Rabies is a neglected zoonotic disease that causes an estimated 60,000 human deaths annually. The main burden lies on developing countries in Asia and Africa, where surveillance and disease detection is hampered by absence of adequate laboratory facilities and/or the difficulties of submitting samples from remote areas to laboratories. Under these conditions, easy-to-use tests such as immunochromatographic assays, i.e. lateral flow devices (LFD), may increase surveillance and improve control efforts. Several LFDs for rabies diagnosis are available but, except for one, there are no data regarding their performance. Therefore, we compared six commercially available LFDs for diagnostic and analytical sensitivity, as well as their specificity and their diagnostic agreement with standard rabies diagnostic techniques using different sample sets, including experimentally infected animals and several sets of field samples. Using field samples the sensitivities ranged between 0% up to 100% depending on the LFD and the samples, while for experimentally infected animals the maximum sensitivity was 32%. Positive results in LFD could be further validated using RT-qPCR and sequencing. In summary, in our study none of the tests investigated proved to be satisfactory, although the results somewhat contradict previous studies, indicating batch to batch variation. The high number of false negative results reiterates the necessity to perform a proper test validation before being marketed and used in the field. In this respect, marketing authorization and batch release control could secure a sufficient quality for these alternative tests, which could then fulfil their potential.
As a neglected zoonotic disease, rabies causes approximately 5.9 × 104 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use.
Dog rabies has commonly been associated with the eastern and southern border areas in Mpumalanga province, and the Nkomazi district in the east has been most affected. In other parts of the province, canid rabies has been under control for many years; however, in 2008, dog rabies spread to other parts of the province and resulted in a widespread outbreak. The objective of this study was to genetically characterize rabies viruses in an attempt to determine the source of this recent outbreak. Fifty-five rabies viruses were recovered from domestic dogs between 2000 and 2008 from Mpumalanga province and bordering areas. The viruses were characterized through nucleotide sequencing of the cytoplasmic domain of the glycoprotein gene and the G-L intergenic region. Phylogenetic analysis of these viruses and those previously characterized from Mpumalanga province and neighboring countries and provinces clearly supported the placement of the viruses from the current outbreak and those from Nkomazi district in one lineage. This demonstrated that the recent emergence of rabies in Mpumalanga province resulted from the spread of rabies from Nkomazi district. A comparative analysis demonstrated close genetic relationships among rabies viruses from Mpumalanga and KwaZulu-Natal provinces, Swaziland, and Mozambique. Findings from this investigation have shown that rabies continues to pose a definite public health threat in South Africa, a situation similar to other African countries.
Rabies is an acute and progressive encephalitis caused by lyssaviruses (family Rhabdoviridae, order Mononegavirales). Approximately 99% of the estimated 59,000 annual human rabies deaths in Africa and Asia are attributed to dog bites and are preventable through parenteral dog vaccination. In addition to dog rabies, the rabies virus also circulates in wildlife carnivores in southern Africa and virus exchange occurs readily across species barriers. In the early 1900s, rabies outbreaks were brought under control by the restriction of animal movements and by killing stray dogs. Subsequently, the disease was effectively controlled through vaccination. One prerequisite for rabies control is a thorough knowledge of dog populations. In Africa, only a few mass dog vaccination campaigns have reached the 70% coverage believed to minimise the spread of the disease. Live attenuated vaccines, such as SAG-2, used to control fox rabies in Europe, are safe for nontarget species, making oral vaccination an appealing complementary approach for dog rabies control in Africa. The success of rabies control in KwaZulu/Natal (South Africa) and Serengeti (Tanzania) is an excellent example of how publicprivate partnerships (PPPs) can contribute to the elimination of dog-mediated human rabies in Africa by 2030. Such PPPs are pivotal and will enhance public health awareness, promote mass dog vaccinations and improve accessibility to post-exposure prophylaxis.
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