The elimination of human African trypanosomiasis: Monitoring progress towards the 2021-2030 WHO road map targets.

BACKGROUND: Human African trypanosomiasis (HAT) is a neglected tropical disease that usually occurs in rural areas in sub-Saharan Africa. It caused devastating epidemics during the 20th century. Sustained, coordinated efforts by different stakeholders working with national sleeping sickness control programmes (NSSCPs) succeeded in controlling the disease and reducing the number of cases to historically low levels. In 2012, WHO targeted the elimination of the disease as a public health problem by 2020. This goal has been reached and a new ambitious target was stated in the WHO road map for NTDs 2021-2030 and endorsed by the 73rd World Health Assembly: the elimination of gambiense HAT transmission (i.e. reducing the number of reported cases to zero). The interruption of transmission was not considered as an achievable goal for rhodesiense HAT, as it would require vast veterinary interventions rather than actions at the public health level. METHODOLOGY/PRINCIPAL FINDINGS: Data reported to WHO by NSSCPs were harmonized, verified, georeferenced and included in the atlas of HAT. A total of 802 cases were reported in 2021 and 837 in 2022. This is below the target for elimination as a public health problem at the global level (< 2000 HAT cases/year); 94% of the cases were caused by infection with T. b. gambiense. The areas reporting ≥ 1 HAT case/10 000 inhabitants/year in 2018-2022 cover a surface of 73 134 km2, with only 3013 km2 at very high or high risk. This represents a reduction of 90% from the baseline figure for 2000-2004, the target set for the elimination of HAT as a public health problem. For the surveillance of the disease, 4.5 million people were screened for gambiense HAT with serological tests in 2021-2022, 3.6 million through active screening and 0.9 million by passive screening. In 2021 and 2022 the elimination of HAT as a public health problem was validated in Benin, Uganda, Equatorial Guinea and Ghana for gambiense HAT and in Rwanda for rhodesiense HAT. To reach the next goal of elimination of transmission of gambiense HAT, countries have to report zero cases of human infection with T. b. gambiense for a period of at least 5 consecutive years. The criteria and procedures to verify elimination of transmission have been recently published by WHO. CONCLUSIONS/SIGNIFICANCE: HAT elimination as a public health problem has been reached at global level, with seven countries already validated as having reached this goal. This achievement was made possible by the work of NSSCPs, supported by different public and private partners, and coordinated by WHO. The new challenging goal now is to reach zero cases by 2030. To reach this goal is crucial to maintain the engagement and support of donors and stakeholders and to keep the involvement and coordination of all partners. Along with the focus on elimination of transmission of gambiense HAT, it is important not to neglect rhodesiense HAT, which is targeted for elimination as a public health problem in the WHO road map for NTDs 2021-2030.

Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of foot-and-mouth disease.

The Nagoya Protocol is an international agreement adopted in 2010 (and entered into force in 2014) which governs access to genetic resources and the fair and equitable sharing of benefits from their utilisation. The agreement aims to prevent misappropriation of genetic resources and, through benefit sharing, create incentives for the conservation and sustainable use of biological diversity. While the equitable sharing of the benefits arising from the utilisation of genetic resources is a widely accepted concept, the way in which the provisions of the Nagoya Protocol are currently being implemented through national access and benefit-sharing legislation places significant logistical challenges on the control of transboundary livestock diseases such as foot-and-mouth disease (FMD). Delays to access FMD virus isolates from the field disrupt the production of new FMD vaccines and other tailored tools for research, surveillance and outbreak control. These concerns were raised within the FMD Reference Laboratory Network and were explored at a recent multistakeholder meeting hosted by the European Commission for the Control of FMD. The aim of this paper is to promote wider awareness of the Nagoya Protocol, and to highlight its impacts on the regular exchange and utilisation of biological materials collected from clinical cases which underpin FMD research activities, and work to develop new epidemiologically relevant vaccines and other diagnostic tools to control the disease.

FOOT-AND-MOUTH DISEASE IN EXPERIMENTALLY INFECTED MULE DEER (ODOCOILEUS HEMIONUS).

The only known outbreak of foot-and-mouth disease (FMD) in wildlife in the US occurred in mule deer (Odocoileus hemionus) in California in 1924-25. There is little recorded information on the pathogenesis and epidemiology of the disease in deer in that outbreak. In this experimental study, we compared the susceptibility of mule deer to FMD virus (FMDV) serotype O to that of cattle (Bos taurus). We also determined the potential for intra- and interspecies transmission of FMDV serotype O in mule deer and cattle, and assessed conventional laboratory tests in their ability to detect FMDV in mule deer. Two mule deer and one steer were each infected by intraepithelial tongue inoculation with 10,000 bovine tongue infective doses of FMDV, strain O1 Manisa. The inoculated steer and deer were kept in the same room with contact animals of both species. Exposed contact animals were moved to rooms with unexposed animals after becoming febrile. All mule deer (n=14) and cattle (n=6) developed clinical signs and lesions consistent with FMDV infection. Deer had a high prevalence of myocarditis and high mortality. Virus was transmitted between mule deer, from cattle to mule deer, and from mule deer to cattle. Virus and antibodies against nonstructural FMDV proteins in mule deer and cattle were detected by conventional laboratory tests. Virus shedding was detected by PCR and virus isolation up to 9 d postexposure in deer.

FOOT-AND-MOUTH DISEASE IN A SMALL SAMPLE OF EXPERIMENTALLY INFECTED PRONGHORN (ANTILOCAPRA AMERICANA).

There is limited information on the pathogenesis and epidemiology of foot-and-mouth disease (FMD) in North American wildlife and none concerning pronghorn ( Antilocapra americana ). In an experimental study of 13 pronghorn and six steers ( Bos taurus ), we compared the susceptibility of pronghorn to FMD virus (FMDV) strain O, with that of cattle ( Bos taurus ). We also determined the potential for intra- and interspecies transmission of FMDV strain O in pronghorn and cattle, assessed the application of conventional laboratory tests in their suitability to detect FMDV infection in pronghorn, and evaluated the potential role of pronghorn as efficient long-term carriers of FMDV. After acclimation to containment at Plum Island Animal Disease Center, two pronghorn and one steer were each infected by intraepithelial tongue inoculation with 10,000 bovine tongue infective doses of FMDV, strain O1 Manisa. Inoculated animals were housed with contact animals. When contact-exposed animals developed fever they were placed in rooms with previously unexposed animals. All inoculated and exposed cattle and pronghorn developed clinical disease typical of FMD. Pronghorn developed severe foot lesions and mild to moderate oral lesions, primarily on the tongue. Duration of clinical signs in both species was 2-3 wk with foot abnormalities evident to the end of the study (51 d postexposure). Other lesions included pancreatitis, myositis of the tongue, and secondary lesions including pleuritis, pneumonia, decubital ulcers, and tenosynovitis. Virus transmission occurred between pronghorn, from cattle to pronghorn, and from pronghorn to cattle. Conventional laboratory tests detected virus and antibodies against nonstructural and structural FMDV proteins in pronghorn and cattle. Virus was present in some animals for 1 wk but was not detectable by virus isolation or PCR at 3 wk postinfection or afterward.

Isolation and characterization of a Cervidpoxvirus from a goitered gazelle (Gazella subgutturosa) from a zoologic park in Minnesota.

Deerpox virus (DPV) is the sole member of the newly ratified Cervidpoxvirus genus in the subfamily Chordopoxvirinae. Presented here is the first diagnostic report of isolation of DPV from a goitered gazelle (Gazella subgutturosa). A tissue homogenate was submitted by a zoologic park to the Minnesota Veterinary Diagnostic Laboratory at the University of Minnesota for poxvirus diagnostic investigation and then referred to Plum Island Foreign Animal Disease Diagnostic Laboratory for confirmation. Poxviral infection was confirmed using electron microscopy. The virus was cultured in vero cells and subjected to further diagnoses for characterization. Polymerase chain reaction targeting the major envelope (B2L) protein and RNA polymerase of parapoxviruses, and the poly-A polymerase gene of capripoxviruses, were all negative. Degenerative pan-poxvirus primers that target the DNA polymerase (DNApol) and DNA topoisomerase (DNAtopo) genes, however, successfully amplified poxviral DNA fragments. Amplification of the DNApol and DNAtopo genes yielded fragments of 543 and 344 base pairs, respectively. DNA sequence and phylogenetic analysis of each gene fragment from the gazelle isolate showed >97% identity in BLAST searches with two DPV virus strains (W848-83 and W-1170-84) isolated from North American mule deer (Odocoileus hemionus) in 1983-1984. Neighbor-joining trees indicate that the isolate is a member of the Cervidpoxvirus genus and shows a more-distant relationship to other ruminant poxviruses, namely the Capripoxvirus genus consisting of lumpy skin disease, sheeppox, and goatpox viruses. This report documents the premiere finding of DPV, a recently characterized virus, in gazelles and demonstrates the need for broadened investigation when diagnosing poxvirus infections in ruminants.

Identification and characterization of mimotopes of classical swine fever virus E2 glycoprotein using specific anti-E2 monoclonal antibodies.

Classical swine fever virus (CSFV) shares high nucleic acid and amino acid sequence homology with the other members of the pestivirus genus, namely bovine viral diarrhea virus and border disease virus. All three viruses are able to infect swine and generate cross reactive antibodies, which is problematic during differential diagnosis for classical swine fever (CSF). Toward the development of a new generation of CSF specific diagnostic tools, monoclonal antibodies specific for CSFV were mapped using phage display technology. Six mimotopes were identified, some of which were found to be antigenic and/or specific for CSF when used as coating antigens in an ELISA for the detection of CSF antibodies in swine serum. Two mimotopes in particular termed V2-2 and V7-1 recognized numerous strains of CSF antisera and bound fewer BVD and BD antisera compared to a commercial CSF antibody ELISA. These two mimotopes may be useful to the pestivirus field in the development of a highly specific CSF antibody ELISA as well as in the development of other potential diagnostic technologies.

Diagnosis of Porcine teschovirus encephalomyelitis in the Republic of Haiti.

In February and March 2009, approximately 1,500 backyard pigs of variable age became sick, and approximately 700 of them died or were euthanized in the Lower Artibonite Valley and the Lower Plateau of the Republic of Haiti. The main clinical sign was posterior ataxia followed by paresis and/or paralysis on the second or third day of illness. No gross lesions were observed at postmortem examinations. The morbidity and mortality were approximately 60% and 40%, respectively. Diagnostic samples (whole blood, brain, tonsil, lymph nodes, spleen, and lung) were negative for Classical swine fever virus and African swine fever virus. Porcine teschovirus type 1 was detected by reverse transcription polymerase chain reactions in brain samples. Results of virus isolation, electron microscopy of virus particles, histopathological analysis on brain tissues, nucleic acid sequencing, and phylogenetic analysis of the viral isolate supported the diagnosis of teschovirus encephalomyelitis. The outbreak of the disease in Haiti is the first appearance of the severe form of teschovirus encephalomyelitis in the Americas. This disease poses a potential threat to the swine industries in other Caribbean countries, as well as to Central and North American countries.

Analysis of clinical samples for early detection of classical swine fever during infection with low, moderate, and highly virulent strains in relation to the onset of clinical signs.

Classical swine fever (CSF) is a transboundary viral disease affecting swine. The clinical course of disease and the best diagnostic samples for early detection were examined using low, moderate, and highly virulent strains of CSFV inoculated into 8-12 week old domestic pigs. Clinical signs were monitored and recorded. Nasal swabs, tonsil scrapings, blood and tonsils were tested using virus isolation, immunohistochemistry, and real-time reverse transcriptase PCR (rRT-PCR).Severe clinical signs appear 3 days post infection (dpi) with the highly virulent strain, correlating with positive tonsil scrapings, tonsil and blood by virus isolation and rRT-PCR (83-100%), whereas nasal swabs become comparable by 5dpi (89-100%). The moderate strain caused less severe clinical signs between 5 and 7dpi, with tonsil scrapings, tonsil and blood positive by 7dpi (83-100%), and nasal swabs were comparable at 10dpi (67-90%). The low virulent strain showed mild clinical signs at 7dpi, with blood, tonsil and tonsil scrapings positive by virus isolation and rRT-PCR. Except for one sample at 10dpi, nasal swabs remained negative throughout the course of infection. This study indicates that irrespective of virulence, whole blood and tonsil scrapings are the sample of choice for early detection of CSFV in live pigs.

Assessment of rodents as animal models for Reston ebolavirus.

The emergence of Reston ebolavirus (REBOV) in domestic swine in the Philippines has caused a renewed interest in REBOV pathogenicity. Here, the use of different rodent species as animal disease models for REBOV was investigated. BALB/c and STAT1(-)(/-) mice, Hartley guinea pigs, and Syrian hamsters were inoculated intraperitoneally with REBOV strain Pennsylvania or Reston08-A. Although virus replication occurred in guinea pigs, hamsters, and STAT1(-/-) mice, progression to disease was only observed in STAT1(-)(/-) mice. Moreover, REBOV Pennsylvania was more pathogenic than REBOV Reston08-A in this model. Thus, STAT1(-)(/-) mice may be used for research of REBOV pathogenicity and intervention strategies.

Discovery of swine as a host for the Reston ebolavirus.

Since the discovery of the Marburg and Ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. Domestic swine in the Philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host Reston ebolavirus (REBOV). Although REBOV is the only member of Filoviridae that has not been associated with disease in humans, its emergence in the human food chain is of concern. REBOV isolates were found to be more divergent from each other than from the original virus isolated in 1989, indicating polyphyletic origins and that REBOV has been circulating since, and possibly before, the initial discovery of REBOV in monkeys.

Foot-and-mouth disease in North American bison (Bison bison) and elk (Cervus elaphus nelsoni): susceptibility, intra- and interspecies transmission, clinical signs, and lesions.

There is limited information about the pathogenesis and epidemiology of foot-and-mouth disease (FMD) in North American bison (Bison bison) or elk (Cervus elaphus nelsoni). In these two experimental infection studies, we compared the susceptibilities of bison and elk to FMD virus (FMDV), respectively, with that of cattle; determined whether intra- and interspecies transmission could occur in bison and cattle, and elk and cattle; determined suitability of conventional available laboratory tests to detect FMDV infection in bison and elk; and investigated whether bison or elk are efficient long-term carriers of FMDV. In both studies, after a period of acclimation to the containment at Plum Island Animal Disease Center, animals were infected by intraepithelial tongue inoculation with 10,000 bovine tongue infective doses of FMDV, strain O1 Manisa. Inoculated animals were kept with contact animals; subsequently, inoculated and/or exposed contact animals were placed in rooms with unexposed animals. All bison developed oral mucosal and foot lesions similar to those of cattle. Bison developed fever, lameness, inappetence, and ptyalism. Physical examinations on bison revealed numerous small vesicles and erosions affecting tongue, gingiva, muzzle, hard and soft palates, coronary bands, and interdigital skin. Inoculated elk developed transient fever and mild focal tongue and foot lesions. Contact elk developed neither clinical signs nor gross pathologic lesions of FMD. At necropsy, lesions in bison included numerous extensive vesicles, erosions, and/or ulcers in the oral cavities, feet, and rumen pillars depending on the stage of disease. Less extensive oral, foot, and rumen lesions were present in the inoculated elk. All bison and inoculated elk developed antibodies to FMDV and were positive for FMDV by reverse transcription-polymerase chain reaction (RT-PCR). Transmission occurred between cattle and bison, and bison and bison. It did not occur between elk and cattle. Elk-to-elk transmission studies resulted in only one contact elk developing serologic evidence of a subclinical infection. Other exposed elk developed neither clinical, pathologic, virologic, nor serologic evidence of disease. FMDV was not isolated from animals past 28 days postinfection.

A pandemic strain of calicivirus threatens rabbit industries in the Americas.

Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) - a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat.