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SCRUB TYPHUS - INDIA (04): (RAJASTHAN) MORE CASES
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Date: Thu 19 Sep 2013
Source: Outlook India [edited]
http://news.outlookindia.com/items.aspx?artid=810698


At least 13 persons have lost their lives due to a mite-borne disease since July this year [2013] in Jaipur [Rajasthan state]. Scrub typhus is caused by the bite of vectors like mites and fleas [scrub typhus is only transmitted by the bite of the larval stage (i.e., chigger) of some species of trombiculid mites (_Leptotrombidium_ species) because the other stages (nymph and adult) do not feed on vertebrate animals], living on lush green grass during the rainy season.

A total of 9 patients died of scrub typhus while 169 others were found positive and are being treated at Sawai Man Singh Hospital, Dr Raman Sharma, nodal officer and professor of medicine at the hospital, said today [19 Sep 2013].

A total of 4 scrub typhus deaths were reported at Santokhba Durlabh Memorial Hospital since July this year [2013] and 118 other positive cases were treated here, Dr G R Singhvi, hospital superintendent said.

Last year [2012], Sawai Man Singh hospital had reported 7 deaths due to the disease and 67 positive cases were treated, Dr Sharma said.

Due to incessant rains and a dense growth of weeds in agriculture fields this season, the disease got rampant in rural areas of Virat Nagar, Amber, Bassi, Chaksu, among others, Dr Sharma said.

"Undoubtedly, this year the disease of mite or flea is in the virulent form and needed a special attention to control it by the state government's medical and health department," Singhvi said.

Earlier, the disease was prevalent in hilly regions, but it migrated to planes of semi-arid regions in Rajasthan slowly, the doctor said.

Suggesting precautions against the disease, Sharma said that people, mainly women, in rural areas should avoid going to open fields with lush greenery during rainy season to relieve themselves.

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[For a discussion of scrub typhus, see moderator ML's comments in prior ProMED-mail posts Scrub typhus - India (07): (RJ) fatal, susp. 20120917.1297397 and Scrub typhus - India (12): (MH) fatal 20121109.1402125.

Jaipur, with a population of 3.1 million, is the capital and largest city of the Indian state of Rajasthan (http://en.wikipedia.org/wiki/Jaipur). A map of India showing the location of Jaipur and the state of Rajasthan is accessible at http://www.mapsofindia.com/maps/india/i ... al-map.htm. - Mod.ML

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/2Arc.]

SCRUB TYPHUS - INDIA (05): (HIMACHAL PRADESH) MORE SUSPECT CASES
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Date: Sat 21 Sep 2013
Source: Hill Post [edited]
http://hillpost.in/2013/09/manali-repor ... hus/96254/


A total of 12 cases of scrub typhus, a disease caused by the bite of an infected mite found in areas with heavy scrub vegetation, have been reported at Lady Willington Hospital Manali, disclosed Dr Philip Alex, Medical superintendent of the Hospital. A total of 12 cases were reported this year [2013], out of which 3 were referred to PGI Chandigarh and [9] others were treated here, said Dr Philips [sic].

Dr Philips said that "Since last year [2012], we have been seeing scrub typhus (presumably) in Manali [Himachal Pradesh state]. Patients present to us with fever, chills, respiratory difficulty, with or without jaundice. They may also have central nervous system symptoms, with confusion and headache". He added that the characteristic eschar alerts us to the possibility of typhus. They invariably have a low platelet count and may also have leucopenia and anemia. The respiratory distress is usually progressive when diagnosed late or when they present to us late. He further disclosed they often need ventilation and are very sick. They may also go into renal failure. The presence of jaundice and altered liver enzymes often compounds the seriousness of the disease. He said an early initiation of doxycycline medication, blood transfusion if appropriate, and steroids with early ventilation saves lives. A 4 percent hospital mortality has been described.

Dr Philips said the [bite of the larval form, called a chigger, of the] trombiculid mite, transmits _Orientia tsutsugamushi_ [the bacterial organism that causes scrub typhus]. The disease can occur a week after being bitten and the eschar by this time is a characteristic central dark necrosed area, often well circumscribed and circular in appearance. [A picture of the eschar is available at the source URL.]

He further disclosed that diagnosis is by the indirect fluorescent antibody test or PCR, or biopsy of the eschar. We have been informed that the Weil Felix test is available in the Kullu zonal hospital. The clinical and laboratory picture is pretty characteristic to allow the early initiation of therapy.

Scrub typhus is becoming a problem both to diagnose and treat in time in Himachal and other areas of North India.

He revealed that the people should take extra care while cutting the grass especially in rainy season and [if] any of the above symptoms appear they should report the matter immediately to the nearest hospital.

[Byline: Sanjay Dutta]

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[For a discussion of scrub typhus, see moderator ML's comments in prior ProMED-mail posts Scrub typhus - India (07): (RJ) fatal, susp. 20120917.1297397 and Scrub typhus - India (12): (MH) fatal 20121109.1402125.

Scrub typhus is effectively treated with doxycycline, and treatment should begin immediately upon suspicion of illness without awaiting laboratory confirmation, because death rates for untreated scrub typhus patients are up to 30 per cent (http://wwwnc.cdc.gov/eid/content/12/2/pdfs/v12-n2.pdf).

The Weil-Felix test, an agglutination test for the diagnosis of rickettsial disease, is based on the detection of antibodies to various _Proteus_ species, which contain antigens that cross-react with rickettsial antigens. This test has poor sensitivity and specificity, but continues to be used in resource-poor regions (http://www.japi.org/august2006/O-619.pdf). Because of the relatively poor sensitivity and specificity of this test, more specific assays can be used for diagnosis, including complement fixation. The gold standard for the diagnosis of scrub typhus is the indirect fluorescent antibody (IFA) assay, but the fluorescence microscopes that are required for performance of this assay are often not available in resource-poor settings where scrub typhus is endemic. Dipstick assays (http://www.ncbi.nlm.nih.gov/pubmed/12479551) have been developed that are easy to perform and do not require sophisticated equipment, making them suitable for use in rural areas where more sophisticated diagnostic tests such as the IFA may not be available.

Manali is a small hill station [towns formerly frequented by European colonials as refuges from the summer heat] in the mountains at an altitude of 2050 meters (6726 feet) of the Indian state of Himachal Pradesh near the northern end of the Kullu Valley (http://en.wikipedia.org/wiki/Manali,_Himachal_Pradesh). It is located about 270 km (168 miles) north of the state capital, Shimla (aka Simla). A map of India showing the location of Shimla and the state of Himachal Pradesh is accessible at http://www.mapsofindia.com/maps/india/i ... al-map.htm. - Mod.ML

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/3kii.]

JAPANESE ENCEPHALITIS AND OTHER- INDIA (16): (UTTAR PRADESH)
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Date: Mon 23 Sep 2013
Source: The Times of India [edited]
http://www.indianexpress.com/news/c=hil ... y/1172834/


Japanese encephalitis vaccine was given [twice] 3 years ago to a 5-year-old child, separated by a 4-month [booster]. The 1st shot, given in August 2010, was part of the child's immunization schedule, the 2nd in December of that year, in a massive campaign across Uttar Pradesh and parts of Bihar to ensure the vaccine reached all "left out" children. The boy was admitted [in 2013] to the Nehru Hospital in BRD Medical College, where he died the next day.

