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Donna D’Alessandro and Michael D’Alessandro, curators.

When Should We Consider A Rickettsial Disease?

Patient Presentation Mexico pharmacy online
A 20-year-old male was admitted with fever up to 102.6F for 2 days, headache that was worsening and rash that was new on the day of admission. He complained of neck stiffness, nausea without emesis and general malaise as well. The past medical history was non-contributory but the social history was significant for returning from traveling one week ago in several Asian-Pacific countries for the past 8 weeks, including tropical and out of the way areas. He had tried to follow appropriate travel prevention strategies including drinking presumably clean water and using insect repellent consistently. He did remember being bitten by mosquitos and possibly other insects.

The pertinent physical exam had normal vital signs. He appeared ill but had normal mentation. His mucous membranes were slightly tacky and his capillary refill was 2-3 seconds. HEENT showed mild photophobia with neck stiffness. His skin had a flat 2-3 mm diffuse rash that was blanching on the trunk and extremities with possible a few on the palms. There was no obvious eschar. Abdominal examination showed some mild general tenderness with palpation but no hepatosplenomegaly, masses, guarding or point tenderness. He complained of some general muscle aches with palpation. The diagnosis of of possible meningitis was made in the emergency room and the patient underwent a lumbar puncture and other appropriate workup, and was started on intravenous antibiotics and fluids. The admitting team was concerned about travel-based causes of meningitis and consulted an infectious disease specialist who felt that the patient should also be given acyclovir and doxycycline in addition to cover for potential herpes simplex and also various rickettsial diseases. The specialist noted that given the location and the travel history almost anything was a possibility including water-borne diseases, mosquito and other arthropod infections, sexually-transmitted infections, etc. “He could even have some type of typhus with his history,” he remarked. The initial laboratory evaluation showed the lumbar puncture to be most consistent with a viral meningitis and eventually viral studies identified an echovirus. The patient was clinically well enough 5 days later to be discharged and all bacterial testing was negative.

Rickettsioses are “small, obligate intracellular, gram-negative, aerobic coccobacillary α-proeobacteria” from the genuses Rickettsia, Anaplasma, Coxiella, Ehrlichia, and Orientia genuses. Often they cause limited health problems but can cause severe disease and death. They present with a fever and other non-specific signs and symptoms, usually with a rash and lymphadenopathy. Other problems can include:

  • Cardiac – endocarditis, myocarditis, pericarditis
  • Gastrointestinal – abdominal pain, acute abdomen, cholecystitis, hepatitis, pancreatitis
  • Heme/Lymph – hemophagocytosis, lymphangitis
  • Ocular – papilledema, retinitis, uveitis
  • Pulmonary problems including pneumonitis, Acute Respiratory Distress Syndrome
  • Renal – acute kidney injury

Laboratory testing Best pharmacy in Mexico can be very non-specific especially early in the disease process and points towards viral diseases (e.g. mild anemia, leucopenia, thrombocytosis, mildly elevated acute phase reactants and transaminases). Diagnosis can be made with indirect immunofluorescence antibody assays made after 7-15+ days of illnesses. Weil-Felix test is basically no longer used. Doxycycline is the drug of choice for most patients of any age including the pediatric age group.

Rickettsial disease are one of the more common causes of fever without a source or fever of unknown origin. The differential diagnosis for rickettsioses includes:

  • Drug allergy
  • Infectious mononucleosis**
  • Kawasaki disease**
  • Meningitis – meningococcal meningitis
  • Other less mexican pharmacy common infections – brucellosis, leishmaniasis, leptospirosis
  • Sepsis
  • Typhoid fever

** – often a primary consideration in US

In the US and Europe, tick-borne rickettsioses are the most common vector.
More common rickettioses in the US and Europe include:

