Tagged Immune System

Think Like a Doctor: The Boy With Nighttime Fevers Solved!


Credit Andreas Samuelsson

On Thursday we asked Well readers to take on the case of a 7-year-old boy who’d been having fevers and drenching sweats nightly for over a month. More than 300 of you wrote in, and although 20 of you came up with the right diagnosis, only three of you figured out both the diagnosis and the test needed to confirm it.

The correct diagnosis is…

Coccidioidomycosis, or valley fever.

The diagnosis was made based on a lymph node biopsy.

The first reader to suggest this diagnosis and the test was Dr. Malkhaz Jalagonia, an internist from Zugdidi, in the Republic of Georgia. He says he’s never seen a case like this, but he’s fascinated by zebras and so recognized the disease immediately. Well done, Dr. Jalagonia!

One of the reasons I chose this case was that, although this diagnosis is rare in life, it was the most frequently suggested diagnosis in my last column – the one about the middle-aged man with a cough for over a year. I thought it would be fun to show what valley fever really looks like. Hope you did too.

The Diagnosis

Coccidioidomycosis is a lung infection usually caused by inhaling the spores of a tiny fungus called coccidioides. This organism grows as a mold, a few inches below the surface of the soil in deserts in parts of the southwestern United States, Mexico and other countries of Central America.

In dry conditions, the fungus becomes fragile and is easily broken up into tiny single-celled spores that can be sent airborne with even the slightest disturbance. And once these single cells are aloft they can remain suspended there for prolonged periods of time.

Infection is usually acquired by inhaling the spores. Once lodged in the lung, the organism begins to reproduce almost immediately. The time course between exposure and disease depends on the inhaled dose and the patient’s immune system.

Symptoms, or No Symptoms

Disease severity varies considerably. Nearly half of those who breathe in these spores have no symptoms, or symptoms are so mild they never visit the doctor’s office.

More severe infection usually takes the form of a slowly progressive pneumonia known as coccidioidomycosis, or valley fever. This illness is characterized by a cough, fevers, chest pain, fatigue and sometimes joint pain. Indeed, because of the prominent joint pain, in some cases — though not this one — the disease is also known as desert rheumatism.

Rashes are also seen in many patients. Those who get a rash seem to have a more benign course of illness. The thinking is that the skin symptoms are the result of an aggressive immune response in the host to the pathogen.

Symptoms can last for months, and in many cases they resolve without treatment. But in some cases they get worse.

Hard to Diagnose

Those who seek medical attention are often not diagnosed — or not diagnosed quickly — because the symptoms of valley fever are not very specific, and few of the tests that doctors usually order have features that are unusual enough to suggest the diagnosis.

Chest X-rays are often normal. Blood tests may be normal as well, though some patients, like this child, have an unusually high number of a type of white blood cell known as eosinophils. These cells are usually seen in allergic responses or with infections due to parasites.

The most important clue to the possibility of this infection is travel to one of the areas where the fungus lives. In the United States, valley fever is endemic primarily in Arizona and southern California, as well as parts of southern New Mexico and West Texas. Indeed, the name valley fever is a shorter and more general term for an earlier name, San Joaquin Valley fever, because it was so common in that part of California.

A Dramatic Rise

There has been a significant increase in the number of cases of coccidioidomycosis in the past 15 years, with nearly 10 times as many in areas where the fungus is found. Development in areas where the fungus is endemic is thought to be the primary cause. Better diagnostic testing may also play a role.

While this infection may cause only a minor illness in many, there are some – like this child – for whom the disease can spread beyond the lungs into the rest of the body. Disseminated coccidioidomycosis is usually seen in those with some problem with the immune system – an underlying disorder such as H.I.V., for example, or because someone is taking immune suppressing medications such as prednisone.

Once out of the lungs, the bugs can go anywhere in the body, though they seem to prefer joints, skin or bones. Those with disseminated disease have to be treated for a long time – often up to a year, or occasionally for life.

How the Diagnosis Was Made

The little boy had been sick for nearly a month, and his parents were getting quite worried. He was pale, thin and really, really tired.

