A people in peril

High levels of Hepatitis B infection among sections of the already minuscule tribal population of the Andaman and Nicobar Islands raise medical and social concerns.

R. RAMACHANDRAN

AN alarmingly high prevalence rate of Hepatitis B infection has been detected among the tribal people of the Andaman and Nicobar Islands. Compared to the average 4 to 5 per cent rate in the general population of mainland India, the prevalence rate in the se tribal populations is over 20 per cent. In the epidemiology of Hepatitis B, less than 2 per cent prevalence is termed 'low endemicity', that between 2 and 8 per cent is 'intermediate endemicity' and that over 8 per cent is 'high endemicity'.

The figure is over 20 per cent here - the highest recorded in recent times. The high-endemicity areas of Africa (Senegal and Gambia) and South-East Asia (Taiwan) now have rates of 15 to 20 per cent. More seriously, the rate appears to have increased from an average of 15.5 per cent in 1989 to 23.3 per cent in 1999.

HBV is transmitted through body fluids, chiefly blood, and circulates in blood. The reasons and risk factors associated with such a high prevalence rate are not fully clear from the findings of this preliminary study. Also, the epidemiological and serolo gical profile of the infection have somewhat unusual features, and call for further studies. How and when the infection was introduced into this tribal population - it certainly predates 1989, given the findings - are even more difficult questions to ans wer, say scientists associated with the study.

Data are not available on the burden of chronic liver diseases or hepatocellular carcinoma (HCC) or liver cancer among these tribes. "However," warns the study, "taking into consideration the extent of chronic HBV infection, especially in children, the p ossibility of chronic liver diseases leading to appreciable morbidity cannot be ruled out." The follow-up study has begun and HBV vaccination has been initiated.

The study was carried out jointly by the ICMR's Regional Medical Research Centre (RMRC) of the Indian Council of Medical Research (ICMR), Port Blair and the National Institute of Virology (NIV), Pune. The findings of the research team, led by M. V. Murhe kar of RMRC, have been reported in the latest issue of the Indian Journal of Medical Research (IJMR), the ICMR publication. According to S. C. Sehgal, Director of the RMRC, the study constitutes the first phase of the investigations into HBV infec tion among the tribes who constitute about 9 per cent of the archipelago's total population of about 300,000.

There are in all six tribes in these islands, divided broadly into two racial groups - the Negrito race living in the Andaman group of islands and the Mongoloid race living in the Nicobar group of islands. The Great Andamanese, Onges, Jarawas and Sentine lese belong to the former while the Nicobarese and Shompens belong to the latter.

All the tribes apparently live as independent closed communities. There is little interaction between the tribes, let alone any with the external civilisation from the Indian mainland (Frontline, July 17, 1998). The Nicobarese number over 25,000 a nd constitute more than 90 per cent of the tribal population. The Nicobarese have apparently slowly integrated into the mainstream life of Port Blair but still, as a community, they lead an isolated existence. Outsiders too, by the government regulations in place, are not allowed direct access to, or contact with, the tribes. The Jarawas and Sentinelese are, however, still hostile to, and cut off from, the outside world. The investigations on disease prevalence could be carried out only among four tribe s - namely Nicobarese, Shompens, Onges and the Great Andamanese.

The respective populations of the three non-Nicobarese tribes are 157, 102 and 32. (Apparently, the Great Andamanese were virtually driven to extinction by the British.) Of these four, the Shompens are said to be more primitive, who lead a nomadic life a nd do not encourage visits by outsiders to their huts which are situated deep in the jungles.

Till recently, the ICMR and the health authorities were largely concerned with controlling leptospirosis, a zoonotic infection (spread from animal hosts and rodents are the primary reservoirs of the microorganism leptospira), which has a significant prev alence in the population of the islands. Leptospirosis itself was discovered here in 1989 following an outbreak of unknown fever in the region.

Given its largely asymptomatic nature, HBV infection was believed to be largely absent in the tribal population. However, according to the report, jaundice apparently is a frequent occurrence. One of the clinical presentations of leptospirosis is jaundic e. Since other possible causes of jaundice had not been investigated, the RMRC instituted an investigation into HBV infection here in 1998. In fact, the apparent asymptomatic condition of the population had resulted in the health authorities of the Minis try stationed in Port Blair viewing the present research findings with scepticism. It was only after an independent survey by the Health Ministry's National Institute of Communicable Diseases (NICD), New Delhi, which also found similar results, that the health authorities woke up to the problem. The intervention programme became possible after the Hyderabad-based company, Shantha Biotech, which has developed a relatively inexpensive indigenous Hepatitis B vaccine, donated 1,000 doses to the programme.

