Relations between Household Livestock Ownership, Livestock Disease, and Young Child Growth.

BACKGROUND: In resource-limited settings in which child malnutrition is prevalent, humans live in close proximity to household livestock. However, the relation between household livestock and child nutrition represents a considerable knowledge gap. OBJECTIVE: We assessed whether household livestock ownership or livestock disease episodes were associated with growth in young children in western Kenya. METHODS: We incorporated monthly anthropometric measurements for children <5 y of age into an ongoing linked human and animal surveillance cohort in rural western Kenya. Using linear mixed models adjusted for age, sex, and household wealth, we tested whether baseline household livestock ownership was related to baseline child height for age or prospective growth rate. We also evaluated whether livestock disease episodes were associated with child growth rate over 11 mo of follow-up. RESULTS: We collected data on 925 children over the course of follow-up. Greater household livestock ownership at baseline was not related to baseline child height-for-age z score (adjusted ß: 0.01 SD; 95% CI: -0.02, 0.04 SD) or child growth rate (adjusted ß: 0.02 cm/y; 95% CI: -0.03, 0.07 cm/y). Livestock disease episodes were not significantly associated with child growth across the entire cohort (adjusted ß: -0.007 cm/mo; 95% CI: -0.02, 0.006 cm/mo). However, children in households with livestock digestive disease between June and November gained less height than did children in households that did not report livestock disease (ß: -0.063 cm/mo; 95% CI: -0.112, -0.016 cm/mo). Children <2 y of age in households with livestock digestive disease gained less weight than did those who did not report disease (ß: -0.033 kg/mo; 95% CI: -0.063, -0.003 kg/mo). CONCLUSION: In this cohort of young children in western Kenya, we did not find an association between ownership of livestock and child growth status. However, disease episodes in household livestock may be related to a lower child growth rate in some groups.

Epidemiology, seasonality, and burden of influenza and influenza-like illness in urban and rural Kenya, 2007-2010.

BACKGROUND: The epidemiology and burden of influenza remain poorly defined in sub-Saharan Africa. Since 2005, the Kenya Medical Research Institute and Centers for Disease Control and Prevention-Kenya have conducted population-based infectious disease surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural community in western Kenya. METHODS: Nasopharyngeal and oropharyngeal swab specimens were obtained from patients who attended the study clinic and had acute lower respiratory tract (LRT) illness. Specimens were tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We adjusted the incidence of influenza-associated acute LRT illness to account for patients with acute LRT illness who attended the clinic but were not sampled. RESULTS: From March 2007 through February 2010, 4140 cases of acute LRT illness were evaluated in Kibera, and specimens were collected from 1197 (27%); 319 (27%) were positive for influenza virus. In Lwak, there were 6733 cases of acute LRT illness, and specimens were collected from 1641 (24%); 359 (22%) were positive for influenza virus. The crude and adjusted rates of medically attended influenza-associated acute LRT illness were 6.9 and 13.6 cases per 1000 person-years, respectively, in Kibera, and 5.6 and 23.0 cases per 1000 person-years, respectively, in Lwak. In both sites, rates of influenza-associated acute LRT illness were highest among children <2 years old and lowest among adults ≥50 years old. CONCLUSION: In Kenya, the incidence of influenza-associated acute LRT illness was high in both rural and urban settings, particularly among the most vulnerable age groups.

Tuberculosis risk among staff of a large public hospital in Kenya.

SETTING: In sub-Saharan Africa, high rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection pose a serious threat for occupationally acquired TB among health care workers. OBJECTIVE: To identify factors associated with TB disease among staff of an 1800-bed hospital in Kenya. DESIGN: We calculated TB incidence among staff and conducted a case-control study where cases (n = 65) were staff diagnosed with TB and controls (n = 316) were randomly selected staff without recent TB. RESULTS: The annual incidence of TB from 2001 to 2005 ranged from 645 to 1115 per 100000 population. Factors associated with TB disease were additional daily hours spent in rooms with patients (adjusted odds ratio [aOR] 1.3, 95%CI 1.2-1.5), working in areas where TB patients received care (aOR 2.1, 95%CI 1.1-4.2), HIV infection (aOR 29.1, 95%CI 5.1-167) and living in a slum (aOR 4.7, 95%CI 1.8-12.5) or hospital-provided low-income housing (aOR 2.6, 95%CI 1.2-5.6). CONCLUSION: Hospital exposures were associated with TB disease among staff at this hospital regardless of their job designation, even after controlling for living conditions, suggesting transmission from patients. Health care facilities should improve infection control practices, provide quality occupational health services and encourage staff testing for HIV infection to address the TB burden in hospital staff.