The boy was one of the 5 confirmed JE cases in Gorakhpur this year [2013]. The adjoining districts saw another 20 cases. Besides one deceased girl whose family had persistently refused vaccination, all the dead children had been given the protective shots.

Since 1 Jan [2013], over 1000 children have been admitted to the hospital, and 258 have died with the same classic symptoms -- high fever, convulsions, altered senses, rigidity in the limbs and nausea -- now associated with acute encephalitis syndrome (AES). Only 61 of these children were found to be JE positive.

A total of 226 admissions and 59 deaths have been from Gorakhpur, and 248 cases and 43 deaths from Kushinagar. These have been the 2 worst affected districts this year [2013]. In all of this, Gorakhpur has seen 5 JE cases and Kushinagar 8.

Until the mid-2000s, it was JE that was considered the annual mysterious killer of children and early teens in the Purvanchal belt of eastern UP and Bihar. Now, a decade later, it has been crossed off as a "minority disease" by scientists. The doubts over JE, which started arising [in] 2006 and saw some vindication in 2009, have been confirmed "to a great extent" now.

Of 1000 samples of cerebrospinal fluid (CSF) collected from children admitted between April and December last year [2012] to Gorakhpur's BRD Medical College, 100 isolates for organisms called enteroviruses (EV) -- specifically the human EV 89 and EV 76 types -- have been identified by the National Institute of Virology (NIV) field station in Gorakhpur. A 10 per cent positivity is considered a huge success for CSF samples. These viruses spread through contaminated water and can cause symptoms similar to JE and are covered under the umbrella of diseases that constitute AES. The JE virus, which causes similar symptoms and is also included under the category of AES diseases, has a completely different route of transmission: it is hosted in pigs, water birds and other livestock and is carried to humans by mosquitoes.

These findings have been heartening for scientists who were initially reluctant to accept the EV theory due to contradictory results between rectal swabs and CSF samples -- considered the more direct evidence of brain tissue -- until 2011. From 2008-11, while rectal swab samples showed a 15-44 per cent positivity for EVs, CSF samples from the same patients showed positivity rates of between 1.8 per cent and 2.3 per cent.

Dr Milind Gore, director of NIV Gorakhpur, who has headed the station's activities since 2006, said: "There were initial doubts that the virus strands which we were identifying in the rectal swabs were not traversing to the brain tissue, since we could not collate them in the CSF samples. To counter this theory, in 2012, we only tested for CSF samples and put them through rigorous testing, and we have managed to identify 100 isolates of enteroviruses. For us, it's a huge boost, since it's coming from hard primary evidence."

The 1st doubts about JE started after deaths continued despite exhaustive mass immunization campaigns, and lab results provided no concrete answers. In 2006, despite JE vaccinations, 700-800 seizures were reported, and over 150 children died. Most of these children had received JE vaccination. The mystery remains to be fully explained.

This year [2013], 6 per cent of cases are JE positive, and about 10-15 per cent EV, which leaves the vast majority of cases still undiagnosed. "We are trying to identify the causative agents in all samples, but there are other factors that need to be considered. The causative agent is the most active in the CSF samples only within the 1st 2-3 days of onset. A majority of children are coming to us late, and hence we are losing out on identifying the pathogens there," said Dr K P Kushwaha, principal and head of the department of paediatrics at BRD Medical College.

Unlike bacteria, viruses need active cell lines to multiply for scientists to examine them. "Earlier, we were using only one such cell line; now we are hoping that more viruses will multiply in our laboratories. We have identified isolated cases of measles and herpes viruses but not in considerable numbers. We are trying to lay our hands on something more, but so far, we have not been successful," Dr Gore said. He adds that even in the best diagnosed international outbreak situations, only about 50 per cent of cases are actually diagnosed. "Considering that, we can say EVs have solved at least some of the mystery, though not all of it."

As scientists and doctors struggle to get a handle on the 3-decade-old disease, many complain that the clinical and administrative management of the outbreaks remain flawed.

In Gorakhpur, the hub of the management of the disease, representatives of the only medical college in the area and district authorities cannot agree on several things.

The hundreds of AES cases that are finding their way into government records are coming only from the one medical college and district hospitals in the area. The disease is still to be officially declared a notifiable disease like other common viral diseases like dengue, where every case has to be reported.

Said Dr Kushwaha: "All the patients who are coming to us are referrals from private hospitals, and by the time they are coming here, they are already so critical that in the majority of the cases, it is too late for us to do anything. Why can't private hospitals report these cases early?" He said this year [2013], only 10 per cent of patients are direct entrants, the rest being referrals from private centres. "The government is losing out on precious data due to this mismanagement."

But district health authorities say there is no monitoring of medical college treatment records, and inflated figures are presented, the definition of AES itself being flawed.

CMO [Chief Medical Officer] of Gorakhpur Dr M P Singh said, "The unwritten protocol the medical college seems to be following is that any patient who comes with the symptoms of fever, nausea and altered sensorium is declared AES, without waiting for laboratory results. Later, if any of these patients tests positive for malaria, typhoid or meningitis, the case records are not changed. They just put it down as AES with any of these other diseases. This is an absurd situation, where eventually you are diagnosing the disease, but still declaring it as AES."

Dr Singh said that last year [2012], of the 8 cases that the medical college declared JE positive, repeat tests on 6 showed only 3 to be actually positive. Cases are being reported round the year; 18 cases came in April [2013], many of them children under the age of one year. "How can a child below the age of one have AES which they say is from EVs? A child that young only has mother's milk, so what is the source of contaminated water," he asked. He said district health authorities had, after "umpteen reminders," managed to access treatment records of deceased patients this year [2013] and were studying them.

[Byline: Pritha Chatterjee]

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[The cases of AES continue to be puzzling. The above report indicates that only a small proportion are due to JEV infections. The occurrence of JEV infections in previously vaccinated children may be due to a decline in protective immunity in individuals who received killed virus vaccine in the more distant past or lack of vaccine potency.

The report does not indicate whether the vaccine was killed or the live attenuated one that would provide longer protection. The massive JEV vaccination campaigns in Uttar Pradesh and Behar states has resulted in a significant reduction in cases due to infection with that virus. As implied in many reports in recent years, apparently, many of the AES cases are due to enterovirus infection. Detection of theses viruses in CSF is more convincing evidence of etiological cause than isolation only from rectal swabs, which may indicate intestinal infections without invasion of the CNS.

The cause of the majority of the AES cases remains undiagnosed, and one hopes that the scientists involved in attempting to determine the etiologies of these undiagnosed cases will continue to find out what is going on so that scientifically sound preventive measures may be devised and implemented. Although JEV outbreaks may continue to be prevented through vaccination, preventing enterovirus infections, in the absence of vaccines, requires improvement of sanitation infrastructure to assure adequate human waste disposal and uncontaminated potable water supplies, a very costly effort.

A HealthMap/ProMED-mail map of India showing the location of Uttar Pradesh state can be accessed at http://healthmap.org/r/3h8J. - Mod.TY]

UNDIAGNOSED ILLNESS, CHILDREN - INDIA (02): (BEHAR) REQUEST FOR INFORMATION
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Date: Sun 22 Sep 2013
Source: The Indian Express [summarized & edited]
http://www.indianexpress.com/news/whats ... -/1172414/


Every year, 3 months before the monsoon arrives, 900 and 1200 children between the ages of 2-5 are afflicted with a mystery illness. It starts with lethargy and a light fever but shows the 1st signs of worsening towards the morning. Many of the children are dead before they can reach a hospital.

