Darryn L. Knobel

The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data

Background Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. Methodology/Principal Findings This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. Conclusions/Significance We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.

Rabies in Endangered Ethiopian Wolves

With rabies emerging as a particular threat to wild canids, we report on a rabies outbreak in a subpopulation of endangered Ethiopian wolves in the Bale Mountains, Ethiopia, in 2003 and 2004. Parenteral vaccination of wolves was used to manage the outbreak.

Designing programs for eliminating canine rabies from islands: Bali, Indonesia as a case study.

Background Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies. Methodology/Principal Findings Using data from Bali, we estimated the basic reproductive number, R 0, of rabies in dogs, to be ∼1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (<0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ∼550 human lives and ∼

Bringing together emerging and endemic zoonoses surveillance: shared challenges and a common solution.

15 million in prophylaxis costs over the next ten years. Conclusions/Significance The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance.

Response to a rabies epidemic, Bali, Indonesia, 2008-2011.

Early detection of disease outbreaks in human and animal populations is crucial to the effective surveillance of emerging infectious diseases. However, there are marked geographical disparities in capacity for early detection of outbreaks, which limit the effectiveness of global surveillance strategies. Linking surveillance approaches for emerging and neglected endemic zoonoses, with a renewed focus on existing disease problems in developing countries, has the potential to overcome several limitations and to achieve additional health benefits. Poor reporting is a major constraint to the surveillance of both emerging and endemic zoonoses, and several important barriers to reporting can be identified: (i) a lack of tangible benefits when reports are made; (ii) a lack of capacity to enforce regulations; (iii) poor communication among communities, institutions and sectors; and (iv) complexities of the international regulatory environment. Redirecting surveillance efforts to focus on endemic zoonoses in developing countries offers a pragmatic approach that overcomes some of these barriers and provides support in regions where surveillance capacity is currently weakest. In addition, this approach addresses immediate health and development problems, and provides an equitable and sustainable mechanism for building the culture of surveillance and the core capacities that are needed for all zoonotic pathogens, including emerging disease threats.

Rickettsia felis Infection in Febrile Patients, Western Kenya, 2007–2010

Emergency vaccinations and culling failed to contain an outbreak of rabies in Bali, Indonesia, during 2008–2009. Subsequent island-wide mass vaccination (reaching 70% coverage, >200,000 dogs) led to substantial declines in rabies incidence and spread. However, the incidence of dog bites remains high, and repeat campaigns are necessary to eliminate rabies in Bali.

Domestic dog demographic structure and dynamics relevant to rabies control planning in urban areas in Africa : the case of Iringa, Tanzania

To determine previous exposure and incidence of rickettsial infections in western Kenya during 2007–2010, we conducted hospital-based surveillance. Antibodies against rickettsiae were detected in 57.4% of previously collected serum samples. In a 2008–2010 prospective study, Rickettsia felis DNA was 2.2× more likely to be detected in febrile than in afebrile persons.

Molecular detection of Rickettsia felis and Candidatus Rickettsia asemboensis in fleas from human habitats, Asembo, Kenya.

BackgroundMass vaccinations of domestic dogs have been shown to effectively control canine rabies and hence human exposure to rabies. Knowledge of dog population demography is essential for planning effective rabies vaccination programmes; however, such information is still rare for African domestic dog populations, particularly so in urban areas. This study describes the demographic structure and population dynamics of a domestic dog population in an urban sub-Saharan African setting. In July to November 2005, we conducted a full household-level census and a cross-sectional dog demography survey in four urban wards of Iringa Municipality, Tanzania. The achievable vaccination coverage was assessed by a two-stage vaccination campaign, and the proportion of feral dogs was estimated by a mark-recapture transect study.ResultsThe estimated size of the domestic dog population in Iringa was six times larger than official town records assumed, however, the proportion of feral dogs was estimated to account for less than 1% of the whole population. An average of 13% of all households owned dogs which equalled a dog:human ratio of 1:14, or 0.31 dogs per household or 334 dogs km-2. Dog female:male ratio was 1:1.4. The average age of the population was 2.2 years, 52% of all individuals were less than one year old. But mortality within the first year was high (72%). Females became fertile at the age of 10 months and reportedly remained fertile up to the age of 11 years. The average number of litters whelped per fertile female per year was 0.6 with an average of 5.5 pups born per litter. The population growth was estimated at 10% y-1.ConclusionsSuch high birth and death rates result in a rapid replacement of anti-rabies immunised individuals with susceptible ones. This loss in herd immunity needs to be taken into account in the design of rabies control programmes. The very small proportion of truly feral dogs in the population implies that vaccination campaigns aimed at the owned dog population are sufficient to control rabies in urban Iringa, and the same may be valid in other, comparable urban settings.

