Hepatitis E and Meningitis Outbreaks in India; Avian Influenza: Is Oseltamivir an Answer?
Abstract & Commentary
By Elliott J. Anderson, MD, and Maria D. Mileno, MD
Dr. Mileno is Director, Travel Medicine, The Miriam Hospital, Associate Professor of Medicine, Brown University, Providence, RI, and Dr. Anderson is former resident of Internal Medicine, Brown University.
Dr. Mileno is a consultant for GlaxoSmithKline and does research for Merck, and Dr. Anderson reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.
Synopsis: Several disease outbreaks present travelers to south Asia with new medical questions for their travel medicine providers. They underscore the dynamics of this field which change on virtually a daily basis.
Sources: Jaundice Outbreak in Alandi, 61 Affected. PUNE Express News Service. March 27, 2005; Normile D. Infectious Diseases. Genetic Analyses Suggest Bird Flu Virus is Evolving. Science. 2005;308:1234-1235.
The International Society for Infectious Diseases (ISID) has provided details on an outbreak of viral hepatitis in India through its ProMED-Mail service. An epidemic in the Maharashtra region (see map) of India has been attributed to the hepatitis E virus (HEV), and felt to be related to leakage from sewage drainage lines that contaminated a parallel drinking water supply. The areas of Baramati and Alandi have been the most affected. As of March 28th, 2005, there have been nearly 350 reported cases of viral jaundice in Baramati and over 60 in Alandi. Approximately 40 patients have required hospital admission in Baramati. There were no reports of mortality from fulminant hepatic failure as of the date of the release. One of the more severely affected patients was several months pregnant, and authorities were offering immunoglobulin to pregnant women, regardless of whether they have already been infected.
Hepatitis E virus is known to be endemic to the region, with occasional cases occurring, but the National Institute of Virology claims this is the first time it has taken on epidemic proportions within this region. Generally, hepatitis secondary to HEV is an enterically transmitted, self-limited inflammatory illness. The non-enveloped, single stranded RNA virus produces its highest incidence of human infection in Asia, Africa, the Middle East, and Central America. In the last reported severe outbreak from 1986 to 1988, over 100,000 persons were afflicted in the Xinjiang region of China. It is an unusual cause of hepatitis in western countries, and sporadic cases will usually be encountered among people who have recently visited and returned from endemic areas. After an incubation period ranging from 15 to 60 days, the illness manifests itself with malaise, anorexia, fever, and jaundice. Nausea, abdominal pain, and vomiting can accompany acute illness, as is the case with most forms of viral hepatitis. Fulminant hepatitis is rare in association with hepatitis E, with a low overall case fatality rate. However, hepatitis E infection during the third trimester of pregnancy may cause very serious illness. Pregnant women are at considerable risk for fulminant hepatic failure and death (20% in the third trimester).
Measures have been taken in affected regions of India to repair leaks in the sewage lines in order to limit further disease. Trials of local water use are now underway again after a ban on hotel use of local water and ice had been enforced. Recommendations were made to the local population to boil water, as well as add medichlor, a chloramphenicol based purification method. Antibiotic measures will not rid contaminated water of the hepatitis E virus, but would be intended to help limit the transmission of other potential enteric pathogens. Travelers to affected areas, as always, should take precautions to avoid water of unknown purity, and native sugarcane, fruit juice, and uncooked fruits or vegetables until word of complete resolution is available. The epidemic is likely nearing resolution, as the source has been identified and was in the process of repair at the time of the last reported information released in early April.
While there is currently no vaccine available to prevent hepatitis E, all travelers to India should now receive meningococcal immunization. There has been a recent outbreak of meningococcal disease in the national capital of India, Delhi, which was outlined in the WHO Communicable Disease Surveillance and Response website. As of May 16, 2005, 303 cases had been reported in the city, with 26 associated deaths. Nearly 40 more cases had been reported from nearby areas outside of the city as well. The majority of patients have been young adults, ages 16-30. All deaths have occurred in this age group. CSF evaluation, cultures, and typing revealed serogroup A as the causative strain in 18 patients where laboratory confirmation of a specific serogroup was possible. The WHO is working closely with local authorities to assist in effective outbreak control through education, chemoprophylaxis, and vaccination. Medical staff who work in regional hospitals are being vaccinated, and contacts of case patients are receiving prophylactic antibiotics, as well as vaccination.