With their pediatrician’s encouragement, they had gone on a long planned, much anticipated vacation to the mountains of Colorado. But the child wasn’t getting better, and so his mother took him to yet another doctor – this one in a walk-in clinic.

The results of some simple blood tests done at that visit worried the doctor, who suggested that the boy be taken to a hematologist, a specialist in diseases and cancers of the blood.

Now the parents were terrified. The mother faxed copies of the lab results to her brother, a researcher in immunology. He wasn’t a physician but showed the results to friends who were. They agreed with the doctor at the walk-in clinic: The boy needed to be seen by a hematologist.

A Series of Specialists

The next morning the family headed home to Minneapolis. They took the boy to his regular pediatrician, who sent them to a hematologist. It wasn’t cancer, that specialist told them. Maybe some kind of severe food allergy, he suggested, and referred them to a gastroenterologist.

Not a GI thing, that specialist told them, and he referred the now nearly frantic family to an infectious disease specialist and a rheumatologist.

Nearly 10 days after getting the alarming blood test results, the couple and their child found themselves in the office of Dr. Bazak Sharon, a specialist in infectious diseases in adults and children at the University of Minnesota Masonic Children’s Hospital. After introducing himself, Dr. Sharon settled down to get a detailed history of the boy and the family.

A Desert Visit, but Other Possibilities

When Dr. Sharon heard that the family had spent a week at a ranch in the desert of Arizona, he immediately thought of coccidioidomycosis. The fungus isn’t found in Minnesota or Colorado – which is probably why other doctors hadn’t considered it. But it is all over the part of Arizona where they’d visited.

Still, there were other possibilities that had to be ruled out, including some types of cancer. After Dr. Sharon examined the boy, he sent the family to the lab for a chest X-ray and some blood tests.

The results of those tests were concerning. The child was getting worse. Dr. Sharon wasn’t going to be back in clinic for a week, and he was certain the child needed to be seen and diagnosed well before then. He called a friend and colleague who was taking care of patients in the hospital, Dr. Abraham Jacob, and asked if he would admit the child and coordinate the needed diagnostic workup for the boy.

First Some Answers, Then More Questions

Once in the hospital, the child had a chest CT scan. The results were frightening. The lymph nodes that surround the trachea, the tube that carries inspired air to the lungs, were hugely enlarged. They were so big that the trachea was almost completely blocked. The opening at one point was just two millimeters wide – basically the dimensions of a cocktail straw. Any worsening of his disease might cause the tube to close completely, making breathing impossible.

A pediatric surgeon was brought in immediately. The enlarged lymph nodes had to be removed. First in order to protect the child’s airways. And second because those nodes would reveal what the little boy had.

But trying to do surgery on a 7-year-old boy’s neck was complicated. Although the surgeon could easily feel the enlarged gland in his neck, it was close to many vital blood vessels, nerves and organs. The child had to lie perfectly still, and with most children that could only be guaranteed if they were under anesthesia.

Risky Surgery

When the anesthesiologist saw the CT scan, the doctors’ concern grew. They could put the child to sleep, but if anything went wrong during surgery and they had to put a tube down his throat into his lungs, they weren’t sure it would be able to fit.

The trachea was so small, there was no guarantee they could get the tube into place. In order to do this safely, they said they needed to use a technique known as ECMO, or extracorporeal membrane oxygenation – basically a machine that allows them to oxygenate blood without sending it to the lungs.

Rather than subject the child to this risky procedure, Dr. Jacob and the surgeon decided to just take a piece of the lymph node out in order to make the diagnosis. Treatment of whatever the boy had would bring the size of the lymph node down.

Don’t Make a Move

When the boy was brought to the procedure room, the surgeon explained that he was going to put numbing medicine all around the bump in the boy’s neck and take out a piece of it. The child listened calmly and agreed.

He wasn’t to move at all, the surgeon explained. The child nodded solemnly. He understood. The boy was remarkably mature and so brave throughout the entire process of anesthetizing the region that the surgeon thought he might be able to continue and get the entire node out.

He paused in his surgery and consulted the parents. Would they allow him to try this? Their son was doing so well he was sure he could get it. They agreed, and the surgeon returned to his task. The lymph node came out without difficulty.



