Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
  Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login  
  Home Print this page Email this page Small font sizeDefault font sizeIncrease font size Users Online: 2213       

   Table of Contents      
Year : 2012  |  Volume : 136  |  Issue : 4  |  Page : 549-562

Helicobacter pylori infection in India from a western perspective

1 Department of Medicine, Baylor College of Medicine; Harris County Hospital District, Houston, Texas, USA
2 Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas, USA

Date of Submission13-Dec-2011
Date of Web Publication8-Nov-2012

Correspondence Address:
David Y Graham
Michael E. DeBakey Veterans Affairs Medical Center, RM 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX 77030
Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 23168695

Rights and PermissionsRights and Permissions

Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of medical research and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here we discuss H. pylori as a problem in India with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments are discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

Keywords: Antibiotic resistance - epidemiology - eradication - Helicobacter pylori - India - treatment

How to cite this article:
Thirumurthi S, Graham DY. Helicobacter pylori infection in India from a western perspective. Indian J Med Res 2012;136:549-62

How to cite this URL:
Thirumurthi S, Graham DY. Helicobacter pylori infection in India from a western perspective. Indian J Med Res [serial online] 2012 [cited 2020 Sep 23];136:549-62. Available from:

Helicobacter pylori is a common and important transmissible bacterial human pathogen. The prevalence of this infection varies world wide being as low as 10 per cent in developed western nations to higher than 80 per cent among the indigent populations of many developing countries. The infection primarily involves the upper gastrointestinal tract causing progressive acute and chronic gastro-duodenal inflammation. Typically these inflammatory changes are silent but clinical disease manifestations occur in approximately 20 per cent, generally after a long latent period [1] . The manifestations of H. pylori infection include gastritis, gastric atrophy, duodenal ulcer disease, gastric ulcer disease, primary gastric B-cell lymphoma, gastric adenocarcinoma, iron deficiency anaemia, and vitamin B12 deficiency [2],[3],[4],[5] . There are often regional differences with regard to which clinical manifestation is predominant ranging from iron deficiency anaemia in childhood to gastric cancer in the elderly. The predominant manifestation can also evolve over time. For example, in the first half of the 20 th century there was a rapid and progressive decline in the incidence of gastric cancer in the west which coincided with a sharp rise in the incidence of duodenal ulcer.

Gastric cancer is one of the most significant out-comes of H. pylori infection and understandably attracts the most attention from the research community. However, in many areas, especially in tropical and semitropical countries (e.g., Africa, southern India), the infection is common but gastric cancer is rare with duodenal ulcer being the dominant clinical manifestation of the disease [5],[6],[7] . Less dramatic, but no less important, is an increased susceptibility to enteric infections due to H. pylori gastritis-related hypochlorhydria and iron deficiency anaemia both of which can have major deleterious effects on physical and intellectual growth of children especially in developing countries [8] .

H. pylori infection is typically acquired in childhood. The risk of infection is inversely related to the overall sanitary conditions and requires exposure to other infected humans. Contaminated water is often the primary mode of transmission in rural areas without reliable supplies of potable water [9],[10] . However, in regions of higher socio-economic status the risk of infection best correlates with the level of household hygiene.

   Outcome of H. pylori infections Top

The outcome of an H. pylori infection reflects a complex interplay of environmental, host and bacterial factors including the virulence of the infecting bacterial strain. There are no nonpathogenic strains of H. pylori as even the least virulent strains cause gastric inflammation and have been associated with peptic ulcer disease and gastric cancer. The virulence of H. pylori strains correlates with the intensity of the inflammatory response to the infection. Established H. pylori virulence factors include the cag pathogenicity island (cag PAI), the vacuolating cytotoxin (VacA) and the outer inflammatory protein, OipA. Host factors involved in disease pathogenesis include polymorphisms of genes that govern the host's inflammatory response (i.e., a genetic predisposition to an increased response is associated with a greater risk of a clinical outcome). A genetically determined increased parietal cell mass is thought to predispose to H. pylori-related duodenal ulcer disease. Environmental factors also contribute to the outcome of H. pylori infection. This is best seen in relation to the association of H. pylori-related gastric cancer with diets low in fresh fruits and vegetables but high in salt and the rapid decline in the incidence of gastric cancer that paralleled dietary changes in those populations. Replacing salt/smoke with refrigeration as the primary means of food preservation and an increased intake of fresh fruits and vegetables has universally been associated with a fall in the incidence of gastric cancer among high risk populations without a change in the prevalence or virulence of H. pylori infections [11],[12],[13],[14] .

   Should H. pylori be eradicated? Top

H. pylori is a significant human pathogen responsible for considerable morbidity and mortality and is the major cause of gastric cancer. The majority of investigators in the field believe that whenever the infection is detected, it should be eradicated [15] . However, that goal may be difficult to attain in some non-western populations. Some have hypothesized that H. pylori infection may even be beneficial and that eradication is not always the best option [16] . H. pylori is a human pathogen. Although H. pylori is not present in wild monkeys, its association with mankind can be traced back to the time when humans migrated out of Africa [17] . Such a long association is neither unique nor evidence of a positive benefit, at least to man. Over the centuries, man has been host to many bacterial, viral, protozoal, and helminthic pathogens. Gradually, as populations dispersed and sanitation improved, most pathogens have been lost. H. pylori is one of the last of those pathogens to undergo clearance associated with improvements in the standards of living. Despite its long-standing presence, H. pylori is not a commensal; it always causes disease (e.g., progressive gastric inflammation). Commensals are very difficult to eliminate, however, with H. pylori, the chain of transmission is easily broken in association with improvements in hygiene and sanitation practices.

