Algorithm for Fever Management

Algorithm for The Diagnosis and Treatment of Common Febrile Disorders
(Novel H1N1, Respiratory Infections, Chikungunya, Dengue, Leptospirosis, Malaria and Hepatitis)
Dr. B. Srinivas Kakkilaya, Consultant Physician, Mangalore
With Inputs From:
Dr. M. Chakrapani, Prof. of Medicine, Kasturba Medical College, Mangalore;
Dr. Ashok Bhat, Assoc. Prof. of Medicine, Kasturba Medical College, Mangalore;
Dr. Shrikanth Hegde, Consultant Physician, Shivamogga

Several parts of our country are now experiencing concurrent epidemics of many infections like Dengue, malaria, leptospirosis (rat fever), various hepatites etc., and had also witnessed epidemics of Chikungunya in the recent past. The arrival of Novel Influenza A (H1N1) virus has further compounded the problem for the common man, the health care system as well as the Govt. agencies alike. All these have created panic and confusion all over as well as logistical problems in the diagnosis and management of these infections. A level headed and rational approach is the need of this critical hour for efficient and appropriate health care delivery. Quick diagnosis and prompt treatment would help in minimising the complications and thereby the mortality from these infections and the following information may be useful in that regard. This algorithm would help in making a clinical diagnosis of these common febrile disorders and also help in rationalising the use of simple diagnostic tests, thereby avoiding the expensive and often unreliable serological tests.

The Novel Influenza A (H1N1), Dengue and Chikungunya are caused by viruses, malaria is caused by the malaria parasites and leptospirosis is caused by a coiled bacterium. Almost all viral infections are self limiting diseases that remit within a week in most cases without any specific treatment and these three are no exceptions. Leptospirosis also manifests as a mild, non-specific and self-limiting illness in the majority of cases and treatment is needed only when it leads to complications in a few. Malaria, on the other, has to be treated with specific anti malaria drugs and any delay in the treatment of falciparum malaria may result in complications that could be fatal.

Therefore, of all these diseases, it is the early and specific diagnosis of malaria that is most important. It is also important to identify early symptoms and signs of severe disease and complications of all these infections, so that early hospitalisation and necessary interventions can be made.

How do these diseases spread?

Novel Influenza A (H1N1) spreads easily and quickly by simple contact and therefore it is almost impossible to prevent the spread of this infection. With our dense population and easy overcrowding, particularly in the urban areas, flu can spread quite rapidly. Measures such as the use of face masks, consumption of herbal or homeopathic remedies or application of eucalyptus or neem oil etc., are of no avail in preventing the spread of this new virus.

Dengue, Chikungunya and malaria are spread by mosquitoes. Malaria is spread by the female Anopheles mosquito whereas Dengue and Chikungunya are transmitted by the female Aedes aegypti mosquito. Anopheles mosquitoes that spread malaria bite predominantly indoors, after midnight. Aedes aegypti bites at dawn and dusk, both inside and outside the households. Both these varieties of mosquitoes breed profusely in clean, stagnant water that collects around human dwellings (in buckets, tyres, bottles, coconut shells etc. that are thrown out in the open as well as in overhead tanks, wells etc.) Malaria and Dengue are more often seen in the urban areas while Chikungunya can spread rapidly all across. Controlling mosquito breeding and protection from mosquito bites are very essential to prevent the spread of these infections.

Leptospirosis is spread by contact with water that is contaminated with rats’ urine. Leptospirosis is a common infection in rats and the bacteria is exreted in their urine. Any body of water that is contaminated with the urine of such rats acts as a source for leptospiral infection. Wading, bathing, washing, drinking etc., from such contaminated streams, rivulets, ponds, paddy fields, water tanks etc., may lead to leptospirosis.