It was sent to the lab and the answer came back almost immediately. The swollen tissue was filled with the tiny coccidioides. You can see a picture of these little critters here.

A Year of Medicine

The boy was started on an intravenous medicine for fungal infections. Then after a week it was changed to one he could take by mouth.

Because the infection had spread beyond the lungs, the child will have to take this medication for a year. After starting the medication, the child began to look a little better. Slowly he was less tired. Slowly he started to eat the way he used to.

It was a long road to the diagnosis, and an even longer road to cure, but at least they were on the right one.

A Perfect Storm?

The mother called the ranch in Arizona where they stayed to let them know what had happened.
The owner told them that their son was not the only person visiting then who got sick. At least one other guest, there at the same time, had come down with the disease.

Apparently the conditions for spread were perfect. Their stay had started off with some rain, followed by heat and some brisk wind. The moisture helped the fungus grow; the heat dried it out so that it could become easily airborne and inhaled when lifted by the wind.

Although the family has loved their visits to this ranch – this was their second year – the child’s mother tells me that she’s not sure she’ll be going back, at least for a couple of years. Most people exposed to valley fever become immune forever, but because her little boy was so very sick, she’s planning to wait a while before they return.

Thumb Suckers and Nail Biters May Develop Fewer Allergies


Credit Getty Images

Babies have been seen sucking on their fingers in utero weeks before birth. But the sight of an older child with his fingers constantly in his mouth, sucking her thumb, biting his nails, can drive parents crazy, bringing up fears about everything from social stigma to germs.

A new study suggests that those habits in children ages 5 to 11 may indeed increase exposure to microbes, but that that may not be all bad.

When a pediatrician discusses thumb-sucking, it’s usually because a parent is worried. The thumb is in the mouth so constantly that there’s a worry about speech or about whether the teeth may be affected. It’s gone on too long, and an older child is being teased about it. And in those situations, especially when a child is over 4, we work with parents and children on how to break the habit.

Nail biting worries parents for similar reasons, and we often end up giving similar advice: Don’t make negative comments; look for the situations that bring on the behavior and find alternate strategies; praise and reward the child for not doing it; put a glove or a bandage on the hand to remind the child.

In a study published Monday in the journal Pediatrics, researchers drew evidence from an ongoing study of New Zealand children to show those whose parents described them as thumb-suckers and nail-biters were less likely to have positive allergic skin tests later in life.

The children were in the Dunedin Multidisciplinary Health and Development Study, in which 1,037 children born in 1972-73 in Dunedin, a coastal city in New Zealand, were assessed and tested as they grew up, with the most recent assessment done at age 38. Stephanie Lynch, a student at Dunedin School of Medicine and the first author of the paper, had the idea of using the data to look at a possible relationship between children who tend to have their fingers in their mouths and allergic sensitization.

The question of such a connection arose because of the so-called hygiene hypothesis, an idea originally formulated in 1989, that there may be a link between atopic disease — the revved-up action of the immune system responsible for eczema, asthma and allergy — and a lack of exposure to various microbes early in life. Some exposure to germs, the argument goes, may help program a child’s immune system to fight disease, rather than develop allergies.

In the study, parents were asked about their children’s nail-biting and thumb-sucking habits when the children were 5, 7, 9 and 11 years old. Skin testing for allergic sensitization to a range of common allergens including dust mites, grass, cats, dogs, horses and common molds was done when the children were 13 years old, and then later when they were 32. Thirty-one percent of the children were described as “frequent” nail biters or thumb suckers (or both) at one or more of those ages.

The study found that children who frequently sucked a thumb or bit their nails were significantly less likely to have positive allergic skin tests both at 13 and again at 32. Children with both habits were even less likely to have a positive skin test than those with only one of the habits.

These differences could not be explained by other factors that are associated with allergic risk. The researchers controlled for pets, parents with allergies, breast-feeding, socioeconomic status and more. But though the former thumb-suckers and nail-biters were less likely to show allergic sensitization, there was no significant difference in their likelihood of having asthma or hay fever.