Says S. K. Acharya, an expert in Hepatitis infection at the All India Institute of Medical Sciences (AIIMS), New Delhi: "It has been known for the last 50 years that a majority of Hepatitis B carriers are asymptomatic. The infection is self limiting but in chronic carriers of the virus, it ultimately affects the liver leading to cirrhosis, cancer and other serious manifestations of the liver. It is for this reason the infection is termed a silent killer," he says. "India," Acharya points out, "is a sign atory to the World Health Assembly (WHA) united declaration in 1992 which recommends routine HBV vaccination in any population with more than 2 per cent prevalence as the most effective preventive strategy and integration of HBV vaccine into the national programme of immunisation for over 8 per cent prevalence. And yet, with over 5 per cent in this country, there is no strategy evolved for HBV vaccination."

Apparently it is the high cost of the imported (SmithKline&Beecham) vaccine that has prevented HBV vaccination from being made part of the national immunisation programme. But, even though the indigenous vaccine is nearly one-third the cost of the import ed vaccine, the health authorities have, for some inexplicable reason, failed to include the vaccine as part of the universal immunisation programme (UIP) of the government. According to Varaprasad Reddy, chairman and managing director of Shantha Biotech , a bulk order for UIP from the government will bring down the cost and make it affordable for a public health programme.

THE discovery of HBV in the recently collected blood samples of the tribal people led the investigating team to look for HBV infection in the decade old samples collected for investigations into leptospirosis, and preserved at the NIV. The 15.5 per cent HBV prevalence rate of that time comes from an analysis of the older samples, indicating very clearly that the HBV infection is certainly not of recent origin. According to Vidya Arankalle of the NIV, who is part of the HBV investigation team, though the earlier 2,000 samples were from both the tribal and settler populations, this high 15.5 per cent prevalence rate was found in the samples belonging to the tribal communities.

The reported findings on the prevalence of HBV infection are based on investigations carried out between April 1998 and March 1999 on 1,266 serum samples collected from among the four tribes, of which 1,144 samples - 535 males and 609 females - were from the Nicobarese. The sample sizes of the other three tribes were 37 (smallest because of their highly secluded existence), 58 and 27 respectively. Given the expected prevalence of HBV infection - that is the population which is the carrier of the HBV - o f around 5 per cent, the above total sample size is stated to be more than the minimum size required for statistically significant conclusions to be drawn.

Following HBV infection, which is self-limiting, the body sets up an immune response and the progression of infection is essentially a competition between the immune response that is mounted and the viral load. In the immediate aftermath of the infection , the immune response is in the form of certain antibodies to the core protein - rather than the surface protein - of the virus called immunoglobulins. These antibodies to the core antigen (anti-HBc) build up quickly, fight the invading virus and reach a plateau after a period. That is, anti-HBc is present all through, in association with HBsAg (the infection period), alone (the window period) and in association with anti-HBs (the recovery period).

Once these immunoglobulins neutralise the virus and clear the body of the viral load, antibodies to the surface protein appear. This is indicative of recovery from infection and onset of immunity to the infection. There is a time gap between the clearanc e of the viral load and the circulation of anti-HBs. During this period, which is called the 'window of infection', only anti-HBc will be circulating. If the infection load is more, the virus wins, the HBsAg continues to be present in the body tissues an d sera and the person becomes a carrier capable of transmitting the virus.

The serum samples were tested for the main disease causing antigen, the surface coat protein of the virus HBsAg, and those who were negative for HBsAg were tested for antibodies to this surface antigen (anti-HBs). Of the 1,144 Nicobarese samples, a total of 267 samples were found to be positive for HBsAg (see table). This implies a seropositivity or prevalence rate of 23.3 per cent and, of those who were negative for HBsAg, only 23.9 per cent were positive for anti-HBs.

According to Acharya, this low anti-HBs positivity is surprising. In a random sample of a highly endemic population such as this one would expect a far greater proportion of the population to have "recovered" from infection and acquired a certain level o f immunity. This would need to be investigated again, he felt. "We are certainly investigating this question again but we find even the larger sample size collected now seems to give a similar profile of low anti-HBs and we do not have an immediate answe r to this," Sehgal says.