The district saw 44 deaths in 2011, 121 in 2012, and 39 this year [2013]. Bihar Health Secretary Sanjay Kumar admits they don't know the reason for this decline. "The cases have dropped this year " he says. "We don't know what we have done right. Right now, we are all groping in the dark."

The latest to draw a blank is a team from the Centers for Disease Control (CDC) in Atlanta, USA, which was roped in by the National Centre for Disease Control (NCDC) to test samples from this year [2013]. A report submitted to the state and Centre by the NCDC in the 1st week of September 2013 said the results have been negative for several known viruses, including Japanese encephalitis (JE), enteroviruses, West Nile virus, dengue, Chandipura and Nipah. In fact, after testing blood samples, rectal swabs and cereobrospinal fluids of patients, as well as brain tissues collected from deceased patients, researchers have not been able to isolate a single strand of a virus. The question now staring them in the face is: is it even a virus?

When the 1st locally tested samples tested negative for JE virus, tests were repeated by multiple agencies last year [2012] and again this year [2013], including the National Institute of Virology in Pune, the NCDC in Delhi, units of the Indian Council of Medical Research such as Patna's Rajiv Memorial Research Institute (RMRI), Delhi's Safdarjung Hospital and Lady Hardinge Medical College, and a team from the CDC, Atlanta. However, all ruled out JE [virus infections].

"Since the disease was not found in patients, we decided to look for it in the vectors, mosquitoes which carry the JE virus from hosts such as pigs, water birds or other livestock to humans," says Dr Pradip Das, director of RMRI. However, no known vector of JE was found on the scene. "Now, we have eliminated the theory of JE [virus] completely," Dr Das says. The RMRI and NCDC conducted similar tests, but to no avail.

Admits Dr Das: "There are several characteristics which make this disease different. JE is a post-monsoon disease, while all the cases here are seen before the rains.

There are other differences: in Gorakhpur, deaths occur within 48-72 hours of convulsions, while in Muzaffarpur, mortality strikes within a few hours of the 1st convulsions.

While the treatment is symptomatic, with doctors managing convulsions with anti-convulsant drugs like Diazepam and fever with paracetamol, in Gorakhpur, other symptoms like internal bleeding, respiratory failure, kidney failure and compromised heart functions assume more importance, Dr Kushwaha adds.

The CDC-NCDC team that went to Muzaffarpur this year [2013] included one of the world's only neurologist-epidemiologists, Dr James J Sejvar, from Atlanta. He was called in as clinicians started looking for more patterns for clues, and noticed increasing neurological symptoms: nausea, seizures, unconsciousness and, in a few, altered brain function. Data from this year shows that 98 per cent of the patients in Muzaffarpur reported generalised seizures, and 85 per cent had loss of consciousness, with 40 per cent having documented fever.

More specialists were brought in, and new investigations to test brain functions were introduced this year [2013]. Samples of cerebrospinal fluid -- the fluid circulating in the spinal cord -- were collected through lumbar puncture, and CT scans were done on all children, funded by the state government.

Other national agencies in previous years had collected their own samples, including 2 samples of brain tissue from deceased patients taken by the NIV in Pune last year [2012]. The results were baffling. All cerebrospinal samples were found to be clear, while the brain tissue held no answers either.

The CDC Atlanta examined MRIs of 10 children and reported no signs of inflammation in the brain tissue, according to preliminary findings published in an NCDC quarterly newsletter. "In fact, there were no signs of any infection at all in the CSF. This throws up a huge question. We don't know if any [infectious] pathogen is involved at all. That could mean our search for viruses as possible causative factors has been in the wrong direction," Dr Das says.

"Liver function tests and kidney function tests on patients to test for toxins have all been negative, with no evidence of absorption of any poisonous agent from fruit or otherwise," Dr Singh says.

Scientists then turned to the environment for clues, looking for triggers that came annually. Heat was picked as one such factor. Doctors at the Sri Krishna Medical College (SKMC) in Muzaffarpur, which has treated the 2nd highest number of cases this year [2013], have published 2 articles -- notably the only peer-reviewed medical publications from the area so far -- saying that high temperatures and peak humidity could be leading to heat strokes, which if untreated for long periods may be contributing to the exaggerated symptoms.

"In India, since the JE virus is the most recognised common cause of encephalitis, especially in an outbreak, physicians and public health and administrative officials have a tendency to attribute all the epidemics of febrile convulsive disorder in children to this virus," the authors state in the July 2013 issue of the Annals of Tropical Medicine and Public Health.

Noting that "no infective organism or its antigen or antibody was found in any of the samples tested," the authors say that the "overall picture of these cases was suggestive of heat stroke." Other clinicians, however, discount this theory, stating that episodes of heat strokes cannot be seen in the hours of the morning [well before dawn], the time when most children take a turn for the worse.

The National Institute of Occupational Health in Ahmedabad is already conducting tests to study the levels of an enzyme known as cholinesterase that is necessary to return neurons to their resting phases after activation.

The children are all malnourished.

--
Communicated by:
Ronan Kelly
Senior Moderator, FluTrackers
<ronankelly@comcast.net>

[It appears that infectious agents have been excluded in the diagnosis of these cases. This report does not indicate which environmental toxicants have been tested for, with negative results. Similarly, there is some doubt about heat stroke as the causative factor in these cases. ProMED would appreciate receiving additional reports relating to the causative factors involved in these unfortunate cases.

Maps of India and Bihar state can be seen at http://www.mapsofindia.com/maps/india/i ... al-map.htm and http://healthmap.org/r/77fN. - Mod.TY]

DENGUE/DHF UPDATE (77): ASIA
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A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org

In this update:
India:
- Nalanda district, Behar state
- Delhi
- Ahmedabad, Gujarat state
- Pune, Maharashtra state
- Mumbai, Maharashtra state
- Odisha state
- Lucknow
Pakistan:
- Punjab province
- Swat district, Khyber Pakhtunkhwa province

******
- India:
- Nalanda district, Behar state. 20 Sep 2013. Dengue 100 cases; Increasing.
http://timesofindia.indiatimes.com/city ... 776645.cms

[Maps of India can be seen at
http://www.mapsofindia.com/maps/india/i ... al-map.htm and
http://healthmap.org/r/1pSH. - Mod.TY]

- Delhi. 20 Sep 2013. Dengue (conf.) 888 cases, 400 cases on 20 Sep 2013.
http://www.indianexpress.com/news/400-d ... h/1171556/

- Ahmedabad, Gujarat state. 17 Sep 2013. Dengue 1-15 Sep 2013, 214 cases.
http://daily.bhaskar.com/article/GUJ-AH ... 2-NOR.html

- Pune, Maharashtra state. 15 Sep 2013. Dengue 336 cases.
http://articles.timesofindia.indiatimes ... orporation

- Mumbai, Maharashtra state. 18 Sep 2013; Dengue past 2 weeks 74 cases, August 2013, 87 cases; Deaths 5.
http://timesofindia.indiatimes.com/city ... 673153.cms