Robert J. Hancox, one of the authors of the study, is an associate professor in the Department of Preventive and Social Medicine at Dunedin School of Medicine, a department that is particularly oriented toward the study of diseases’ causes and risk factors. He said in an email, “The hygiene hypothesis is interesting because it suggests that lifestyle factors may be responsible for the rise in allergic diseases in recent decades. Obviously hygiene has very many benefits, but perhaps this is a downside. The hygiene hypothesis is still unproven and controversial, but this is another piece of evidence that it could be true.”

Malcolm Sears, one of the authors of the paper, a professor of medicine at McMaster University in Hamilton, Ontario, who was the original leader for the asthma allergy component of the New Zealand study, said, “Early exposure in many areas is looking as if it’s more protective than hazardous, and I think we’ve just added one more interesting piece to that information.”

Dr. Hancox pointed out that the study does not show any mechanism to account for the association. “Even if we assume that the protective effect is due to exposure to microbial organisms, we don’t know which organisms are beneficial or how they actually influence immune function in this way.”

Thumb sucking, especially in an older child, can still be a problem if it interferes with the teeth, or causes infections on the fingers, or gets a child teased. Lynn Davidson, a developmental pediatrician who is an attending physician at the Children’s Hospital at Montefiore in the Bronx, and the author of a review article on thumb sucking, said she tends to be “very low-key” about thumb sucking, since children often stop on their own as they grow.

With older children, Dr. Davidson suggests that parents, if they are worried, should try to analyze when and why the child resorts to thumb sucking or nail biting, and then try behavioral techniques, like offering a child a foam ball to hold and squeeze at those moments. “In an older child you can use their input, ask, what would you do with your hands instead of putting them in your mouth,” she said.

Dr. Sears said, “My excitement is not so much that sucking your thumb is good as that it shows the power of a longitudinal study.” (A longitudinal study is one that gathers data from the same subjects repeatedly over a period of time.) And in fact, as researchers tease out the complex ramifications of childhood exposures, it’s intriguing to look at long-term associations between childhood behavior and adult immune function, by watching what happens over decades.

So perhaps the results of this study help us look at these habits with slightly different eyes, as pieces of a complicated lifelong relationship between children and the environments they sample as they grow, which shape their health and their physiology in lasting ways.

Day Care Infections May Mean Fewer Sick Days Later


Credit Getty Images

All three of my children started out in day care as infants, and the day care center was, in so many ways, at the center of our lives for years. The teachers taught us most of what we knew about young children (including, I am sorry to say, the difference between well-meaning parents and truly talented professionals). The day care cohort provided my children with their close friends (who keep turning up in their high school and college classes). We even bought our house so we could live near the day care center.

But yes, there were the infections. The worst battles my husband and I had were fought when a small child had to stay home with fever or diarrhea, and we had the eternally nasty whose-work-day-is-more-important-mine-or-yours-and-just-what-makes-you-think-so discussion. On the other hand, as our children got a little bigger, the infections essentially vanished — they had nearly perfect attendance records by the time they got to kindergarten and beyond.

In a study published last month in the journal Pediatrics, researchers in the Netherlands followed a large group of children over the first six years of their lives, looking at how often doctors diagnosed acute gastroenteritis, the stomach bugs so familiar to parents; 1,344 out of the total 2,220 children studied attended day care during the first year of life. Being in day care as an infant increased a child’s risk of having acute gastroenteritis in the first year of life, but it also had a protective effect after that.

Interestingly, the protective effect lasted at least till age 6, which is as far as the study went; the children who were in day care by the age of 1 had more gastroenteritis earlier, but the non-day care children got sick more often as they got older. By age 6, children in the two groups averaged similar numbers of total episodes.

“We think if you are infected at an early age you build up immunity against these viruses or bacteria,” said Marieke de Hoog, an epidemiologist at University Medical Center Utrecht and the senior author on the study. “There is even a possibility that the protective effect we have seen will continue when children grow up — we need more research.”

