Charles K. Nfon

Antibiotic Chemotherapy of Onchocerciasis: In a Bovine Model, Killing of Adult Parasites Requires a Sustained Depletion of Endosymbiotic Bacteria (Wolbachia Species)

Development of a drug lethal to adult Onchocerca volvulus (i.e., macrofilaricide) is a research priority for the control of human onchocerciasis. Using bovine O. ochengi infections, we investigated the effects of oxytetracycline administered in a short intensive regimen (SIR; 10 mg/kg daily for 14 days), compared with a prolonged intermittent regimen (PIR; 20 mg/kg monthly for 6 months) or a combination of both (COM), on the viability of adult worms and their endosymbiotic bacteria (Wolbachia species). The long-term treatments eliminated >80% (COM) or >60% (PIR) of adult female worms (P<.001), and the COM regimen effected a sustained depletion of Wolbachia organisms. Conversely, SIR was not macrofilaricidal and only transiently depleted Wolbachia densities, which repopulated worm tissues by 24 weeks after treatment. These results unequivocally demonstrate the macrofilaricidal potential of tetracyclines against Onchocerca infection and suggest that intermittent, protracted administration will be more effective than continuous shorter term treatment.

Molecular Epidemiology of Foot-and-Mouth Disease Viruses in the Adamawa Province of Cameroon

ABSTRACT Foot-and-mouth disease virus (FMDV) causes a highly contagious viral disease of even-toed ungulates and is one of the most important economic diseases of livestock. Most studies of FMDV are done in countries where control measures are being implemented. In contrast, in areas such as sub-Saharan Africa, where FMDV is endemic and new strains are likely to emerge, there are only sporadic submissions to the World Reference Laboratory, Pirbright, United Kingdom. This paper describes the molecular epidemiology of FMDV in the Adamawa province of Cameroon based on a population sample of cattle herds. Serotypes SAT2 and A were isolated in the cross-sectional study. SAT2 isolates were all similar, with phylogenetic distances of <6%, and were most closely related to published sequences of isolates from Eritrea and Saudi Arabia. Serotype A isolates were more variable, with phylogenetic distances of 0 to 11%, and were most closely related to historic isolates from Cameroon. Use of a population-based sample gives a representative sample of virus diversity and will improve our understanding of the evolution of FMDV and its epidemiology. A supplementary study of pigs passing through the railhead collection yard at Ngaoundere detected a serotype O virus. A third pilot longitudinal study monitored viral persistence in three cattle herds over 12 months, and serotype O and A viruses were recovered from a herd 12 months after it was first recorded as being infected with SAT2 virus. The pig type O isolate was not closely related to that recovered from the cattle, suggesting that the pigs had not introduced the O virus into the cattle herds.

Foot and mouth disease and livestock husbandry practices in the Adamawa Province of Cameroon.

Foot and mouth disease (FMD) is a highly contagious viral disease of even-toed ungulates and is endemic in most of the tropics. A cross-sectional study using a stratified, two-stage random sample design was undertaken in the Adamawa Province of Cameroon. The objectives were to measure the reported herd-level prevalence of FMD and a range of husbandry practices important for its transmission. The owner-reported prevalence for the previous 12 months was 57.9% (50.4–65.4%), although there was a significant variation across the Province. During the previous dry season, 46.5% (38.6–54.4%) of herds had gone on transhumance. Herds had high numbers of contacts with other herds while on transhumance (98.6%), at pasture (95.8%) and at night (74.4%), with medians of 7–10, 4–6 and 1–3 daily contacts, respectively. The high level of endemic FMD and potential for disease spread presents a significant challenge for control and eradication. Locally sustainable methods need to be developed upon which larger regional control programmes could be built in the future.

Immunisation with a multivalent, subunit vaccine reduces patent infection in a natural bovine model of onchocerciasis during intense field exposure.