- Odisha state. 21 Sep 2013. Dengue (conf.) 4321 cases; Deaths 5; Most affected: Cuttack 1220 cases, Khordha 827 cases, Jaipur 605 cases, Angul 527 cases.
http://odishatoday.com/viewnews.php?news_id=5551

- Lucknow, Uttar Pradesh state. 22 Sep 2013. Dengue 169 cases; Increasing.
http://timesofindia.indiatimes.com/city ... 874839.cms

- Pakistan:
- Punjab province. 19 Sep 2013. Dengue 176 cases; 20 new cases in 24 hours; Increasing.
http://www.brecorder.com/pakistan/gener ... 36751.html

[Maps of Pakistan can be accessed at http://www.ezilon.com/maps/images/asia/ ... kistan.gif and http://healthmap.org/r/1kc-. - Mod.TY]

- Swat district, Khyber Pakhtunkhwa province. 19 Sep 2013. Dengue 4934 cases; Deaths 12; Increasing with epidemic declared.
http://tribune.com.pk/story/606416/deng ... d-in-swat/

JAPANESE ENCEPHALITIS AND OTHER - INDIA (17): (UTTAR PRADESH)
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Date: Thu 19 Sep 2013
Source: The Times of India [edited]
http://articles.timesofindia.indiatimes ... -hospitals


With the death of 9 children on Thursday [19 Sep 2013], a total of 15 kids have succumbed to encephalitis during the past 3 days here.

With this, the toll in the region this year [2013] due to the disease has risen to 271, health officials said.

While 6 children died on Tuesday [14 Sep 2013], 9 others succumbed today [19 Sep 2013], they said, adding that the victims belonged to Gorakhpur and its adjoining districts of Kushinagar, Siddharthanagar and Sant Kabirnagar.

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[The etiology of these encephalitis cases is not stated. In previous reports, some have been diagnosed as due to Japanese encephalitis infections and other associated with contaminated water, suggesting enterovirus infections. The massive JEV [Japanese encephalitis virus] vaccination campaigns in Uttar Pradesh and Behar states has resulted in a significant reduction in cases due to infection with that virus. Detection of enteroviruses in CSF [cerebrospinal fluid] has provided convincing evidence of their involvement in previously reported cases.

The cause of the majority of the AES [acute encephalitis syndrome] cases remains undiagnosed, and one hopes that the scientists involved in attempting to determine the etiologies of these undiagnosed cases will continue to find out what is going on so that scientifically sound preventive measures may be devised and implemented. Although JEV outbreaks may continue to be prevented through vaccination, preventing enterovirus infections, in the absence of vaccines, requires improvement of sanitation infrastructure to assure adequate human waste disposal and uncontaminated potable water supplies, a very costly effort.

A HealthMap/ProMED-mail map of India showing the location of Uttar Pradesh state can be accessed at http://healthmap.org/r/3h8J. - Mod.TY]

CHOLERA, DIARRHEA AND DYSENTERY UPDATE (50): IRAN
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Date: Wed 25 Sep 2013
Source: Trend [edited]
http://en.trend.az/regions/iran/2194161.html


A total of 4 people have become infected with cholera in Iran's capital city of Tehran, deputy Minister of Health and Medical Education, Ali Akbar Sayyari said, Fars news agency reported.

Cholera infection has spread to 10 Provinces in Iran, Sayyari said, adding that some 174 people were infected across the country. Sayyari went on to note that the [incidence of] infection is rising continuously.

The official of the Center for Disease Management of the Ministry of Health and Medical Education, Mohammad Nabavi, announced on 21 Sep 2013 that some 170 cholera infection cases have been registered in Iran, adding that 144, 1 and 25 infected people are Afghanistan, Pakistan and Iran citizens, respectively.

On 4 Sep 2013, the head of the Center for Disease Management of the Ministry of Health and Medical Education Mohammad Mehdi Gouya said that the infected persons are illegal migrants from bordering countries to the east. Gouya added that cases of infection with cholera were registered in the provinces of Sistan, Balujistan and Kerman, and those under the threat of getting infected were put under supervision.

According to information from Iranian media outlets, cholera infection cases in Iran have been being registered for nearly 45 years; in 2012, some 15 such cases were registered.

--
Communicated by:
ProMED-mail
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[A total of 64 cases were reported 3 weeks ago, so the number is substantially higher at this point. It appears that the infection has spread from the areas adjacent to Iran in Afghanistan and Pakistan to the capital city of Tehran. - Mod.LL

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1Cfu.]

DENGUE/DHF UPDATE (80): ASIA
*****************************************
A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org

In this update:
India
- Delhi
- Rohini district, northwestern Delhi
- Jaipur, Rajasthan state
- Ranchi, Jharkhand state
- Patiala district, Punjab state
- Uttar Pradesh state
Pakistan
- Sindh province
- Swat district, Khyber Pakhtunkhwa province

*****

India
- Delhi. 27 Sep 2013. Dengue 1729 cases; deaths (conf.) 3, (susp.) 7.
http://www.ndtv.com/article/cities/rapi ... lhi-424767

[Maps of India can be seen at http://www.mapsofindia.com/maps/india/i ... al-map.htm and http://healthmap.org/r/1pSH. - Mod.TY]

- Rohini district, northwestern Delhi. 28 Sep 2013. Dengue 397 cases; deaths (susp.) 3.
http://www.indianexpress.com/news/dengu ... r/1175345/

- Jaipur, Rajasthan state. 24 Sep 2013. Dengue 569 cases; deaths 1. Increasing.
http://articles.timesofindia.indiatimes ... ment-cases

- Ranchi, Jharkhand state. 27 Sep 2013. Dengue 1 Aug-23 Sep 2013, 25 cases; deaths 2.
http://timesofindia.indiatimes.com/city ... 118779.cms

- Patiala district, Punjab state. 23 Sep 2013. Dengue (conf.) 30 cases. Increasing rapidly.
http://www.hindustantimes.com/Punjab/Pa ... 26258.aspx

- Uttar Pradesh state. 28 Sep 2013. Dengue 647 cases. Municipalities most affected: Lucknow 213 cases with 2 deaths, Kanpur 139 cases, Bareilly 74 cases.
http://www.indianexpress.com/news/dengu ... d/1175533/

Pakistan
- Sindh province. 28 Sep 2013. Dengue 1634 cases. Municipality most affected: Karachi 1425 cases.
http://www.thenews.com.pk/Todays-News-4 ... ed-in-city

[Maps of Pakistan can be accessed at http://www.ezilon.com/maps/images/asia/ ... kistan.gif and http://healthmap.org/r/1kc. - Mod.TY]

- Swat district, Khyber Pakhtunkhwa province. 28 Sep 2013. Dengue 6667 cases.
http://tribune.com.pk/story/610353/batt ... ouches-40/

[A 26 Sep 2013 report indicated that there were 23 deaths in the past month (http://medicalxpress.com/news/2013-09-d ... istan.html). - Mod.TY]

LEPROSY - INDIA (02): (GUJARAT) INCREASED INCIDENCE
***************************************************
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Date: Thu 3 Oct 2013
Source: The Indian Express [edited]
http://www.indianexpress.com/news/lepro ... t/1177663/


The number of leprosy patients in Gujarat has increased by 17 percent during the last couple of years. Compared to the 7500-odd patients in 2011-12, there were over 9000 persons affected by the disease in the state during the 2012-13 fiscal year, stated the health minister in a written reply to a question posed by Congress MLA [Member of Legislative Assembly] Tejashree Patel.

