Background. The number of human deaths due to rabies is currently underestimated to be 55,000 deaths per year. Biological diagnostic methods for confirmation of rabies remain limited, because testing ...on postmortem cerebral samples is the reference method, and in many countries, sampling brain tissue is rarely practiced. There is a need for a reliable method based on a simple collection of nonneural specimens. Methods. A new reverse-transcription, heminested polymerase chain reaction (RT-hnPCR) protocol was standardized at 3 participating centers in Cambodia, Madagascar, and France. Fifty-one patients from Cambodia, Madagascar, Senegal, and France were prospectively enrolled in the study; 43 (84%) were ultimately confirmed as having rabies. A total of 425 samples were collected from these patients during hospitalization. We studied the accuracy of the diagnosis by comparing the results obtained with use of biological fluid specimens (saliva and urine) and skin biopsy specimens with the results obtained with use of the standard rabies diagnostic procedure performed with a postmortem brain biopsy specimen. Results. The data obtained indicate a high specificity (100%) of RT-hnPCR and a higher sensitivity (⩾98%) when the RT-hnPCR was performed with skin biopsy specimens than when the test was performed with fluid specimens, irrespective of the time of collection (i.e., 1 day after the onset of symptoms or just after death). Also, a sensitivity of 100% was obtained with the saliva sample when we analyzed at least 3 successive samples per patient. Conclusions. Skin biopsy specimens should be systematically collected in cases of encephalitis of unknown origin. These samples should be tested by RT-hnPCR immediately to confirm rabies; if the technique is not readily available locally, the samples should be tested retrospectively for epidemiological purposes.
Rabies virus (RABV), the causative agent for rabies disease is still presenting a major public health concern causing approximately 60,000 deaths annually. This neurotropic virus (genus
Lyssavirus
, ...family
Rhabdoviridae
) induces an acute and almost always fatal form of encephalomyelitis in humans. Despite the lethal consequences associated with clinical symptoms of rabies, RABV limits neuro-inflammation without causing major histopathological lesions in humans. Nevertheless, information about the mechanisms of infection and cellular response in the central nervous system (CNS) remain scarce. Here, we investigated the expression of inflammatory genes involved in immune response to RABV (dog-adapted strain Tha) in mice, the most common animal model used to study rabies. To better elucidate the pathophysiological mechanisms during natural RABV infection, we compared the inflammatory transcriptome profile observed at the late stage of infection in the mouse brain (cortex and brain stem/cerebellum) with the ortholog gene expression in
post-mortem
brain biopsies of rabid patients. Our data indicate that the inflammatory response associated with rabies is more pronounced in the murine brain compared to the human brain. In contrast to murine transcription profiles, we identified CXC motif chemokine ligand 16 (
CXCL16
) as the only significant differentially expressed gene in
post-mortem
brains of rabid patients. This result was confirmed
in vitro
, in which Tha suppressed interferon alpha (IFN-α)-induced
CXCL16
expression in human CNS cell lines but induced
CXCL16
expression in IFN-α-stimulated murine astrocytes. We hypothesize that RABV-induced modulation of the CXCL16 pathway in the brain possibly affects neurotransmission, natural killer (NK) and T cell recruitment and activation. Overall, we show species-specific differences in the inflammatory response of the brain, highlighted the importance of understanding the potential limitations of extrapolating data from animal models to humans.
Rabies, a fatal but preventable zoonosis, is a major public health problem in developing countries. In Cambodia the disease burden is largely underestimated because patients with encephalitis ...following dog bites are rarely hospitalized and die at home. Since 1998 Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post-mortem diagnosis.
The 1998-2007 data compiled by IPC was analyzed to describe all treated patients for PEP, results of human testing and confirmed rabies cases, and results of animal testing. From dog bites' characteristics, we defined a suspected rabid dog bite injury (SRDBI) in humans as a bite that was unprovoked, from a dog that died spontaneously, or from a dog that was reported sick. We applied a deterministic probability model to estimate 2007 rabies human mortality nationwide from the estimated incidence of rabid dog bites, the body distribution of bite wounds, and the probability of PEP access.
During 1998-2007, 124,749 patients received PEP at IPC (average 12,470; range 8,907-14,475), and 63 fatal human cases presenting with encephalitis following a dog bite were reported, in which 73% were confirmed positive for rabies by direct immunofluorescence assay or by reverse-transcriptase polymerase chain reaction. During 1998-2007, IPC tested 1,255 animal brain samples; 1,214 (97%) were from dogs including 610 (49%) positive samples. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh (615 PEP/100,000) or five neighboring provinces. The predictive model estimated 810 human rabies deaths would occur in 2007 (95%confidence interval CI 394-1,607), an incidence of 5.8/100,000 (95% CI 2.8-11.5).
Access to PEP is only sufficient for Phnom Penh residents. In 2007, the estimated rabies related mortality exceeded that of malaria and that of dengue. A national rabies control program is needed to improve surveillance and access to PEP, and to initiate vaccination campaigns in dogs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A case of confirmed rabies in a French resident is a wake-up call for improved access to timely and adequate rabies post-exposure prophylaxis for all those living in Cambodia, as well as for improved ...pre-exposure prevention in travellers to Cambodia and other highly endemic settings.
The capacity to care for the critically ill has long been viewed as a fundamental element of established and comprehensive health care systems. Extending this capacity to health care systems in low- ...and middle-income countries is important given the burden of disease in these regions and the significance of critical care in overall health system strengthening. However, many practicalities of improving access and delivery of critical care in resource-limited settings have yet to be elucidated. We have initiated a program to build capacity for the care of critically ill patients in one low-income Southeast Asian country, Cambodia. We are leveraging existing international academic partnerships to enhance postgraduate critical care education in Cambodia. After conducting a needs assessment and literature review, we developed a three-step initiative targeting training in mechanical ventilation. First, we assessed and revised the current resident curriculum pertaining to mechanical ventilation. We addressed gaps in training, incorporated specific goals and learning objectives, and decreased the hours of lectures in favor of additional bedside training. Second, we are incorporating e-learning, e-teaching, and e-assessment into the curriculum, with both live, interactive and independent, self-paced online instruction. Third, we are developing a train-the-trainer program defined by bidirectional international faculty exchanges to provide hands-on, case-based, and bedside training to achieve competency-based outcomes. In targeting specific educational needs and a key population-the next generation of Cambodian intensivists-this carefully designed approach should address some existing gaps in the health care system and hopefully yield a lasting impact.
A case of confirmed rabies in a French resident is a wake-up call for improved access to timely and adequate rabies post-exposure prophylaxis for all those living in Cambodia, as well as for improved ...pre-exposure prevention in travellers to Cambodia and other highly endemic settings.
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