   Are there adverse consequences to H. pylori eradication? Top

In epidemiology, when one variable is associated with a reduction of another (e.g., a disease) it is said to be "protective". For example, populations with limited sanitation, high rates of malnutrition and early mortality have a low incidence of age-related diseases such as diabetes, stroke, and cancer. One could conclude that from an epidemiologic standpoint poor sanitation "protects" against those diseases. This would clearly be a misuse of the medical concept of "protection". However, the same approach has been used to show that H. pylori infection possibly "protects" against other diseases [18] . For example, atrophic gastritis, the precursor lesion for gastric cancer, leads to low levels of gastric acid secretion (i.e., it can be considered to be a biologic anti-secretory agent) and thus protects against gastroesophageal reflux disease and its dreaded complication, oesophageal adenocarcinoma [19] . It has been suggested that possibly one should not eradicate H. pylori because H. pylori infection may protect against development of oesophageal adenocarcinoma, a clear misunderstanding of the concept of protection [19],[20],[21] . Similarly, H. pylori infection has been suggested to protect against obesity and childhood asthma [22],[23] . Childhood asthma is often thought to be related to a failure of exposure of the immune system to important environmental antigens (the hygiene hypothesis). Does H. pylori infection contain some of those critical antigens? The available data suggest that the presence of H. pylori infection is not responsible but is instead a surrogate or marker for inadequate household hygiene. Experience in rural Malaysia allowed the H. pylori protective hypothesis to be tested. In rural Malaysia hygiene is often poor, and enteric diseases are common, but H. pylori is essentially absent [24] . One would therefore expect childhood asthma to be common, gastroesophageal reflux, oesophagitis, adenocarcinoma of the oesophagus, and obesity to be significant problems. However, childhood asthma, obesity, gastroesophageal reflux, and oesophageal adenocarcinoma are all rare [19] . These data are directly in contrast to what was predicted by those who espouse dire consequences associated with H. pylori eradication. In terms of childhood asthma, the experience in Malaysia is consistent with the hygiene hypothesis (i.e., the likelihood of environmental antigens in priming the immune system) but is direct evidence that the critical antigens are unlikely to be related to H. pylori infection and support the premise that the presence of H. pylori infections is a marker for poor household hygiene [24] .

In summary, H. pylori is an important human pathogen and should be eradicated whenever possible. However, eradication is more complex than the simple matter of writing a prescription for antibiotics. This paper will review H. pylori treatment strategies and the approach to identifying the best regimens for a particular population with a special emphasis on H. pylori eradication in India.

   H. pylori as an Indian problem Top

India is a vast country known for its rich history, culture and food. It is also the prototypical developing country with a vast rural population living in poverty. The prevalence of H. pylori in the Indian subcontinent can be as high as 80 per cent or more in rural areas. The most commonly recognized manifestation of H. pylori infection in India is peptic ulcer disease, particularly duodenal ulcer disease, which outnumbers gastric ulcers between 8:1 and 30:1 [25] . Singh et al[26] calculated the point prevalence of active peptic ulcer disease at 3% with a lifetime prevalence of 9 per cent. As in other regions, the actual risk of a particular outcome from an H. pylori infection is predicated on the pattern of gastritis [7] . Antral predominant gastritis leaves an intact gastric corpus, poorly controlled acid secretion and promotes duodenal ulcer formation. In contrast, with pangastritis acid secretion often falls below the level needed to produce and sustain duodenal ulcer disease (e.g., approximately 12 mmol/h), gastric ulcer becomes more common than duodenal ulcer and the incidence of gastric cancer rises. Finally, atrophic pangastritis is the main precursor lesion associated with gastric cancer [27] .

Environmental factors, especially diet, play a role in the pattern of gastritis and this likely underlies the differences in the prevalence of H. pylori diseases in India. Tropical diets with plentiful fruits and vegetables year-round promote antral predominant non-atrophic gastritis and duodenal ulcer disease [5],[7] . Seasonal diets where fresh fruits and vegetables are not available during the winter or dry season and food is commonly preserved with salt promote pangastritis, a lower incidence of duodenal ulcer disease and more gastric ulcers. These environmental factors are likely responsible for the higher prevalence of duodenal ulcer in the south and for the wide range in the age-adjusted incidence rate of gastric cancer (range from 2 to 57 per 100,000) [7],[11],[28] .

The population of India is approximately 1.2 billion people. If the H. pylori prevalence was 60 per cent, more than 726 million individual would be infected with H. pylori[29] . The estimated prevalence of duodenal ulcers in India is 3 per cent and means that at least 18 million people could need anti-H. pylori therapy (approximately 50,000 per day if treated over one year). The enormity of the task of treating H. pylori infection is daunting and might dissuade some physicians and the government from aggressively managing the infection. However, when one considers the problem one patient at a time, the issue becomes much simpler.

   H. pylori diagnosis Top

The first step in managing H. pylori infections is to establish the diagnosis. Physicians in India, as in many developing countries, face issues of availability and cost to establish the diagnosis of H. pylori infection. Worldwide, non invasive tests for active infection are preferred (e.g., urea breath test or stool antigen test) over tests that require endoscopy. Western versions of these tests are relatively expensive but all have been used at one time or another in India. The [14] C-urea breath test (UBT) is probably the least expensive. In China, it is available clinically for approximately 26 per test (DY Graham, personal communication). Endoscopy is available at tertiary care centers but can cost up to 150 at a public hospital and between 450 and 3000 at private clinics [30] . The advantage of endoscopy is that symptomatic patients can be evaluated for mucosal disease. Endoscopy also allows one to take biopsy specimens that can be examined by histology, rapid urease testing, brush cytology, or even culture. Rapid urease tests can be made very cheaply by any hospital laboratory and are reasonably accurate [30],[31] . Saksena et al[32] showed that the rapid urease test (RUT) and brush cytology had the highest degree of agreement whereas histology was the most specific diagnostic test. The current gold standard to diagnose H. pylori infection invasively is two positive tests, which in India could be the combination of the rapid urease test and brush cytology [31],[32] . Importantly, the endoscope, the biopsy forceps, and other parts of the system (e.g., water bottles, tubes, rubber ports, etc.) can easily become contaminated with H. pylori, therefore, it is critical that high-level disinfection be done of all endoscopic equipment and any reusable devices to prevent the iatrogenic spread of the infection or for iatrogenic reinfection post H. pylori eradication. The minimally invasive oral brush culture method would seem to be ideal for obtaining culture specimens for susceptibility testing in India [33] .