While the districts of south Gujarat, like Surat (1339), Vadodara (1146), and Valsad (1009) have the maximum number of leprosy patients, the highest percentage increase in patients was seen in the predominantly tribal district of the Dangs where the number of patients more than doubled from 143 in 2011-12 to 327 patients in 2012-13. Similar was the case in the adjoining district of Tapi where the numbers swelled to 786 in 2012-13 compared to 493 patients a year ago.

The number of such patients has been on a steady rise in the state since 2010-11, the figures provided by the state government reveal. The administration also provides a monthly assistance of Rs 800 [about USD 13] to these patients. This aid is continued till they are cured, the reply added.

--
Communicated by:
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[Leprosy is a chronic disease caused by a bacillus, _Mycobacterium leprae_ (http://www.who.int/mediacentre/factsheets/fs101/en/). _M. leprae_ multiplies very slowly and the incubation period of the disease is about 5 years, but symptoms can take as long as 20 years to appear. Although leprosy is not highly contagious, because patients with the lepromatous form of leprosy excrete enormous numbers of leprosy bacilli in their nasal secretions (that is, are multibacillary), a patient with untreated lepromatous leprosy poses increased risk for transmission of the infection to close, long-term contacts, such as household members. As the organism is also present in skin lesions in these patients, skin contact is thought to be another mode of spread. Because the organisms that are shed by lepromatous patients can persist on surfaces in the environment, fomites are also a potential source of infection. Casual and short-term contact does not seem to pose a risk for spread of the disease.

Although India achieved what WHO refers to as "the elimination of leprosy as a public health problem" (that is, a prevalence of less than one case per 10 000 population) in December 2005 (http://209.61.208.233/en/Section10/Section20_16172.htm), leprosy has not been eradicated in India. In 2012 India contributed 58 percent of new cases detected worldwide (http://www.who.int/wer/2013/wer8835.pdf). In fact, India was among countries that reported more new cases in 2012 (134 752 new cases) than in the previous year (http://www.who.int/wer/2013/wer8835.pdf). In 2012, 50 percent of new cases in India had multibacillary leprosy, which is an indication of the proportion of new cases with contagious disease in the community; 10 percent of new cases occurred in children, which is an indication of ongoing disease transmission; and 0.5 percent of new cases of leprosy had chronic deformities and disability, which reflects problems in case finding (http://www.who.int/wer/2013/wer8835.pdf).

A discussion of the problem of leprosy in India appeared last month (12 Sep 2013) in the New York Times (http://india.blogs.nytimes.com/2013/09/ ... t-leprosy/). The article cites a study published in 2009 "showing that [the number of] those affected by the disease in parts of rural and urban Maharashtra was 3 to 9 times more than the official figures" and "a third of those afflicted were children." The article reports, "In 2011, the WHO warned India that the disease was spreading, and that same year, the government's leprosy eradication department began active detection surveillance in high endemic areas. Instead of relying on voluntary reports, government officials initiated door-to-door surveys. These measures account for the rise in new cases seen in the government statistics, said Dr V.V. Pai, director of the Bombay Leprosy Program." This article reports, "In the fiscal year that ended on 31 Mar [2013], the [Indian] government's National Leprosy Eradication Programme recorded an annual new case detection rate of 10.78 for a population of 100 000 people -- an increase of 4.15 percent from the previous fiscal year."

In addition to case detection, the strategy to control leprosy is antimicrobial therapy of the contagious human reservoir. Leprosy is a curable disease with multidrug therapy (MDT) that is provided free of cost to all affected people worldwide (http://www.novartisfoundation.org/page/ ... Item=44.19). Patients with paucibacillary leprosy treated with rifampin and dapsone are cured within 6 months of therapy and multibacillary patients treated with rifampin, dapsone, and clofazimine are cured within 12 months of therapy.

However, a recent article in The Hindu (13 Jan 2013) quotes V Narasappa of the National Federation of Leprosy Cured People in India, who says that, "People in the rural areas do not even know MDT is available free and, importantly, they keep away from health facilities for fear of stigma" (http://www.thehindu.com/news/national/l ... 358263.ece). This article also says that only 69.5 percent people were able to complete their treatment in Delhi, 66.7 percent in Tripura, 67.7 in Meghalaya, and 32.4 percent in Himachal Pradesh (http://www.thehindu.com/news/national/l ... 358263.ece).

A HealthMap/ProMED-mail interactive map of India can be seen at http://healthmap.org/r/27Ix. The state of Gujarat is located on the Arabian Sea in northwestern India (http://www.mapsofindia.com/maps/india/i ... al-map.htm). A map of Gujarat, on which the cities of Surat, Vadodara, and Valsad can be found, is accessible at http://www.mapsofindia.com/maps/gujarat ... troads.htm. - Mod.ML]

LEPROSY - INDIA (03): (GUJARAT) INCREASED INCIDENCE, COMMENT
************************************************************
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Date: Sat 5 Oct 2013
From: T Jacob John <tjacobjohn@yahoo.co.in> [edited]


Re: ProMED-mail post Leprosy - India (02): (GJ) increased incidence
-------------------------------------------------------------------
It is disturbing, but not unanticipated, that leprosy continues to be prevalent and is increasing in many parts of India. Had the transmission been exclusively human-to-human (anthroponotic), one would expect the disease to disappear or at least continue to decline in a downward spiral when the prevalent cases are reduced to less than 1 per 10 000 population (elimination by definition) by multi-drug therapy of all detected cases. While it is true that leprosy bacilli are amplified in humans, there is no good evidence that transmission is anthroponotic.

There is a little-known alternative possibility of the organism amplifying in soil as saprophytes and getting transmitted to humans by soil contact (1,2). Wherever leprosy was known to occur, like in the USA, Japan and Scandinavia, occasionally new cases do appear de novo supporting the soil-transmission hypothesis. Armadillos and humans in the southern USA probably get infected from soil, and the interpretation that there alone leprosy is zoonotic (vertebrate-to-human transmitted) is unconvincing.

The bottom line is that the term "elimination" is misleading; complacency leads to misclassification and delays in diagnosis of new cases; leprosy control programs should not be wound up after reaching "elimination by definition".

References:
1. Blake LA et al. Environmental non-human source of leprosy. Clin Infect Dis 1987; 9: 562-577.
2. Lavania M et al. Detection of viable _Mycobacterium leprae_ in soil samples: Insights into possible transmission of leprosy. Infect Genetics and Evol 2008; 6: 627-631.

--
T Jacob John
Retired Professor of Clinical Microbiology and Virology
Christian Medical College
Vellore, India
<tjacobjohn@yahoo.co.in>

[ProMED-mail thanks Dr. John for his contribution that emphasizes the possibility of an environmental source for human leprosy. _Mycobacterium leprae_ has been shown to survive outside the human body for varying periods of time under different environmental conditions that occur in regions where the disease is endemic (Desikan KV, Sreevatsa. Extended studies on the viability of _Mycobacterium leprae_ outside the human body. Leprosy Review 1995; 66(4):287-295. Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/8637382). In this study, viability was verified by multiplication in the footpads of normal mice. _M. leprae_ survived after drying in the shade for up to 5 months and on wet soil for 46 days.