Absence of spontaneous central nervous system remyelination in class II-deficient mice infected with Theiler's virus.

We previously showed that Theiler's murine encephalomyelitis virus (TMEV)-infected major histocompatibility complex (MHC) class II-deficient mice develop both demyelination and neurologic deficits, whereas MHC class I-deficient mice develop demyelination but no neurologic deficits. The absence of neurologic deficits in the class I-deficient mice was associated with preserved sodium channel densities in demyelinated lesions, a relative preservation of axons, and extensive spontaneous remyelination. In this study, we investigated whether TMEV-infected class II-deficient mice, which have an identical genetic background (C57BL/6 x 129) as the class I-deficient mice, have preserved axons and spontaneous myelin repair following chronic TMEV-infection. Both class I- and class II-deficient mice showed similar extents of demyelination of the spinal cord white matter 4 months after TMEV infection. However, the class I-deficient mice demonstrated remyelination by oligodendrocytes, whereas class II-deficient mice showed minimal if any myelin repair. Demyelinated lesions, characterized by inflammatory infiltrates in both mutants, revealed disruption of axons in class II- but not class I-deficient mice. Further characterization revealed that even though class II-deficient mice lacked TMEV-specific IgG, they had virus-specific IgM, which, however, did not neutralize TMEV in vitro. In addition, class II-deficient mice developed TMEV-specific cytotoxic T-lymphocytes in the CNS during the acute (7 days) disease, but these cytotoxic lymphocytes were not present in the chronic stage of disease, despite a high titer of infectious virus throughout the disease. We envision that the presence of demyelination, high virus titer, absence of remyelination, and axonal disruption in chronically infected class II-deficient mice contributes to the development of paralytic disease.

Theiler's virus-infected L-selectin-deficient mice have decreased infiltration of CD8(+) T lymphocytes in central nervous system but clear the virus.

Mice with targeted deletion of L-selectin gene (L-sel(-/-)) were used to investigate the role of adhesion molecule in immunologic responses following virus infection in the central nervous system (CNS). L-Sel(-/-) mice from a resistant H-2(b) genetic background and parental wild-type H-2(b) (C57BL/6) mice were infected with Theiler's murine encephalomyelitis virus (TMEV) intracerebrally and the kinetics of virus replication and infiltration of immune cells in the CNS determined. The levels of infectious TMEV, as measured by plaque assay at 3, 7, 14, and 28 days after infection were between 4 and 6 log(10) PFU of virus per gram of CNS tissues at days 3 and 7 post-infection, and then decreased to undetectable levels by day 14 after infection in both strains of mice. The L-sel(-/-) mice had decreased numbers of CD8(+) T lymphocytes (17.72%+/-2.4) infiltrating into the CNS at 7 days post-infection when compared to wild-type mice (31.02%+/-7.5). In addition, the L-sel(-/-) mice had significantly lower levels of TMEV-specific serum IgG resulting in lower virus neutralizing activity of the serum when compared to wild-type mice. However, the L-sel(-/-) mice had 2.5-fold increase in B lymphocytes in the CNS (8.29%+/-1.1) when compared to wild-type mice (3.2%+/-0.4). Taken together, these data indicate that L-selectin plays a role in recruitment of B and CD8(+) T lymphocytes into the CNS following virus infection, which, however, did not affect the ability of the mice to clear TMEV infection.

Multi-organ reactivity of a monoclonal natural autoantibody that promotes remyelination in a mouse model of multiple sclerosis.

A contemporary view of autoimmunity suggests that self-reactivity is a normal phenomenon, in contrast to the classical association between autoimmunity and immunopathology. We have previously demonstrated that monoclonal antibody SCH94.03, a natural autoantibody with polyreactivity towards several purified protein and hapten antigens, promotes central nervous system remyelination when passively transferred to SJL/J mice chronically infected with Theiler's murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we characterized the autoreactivity of SCH94.03 with endogenous mouse tissue using immunoperoxide and multiple-color immunofluorescence staining techniques on frozen tissue sections. Within the nervous system, SCH94.03 labeled fibrous astrocytes, ependymal cells, ganglion satellite cells, and a sub-population of microglia, oligodendrocytes, and peripheral nervous system neurons. Outside the nervous system, SCH94.03 labeled gastrointestinal tract smooth muscle and luminal epithelium, erythrocytes, and interdigitating dendritic cells in peripheral lymphoid organs. These data indicate that SCH94.03 is a multi-organ reactive autoantibody and support the hypothesis that autoantibodies can have a beneficial rather than a pathogenic function in central nervous system demyelinating diseases.

