The two new drugs are Olysio (simeprevir) capsules and Sovaldi (sofosbuvir) tablets. Both work by stopping the replication of the Hepatitis C virus.

Olysio 150 mg capsules are a once-daily treatment that must be used in combination with pegylated interferon (peginterferon alfas like Pegasys or Pegintron) and ribavirin. It cannot currently be used as monotherapy, which means it can’t be used alone. Sovaldi 400 mg tablets are a once-daily treatment that can be used without the injectable peginterferon alfa. This is novel and helpful in hepatitis therapy because the peginterferon alfa injectable often contributes to patients not finishing their course of Hep C therapy due to the unfavorable side effects.

Based on a side-by-side review if disparate studies, Sovald appears to be more versatile than Olysio as it is approved for treatment of genotypes 1, 2, 3 and 4. Also, for genotype 2 and 3, Sovaldi can be taken with ribavirin alone, excluding the need for interferon altogether. (Interferon, perhaps the most dreaded component of HCV therapy, is administered by injection and many side effects.  On the other hand, Olysio must always be used in combination with interferon and ribavirin for the duration of either 24 weeks (for treatment-naive patients) or 48 weeks (for patients previously exposed to HCV therapy). However ,it cannot be used with many retroviral drugs.

Using the two together is beginning to be explored, with early results showing efficacy in even hard-to-treat cases. In early January, the New England Journal published a study of the combination of these two drugs. he New England Journal of Medicine, investigators designed a Phase II open-label study of Gilead Sciences’ recently approved nucleotide analogue NS5B polymerase inhibitor Sovaldi and Bristol-Myers Squibb’s NS5A replication complex inhibitor daclatasvir.

Sulkowski MS, et al “Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection” N Engl J Med 2014; 370: 211-221.

Sovaldi, Prescribing Information 2014

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Sore throat, or pharyngitis, is diagnosed in 11 million people annually in theUnited States. Although most cases are viral, group A beta-hemolytic streptococcus causes 15—30% of the cases in children and 5—20% in adults.Cases usually occur in late winter and early spring. Strep throat is a common problem in large households, where it is a dreaded visitor. After one child picks it up, it is not long before every boy and girl in the family is lined up in the doctor’s office to get their “culture”, and sometimes adults follow too.

Strep throat, as patients know it, or streptococcal pharyngitis, which is what doctors call it, is a serious and potentially fatal disease. Caused by the group A streptococcus bacterium (Streptococcus Pyogenes) it is a form of β-hemolytic Stretococcus bacteria. It  called “hemolytic” because it breaks apart red cells on a culture plate. There is no sure way of telling that a sore throat is a strep throat merely by symptoms. Coughing, nasal discharge, diarrhea, red eyes in addition to fever and sore throat are more indicative of a viral sore throat than of strep throat. Mononucleosis often has swollen nodes, enlarged tonsils, sensation of filling up quickly after eating and prolonged fever.Other kinds of Stretpococcus bacteria, and a host of other bacteria and viruses can also cause a sore throat; however, identifying the A type is important because it can cause specific complications and it must be promptly treated. These complications can be serious and include acute rheumatic fever, a disease that affects heart valves; scarlet fever, which causes a red rash and high fever; kidney disease;  toxic shock and the recently described PANDAS syndrome. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) can cause the rapid onset of obsessive compulsive disorder and tic syndromes, such as Tourette. The connection between group A strep and PANDAS is not yet fully established. Antibiotic treatment reduces the risk of these complications. Whether  antibiotic treatment of group A streptococci infection reduces the risk of lasting kidney damage is still being debated, but one recent review noted a trend showing some protection from treatment.

