Africa presents unique challenges for rotavirus immunization. First, the continent carries the highest burden of rotavirus mortality, where 12 of the 13 countries with greatest mortality rates per capita are located [2, 34], and more than 250,000 children perish annually due to rotavirus [29, 35]. Rotavirus vaccines are urgently needed in this region which would make a substantial contribution in reducing childhood deaths and hospitalizations due to rotavirus . Most GAVI (Global Alliance for Vaccines and Immunization)-eligible countries are concentrated in Africa and the lowest global immunization coverage is also recorded here . Given the high burden of rotavirus disease in Africa, the WHO recommends the early administration of rotavirus vaccines with the first two immunizations at 6 and 10 weeks of age .
Secondly, rotavirus strain diversity is extremely high in Africa with some novel G- and P-types circulating commonly [17, 27–30]. Besides the globally emerging novel rotavirus strains, G9 and G12, which also occur commonly in Africa [21, 24, 25, 38, 39], G8 strains are frequently identified and seem to have an unusual affinity for Africa [17–21]. Furthermore, strains with the P genotype circulate commonly in young African children with symptomatic rotavirus infection [17, 28].
The wide circulation of diverse and unusual rotavirus strains in the region, emphasizes the importance of demonstrating cross-protective efficacy of the monovalent rotavirus vaccine, Rotarix™ in preventing severe gastroenteritis [24, 28, 40]. Previous study has demonstrated that heterotypic protection may be due to the expression of serologically or genotypically identical proteins other than those encoded by the different G-types . The immune response to the VP4 antigen has been demonstrated to be significant , and there are cross-reactive epitopes on the VP4 protein . The relative lack of diversity among P-types  when compared with the G types, may aid in heterotypic protection as suggested previously . In addition, protection may be offered via immune effector mechanisms other than neutralizing antibody .
In the present paper, in addition to the common G1 and P types, we observed five G types (G2, G3, G8, G9 and G12) and two P types (P and P) in circulation during the study period. Importantly, the G8 and G12 types have not been observed in earlier efficacy studies providing the opportunity to assess vaccine efficacy against these novel types [9–11]. Similarly, the numbers of strains bearing the P genotype with various G-types, all heterotypic to the G1P vaccine strain, enable an assessment of vaccine efficacy against truly heterotypic strains. The strain combinations used to generate the results include 8 G2P strains, 19 G8P strains and a single G8P, and 23 strains bearing G12P specificity.
The overall vaccine efficacy of the monovalent rotavirus vaccine in preventing severe rotavirus gastroenteritis in African infants was previously reported as 61.2% (95% CI: 44%; 73.2%) . G1 wild-type was the predominant circulating rotavirus type isolated from 23 severe rotavirus gastroenteritis episodes in placebo group. Interestingly, the pattern of circulation of rotavirus types differed considerably between South Africa and Malawi during the study period. Unlike South Africa, where G1 was predominantly circulating (isolated from 18 severe rotavirus gastroenteritis episodes in placebo group) similar to worldwide epidemiology, this was not the case in Malawi, where G1 wild-type strains were the lowest seen in more than a decade of surveillance . In Malawi, G12 was the predominant rotavirus type (isolated from 13 severe rotavirus gastroenteritis episodes in placebo group), as observed in an earlier study by Cunliffe et al, where G12 was identified as a newly emerging rotavirus type in Malawi . Furthermore, G9 was circulating only in Malawi during the study period and hence the overall efficacy data on G9 rotavirus type reflected the Malawi-specific situation.
We can anticipate that the monovalent rotavirus vaccine will provide protection against the circulating rotavirus types that shared either the G or the P type with the vaccine strain (homotypic protection). However, the G2 and G8 types were all circulating in combination with P type (with a single strain bearing G8P specificity), sharing neither the G or the P type with the vaccine strain. It is therefore important to note that significant protection was afforded by the vaccine against severe gastroenteritis caused by these dually heterotypic rotavirus types (vaccine efficacy against G2: 79.2% [95% CI: 8.9%; 96.5%; p -value = 0.017]; vaccine efficacy against G8: 64.4% [95% CI: 17.1%; 85.2%; p-value 0.010]; vaccine efficacy against P: 70.9% [95% CI: 37.5%; 87.0%]). This is an important observation as the earlier efficacy studies showed limited heterotypic protection [9–11], and there has been some suggestion that the monovalent vaccine may not confer cross protection against non-vaccine strains.
These data are encouraging because with the diversity of the rotavirus types in circulation and the global emergence of new strains in the human population, homotypic protection alone will be unlikely to provide complete protection against severe rotavirus gastroenteritis. Heterotypic protection of the rotavirus vaccine is important to effectively reduce the rotavirus disease burden.