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

HIV gp120 induces TRAIL sensitivity in Huh7 cells in a JNK dependent manner.

<p>(A) Huh7 cells were pre-incubated or not with AMD3100 for one hour and then treated with HIV gp120 or BSA for six hours followed by treatment of skTRAIL. Cell viability was determined by reduction of MTS by live cells. (B) Huh7 cells were pre-incubated with JNK II inhibitor, p38 inhibitor or the G-protein inhibitor, Pertussis toxin, for one hour followed by treatment with HIV gp120 or control protein for six hours. Cell viability was determined by reduction of MTS in live cells. Values are expressed as the mean±SD of three independent experiments from duplicate wells.</p

HIV IIIb makes Huh7 cells sensitive to TRAIL mediated apoptosis.

<p>Huh7 cells were pre-incubated or not with AMD3100 for one hour followed by treatment with purified HIV IIIb or mock virus for six hours. Selective points were then treated with skTRAIL for twelve hours. Cells were then fixed, permeabilized, and stained with fluorescently labeled anti-active caspase-3 antibodies and analyzed by flow cytometry. Camptothesin (10 µM) was used as positive control for caspase-3 activation. (A) A single representative dot plot for each group is given. In each plot, the percentage of cells positive for active caspase-3 is shown in the upper right quadrant. (B) Values are expressed as the mean±SD of three independent experiments.</p

HIV gp120 up-regulates TRAIL R2 expression in Huh7 cells.

<p>(A) Huh7 cells were treated with HIV gp120 or control protein for six hours, stained with fluorescently conjugated antibodies specific for TRAIL receptors and analyzed by flow cytometry. BSA control protein is shown as a dotted line, and HIV gp120 is shown as a solid line. A single representative histogram from three independent experiments is given for each group. (B) Huh7 cells were treated with HIV gp120 for one, two, or three hours, lysed, and resolved on 15% SDS-PAGE, electrotransferred to PVDF membrane, and probed for TRAIL R2. Densitometer readings are presented as the relative intensity of TRAIL R2 normalized to actin. The data represents the mean±SD of three independent experiments. (C) Huh7 cells were pre-incubated or not with AMD3100 for one hour followed by treatment with HIV gp120 or BSA and analyzed for TRAIL R2. Data of mean channel fluorescence represents the mean±SD of three independent experiments.</p

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