If endoscopy is not available, for symptomatic patients, barium contrast imaging can be used to detect peptic ulcer disease followed by a non-invasive test to confirm H. pylori infection. Serologic testing for H. pylori antibodies has greater than 80 per cent sensitivity and greater than 90 per cent specificity and is widely available but can cost between 200 to 300 [30] . Serologic testing is not recommended as the single diagnostic test in asymptomatic patients as it can remain positive for decades after successful H. pylori therapy and gives a false positive test result. However, it can be one of the two tests to confirm H. pylori infection or combined with a high pretest probability condition such as a duodenal ulcer to confirm the diagnosis.

   Choosing the treatment regimen - the effect of antibiotic resistance Top

Treatment logically follows diagnosis. The goal is to choose a regimen that will reliably produce a 90 per cent or preferably >95 per cent treatment success [2],[34],[35] . Recommendations from consensus statements should be ignored unless the antibiotic combinations have been proven to be effective locally. Bacterial resistance is the most common cause of treatment failure with what would otherwise be an effective regimen. Resistance is an evolving process such that antibiotic susceptibility and local treatment success rates must be monitored to update treatment selections. Because of the rapid development of resistance, it is recommended that the outcome of every treatment be confirmed with a non invasive test to confirm cure and provide an early warning of changes in local patterns of resistance.

Different antimicrobial agents have been used to treat H. pylori infection. Most successful regimens consist of an anti-secretory agent, most often a proton pump inhibitor (PPI) and two or three antimicrobial agents [2],[35] . Successful treatment requires consideration of a number of factors (Box 1) including drug, dose, duration, and frequency of drug administration, formulation, and whether the drugs are taken fasting or with meals [37] . These factors are all largely under control of the prescribing physician. If one knows the local resistance rates to the different antibiotics one can generally choose a regimen that will reliably provide at least 90 per cent treatment success. As far as treatment is concerned, it is important to stop considering H. pylori as a "gastroenterology problem" (i.e., in the same light as we might consider gastroesophageal reflux, constipation, or functional bowel disease) and instead consider it as a common bacterial infectious disease more akin to urinary tract infection or pneumonia [38] . Most gastrointestinal diseases are not curable and have a considerable placebo response. In contrast, most common bacterial infectious diseases can be cured and with H. pylori there is no placebo response. The lessons learned regarding evaluation of common infections are also applicable to H. pylori (i.e., one should expect to cure them all). In addition, the reason for treatment failure should never be a mystery but rather is typically related to resistance or a poor choice of drugs, durations, etc.

Easy access to antibiotics contributes to overuse. In India, antibiotics can be obtained without a prescription which leads to overuse or misuse. Worldwide, antibiotics are frequently misprescribed or dispensed incorrectly due to lack of appropriate knowledge, desire to meet patient demands, mistrust in or delayed laboratory results and for economic incentives [39] . Metronidazole is inexpensive, available over the counter and widely used as an anti-diarrhoeal agent and for functional bowel disease. As such, there is generally a high prevalence of metronidazole resistance in India and in other tropical and sub-tropical developing countries [40] . If one were to start with a blank slate, one would probably start by testing locally obtained strains for antimicrobial resistance and use these data to select initial regimens. There are however, data available regarding antimicrobial resistance in India [Table 1] & [Table 2], and these data suggest that resistance is both common and widespread but with considerable regional variation. Are these data accurate and valuable? To be useful, one would like to know whether the patients tested represented treatment naive patients or H. pylori treatment failures, whether they had received the antibiotic in question in the past, their age and socio-economic status and presentation. Accuracy can be assessed in terms of the methods used, whether known susceptible and resistant controls were included and how the results correlated with the results of treatment. In general, the E-test is more difficult to master than agar dilution. The laboratories should present data regarding their methods especially when the results are unexpected (e.g., high levels of amoxicillin resistance) and provide confirmatory testing. The E-test tends to overestimate the prevalence of metronidazole resistance but in experienced laboratories provides accurate results for clarithromycin and amoxicillin resistance [50],[51],[52].
Table 1: Regional H. pylori in vitro antibiotic resistance in India

Click here to view
Table 2: Regional H. pylori in vitro metronidazole resistance in India

Click here to view

Based on the available data regarding antimicrobial resistance, one would expect regimens using clarithromycin or metronidazole to provide unacceptably low eradication rates [Table 3]. As noted earlier, when examining the results of a clinical trial it is important to take note of the drugs, doses and durations. The report by Bhatia et al[47] tested appropriate doses of proton pump inhibitor (PPI), amoxicillin, tinidazole or clarithromycin for 14 days in a sufficient sample of patients (i.e., approximately 70 each) and used three tests to confirm cure to provide reliable data. The treatment success with clarithromycin-containing triple therapy was 42 and 65 per cent for tinidazole-containing triple therapy thus confirming the hypothesis that in Mumbai, legacy triple therapy provides unacceptably low treatment results. By contrast, in New Delhi the same regimen provided 80 per cent success after 14 days and 91 per cent after 21 days [55] . However, in this study the sample sizes were too small to provide a meaningful comparison between the 14 and 21 day groups. Without having concomitant susceptibility data, it is difficulty to suggest the mechanisms responsible for this surprising result. Most of the Indian studies have used less than optimal dosing, duration, or both and thus are not very helpful in deciding what to use and in which situation. The fact that sequential therapy provided 87 per cent treatment success in Puducherry suggests that the local resistance rate for clarithromycin was less than 20 per cent [53] .
Table 3: H. pylori treatment regimens in India