Symptoms and Signs

Influenza involves the respiratory tract and manifests with fever, body ache, headache, sore throat and cough, with some patients also having vomiting or diarrhea. More than 99% patients recover in 3-5 days without any treatment. Severe illness, characterized by high fever or severe sore throat, vomiting or diarrhea, bloody sputum, difficulty in breathing, bluish discoloration of the lips, tongue and nails etc., can occur in 1-2% of cases and would
require hospitalization.

Dengue fever presents with severe muscular pain, back ache, head ache, pain on moving the eye balls and a fine rash or flushed appearance (that blanches on pressure) over the trunk and extremities. Some patients may have bleeding from the nose or under the skin. Nausea and vomiting may also be seen. Most patients recover within a week without any treatment. In about 5% of cases dengue can lead to serious complications. As the fever starts subsiding, capillary leak can progress during the next 24-48 hours, leading to the critical phase, characterised by decreased platelet counts, increased bleeding and drop in blood pressure. Abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation such as pleural effusion or ascites, mucosal bleed, lethargy, restlessness, liver enlargment >2 cm, increased hematocrit concurrent with rapid decrease in platelet count are warning signs of severe dengue and such patients must be keenly observed, and admitted if required. If carefully managed, most of these patients make an uneventful recovery. [See DENGUE GUIDELINES FOR DIAGNOSIS, TREATMENT, PREVENTION AND CONTROL. WHO. 2009. At http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

Leptospirosis also manifests with sudden fever, muscular pain and back ache. As the fever continues, redness of the eyes, head ache, cough etc. may appear in 4-7 days. In some the fever recurs after a gap of 1-3 days and complications like jaundice, decreased urine output, bleeding tendencies etc., may occur. In most patients, leptospirosis recovers spontaneously and passes off as a simple febrile illness. Only those patients who develop complications involving the liver, kidney etc., require hospitalization and specific treatment and most of these patients also recover with supportive care.

Chikungunya is characterized by sudden onset fever, pain and swelling of joints and raised rashes over the face, trunk and extremities that may itch. The fever and rash usually disappear in 3-5 days; however in about 12% of cases, the joint pain may remain for many weeks and may be severe enough to prevent them from moving out. Deaths due to Chikungunya are extremely rare; however, patients already suffering from diseases of major organs may succumb
after contracting Chikungunya.

Malaria is characterized by high fever with or without chills that can occur daily or on alternate days. One should not wait for chills or rigors to do a blood test for malaria. As many as 60% of malaria cases may have a dry cough, more so in P. vivax infections. Some patients may have jaundice. Severe body ache, joint pain or rash are not seen in malaria.

About 10% of patients with falciparum malaria may develop complications involving the brain, kidneys, lungs or drop in blood pressure. Early diagnosis and prompt treatment with antimalarial drugs and life support (ventilation, dialysis etc.) will help majority of patients to recover.

Diagnosis

As many of these infections share several common manifestations, it may be difficult at times to
differentiate between them. However, a careful examination to identify certain subtle differences in their clinical manifestations and some simple blood and urine tests would help in the diagnosis.

Algorithm for Diagnosis and Treatment of Febrile Disorders (Click to open enlarged image in new window)

Fever and Cough

Anyone suffering from fever, sore throat and cough these days will be suspected of having the new H1N1 infection! Until a few weeks ago, anyone suffering these common symptoms would have waited for a couple of days, may be taking some home remedies, for the ‘common cold’ to subside on its own. But in these changed times, even this simple infection is forcing people to stand in hour long queues in front of the hospitals, with masks on their faces!

Many viruses and bacteria can cause respiratory tract infections and Novel Influenza H1N1 is just one among them. Symptoms such as fever, sore throat, cough, body ache and head ache are common for most of them. Significant body ache and headache is more common in viral infections whereas pain on swallowing, presence of follicles over the throat or tonsils, enlarged and painful lymph nodes beneath the lower jaw, yellowish or rusty sputum or pain on any side of the chest on breathing or coughing are suggestive of a bacterial infection. A secondary bacterial infection is likely if the fever recurs after tending to subside over 3-4 days following a viral infection. An elevated white cell count suggests a bacterial infection. A chest x ray is useful in identifying a consolidation due to pneumonia.