Is there a way to tell that a child is suffering from a strep throat without doing a culture? Strep throat can come with headache, stomach and muscle pains, nausea and vomiting and rash. However, not all sore throats are strep. Some doctors advocate the modified Centor score to determine how to treat a sore throat, even before a throat culture results is obtained. One point is given for each of the criteria:

• Absence of a cough
• Swollen and tender neck lymph glands
• Temperature > 38 °C (100 °F)
• A whitish pus or  liquid or swelling on the tonsils
• Age less than 15 (a point is subtracted if age > 44 )

One point or less means no treatment and that a culture is probably not necessary (less than 10% chance of Strep A infection).  Score of 2 or 3 indicates antibiotic treatment based on culture results (11-25% chance) and the score of 5 means immediate antibiotic treatment (risk of 58+%).

Many practicing pediatricians do not put much faith into Centor score. Based on their experience of seeing strep throats that have low Centor scores, they say that there is no substitute for a throat culture for a secure diagnosis of strep throat. This is also what the American Society of Infectious Diseases recommends. We can understand why this may be so when we recall that a properly done throat culture establishes the diagnosis of a strep throat with a sensitivity of 90—95%. A rapid strep test, also called RADT (rapid antigen detection tests) is less sensitive, detecting only about 70% of strep infections in the throat. On the other hand, when positive, it is as specific as the traditional throat culture, and provides immediate results. For the children in the community, who cannot return to school until after being on antibiotics for 24 hours, the rapid test can speed their return to school. The best person to recommend whether a child with a sore throat should be treated is your pediatrician.

 Although untreated strep throat usually resolves by itself within a few days, treatment with antibiotics, such as penicillin or Amoxacillin, shortens the duration of the acute illness by about 16 hours. I must add that many pediatricians prefer the cephalosporin class of antibiotics (an example of a cephalosporin is Keflex). Although eradication rates conferred by cephalosporins may be superior to those achieved with penicillin, the latter remains the recommended drug of choice by the American Heart Association and the Infectious Diseases Society of America. Tylenol and pain relieving throat gargles can help decrease pain and steroids can be used in severe cases.

People who do not have symptoms should not be routinely tested with a throat culture or rapid test because a certain percentage of the population persistently “carries” the streptococcal bacteria in their throat without any harmful results. Treating these people exposes them to the risks of treatment, worry and absences from school for no demonstrable gain. Some pediatricians, however, feel that in our large families, the risk of under-treating and allowing strep to spread from one child to another, justifies repeat cultures under certain circumstances and sometimes even justifies re-treatment. This is especially a factor when a child has repeated sore throats. Interestingly, the proportion of positive carriers may be higher in our communities than in the general population. One study found that the proportion of adults with group A streptococci with and without sore throats was 6.4% and 2.4% respectively in the Orthodox Jewish group and 0.45% and 1% respectively in the general population. The proportion of children with group A streptococci with and without sore throats was 17.4% and 5.9% respectively in frum patients and 3.4% and 0% respectively in the others. These differences were not explained by the larger family size and domestic overcrowding in the Orthodox Jewish group (Br J Gen Pract. 2001 February; 51(463): 101–105).

Strep throat is a minor medical condition but one that still requires attention and appropriate care. A concerned and educated parent working together with a pediatrician can ensure that this “minor” condition remains just that, minor, and passes quickly and without complications.

What is Fever?

Fever is defined as an elevation of body temperature above the normal range of 36.5–37.5 °C (98–100 °F). It is triggered by a signal from the temperature regulatory center in the brain in response to a message from the body that there is a threat to the body’s well-being. Raising temperature is the body’s way of fighting back. Many bacteria and viruses function best at regular body temperature and the defensive action of the body in raising the temperature may make them less efficient, or it may decrease levels of certain nutrients or minerals in the blood that they need to function. Some tumors can also be damaged by increased body temperature, and artificial, medically produced elevation of body temperature, called hyperthermia, is sometimes used to treat certain cancers.