Click here to view

   Which regimens are likely to be effective in India? Top

The available data from India do not provide the information one requires to prospectively identify a successful treatment regimen. India is ripe for prospective studies of different anti-H. pylori therapies. The investigators should follow the recommendations for efficient identification of effective regimens that allows one to expose the minimal number of subjects to a new regimen but at the same time, starts with one's "best shot" in terms of dose, duration, frequency of drug administration, etc[2],[35],[63] . Treatment failures are very difficult to interpret unless one has susceptibility data. Such data do not need to be acquired before the trial but a biopsy or two can be saved frozen at -70C in transport media for subsequent culture and susceptibility testing locally or following shipment to a central laboratory in India or elsewhere.

If it were decided to routinely treat all H. pylori infections diagnosed in India, what regimen or regimens would be most likely be successful? Ideally, for an infectious disease, one would have information from clinical trials regarding which regimens were most effective (e.g., reliably provide 90% or greater treatment success) in that population as well as the effect of resistance to the antibiotics used both individually and in combination. The regimens would also have been optimized in terms of dose, drugs, and duration. This has been accomplished, at least partly, for most commonly used regimens in the West [Table 4] and [Box 2]. In general, the results from one location are transferrable to another region provided the patterns of resistance are the same. Clearly in India, the problem of antibiotic resistance differs greatly from that in developed western countries. In addition, the pattern of resistance appears to vary widely and data regarding resistance in most areas are scant and not necessarily reflective of that population. In addition, although several trials have been done in India, most were small, rarely evaluated what are now known to be the optimal formulations, and often used lower than optimal doses and durations. An India-wide systematic approach is needed to identify the best regimen in general and specifically for each area. These results would be enhanced by simultaneous collection of susceptibility data and effectiveness from different populations throughout India.
Table 4: Antimicrobials used for H. pylori eradication therapy

Click here to view

Until accurate treatment data combined with susceptibility testing data are available, one must rely on first principles, (e.g., cannot overcome clarithromycin resistance or fluoroquinolone resistance by increasing either the dose or duration of therapy and these antibiotics are best avoided in regions where resistance is known to be high either from direct assessment or from a history of poor treatment success). In contrast, metronidazole/tinidazole resistance can be partly or largely overcome by using full doses (1,500 to 1,600 mg) and a 14 days of therapy. The quadruple therapy consisting of tetracycline, metronidazole, bismuth, and a PPI (Box 2) has been tested directly in metronidazole resistance and has generally had a success rate of 90 per cent or greater provided that therapy is at least 10 and preferably 14 days [66],[67],[68],[69] . Bismuth quadruple therapy would be one of our first choices for testing. The reports of tetracycline resistance in India are troubling but the intragastric doses are very high and the effect of different levels of tetracycline resistance on outcome has not been assessed directly. An alternate would be the same combination but substituting furazolidone (or possibly secnidazole or even clarithromycin) for the metronidazole. The optimal dose of furazolidone is unknown; we use 100 mg t.i.d. with meals. A few caveats are necessary when using furazolidone. The drug is an monoamine oxidase inhibitor and thus interacts with many other drugs and foods (e.g., we provide patients with an information sheet that cautions against aged cheese, sausage including bologna, salami and pepperoni, lima beans, lentils, snow peas, and soybeans, canned figs and raisins, beer, ale and wine, licorice, soy sauce and any food product that is made with soy sauce, monamine oxidase inhibitors, phenylpropanolamine, ephedrine, and phenylephrine). A widely read letter to the editor stated that furazolidone had been removed from the US market because it was a proven carcinogen [70] . That information is erroneous; the author mixed animal food supplement regulations with human medicine. Furazolidone was originally sold in the U.S. by Roberts Pharmaceuticals which was purchased by Shire Pharmaceuticals which because there was almost no commercial market for the drug, chose not to continue to market the drug and notified the Food and Drug Administration (FDA) that they would stop marketing it. The FDA responded that they would "publish a notice in the Federal Register stating that you have voluntarily requested withdrawal of approval of these applications because you have stopped marketing the drug products under the NDA". That notice was subsequently published (Federal Register / Vol. 70, No. 42 / Friday, March 4, 2005 / Notices, pp 11652). The letter to the editor described furazolidone as a carcinogen although it is listed by the IARC as a Group 3 carcinogen which is defined as "unclassifiable as to carcinogenicity in humans" [70] .

Clarithromycin-containing triple therapies are very effective regimens provided the appropriate doses and duration are used and local resistance to clarithromycin is low. The success rate with legacy triple therapy consisting of a twice a day PPI plus amoxicillin and clarithromycin or clarithromycin and metronidazole falls below 90 per cent when the level of clarithromycin resistance is 7 to 10 per cent [38] . Sequential therapy is an effective alternative until clarithromycin resistance exceeds 20 per cent and metronidazole resistance exceeds 40 per cent and then treatment success falls to unacceptable levels [71] . As such triple therapy should be avoided unless it were proven to be locally effective; there are likely few places in India where sequential therapy would provide 90 per cent or greater success. If one were to try a 4 drug clarithromycin containing regimen we suggest trying hybrid therapy (Box 2) as it has the best chance of being successful [72] . Alternatively, one could use bismuth-clarithromycin quadruple therapy but this would also need to be optimized for India (Box 2).