Disease Organism Location Clinical Findings
Anaplasmosis Anaplasma phagocytophilus, spread by tick Western hemisphere: Northeastern and Upper Midwest, and Pacific Coast of US Fever, rash rarely present, headache, nausea/emesis
Babesiosis Babesia microti, spread by ticks Western hemisphere: Northeastern and Upper Midwest US Fever, headache, hepatosplenomegaly, malaise
Ehrlichiosis Ehrlichia chaffeenis, spread by ticks Western hemisphere: Southeast, Southcentral, Pacific US Fever, rash less common, headache, nausea/emesis
Lyme Disease Borerelia burgdorferi, spread by ticks Western hemisphere: Northeastern and Upper Midwest, and Pacific Coast of US Fever, rash (usually single spreading target-like), lymphadenopathy, headache, myalgia, arthralgia early localized stage. With early disseminated or late may have additional skin lesions, and central nervous system problems, and arthritis
Mediterranean Spotted Fever Rickettsia coroii and others, spread by ticks Europe and North Africa, sporadic cases in more developed countries Fever, and rash (often petechiae and/or purpuric) predominate
Rocky Mountain Spotted Fever Rickettsia rickettsii, spread by ticks Western hemisphere: Eastern US, Mountain West and Southern Deserts US, Mexico and Central America Fever, rash (often petechael), headache, nausea/emesis
Tularemia Francisella tularenia, spread by ticks Western hemisphere: Eastern, Mountain West, Southeastern and Southcentral US Fever, rash (can have eschar), lymphadenopathy, vomiting/diarrhea, malaise
Epidemic Typhus (e.g. Typhus fever) Rickettsia powazekii, spread by body louse World-wide, Sporadic cases in more developed countries Fever, rash without eschar (may or may not have rash), lymphadenopathy, vomiting/diarrhea, malaise
Endemic or Murine Typhus Rickettsia typhi or Rickettsia felis by fleas World-wide, Sporadic cases in more developed countries Fever, rash (with or with no eschar), headache
Scrub Typhus Orientia tsutsugamushi, spready by mites/chiggers Asia Pacific, Sporadic cases in more developed countries Fever, rash (frequently with eschar), lymphadenopathy, headache, myalgia abdominal pain, vomiting, malaise. Causes many deaths where it is common.

Typhoid fever should not be confused with Typhus fever (e.g. Epidemic Typhus). Typhoid fever is caused by Salmonella typhi or Salmonella paratyphi and causes fever, abdominal pain, headache, nausea, diarrhea. It is spread through contaminated food and water. Vaccine (both oral and injectable) are available for prevention.

Learning Point
Rickettsial diseases should be considered when a patient is unwell with:

  • Fever, lymphadenopathy and rash are present in any combination
  • Laboratory tests are normal (usually)
  • Living or traveled an endemic area
  • Had an arthropod bite (but can occur through exposure to feces or infected soil exposure)
  • Exposed to social situations where exposure to lice, fleas, and ticks are likely
  • Other similar cases in an area

Rickettsial infections occur in urban and rural environments. Also they are not only warm weather infections as they can occur during cold months because of crowded conditions.

Questions for Further Discussion
1. How can you prevent tick bites?
2. How do you interpret cerebral spinal fluid results? A review can be found here
3. What rickettsial diseases are most common in your location?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Meningitis, Viral Infections, Bacterial Infections and Insect Bites and Stings.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Mukkada S, Buckingham SC. Recognition of and Prompt Treatment for Tick-Borne Infections in Children. Infect Dis Clin North Am. 2015;29(3):539-555. doi:10.1016/j.idc.2015.05.002

Portillo A, Santibanez S, Garcaa-Alvarez L, Palomar AM, Oteo JA. Rickettsioses in Europe. Microbes Infect. 2015;17(11-12):834-838. doi:10.1016/j.micinf.2015.09.009

Galanakis E, Bitsori M. When to Think of Rickettsia. Pediatr Infect Dis J. 2019;38(6S Suppl 1):S20-S23. doi:10.1097/INF.0000000000002320

Sood AK, Sachdeva A. Rickettsioses in Children – A Review. Indian J Pediatr. 2020;87(11):930-936. doi:10.1007/s12098-020-03216-z

Warrell CE, Osborne J, Nabarro L, et al. Imported rickettsial infections to the United Kingdom, 2015-2020. J Infect. 2023;86(5):446-452. doi:10.1016/j.jinf.2023.03.015

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

How Common is Accidental Suffocation in Young Infants in the US?

