Helicobacter pylori recurrence after eradication in Latin America: Implications for gastric cancer prevention

Table 1 Characteristics of eradication trials included in Latin America

Ref.	Year	Country	Patients enrolled or randomized	Mean age ± SD (age range)	Patient population	Treatment arm(s)	Antibiotic duration (d)	Second antibiotic treatment	Eradi-cation success rate	Wait time (wk)	Diagnostic method(s)	Follow-up, yr	Study design and quality[17]
Morgan et al[22]	2013	6 countriesa	1463	(21-65)	Community populations	3 options:	Variable:	PPI + M + Bis + Tetrab	Total 77.4%	6-8	13C, CagA IgG	1	5
						PPI + A + C	14		82.20%
						PPI + A/PPI + A + M	5/5		76.50%
						PPI + A + C + M	5		73.60%
Silva et al[34]	2010	Brazil	150	46.7 (16-85)	Duodenal ulcer	PPI + A + C	7	PPI + Tetra + Furazolidone	92.50%	13	14C, H (RUT, PCR)	5	3
Mesquita et al[35]	2005	Brazil	50	49 ± 14 (> 18)	Duodenal ulcer	H2 + Bis + C	14	NA	100%	13	H (RUT, H and E)	3	2
Coelho et al[36]	1991	Brazil	48	40.4 (adults)	Duodenal ulcer	A + M + Furaz	5	NA	60.40%	8.5	14C	1.5	2
Rollan et al[37]	2000	Chile	111	38 (16-75)	Duodenal ulcer	2 options: H2 + A + M PPI + A + Tinidazole	14 14	Cross-over	Total 75.7% 79% 73%	4-6	14C, H (RUT, Warthin-S, PCR)	3	3
Figueroa et al[38]	1996	Chile	57	49.1 (16-65)	Duodenal ulcer	PPI + A + M + Bis	28	NA	80.70%	4	H (RUT, Gram, Clt)	1	5
Novoa-Reyes et al[39]	2014	Peru	140	48.9 ± 12.3 (18-85)	Non-ulcer dispepsia	PPI + A + C	10	NA	72.10%	4	14C, H (H and E)	2	3
Soto et al[40]	2003	Peru	235	37 ± 8.7 (18-55)	Non-ulcer dispepsia	PPI + A + C	14	NA	85.50%	4	14C, H (Warthin-S, Clt)	1.5	5
Leal-Herrera et al[41]	2003	Mexico	467	(> 5)c	Non-ulcer dispepsia	PPI + A + C	14	NA	30.20%	4-6	14C, H (Giemsa, Clt, PCR), Serology	2	4
Mohar et al[42]	2002	Mexico	131	51.4 ± 9.3 (> 40)	Healthy volunteers	PPI + A + C	7	NA	76.30%	6	H (H and E, Elisa), CagA IgG	1	4
Sivapa- lasingam et al[43]	2014	Bolivia	848	(> 6 mo)d	Community populations	PPI + A + C	10	“Triple therapy”	64.00%	6	13C, CagA IgG	1	3
Mera et al[19,44]	2005	Colombia	976	50.8 (29-69)	Intestinal metaplasia	Variable (the majority A + M + Bis)	14	NA	51.60%	156	13C, H (H and E, Steiner)	16	5

^aSix countries were Colombia, Costa Rica, Nicaragua, Chile, Honduras, and 2 sites in Mexico (Sonora and Chiapas);

^bVoluntary treatment;

^c66.7% were > 30 years old;

^d41.2% were > 15 years old. PPI: Proton pump inhibitor; A: Amoxicillin; C: Clarithromycin; H2: H2 Blockers; Bis: Bismuth; Furaz: Furazolidone; C: Urea breath test; H: Histology; RUT: Rapid urea test; Clt: Culture.

