The neglected challenge: Vaccination against rickettsiae.

Over the last decades, rickettsioses are emerging worldwide. These diseases are caused by intracellular bacteria. Although rickettsioses can be treated with antibiotics, a vaccine against rickettsiae is highly desired for several reasons. Rickettsioses are highly prevalent, especially in poor countries, and there are indications of the development of antibiotic resistance. In addition, some rickettsiae can persist and cause recurrent disease. The development of a vaccine requires the understanding of the immune mechanisms that are involved in protection as well as in immunopathology. Knowledge about these immune responses is accumulating, and efforts have been undertaken to identify antigenic components of rickettsiae that may be useful as a vaccine. This review provides an overview on current knowledge of adaptive immunity against rickettsiae, which is essential for defense, rickettsial antigens that have been identified so far, and on vaccination strategies that have been used in animal models of rickettsial infections.

Amblyomma hebraeum is the predominant tick species on goats in the Mnisi Community Area of Mpumalanga Province South Africa and is co-infected with Ehrlichia ruminantium and Rickettsia africae.

BACKGROUND: In sub-Saharan Africa, Amblyomma ticks are vectors of heartwater disease in domestic ruminants, caused by the rickettsial pathogen Ehrlichia ruminantium. Immature tick stages often bite humans, whereby they act as vectors of tick-bite fever caused by Rickettsia africae. Moreover, Amblyomma ticks cause damage to livestock due to their feeding behaviour. In South Africa, we studied the abundance of Amblyomma hebraeum ticks on goats of emerging farmers in Mpumalanga Province. A selected number of A. hebraeum nymphs and adult ticks was tested for co-infection with E. ruminantium and R. africae. METHODS: A total of 630 indigenous goats, belonging to farmers in the Mnisi Community area, were examined for ticks in 2013 and 2014. All ticks were identified, and a selected number was tested by PCR with reverse line blot hybridisation. RESULTS: In total, 13,132 ticks were collected from goats distributed over 17 different households. Amblyomma hebraeum was the predominant species, followed by R. microplus. Rhipicephalus appendiculatus, R. simus and R. zambeziensis were also identified. Amblyomma hebraeum was present throughout the year, with peak activity of adults in summer (November) and nymphs in winter (July). The ratio between adults and nymphs ranged from 1:2.7 in summer to 1:55.1 in winter. The mean prevalence of infection for E. ruminantium by PCR/RLB in adult ticks was 17.4% (31/178), whereas 15.7% (28/178) were infected with R. africae. In pooled nymphs, 28.4% were infected with E. ruminantium and 38.8% carried R. africae infection. Co-infections of E. ruminantium and R. africae in adult and pooled nymphal ticks were 3.9% (7/178) and 10% (14.9), respectively. Lameness of goats due to predilection of ticks for the interdigital space of their feet was observed in 89% of the households. CONCLUSIONS: Goats act as important alternative hosts for cattle ticks, which underscored the necessity to include goats in control programs. It is suggested to use acaricide-impregnated leg-bands as a sustainable method to kill ticks and prevent lameness in goats. The challenge of goats by considerable numbers of E. ruminantium-infected ticks is a major obstacle for upgrading the indigenous goat breeds. Humans may be at risk to contract tick-bite fever in this area.

Rickettsia parkeri and Candidatus Rickettsia andeanae in Amblyomma maculatum Group Ticks.

We determined prevalence of Rickettsia spp. in 172 ticks of the Amblyomma maculatum group collected from 16 urban sites in Oklahoma City, Oklahoma, USA, during 2017 and 2018. Most ticks (59.3%) were collected from 1 site; 4 (2.3%) were infected with Rickettsia parkeri and 118 (68.6%) with Candidatus Rickettsia andeanae.

Evaluation of an association of alpha-cypermethrin and flufenoxuron for tick control in an area at risk of Brazilian spotted fever.

Brazilian spotted fever (BSF) is an endemic anthropozoonosis caused by Gram-negative bacteria (Rickettsia rickettsii) that is associated with the risk of human infection by ticks. In the city of Americana, São Paulo (SP), Brazil, there were 12 cases (67% lethal) between 2004 and 2015. This study evaluated the effectiveness of control over tick infestations in an area at risk of BSF, in a field trial on an association of alpha-cypermethrin (3%) and flufenoxuron (3%) (Tenopa®) conducted in Americana. The infestation levels of the target species (Amblyomma sculptum and Amblyomma dubitatum) in the field trial were evaluated through acarological surveys (CO2 traps) on days 0, 22, 43 and 62 after treatment, both in the treatment area and in a control area. In the treatment area, the insecticide formulation was applied using a motorized sprayer, at the dosage of 80mL/10L of water per 200m2. These surveys in the treatment area showed that there were reductions in the infestation levels of the adult stage on days 22 (33%), 43 (87%) and 62 (70%) and immature stages (nymphs and larvae) on days 22 (54%), 43 (87%) and 62 (97%), in relation to day zero and to infestation levels in the control area. This study demonstrated that the product applied was effective for reducing the environmental infestation of ticks and that this effect persisted two months after a single application in areas of proven risk of BSF.

IAP Guidelines on Rickettsial Diseases in Children.

OBJECTIVE: To formulate practice guidelines on rickettsial diseases in children for pediatricians across India. JUSTIFICATION: Rickettsial diseases are increasingly being reported from various parts of India. Due to low index of suspicion, nonspecific clinical features in early course of disease, and absence of easily available, sensitive and specific diagnostic tests, these infections are difficult to diagnose. With timely diagnosis, therapy is easy, affordable and often successful. On the other hand, in endemic areas, where healthcare workers have high index of suspicion for these infections, there is rampant and irrational use of doxycycline as a therapeutic trial in patients of undifferentiated fevers. Thus, there is a need to formulate practice guidelines regarding rickettsial diseases in children in Indian context. PROCESS: A committee was formed for preparing guidelines on rickettsial diseases in children in June 2016. A meeting of consultative committee was held in IAP office, Mumbai and scientific content was discussed. Methodology and results were scrutinized by all members and consensus was reached. Textbook references and published guidelines were also used in few instances to make recommendations. Various Indian and international publications pertinent to present study were collated and guidelines were approved by all committee members. Future updates in these guidelines will be dictated by new scientific data in the field of rickettsial diseases in children. RECOMMENDATIONS: Indian tick typhus and scrub typhus are commonly seen rickettsial diseases in India. It is recommended that practicing pediatricians should be well conversant with compatible clinical scenario, suggestive epidemiological features, differential diagnoses and suggestive laboratory features to make diagnosis and avoid over diagnosis of these infections, as suggested in these guidelines. Doxycycline is the drug of choice and treatment should begin promptly without waiting for confirmatory laboratory results.

Tick-Borne Diseases in Turkey: A Review Based on One Health Perspective.

The importance of tick-borne diseases is increasing all over the world, including Turkey. Global warming, environmental and ecological changes and the existence of suitable habitats increase the impact of ticks and result in frequent emergence or re-emergence of tick-borne diseases (TBDs) with zoonotic characteristics. In Turkey, almost 19 TBDs have been reported in animals and men, involving four protozoa (babesiosis, theileriosis, cytauxzoonosis, hepatozoonosis), one filarial nematode (acanthocheilonemasis), ten bacterial agents (anaplasmosis, ehrlichiosis, aegyptianellosis, tick-borne typhus, Candidatus Rickettsia vini, Lyme borreliosis, tick-borne relapsing fever [TBRF], tularaemia, bartonellosis, and hemoplasmosis), and four viral infections (tick-borne encephalitis [TBE], Crimean-Congo Haemorrhagic Fever [CCHF], louping-ill [LI], and lumpy skin disease [LSD]). The growing number of TBD cases, in particular the fatal viral epidemics in humans, have led to increased public awareness and concern against TBDs in recent years. The World Health Organization (WHO) has developed a new political concept, called the "One Health" initiative, which is especially relevant for developing strategies against tick infestations and TBD control in humans and animals. It would be beneficial for Turkey to adopt this new strategy and establish specific research and control programs in coordination with international organizations like WHO, the World Organization for Animal Health (OIE), the Food and Agriculture Organization (FAO), the Centers for Disease Control and Prevention (CDC), and the European Center for Disease Prevention and Control (ECDC) to combat TBDs based on the "One Health Initiative" concept. In this article, we review the occurrence of primary TBDs in man and animals in Turkey in light of the "One Health" perspective.

Prevalence of selected rickettsial infections in cats in Southern Germany.

Prevalence of Anaplasma, Ehrlichia, Neorickettsia, and Wolbachia DNA in blood of 479 cats collected in different veterinary clinics in Southern Germany was determined using a previously published conventional PCR using 16S-23S intergenic spacer primers (5' CTG GGG ACT ACG GTC GCA AGA C 3' - forward; 5' CTC CAG TTT ATC ACT GGA AGT T 3' - reverse). Purified amplicons were sequenced to confirm genus and species. Associations between rickettsial infections, and feline immunodeficiency virus (FIV), as well as feline leukemia virus (FeLV) status were evaluated. Rickettsial prevalence was 0.4% (2/479; CI: 0.01-1.62%). In the two infected cats, Anaplasma phagocytophilum DNA was amplified. These cats came from different environment and had outdoor access. Both were ill with many of their problems likely related to other diseases. However, one cat had neutrophilia with left shift and the other thrombocytopenia potentially caused by their A. phagocytophilum infection. There was no significant difference in the FIV and FeLV status between A. phagocytophilum-negative and -positive cats. A. phagocytophilum can cause infection in cats in Southern Germany, and appropriate tick control is recommended.

[Rickettsioses]. / Rickettsiosen.

Rickettsioses are a diverse group of bacterial infections of the genus Rickettsia which are transmitted by arthropods. They are increasingly being recognised as the cause of acute febrile illness in travellers and in the inhabitants of tropical areas. In general, rickettsial disease should be considered if a patient presents with an acutely occurring febrile illness within less than 3 weeks of leaving an area where it is endemic. Other possible symptoms include malaise, myalgia, headache, and skin rash. An inoculation eschar is strongly suggestive of the diagnosis, but is often absent. As antibodies can sometimes only be demonstrated late in the disease process or after recovery, antibiotic therapy should be started as soon as the diagnosis is suspected on clinical grounds.

Recombinant protein YbgF induces protective immunity against Rickettsia heilongjiangensis infection in C3H/HeN mice.

BACKGROUND: Surface proteins YbgF and PrsA are major seroreactive antigens of Rickettsia heilongjiangensis, the etiological agent of Far-Eastern spotted fever. This study investigated their potential immunogenicity for protective immunity. METHODS: Recombinant YbgF and PrsA were used to immunize C3H/HeN mice and rickettsial loads in immunized mouse organs were assessed after R. heilongjiangensis challenge. Anti-sera from immunized mice were applied to neutralize rickettsiae. CD4⁺ and CD8⁺ T cells isolated from R. heilongjiangensis-infected mice were stimulated with YbgF or PrsA, and proliferation and cytokine production assessed. RESULTS: The IgG2a/IgG1 ratio of sera was markedly increased in YbgF-immunized mice but was unaltered in PrsA-immunized mice after immunization. The rickettsial load in YbgF-immunized mice was significantly lower than in PrsA-immunized mice after R. heilongjiangensis challenge. Incubation with anti-serum to YbgF, but not PrsA, significantly reduced the number of rickettsiae adhering to and invading endothelial cells. The proliferation level and tumor necrosis factor-α secretion level of CD4⁺ T cells from R. heilongjiangensis-infected mice were significantly higher than in uninfected mice after stimulation with YbgF but not PrsA. CONCLUSION: YbgF is a novel protective antigen that induces a Th1-type of protective immune response against R. heilongjiangensis infection.

Future challenges for parasitology: vector control and 'One health' in Europe: the veterinary medicinal view on CVBDs such as tick borreliosis, rickettsiosis and canine leishmaniosis.

