Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV) in Ugandan women
- Katie Wakeham1, 2Email author,
- Emily L Webb3,
- Ismail Sebina1,
- Lawrence Muhangi1,
- Wendell Miley4,
- W Thomas Johnson2,
- Juliet Ndibazza1,
- Alison M Elliott†1, 5,
- Denise Whitby†4 and
- Robert Newton†2, 6
© Wakeham et al; licensee BioMed Central Ltd. 2011
Received: 12 July 2011
Accepted: 30 September 2011
Published: 30 September 2011
Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda.
Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education.
Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.
Infection with KSHV is the underlying cause of Kaposi's sarcoma (KS), although it may not be sufficient . Immune suppression, such as that caused by human immunodeficiency virus (HIV), significantly increases the risk of KS among KSHV infected people and is associated with increased viral load and viral shedding [2–8]. Among people without HIV infection or other forms of overt immune suppression, geographic and temporal variation in the incidence of KS and in the prevalence of KSHV suggest that cofactors may be important in facilitating both transmission and disease [9–18]. Whether cofactors act directly or via effects on the immune system is unclear .
Many environmental co-factors for KSHV transmission and disease have been suggested, including volcanic soils , limestone  and 'oncoweeds' - that is plants with carcinogenic properties or the ability to reactivate KSHV in vitro - although epidemiologic evidence of a role for these agents remains scant . Ecological studies in the Mediterranean area found that eradication of mosquitoes and other blood sucking arthropods was associated with declines both in the prevalence of KSHV and in the incidence of KS [9–14, 18, 23]. The 'promoter arthropod hypothesis' suggests that insect blood feeding increases KSHV transmission through viral reactivation and KS through inflammatory mechanisms associated with the bite [11, 14].
Studies of KS in Africa have identified risk factors for KS that might be common to risk of certain parasites, such as exposure to water, high rainfall and walking barefoot [15, 24–26]. Previously reported risk factors for KSHV, such as use of surface rather than piped water, may also be consistent with increased exposure to parasites . Ecological associations between malaria and KSHV or KS in Africa are inconclusive . Only one study has attempted to measure parasite burden among cases with KS and controls; KS patients had a higher carriage of certain intestinal helminths than did controls .
Parasites impact on immune function [29, 30] and could, therefore, modulate the host response to KSHV. The association between EBV (another gamma herpesvirus) and malaria is well documented [31–34]. Parasite-related immune modulation may increase susceptibility to KSHV infection and may also be associated with increased viral shedding and transmission, leading to an increased prevalence of KSHV infection and increased incidence of KS. We tested the hypothesis that parasites may be associated with KSHV by examining associations between current parasite infections and presence of antibodies against KSHV.
The investigation was conducted within an existing study in Uganda - the Entebbe Mother and Baby Study (EMaBS) - a large on-going double blind randomised placebo controlled trial designed to determine the impact of helminth infections and their treatment on vaccine responses and infectious disease outcomes. Detailed information about the study design has been reported elsewhere . Briefly, consenting pregnant women resident in Entebbe and Katabi were recruited from the government funded antenatal clinic at Entebbe hospital, Uganda. Blood samples were obtained by venepuncture, and processed for syphilis, HIV serology, CD4 count and for examination for malaria parasites and Mansonella perstans. A stool sample was obtained for examination for intestinal helminths. Of note, women were apparently well on the day of enrollment, so infections identified were essentially asymptomatic. Information was collected on clinical and socio-demographic variables and socio-economic status was defined according to a composite variable comprising information on several relevant factors .
Maternal plasma samples from the enrolment visit- stored at -80°C at the Uganda Virus Research Institute (UVRI), Entebbe, Uganda - were identified for 1915 women. KSHV serologic testing was based on ELISA for recombinant proteins to K8.1, a KSHV structural glycoprotein expressed during lytic infection, and for ORF 73, a nuclear antigen expressed during latency as previously described [36, 37]. Each ELISA plate contained three positive and three negative controls for quality control and cut-off calculation. Both K8.1 and ORF 73 assay have high performance accuracy with a sensitivity of 98.78% and 89.02% respectively and specificity of 98.79% and 97.57% respectively . The ELISAs were performed at the Uganda Virus Research Institute (UVRI) by the study lead and a technician, both of whom were blinded to patient details. The two assays were used to define evidence of KSHV - individuals were considered to be seropositive if they were positive to either assay and negative if both ELISA assays were negative. The assays were transferred to UVRI from the Viral Oncology Section (VOS), National Cancer Institute (NCI), USA and analysis of the positive and negative controls showed comparable performance at NCI and UVRI. The geometric mean optical density (OD) of the ORF 73 positive and negative controls was 2.50 and 0.04 respectively at VOS, NCI and 2.62 and 0.06 respectively at UVRI. The K8.1 positive and negative controls were 2.23 and 0.10 at NCI and 2.22 and 0.06 at UVRI. Analysis of 375 samples tested in duplicate at both VOS, NCI and UVRI resulted in Kappa values of 0.89 for the K8.1 ELISA and 0.86 for the ORF 73 ELISA.
For parasite intensities, hookworm was measured by egg counts in stool and catogorised as light (< 1,000 eggs per gram (epg) of stool), moderate (1,000 to 3,999 epg) and heavy infection (≥4,000 epg) [35, 38]. The intensity of malaria infection was categorised as being below ("low") or above ("high") the median parasite count, per 200 white blood cells. For microfilariae, tertiles of the number of filaria per millilitre of blood were used to categorise into low, medium and high infection intensity.
Data were analysed using Stata11SE (StataCorp LP, College Station, Texas, USA). Potential associations between KSHV seropositivity and each potential risk factor were estimated using the Pearson chi-squared test or Fisher's exact test where expected numbers were small. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression modeling controlling for age and other possible confounders. The possibility of multiple parasite infections increasing risk of KSHV seropositivity more or less than expected under a multiplicative model was assessed by fitting terms for interactions between parasites in the logistic regression model. The agreement between K8.1 and ORF73 ELISA assays was assessed formally by calculating a Kappa statistic. All p values were 2-sided and we considered p<0.05 to be statistically significant.
Results and Discussion
The median age of women in the study was 23 years (IQR 19-27); most were in the third trimester of pregnancy (54% (1032/1915) with 46% (879/1915) in the second). The seroprevalence of HIV was 10% (193/1915) and the median CD4 count among those who were seropositive was 551 (IQR 368-796). The highest level of educational attainment reached by the majority of women was primary (50% [961/1911]), with 62% (1191/1915) describing themselves as unemployed or housewives and 82% (1561/1905) reporting a personal income of less than 30,000 Ugandan Shillings (approx. $12USD) per month. The prevalence of antibodies to K8.1 was 41% and to ORF 73 was 52%. 32% of women were seropositive to both antigens and 61% had antibodies to either ORF 73 and/or K8.1. There was moderate concordance between latent KSHV ORF 73 and lytic KSHV K8.1 assays in detecting KSHV seropositivity (k = 0.43), consistent with previous studies [37, 39]. Prevalence of antibodies did not change significantly with age, although the age range of study participants was relatively narrow. Previous studies of women in a similarly narrow age range in Africa have showed little or no association with age [27, 37, 39, 40]. As expected, prevalence decreased with increasing maternal education and household socioeconomic status 
Crude associations with antibodies against KSHV and sociodemographic and clinical risk factors among Ugandan women.
Prevalence of women KSHV seropositive*
OR (95% CI)
> = 35 years
Use of mosquito spray in the home
Use of bed net
Adjusted associations with antibodies against KSHV and sociodemographic and clinical risk factors among Ugandan women.
OR (95% CI)
Crude associations with antibodies against KSHV and intensity of parasite infection in Uganda women.