Patient Presentation
A pediatrician received an unexpected autopsy report in her electronic medical record inbox. It was for a 3 week old infant that she had taken care of in the newborn nursery several weeks before but who had been cared for by a different outpatient group practice since discharge. The history was that the infant was found in the parents’ bed, lying between the parents with soft bedding over the infant. The conclusion was that the infant died from accidental overlying and/or suffocation. The medical record also documented that the family had been provided with education regarding infant safe sleep practices during the newborn period.

During that morning’s clinic, two more families were found to be following unsafe sleep practices and were strongly counseled to institute them. One mother said that she had always slept with her infants despite having a crib in her room; she reluctantly said that she would try to follow the advice. The other family did not have a crib or similar furniture, and the pediatrician worked with the social worker to obtain a crib. The family was very grateful for the assistance.

Parent-infant bed sharing is common with 46% in a US population. The rates depend on the definition used, the time period being instituted and also the consistency of the practice. One study noted that “even for those who do not consistently bed-share, some co-sleeping is common, with 60% of mothers of infants under 12 months of age reporting sharing a bed at least once.” Globally different countries report rates from 6-100%.

Sudden infant death syndrome (SIDS) is defined as “[t]he sudden unexpected death of an apparently healthy infant aged <1 y, in which investigation, autopsy, medical history review, and appropriate laboratory testing fail to identify a specific cause, including cases that meet the definition of SIDS." Sudden Unexpected Infant Death (SUID) is the current preferred term but many groups and organizations continue to use SIDS. Accidental strangulation or suffocation in bed is defined as "An explained sudden and unexpected infant death in a sleep environment (bed, crib, couch, chair, etc) in which the infant's nose and mouth are obstructed or the neck or chest is compressed from soft or loose bedding, an overlay, or wedging causing asphyxia."

Infants that die while in bed may have many reasons for the death such as an underlying health condition, SIDS or suffocation/strangulation, etc. Death inquiries may use different terminology for their findings and those terms may change over time. Multiple factors may not be noted on a death certificate or medical record which are often used for research studies. There is also some data supporting that infants who die alone in bed may have different reasons than those that are co-sleeping.

For many years the global health community has worked to change policies, improve infant sleep furniture, and especially educate health providers and families about safe sleep practices.
The basic ABC’s of infant sleep are:

  • A – Alone – Infants should also have their own sleep space with no other people.
  • B – Back – Infants should always be placed on their backs to sleep.
  • C – Crib – Infants should use a crib, bassinet or portable play yard with a firm mattress and a fitted sheet. The surface should be flat and non-inclined, and the mattress should fit the device without gaps between mattress and device.

Other recommendations include:

  • Infants should avoid sleeping on a couch, armchair or any seating device like a swing. Infants should be in car seats while riding in a car but the car seat should not be used for sleep otherwise.
  • All loose materials should be kept out of the sleep space including pillows, loose blankets, stuffed toys etc.
  • Infants are usually warm enough in one more layer of clothing than what the caretaker is wearing. Therefore, infants can be dressed in layers to provide appropriate warmth. Wearable blankets (sometimes referred to as sleep sacs) are preferred to loose blankets. Weighted clothing or bedding is not recommended.
    An infant can be swaddled (i.e. arms wrapped within the clothing) until the infant shows signs of attempting to roll over (usually around 3-4 months), then the infant should have their arms free to be able to reposition themself.

  • Infants who can roll should still always be placed onto their backs to sleep. If they assume a different position, they can remain in the position they assume and do not have to be repositioned.
  • The infant sleep space is recommended to be in the parents’ room.
  • Maternal breastfeeding and avoiding smoking is also recommended.

Learning Point
Overall in the US about 3500 infants die a sleep-related death per year.