Antigens to viral capsid and non-capsid proteins are present in brain tissues and antibodies in sera of Theiler's virus-infected mice.

Recombinant proteins to the LP, VP1, VP2, VP3, VP4, 2A, 2B, 2C, 3A, and 3D genes of Theiler's murine encephalomyelitis virus (TMEV) were generated and antibodies were produced against them for use in analysis of the TMEV epitopes responsible for eliciting the antibody responses observed during acute and chronic disease. Antibodies against recombinant VP1, VP2, and VP3 recognized the corresponding proteins from purified TMEV particles. In immunohistochemical analysis, antibodies against recombinant capsid (VP1, VP2, and VP3), and non-capsid (2A, 2C, 3A) proteins were reactive with PO-2D cells (astrocytes) infected with TMEV in vitro and with brain tissues of acutely infected mice. Antibodies against VP4, 2B, and 3D antigens were not reactive with corresponding viral proteins in infected astrocytes cells or brain tissues, but they reacted with TMEV precursor proteins produced during the early viral replication phase. Sera from SJL/J mice infected with TMEV acutely (14 days) and chronically (45 days) reacted with VP1, VP2, VP4, 2A, and 2C proteins. In an in vitro assay for neutralization, only anti-VP1 antibodies neutralized TMEV infection. These findings suggest that both capsid and non-capsid proteins of TMEV play a role in the immunopathology of the TMEV disease in the central nervous system.

Pathogenic and immunosuppressive effects of avian pneumovirus in turkeys.

Avian pneumovirus (APV) causes a respiratory disease in turkeys. The virus has been associated with morbidity and mortality due to secondary infections. Our objective was to determine if APV caused immunosuppression in the T-cell or B-cell compartments and to study the pathogenesis of the disease in APV maternal antibody-lacking 2-wk-old commercial turkeys. APV was administered by the eyedrop/intranasal route. Observations were made for gross lesions, viral genome, and T-cell mitogenesis and cytokine secretion at 3, 5, 7, 14, and 21 days postinoculation (DPI). During the acute phase of the disease that lasted for about 1 wk, the turkeys exposed to APV showed clinical signs characterized by nasal discharge and sinus swelling. Virus genome was detected by in situ hybridization in cells of turbinates and trachea at 3 and 5 DPI. At 3 and 5 DPI, spleen cells of the birds infected with APV markedly decreased proliferative response to concanavalin A (Con A). Con A and lipopolysaccharide stimulation of spleen cells from virus-exposed turkeys resulted in accumulation of nitric oxide-inducing factors (NOIF) in the culture fluid. NOIF were not detected in culture fluids of Con A-stimulated spleen cells of virus-free turkeys. APV did not compromise the antibody-producing ability of turkeys against several extraneous antigens such as Brucella abortus and tetanus toxoid.

Detection of avian pneumovirus in wild Canada (Branta canadensis) and blue-winged teal (Anas discors) geese.

Choanal cleft swab samples from 770 wild Canada geese (Branta canadensis) and 358 blue-winged teal (Anas discors), captured for relocation or banding, were examined for the presence of avian pneumovirus (APV) RNA by reverse transcription (RT)-polymerase chain reaction (PCR) and for virus isolation. The swab samples were pooled into groups of 5 or 10. Sixty eight of 102 (66.7%) pooled goose samples were RT-PCR positive for APV RNA. Thirteen of 52 (25.0%) pooled blue-winged teal samples were RT-PCR positive for APV RNA. APV RNA-positive samples were inoculated onto chick embryo fibroblasts (CEF) and QT-35 cells. Infectious APV was isolated from five Canada goose pooled samples in CEF and from one Canada goose pool in QT-35 cells but not from blue-winged teal.

Neonatal avian pneumovirus infection in commercial turkeys.

Eleven market turkey flocks developed a respiratory disease characterized by coughing, swollen sinuses and nasal discharge. These symptoms first appeared between 3 and 16 days of age. Avian pneumovirus (APV) RNA was detected by reverse transcriptase (RT)-polymerase chain reaction (PCR) in six of six flocks tested. APV was detected by immunohistochemistry in turbinates of three of three affected flocks tested. Virus isolation attempts were negative. Ten of 11 flocks became seropositive on the APV enzyme-linked immunosorbent assay. Five weeks prior to hatch of these affected market turkeys, several breeder flocks in one geographic area had developed clinical signs and experienced decline in egg production typical of APV infection. In two breeder flocks, acute and convalescent sera indicated APV infection during the period of declining egg production. Attempts to detect APV RNA by RT-PCR from choanal cleft swabs of newly hatched poults were successful. Attempts to isolate the virus from these PCR-positive samples were negative.