This issue becomes more intriguing if one tries to estimate the exposure rate of the population. The exposure rate is clearly the sum of HBsAg positives (the virus carriers), the anti-HBs positives (the surface antibody carriers) and positives to anti-HB c (those in the window period). In a random sample of 95 HBsAg negatives, the study found a high percentage (nearly 57 per cent) of people were positive only for anti-HBc; that is, a very high proportion was in the window period. This is unusual because the window period is usually short (though this could vary from region to region and from population to population). This would imply the existence of a prolonged window period before the circulating surface antibodies build up to detectable levels. This also implies that the total exposure rate is enormously high.

According to Vidya Arankalle, such a long window period was not inconceivable though she was not aware of such a feature being reported from elsewhere. Another possibility, according to the study, is that, if there are variants of the virus with surface mutations, the assay designed to detect the normal anti-HBs may not pick up the antibodies to the mutated viral surface protein. This needs further investigation. The age distribution of the seropositivity for HBV, besides other epidemiological features, reflects the susceptibility of various age groups. It shows that over 30 per cent of children below age 10 were exposed to infection suggesting that transmission in childhood - which would be horizontal through child-child interaction - is an important mode. This also stands to reason for closed communities where children of the tribe are in constant interaction with one another.

That horizontal transmission is perhaps the basic mode of transmission is also evident from the fact that the virus carrying fraction in the 5 to 10 age group is low. However, since the study did not look at samples of newborns and children below five ye ars, direct evidence for vertical transmission - from mother to child at birth - cannot as yet be ascertained. In the second phase of the study, pregnant women and new borns will be focussed on, says Sehgal. But the possibility of vertical transmission i s certainly indicated, says Vidya Arankalle, because almost 20 per cent women in the reproductive age group were found to be carriers.

According to Acharya, however, the pattern of infection suggests that the situation is similar to what was found in tribes of Senegal and Gambia in Africa, where horizontal transmission was dominant. In some of these African tribal populations, this led to the prevalence rate being as high as 50 per cent, he says. However, the World Health Organisation's (WHO) intervention through intensive immunisation has brought down the rate enormously, he points out. In Taiwan, an area of high endemicity, the trans mission is largely vertical and, perhaps because of other environmental conditions, the rate of horizontal transmission is low. Vertical transmission leads to a carrier state. As a result, the prevalence rate has more or less stabilised and is, therefore , more amenable to prevention and control.

In mainland India the rate of vertical transmission is very low, according to Acharya. Of course, being populations of entirely different genetic make up, transmission modes among the Andaman and Nicobar tribes could be different from the mainland. The s tudy speculates that the low anti-HBs positivity rate could be owing to the "combined effect of an extensive vertical and horizontal transmission".

Investigation into the possible risk factors that could be associated with HBV infection did not single out any one of them with any statistical significance. However, the study found that a high fraction (over 50 per cent) of the persons tested gave a h istory of parenteral treatment. Nearly the same fraction had also undergone ear-piercing. Fractions that had a history of surgery or blood transfusion or promiscuous sexual behaviour were low, though the study believes that there could be under-reporting of the last of the factors.

The source of parenteral treatment is suspected to be the local primary health centres (PHCs) in Port Blair which Nicobarese, who have tried to join the mainstream, have in recent times begun making use of. According to some other research groups working in this region the state of these PHCs and resource constraints they face, could easily result in multiple uses of syringe needles and thereby spread HBV infection. However, the present data do not unequivocally associate any single risk factor with the infection. A larger sample size might be required to arrive at a more definitive association of risk factor(s) with the infection, says the study.

The study also found the prevalence of HBV in the three non-Nicobarese tribes to be significant. The prevalence rate among the Shompens was found to be the highest with 37.8 per cent. It was 31 per cent among the Onges and a low 3.7 per cent among the Gr eat Andamanese.

"There are certainly a whole lot of questions that need to be answered. But we have made a start and brought the awareness home that we have a serious public health problem at hand. This dawning of awareness has led to one good thing for the community: i ntervention has begun though in a limited way. Hopefully, the government would step in to immunise the tribes on a larger scale on a routine basis," says Sehgal.