DNA and RNA from _M. leprae_ has been found in soil, but is found mostly in soil samples from areas where patients with leprosy were living. In addition, _M. leprae_ from the environment and the patients has been found to exhibit the same genotype (Turankar RP, Lavania M, Singh M, Siva Sai KS, Jadhav RS. Dynamics of _Mycobacterium leprae_ transmission in environmental context: deciphering the role of environment as a potential reservoir. Infect Genet Evol. 2012 Jan;12(1):121-6. Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/22101333). Did some of the patients acquire their infection from contact with soil, or did the patients incidentally contaminate the soil?

The following is the abstract from Dr. John's reference 2:

"Leprosy has ceased to be a public health problem world wide, after the successful implementation of effective chemotherapy (MDT) [multidrug therapy] and use of control measures. However, new cases of leprosy continue to occur. _Mycobacterium leprae_ cannot be grown in any acceptable culture medium and besides the wild armadillos, there is no known animal reservoir for leprosy. The transmission of leprosy is believed to be due to a large extent by droplet discharge of bacilli through nose and mouth and to a lesser extent by direct contact of susceptible host with a patient for long duration. The exact role of the environment in the transmission dynamics is still speculative. In the present study, we have tried to detect viable _M. leprae_ from soil samples in endemic areas by using molecular methods. Eighty soil samples were collected from villages of this area, DNA and RNA of _M. leprae_ extracted and identified using specific _M. leprae_ primers. PCR amplification was done and real-time RT-PCR was used to detect viable _M. leprae_. DNA targeting the 16S region of _M. leprae_ was detected in 37.5 percent, whereas _M. leprae_ RNA targeting the same region was detected in 35 percent of these samples. Of the total 80 samples, 40 were collected from residential areas of leprosy patients whereas 40 samples were from no-patient areas. 55 percent positivity for 16S rRNA of M. leprae was observed from the "patient" area in comparison to 15 percent positivity from the "no-patient" area (p less than 0.001) [probability very significant]. This study thus provides valuable information of the presence of viable _M. leprae_ in soil specimens, which would be of use in investigating the transmission dynamics in leprosy." - Mod.ML

Photo of leper in Norway, where Hansen identified the leprosy bacillus in 1873 (hence Hansen's disease):
http://upload.wikimedia.org/wikipedia/c ... eprosy.jpg
- Mod.JW

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1pSH.]

DENGUE/DHF UPDATE (82): ASIA
****************************
A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
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In this update:
Pakistan
- Rawalpindi, Punjab province
- Ludhiana and nearby districts, Punjab province
- Swat district, Khyber Pakhtunkhwa province
- Sindh province
India
- Various localities
- Jaipur, Rajasthan state
- Samba district, Jammu and Kashmir state

******
Pakistan
- Rawalpindi, Punjab province. 6 Oct 2013. Dengue 73 cases. Increasing.
http://www.dailytimes.com.pk/default.as ... 013_pg11_4

[Maps of Pakistan can be accessed at http://www.ezilon.com/maps/images/asia/ ... kistan.gif and http://healthmap.org/r/1iGJ. - Mod.TY]

- Ludhiana and nearby districts, Punjab province. 29 Sep 2013. Dengue 191 cases.
http://www.hindustantimes.com/Punjab/Lu ... 28731.aspx

- Swat district, Khyber Pakhtunkhwa province. 2 Oct 2013. Dengue cases currently under treatment 233, 70 new cases.
http://www.dailytimes.com.pk/default.as ... 2013_pg7_6

- Sindh province. 1 Oct 2013. Dengue 1783 cases. Municipality most affected: Karachi 1551 cases with 12 deaths. Increasing.
http://www.thefrontierpost.com/article/45065/

India
- Various localities. 2 Oct 2013. Dengue in various localities: Delhi 1729 cases. Uttar Pradesh state 650 cases, Punjab 340 cases, Haryana state 383 cases.
http://www.indiatvnews.com/news/india/- ... 28679.html

[A 3 Oct 2013 report indicates over 2500 dengue cases in Delhi and 433 in just the 1-3 Oct 2013 period. http://timesofindia.indiatimes.com/city ... 475892.cms

Maps of India can be seen at http://www.mapsofindia.com/maps/india/i ... al-map.htm and http://healthmap.org/r/1pSH. - Mod.TY]

- Jaipur, Rajasthan state. 30 Sep 2013. Dengue 105 patients hospitalized in one day, with 1 death.
http://www.dnaindia.com/india/1895986/r ... -tentacles

- Samba district of Jammu and Kashmir state. 30 Sep 2013. Dengue [exact case dates uncertain] 65 cases; deaths 1.
http://news.outlookindia.com/items.aspx?artid=812006

JAPANESE ENCEPHALITIS AND OTHER - INDIA (18): (UTTAR PRADESH)
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Date: Wed 9 Oct 2013
Source: BBC News [edited]
http://www.bbc.co.uk/news/world-asia-india-24440141


The Press Trust of India on Tuesday [8 Oct 2013] reported that in the past few days, 15 children have died in a fresh outbreak of viral encephalitis in India's Uttar Pradesh state, taking this year's [2013] toll to 358. Doctors say affected patients come from between 10 and 12 districts in the region, and are mostly the rural poor. The disease usually occurs during the monsoon season in Gorakhpur and adjoining areas and children are the worst affected.

More than 200 patients are still being treated at government hospitals.

At least 6500 children have died of encephalitis in the region since the 1st case was detected in 1978.

Gorakhpur and adjoining districts, which border Nepal in the foothills of the Himalayas, are low-lying and prone to floods, providing a breeding ground for mosquitoes which commonly transmit the virus.

Until 2005, doctors say that the majority of deaths were caused by Japanese encephalitis, a mosquito-borne virus. But in the past 7 years, children have been dying of other forms of viral encephalitis, the exact cause of which is unclear.

The diseases cause headaches and vomiting and can lead to coma, brain dysfunction, seizure, and inflammation of the heart and kidney.

Doctors say children between the age of 6 months and 15 years are the worst affected. A 5th of the children who survive have to live with neurological weaknesses, doctors say.

The government says it has tried to check the regular outbreak of encephalitis in the region. Last week [week of 1 Oct 2013], India launched a vaccine [campaign] against Japanese encephalitis as part of a national programme to fight the virus.

"Beginning with the 1st report in 1955 in Tamil Nadu state, the Japanese encephalitis virus has now spread to more than 171 districts in 19 states," Health Minister Ghulam Nabi Azad said at the launch of the vaccine. In 2005, a virulent outbreak of Japanese encephalitis in Gorakhpur killed 1000 people, mostly children. This was the worst outbreak since 1978.

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Communicated by:
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[As with previous reports of viral encephalitis in Uttar Pradesh state, there is no indication of the proportion of these cases due to Japanese encephalitis virus infections or to other, undetermined causes. In previous reports, some have been diagnosed as due to Japanese encephalitis infections and other associated with contaminated water, suggesting enterovirus infections. The massive Japanese encephalitis virus vaccination campaigns in Uttar Pradesh and Behar states has resulted in a significant reduction in cases due to infection with that virus.

The cause of the majority of the AES (acute encephalitis syndrome) cases remains undiagnosed, and one hopes that the scientists involved in attempting to determine the etiologies of these undiagnosed cases will continue to find out what is going on, so that scientifically sound preventive measures may be devised and implemented. Although JEV outbreaks may continue to be prevented through vaccination, preventing enterovirus infections, in the absence of vaccines, requires improvement of sanitation infrastructure to assure adequate human waste disposal and uncontaminated potable water supplies, a very costly effort.