Day care attendance is known to be a risk factor for upper respiratory infections, which are much more frequent than gastroenteritis — the average child may have as many as eight upper respiratory infections a year, to maybe one bout of gastroenteritis, said Dr. Timothy Shope, an associate professor of pediatrics at Children’s Hospital of Pittsburgh, who is the co-editor of the American Academy of Pediatrics book Managing Infectious Diseases in Childcare and Schools: A Quick Reference Guide,” the fourth edition of which is due out next month. And going to day care also puts a child at higher risk for the ear infections that can follow those upper respiratory infections.

In fact, the gastroenteritis study from the Netherlands was an offshoot of a larger study focused on respiratory infections in children, and Dr. de Hoog and her colleagues published an article in 2014 in which they demonstrated a similar pattern in upper respiratory infections and ear infections: Children who attended day care in the first year of life had more infections earlier and fewer later. For the early day care group, this led to more doctor visits overall, and more antibiotics.

Some infections can be more severe or more dangerous in babies, which is probably one reason children who get sick younger get more medical attention. And there can certainly be moments in those early years of day care when, even though children are not dangerously ill, parents can feel overwhelmed by the parade of runny noses and runny bowel movements.

There is a more complex relationship between day care attendance and the risk of developing asthma and eczema, where there are several other important factors, like family history, antibiotic exposure, and the risk of infection with one particular virus called respiratory syncytial virus, or R.S.V., which has been linked to developing asthma. Still, Dr. Shope said, day care attendance may protect against these so-called “atopic” diseases, which are related to hypersensitivity reactions in which the body’s immune system is overreactive, and it has been suggested that this connects to the “hygiene hypothesis,” that early exposures may be beneficial for the immune system.

There are three basic lines of prevention for bringing down the frequency of infections in day care children, and the most effective is immunization. We immunize against several of the most common organisms that cause gastroenteritis (oh, how I wish there had been a vaccine against rotavirus when my children were born — that diarrhea lasted for weeks) and also against some of the organisms that can complicate respiratory infections. But we have to get better at making sure all young children get the influenza vaccine, which unfortunately has to be given every year, since the virus is particularly dangerous to children.

Infection control is also important in day care, especially around diaper changing and hand-washing. However, there are limits to how much young children can cooperate regarding what they put in their mouths, or whether they cover their coughs. Studies show some benefit of infection control measures, but “not as much as we would like,” Dr. Shope said.

Then there is the always complex pediatric decision about who needs to stay home. Although there are very specific recommendations around diarrhea and diaper changing, for example, it’s also true that with many viral illnesses, children are infectious before symptoms develop and after they cease, while other children are infected and infectious but never develop symptoms, so the protective value of excluding the symptomatic children is limited.

I often see parents who are told their children have to stay home from day care, and I still identify with them. So does Dr. Shope. “When I’m seeing a typical parent with a child under a year who’s in child care, and they’re missing work, they’re wondering if something is wrong with the child,” he told me. “I tell them this is normal, they’re making an investment for the future, their child is less likely to be ill going into kindergarten when other children raised with less contact are more likely to be ill.”


Interested in more Well Family? Sign up to get the latest news on parenting, child health and relationships with advice from our experts to help every family live well.

Post-Cesarean Bacteria Transfer Could Change Health for Life, Study Shows


Credit iStock

The first germs to colonize a newborn delivered vaginally come almost exclusively from its mother. But the first to reach an infant born by cesarean section come mostly from the environment — particularly bacteria from inaccessible or less-scrubbed areas like lamps and walls, and skin cells from everyone else in the delivery room.

That difference, some experts believe, could influence a child’s lifelong health. Now, in the first study of its kind, researchers on Monday confirmed that a mother’s beneficial microbes can be transferred, at least partially, from her vagina to her baby after a C-section.

The small proof-of-principle study suggests a new way to inoculate babies, said Dr. Maria Gloria Dominguez-Bello, an associate professor of medicine at New York University and lead author of the report, published on Monday in Nature Medicine.

“The study is extremely important,” said Dr. Jack Gilbert, a microbial ecologist at Argonne National Laboratory who did not take part in the work. “Just understanding that it’s possible is exciting.”

But it will take further studies following C-section babies for many years to know to what degree, if any, the method protects them from immune and metabolic problems, he said.