The medical as well as the veterinary importance of parasitic arthropods or ectoparasites in general terms, is characterized by the primary or secondary impact on the health of humans and companion animals alike. The parasitic arthropods addressed here are those ectoparasites belong to the class of insects, such as fleas and sand flies, or the subclass of acarids, such as ticks. These parasitic arthropods interact intensively with their hosts by blood feeding. Fleas, sand flies and ticks hold the vector capacity to transmit pathogens such as virus, bacteria or protozoa to cats, dogs and humans. The diseases caused by these pathogens are summarized under the terms canine vector-borne diseases (CVBD), feline vector-borne diseases (FVBD) or metazoonoses. In small animal practice, it is important to understand that the transmitted pathogen may either lead to a disease with clinical signs, or more often to asymptomatic, clinically healthy, or silent infections. Blocking of the vector-host interactions, the blood feeding and subsequently the transmission of pathogens during blood feeding is a key element of CVBD control. The focus of this review is on the current knowledge of the epidemiology of parasitic vectors and three important CVBDs they transmit; rickettsiosis, tick borreliosis and canine leishmaniosis from a European perspective, and how veterinary medicine may contribute to the challenges of CVBDs and their control. Prevention of CVBDs is fundamentally based on ectoparasite control. Ectoparasite management in cats and dogs is important not only for the health and well-being of the individual companion animal but for public health in general and is therefore a perfect example of the 'One health' approach.

[Diseases transmitted by ticks locally and abroad]. / Maladies transmises par des tiques d'ici et d'ailleurs.

This article provides a brief overview of some diseases transmitted by ticks. These vectors do not transmit only Lyme disease and tickborne-encephalitis, even in Switzerland. Several tick-borne diseases cause nonspecific flu-like symptoms. Nevertheless sometimes severe, some of these diseases can be treated with specific treatments. Repellents, appropriate clothes impregnated with permethrine and prompt removal of the tick are effective preventive measures to limit the risk of infection. There is an effective vaccine which protects against tick-borne encephalitis.

Vector-borne rickettsioses in North Africa.

The purpose of this article is to overview vector-borne rickettsioses in North Africa, focusing on epidemiologic aspects, clinical features, diagnosis procedures, and treatment. The protective measures, the exposure to risk, and the dynamics of endemic emerging and re-emerging diseases in the region are detailed to minimize the risk when traveling in this area. In addition, the article describes the scientific contribution on the rickettsial field of North-African researchers from the beginning of the 20th century until today.

Travel-associated zoonotic bacterial diseases.

PURPOSE OF REVIEW: Bacterial zoonoses are increasingly described in association with travel. Some bacterial zoonoses constitute important causes of post-travel illness. We focus on leptospirosis and rickettsiosis - the most common travel-associated bacterial zoonoses. RECENT FINDINGS: Leptospirosis is regarded to be the most common zoonotic disease worldwide. In industrialized countries recreational exposures, both domestic and overseas, are increasingly becoming a major source of infection. Asymptomatic infection is rare among travelers. Rickettsial diseases account for approximately 1.5-3.5% of febrile travelers. In several series of travel-related rickettsioses, the most common travel-related rickettsial disease is Rickettsia africae. Other rickettsioses including Q fever, scrub typhus and murine typhus are considered rare among travelers. Whereas timely diagnosis of both diseases is still based on exposure history, antigen detection tools to aid the diagnosis during the acute illness are under research and far from being available. Due to these constrains, currently, the true incidence of both diseases is probably underestimated. SUMMARY: Both leptospirosis and spotted fever may be rapidly fatal. Empiric doxycycline in severely ill febrile travelers should be considered. There is an urgent need for widely available antigen detection diagnostic tools to improve the detection of leptospirosis and rickettsial infections during the acute illness.

Treatment and control of chlamydial and rickettsial infections in sheep and goats.

Small ruminants are susceptible to several chlamydial and rickettsial infections. Some of them, such as Ehrlichia ruminantium, have a great impact on the sheep and goat industry while others, such as Coxiella burnetii, are important zoonotic agents. This review focuses on measures of treatment and control for the following organisms: Chlamydophila abortus (formerly Chlamydia psittaci immunotype 1), Coxiella burnetii, Anaplasma ovis, Anaplasma phagocytophilum, and Ehrlichia ruminantium.