The signal to the brain to raise temperature is most often caused by a substance released by or in response to an infection by a bacteria or a virus. In response to this threat, the brain sets a new, higher temperature as its goal and it sends signals to the muscles to cause activity such as shivering. Shivering produces heat and raises the body’s temperature. Even though the temperature is rising, the sick person may feel cold and even experience chills or shivers, because the brain perceives the current body temperature as too low, and because the desired temperature has not yet been reached. Once the new temperature goal is reached, the chills go away and there is a sensation of warmth. At that point, the brain may decide that the new temperature is too high and directs the body to sweat in order to lose some heat. So when the temperature is rising, the sick person feels himself to be cold, and when it is falling, he or she feels hot.

However, fever can also be due to inflammation or auto-immune illness, such as lupus, in which the immune system is dysregulated, or in response to substances secreted by tumors. In such cases, fever becomes a part of the illness process. Even when fever is a part of fighting illness, it can go too high and cause damage.

 How is fever measured?

Different parts of the body have slightly different temperatures. In the United States, temperature is usually measured with a thermometer in the mouth or rectally; in some Eastern European countries temperatures are commonly measured in the armpit and normal temperatures there are slightly lower, because armpits are farther from the core of the body. The temperature in the mouth is also slightly lower than in the core. The commonly accepted average core body temperature (taken rectally) is 37.0 °C (98.6 °F). The typical oral (under the tongue) measurement is 36.8C (98.2F). Since the year 2000, small ear thermometers have become available and they take the core temperature. They work by detecting the infrared heat emission from the ear membrane. They provide an immediate readout and are popular with children and pediatricians.  In hospitals, daily measurements of  body temperature is one of the vital signs, which also include blood pressure, pulse( how many heart beats per minute),  and respiratory rate (how many breaths per minute).

When should fever be treated?

Because fever is a symptom and not a disease, it is imperative to understand the cause of fever before it is treated. Remember that fever is helping to fight  infection, so use fever medications only if the fever is high or if it is in the  moderate range and the adult or the child with fever is uncomfortable. In general, you should call your pediatrician if your infant under three months of age has a rectal temperature above 100.4 F, if your infant aged 3-6 months has a temperature above 101 F, or if an infant above 6 months has a temperature above 103 F. For older children, if your older child is alert, active and playful, is not having difficulty breathing, and is eating and sleeping well, or if the temperature comes down quickly with home treatments (and he is feeling well), then you don’t necessarily need to call your doctor immediately.

Most fevers in healthy adults are transitory and harmless but they can be uncomfortable. Once the diagnosis of what is causing the fever is established, Tylenol (acetominophen) or other fever lowering medications can be used for comfort.  Aspirin should be avoided in children to treat the fever of viral infections because it can rarely cause Reye’s syndrome, a serious complication.

Keep in mind that infection and fever responses in children and the elderly may vary. Some older patients have a decreased or no-fever response to infection, and children usually develop higher temperatures than adults with minor infections.

Fever should also be treated when it exacerbates an underlying condition. For example, if the patient has a heart condition, a fever may increase his or her heart rate, stress the heart and increase the risk of suffering a heart related complication. Patients with fever, especially the elderly, loose more moisture in the form of sweat and should increase their fluid intake.

A medical evaluation is warranted for adults if the temperature:

* rises to 104 deg F (40 deg C or above)

* stays at or above 101 deg F (38.3 deg C) for more than 3 days

* stays at or above 100.5 deg F (38.1 deg C) for 3 weeks or more, even if there are no other symptoms, or

* is accompanied by other symptoms or discomfort.

Fever can produce fatigue and dehydration. High fevers can produce convulsions, especially among young children, but they are rarely dangerous. Brain damage from a fever generally will not occur unless the fever is over 107.6 °F (42 °C). It is rare for a fever from an infection to go over 105 °F unless the child is overdressed or trapped in a hot place. Temperature that approaches 107 degrees F is considered a medical emergency.