Patients with high fever, severe throat pain, bloody sputum, difficulty in breathing, persistent vomiting or diarrhea, altered sensorium etc., should consult a specialist and get admitted to a hospital. Age older than 65 years or less than 5 years, pregnancy, pre-existing diseases of major organs like the heart, kidneys, lungs, liver or the nervous system, diabetes, cancer, HIV/AIDS, immunocompromised or immunosuppressed (on steroids, transplant recipients) states and obesity have been associated with higher risk of complications and such patients should therefore be under observation or even hospitalized. Increased respiratory rate, breathlessness and cyanosis of lips, tongue or nails indicate respiratory failure and such patients should be immediately admitted in a well equipped tertiary care centre and treated with antibiotics, oxygen and if required, artificial ventilation. Delay in initiating these life saving measures may prove fatal.

Fever and Aches/Pains and Rash

Severe body ache, back ache, pain on moving the eyeballs are common symptoms of Dengue fever and leptospirosis. In Dengue fever, a fine, macular rash appears over the trunk and extremities after 1-2 days of onset or the skin over the face and the trunk may appear flushed, blanching on pressure. In leptospirosis, hemorrhagic rash may appear on the legs after 6-7 days. Chikungunya can be easily identified with its typical manifestations of fever with severe joint pains and maculopapular rashes over the face, trunk and extremities.

Lab. Investigations:

The total leukocyte count (TLC) is usually low in Dengue, whereas the TLC and ESR are significantly increased in leptospirosis. However, during the critical period or with the onset of severe dengue due to capillary leak, the white blood count can increase, along with increase in the hematocrit. Presence of albumin and cellular sediments in the urine is invariably found in leptospirosis and this simple test is a helpful hint.

Platelet counts can be low in any severe infection, including dengue, malaria and leptopsirosis and as such, has no diagnostic value. At best, patients with low platelet counts need to be monitored for bleeding or other complications. Platelet transfusions serve no purpose.[See DENGUE GUIDELINES FOR DIAGNOSIS, TREATMENT, PREVENTION AND CONTROL. WHO. 2009. At http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

Every case of fever must be tested for malaria parasites by either a peripheral smear microscopy or QBC test. RDTs (strip tests) are not very reliable and can be used only when microscopy is not available at all. The confirmatory tests for dengue, chikungunya and leptospirosis involve detection of antibodies against the respective organisms and these tests are expensive, time consuming and not widely available and therefore are not of much help in the early diagnosis and treatment of these diseases. Therefore the above mentioned differentiating clinical features and simple blood and urine tests are of great help in the diagnosis of dengue and leptospirosis.

Malaria, Leptospirosis, Hepatitis

Both malaria and leptospirosis can lead to jaundice. Viral hepatitis are also common causes for jaundice in our country. In viral hepatitis, patient has fever, upper abdominal discomfort and vomiting during the initial 3-4 days and these symptoms subside as the jaundice increases and the urine and eyes turn yellowish. In malaria and leptospirosis, fever continues as the jaundice increases. In cases of viral hepatitis, the liver enzymes are significantly increased and levels of ALT more than 350 U should suggest a possibility of viral hepatitis. In malaria and leptospirosis, the liver enzymes are moderately elevated and in addition, other alterations in the blood count, peripheral smear and urine, as mentioned above, would be present.