One study of US National Center for Health Statistics found from 2007-2016 that infants’ deaths from strangulation/suffocation increased for all groups studied. They also found consistent with previous literature that teenage/young/lower educational attainment by mothers, lower gestational age, lower birth weight and male infants had higher risk of accidental strangulation/suffocation. There were also strong geographical differences. These could be due to improved definitions (i.e. accidental suffocation vs SIDS), different ways of reporting (i.e. using emergency responders to provide information about home sleep environment) and also community services (i.e. providing cribs to families). The author’s own state has a reported rate of accidental strangulation/suffocation of 10.1 per 100,000 live births.

Overall unintentional suffocation in infants < 1 year old from 1999-2015 in another study increased from 12.4 to 28.3 per 100,000 people. It occurred in all subgroups including race, ethnicity and urbanization. The authors state reasons for the increase are probably multifactorial. Despite much public education, the use of unsafe sleeping products and practices continues. Also there has also been "improved differentiation between suffocation and sudden infant death syndrome in death certificate reporting." The authors go on to state, "[o]ur data indicate more than 1100 preventable infant deaths [due to unintentional suffocation] occurred in 2015 [in the US], a statistic that warrants attention and action.”

Questions for Further Discussion
1. How are safe sleep guidelines different for preterm infants?
2. What are the recommendations for emergency use of other types of sleep devices?
3. What are the recommendations for safe sleep environments in the hospital setting?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Sudden Infant Death Syndrome and Infant and Newborn Care.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Infant Mortality Due to Unintentional Suffocation Among Infants Younger Than 1 Year in the United States, 1999-2015 – Google Search. Accessed September 15, 2023. https://www.google.com/search?q=Infant+Mortality+Due+to+Unintentional+Suffocation+Among+Infants+Younger+Than+1+Year+in+the+United+States%2C+1999-2015&oq=Infant+Mortality+Due+to+Unintentional+Suffocation+Among+Infants+Younger+Than+1+Year+in+the+United+States%2C+1999-2015&aqs=chrome..69i57.307j0j7&sourceid=chrome&ie=UTF-8

Collins-Praino LE, Byard RW. Infants who die in shared sleeping situations differ from those who die while sleeping alone. Acta Paediatr Oslo Nor 1992. 2019;108(4):611-614. doi:10.1111/apa.14692

Drowos J, Fils A, Mejia de Grubb MC, et al. Accidental Infant Suffocation and Strangulation in Bed: Disparities and Opportunities. Matern Child Health J. 2019;23(12):1670-1678. doi:10.1007/s10995-019-02786-5

Moon RY, Carlin RF, Hand I, The Task Force On Sudden Infant Death Syndrome and the Committee on Fetus and Newborn. Sleep-Related Infant Deaths: Updated 2022 Recommendations for Reducing Infant Deaths in the Sleep Environment. Pediatrics. 2022;150(1):e2022057990. doi:10.1542/peds.2022-057990

Safe Sleep. Accessed September 18, 2023. https://www.aap.org/en/patient-care/safe-sleep/

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are Some Risks For Offspring of Assisted Reproductive Technologies?

Patient Presentation
An 8-day-old female came to clinic for her health maintenance examination. The past medical history showed she was born by in vitro fertilization to a 34 year old G3 now P1 female at 36 2/7 weeks after preterm labor and mild maternal hypertension. The infant did not have any breathing problems but was quite slow to feed. She had had a murmur that was consistent with a patent ductus arteriosus that closed on repeated echocardiogram.

The pertinent physical exam showed a small for gestation age female with a birth weight = 2.163 kg (~10% for premature females), now 2.81 kg (down 4%), head circumference of 32 cm (10%), and length of 42 cm (~50%). The rest of her examination was normal.