A fever is usually accompanied by weakness, depression, loss of appetite, sleepiness, generalized discomfort and inability to concentrate. This is why the decision to bring down a fever is best individualized in consultation with a physician. Allowing a mild fever to remain somewhat shortens the duration of an illness but it makes it more uncomfortable. It is important to remember, however, that the goal of treating fever is solely to prevent it from rising too high or to provide comfort.

In the past, before medical science sharply separated diseases and the symptoms they produced, many conditions were called “fevers”. Even now one encounters the name of fever as a name of certain illness, for example, Yellow Fever, Rheumatic Fever and the like. However, medical science now sees fever as indicating that there is an illness, not as an illness itself. Consequently, it is imperative to establish a diagnosis before tackling fever.

Conclusion

Fever is a manifestation of an illness and not a disease in itself. Most often it is a friend of the sick individual and helps speed recovery. However, there are times when it is a hindrance to recovery or can cause complications. A competent medical professional should be consulted when the fever is high, is present in an infant, pregnant woman or the elderly, or when it does not go away.

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While retrospective studies indicate that long-term steroid use increases the risk of PCP infection it is not known how these patients should be prophylaxed. The threshold for potential infection that warrants prophylaxis with its costs in side effects and expense is unknown, and the critical amount of immunosuppression necessary to increase risk for PCP is also unknown. Prophylaxis has been suggested for patients immunosuppressed owing to an underlying disease or immunosuppressive therapy. In some cancer centers, patients who receive corticosteroid therapy for longer than 4 weeks at a dose equivalent to 20 mg of prednisone per day are routinely are given PCP prophylaxis, as well as those in high-risk groups such as bone marrow transplant recipients and children with ALL.

In 2009, Kovacs and Masur summarized the first 100 years since identification of Pneumocystis. They concluded that in HIV-negative patients there is no reliable laboratory marker for risk of this infection, but that in these patients PCP is more likely to be an acute illness causing severe respiratory distress of rapid onset when compared with HIV-positive patients. That makes routine prophylaxis more reasonable. Their recommended approach is to use PCP prophylaxis in patients receiving at least 20 mg of prednisone per day for at least 1 month. They also note that steroid therapy can accelerate symptomatic and physiologic improvement and improve survival in patients with moderate or severe PCP. Since steroids are in themselves immunosupressive, management of corticosteroids in PCP-infected patients is quite complex.

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In two recent studies, the addition of RSV immune globulin (palivizumab at 15 mg/kg IM monthly) to traditional ribavirin therapy has shown promise in preventing the progression of RSV upper respiratory infection (URI) to lower respiratory disease and also in the treatment of RSV pneumonia. The key is being vigilant about URI and making the diagnosis quickly. It is imperative to determine the etiology of a URI in a stem cell recipient, if possible, because respiratory syncytial virus (RSV), influenza, parainfluenza, and adenovirus URIs can progress to more serious Lower Respiratory Infection. Appropriate routine diagnostic samples to investigate URO in recent transplant recipients include nasopharyngeal washes, swabs or aspirates; throat swabs (in combination with nasal samples); and bronchoalveolar lavage (BAL) fluid. Without an URI, prophylactic use of Ribavirin alone is currently experimental.

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In two recent studies, the addition of RSV immune globulin (palivizumab at 15 mg/kg IM monthly) to traditional ribavirin therapy has shown promise in preventing the progression of RSV upper respiratory infection (URI) to lower respiratory disease and also in the treatment of RSV pneumonia. The key is being vigilant about URI and making the diagnosis quickly. It is imperative to determine the etiology of a URI in an HCT recipient, if possible, because respiratory syncytial virus (RSV), influenza, parainfluenza, and adenovirus URIs can progress to more serious lower respiratory infections. Appropriate diagnostic samples include nasopharyngeal washes, swabs or aspirates; throat swabs (in combination with nasal samples); and bronchoalveolar lavage (BAL) fluid. Without an URI, prophylactic use of Ribavirin is experimental.

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