Rabies Situation in Cambodia

In Cambodia, rabies still elicits fear in the communities. Since 1998 the Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post mortem diagnosis. During 1998–2007, on average ∼12,400 patients received PEP annually at IPC (range 8,907–14,475) and 63 fatal human cases presenting with encephalitis following a dog bite were reported including 73% who tested positive by fluorescent-antibody test on brain samples or/and by reverse-transcriptase polymerase chain reaction on skin, cerebrospinal fluid, or urine. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh city (615 PEP/100,000) or five neighboring provinces. Using a step-by-step probability model, we estimated that 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). As a result, despite high attendance at the IPC's PEP center most Cambodians living in peripheral provinces in Cambodia may not have adequate access to PEP. Finally, the model generated one of the highest incidences of rabies worldwide. A national rabies control program is needed to improve surveillance and access to PEP, and to initiate vaccination campaigns in dogs

Bolstering Medical Education to Enhance Critical Care Capacity in Cambodia

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

Geographic distribution of rabies in dogs and humans, and incidence of post-exposure treatment, Cambodia, 1998–2007.

<p>Geographic distribution of rabies in dogs and humans, and incidence of post-exposure treatment, Cambodia, 1998–2007.</p

Model parameters for estimating the probability of human deaths caused by rabies virus infection, Cambodia, 2007.

<p>Note: SRDBI: Suspected rabid dog bite injuries; PEP: Post-exposure treatment; IPC: Institut Pasteur in Cambodia.</p

Probability tree for estimating the probability of death following a suspected rabid dog bite injury.

<p>Probability tree for estimating the probability of death following a suspected rabid dog bite injury.</p

Positive predictive values of suspected rabid dog characteristics when reported alone - dogs from 14 provinces in Cambodia, 2007.

<p>Positive predictive values of suspected rabid dog characteristics when reported alone - dogs from 14 provinces in Cambodia, 2007.</p

Transcriptome Profile During Rabies Virus Infection: Identification of Human CXCL16 as a Potential New Viral Target

International audienceRabies 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

A Reliable Diagnosis of Human Rabies Based on Analysis of Skin Biopsy Specimens

International audienceBACKGROUND: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