Some epidemiological studies have suggested that C-section babies may have an elevated risk for developing immune and metabolic disorders, including Type 1 diabetes, allergies, asthma and obesity.

Scientists have theorized that these children may be missing key bacteria known to play a large role in shaping the immune system from the moment of birth onward. To replace these microbes, some parents have turned to a novel procedure called vaginal microbial transfer.

A mother’s vaginal fluids — loaded with one such essential bacterium, lactobacillus, that helps digest human milk — are collected before surgery and swabbed all over the infant a minute or two after birth.

An infant’s first exposure to microbes may educate the early immune system to recognize friend from foe, Dr. Dominguez-Bello said.

Friendly bacteria, like lactobacilli, are tolerated as being like oneself. Those from hospital ventilation vents or the like may be perceived as enemies and be attacked.

These early microbial interactions may help set up an immune system that recognizes “self” from “non-self” for the rest of a person’s life, Dr. Dominguez-Bello said.

In the United States, about one in three babies are delivered by C-section, a rate that has risen dramatically in recent decades. Some hospitals perform the surgery on nearly seven in ten women delivering babies.

An ideal C-section rate for low-risk births should be no more than 15 percent, according to the World Health Organization.

Dr. Dominguez-Bello’s study involved 18 babies born at the University of Puerto Rico hospital in San Juan, where she recently worked. Seven were born vaginally and 11 by elective C-section. Of the latter, four were swabbed with the mother’s vaginal microbes and seven were not.

Microbes were collected on a folded sterile piece of gauze that was dipped in a saline solution and inserted into each mother’s vagina for one hour before surgery. As the operations began, the gauze was pulled out and placed in a sterile collector.

One to two minutes after the babies were delivered and put under a neonatal lamp, researchers swabbed each infant’s lips, face, chest, arms, legs, back, genitals and anal region with the damp gauze. The procedure took 15 seconds.

Dr. Dominguez-Bello and her colleagues then tracked the composition of microbes by taking more than 1,500 oral, skin and anal samples from the newborns, as well as vaginal samples from the mothers, over the first month after birth.

For the first few days, ambient skin bacteria from the delivery room predominated in the mouths and on the skin of C-section babies who were not swabbed, Dr. Dominguez-Bello said.

But in terms of their bacterial colonies, the infants swabbed with the microbes closely resembled vaginally delivered babies, she found, especially in the first week of life. They were all covered with lactobacilli.

Gut bacteria in both C-section groups, however, were less abundant than that found in the vaginally delivered babies.

Anal samples from the swabbed group, oddly, contained the highest abundance of bacteria usually found in the mouth.

The results show the complexity of labor, said Dr. Alexander Khoruts, a microbial expert and associate professor of medicine at the University of Minnesota. “It cannot be simplified to a neat, effortless passage of the infant through the birth canal,” he said.

As the month progressed, the oral and skin microbes of all infants began to resemble normal adult patterns, Dr. Dominguez-Bello said. But fecal bacteria did not, probably because of breast or formula feeding and the absence of solid foods.

The transfer fell short of full vaginal birth-like colonization for two reasons, Dr. Dominguez-Bello said. Compared to infants who spent time squeezed inside the birth canal, those who were swabbed got less exposure to their mother’s microbes.

And all infants delivered by C-section were exposed to antibiotics, which also may have reduced the number and variety of bacteria colonizing them.

A larger study of vaginal microbial transfer is underway at N.Y.U., Dr. Dominguez-Bello said. Eighty-four mothers have participated so far.

Infants delivered both by C-section and vaginally will be followed for one year to look for differences in the treated and untreated groups and to look for complications. Thus far the swabbing has proved entirely safe.

The procedure is not yet recommended by professional medical societies, said Dr. Sara Brubaker, a specialist in maternal and fetal medicine at N.Y.U. Until more is known, physicians are hesitant to participate.

“But it has hit the lay press,” she said. “Patients come in and ask for it. They are doing it themselves.”

Dr. Brubaker is one of them. When her daughter was born three-and-half months ago, she arranged to have her baby swabbed.

For more fitness, food and wellness news, follow us on Facebook and Twitter, or sign up for our newsletter.