Our findings can be interpreted in many ways. First, we documented colonization with MRSA among PLWHA from inner São Paulo State. The point prevalence rate (2.4%) is not particularly high when compared to the international literature – where prevalence of up to 16.8% are reported [23]. In fact, our rate is lower than the pooled prevalence of 6.9% reported in a recent meta-analysis [33]. On the other hand, a survey performed in the early 2000s including HIV-positive outpatients from inner São Paulo did not find any subject harboring MRSA [34]. Even though that study was conducted in another city, it is reasonable to infer that prevalence of MRSA colonization may be growing. It is also worth noting that, among our subjects who were studied in three surveys, the cumulative prevalence (i.e., MRSA positive in any of the surveys) was higher than 10%.
The emergence of CA-MRSA was a turning point both in the epidemiology and in the clinical relevance of staphylococcal infections [35]. However, authors have recently reported a blurring of the definitions of “community-associated” and “healthcare-associated” infections [36]. This is especially the case for special groups. PLWHA are a heterogeneous population that includes both seemingly “healthy” persons (asymptomatic, most achieving viral control with proper therapy) and others with poor compliance to therapy and a history of several opportunistic infections. Often, this latter group presents variable amounts of social vulnerability, including poverty, alcoholism and addiction to illicit drugs [38]. In countries – such as Brazil – where the poorest people have access to public health, this group is more often admitted to acute care hospitals. Therefore the same population may be exposed to risk factors associated with CA-MRSA (illicit drugs, poor hygiene practices) and HA-MRSA (frequent admissions), making it difficult to ascertain the origin of isolates on epidemiological grounds [37], [38].
Our results are exemplary. Eighteen out of 19 isolates tested positive for SCCmec type IV, usually found in CA-MRSA. However, recent hospital admission was epidemiologically associated with MRSA carriage in one of the logistic regression models. An alternative model associated MRSA with previous neurocryptococosis (an infection that invariably requires hospital admission) and the use of crack. Neurocryptococosis may be a proxy that suggests an association of MRSA to admissions that took place more than a year before the survey (and therefore did not meet the “recent admission” criteria). On the other hand, the use of crack has become epidemic in Brazil, and is part of a common milieu that combines poverty, violence and sexually transmitted diseases [39].
It is worth noting that, despite the small number of subjects colonized with MRSA in the first survey, the factors associated with this outcome were more meaningful than those associated with overall S. aureus. Indeed, subjects colonized with S. aureus were less likely to have received beta-lactams antimicrobials and more likely to use illicit drugs. This latter finding is puzzling, but it may reflect changes in microbial ecology of nares and throat that favor overgrowth of competing microorganisms. One should notice that the use of intravenous drugs – a reported risk factor for MRSA – is rare in Brazil, a pattern reflected in our sample. [40]
There is now sufficient evidence for international spread of specific MRSA clones [41]. However – and contrary to the case for HIV – the routes for this dissemination are far less clear [42]. Therefore, studies that approach networks of transmission – such as households and neighborhoods - are required [43], [44]. Miller et al [45] carried out a survey selecting subjects in a household level, and found that, in dwellings with more than one member colonized with S. aureus, 50% carried that same strains. Sexual transmission has been demonstrated [46], but it obviously does not explain all events of spread among household members. We addressed this issue by performing a survey among HIV-negative household contactants of study subjects. As presented above, a positive index subject was associated with greater risk of colonization of household members in analysis for both overall S. aureus and MRSA. However, only one patient had a household contact colonized with the same strain as his. We did not type methicillin-susceptible S. aureus, and therefore could not detect possible transmission of those strains among family members.
Interesing insights arise from comparison of this study with the population-based survey of nasal S. aureus colonization, conducted in Botucatu in 2011. In that study, we identified two instances of MRSA transmission among family members [25]. Also, two subjects living in the same street harbored similar isolates. It is worth noting that 3 out of 6 isolates from that study grouped with strains from the present investigation. This finding suggests the long-term persistence of specific clones in the population. The fact that clusters grouped isolates from people living in Botucatu and in other neighboring cities points out either to regional spread or to cross-transmission during outpatients appointments.
The clinical significance of MRSA colonization among PLWHA is not completely clear. While for some authors colonization is a major risk factor for invasive infections [47], others believe this association does not apply to the dinamics of CA-MRSA [48]. Our study was not designed to address those issues, and we found no association between MRSA (or S. aureus) colonization and presumed bacterial infections. But, interestingly, in all subjects submitted to serial collections of swabs, MRSA was found in only one occasion. Furthers research is necessary in order to clarify if MRSA carriage among PLWHA in Brazil is generally transient. This issue – transient versus persistant S. aureus colonization in PLWHA – was addressed previously, but in that study no subject carried MRSA. [34] In that study, advanced HIV disease was associated with persistent colonization.
In order to assess both the distribution of PLWHA and of colonization, we georreferenced dwellings of subjects who lived in Botucatu. This allowed us to identify “hot spots” concentrating cases of HIV/Aids and colonized subjects. However, we failed to demonstrate special correlations with two important measures of social vulnerability – the average number of people in dwellings and the average family monthly income. The number of MRSA-positive subjects was too low to warrant a specific analysis.
Our study has some limits, which regard the relatively small sample (especially in serial surveys), not collecting swabs from other body sites (e.g., groin) and the fact that typing of methicillin-susceptible strains was not performed. However, it also has strengths, including an effort to address extensively the subjects vulnerability and the combined use of classical, molecular and spatial epidemiologic methods.
In conclusion, we documented small but relevant prevalence of MRSA among PLWHA from small cities in inner São Paulo State, Brazil. Despite the small number of MRSA-colonized subjects, we found association of this carriage to previous hospital admission and use of crack. Findings from PFGE typing point out to spread in different levels – household, city, neighboring municipalities. While more research is needed to fully acknowledge the threat posed by MRSA to PLWHA, it is clear that any policy directed at preventing and/or controlling that agent must not be restricted to great urban centers.