Table 2 Estimated Helicobacter pylori recurrence rates in Latin America studies

Ref.	Patients that received antibiotics	Patients present at f/u appointment	Recurrent cases total	Crude reinfection rate1	Follow-up (yr)	Year patients (present at f-u appointment)	Recurrence rate per 100 PY (95%CI)
Morgan et al[22]	1133	1091	125	11.46	1	1091	11.46 (9.54-13.65)
Silva et al[34]	147	112	10	8.98	5	557	1.80 (0.86-3.30)
Mesquita et al[35]	50	50	6	12.00	3	150	4.00 (1.47-8.71)
Coelho et al[36]	29	43	6	13.95	1.5	64.5	9.30 (3.41-20.25)
Rollan et al[37]	84	96	12	12.50	3	260	4.62 (2.39-8.06)
Figueroa et al[38]	47	53	1	1.89	1	53	1.89 (0.05-10.52)
Novoa-Reyes et al[39]	101	65	5	7.69	2	130	3.85 (1.25-8.98)
Soto et al[40]	201	216	44	20.37	1.5	324	13.58 (9.87-18.23)
Leal-Herrera et al[41]	141	131	32	24.43	2	262	12.21 (8.35-17.24)
Mohar et al[42]	183	109	26	23.85	1	109	23.85 (15.58-34.95)
Sivapalasingam et al[43]	543	462	57	12.34	1	462	12.34 (9.34-15.98)
Mera et al[19,44]	679	126	108	85.37	16	2024	5.34 (4.38-6.44)
Total	3338	2554	432	16.92		5487	7.89 (5.27-10.51)

¹Crude reinfection rate: Recurrent cases total/Patients present at follow-up appointment.

Table 3 Implementation of Helicobacter pylori eradication programs for gastric cancer prevention in Latin America

Components	Challenges and considerations	Implementation approaches
Public policy	Lack of awareness among the Ministries of Health, stakeholders, and the public	Large scale education campaigns for cancer and gastric cancer Joint initiatives with international stakeholders: WHO, IARC, PAHO, UICC, NCI, and CDC
Economic investment	Cost of H. pylori eradication program Economics of growing gastric cancer burden	Conduct CEAs at the country and regional level. The CEAs may differ for HICs and LMICs
Program design	Uncertainties and regional variation for target age, screening approach, treatment regimen, and follow-up	Pilot-test eradication campaigns and perform community implementation trials Adapt evidence from cost-effectiveness models and available epidemiologic data. Incorporate screening into existing public health practices (e.g., cervical cancer)
Appropriate technologies	Technical difficulties in H. pylori testing Consistent eradication confirmation norms Management of high risk patients	Develop economic, point-of-care H. pylori testing Coordinate endoscopy protocols for high risk patients (e.g., premalignant lesions) Implement information networks to coordinate eradication programs, health centers, and endoscopy centers
Adherence measures	Poor compliance with H. pylori eradication regimen, leading to treatment failure and increased infection recrudescence	Consider medication side effect profiles Pre-regimen counseling for common side effects Consider adherence measures, usual (e.g., direct observed therapy), or novel (e.g., cell phone contact)
H. pylori recurrence	Elevated reinfection rate may affect program efficacy and feasibility	Improve living conditions to reduce potential environmental sources of reinfection Consider the family or the village as the intervention target
Potential overall program risks and unknowns	Alteration of the human microbiome Induction of antibiotic resistance Potential increased risk for certain diseases (e.g., allergic diseases, esophageal cancers) Unknown role(s) of H. pylori as a component of the human microbiome: Commensal and pathogen, which may be strain and/or age dependent	H. pylori eradication programs should be considered investigational, with use of rigorous methodology and long term surveillance Monitoring of antibiotic resistance and microbiome profiles Global antibiotic stewardship programs (e.g., OTC antibiotic use, veterinary use)
Parallel research agendas	Incorporate evolving approaches and technologies	Develop novel biomarkers for host risk and H. pylori virulence Develop biomarkers for premalignant lesions (e.g., intestinal metaplasia) to facilitate endoscopy surveillance Incorporate endoscopy technologies, including advanced imaging and low-cost approaches
H. pylori Vaccination	Unknown long-term effectiveness and side effects Lack of data showing impact in clinical outcomes	Evaluate long-term (> 3 yr) effectiveness in other centers, populations and countries[23] Complete regulatory evaluations, collect additional safety data and approval by national agencies. Phase IV studies

WHO: World Health Organization; IARC: International Agency for Research on Cancer; PAHO: Pan American Health Organization; UICC: Union for International Cancer Control; NCI: National Cancer Institute; CDC: Centers for Disease Control and Prevention; HIC: High income country; LMIC: Low/middle income country; OTC: Over the counter; CEAs: Cost-effectiveness analyses; H. pylori: Helicobacter pylori.