Treatment guidelines for the management of H. pylori infection in developing countries have recommended first, second and rescue therapy depending on the local susceptibility pattern [8, 9] however, this is not routinely practiced due to the poor resources in these regions. As a result of increased resistance to H. pylori, the eradication rates of H.pylori have been found to be lower than 80% [9,10,11].

The worldwide prevalence of metronidazole resistance has been found to range from is 31% - 53% in Europe and South America, and between 64% and 80% in Iran and Saudi Arabia [15, 35, 36]. In this review despite high heterogeneity of the studies the overall metronidazole resistance was 75.8% which is significantly higher than that observed in Europe and America. The use of metronidazole in the treatment of other endemic diseases such as diarrheal and protozoa diseases, could explain the significantly high rate of metronidazole resistance in Africa. It should be noted that the regimen used to treat other conditions provide sub-optimal concentration that cannot eradicate H. pylori strains hence selection of resistant H.pylori strains [37, 38].

In contrast to the observed high metronidazole resistance, the overall clarithromycin resistance in Africa was almost the same as that observed in North America (30.8%) and in Portuguese (42.3%). However, the observed resistance was significantly higher than that observed in middle Eastern countries (0-8%) [10, 36] and that documented in some parts of Europe and South America [15]. The use macrolides in outpatients setting has been associated with clarithromycin resistance [39]. In Africa, the resistance to clarithromycin could be linked to the high use of macrolides in the treatment of communicable diseases which are very prevalent, further studies to confirm this are warranted.

Regarding amoxicillin, the observed overall resistance was 72.6%, which is significantly higher than that observed in Europe (0.35%), North America (2%), South America (6.6%) and Asia (23.6%). Similar trend of the amoxicillin resistance has been observed in other pathogens [40]. In Africa amoxicillin/ampicillin is the most abused antibiotics both in rural and in urban areas [41] because it is cheaply available in oral formulation. Additionally, in Africa the observed tetracycline resistance (49.8%) was comparable to that in Asia which was found to range from 0.01% in Japan to 53.8% in India [15]. This high resistance to tetracycline could lead to the failure of novel three-in-one capsule of bismuth quadruple therapy that has proven effective as the first line of treatment in areas of high clarithromycin or metronidazole resistance [13]. It should be noted that this high resistance to tetracycline in Africa could be explained by the fact that tetracycline is readily misused in the treatment of pneumonia, acne and sexually transmitted infections [42] hence selecting for H.pylori resistant strains.

The rate of quinolone resistance observed in Africa is almost similar to that documented in South America (21%), Asia(25.3%) and North America (19%) but higher than that in Europe (14.2%) [15].

Rifabutin-based triple therapy has been found to be a useful salvage therapy in treatment of H.pylori. Rifabutin is derived from rifampicin and is used in rescue treatment of tuberculosis, this has also antimicrobial activity against H. pylori. In Africa there is no studies which were done on rifabutin instead two studies reported on rifamycin 87% in 2009 and rifampicin 0% in 2016 which shows the resistance is declining in this drug group. This might be due to the careful use of anti-Tuberculosis drugs.

Mutations

H, pylori strains in Africa were found to carry A2143G, A2142G, A2147G and A2146C mutations that can lead to clarithromycin-resistance. Similar mutations have been observed in Asia [43, 44] and in South America, Europe and North America [45,46,47,48,49]. This can be due to migration process of human being [50]. In other part of the World in addition to these mutations other mutations in different positions have been found to confer clarithromycin resistance in H pylori strains (T2182C, T2190C, C2195T, A2223G, G2141A, C2694A, G2224A, C2245T, T2289C) [51,52,53]. The addition mutations in other part of the World can be due to phylogeographic tree differences of H. pylori by either gain(recombination) or gene loss(loss by deletion) in multiple strains which result in sequence and gene content diversity [54]. Metronidazole mutations [22, 25, 55] and quinolones mutations [56,57,58] observed in Africa were similar to that observed in Europe, in Asia and America.

In our review H.pylori mutation conferring resistance to tetracycline had two base pair mutation AGC926-928 as observed in Congo Brazzaville, similar mutation was obtained in other parts of the world, in America [59, 60], Europe and Asia [61, 62].

One of the major limitation of this review is significantly high heterogeneity of the studies, this could be due to lack of methods standardization, heterogeneity of the population, and difference in discs quality. Despite this limitation the magnitude the data have been presented to highlight the importance of the problem and the need for standardized surveillance system.