- no title specified

HIV AND HUMAN PARVOVIRUS B19 CO-INFECTION: SEROPREVALENCE OF SERUM IgM and IgG SPECIFIC ANTIBODY AND ASSOCIATION WITH C D4+ T LYMPHOCYTES SUBSETS

1Department of Haematology & Blood Transfusion, Ahmadu Bello University Zaria 2Department of Medicine, Immunology Unit, Ahmadu Bello University Teaching Hospital, Shika – Zaria, Nigeria, 3Department of Medical Laboratory Science, Ahmadu Bello University Zaria

Table 1: Socio-demographic Characteristics of the

Participants

Parameters	Study Group (%)	Control (%)	Total (%)	Statistical
Age (years)
Mean (SD)	32.61±11.43	34.63±9.38	92	P = 0.543
Sex
Male	31(16.8)	29(15.8)	60(32)6)	ϰ2 = 0.099 p = 0.753
Female	61(33.2)	63(34.2)	124(67.4)	ϰ2 = 0.099 p = 0.753
Total	92(50.0)	92(50.0)	184(100.0)
Ethnicity
Hausa Yoruba Igbo Others	52(28.4)	41(22.4)	93(50.8)	ϰ2 = 4.789 p = 0.188
	12(6.6)	18(9.8)	30(16.4)
	4(1.6)	8(4.4)	11(6.0)
	24(13.1)	25(13.7)	49(26.8)
Total	92(49.7)	92(50.3)	184 (100)

DISCUSSION

In this study, the ratio of the study to control groups was 1:1, although unmatched, the two groups come from the same population since their sociodemographic characteristics were not significantly different, when HIV-positive study group was compared to the control group (HIV-negative) table 1. However, there are more female participants than males in the study group. This could indicate that more females attended Nasara clinic (HIV clinic) than their males’ counterpart due to various reasons such as avoidance of stigma and the responsibility of work in males, also female may have a more health seeking behaviour than the males.

The sero-prevalence of PV-B19 specific IgG antibody in HIV patients reported in this study is significantly higher than that of the HIV negative control group (52.1% Vs 36.2% p 0.007, OR 0.244, CI 0.806) but lower than 62% sero-prevalence reported in a study carried out in Keffi, Nasarawa State, Nigeria.16 However, the sero-prevalence of PV-B19 specific IgG antibody in HIV negative control was lower than the prevalence of 85.4% reported among the paediatric age group from the same environment, Zaria.18 The sero-prevalence of PV-B19 IgG antibody in this study is also lower than the 60-70% reported from England36 but higher than 16.2% reported in Singapore37, 39.5% reported in Jos38 and 41.5% in Kano19.

In this study, the sero-prevalence of PV-B19 specific IgM antibody in HIV patients is significantly higher than that of the HIV negative control group (28.8% Vs 15.2% p 0.032, OR 0.456, 95% CI 0.220, 0.943), which is indicative of recent infection because IgM antibodies is the first antibodies produced during humoral immune response and later substituted by IgG antibodies.39 In HIV infected patients, PV-B19 specific IgG antibodies sometime persists, this suggest that chronic PV-B19 infection occurs in HIV infected patients whose immune system are not capable of mounting a sufficient response which agrees with the findings of Naides et al.,20 who concluded that patients with HIV infection and in people with defective immune system, PV-B19 infection may often results in chronic infection. The higher PV-B19 IgM and IgG antibody observed in this work compared to the works of Yoto et al.,40 may be due to difference in sampling methods, population size and assay method (DNA test in their case). Although the sero-prevalence of PV-B19 antibodies was significantly higher in the HIV positive patients, the sero-prevalence of both PV-B19 specific serum IgM and IgG (15.2% vs 28.8%) in the control group, implies that the prevalence of PV-B19 is also high even in the general population. This may not be unconnected to the influence of immunosuppression in HIV positive patients. The relatively high sero-prevalence among the healthy controls is consistent with reports from other studies in other part of the world, Heegard et al41, in Copenhgen, Demark with B19 sero-prevalence range of 30-60% in healthy adults, 6.79% in China42, 26% in Egypt43, 27.96% in Pune44, 63.3% in Khartoum45. In Nigeria, a research conducted in Ayingba and Lokoja in Kogi state of PV-B19 infections in blood donors; a sero-prevalence of 42.0% PV-B19 for both IgG and IgM antibodies was reported13, 56.7% in Lagos15, 42.2% in North Eastern Nigeria,14 but much more higher PV-B19 specific-IgG antibody sero-prevalence was obtained in blood donors; 74% in Belgium46, 76.3% in Makkah47,79.1% in Italy48 and Vemazza et al20., found a significantly higher prevalence of B19-specific IgG in their cohort of HIV-infected patients than in a cohort of HIV-negative controls (81% vs. 57%, respectively; P < 0.01). Thus, our observations in this study are unexpected as different seroprevalence rates has been previously reported for selected groups of healthy individuals and patients with HIV infection. These variations in the rate of seropositivity among both the patients with HIV infection and healthy population might indicate an increased susceptibility to parvovirus B19 infection, or differences in the epidemiological and demographic characteristics resulting in different rates of exposure to co-infection with PV B-19. It may also be due to the differences in the specificity and sensitivity of the assay method used.