Treatment

Infections of respiratory tract, including Novel Influenza A (H1N1): Most viral infections, including the Novel Influenza H1N1, subside on their own over 3-7 days and antibacterial drugs are needed only in case of bacterial infection. Antipyretics such as paracetamol or other pain killers are preferably avoided. If high fever or severe body ache or head ache cause unbearable discomfort, antipyretics like paracetamol can be used. As per the new guidelines issued by the Dept of Health, Govt. of India, only patients of suspected H1N1 infections who have developed or are at risk of developing the manifestations of severe disease need to take Oseltamivir and test for the virus; the large majority of cases (99.9%) of the novel H1N1 infection would recover spontaneously without any specific treatment and therefore would neither require the test nor the antiviral drugs. It is notable that even in countries like the US, Canada and Australia wherein more than a million people have already been infected with the new H1N1 virus, antiviral drugs and H1N1 tests have been used very sparingly and most of the patients have recovered without any specific treatment [16,17,18] (no Tamiflu, Ayurveda, Homeopathy, Unani, onions, garlic, ginger, neem, Amritaballi or else)!

Bacterial infections of the upper respiratory tract can be treated with penicillins or macrolides. Community acquired pneumonia can be treated with penicillins, cephalosporins or macrolides. Hospital acquired pneumonias would require a third generation cephalosporin along with an aminoglycoside like gentamicin or co-amoxyclav.

All patients with tachypnoea, hypoxemia, hypotension or acidosis should be administered oxygen so as to maintain PaO₂ at >60mmHg or SaO₂ at >92% as well as other supportive care. If hypoxemia fails to improve with adequate oxygen therapy, assisted ventilation should be started early.

Dengue and Chikungunya: In Dengue, it is preferable to avoid all drugs, including paracetamol. In chikungunya, if the fever and/or joint pains are very severe, simple analgesic like paracetamol can be used. Potent pain killers can cause more harm than good. Reckless use of NSAIDs can result in gastrointestinal bleeding or other haemorrhagic manifestations. Paracetmol may worsen liver failure in dengue. Prescribing NSAIDs to patients with pre-existing renal disease or cardiac failure may aggravate the condition. Steroids have absolutely no role to play in the treatment of acute chikungunya and dengue. If the joint pain and swelling in chikungunya persist even after 10-15 days, hydroxychloroquine or salazopyrine have been found to be useful.

Leptospirosis: If a diagnosis is made during the primary phase of the infection, penicillin (1.5 million 6 hourly) or doxycyline (100mg 12 hourly) or ceftriaxone (1 g 12 hourly) may be helpful. However, these may not prevent the complications. Patients who develop complications should be managed with careful supportive therapy.

Malaria is treated with antimalarial drugs like chloroquine or artemisinin based combinations. Patients who develop complications require careful supportive therapy. Antibiotics (third generation cephalosporins) are recommended for patients with algid malaria.[See]

Viral hepatitis is a self limiting illness that does not require any specific treatment.

Complications: Malaria, Dengue and leptospirosis can result in many serious complications that can be life threatening. Dengue Hemorrhagic Fever and Dengue Shock Syndrome are well recognized complications of Dengue fever. Acute respiratory distress, renal failure, altered sensorium or coma, convulsions, drop in blood pressure, jaundice, bleeding etc., can occur in both malaria and leptospirosis.

Most of these patients can be saved by early diagnosis, prompt treatment and careful supportive care. Patients of dengue who show signs of increasing capillary leak should be treated with careful infusion of crystalloids. Massive bleeding or its high likelihood can be managed with whole blood transfusion. There is no role for platelet transfusion in any case of thrombocytopenia. Overenthusiastic transfusion of blood or platelets may do more harm than good; most cases of thrombocytopenia recover spontaneously and watchful expectancy and masterly inactivity is all that is needed. There is no role for steroids in the management of any of these diseases or their complications. There is no evidence to show that homeopathy or ayurveda or any other alternative medicines have any beneficial effects in the treatment of any of these diseases.

Summary

Therefore, with a careful and rational approach, it is not difficult to promptly diagnose and treat most of the infectious diseases that are prevalent today. Only malaria and bacterial infections need specific treatment and most cases of viral infections recover on their own. Creating unnecessary panic only leads to confusion and unbearable burden on the healthcare delivery system, thereby depriving the life saving support to the needy. Let rationalism prevail.

