Spotted fever: disease presents frightening lethality that can reach 80%

The treatment, available in all Basic Health Units, is safe and effective. If started early, it results in low risk of complications and high cure rate

Super resistant, they climb walls, manage to hide up to 10 cm below the ground, survive with low oxygen demand and can withstand up to two years without eating. This is how ticks spread around the world. Although not poisonous or toxic, such as spiders and scorpions, ticks are vectors of major diseases, being as dangerous as mosquitoes. To give you an idea, among the diseases transmitted by vectors, spotted fever is as lethal as yellow fever. Because it is endemic, it kills even more than yellow fever, which tends to occur in epidemic outbreaks. It is estimated that there are more than 850 different species in the world, but the Cayenne tick deserves attention due to its impact on public health. Also known in Brazil as horse tick, ruddy tick or micuim, it is responsible for the transmission of Brazilian spotted fever (BSF), a serious disease caused by the bacterium of the genus Rickettsia rickettsii, which can lead to death. In Brazil, two rickettsias are recognized for causing spotted fever in humans: Rickettsia rickettsii and Rickettsia parkeri.

Difficult to diagnose and with a high mortality rate, spotted fever has worried the country’s health authorities. According to data from the Ministry of Health, until September 22, 2022, 67 cases were confirmed that year, resulting in 18 deaths (26%). The Southeast region was, by far, the one that recorded the most, totaling 13 deaths. The deaths occurred in São Paulo (11), Minas Gerais (1) and Rio de Janeiro (1). The city of Campinas (SP) had the second highest number of deaths, where of the 11 people who contracted spotted fever last year, 7 died. Maranhão also recorded a death from the disease. Four other deaths did not have the states informed as to the place of infection. In 2021, about 233 confirmed cases were recorded in the country, with 70 deaths.

Dr. Marcelo Bahia Labruna, a professor at the School of Veterinary Medicine and Zootechnics of the University of São Paulo (FMVZ-USP), one of the leading experts on the subject, explains that Rickettsia rickettsii, a classic BSF-causing bacterium known in Brazil since the 1920s, the same agent of the Rocky Mountain’s spotted fever in the United States, where it was first described, is restricted to the four states of the Southeast region and north of Paraná. “The disease remains endemic in the Southeast region. In São Paulo, for example, it has occurred in the last 10 years in an endemic manner, that is, the number of cases is stable and ranges between 70 and 100, without showing an increase or decrease trend in this period. Since 2001, when the disease was included in the compulsory notification list in Brazil, that is, it must be communicated to public health authorities, there has been a substantial increase in cases,” he adds.

With a lethality rate of around 50%, considered scary and severe by Dr. Labruna, this is due to the delay of the diagnostic suspicion and initiation of specific treatment. “You only die from spotted fever because there was an inaccurate diagnosis at the early stage,” he says. Timely diagnosis, especially during the first days of illness, is difficult, since the symptoms are also similar to other diseases, such as leptospirosis, dengue fever, viral hepatitis, malaria, measles and pneumonia, but imperative. The delay in clinical suspicion, according to Dr. Labruna can be justified by being a relatively rare disease, but, in addition, he classifies that there is a lack of epidemiological knowledge by health professionals, especially the physician, who is often unaware that there is spotted fever in the area where he works. “If you are not trained locally to know that the disease is in your municipality or in your region, this means that you do not consider spotted fever. When a clinical picture of febrile hemorrhagic syndrome arrives, one will think of numerous diseases, but if there is a history of spotted fever in the place, it is essential to keep that in mind so that immediate treatment can be prescribed, even without the diagnosis,” he points out when stressing the importance of periodic training of health professionals in all areas where the disease occurs.

Expansion of spotted fever in Brazil

In the last 20 years, we have observed the spread of the disease throughout the Brazilian territory, and today cases occur in all regions. Professor Labruna points out that this is another spotted fever, also transmitted by ticks, caused by Rickettsia parkeri. Its highest incidence is in Santa Catarina, followed by São Paulo. There are also confirmed cases in Bahia and Ceará, as well as serologically confirmed cases in the Midwest and North regions. “In addition to these sites, there are others in which there was no confirmation of the etiological agent and certainly were not caused by Rickettsia rickettsii, since they were mild cases. It is likely to be Rickettsia parkeri, or some Rickettsia that we do not yet know, but belonging to the group of spotted fever,” he details.

Mild spotted fever, caused by Rickettsia parkeri, is expanding throughout Brazil. It has been increasingly found in human-parasitizing ticks in areas where experts were unaware of their presence and has caused clinical conditions reported for the first time in some states. The professor points out that Rickettsia parkeri is a spotted fever that draws attention because the clinical picture is quite similar to classical spotted fever. In terms of surveillance, diagnosis and treatment, the two end up reported to the Ministry of Health together, but it is important to mention that lethal spotted fever, caused by Rickettsia rickettsii, has occurred only in the Southeast region and in Paraná, in other regions there is still little information about it. “The studies have been concentrated in the Southeast region, where we know more about the epidemiology of the disease, diagnosis and treatment. In other regions, there have been discoveries of new agents such as Rickettsia parkeri, which until then did not cause very severe conditions, but caused debilitating clinical conditions, that is, it is not a simple disease, but until now it has not killed anyone. We certainly have new agents that cause tick-borne spotted fever in other regions of Brazil that still need to be investigated. Given the great territorial extent of the country, we certainly know very little about tick-borne agents in Brazil, especially those that can cause clinical conditions similar to the spotted fever,” concludes Dr. Labruna.

Treatment “in the dark” in suspected cases

According to the professor, in case of clinical suspicion, the professional must immediately prescribe an antibiotic based on doxycycline, since the patient is still able to receive the medication in oral form, before it progresses to an advanced condition. Confirmation of the laboratory result, whether serological or molecular, can be performed later. For Dr. Labruna, this is the way to prevent deaths. “There is no quick diagnostic response. Today we have the option of serology, which is negative most of the time in the acute cases, and there was no time to generate antibodies. To have the serological diagnosis, we need a sample in the acute phase, when the individual is often still serologically non-reactive. The second sample is taken around two weeks later, when he is already in the convalescence phase. So, if he was given antibiotics, he will already be without any clinical symptoms,” he explains.

Dr. Labruna is categorical in repeating that one cannot wait, since in 80% of the times, the patient dies. “The lethality of the disease in cases not treated with antibiotics is 80%. Once suspected, the first blood samples must be taken and treatment with antibiotics should begin immediately. Two weeks later, a second sample should be taken to check the serology,” he says. What about PCR and molecular diagnosis? He notes that if it is performed on the first sample, it is not reliable, since the sensitivity of blood PCR to spotted fever is very low and more than 90% of the clinical conditions treated in the acute form at the beginning will be negative on CPR. “It will be a result with a high chance of being negative. It will have a sensitivity of less than 10% in the acute phase, at the beginning of the disease, maybe even zero,” he recalls.

Asked about the ideal time to make the diagnosis by blood PCR, the professor answers that practically only in severe cases, already advanced, with a week of clinical course or more, in which it presents severe endothelial destruction in the whole body and the patient is on the verge of death. “At that time there will be a large number of rickettsias and bacteria circulating in the blood, because there was extensive endothelial destruction, and then we can have a positive PCR, but there is no way, the damage has already been done and there is no use starting antibiotic treatment at this stage, because it just prevents the bacteria from multiplying, it does not regenerate the endothelial cells   destroyed by the bacteria. If there is extensive endothelial destruction, whether antibiotic is given or not, the individual will die”, he laments when adding that, unfortunately, positive PCR in a living person is a predictive factor for death, as it means that there has already been extensive endothelial destruction. “Therefore, we do not count on PCR in the first clinical care in the outpatient clinic, because the chance of testing positive is very low,” he says.

