Rabies Post-Exposure Prophylaxis in the Philippines: Health Status of Patients Having Received Purified Equine F(ab')2 Fragment Rabies Immunoglobulin (Favirab)

Infection from a bite by a rabid animal is fatal unless rapid treatment (thorough cleaning of the wound, administration of rabies immunoglobulins (RIG), and a full anti-rabies vaccination course) is provided. Ideally human RIG should be used, but cheaper, more readily available purified horse RIG (pERIG) are widely used in developing countries. Follow-up of over 7,600 patients previously given pERIG at the rabies treatment reference center in Manila (Philippines) provided updated health status for 6,458 patients 39 days to 29 months after treatment. A total of 151 patients had been bitten by animals with laboratory-confirmed rabies. Two rabies deaths were reported, one in a 4-year-old girl with bites on the back, shoulder, and neck so severe that stitching was required to prevent bleeding (against recommended practice), and another in an 8-year-old boy who only received rabies vaccination on the day of initial treatment. A 7-year-old cousin of this boy, bitten by the same animal, who did receive the full vaccination course was still healthy 10 months later. Fourteen other reported deaths had causes unrelated to rabies. These data illustrate the effectiveness of pERIG as part of the recommended treatment regimen, while highlighting the importance of adhering to current recommendations

Cultural drivers and health-seeking behaviours that impact on the transmission of pig-associated zoonoses in Lao People's Democratic Republic

Pig rearing is an important income source in the Lao People’s Democratic Republic (PDR), with many smallholder farmers using traditional free-range pig production systems. Despite the potentially significant health risks posed by pig production regarding pig-associated zoonoses, information on the sociocultural drivers of these zoonoses is significantly lacking. This review summarises the existing sociocultural knowledge on eight pig-associated zoonoses suspected to be endemic in Southeast Asia: brucellosis, Q fever (Coxiella burnetii), trichinellosis, hepatitis E virus, leptospirosis, Japanese encephalitis, Streptococcus suis and Taenia solium taeniasis-cysticercosis. It summarises current knowledge on these diseases grouped according to their clinical manifestations in humans to highlight the propensity for underreporting. A literature search was conducted across multiple databases for publications from 1990 to the present day related to the eight pig-associated zoonoses and the risk and impact connected with them, with Lao PDR as a case study. Many of these pig-associated zoonoses have similar presentations and are often diagnosed as clinical syndromes. Misdiagnosis and underreporting are, therefore, substantial and emphasise the need for more robust diagnostics and appropriate surveillance systems. While some reports exist in other countries in the region, information is significantly lacking in Lao PDR with existing information coming mainly from the capital, Vientiane. The disease burden imposed by these zoonoses is not only characterised by morbidity and mortality, but directly impacts on livelihoods through income reduction and production losses, and indirectly through treatment costs and lost work opportunities. Other factors crucial to understanding and controlling these diseases are the influence of ethnicity and culture on food-consumption practices, pig rearing and slaughter practices, hygiene and sanitation, health-seeking behaviours and, therefore, risk factors for disease transmission. Published information on the knowledge, attitudes and beliefs of people regarding pig zoonoses and their risk factors is also extremely limited in Lao PDR and the broader Southeast Asian region. The need for more transdisciplinary research, using a One Health approach, in order to understand the underlining social determinants of health and their impacts on health-seeking behaviours, disease transmission and, ultimately, disease reporting, cannot be more emphasized

siRNA inhibition of JNK II inhibits gp120 induced TRAIL R2 upregulation.

<p>Huh7 cells were treated with either BSA or gp120 in the presence or absence siRNA constructs for JNK I, JNK II, and p38; and analyzed for TRAIL R2 content (A). The results presented below are pooled TRAIL R2 densitometry normalized to Actin. Parallel experiments demonstrate that siRNA for JNK I, JNK II, and p38 did not alter TRAIL R2 expression (B), and these siRNA constructs were specific for the proteins against which they were directed (C).</p

Role of TRAIL in HIV/HCV co-infection.

<p>Schematic model of synergy between HIV gp120/CXCR4-induced TRAIL sensitivity and other proapoptotic stimuli (e.g., HBV, HCV, Bile salts), causing hepatocyte death and consequent cirrhosis.</p

Allelic variation in the Tyk2 and EGF genes as potential genetic determinants of CNS repair

The potential for endogenous remyelination and axonal protection can be an important factor in determining disease outcome in demyelinating diseases like multiple sclerosis. In many multiple sclerosis (MS) patients CNS repair fails or is incomplete whereas in others the disease is accompanied by extensive repair of demyelinated lesions. We have described significant differences in the ability of two strains of mice to repair CNS damage following Theiler’s virus-induced demyelination: FVB/NJ (FVB) mice repair damaged myelin spontaneously and completely, whereas B10.D1-H2q/SgJ (B10.Q) mice are deficient in the repair process. A QTL analysis was performed to identify genetic loci that differentially regulate CNS repair following chronic demyelination in these strains and two QTL were detected: one on chromosome 3 with a LOD score of 9.3 and a second on chromosome 9 with a LOD score of 14.0. The mouse genes for epidermal growth factor (EGF) and Tyk2 are encoded within the QTL on chromosomes 3 and 9, respectively. Sequence polymorphisms between the FVB and B10.Q strains at both the EGF and Tyk2 loci define functional variations consistent with roles for these genes in regulating myelin repair. EGF is a key regulator of cell growth and development and we show a sevenfold increase in EGF expression in FVB compared to B10.Q mice. Tyk2 is a Janus kinase that plays a central role in controlling the TH1 immune response and we show that attenuation of Tyk2 function correlates with enhanced CNS repair