   Development of India-specific regimens Top

The old concept of trial and error that was the norm for early H. pylori therapies has passed as it has become recognized that the same approaches used for other common infectious disease is likely to provide better results [36] . We now recognize that treatment results are predictable provided we know the pattern of resistance in a community. This allows us to quickly identify and optimize, (or reject) potential regimens, exposing the fewest patients to ineffective therapy. Simply trying some combination in an arbitrary number of subjects is no longer considered rational or ethical. For example, secnidazole has been used with some success in India although attempts to optimize its use and identify its effectiveness in the presence of metronidazole resistance are lacking. India has been on the forefront of suggesting new antibiotic formulations that differ in their intragastric time [73],[74] . However, this idea has not been advanced further with in vivo testing.

   Recurrence of H. pylori after treatment Top

A high rate of reinfection after eradication in developing countries would undermine attempts to eradicate the infection in individuals, families, villages, or larger groups of individuals. Recurrence of infection following what appears to have been successful therapy is classified as either recrudescence, a form of failed therapy in which the same H. pylori strain is still present, or as reinfection when a different strain is present [75] . These definitions are general as recrudescence can actually be reinfection from a common source and reinfection from outgrowth of a minor population of a mixed infection. Recurrence, either reinfection or recrudescence, is more common following low treatment success regimens suggesting that most cases represent recrudescence. Recurrence within 12 months of treatment in developed countries is generally due to recrudescence [76] . Since sanitation in developed countries is generally good there and the prevalence of H. pylori is low, particularly in children, re-exposure is less problematic. However, in developing countries sanitation is often suboptimal and the presence of the infection is almost universal thus the potential for reinfection is high. Whether this is an actual problem in India is unclear [Table 5] and is an excellent area for research. Studies in India in which individuals or families are followed prospectively using non-invasive tests after successful eradication are needed. Molecular characterization of the infecting strains such as RFLP (restriction fragment length polymorphism) checked before treatment and following recurrence would be needed to help unravel this problem and discover whether recurrence following eradication is a problem that must be addressed or mostly a theoretically concern [76],[81],[82] . Routine endoscopy for surveillance should probably be avoided to reduce the possibility of iatrogenic reinfection from confusing the picture. One would imagine that the population at highest risk would be one living in poverty in relatively unsanitary conditions without access to potable water. Data over a longer interval (e.g., 5 year) regarding reinfection from the Indian subcontinent are needed in populations that eradication was definitely confirmed using 2 or 3 tests or a single test (e.g. urea breath test) on at least 2 occasions.
Table 5: Recurrence of H. pylori infection studies from India and Bangladeshi

Click here to view

   Recommendations for the future Top

India is an ideal place for investigation of new ideas in a systematic and organized way as the infrastructure is present, the pharmaceutical industry is among the most innovative, and the medical expertise highly regarded and up to date. Questions that might be addressed include what is the recurrence rate of H. pylori infection after successful eradication. If the recurrence rate is high, what factors are responsible and how can it be reduced (e.g., the source of reinfection and whether it can be managed) and whether eradication of the infection from entire families or villages would eliminate recurrence. The high level of antimicrobial resistance allows direct study of agents in the presence of different patterns of resistance. It is imperative that susceptibility be assessed accurately and, if required laboratory personnel or individual technicians can be trained in the details of susceptibility testing for H. pylori and in designing treatment trials to investigate current and innovative treatment regimens. India should be leading the way in the research of treatment of H. pylori infections. Ultimately, eradication of H. pylori from India and other developing countries may need to await development of an effective vaccine [83] .

   Acknowledgment Top

Dr Graham acknowledges the financial support in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center, DK067366 and CA116845.

Conflicts of interest: Dr Graham is an unpaid consultant for Novartis in relation to vaccine development for treatment or prevention of H. pylori infection. Dr Graham is a also a paid consultant for Otsuka Pharmaceuticals regarding diagnostic testing and has received royalties on the Baylor College of Medicine patent covering materials related to [13] C-urea breath test.

   References Top

1.Axon A, Forman D. Helicobacter gastroduodenitis: a serious infectious disease. BMJ 1997; 314 : 1430-1.   Back to cited text no. 1
2.Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011; 8 : 79-88.   Back to cited text no. 2
3.Cardenas VM, Ortiz M, Graham DY. Helicobacter pylori eradication and its effect on iron stores: A reappraisal. J Infect Dis 2006; 194 : 714.  Back to cited text no. 3
4.Devarbhavi H, Nanivadekar S, Sawant P, Saraswathy K. Sensitivity of Helicobacter pylori isolates from Indian patients to different antibacterial agents. Indian J Gastroenterol 1998; 17 (Suppl 1): S53.  Back to cited text no. 4
5.Graham DY. Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model. Gastroenterology 1997; 113 : 1983-91.  Back to cited text no. 5
6.Agha A, Graham DY. Evidence-based examination of the African enigma in relation to Helicobacter pylori infection. Scand J Gastroenterol 2005; 40 : 523-9.  Back to cited text no. 6
7.Graham DY, Lu H, Yamaoka Y. African, Asian or Indian enigma, the East Asian Helicobacter pylori: facts or medical myths. J Dig Dis 2009; 10 : 77-84.  Back to cited text no. 7
8.Walker SP, Wachs TD, Gardner JM, Lozoff B, Wasserman GA, Pollitt E, et al. Child development: risk factors for adverse outcomes in developing countries. Lancet 2007; 369 : 145-57.  Back to cited text no. 8
9.Ahmed KS, Khan AA, Ahmed I, Tiwari SK, Habeeb A, Ahi JD, et al. Impact of household hygiene and water source on the prevalence and transmission of Helicobacter pylori: a South Indian perspective. Singapore Med J 2007; 48 : 543-9.  Back to cited text no. 9
10.Nurgalieva ZZ, Malaty HM, Graham DY, Almuchambetova R, Machmudova A, Kapsultanova D, et al. Helicobacter pylori infection in Kazakhstan: effect of water source and household hygiene. Am J Trop Med Hyg 2002; 67 : 201-6.  Back to cited text no. 10
11.Dikshit RP, Mathur G, Mhatre S, Yeole BB. Epidemiological review of gastric cancer in India. Indian J Med Paediatr Oncol 2011; 32 : 3-11.  Back to cited text no. 11
12.Correa P, Cuello C, Fajardo LF, Haenszel W, Bolanos O, de Ramirez B. Diet and gastric cancer: nutrition survey in a high-risk area. J Natl Cancer Inst 1983; 70 : 673-8.  Back to cited text no. 12
13.Hwang H, Dwyer J, Russell RM. Diet, Helicobacter pylori infection, food preservation and gastric cancer risk: are there new roles for preventative factors? Nutr Rev 1994; 52 : 75-83.  Back to cited text no. 13
14.Thomson CA, LeWinn K, Newton TR, Alberts DS, Martinez ME. Nutrition and diet in the development of gastrointestinal cancer. Curr Oncol Rep 2003; 5 : 192-202.  Back to cited text no. 14
15.Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, el-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56 : 772-81.  Back to cited text no. 15
16.Blaser MJ. An endangered species in the stomach. Sci Am 2005; 292 : 38-45.  Back to cited text no. 16
17.Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, et al. An African origin for the intimate association between humans and Helicobacter pylori. Nature 2007; 445 : 915-8.  Back to cited text no. 17
18.Graham DY. Helicobacter pylori is not and never was "protective" against anything, including GERD. Dig Dis Sci 2003; 48 : 629-30.  Back to cited text no. 18
19.Graham DY, Yamaoka Y, Malaty HM. Contemplating the future without Helicobacter pylori and the dire consequences hypothesis. Helicobacter 2007; 12 (Suppl 2): 64-8.  Back to cited text no. 19
20.Blaser MJ. Disappearing microbiota: Helicobacter pylori protection against esophageal adenocarcinoma. Cancer Prev Res (Phila) 2008; 1 : 308-11.  Back to cited text no. 20
21.Blaser MJ. Helicobacter pylori and esophageal disease: wake-up call? Gastroenterology 2010; 139 : 1819-22.  Back to cited text no. 21
22.Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest 2009; 119 : 2475-87.  Back to cited text no. 22
23.Blaser MJ, Falkow S. What are the consequences of the disappearing human microbiota? Nat Rev Microbiol 2009; 7 : 887-94.  Back to cited text no. 23
24.Raj SM, Choo KE, Noorizan AM, Lee YY, Graham DY. Evidence against Helicobacter pylori being related to childhood asthma. J Infect Dis 2009; 199 : 914-5.  Back to cited text no. 24
25.Abraham P, Bhatia SJ. Position paper on Helicobacter pylori in India. Indian Society of Gastroenterology. Indian J Gastroenterol 1997; 16 (Suppl 1): S29-33.  Back to cited text no. 25
26.Singh V, Trikha B, Nain CK, Singh K, Vaiphei K. Epidemiology of Helicobacter pylori and peptic ulcer in India. J Gastroenterol Hepatol 2002; 17 : 659-65.  Back to cited text no. 26
27.Graham DY, Asaka M. Eradication of gastric cancer and more efficient gastric cancer surveillance in Japan: two peas in a pod. J Gastroenterol 2010; 45 : 1-8.  Back to cited text no. 27
28.Tovey FI. Helicobacter pylori infection and upper gastrointestinal pathology in a British immigrant Indian community. Eur J Gastroenterol Hepatol 1997; 9 : 647-8.  Back to cited text no. 28
[PUBMED] Available from:, accessed on October 14, 2011.  Back to cited text no. 29
30.Bhatia SJ, Kulkarni SG. Cost-effectiveness of Helicobacter pylori eradication in India: to live and let live ... expensively? Indian J Gastroenterol 1997; 16 (Suppl 1): S25-8.  Back to cited text no. 30
31.Dewan R, Sachdev GK. Diagnosis of Helicobacter pylori infection in primary and tertiary care centers. Indian J Gastroenterol 2000; 19 (Suppl 1): S11-4.  Back to cited text no. 31
32.Saksena S, Dasarathy S, Verma K, Ahuja V, Sharma MP. Evaluation of endoscopy-based diagnostic methods for the detection of Helicobacter pylori. Indian J Gastroenterol 2000; 19 : 61-3.  Back to cited text no. 32
