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Microsoft word - upcoming tropical diseasesPediatric Infectious Diseases Conference – Clinicomicrobial Fusion 2010 (PIDC 2010), Mumbai, 24th October 2010
UPCOMING TROPICAL INFECTIONS
Mala V. Kaneria
Associate Professor, Unit Chief, Department of Medicine, B.Y.L.Nair Ch. Hospital and T.N.Medical
An emerging or upcoming infectious disease is one whose incidence has increased in the past
20 years and threatens to increase in the near future. Emerging infections account for at least
12% of all human pathogens. They include diseases caused by newly identified microorganisms
or newly identified strains of a known microorganism, new infections resulting from change or
evolution of an existing organism, a known infection which spreads to a new geographic area or
population, newly recognized infection in an area undergoing ecologic transformation, and pre-
existing and recognized infections reemerging due to drug resistance of their agent or to a
breakdown in public health.
Chikungunya is an arboviral disease transmitted by aedes mosquitoes. The virus was first isolated in 1953 in Tanzania. Chikungunya virus is a member of the genus Alphavirus and the family Togaviridae. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia. The word chikungunya, used for both the virus and the disease, means “to walk bent over” in some east African languages, and refers to the effect of the joint pains that characterise this dengue -like infection. The reasons for the re-emergence of chikungunya on the Indian subcontinent, and for its unprecedented incidence rate in the Indian Ocean region, are unclear. Plausible explanations include increased tourism, chikungunya virus introduction into a naive population, and viral mutation. After infection with chikungunya virus, there is a silent incubation period lasting 2–4 days on average (range 1–12 days). Clinical onset is abrupt, with high fever, headache, back pain, myalgia, and arthralgia; which can be intense, affecting mainly the extremities (ankles, wrists, phalanges) but also the large joints. Skin involvement is present in about 40–50% of cases. Erratic, relapsing, and incapacitating arthralgia is the hallmark of chikungunya, although it rarely affects children. Arthralgia/arthritis appear to affect 73–80% of patients with serologically confirmed chikungunya virus. Radiological findings are normal, and biological markers of inflammation are normal or moderately elevated. There are very few case reports of destructive arthritis following post chikungunya virus chronic rheumatism. In less than 10% of cases, the arthralgia persists for months. In another 10% of patients, it subsides and then reappears with every febrile illness, affecting the same joints. Chikungunya is not generally considered to be a life threatening disease and may rarely lead to neurologic and hepatic manifestations and an associated mortality. Chikungunya virus infection is thought to confer life-long immunity. Indian scenario – Epidemics of chikungunya were reported in the last millennium
following which there was a lull of three decades and in 2006 there was a massive epidemic. A total of 1958 confirmed cases have been reported from 13 states in India during 2006-2007 (upto 17.1.2007). Chikungunya was considered a non-fatal arbovirus. However, 237 deaths during the 2005-2006 epidemic in the French Republic changed this perception. A study from Ahmedabad in 2007 reported 3112 excess deaths providing evidence that the virus may have mutated and become more virulent. Pediatric Infectious Diseases Conference – Clinicomicrobial Fusion 2010 (PIDC 2010), Mumbai, 24th October 2010
• Isolation of virus • PCR • Detection of IgM antibodies in a single serum sample collected in acute or convalescent • Demonstration of rising titres of IgG antibodies (fourfold increase in samples collected
Difficult to distinguish from dengue especially because simultaneous co-infection can occur.
Chikungunya symptom onset was more abrupt, fever was short-lived and rash, conjunctival
injection and arthralgia were more frequent than in dengue according to a study from Thailand.
Thrombocytopenia and bleeding manifestations seen in dengue are hardly ever seen in
chikungunya. Besides, chikungunya causes explosive outbreaks before apparently disappearing
for a period of several years to decades whereas dengue is endemic in nature. In chikungunya,
the total counts are less than 5000/cumm and counts more than 10,000/cumm suggest a
possibility of leptospirosis. A low platelet count should make one alert to the possibility of
dengue. Other monsoon related illnesses should be ruled out.