The relationship between human PV-B19 IgM and IgG status in both HIV treatment naïve study and control participants were also analysed (Tables 3 and 4), and both showed a significant relationship between IgG and IgM (p=0.009, p=0.015) respectively. Acute infection with PV-B19 is controlled by neutralizing antibodies of the humoral immune response, characterized by the appearance of serum IgM and IgG in the natural course of the infection. Antibodies directed at the unique portion of the linear B19 epitopes within the viral protein are functionally important as their ability to react correlates with their capacity to neutralize virus infectivity and patients with an underlying immunodeficiency and PV-B19 infection may have B19 specific antibodies that fail to recognize linear epitopes.33, 49 Thus PV-B19 IgM and IgG status is associated with both acute and chronic infection, the virus is cytotoxic to host cells.50

The CD4+ T-cells count of the healthy controls were significantly higher (P= 0.001) than that of the HIV infected patients (study group) which are immunocompromised compared to the former who are largely immunocompetent (Table 5). The low CD4+ T-cells count of the study group is due to the destruction of CD4+ T cells in HIV-infection which has been attributed to both direct infection and Fas/Fas ligand-mediated apoptosis.51 Studies in HIV-infected patients have since shown a similar pattern of preferential and profound depletion of CD4+ T cells within the systemic tract during infection.52

Following stratification of the level of CD4+ T count, the relationship between PV-B19 IgM and IgG status and CD4+ T-cells count of the study and control group were studied, although a higher number of the participants had positive antibodies with severe immunosuppression (CD4+T cell < 350) and fewer number had CD4+T cell > 350, a trend towards increase seroprevalence rates that paralleled a declining CD4+ T lymphocyte count was observed. However, this trend was not significant when analysed with the use of X2 test (PV-B19 IgM and IgG with CD4+ T cell count of HIV infected positive patients and negative controls p=0.677, p=0.783 respectively Figure 1). Therefore, this implies that infection with PV-B19 may not necessarily be related to the degree of immunosuppression. Our finding is similar to the report of Petrol et al who reported a significantly higher prevalence of IgG antibodies to B19 in the HIV-positive group than among the controls (81% vs. 57%; P < .01, X2 test).53 IgM antibody is the first immune response that appears in order to neutralize the virus but do not last for a long period of time and therefore may not affect the CD4+ T-cells at this initial stage of the infection. However, IgG antibodies play a vital role in immune response to PV-B19 infection and when produced, persist for several months to years. It also forms memory against future attack, IgG is directed to VP1 and VP2 conformation and to some extent VP1 linear epitope.54 The virus replicates in human erythroid progenitor cells of the bone marrow and peripheral blood to inhibit erythropoiesis. It requires P-blood group antigen which is found mostly on cells of the erythroid lineage but also in platelets where it induces anaemia and thrombocytopaenia.13, 55

The prevalence of PV-B19 IgM and IgG positivity among the controls participants was assessed based on enrolment category Table 4). The result shows a relatively high percentage of PV-B19 infection in each of the five categories of the controls group, however though there was no significant difference between the categories (IgM p=0.476, IgG p=0.751). This implied, that blood donors, hospital staff, patients relative, student and every other person are at risk of Parvovirus B19 infection, and this agrees with the finding of other studies.56, 57 Transmission of PV-B19 infection occurs via the respiratory route, through blood-derived products administered parentally and vertically from mother to foetus. Parvovirus B19-specific DNA has been detected in respiratory secretions, suggesting that virus is generally spread in the community by a respiratory route. Nosocomial transmission has been reported, and transmission has also been reported among staff in laboratories handling native virus. 58, 59

CONCLUSION

Parvovirus B19 infection is higher in treatment naïve HIV infected adult patients than HIV negative individuals and this may not be necessarily associated with the severity of immunosuppression. Thus, we advise a high index of suspicion both the general population and HIV infected individuals irrespective of the immunological stage of the disease.

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PV-B19 IgM	PV-B19 IgG
	Study Group				Control
	Positive (%)	Negative (%)		Total (%)	Positive (%)	Negative (%)	Total (%)
Positive	8(8.7)	18(19.6)	26(28.3)		9(9.8)	5(5.4)	14(15.2)
Negative	40(43.5)	26(28.3)	66(71.7)		21(22.8)	57(62.0)	78(84.8)
Total	48(52.2)	44(47.8)	92(100.0)		30(32.6)	62(67.4)	92(100.0)

Category	PV-IgM			PV-IgG
Category	Positive(%)	Negative(%)	Total (%)	Positive(%)	Negative(%)	Total (%)
Blood donors	3(3.3)	24(26.1)	27(29.3)	8(8.7)	19(20.7)	27(29.3)
Hospital Staff	7(7.6)	21(22.8)	28(30.4)	10(10.9)	18(19.6)	28(30.4)
Non-Hospital Staff	4(4.4)	33(35.9)	37(40.2)	12(13.0)	25(27.2)	27(40.2)