To address gaps in knowledge about PARV4, we have recently developed an ELISA for antibodies to the viral protein 2 (VP2) of PARV4 genotype 1 to expand investigations of epidemiology and transmission of the virus (10). Larger scale screening confirmed the previously noted association between PARV4 infection and parenteral routes of exposure (injection drug use) in the United Kingdom and United States, much lower infection frequencies in HIV-infected gay men, and zero seropositivity in low-risk controls. We additionally found serologic evidence for high rates of PARV4 exposure among persons with hemophilia exposed to nonvirally inactivated factor VIII/IX concentrates but a virtual absence of infection in sibling controls occupying the same households.

To investigate further the epidemiology of PARV4 in sub-Saharan Africa, we assembled large sets of serum or plasma samples collected from a range of adult populations in several countries in Africa (Table). Samples were screened in duplicate by our previously described ELISA (10) by using protein purified in parallel from empty baculovirus constructs as control antigen to minimize assay nonspecificity. Low-risk orthopedic outpatient attendees (United Kingdom) and HIV-negative and HCV-negative nonremunerated blood donors (France) were used as negative control populations.

Serologic screening for PARV4 antibodies showed that the combined set of 360 blood donor and control samples from the United Kingdom and France were nonreactive by ELISA (Table). In marked contrast, high rates of anti-PARV4 reactivity were detected in populations from sub-Saharan Africa. The highest rates were observed in Burkina Faso, where a frequency of 37% was recorded among a screened HIV-negative and HCV-negative blood donor population. Frequencies of seropositivity were 25% and 35% in Cameroon and Democratic Republic of the Congo, respectively, and lowest in South Africa (4% in HIV-negative persons). However, within the latter group, HIV-1–infected donors were significantly more frequently seropositive for PARV4 than those who were not infected with HIV (36%; p<0.0001 by Fisher exact test). However, even with this risk factor, the overall prevalence was not as high as observed in the HIV-negative blood donors in Burkina Faso.

These findings provide new and unexpected information on the epidemiology and transmission of PARV4. First, although there is no evidence of PARV4 infection in nonpotentially exposed persons in Western countries (from the limited number currently surveyed), populations in sub-Saharan Africa, particularly in Central Africa, show high rates of exposure that cannot plausibly be accounted for by parenteral exposure. For example, the highest rate of seropositivity was observed among blood donors in Burkina Faso and Democratic Republic of the Congo who were uniformly negative for HCV antibodies, as well as for HIV-1 antibodies, by third-generation screening. In this setting, HCV infections are a frequent correlate of multiple blood transfusions and use of unsterilized needles in medical treatment or vaccination, as well as injection drug use. The high rate of seropositivity among HCV screen-negative samples from all 4 countries in Africa provides strong evidence for an alternative route of PARV4 transmission that is largely or entirely absent in Western countries.

These findings are consistent with PCR-based evidence for PARV4 viremia, presumably associated with acute infection, among young children in rural Ghana (11), a country adjacent to Burkina Faso where similar conditions for virus transmission may exist. In this study group, parenteral exposure was not identified, although infections were more frequent in families in low socioeconomic groups and those living near rivers and without a domestic water supply. In a separate study, autopsy samples from 2 HIV-infected African men (from Nigeria and Democratic Republic of the Congo) were PARV4 positive, despite not being infected with HCV and without a history of parenteral exposure (12). Neither study identified the specific risk factors and PARV4 infection sources.

It clearly is a challenge to conceive transmission routes for a virus that will not be directly transmitted among members of the same household, as demonstrated by the hemophiliac sibling data for the United States (10). Hypotheses such as possible arthropod-borne or parasite-associated transmission require careful evaluation, bearing in mind that parvoviruses, in common with other DNA viruses, are highly host species specific, and no other instances of vector-borne transmission in this virus family have been recorded.

The second major observation was a substantial difference in the rate of PARV4 seropositivity between those who were HIV infected and those uninfected (in South Africa, 36% and 4%, respectively). This association with HIV appears initially consistent with higher frequencies of PARV4 seropositivity reported among HIV (and HCV) co-infected injection drug users in Western countries. However, in the latter group, the association with HIV-1 was thought to reflect a greater frequency of illicit injection with shared needles (4,9). Furthermore, low frequencies or absence of PARV4 infections were observed in HCV-uninfected persons acquiring HIV-1 infection by sexual contact. How HIV-1 facilitates or becomes epidemiologically associated with PARV4 infection in HCV-negative South African blood donors thus remains unexplained in a population where HIV-1 infections are primarily acquired through sexual contact.

Although this study leaves many questions on the transmission of PARV4 unanswered, the striking differences in seroprevalence and risk-group associations between sub-Saharan Africa and Western countries provides the basis for future more detailed investigations of its transmission routes, epidemiology, and potential clinical outcomes of infections. The previously noted sequence homogeneity of PARV4 nucleotide sequences between variants detected in Western countries (4,13) is consistent with its recent global spread. A possible source in sub-Saharan Africa for PARV4 would contain many potential parallels with the emergence and global spread of HIV-1 and HCV in the 20th century.