A HealthMap/ProMED-mail map of India showing the location of Uttar Pradesh state can be accessed at http://healthmap.org/r/1-k3. - Mod.TY]

JAPANESE ENCEPHALITIS AND OTHER - INDIA (19): (UTTAR PRADESH) COMMENT, REQUEST FOR INFORMATION
**********************************************************************************************
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Date: Wed 9 Oct 2013
From: Lloyd Olson <lolson@cmh.edu> [edited]


It is important to remember that not all acute central nervous syndromes in children are inflammatory or infectious. A number of years ago an acute encephalopathy syndrome was endemic in many tropical countries. In India it was referred to as "Jamshedphur fever" (Br med J 1955: 2: 1298-308) with subsequent reports noting its similarity to Reye syndrome -- a syndrome of acute cerebral edema with microvesicular fat deposits in the viscera (Indian J Med Res 1969: 57: 1865-71; Clin Pediatr 1972; 11: 128-30). Similar syndromes were noted in Indonesia, Brazil, and East Africa.

In the province of Udorn, northeastern Thailand, of 3000 children admitted to the provincial hospital during 1969, we observed at least 83 children with the clinical features of acute encephalopathy (Pediatrics 1971; 47: 707-16). 46 died, all within 72 hours of the onset of symptoms. The disease was characterized by the sudden onset of fever, vomiting, and headaches progressing to seizures and coma. Almost all children were less than 6 years of age and the majority of cases occurred during the late rainy season (August to October). This area is also endemic for JEV and without autopsy and laboratory data it would have been easy to confuse this syndrome with acute infection.

The histopathologic features from autopsies conducted on 40 children has been reported (Amer J Clin Path 1971; 56: 558-71) and were characterized by those findings associated with acute Reye syndrome. The latter report also details the evidence pointing to acute aflatoxin poisoning as the etiology of the condition in Udorn.

Subsequent private communication indicated to me that by the 1980s "Udorn encephalopathy" had disappeared from northeastern Thailand, for unknown reasons. It would be of interest to learn what the subsequent experience in India was with Jamshedphur fever, if known. In any event, the syndrome being reported as AES in India is not inconsistent with an acute encephalopathy and should be explored for this possibility.

Finally, note is made of a syndrome reported from Viet Nam referred to as "Litchi-associated" encephalitis (Emerg Infect Dis. 2012; 18: 1817-24). It is described as a seasonal, acute syndrome in children during the rainy season with a 25 per cent mortality and cerebral edema as an important component. It would be of obvious interest to know whether autopsy data have found changes consistent with those of Reye syndrome.

--
Lloyd C Olson, MD (retired)
The Children's Mercy Hospital
Kansas City Missouri
USA
<lolson@cmh.edu>

[ProMED-mail thanks Dr Olson for his comments and suggestions. Clearly, the list of possible etiological agents and factors for cases of acute encephalitis syndrome (AES) should be expanded.

ProMED-mail would appreciate the response to Dr Olson's question -- what has been the experience in India with Jamshedphur fever? Have AES cases in Uttar Pradesh been tested for acute aflatoxin poisoning?

A HealthMap/ProMED-mail map of India showing the location of Uttar Pradesh state can be accessed at http://healthmap.org/r/1-k3. - Mod.TY]

UNDIAGNOSED DEATHS - INDIA: (GUJARAT) REQUEST FOR INFORMATION
*************************************************************
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Date: Wed 9 Oct 2013
Source: The Times of India [edited]
http://articles.timesofindia.indiatimes ... tospirosis


One more patient suffering from fever died in the Kadarsha ni Naal area of the Walled City [Surat, Gujarat state] on Wednesday [9 Oct 2013]. A total of 4 deaths in the last 2 days resulting from a mysterious illness have led to a scare in the area with the locals suspecting outbreak of leptospirosis. However, health department officials of Surat Municipal Corporation (SMC) maintain that deaths are not due to leptospirosis or dengue fever. A total of 3 samples have been [sent] to National Institute of Virology (NIV) at Pune to ascertain the cause of deaths.

A 22-year-old man died in the area on Wednesday after 4 days of acute fever, cough and having thrown up blood in Maskati Hospital. A social worker in the area said, "People are scared, and if the deaths don't stop they might flee the place." Dr KI Khatri, health officer of central zone of SMC said, "The cause of death is shown as acute viral hemorrhagic fever by the hospital authorities. All the deceased have shown the same signs of high fever, cough, cold, and have vomited blood."

"Once the sample reports come from NIV, we would be able to treat the people better," said Dr Hemant Desai, chief medical officer of SMC. At present there are 7 patients from the area undergoing treatment in different hospitals. The locals claim that the number is 15. The SMC is carrying out a door-to-door survey and people showing symptoms of fever are being given treatment. Officials claim that the people are suffering from some kind of viral infection. They suspect that it might have spread to many people in the area that was badly affected during the recent floods. The health department has undertaken a massive sanitation operation in the area.

--
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[Insufficient information is provided in this report to suggest a possible aetiology. It is not clear even that the condition is infectious. There have been 4 deaths and no more than 15 people are receiving treatment. Until the results of investigations by the National Institute of Virology in Pune are released, it cannot be assumed that the illness is the result of virus infection. The most likely aetiology -- leptospirosis -- appears to have been excluded. Further information is awaited.

Surat is a city in the Indian state of Gujarat. It is also administrative capital of the Surat district. The city is located 306 km (190 miles) south of the state capital, Gandhinagar, and is situated on the left bank of the Tapti River (Tapi), the center being around 22 km (14 miles) from the river's mouth. Surat is Gujarat's 2nd largest city and India's 8th most populated city (in terms of population living in what is known as the Municipal Corporation area), with a population of 4.5 million. A map of Surat showing the administrative districts can be accessed at: http://www.mapsofindia.com/maps/gujarat/surat.htm. - Mod.CP

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/27Ix.]

UNDIAGNOSED DEATHS - INDIA (02): (GUJARAT) COMMENTS
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[1]
Date: Sat 12 Oct 2013 Oct 2013
From: T Jacob John <tjacobjohn@yahoo.co.in> [edited]


Comment on the undiagnosed deaths in Surat
------------------------------------------
In October 1994 there was panic, pandemonium, and enormous out-migration after Surat city (Gujarat State) was declared affected with an outbreak of pneumonic plague. The picture was that of adults, not old, mostly men, developing fever, blood in sputum, and high case-fatality. My guess is that the present situation is reminiscent of that old scary experience and the present anxiety is understandable against this background.

Pneumonic plague is easily diagnosed in a bacteriology laboratory with readily available clinical specimen by way of sputum and commonly used culture media. Although not mentioned in the report, plague would have been excluded before specimens are dispatched to the National Institute of Virology (NIV) in Pune (in Maharashtra State). Moreover, Crimean-Congo hemorrhagic fever has been reported in recent years in Ahmedabad (also in Gujarat State) and that was diagnosed by NIV.

The report does not say how leptospirosis was excluded but I wonder if that is the real case. Post-floods leptospirosis is very likely to occur and pulmonary hemorrhagic leptospirosis has been reported previously in 1994 in Surat and in nearby Valsad. Diagnosis of leptospirosis is not easy -- most laboratories rely on serological (antibody) tests -- and we need more details before concluding that the disease is not leptospirosis.

