In this study the combined use of coproscopy and serology not only improved the diagnosis of helminthiasis, but also facilitated the distinction of four phenotypically different infection profiles: (i) stool egg positive and high IgE (egg+IgEhi), (ii) the stool egg positive and low IgE (egg+IgElo), (iii) the stool egg negative and high IgE (egg-IgEhi) and (iv) the egg negative, IgE low (egg-IgElo) subgroups. Similarly, Maizels and Yazdanbakhsh  also described three phenotypic outcomes of helminth infections. In the present study, different forms of immune alterations and their possible effect on HIV infection were assessed within the defined subgroups.
Overall the prevalence of intestinal helminth infections was high (40-60%) in adults residing in this resource-limited study setting. Furthermore, the participants presented with a high IgE responder profile as shown by more than six-fold total and specific IgE above the reference ranges in both HIV+ and HIV- groups. This finding concurs with earlier suggestions that Africans generally present with elevated IgE levels as demonstrated in studies conducted in a similar ethnic group [30, 31]. IgE class switching is mediated by CD4+ Th2 cells , and it is at present unclear whether the high IgE in this population is due to a genetic predisposition or environmental influences that mediate Th2 cell predominance.
The expected hypothetical study outcome was that dual infection would adversely impact on the immune profile of affected hosts compared to singly-or non-infected counterparts. Comparisons between singly and dually-infected HIV positive subgroups revealed no significant differences in lymphocyte profiles. There was significant eosinophilia in the HIV-helminth co-infected subgroup. In the absence of HIV infection, a tendency to increased lymphocytes and marginally lower eosinophils was observed in the egg-IgElo compared to the typical helminth infected egg+IgEhi subgroup. The differences in the other cell types were not statistically significant between these two groups. The relatively smaller numbers in the HIV negative subgroups could have influenced the power to obtain statistically significant differences. The fact that no such differences were noted in the HIV positive subgroups suggests that HIV-induced immunosuppression could be responsible for masking any differences in the latter. Firstly the HIV+, egg-IgElo subgroup had the lowest median CD4+ counts. Secondly, similar percentages of participants in the egg+IgEhi and egg-IgElo subgroups were severely immunocompromised (less than 0, 2 × 109 cells/L CD4+ counts) and virus burden was similar in the two subgroups (Figure 3).
When the dually-infected subgroups were analysed, several observations revealed that certain immunological phenoytypes of helminth infection may favour HIV replication, thus by inference lending support to the study hypothesis that helminthiasis might enhance virus replication. Firstly, typical helminth infection (as reflected by the egg+IgEhi status) was accompanied by eosinophilia, approximately three-fold higher viral loads and generally lower absolute counts for all lymphocyte populations when compared to the other three subgroups. This tendency was observed in both HIV positive and negative groups. This finding concurs with the report that chronic helminth infections in adults resulted in disruptions in peripheral T cell populations . In addition, all measured activation markers were significantly elevated in the egg+IgEhi and HIV co-infected subgroup. Nearly all the CD8+ cells were CD38-positive in the egg+IgEhi subgroup (Figure 4). Immune activation has been widely implicated as playing a pivotal role in HIV pathogenesis through various pathways [1, 2, 34–36].
The observed decrease in lymphocyte populations among the egg+IgEhi individuals in this study, could indirectly relate to a compromised immunological ability to respond to HIV infection. Lymphocytes play a pivotal role in immune response to infection in general and in containing the HI virus . Eosinophils are proposed to increase the number of activated cells that are infectable with HIV since they express the CD4 receptor molecule and in vitro studies showed that when these cells are activated, they can be infected by HIV [37, 38]. These suggestions are in agreement with the study hypothesis and findings.
Furthermore, both subgroups with elevated IgE (egg+IgEhi and egg-IgEhi had eosinophilia, low CD4+ counts (especially in the HIV- group) and three-fold higher viral load (in HIV+group) compared to the low IgE subgroups (the egg+IgElo and egg-IgElo). Both eosinophilia and high IgE are classic Th2 responses that are universally induced by helminth infections [21, 32]. The association of these mediators with higher viral loads supports the concept that Th2 polarisation by helminths suppresses the protective Th1 responses and hence promotes HIV replication [1, 39, 40].
In direct contrast to these responses of high IgE subgroups, the egg+IgElo subgroup had significantly higher absolute CD4+ counts and helper/suppressor ratios and generally higher absolute numbers of all lymphocyte subsets accompanied by the lowest viral load. This finding suggests a low IgE phenotype with a better ability to control the HIV viral infection in these individuals presenting as modified Th2 responders .
Several limitations are noted in this study. The cross sectional design was a major shortcoming as both HIV and helminth infections are chronic conditions. HIV infection has different stages, each characterised by different pathogenesis and immunologic features. Likewise, helminth infections have different life cycle phases that are associated with specific immune responses. Thus, an ideal design for studies of co-infections with these two organisms would be a prospective cohort study with randomised sampling. The small sample size also limited the study. The majority of participants were females in both HIV positive and negative groups and the HIV negative participants were slightly older (10 years difference in median ages) than the HIV positive group. Both age and gender may affect many immunological and haematological parameters . These factors could possibly confound the study; nevertheless, it was encouraging to find some significant results despite the listed limitations.