A foresight vision for infectious diseases in Africa

The work in the papers and abstracts was supported by Wellcome Trust Grant WT087546MA to the Southern African Centre for Infectious Disease Surveillance (http://www.sacids.org) and its collaborating UK partner institutions, namely the London School of Hygiene and Tropical Medicine (http://www.lshtm.ac.uk), the Royal Veterinary College (http://www.rvc.ac.uk) and the London International Development Centre (http://www.lidc.org.uk). The work presented by Esron Karimuribo et al. was supported by Rockefeller Foundation.

One Health concepts and ideas are some of the oldest in the health discipline, yet they have not become main stream. Recent discussions of the need for One Health approaches require some reflection on how to present a case for greater investments. The paper approaches this problem from the perspective of the control and management of resources for health in general. It poses the following questions, (1) where do we need extra resources for One Health, (2) where can we save resources through a One Health approach and (3) who has control of the resources that do exist for One Health? In answering these questions three broad areas are explored, (1) The management and resources allocated for diseases, (2) The isolation of parts of the society that require human and animal health services and (3) The use of resources and skills that are easily transferable between human and animal health. The paper concludes that One Health approaches are applicable in many scenarios. However, the costs of getting people from different disciplines to work together in order to achieve a true One Health approach can be large. To generate tangible benefits requires careful management of specialist skills, knowledge and equipment, which can only be achieved by a greater openness of the human and animal health disciplines. Without this openness, policy makers will continue to doubt the real value of One Health. In summary the future success of One Health is about people working in the research, education and provision of health systems around the world embracing and managing change more effectively.

The dynamic nature of new information and/or knowledge is a big challenge for information systems. Early knowledge management systems focused entirely on technologies for storing, searching and retrieving data; these systems have proved a failure. Juirsica and Mylopoulos1 suggested that in order to build effective technologies for knowledge management, we need to further our understanding of how individuals, groups and organisations use knowledge. As the focus on knowledge management for organisations and consortia alike is moving towards a keen appreciation of how deeply knowledge is embedded in people’s experiences, there is a general realisation that knowledge cannot be stored or captured digitally. This puts more emphasis in creating enabling environments for interactions that stimulate knowledge sharing. Our work aims at developing an un-obtrusive intelligent system that glues together effective contemporary and traditional technologies to aid these interactions and manage the information captured. In addition this system will include tools to aid propagating a repository of scientific information relevant to surveillance of infectious diseases to complement knowledge shared and/or acts as a point of reference. This work is ongoing and based on experiences in developing a knowledge network management system for the Southern African Centre of Infectious Disease Surveillance (SACIDS), A One Health consortium of southern African academic and research institutions involved with infectious diseases of humans and animals in partnership with world-renowned centres of research in industrialised countries.

Cholera remains a significant cause of mortality in developing countries. Outbreaks of the disease are associated with poverty, lack of potable water and poor sanitation. The survival and persistence of Vibrio cholerae in water has been shown to depend on physico-chemical factors. We studied water sources in Bepanda, an overcrowded neighbourhood in Douala, Cameroon, with limited access to portable water and very poor sanitary conditions as reservoirs of V. cholerae. We analysed 318 samples from various sources (well, tap, stream) from February to July 2009 using standard microbiological techniques and characterised isolates serologically using the polyvalent O1/O139 antisera. Susceptibility to antibiotics previously used for cholera treatment in Douala was studied using the disk diffusion method. Physico-chemical factors (temperature, pH and salinity) that could maintain the endemicity of the organism were analysed using standard methods. Eighty-seven (27.4%) samples were contaminated, with high isolation rates being obtained from streams (52.4%) and wells (29.8%). The number of isolates was significantly higher (P < 0.05) in the rainy season (35.5%). We detected 23 (24%) O1 serogroup isolates in streams and wells, whilst 64 (66.6%) were non-O1/non-O139. Temperature and salinity correlated positively with the occurrence of the organisms. All isolates were susceptible to fluoroquinolones but high resistance rates to trimethoprim or sulfamethozaxole and tetracycline were observed. Vibrio cholerae is endemic in Bepanda with O1 and non-O1/non-O139 serogroups co-existing in the streams and wells hence the possibility of future outbreaks of cholera if sanitation and drinking water quality are not improved. Temperature and salinity are amongst the factors maintaining the endemicity of the organism.

Foot-and-mouth disease (FMD) is endemic in Tanzania. Since the first reports in 1954, FMD has caused significant economic losses in the country due to mortality and morbidity of livestock and costs associated with controlling the disease. The aim of this study was to review the serotype and genetic relationships of the FMD virus (FMDV) recovered from outbreaks in Tanzania, and compare them with viruses detected from elsewhere in the sub-Saharan region. At the World Reference Laboratory for foot-and-mouth disease (WRLFMD), a total of 106 FMD viruses have been isolated from samples collected between 1967 and 2009 from northern, southern, eastern and central parts of Tanzania. The presence of FMDV was determined by laboratory methods such as VI, CF, antigen ELISA and RT-PCR. Phylogenies of VP1 sequences were determined by the Neighbour-joining method. Foot-and-mouth disease virus SAT1 was the most frequent serotype (46.2%; n = 49) isolated in Tanzania followed by O (26.4%; n = 27), A (14.1%; n = 15) and SAT 2 (11.3%; n = 13). Genotyping showed that type O viruses fell into either the EAST AFRICA 1 (EA-1) or EA-2 topotypes, type A’s into the AFRICA topotype (genotype I), type SAT 1’s into topotype I and type SAT 2’s into topotype IV. This study reveals that serotypes A, O, SAT1 and SAT2 cause FMD outbreaks in Tanzania. Recent samples from outbreaks in 2008, 2009 and 2010 have been typed as serotypes A, O, SAT1 and SAT2. Phylogenetic analysis of FMDV isolates from Tanzania showed that they are genetically related to lineages and topotypes from West and East Africa. In Tanzania, lack of comprehensive animal movement records and inconsistent vaccination programs make it difficult to determine the exact source of FMD outbreaks or to trace the transmission of the disease over time. Therefore, further collection and analysis of samples from domestic and wild animals, together with improved local epidemiological investigation of FMD outbreaks is required to elucidate the complex epidemiology of FMD in the sub-Saharan region.