References:

1. Ann M. Powers, Christopher H. Logue. Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. Available at
   http://www.sgm.ac.uk/jgvdirect/82858/82858ft.pdf
2. Judith Green-McKenzie. Leptospirosis in Humans Available at
   http://www.emedicine.com/EMERG/topic856.htm
3. Connelly CR, Mores CN, Smartt CT, Tabachnick WJ. Chikungunya. Available at
   http://edis.ifas.ufl.edu/IN696
4. Sathiavathy KA. Chikungunya fever-Perceptive of Current Epidemic – 2007. Available at
   http://www.articleset.com/health_articles_en_Chikungunya-fever-Perceptive-of-Current-Epidemic-2007.htm
5. Chhabra M, Mittal V, Bhattacharya D, Rana U, Lal S. Chikungunya fever: A re-emerging viral infection. Indian J Med Microbiol [serial online] 2008 [cited 2008 Jun 24];26:5-12. Available from: http://www.ijmm.org/text.asp?2008/26/1/5/38850
6. Ashok Swaroop, Arvind Jain, Maniram Kumhar, Naveen Parihar, Sachin Jain. Chikungunya Fever. JIACM 2007;8(2):164-8. Available at
   http://medind.nic.in/jac/t07/i2/jact07i2p164.pdf
7. MM Parida, SR Santhosh, PK Dash, PV Lakshmana Rao. Rapid and Real-time Assays for Detection and Quantification of Chikungunya Virus Available at
   http://www.medscape.com/viewarticle/571272
8. Mohan, Alladi “Chikungunya fever: clinical manifestations & management”. Indian Journal of Medical Research. Nov 2006. FindArticles.com. 06 Jul. 2008. Available at http://findarticles.com/p/articles/mi_qa3867/is_200611/ai_n19198542
9. Robert V Gibbons. Dengue: an escalating problem. BMJ 2002;324:1563-1566 (29 June) Available at http://bmj.bmjjournals.com/cgi/content/full/324/7353/1563
10. Carlos CC, Oishi K, Cinco MTDD et al. Comparison Of Clinical Features And Hematologic Abnormalities Between Dengue Fever And Dengue Hemorrhagic Fever Among Children In The Philippines. Am. J. Trop. Med. Hyg. 2005;73(2):435-440. Available at
    http://www.ajtmh.org/cgi/content/full/73/2/435
11. Sunil Karande, Dipak Gandhi, Madhuri Kulkarni, Renu Bharadwaj, Sae Pol, Jyotsna Thakare, Anuradha De. Concurrent Outbreak of Leptospirosis and Dengue in Mumbai, India, 2002. Journal of Tropical Pediatrics 2005;51(3):174-181. Abstract at
    http://tropej.oxfordjournals.org/cgi/content/abstract/51/3/174
12. Vinod H. Ratageri, T.A. Shepur, P.K. Wari, S.C. Chavan, I.B. Mujahid, P.N. Yergolkar.
    Clinical Profile and Outcome of Dengue Fever Cases. Indian J Pediatr 2005;72(8):705-706. Available at http://medind.nic.in/icb/t05/i8/icbt05i8p705.pdf
13. Leptospirosis. Available at http://www.merck.com/mmpe/sec14/ch174/ch174c.html
14. http://www.leptospirosis.org/topic.php?t=50
15. New Guidelines for Screening, Testing, and Isolation for H1N1. Available at
    http://pib.nic.in/release/release.asp?relid=51875
16. Public Health Agency of Canada Guidelines on Novel H1N1. Available at
    http://www.phac-aspc.gc.ca/alert-alerte/swine-porcine/faq_rg_swine-eng.php
17. CDC Recommendations Guidelines on Novel H1N1. Available at http://www.cdc.gov/h1n1flu/recommendations.htm
18. Statement of Australian Health Minister. Available at
    http://en.chinagate.cn/features/swineflu/2009-06/11/content_17930926.htm
19. WHO Guidelines for Pharmacological Management of Pandemic (H1N1) 2009 Influenza and other Influenza Viruses. Available at
    http://www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf