last 15 years, hand, foot, and mouth disease (HFMD) has emerged as a major public health burden across the Asia-Pacific region. A small proportion of HFMD patients, typically those infected with enterovirus 71 (EV71), develop brainstem encephalitis with autonomic nervous system (ANS) dysregulation and may progress rapidly to cardiopulmonary failure and death. Although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a number of children still deteriorate despite this treatment. Magnesium sulfate (MgSO4) is a cheap, safe, and readily available medication that is effective in managing tetanus-associated ANS dysregulation and has shown promise when used empirically in EV71-confirmed severe HFMD cases.We describe the protocol for a randomized, placebo-controlled, double-blind trial of intravenous MgSO4 in Vietnamese children diagnosed clinically with HFMD plus ANS dysregulation with systemic hypertension. A loading dose of MgSO4 or identical placebo is given over 20 min followed by a maintenance infusion for 72 h according to response, aiming for Mg levels two to three times the normal level in the treatment arm. The primary endpoint is a composite of disease progression within 72 h defined as follows: development of pre-specified blood pressure criteria necessitating the addition of milrinone, the need for ventilation, shock, or death. Secondary endpoints comprise these parameters singly, plus other clinical endpoints including the following: requirement for other inotropic agents; duration of hospitalization; presence of neurological sequelae at discharge in survivors; and neurodevelopmental status assessed 6 months after discharge. The number and severity of adverse events observed in the two treatment arms will also be compared. Based on preliminary data from a case series, and allowing for some losses, 190 patients (95 in each arm) will allow detection of a 50 % reduction in disease progression with 90 % power at a two-sided 5 % significance level.Given the large numbers of HFMD cases currently being seen in hospitals in Asia, if MgSO4 is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications, this finding would be important to pediatric care throughout the region.ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 August 2013)