Objective: To assess the agreement and reliability of cardiac measurements obtained with 3 echocardiographic techniques in anesthetized red-tailed hawks (Buteo jamaicensis). Animals: 10 red-tailed hawks. Procedures: Transcoelomic, contrast transcoelomic, and transesophageal echocardiographic evaluations of the hawks were performed, and cineloops of imaging planes were recorded. Three observers performed echocardiographic measurements of cardiac variables 3 times on 3 days. The order in which hawks were assessed and echocardiographic techniques were used was randomized. Results were analyzed with linear mixed modeling, agreement was assessed with intraclass correlation coefficients, and variation was estimated with coefficients of variation. Results: Significant differences were evident among the 3 echocardiographic methods for most measurements, and the agreement among findings was generally low. Interobserver agreement was generally low to medium. Intraobserver agreement was generally medium to high. Overall, better agreement was achieved for the left ventricular measurements and for the transesophageal approach than for other measurements and techniques. Conclusions and Clinical Relevance: Echocardiographic measurements in hawks were not reliable, except when the left ventricle was measured by the same observer. Furthermore, cardiac morphometric measurements may not be clinically important. When measurements are required, one needs to consider that follow-up measurements should be performed by the same echocardiographer and should show at least a 20% difference from initial measurements to be confident that any difference is genuine.

Objective: To investigate the relationship between runt-related transcription factor 2 (RUNX2) expression in canine nucleus pulposus (NP) cells and intervertebral disk aging in chondrodystrophoid dogs. Animals: 7 healthy Beagles (mean age, 35.6 months) and 11 Dachshunds with herniated disks (mean age, 61 months). Procedures: All dogs underwent MRI examination of the thoracic and lumbar vertebral column immediately before sample collection under general anesthesia. The disk center–to–CSF T2-weighted signal intensity ratio was determined for healthy Beagles. Samples of NP were obtained from nonherniated disks in healthy Beagles and from herniated disks during surgical treatment of hospitalized Dachshunds. Samples were evaluated for RUNX2 and matrix metalloproteinase 13 transcript expression via reverse transcriptase PCR assay; RUNX2 protein expression was evaluated via immunohistochemical analysis, and correlation between these variables and age of dogs was evaluated. A 3′ and 5′ rapid amplification of cDNA ends method was used to identify the RUNX2 coding region. Results: RUNX2 cDNA had > 97% conservation with the human cDNA sequence and approximately 95% conservation with the mouse cDNA sequence; RUNX2 and matrix metalloproteinase 13 mRNA expression and RUNX2 protein expression in NP cells were positively correlated with age. The disk center–to–CSF T2-weighted signal intensity ratio was negatively correlated with RUNX2 protein expression in the NP of healthy dogs. Conclusions and Clinical Relevance: Results indicated that RUNX2 mRNA and protein expression in the NP are enhanced in aging intervertebral disks in dogs.

Objective: To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. Animals: 14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. Procedures: Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. Results: After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. Conclusions and Clinical Relevance: The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1–1Δ mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.

Objective: To evaluate the anterior chamber approach and energy levels for endoscopic cyclophotocoagulation (ECPC) and assess ECPC-induced tissue damage in phakic eyes of bovine cadavers. Sample: 12 bovine cadaver eyes. Procedures: Angle of reach was measured in 6 eyes following placement of a curved endoscopic probe through multiple corneal incisions. In another 6 eyes, each ocular quadrant underwent ECPC at 1 of 3 energy levels (0.75, 0.90, and 1.05 J) or remained untreated. Visible effects on tissues (whitening and contraction of ciliary processes) were scored (scale of 0 [no effects] to 6 [severe effects]), and severity and extent of histologic damage to the pigmented and nonpigmented ciliary epithelium and fibromuscular stroma were each scored (scale of 0 [no effect] to 3 [severe effect]) and summed for each quadrant. Overall mean scores for 6 quadrants/treatment were calculated. Results: Mean ± SD combined angle of reach was 148 ± 24° (range, 123 ± 23° [ventromedial] to 174 ± 11° [dorsolateral]). At the 0.75-, 0.90-, and 1.05-J levels, mean visible tissue effect scores were 3.12 ± 0.47, 3.86 ± 0.35, and 4.68 ± 0.58, respectively; mean histologic damage scores were 4.79 ± 1.38 (mild damage), 6.82 ± 1.47 (moderate damage), and 9.37 ± 1.42 (severe damage), respectively. Occasional popping noises (venting of vaporized interstitial water) were heard at the 1.05-J level. Conclusions and Clinical Relevance: Multiple incisions were necessary to facilitate 360° ECPC treatment in bovine eyes. For ECPC in vivo, the 0.75- and 0.90-J energy levels had the potential to effectively treat the ciliary epithelium.