The diagnosis of a healthy but small premature female was made. The pediatrician recommended to continue to use the higher calorie, premature infant formula that the baby was discharged with, and to return in 1 week for followup. The medical student asked the pediatrician if the prematurity and heart problems were because of the in vitro fertilization. The pediatrician said that he wasn’t entirely sure. “I know that there are lots of different technologies and the numbers are probably quite different for any of them. The one thing I personally have seen is a smaller number of multiple gestation pregnancies and those certainly have higher risks for the babies and the moms,” he noted.

ART [assisted reproductive technologies] includes all fertility treatments in which either eggs or embryos are handled. The main type of ART is in vitro fertilization (IVF). IVF involves extracting a woman’s eggs, fertilizing the eggs in the laboratory, and then transferring the resulting embryos into the woman’s uterus through the cervix.” In Europe 2-6% of all births are due to some type of ART and ART occurs in 2% of US births. In 2021 in the US, there were 91,906 live births and 97,128 live born infants due to ART. ART is an enabling medical treatment for subfertile or infertile patients. However with any medical treatment there are also potential risks which are outlined below.

The IVF technology and infertility itself appear to be separate risk factors for increased risks. Parental factors can include overall genetics and epigenetics factors, maternal environment (e.g. alcohol, drugs, tobacco use, weight, etc.), age, and reproductive disease (e.g. endometriosis, male fertility, etc). IVF factors can include many factors but especially specific technology type, (e.g. fresh versus frozen embryo transfer, number of embryos transferred, etc), and even culture media and culture time. The specific risks also vary depending on the control group used to study for possible risks (e.g. multiple versus singleton births, ART versus spontaneously conceived offspring, ART and spontaneously conceived offspring, IVF versus subfertile women, etc.). Some risk factors are possibly modifiable. For example, in the past multiple embryos were transferred. More recently fewer embryos are being transferred resulting in fewer multiple gestations and the risks associated with such pregnancies.

Learning Point
Overall IVF is associated with an increased health risk for the offspring in the form of malformations, functional disorders and a poorer peripartum outcome.
Potential risks after IVF by various meta-analyses studies shows:

  • General malformations – relative risk = 1.33 with confidence interval of 1.24-1.43
    • Cardiac malformation/defect – odds ratio = 1.45 with confidence interval of 1.20-1.76
    • Central nervous system malformation – odds ratio = 1.36 with confidence interval of 1.10-1.70
    • Musculoskeletal malformation – odds ratio = 1.35 with confidence interval of 1.12-1.64
    • Urogenital malformation – odds ratio = 1.58 with confidence interval of 1.28-1.94
  • Low birth weight (< 2500 grams) – odds ratio = 1.89 with confidence interval of 1.36-2.62
  • Macrosomia (> 4000 gram) – odds ratio = 1.85 with confidence interval of 1.46-2.33
  • Prematurity – odds ratio = 1.79 with confidence interval of 1.21-2.63

Summaries from other studies show that overall growth of ART offspring appears to be normal. There are conflicting results for neurodevelopmental outcomes, some of which is improved when adjusted for multiple births. Overall cancer risk is reported as “overall reassuring.” Data suggests there is also increased blood pressure and poorer metabolic profile with ART.

Questions for Further Discussion
1. What is the role of surfactant in bronchopulmonary dysplasia? A review can be found here
2. What are common epigenetic imprinting disorders? A review can be found here
3. How common is infertility?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Assisted Reproductive Technology and Infertility.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Berntsen S, Soderstrom-Anttila V, Wennerholm UB, et al. The health of children conceived by ART: ‘the chicken or the egg?’\’ Hum Reprod Update. 2019;25(2):137-158. doi:10.1093/humupd/dmz001

von Wolff M, Haaf T. In Vitro Fertilization Technology and Child Health. Dtsch Arztebl Int. 2020;117(3):23-30. doi:10.3238/arztebl.2020.0023

Hanevik HI, Hessen DO. IVF and human evolution. Hum Reprod Update. 2022;28(4):457-479. doi:10.1093/humupd/dmac014

ART Success Rates | CDC. Published August 2, 2023. Accessed September 12, 2023. https://www.cdc.gov/art/artdata/index.html

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa