Rabies Diagnosis for Developing Countries

A new diagnostic test for rabies in animals was evaluated in N'Djaména, capital of Chad. The test is based on a direct immuno-histochemical detection of rabies virus in brain tissue (dRIT) visible by normal light microscopy. Rabies detection by dRIT light microscopy is 10 times less expensive than fluorescence microscopy required for the current gold standard of rabies diagnosis. The test showed ideal results in fresh samples with 100% agreement with the gold standard and confirms the results of a first study in Tanzania. Thus, it has a significant potential for diagnosing rabies in low-income countries, and under field conditions where rabies diagnosis is unavailable for the moment. This new test opens up a great potential to train technical staff and to establish rabies diagnosis without delay in low-income countries with urban rabies

The importance of dog population contact network structures in rabies transmission

<div><p>Canine rabies transmission was interrupted in N’Djaména, Chad, following two mass vaccination campaigns. However, after nine months cases resurged with re-establishment of endemic rabies transmission to pre-intervention levels. Previous analyses investigated district level spatial heterogeneity of vaccination coverage, and dog density; and importation, identifying the latter as the primary factor for rabies resurgence. Here we assess the impact of individual level heterogeneity on outbreak probability, effectiveness of vaccination campaigns and likely time to resurgence after a campaign. Geo-located contact sensors recorded the location and contacts of 237 domestic dogs in N’Djaména over a period of 3.5 days. The contact network data showed that urban dogs are socially related to larger communities and constrained by the urban architecture. We developed a network generation algorithm that extrapolates this empirical contact network to networks of large dog populations and applied it to simulate rabies transmission in N’Djaména. The model predictions aligned well with the rabies incidence data. Using the model we demonstrated, that major outbreaks are prevented when at least 70% of dogs are vaccinated. The probability of a minor outbreak also decreased with increasing vaccination coverage, but reached zero only when coverage was near total. Our results suggest that endemic rabies in N’Djaména may be explained by a series of importations with subsequent minor outbreaks. We show that highly connected dogs hold a critical role in transmission and that targeted vaccination of such dogs would lead to more efficient vaccination campaigns.</p></div

Partial Rank Correlation Coefficient sensitivity analysis of the outbreak size and outbreak duration.

The parameter κ is a network construction parameter involved in the scaling of the spatial connection. The parameter τ is a network construction parameter that alters the proportion of far roaming dogs. The parameter λ is a network construction parameter that alters the mean number of peers of far roaming dogs. The parameter δ is the infectious period. The parameter σ is the incubation period. The parameter β is the transmission rate.</p

Outbreak probabilities and rabies cases north of the river Chari from 2012 and 2016.

<p>For each week the vaccination coverage was calculated using a deterministic transmission model. Vaccination coverages were then translated to outbreak probabilities using the contact network model.</p

Outbreak probability, size and duration on a network of 4930 dogs for different vaccination coverages.

In each simulation run, a proportion of the dogs is randomly assigned the status vaccinated and one randomly chosen susceptible dog is infected from the outside. The simulation ends when there is no more transmission. Simulation runs where more than one dog gets infected are classified as incursion. Simulation runs where more than one dog and less than 1% of the population get infected are classified as minor outbreaks. Simulation runs where more than 1% of the population gets infected are classified as major outbreaks. Incursions include minor and major outbreaks. The outbreak probability is the proportion of simulation runs with outbreaks. The outbreak size is the cumulative proportion of infected dogs over the whole course of the infection. The outbreak duration is the number of weeks until the last infected dog dies. In the left panel the lines correspond to the mean over 1000 simulation runs for each value of the vaccination coverage. In the center and the right panel the lines correspond to the mean over 1000 simulation runs for each value of the vaccination coverage and the shaded areas correspond to the interquartile ranges. The axis of the indented figure in the center panel are the same as in the surrounding figure.</p

The location of the three study zones (red squares) and Chagoua and Abena quarters (green rectangle) in N’Djamena.

<p>The solid purple line denotes the border to Cameroun. The maps were generated using OpenStreetMap contributors.</p

Characteristics of the three study zones.

<p>The reason for the discrepancy between the number of dogs and the number of deployed devices is that some collars could not be attached because dogs resisted. In study zone 1 the number of deployed devices was also limited by the fact that we had only 300 devices at our disposal. The discrepancy between deployed and usable devices is due to broken or lost GCS units, battery failure or failure in the data downloading process.</p

Contact network and home location of the 237 dogs in study zone 1.

<p>In the left panel each node corresponds to a dog. The size of the node is proportional to the degree of the node and the color corresponds to the community the node belongs to. Contacts between dogs are shown as grey lines. In the right panel each dot on the map corresponds to a home location of a dog. The colors correspond to the community in the network. The maps were generated using OpenStreetMap contributors.</p

Properties of the empirical and the synthetic contact networks for the two study zones.

<p>For the synthetic network five point summary statistics of 1000 runs of the construction algorithm are displayed.</p