• There is no specific antiviral drug available. • Treatment is entirely symptomatic with paracetamol or other NSAIDS • Aspirin is to be avoided (GI side effects and Reye’s syndrome) • In incapacitating arthralgia, hydroxychloroquine or chloroquine 300 mg orally daily for 4 • In chronic cases, a short course of steroids has been tried • Ribavirin in a dose of 200 mg bd for 7 days has been tried in arthralgia patients with success, showing that this may have a direct antiviral effect against chikungunya virus and lead to faster resolution of symptoms.
Leptospirosis is a spirochaetal zoonosis widely recognized as being emerging or re- emerged. In tropical and subtropical regions, the disease is endemic with an increased incidence noted during monsoon. In Mumbai, post the 2005 deluge, leptospirosis has returned with a bang. It is caused by different serovars of the spirochaete Leptospira – L. Interrogans icterohemmorrhagica, biflexa, etc. Different animals act as reservoirs for these serovars and shed them in their urine. The organism enters the body through abraded skin or mucous membrane. In Mumbai, the commonest mode of exposure is wading through contaminated water during monsoon. The spectrum of disease ranges from a mild inconsequential febrile illness to a severe fatal form presenting with multi organ failure called Weil’s disease. This variability in the course causes diagnostic dilemmas and confusion with a broad spectrum of diseases such as acute viral hepatitis, haemorrhagic fevers, dengue fever, malaria, etc. It is a biphasic illness with an acute phase of bacteremia lasting for a week followed by an immune Pediatric Infectious Diseases Conference – Clinicomicrobial Fusion 2010 (PIDC 2010), Mumbai, 24th October 2010
phase in the second week which is characterized by antibody production and leptospiriuria. The fever may be associated with chills, severe myalgia, headache, conjunctival suffusion and jaundice. Myalgia which is a classic manifestation usually affects the lower back, thighs and calves. Jaundice may be severe with high bilirubin levels and only mild to moderate elevation in transaminase levels. Due to this derangement in the liver function tests, acute viral hepatitis is a close differential. The difference in the transaminase rise and elevated creatine phosphokinase seen in leptospirosis may aid in the diagnosis. Complications observed are usually multisystemic. Acute renal failure is commonly seen, the hallmark of which is hypokalemia and non-oliguria. Acute interstitial nephritis and acute
tubular necrosis are the main histological findings. Newer data support the role of peculiar ion
transport defects in leptospiral nephropathy. Pulmonary involvement with the presence of intra
alveolar haemorrhages is another common complication associated with a high mortality. The
radiological appearance may mimic that of miliary tuberculosis and patients have been
erroneously started on anti tuberculous treatment for the same. Linear deposition of
immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in
the pathogenesis. Thrombocytopenia and bleeding manifestations are common.
Laboratory diagnosis Serology is the method of choice for diagnosis. Microscopic agglutination
test (MAT) is the reference method for serological diagnosis. This method is cumbersome and
available only in reference laboratories. Detection of IgM antibodies by ELISA is widely used.
Management Mild cases can be managed with oral Doxycycline in a dose of 100 mg bd for 7
days (Doxycycline should not be used in children < 8 years of age). Severe cases should be
treated with intravenous Penicillin G in the dose of 20 lac units 6 hourly for 7 days. Third
generation cephalosporins such as ceftriaxone have a superior safety profile and are as
effective. Severe cases with complications like ARDS, ARF, hepatic encephalopathy, myocarditis,
etc. may require ICU care. For ARF, dialysis is the standard supportive therapy though recent
studies suggest clinical benefit from plasmapheresis and hemofiltration. ARDS may warrant lung
protective ventilation. Intravenous methylprednisolone in a dose of 1 gm for 3-5 days has shown
significant benefit in ARDS. Cyclophosphamide in a dose of 60 mg/kg single dose has been tried
in addition to methylprednisolone. Platelet transfusions in case of thrombocytopenia with
bleeding have a significant role. Doxycycline in a weekly dose of 200 mg is commonly advocated
for prophylaxis, but has unclear benefit.