The specialist acknowledges that not being able to confirm a diagnosis to start or prescribe treatment is a very difficult situation. In the state of São Paulo, for example, of every thousand notifications per year, only 10% are confirmed as spotted fever. This means that 900 cases, on average, are being treated with antibiotics other than for spotted fever. “It doesn’t make a difference; the antibiotic is safe and if we treat 900 people to save a single life it has paid off. We should not wait for laboratory diagnosis, first we treat and then we confirm, after having saved that life,” he reinforces. It is worth mentioning that the manual of the Ministry of Health and the guidance of the São Paulo Department of Health recommend the beginning of antibiotic treatment at the slightest clinical suspicion, already in outpatient care. Because it is a disease of compulsory notification, in clinical suspicion, the health professional is obliged to collect a sample and send it to the Central State Laboratory (Lacen) of their region, such as the Adolfo Lutz Institute (IAL), the Ezequiel Dias Foundation (FUNED) and the Oswaldo Cruz Foundation (Fiocruz). The diagnosis is offered free of charge in the public health network.

The treatment is antibiotic therapy based on doxycycline, quite safe and effective. After the start of treatment, in one or two days, the patient should already have no more fever. If it does not cease within 48 hours, possibly the clinical picture is not spotted fever. The lethality in cases treated early, until the third or fourth day of the clinical course, is practically zero. From the fourth or fifth day, the prognosis becomes somewhat reserved, since endothelial destruction can cause more severe clinical conditions, especially pulmonary edema, nervous disorders, liver or kidney failure, which can compromise the course of the disease. If the patient is already on the seventh day of fever or longer, then the prognosis is quite unfavorable and the lethality can reach 80%, the antibiotic will no longer have an effect and there was a lot of destruction. There are no vaccines available to prevent spotted fever.

The professor draws attention to the fact that the literature points out that doxycycline cannot be prescribed to pregnant women or children, because it causes incorporation of the antibiotic in the tooth enamel and this leads to changes in tooth color for the rest of life, and that it is incorporated into the bones. “This no longer applies to spotted fever and, as much as the package insert says not to prescribe this drug to children, the doctor must rely on official documents. Today the recommendation of the Ministry of Health and international guides is doxycycline, including for children and pregnant women. The treatment is so effective that, when prescribed early, in three to four days it has already controlled the clinical picture and these five to seven days will not interfere with the coloration of the tooth enamel,” says Dr. Labruna. Treatment is available in all Basic Health Units, especially in areas where there is a history of spotted fever.

About spotted fever

The first cases in Brazil date back to 1929 in the state of São Paulo. It is mainly transmitted by the star-tick (Amblyomma sculptum), which in endemic areas can be found in horses, dogs, and especially capybaras, the largest of all natural reservoirs. In the metropolitan region of São Paulo, transmission occurs exceptionally by the yellow dog tick (Amblyomma aureolatum), without any relation to the capybaras. Spotted fever is an infectious, acute febrile disease. The main symptoms include fever, severe headache, nausea and vomiting, diarrhea and abdominal pain, constant muscle pain, swelling and redness in the palms and soles of the feet, gangrene in the fingers and ears, paralysis of the limbs that starts in the legs and goes up to the lungs causing respiratory arrest. As soon as the first symptoms appear, it is important to seek a health unit for medical evaluation.

Staying away from the tick is the best way to prevent the disease. The adoption of some measures, especially in places where there is exposure, can prevent: wearing light-colored clothing helps identify the tick; wearing trousers, boots and sweaters with long sleeves when walking in wooded and grassy areas; all pieces of clothing should be placed in boiling water after use; avoid walking in places with grass or tall vegetation; use insect repellents on the body. It is also important to always check if there are any ticks attached to your body or on your pet. If you find it, the ideal is to remove it with tweezers, without tightening or crushing. Then, the area should be washed with soap and water or rubbed with alcohol. Remember that the sooner the tick is removed from the body, the lower the risk of contracting the disease, because an infected tick, after attaching to the skin of its host, can take more than 10 hours to effectively transmit the bacteria.

In Brazil, two species of rickettsia are associated with clinical conditions of spotted fever: Rickettsia rickettsii, considered a serious disease, registered in the north of the state of Paraná and in the states of the Southeast region. And Rickettsia parkeri, which has been registered in all regions of Brazil, responsible for less severe clinical conditions. Similar to Brazil, in the United States spotted fever caused by R. rickettsii is endemic and cases of spotted fever by R. parkeri and other rickettsias of the spotted fever group are in full expansion, but always associated to species of local ticks.

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