Coxiella burnetii in humans, domestic ruminants, and ticks in rural western Kenya.

The flea-borne rickettsioses murine typhus (Rickettsia typhi) and flea-borne spotted fever (FBSF) (Rickettsia felis) are febrile diseases distributed among humans worldwide. Murine typhus has been known to be endemic to Kenya since the 1950s, but FBSF was only recently documented in northeastern (2010) and western (2012) Kenya. To characterize the potential exposure of humans in Kenya to flea-borne rickettsioses, a total of 330 fleas (134 pools) including 5 species (Xenopsylla cheopis, Ctenocephalides felis, Ctenocephalides canis, Pulex irritans, and Echidnophaga gallinacea) were collected from domestic and peridomestic animals and from human dwellings within Asembo, western Kenya. DNA was extracted from the 134 pooled flea samples and 89 (66.4%) pools tested positively for rickettsial DNA by 2 genus-specific quantitative real-time PCR (qPCR) assays based upon the citrate synthase (gltA) and 17-kD antigen genes and the Rfelis qPCR assay. Sequences from the 17-kD antigen gene, the outer membrane protein (omp)B, and 2 R. felis plasmid genes (pRF and pRFd) of 12 selected rickettsia-positive samples revealed a unique Rickettsia sp. (n=11) and R. felis (n=1). Depiction of the new rickettsia by multilocus sequence typing (MLST) targeting the 16S rRNA (rrs), 17-kD antigen gene, gltA, ompA, ompB, and surface cell antigen 4 (sca4), shows that it is most closely related to R. felis but genetically dissimilar enough to be considered a separate species provisionally named Candidatus Rickettsia asemboensis. Subsequently, 81 of the 134 (60.4%) flea pools tested positively for Candidatus Rickettsia asemboensis by a newly developed agent-specific qPCR assay, Rasemb. R. felis was identified in 9 of the 134 (6.7%) flea pools, and R. typhi the causative agent of murine typhus was not detected in any of 78 rickettsia-positive pools assessed using a species-specific qPCR assay, Rtyph. Two pools were found to contain both R. felis and Candidatus Rickettsia asemboensis DNA and 1 pool contained an agent, which is potentially new.

Urban leptospirosis in Africa: a cross-sectional survey of Leptospira infection in rodents in the Kibera urban settlement, Nairobi, Kenya.

We conducted serological surveys for Coxiella burnetii in archived sera from patients that visited a rural clinic in western Kenya from 2007 to 2008 and in cattle, sheep, and goats from the same area in 2009. We also conducted serological and polymerase chain reaction-based surveillance for the pathogen in 2009–2010, in human patients with acute lower respiratory illness, in ruminants following parturition, and in ticks collected from ruminants and domestic dogs. Antibodies against C. burnetii were detected in 30.9% (N = 246) of archived patient sera and in 28.3% (N = 463) of cattle, 32.0% (N = 378) of goats, and 18.2% (N = 159) of sheep surveyed. Four of 135 (3%) patients with acute lower respiratory illness showed seroconversion to C. burnetii. The pathogen was detected by polymerase chain reaction in specimens collected from three of six small ruminants that gave birth within the preceding 24 hours, and in five of 10 pools (50%) of Haemaphysalis leachi ticks collected from domestic dogs.