Human onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is controlled almost exclusively by the drug ivermectin, which prevents pathology by targeting the microfilariae. However, this reliance on a single control tool has led to interest in vaccination as a potentially complementary strategy. Here, we describe the results of a trial in West Africa to evaluate a multivalent, subunit vaccine for onchocerciasis in the naturally evolved host-parasite relationship of Onchocerca ochengi in cattle. Naïve calves, reared in fly-proof accommodation, were immunised with eight recombinant antigens of O. ochengi, administered separately with either Freunds adjuvant or alum. The selected antigens were orthologues of O. volvulus recombinant proteins that had previously been shown to confer protection against filarial larvae in rodent models and, in some cases, were recognised by serum antibodies from putatively immune humans. The vaccine was highly immunogenic, eliciting a mixed IgG isotype response. Four weeks after the final immunisation, vaccinated and adjuvant-treated control calves were exposed to natural parasite transmission by the blackfly vectors in an area of Cameroon hyperendemic for O. ochengi. After 22 months, all the control animals had patent infections (i.e., microfilaridermia), compared with only 58% of vaccinated cattle (P = 0.015). This study indicates that vaccination to prevent patent infection may be an achievable goal in onchocerciasis, reducing both the pathology and transmissibility of the infection. The cattle model has also demonstrated its utility for preclinical vaccine discovery, although much research will be required to achieve the requisite target product profile of a clinical candidate.

Geographical and age-stratified distributions of foot-and-mouth disease virus-seropositive and probang-positive cattle herds in the Adamawa province of Cameroon.

Six of the seven known serotypes of foot-and-mouth disease (fmd) virus occur in Africa. This paper describes the results of a population-based cross-sectional study of the seroprevalence of fmd and the persistence of the virus in cattle herds and associated sheep flocks in the Adamawa province of Cameroon. Antibody titres measured by the virus neutralising test indicated that serotypes O, A and sat2 viruses had been circulating in the province. The estimates of apparent seroprevalence in cattle herds, based on five juvenile animals (eight to 24 months old) per herd, were 74·8 per cent for serotype sat2, 30·8 per cent for serotype A and 11·2 per cent for serotype O, indicating recent exposure; the estimates based on animals more than 24 months of age were 91·1 per cent for sat2, 83·6 per cent for A and 34·2 per cent for serotype O. Epithelial and oropharyngeal samples were collected from cattle and small ruminants, cultured and typed by elisa; serotypes A and sat2 were isolated from both types of sample. The herd-level estimate of apparent prevalence of probang-positive herds was 19·5 per cent and the animal-level estimate of apparent prevalence was 3·4 per cent. The geographical distribution of the seropositive herds based on juveniles suggested that recent sat2 exposure was widespread and particularly high in the more northern and western parts of the province, whereas recent exposure to serotype A was patchy and more concentrated in the south and east. This distribution corresponded very closely with the distribution of herds from which virus was recovered by probang, indicating recent exposure or infection. No serotype O viruses were recovered from cattle, and the distribution of seropositive herds suggested very localised recent exposure. The apparent prevalence of probang-positive animals declined with the age of the animal and the period since the last recorded outbreak in the herd.

Redefining the “carrier” state for foot-and-mouth disease from the dynamics of virus persistence in endemically affected cattle populations

The foot-and-mouth disease virus (FMDV) “carrier” state was defined by van Bekkum in 1959. It was based on the recovery of infectious virus 28 days or more post infection and has been a useful construct for experimental studies. Using historic data from 1,107 cattle, collected as part of a population based study of endemic FMD in 2000, we developed a mixed effects logistic regression model to predict the probability of recovering viable FMDV by probang and culture, conditional on the animal’s age and time since last reported outbreak. We constructed a second set of models to predict the probability of an animal being probang positive given its antibody response in three common non-structural protein (NSP) ELISAs and its age. We argue that, in natural ecological settings, the current definition of a ”carrier” fails to capture the dynamics of either persistence of the virus (as measured by recovery using probangs) or the uncertainty in transmission from such animals that the term implies. In these respects it is not particularly useful. We therefore propose the first predictive statistical models for identifying persistently infected cattle in an endemic setting that captures some of the dynamics of the probability of persistence. Furthermore, we provide a set of predictive tools to use alongside NSP ELISAs to help target persistently infected cattle.

Accuracy of herdsmen reporting versus serologic testing for estimating foot-and-mouth disease prevalence.

In an endemic area, herdsmen’s reports were as accurate as serologic test results.