33.Graham DY, Kudo M, Reddy R, Opekun AR. Practical rapid, minimally invasive, reliable nonendoscopic method to obtain Helicobacter pylori for culture. Helicobacter 2005; 10 : 1-3.  Back to cited text no. 33
34.Graham DY, Lu H, Yamaoka Y. A report card to grade Helicobacter pylori therapy. Helicobacter 2007; 12 : 275-8.  Back to cited text no. 34
35.Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 2010; 59 : 1143-53.  Back to cited text no. 35
36.Graham DY. Efficient identification and evaluation of effective Helicobacter pylori therapies. Clin Gastroenterol Hepatol 2009; 7 : 145-8.  Back to cited text no. 36
37.Graham DY. Helicobacter pylori eradication therapy research: Ethical issues and description of results. Clin Gastroenterol Hepatol 2010; 8 : 1032-6.  Back to cited text no. 37
38.Graham DY, Dore MP. Helicobacter pylori therapy demystified. Helicobacter 2011; 16 : 343-5.  Back to cited text no. 38
39.Radyowijati A, Haak H. Improving antibiotic use in low-income countries: an overview of evidence on determinants. Soc Sci Med 2003; 57 : 733-44.  Back to cited text no. 39
40.Chowdhury A, Berg DE, Jeong JY, Mukhopadhyay AK, Nair GB. Metronidazole resistance in Helicobacter pylori: magnitude, mechanism and implications for India. Indian J Gastroenterol 2002; 21 : 23-8.  Back to cited text no. 40
41.Thyagarajan SP, Ray P, Das BK, Ayyagari A, Khan AA, Dharmalingam S, et al. Geographical difference in antimicrobial resistance pattern of Helicobacter pylori clinical isolates from Indian patients: Multicentric study. J Gastroenterol Hepatol 2003; 18 : 1373-8.  Back to cited text no. 41
42.Mhaskar M, Sandhu N, Abraham P. In vitro antimicrobial susceptibility of Helicobacter pylori in Indian patients. Indian J Gastroenterol 1997; 16 (Suppl 1): S53.   Back to cited text no. 42
43.Abraham P, Sandhu N, Naik SR. In vitro sensitivity of Helicobacter pylori in India. Indian J Gastroenterol 1997; 16 (Suppl 1): S20-1.  Back to cited text no. 43
44.Krishna MM, Teja V, Prabhakar B. In vitro antibiotic sensitivity of H. pylori in India. Indian J Gastroenterol 1995; 14 (Suppl 1): A45.   Back to cited text no. 44
45.Datta S, Chattopadhyay S, Patra R, De R, Ramamurthy T, Hembram J, et al. Most Helicobacter pylori strains of Kolkata in India are resistant to metronidazole but susceptible to other drugs commonly used for eradication and ulcer therapy. Aliment Pharmacol Ther 2005; 22 : 51-7.  Back to cited text no. 45
46.Sharma S, Prasad KN, Chamoli D, Ayyagari A. Antimicrobial susceptibility pattern & biotyping of Helicobacter pylori isolates from patients with peptic ulcer diseases. Indian J Med Res 1995; 102 : 261-6.  Back to cited text no. 46
47.Bhatia V, Ahuja V, Das B, Bal C, Sharma MP. Use of imidazole-based eradication regimens for Helicobacter pylori should be abandoned in North India regardless of in vitro antibiotic sensitivity. J Gastroenterol Hepatol 2004; 19 : 619-25.  Back to cited text no. 47
48.Mukhopadhyay AK, Kersulyte D, Jeong JY, Datta S, Ito Y, Chowdhury A, et al. Distinctiveness of genotypes of Helicobacter pylori in Calcutta, India. J Bacteriol 2000; 182 : 3219-27.  Back to cited text no. 48
49.Banatvala N, Davies GR, Abdi Y, Clements L, Rampton DS, Hardie JM, et al. High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodenal disease. Gut 1994; 35 : 1562-6.  Back to cited text no. 49
50.Osato MS, Reddy R, Reddy SG, Penland RL, Graham DY. Comparison of the E test and the NCCLS-approved agar dilution method to detect metronidazole and clarithromycin resistant Helicobacter pylori. Int J Antimicrob Agents 2001; 17 : 39-44.  Back to cited text no. 50
51.Osato MS, Graham DY. E test for metronidazole susceptibility in H. pylori: use of the wrong standard may have led to the wrong conclusion. Am J Gastroenterol 2004; 99 : 769.  Back to cited text no. 51
52.Wang WH, Wong BC, Mukhopadhyay AK, Berg DE, Cho CH, Lai KC, et al. High prevalence of Helicobacter pylori infection with dual resistance to metronidazole and clarithromycin in Hong Kong. Aliment Pharmacol Ther 2000; 14 : 901-10.  Back to cited text no. 52
53.Valooran GJ, Kate V, Jagdish S, Basu D. Sequential therapy versus standard triple drug therapy for eradication of Helicobacter pylori in patients with perforated duodenal ulcer following simple closure. Scand J Gastroenterol 2011; 46 : 1045-50.  Back to cited text no. 53
54.Ahuja V, Bhatia V, Dattagupta S, Raizada A, Sharma MP. Efficacy and tolerability of rifampicin-based rescue therapy for Helicobacter pylori eradication failure in peptic ulcer disease. Dig Dis Sci 2005; 50 : 630-3.  Back to cited text no. 54
55.Chaudhary A, Ahuja V, Bal CS, Das B, Pandey RM, Sharma MP. Rank order of success favors longer duration of imidazole-based therapy for Helicobacter pylori in duodenal ulcer disease: a randomized pilot study. Helicobacter 2004; 9 : 124-9.  Back to cited text no. 55
56.Pai CG, Thomas CP, Biswas A, Rao S, Ramnarayan K. Quadruple therapy for initial eradication of Helicobacter pylori in peptic ulcer: comparison with triple therapy. Indian J Gastroenterol 2003; 22 : 85-7.  Back to cited text no. 56
57.Kumar D, Ahuja V, Dhar A, Sharma MP. Randomized trial of a quadruple-drug regimen and a triple-drug regimen for eradication of Helicobacter pylori: long-term follow-up study. Indian J Gastroenterol 2001; 20 : 191-4.  Back to cited text no. 57
58.Bhasin DK, Sharma BC, Ray P, Pathak CM, Singh K. Comparison of seven and fourteen days of lansoprazole, clarithromycin, and amoxicillin therapy for eradication of Helicobacter pylori: a report from India. Helicobacter 2000; 5 : 84-7.  Back to cited text no. 58