--
T Jacob John
Former (Retired) Professor of Clinical Microbiology and Clinical Virology
Christian Medical College,
Vellore, Tamil Nadu
India
<tjacobjohn@yahoo.co.in>

[ProMED-mail thanks Professor T Jacob John for his prompt response to the ProMED-mail request for information. His recollection of an outbreak of pneumonic plague with similar characteristics in Surat city in 1994 is intriguing and certainly worthy of further investigation. Until results become available from the National Institute of Virology it is too early to attribute the outbreak to viral infection. As Professor John concludes, leptospirosis remains a possibility and further diagnostic testing should be undertaken. - Mod.CP]

******
[2]
Date: Sun 13 Oct 2013
From: Jan Clement <jan.clement.dr@telenet.be> [edited]


Possible involvement of hantavirus fever in the Surat outbreak
--------------------------------------------------------------
In summary, and despite insufficient information so far, a hitherto unknown but sometimes fatal viral hemorrhagic fever (VHF), first suspected of being leptospirosis, seems to have spread in the Surat (Gujarat state) region, after heavy local floods. Several points of interest may help the local health authorities and the National Institute of Virology (NIV) in Pune to elucidate this mysterious illness:

1. Hantavirus fever (HTVF), and particularly the so-called "hemorrhagic fever with renal syndrome" (HFRS) form is the great imitator of leptospirosis in virtually every aspect: clinics, lab anomalies, most anatomo-pathological findings (including kidney biopsies), and even most epidemiological aspects. HTVF (worldwide an estimated 150 000 cases/year) is after leptospirosis (worldwide an estimated 200 000 cases/year) the most globally spread zoonosis, and both are mainly rodent-borne (Clement J, Maes P, Van Ranst M: Acute kidney injury in emerging, non-tropical infections. Acta Clin Belg 2007; 62(6): 387-95).

2. The rodent-borne origin explains why both diseases can occur, often even concomitantly, after local floods: rats, or other rodent carriers of pathogenic hantaviruses, fleeing from the water, often take refuge in human habitats. The 1st serologically confirmed cases of HTVF in the New World were documented in Recife (Brazil), after heavy floods (Hinrichsen S, Medeiros de Andrade A, Clement J, et al: Evidence of Hantavirus infection in Brazilian patients from Recife with suspected Leptospirosis. Lancet 1993; 341: 50). In Europe, the most important hantaviral pathogen is Puumala virus (PUUV), carried by the bank vole (_Myodes glareolus_), and causing often dense local outbreaks of HTVF, aptly called "nephropathia epidemica" (NE). The 1st Franco-Belgian NE outbreak was documented in 1993, after heavy rains causing floods of the local river Meuse in both countries (Clement J, Mc Kenna P, Colson P, et al: Hantavirus epidemic in Europe. Lancet 1994; 343(8889): 114-6. doi:10.1016/S0140-6736(94)90841-9).

3. All forms of HTVF, and even the New World forms of so-called "hantavirus pulmonary syndrome" (HPS), have also a clear RENAL involvement, that is earlier, cheaper, and easier to detect than its pulmonary counterpart (Clement J, Maes P, Lagrou K, et al: A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease. Eur J Clin Microbiol Infect Dis 2012; 31(1): 1-5. doi: 10.1007/s10096-011-1456-y). Whereas so-called acute kidney injury (AKI) still needs a serum creatinine dosage for confirmation, initial and frequently massive (nephrotic-range) proteinuria is often present prior to AKI, but can be very transient, often disappearing within 2 to 3 weeks. Such a + to +++ dipstick degree of initial proteinuria can be performed as a bed-side test everywhere, even in resource-poor regions. If positive, this finding can exclude practically from the start other similar infections occurring in outbreaks such as plague, tularemia, rickettsioses, and even leptospirosis, since in the latter, nephrotic-range proteinuria is never present.

4. Vomiting of blood is an unusual sign of HTVF, but this symptom is not exclusive, since HTVF is and remains the only VHF present throughout the Northern Hemisphere. Moreover, some "newer" hantaviral strains, such as the different subspecies of Dobrava virus (DOBV), are characterized by hemorrhagic complications, which can be life-threatening.

5. Whereas it is clear that the wild rat-transmitted Seoul virus (SEOV) is present in India (but no human SEOV nephropathy has been documented so far), the 1st 2 fatal, and some non-fatal HTVF cases, have been demonstrated in India to be serologically related to PUUV (Clement J, Maes P, Muthusethupathi M, et al: First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis. Nephrol Dial Transpl 2006; 21(3): 826-7 http://ndt.oxfordjournals.org/cgi/conte ... 3/826?etoc). This should be interpreted as a cross-reaction, since PUUV is absent in India, given the total absence of its carrier _Myodes glareolus_. However, the 2 fatal Indian cases had both renal and pulmonary involvement, and both died in shock, a combination reminiscent of the American HPS infection, still bearing a 35 percent fatality rate, even in tertiary care centres. It should be remembered that in the USA, a country where up to 1993, HTVF was (incorrectly) considered as being absent, the 1st step in unravelling the mystery of the reputed 1993 HPS outbreak, was a similar serological cross-reaction with PUUV (Jonsson CB, Figueiredo LT, Vapalahti O: A global perspective on hantavirus ecology, epidemiology, and disease. Clin Microbiol Rev 2010; 23(2): 412-41 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863364/). Since all American HPS-inducing hantaviruses are genetically more closely related to PUUV than to any other hantaviral pathogen, PUUV cross-reactions in severe HFRS + HPS cases may point to a hitherto unknown Indian hantavirus, with a hitherto unknown rodent (or insectivore?) reservoir.

6. Finally, in a prospective study of cases with AKI and fever, hospitalized in Sri-Lanka, a country highly endemic for leptospirosis, serological evidence was found for sympatric occurrence of SEOV and PUUV. Sri-Lanka has exactly the same small mammal fauna as neighbouring India, suggesting that a PUUV-like agent is probably spread by the same carrier in the 2 countries. Moreover and more importantly, for the 1st time concomitant presence of both leptospirosis and hantavirus was demonstrated in some more severe cases, meaning that even a lab confirmation of (well-known) leptospirosis, does not automatically exclude concomitant (but underestimated) HTVF. (Sunil-Chandra NP, Clement J, Maes P, et al: A new hantaviral pathogen in Sri-Lanka. Proceedings of the European Society for Clinical Virology, Annual Meeting Saariselka, Finland, 12-15 Mar 2008. Abstract P8-10, p. 46).

--
Clement J MD, Maes P Ph D, & Marc Van Ranst MD, PhD
National Belgian Reference Laboratory for Hantavirus Infections,
Clinical Virology,
University Hospital Gasthuisberg
University of Leuven
Leuven
Belgium
<jan.clement.dr@telenet.be>

[ProMED-mail thanks Dr Clement and colleagues for this carefully argued statement in favour of the involvement of hantavirus infection in the hemorrhagic fever cases reported from the city of Surat in Gujarat state, India.

As commented above in part 1, the results of the analysis of clinical samples at the Indian National Institute of Virology in Pune (Maharashtra) are awaited. - Mod.CP

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/8OE5.]