Meningococcal disease is endemic to the Delhi region, and there are sporadic cases occurring yearly. However, the last outbreaks of this proportion were in 1985 and 1966. In 1966, over 600 cases were reported, with a 21% fatality rate. In the larger epidemic of 1985, 6133 cases with a 13% fatality rate occurred. The gram-negative diplococci, Neisseria meningitides, is transmitted through droplets of respiratory and throat secretions. There is no animal reservoir other than humans, where it is carried in the pharynx. An estimated 10-25% of the general population are carriers, and this percentage surely climbs during outbreaks. The factors that lead to the ability of the bacteria to invade hematogenously and reach the meninges are still obscure, but include antecedent viral or bacterial respiratory infection, asplenia, and other immunodeficiencies, particularly of terminal complement components.
Effective control of the outbreak and successful treatment of case patients are dependent upon early recognition and institution of appropriate antimicrobial therapy, in addition to chemoprophylaxis and vaccination. The vaccines typically take 10-14 days to confer reasonable immunity, and are known to protect against 4 strains of N. meningitidis (A/C/Y/W-135). In the interim, contacts can receive prophylactic antibiotics with one of several effective agents including ciprofloxacin, rifampicin, minocycline, or ceftriaxone among others. Measures to limit over-crowding and to promote appropriate hygiene and sanitation are always part of the efforts to control further spread during an outbreak. All travelers to India at this time should be educated about meningococcal meningitis and immunized.
Outbreaks of hepatitis and meningococcal meningitis carry significant morbidity and mortality, and the consequences of these diseases are, to some extent, predictable. Fortunately, there have been relatively few deaths related to avian influenza to date. However, a highly pathogenic strain of avian influenza is endemic in southeast Asia. There is a persistent H5N1 reservoir in domesticated ducks and wild birds, which was responsible for the deaths of 6 persons in Hong Kong and China in 1997 and has killed over 50 people in Vietnam, Thailand, and Cambodia since 2003. Should this avian strain acquire the ability to transmit from person to person, it could spread across the world within a few months. The May 26th issue of Nature featured the topic of avian flu, our nation’s capacity to produce a vaccine, and the availability of antiviral agents as part of preparing for a potential pandemic. WHO recommends that antiviral drugs be available for early treatment and prophylaxis of "groups at highest risk of infection" and "essential workers," although these definitions are open to interpretation. Tamiflu® (oseltamivir) is a neuraminidase inhibitor that is considered the best of the 4 antiviral drugs available for such. Neuraminidase inhibitors (NAIs) do not eliminate virus from cells, but they do reduce the release of virus from infected cells by blocking this critical enzyme. They have been shown to reduce duration and severity of illness for non-pandemic influenza victims. Thus far, NAIs have encountered few problems with antiviral drug resistance. Mutations seem to be rare and seem to weaken viral potency. Older drugs, such as amantadine and rimantadine are effective, but viral resistance develops rapidly. These agents also have some disturbing side effects.
Our clinic staff has advised travelers headed to southeast Asia to attempt frequent hand washing and to have oseltamivir available for use as either treatment or prophylaxis, should they find themselves in the midst of an actual outbreak. This whole topic is a moving target. According to a recently published Science article, new genetic viral strains are emerging, and one resistant strain was found in North Vietnam. Having oseltamivir on hand may feel like a security blanket, but it could be important for some travelers who are in the wrong place at the wrong time.
- Abbott A. Avian Flu Special: What’s in the Medicine Cabinet? Nature. 2005;435:407-409.