59.Bhasin DK, Sharma BC, Sinha SK, Ray P, Vaiphei K, Singh K. Helicobacter pylori eradication: comparison of three treatment regimens in India. J Clin Gastroenterol 1999; 28 : 348-51.  Back to cited text no. 59
60.Ahuja V, Dhar A, Bal C, Sharma MP. Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country. Aliment Pharmacol Ther 1998; 12 : 551-5.  Back to cited text no. 60
61.Gupta VK, Dhar A, Srinivasan S, Rattan A, Sharma MP. Eradication of H. pylori in a developing country: comparison of lansoprazole versus omeprazole with norfloxacin, in a dual- therapy study. Am J Gastroenterol 1997; 92 : 1140-2.  Back to cited text no. 61
62.Dayal VM, Kumar P, Kamal J, Shahi SK, Agrawal BK. Triple-drug therapy of Helicobacter pylori infection in duodenal ulcer disease. Indian J Gastroenterol 1997; 16 : 46-8.  Back to cited text no. 62
63.Sawant P, Gopanpallikar A, Chodankar C, Rathi P, Gupta R, Dhadphal S. et al. Effect of short-term regimens on eradication of Helicobacter pylori. Indian J Gastroenterol 1997; 16 (Suppl 1): S35.   Back to cited text no. 63
64.Sun Q, Liang X, Zheng Q, Liu W, Xiao S, Gu W, et al. High efficacy of 14-day triple therapy-based, bismuth-containing quadruple therapy for initial Helicobacter pylori eradication. Helicobacter 2010; 15 : 233-8.  Back to cited text no. 64
65.Furuta T, Graham DY. Pharmacologic aspects of eradication therapy for Helicobacter pylori Infection. Gastroenterol Clin North Am 2010; 39 : 465-80.  Back to cited text no. 65
66.Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther 2007; 26 : 343-57.  Back to cited text no. 66
67.Graham DY, Osato MS, Hoffman J, Opekun AR, Anderson S, Kwon DH, et al. Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study. Aliment Pharmacol Ther 2000; 14 : 745-50.  Back to cited text no. 67
68.Laine L, Hunt R, El Zimaity H, Nguyen B, Osato M, Spenard J. Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Am J Gastroenterol 2003; 98 : 562-7.  Back to cited text no. 68
69.Malfertheiner P, Bazzoli F, Delchier JC, Celinski K, Giguere M, Riviere M, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet 2011; 377 : 905-13.  Back to cited text no. 69
70.De Francesco V, Ierardi E, Hassan C, Zullo A. Furazolidone therapy for Helicobacter pylori: is it effective and safe? World J Gastroenterol 2009; 15 : 1914-5.  Back to cited text no. 70
71.Graham DY, Rimbara E. Understanding and appreciating sequential therapy for Helicobacter pylori eradication. J Clin Gastroenterol 2011; 45 : 309-13.  Back to cited text no. 71
72.Hsu PI, Wu DC, Wu JY, Graham DY. Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (Hybrid) therapy for the final 7 days. Helicobacter 2011; 16 : 139-45.  Back to cited text no. 72
73.Ramteke S, Ganesh N, Bhattacharya S, Jain NK. Amoxicillin, clarithromycin, and omeprazole based targeted nanoparticles for the treatment of H. pylori. J Drug Target 2009; 17 : 225-34.  Back to cited text no. 73
74.Ramteke S, Ganesh N, Bhattacharya S, Jain NK. Triple therapy-based targeted nanoparticles for the treatment of Helicobacter pylori. J Drug Target 2008; 16 : 694-705.  Back to cited text no. 74
75.Eapen CE. Recurrence of Helicobacter pylori infection after eradication. Indian J Gastroenterol 2000; 19 (Suppl 1): S25-7.  Back to cited text no. 75
76.Xia HX, Gilvarry J, Beattie S, Hamilton H, Keane CT, Sweeney EC, et al. Recrudescence of Helicobacter pylori infection in patients with healed duodenal ulcer after treatment with different regimens. Am J Gastroenterol 1995; 90 : 1221-5.  Back to cited text no. 76
77.Ahmad MM, Ahmed DS, Rowshon AH, Dhar SC, Rahman M, Hasan M, et al. Long-term re-infection rate after Helicobacter pylori eradication in Bangladeshi adults. Digestion 2007; 75 : 173-6.  Back to cited text no. 77
78.Hildebrand P, Bardhan P, Rossi L, Parvin S, Rahman A, Arefin MS, et al. Recrudescence and reinfection with Helicobacter pylori after eradication therapy in Bangladeshi adults. Gastroenterology 2001; 121 : 792-8.  Back to cited text no. 78
79.Bapat MR, Abraham P, Bhandarkar PV, Phadke AY, Joshi AS. Acquisition of Helicobacter pylori infection and reinfection after its eradication are uncommon in Indian adults. Indian J Gastroenterol 2000; 19 : 172-4.  Back to cited text no. 79
80.Nanivadekar SA, Bhat PP, Sawant PD, Shroff CP, Patel HD. Unusual features of Helicobacter (Campylobacter) pylori--associated gastritis in India. A study of 200 cases. J Assoc Physicians India 1990; 38 (Suppl 1): 695-8.  Back to cited text no. 80
81.Langenberg W, Rauws EA, Widjojokusumo A, Tytgat GN, Zanen HC. Identification of Campylobacter pyloridis isolates by restriction endonuclease DNA analysis. J Clin Microbiol 1986; 24 : 414-7.  Back to cited text no. 81
82.Schutze K, Hentschel E, Dragosics B, Hirschl AM. Helicobacter pylori reinfection with identical organisms: transmission by the patients' spouses. Gut 1995; 36 : 831-3.  Back to cited text no. 82
83.Czinn SJ, Blanchard T. Vaccinating against Helicobacter pylori infection. Nat Rev Gastroenterol Hepatol 2011; 8 : 133-40.  Back to cited text no. 83


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Outcome of H....
    Should H. pyl...
    Are there advers...
    H. pylori...
    H. pylori...
    Choosing the tre...
    Which regimens a...
    Development of I...
    Recurrence of
    Recommendations ...
    Article Tables

 Article Access Statistics
    PDF Downloaded703    
    Comments [Add]    

Recommend this journal