Scrub typhus is a zoonosis widely prevalent in many parts of Asia including India. It is endemic to a part of the world known as the “tsutsugamushi triangle”. It is caused by Orientia tsutsugamushi which is a small, intracellular, gram negative coccobacillus which is transmitted to humans and rodents by some species of trombiculid mites (“chiggers”, Leptotrombidium deliense and others). It is the commonest rickettsial infection seen in India. It presents with an acute onset of high fever, headache, myalgia, rash and gastrointestinal symptoms. The characteristic hallmarks of rickettial infection are: the eschar of the tick bite and the confluent petechial nature of the rash. Eschar may be found in 10-92% of patients and has to be actively sought. Its presence not only confirms the diagnosis but is also a vital sample for confirmation Pediatric Infectious Diseases Conference – Clinicomicrobial Fusion 2010 (PIDC 2010), Mumbai, 24th October 2010
through immunohistochemical staining or PCR. It is preferentially located in the perineum,
inguinal area, axilla and the front of the chest wall.
Diagnosis: Immunofluorescence assay (IFA) remains the gold standard technique and is the
reference technique used in many laboratories. Weil-Felix test, scrub typhus IgM ELISA and
eschar PCR are other useful diagnostic modalities.
Treatment: Doxycycline is the drug of choice which is cheap and effective. Chloramphenicol and
Azithromycin are also known to be effective. Prompt treatment is essential as delay can cause
significant mortality. It is suggested that the diagnosis of scrub typhus should be based on a high
index of suspicion and careful clinical laboratory and epidemiological evaluation.
HAND FOOT AND MOUTH DISEASE (HFMD)
Hand, foot, and mouth disease (HFMD) is a common viral illness of infants and children. The disease causes fever and blister-like eruptions in the mouth and/or a skin rash. It is often confused with foot-and-mouth (also called hoof-and-mouth) disease, a disease of cattle, sheep, and swine; however, the two diseases are not related. HFMD is caused by human enteroviruses, with Coxsackievirus A16 (CA16) and enterovirus 71 (EV71) being the two major causative agents. In spite of repeated epidemics in many countries of the Asia-Pacific regions since 1997, this disease did not affect India till 2003, when the first ever epidemic was observed in Kerala. Due to the presence of multiple genotypes and sub genotypes of the two viruses, repeated epidemics of HFMD have occurred and are possible in future. The clinical feature is characteristic and classically consists of a combination of exanthem and enanthem. Papulo-vesicular lesions are present over the hands, feet, buttocks, knee and oral mucosa. The incubation period averages 3-6 days. Coxsackievirus infection is highly contagious. During epidemics, the virus is spread by horizontal transmission from child to child and from mother to fetus. Transmission occurs by means of direct contact with nasal and/or oral secretions, fecal material, or aerosolized droplets in a fecal-oral or oral-oral route. HFMD is not transmitted to or from pets or other animals. Infected persons are most contagious during the first week of the illness. HFMD occurs mainly in children under 10 years old but can also occur in adults. Coxsackievirus A16 generally causes benign disease whereas EV71 infection can be associated with serious neurological complications like aseptic meningitis, encephalitis or poliomyelitis like-acute flaccid paralysis. It has been observed that the disease that was benign initially, has acquired more virulence in the subsequent years. Considering all these facts, it becomes imperative that close monitoring of the disease in India is important. Unfortunately, awareness among the doctors or medical staff regarding the disease is lacking. Diagnosis of HMFD can be made clinically with certainty, provided there is strong suspicion. Differentials are mosquito bite, papular urticaria or chicken pox etc. There is every possibility of missing the individual cases and even small sized epidemics, due to the rarity of the cases, lack of suspicion among clinicians, similarity to common skin diseases and, most importantly, rapid and uneventful recovery. There is no specific treatment for HFMD. Pain and fever can be treated with over-the- counter medications (caution: aspirin should not be given to children). Mouthwashes or sprays that numb pain can be used to lessen mouth pain. Good hygiene practices that can lower the Pediatric Infectious Diseases Conference – Clinicomicrobial Fusion 2010 (PIDC 2010), Mumbai, 24th October 2010
risk of infection include washing hands frequently and correctly, cleaning dirty surfaces and
soiled items and avoiding close contact with persons with HFMD.
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A Miracle Cure The theme of medicinal plants has been extensively explored in the University of Oxford Botanic Garden and was one of the themes for a joint study day at the Museum in December. The accompanying activities are designed to make the relevance of science clearer and give an insight into how scientists really work, as well as reveal more about the origin of medicines and the processes o