Prevalence of women KSHV seropositive*
OR (95% CI)
Mode of KSHV transmission is yet to be fully elucidated, but high acquisition rates during childhood imply a non-sexual route [7, 27, 37, 40–49]. In studies of mother-child pairs [37, 40, 50], the impact of HIV on KSHV seropositivity is unclear with some studies reporting a positive impact  and others reporting borderline or null association [40, 50]. We observed no statistically significant association between HIV and KSHV seropositivity. There was no association between KSHV seropositivity and CD4 count in HIV infected women (p = 0.13). The lack of association with syphilis is consistent with previous studies reporting no association with KSHV and markers of sexual behavior [37, 47, 51, 52]. In unadjusted analyses, the use of insecticide in the home was associated with a lower prevalence of antibodies against KSHV (p = 0.005) although use of a bed net and walking barefoot (a risk factor for hookworm infection) was not. Effects of increasing numbers of infections on KSHV seropositivity combined multiplicatively; there were no interactions between the effects of HIV, malaria parasitaemia, hookworm or Mansonella perstans on KSHV infection (results not shown). KSHV seropositivity was not associated with trimester or pregnancy duration as measured in months. The results for ORF 73 and K8.1 separately, did not materially differ.
This study has a number of important limitations. It is possible that associations arose as a result of residual confounding by socio-economic status (SES), although adjustment for certain markers of SES had no effect on the findings. Furthermore, the work was cross sectional and so associations identified should be confirmed in longitudinal studies. Also, the study participants were pregnant and pregnancy itself may modulate immune function. However, since all comparisons were internal within the study (i.e. comparing one group of pregnant women with another), it is difficult to see how this could have impacted on the results.
The findings reported here provide evidence of an association between specific parasites and presence of antibodies against KSHV. Specific parasite infections may increase KSHV replication or cause reactivation, thereby increasing the likelihood of detecting antibodies against KSHV. Alternatively, specific parasites may increase susceptibility to infection - we cannot, in this study, distinguish between these two possibilities. Co-factors for KSHV transmission and disease have been sought to explain the elevated prevalence of KSHV and incidence of KS in sub-Saharan Africa. Data presented here suggest that parasites may constitute one such co-factor. Further epidemiological and laboratory studies are needed to fully understand the role of parasites as a risk factor for infection with KSHV.
Ethical approval for this study was obtained from three bodies: Uganda Virus Research Institute Science and Ethics Committee, Entebbe, Uganda; Uganda National Council for Science and Technology; and the University of York, UK.
Wellcome Trust as a PhD Training Fellowship held by KW (grant number 090132), a Wellcome Trust Senior Fellowship held by AME (grant number 064693) and funded in part by the Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services (contract HHSN261200800001E). Wellcome Trust is a UK registered charity No.210183. We thank all the participants and the staff of the Entebbe Mother and Baby Study and the staff of the laboratory and statistics departments of the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS who made this study possible.
- Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V: A review of human carcinogens--Part B: biological agents. Lancet Oncol. 2009, 10: 321-322. 10.1016/S1470-2045(09)70096-8.PubMedView ArticleGoogle Scholar
- Engels EA, Biggar RJ, Marshall VA, Walters MA, Gamache CJ, Whitby D, Goedert JJ: Detection and quantification of Kaposi's sarcoma-associated herpesvirus to predict AIDS-associated Kaposi's sarcoma. AIDS. 2003, 17: 1847-1851. 10.1097/00002030-200308150-00015.PubMedView ArticleGoogle Scholar
- Laney AS, Dollard SC, Jaffe HW, Offermann MK, Spira TJ, Gunthel CJ, Pellett PE, Cannon MJ: Repeated measures study of human herpesvirus 8 (HHV-8) DNA and antibodies in men seropositive for both HHV-8 and HIV. AIDS. 2004, 18: 1819-1826. 10.1097/00002030-200409030-00011.PubMedView ArticleGoogle Scholar
- Laney AS, Cannon MJ, Jaffe HW, Offermann MK, Ou CY, Radford KW, Patel MM, Spira TJ, Gunthel CJ, Pellett PE, Dollard SC: Human herpesvirus 8 presence and viral load are associated with the progression of AIDS-associated Kaposi's sarcoma. AIDS. 2007, 21: 1541-1545. 10.1097/QAD.0b013e3282202b7d.PubMedView ArticleGoogle Scholar
- Merat R, Amara A, Lebbe C, de The H, Morel P, Saib A: HIV-1 infection of primary effusion lymphoma cell line triggers Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation. Int J Cancer. 2002, 97: 791-795. 10.1002/ijc.10086.PubMedView ArticleGoogle Scholar
- Bagni R, Whitby D: Kaposi's sarcoma-associated herpesvirus transmission and primary infection. Curr Opin HIV AIDS. 2009, 4: 22-26. 10.1097/COH.0b013e32831add5a.PubMedView ArticleGoogle Scholar
- Sitas F, Carrara H, Beral V, Newton R, Reeves G, Bull D, Jentsch U, Pacella-Norman R, Bourboulia D, Whitby D, Boshoff C, Weiss R: Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med. 1999, 340: 1863-1871. 10.1056/NEJM199906173402403.PubMedView ArticleGoogle Scholar
- Grundhoff A, Ganem D: Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J Clin Invest. 2004, 113: 124-136.PubMedPubMed CentralView ArticleGoogle Scholar
- Ascoli V, Belli S, Benedetti M, Trinca S, Ricci P, Comba P: High incidence of classic Kaposi's sarcoma in Mantua, Po Valley, Northern Italy (1989-1998). Br J Cancer. 2001, 85: 379-382. 10.1054/bjoc.2001.1912.PubMedPubMed CentralView ArticleGoogle Scholar
- Ascoli V, Facchinelli L, Valerio L, Zucchetto A, Dal Maso L, Coluzzi M: Distribution of mosquito species in areas with high and low incidence of classic Kaposi's sarcoma and seroprevalence for HHV-8. Med Vet Entomol. 2006, 20: 198-208. 10.1111/j.1365-2915.2006.00624.x.PubMedView ArticleGoogle Scholar
- Ascoli V, Senis G, Zucchetto A, Valerio L, Facchinelli L, Budroni M, Dal Maso L, Coluzzi M: Distribution of 'promoter' sandflies associated with incidence of classic Kaposi's sarcoma. Med Vet Entomol. 2009, 23: 217-225. 10.1111/j.1365-2915.2009.00811.x.PubMedView ArticleGoogle Scholar
- Ascoli V, Zambon P, Manno D, Guzzinati S, Zorzi M, Arca B, Costantini C, Coluzzi M: Variability in the incidence of classic Kaposi's sarcoma in the Veneto region, Northern Italy. Tumori. 2003, 89: 122-124.PubMedGoogle Scholar
- Coluzzi M, Calabro ML, Manno D, Chieco-Bianchi L, Schulz TF, Ascoli V: Reduced seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), human herpesvirus 8 (HHV8), related to suppression of Anopheles density in Italy. Med Vet Entomol. 2003, 17: 461-464. 10.1111/j.1365-2915.2003.00465.x.PubMedView ArticleGoogle Scholar
- Coluzzi M, Manno D, Guzzinati S, Tognazzo S, Zambon P, Arca B, Costantini C, Ascoli V: The bloodsucking arthropod bite as possible cofactor in the transmission of human herpesvirus-8 infection and in the expression of Kaposi's sarcoma disease. Parassitologia. 2002, 44: 123-129.PubMedGoogle Scholar
- Cook-Mozaffari P, Newton R, Beral V, Burkitt DP: The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic. Br J Cancer. 1998, 78: 1521-1528. 10.1038/bjc.1998.717.PubMedPubMed CentralView ArticleGoogle Scholar
- Dedicoat M, Newton R: Review of the distribution of Kaposi's sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi's sarcoma. Br J Cancer. 2003, 88: 1-3. 10.1038/sj.bjc.6600745.PubMedPubMed CentralView ArticleGoogle Scholar
- Dollard SC, Butler LM, Graves Jones AM, Mermin JH, Chidzonga M, Chipato T, Shiboski CH, Brander C, Mosam A, Kiepiela P, Hladik W, Martin JN: Substantial regional differences in human herpesvirus 8 seroprevalence in sub-saharan Africa: Insights on the origin of the "KS Belt". Int J Cancer. 2010Google Scholar
- Tanzi E, Zappa A, Caramaschi F, Amendola A, Lasagna D, Gatti L, Ascoli V, Rezza G, Zanetti AR: Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi's sarcoma. J Med Virol. 2005, 76: 571-575. 10.1002/jmv.20400.PubMedView ArticleGoogle Scholar
- Brown EE, Whitby D, Vitale F, Marshall V, Mbisa G, Gamache C, Lauria C, Alberg AJ, Serraino D, Cordiali-Fei P, Messina A, Goedert JJ: Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. Cancer. 2006, 107: 2282-2290. 10.1002/cncr.22236.PubMedView ArticleGoogle Scholar
- Montesu MA, De Marco R, Cottoni F: Soil silicates and Kaposi's sarcoma in Sardinia. Lancet. 1995, 346: 1436-1437.PubMedView ArticleGoogle Scholar
- Ziegler JL: Endemic Kaposi's sarcoma in Africa and local volcanic soils. Lancet. 1993, 342: 1348-1351. 10.1016/0140-6736(93)92252-O.PubMedView ArticleGoogle Scholar
- Whitby D, Marshall VA, Bagni RK, Miley WJ, McCloud TG, Hines-Boykin R, Goedert JJ, Conde BA, Nagashima K, Mikovits J, Dittmer DP, Newman DJ: Reactivation of Kaposi's sarcoma-associated herpesvirus by natural products from Kaposi's sarcoma endemic regions. Int J Cancer. 2007, 120: 321-328. 10.1002/ijc.22205.PubMedPubMed CentralView ArticleGoogle Scholar
- Ascoli V, Facchinelli L, Valerio L, Manno D, Coluzzi M: Kaposi's sarcoma, human herpesvirus 8 infection and the potential role of promoter-arthropod bites in northern Sweden. J Med Virol. 2006, 78: 1452-1455. 10.1002/jmv.20718.PubMedView ArticleGoogle Scholar
- Ziegler JL, Newton R, Katongole-Mbidde E, Mbulataiye S, De Cock K, Wabinga H, Mugerwa J, Katabira E, Jaffe H, Parkin DM, Reeves G, Weiss R, Beral V: Risk factors for Kaposi's sarcoma in HIV-positive subjects in Uganda. AIDS. 1997, 11: 1619-1626. 10.1097/00002030-199713000-00011.PubMedView ArticleGoogle Scholar
- Ziegler J, Newton R, Bourboulia D, Casabonne D, Beral V, Mbidde E, Carpenter L, Reeves G, Parkin DM, Wabinga H, Mbulaiteye S, Jaffe H, Weiss R, Boshoff C: Risk factors for Kaposi's sarcoma: a case-control study of HIV-seronegative people in Uganda. Int J Cancer. 2003, 103: 233-240. 10.1002/ijc.10818.PubMedView ArticleGoogle Scholar
- Hutt MS: The epidemiology of Kaposi's sarcoma. Antibiot Chemother. 1981, 29: 3-11.PubMedView ArticleGoogle Scholar
- Mbulaiteye SM, Biggar RJ, Pfeiffer RM, Bakaki PM, Gamache C, Owor AM, Katongole-Mbidde E, Ndugwa CM, Goedert JJ, Whitby D, Engels EA: Water, socioeconomic factors, and human herpesvirus 8 infection in Ugandan children and their mothers. J Acquir Immune Defic Syndr. 2005, 38: 474-479. 10.1097/01.qai.0000132495.89162.c0.PubMedView ArticleGoogle Scholar
- Lin CJ, Katongole-Mbidde E, Byekwaso T, Orem J, Rabkin CS, Mbulaiteye SM: Intestinal parasites in Kaposi sarcoma patients in Uganda: indication of shared risk factors or etiologic association. Am J Trop Med Hyg. 2008, 78: 409-412.PubMedGoogle Scholar
- Maizels RM: Parasite immunomodulation and polymorphisms of the immune system. J Biol. 2009, 8: 62-10.1186/jbiol166.PubMedPubMed CentralView ArticleGoogle Scholar
- Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M, Wynn TA: Regulation of pathogenesis and immunity in helminth infections. J Exp Med. 2009, 206: 2059-2066. 10.1084/jem.20091903.PubMedPubMed CentralView ArticleGoogle Scholar
- Moormann AM, Chelimo K, Sumba OP, Lutzke ML, Ploutz-Snyder R, Newton D, Kazura J, Rochford R: Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. J Infect Dis. 2005, 191: 1233-1238. 10.1086/428910.PubMedView ArticleGoogle Scholar
- Moormann AM, Chelimo K, Sumba PO, Tisch DJ, Rochford R, Kazura JW: Exposure to holoendemic malaria results in suppression of Epstein-Barr virus-specific T cell immunosurveillance in Kenyan children. J Infect Dis. 2007, 195: 799-808. 10.1086/511984.PubMedView ArticleGoogle Scholar
- Piriou E, Kimmel R, Chelimo K, Middeldorp JM, Odada PS, Ploutz-Snyder R, Moormann AM, Rochford R: Serological evidence for long-term Epstein-Barr virus reactivation in children living in a holoendemic malaria region of Kenya. J Med Virol. 2009, 81: 1088-1093. 10.1002/jmv.21485.PubMedPubMed CentralView ArticleGoogle Scholar
- Rainey JJ, Mwanda WO, Wairiumu P, Moormann AM, Wilson ML, Rochford R: Spatial distribution of Burkitt's lymphoma in Kenya and association with malaria risk. Trop Med Int Health. 2007, 12: 936-943. 10.1111/j.1365-3156.2007.01875.x.PubMedView ArticleGoogle Scholar
- Elliott AM, Kizza M, Quigley MA, Ndibazza J, Nampijja M, Muhangi L, Morison L, Namujju PB, Muwanga M, Kabatereine N, Whitworth JA: The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]. Clin Trials. 2007, 4: 42-57. 10.1177/1740774506075248.PubMedPubMed CentralView ArticleGoogle Scholar
- Mbisa GL, Miley W, Gamache CJ, Gillette WK, Esposito D, Hopkins R, Busch MP, Schreiber GB, Little RF, Yarchoan R, Ortiz-Conde BA, Labo N, Whitby D: Detection of antibodies to Kaposi's sarcoma-associated herpesvirus: a new approach using K8.1 ELISA and a newly developed recombinant LANA ELISA. J Immunol Methods. 2010, 356: 39-46. 10.1016/j.jim.2010.02.015.PubMedPubMed CentralView ArticleGoogle Scholar
- Malope BI, Pfeiffer RM, Mbisa G, Stein L, Ratshikhopha EM, O'Connell DL, Sitas F, MacPhail P, Whitby D: Transmission of Kaposi sarcoma-associated herpesvirus between mothers and children in a South African population. J Acquir Immune Defic Syndr. 2007, 44: 351-355. 10.1097/QAI.0b013e31802f12ea.PubMedView ArticleGoogle Scholar
- Ndibazza J, Muhangi L, Akishule D, Kiggundu M, Ameke C, Oweka J, Kizindo R, Duong T, Kleinschmidt I, Muwanga M, Elliott AM: Effects of deworming during pregnancy on maternal and perinatal outcomes in Entebbe, Uganda: a randomized controlled trial. Clin Infect Dis. 2010, 50: 531-540. 10.1086/649924.PubMedPubMed CentralView ArticleGoogle Scholar
- de Sanjose S, Marshall V, Sola J, Palacio V, Almirall R, Goedert JJ, Bosch FX, Whitby D: Prevalence of Kaposi's sarcoma-associated herpesvirus infection in sex workers and women from the general population in Spain. Int J Cancer. 2002, 98: 155-158. 10.1002/ijc.10190.PubMedView ArticleGoogle Scholar
- Dedicoat M, Newton R, Alkharsah KR, Sheldon J, Szabados I, Ndlovu B, Page T, Casabonne D, Gilks CF, Cassol SA, Whitby D, Schulz TF: Mother-to-child transmission of human herpesvirus-8 in South Africa. J Infect Dis. 2004, 190: 1068-1075. 10.1086/423326.PubMedView ArticleGoogle Scholar
- Wawer MJ, Eng SM, Serwadda D, Sewankambo NK, Kiwanuka N, Li C, Gray RH: Prevalence of Kaposi sarcoma-associated herpesvirus compared with selected sexually transmitted diseases in adolescents and young adults in rural Rakai District, Uganda. Sex Transm Dis. 2001, 28: 77-81. 10.1097/00007435-200102000-00003.PubMedView ArticleGoogle Scholar
- Olsen SJ, Chang Y, Moore PS, Biggar RJ, Melbye M: Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985. AIDS. 1998, 12: 1921-1925. 10.1097/00002030-199814000-00024.PubMedView ArticleGoogle Scholar
- Minhas V, Crabtree KL, Chao A, M'Soka TJ, Kankasa C, Bulterys M, Mitchell CD, Wood C: Early childhood infection by human herpesvirus 8 in Zambia and the role of human immunodeficiency virus type 1 coinfection in a highly endemic area. Am J Epidemiol. 2008, 168: 311-320. 10.1093/aje/kwn125.PubMedPubMed CentralView ArticleGoogle Scholar
- Mbulaiteye SM, Walters M, Engels EA, Bakaki PM, Ndugwa CM, Owor AM, Goedert JJ, Whitby D, Biggar RJ: High levels of Epstein-Barr virus DNA in saliva and peripheral blood from Ugandan mother-child pairs. J Infect Dis. 2006, 193: 422-426. 10.1086/499277.PubMedView ArticleGoogle Scholar
- Mbulaiteye SM, Pfeiffer RM, Engels EA, Marshall V, Bakaki PM, Owor AM, Ndugwa CM, Katongole-Mbidde E, Goedert JJ, Biggar RJ, Whitby D: Detection of kaposi sarcoma-associated herpesvirus DNA in saliva and buffy-coat samples from children with sickle cell disease in Uganda. J Infect Dis. 2004, 190: 1382-1386. 10.1086/424489.PubMedView ArticleGoogle Scholar
- Mbulaiteye S, Marshall V, Bagni RK, Wang CD, Mbisa G, Bakaki PM, Owor AM, Ndugwa CM, Engels EA, Katongole-Mbidde E, Biggar RJ, Whitby D: Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host. J Infect Dis. 2006, 193: 1250-1257. 10.1086/503052.PubMedView ArticleGoogle Scholar
- Malope BI, MacPhail P, Mbisa G, MacPhail C, Stein L, Ratshikhopha EM, Ndhlovu L, Sitas F, Whitby D: No evidence of sexual transmission of Kaposi's sarcoma herpes virus in a heterosexual South African population. AIDS. 2008, 22: 519-526. 10.1097/QAD.0b013e3282f46582.PubMedView ArticleGoogle Scholar
- Klaskala W, Brayfield BP, Kankasa C, Bhat G, West JT, Mitchell CD, Wood C: Epidemiological characteristics of human herpesvirus-8 infection in a large population of antenatal women in Zambia. J Med Virol. 2005, 75: 93-100. 10.1002/jmv.20242.PubMedView ArticleGoogle Scholar
- Butler LM, Dorsey G, Hladik W, Rosenthal PJ, Brander C, Neilands TB, Mbisa G, Whitby D, Kiepiela P, Mosam A, Mzolo S, Dollard SC, Martin JN: Kaposi sarcoma-associated herpesvirus (KSHV) seroprevalence in population-based samples of African children: evidence for at least 2 patterns of KSHV transmission. J Infect Dis. 2009, 200: 430-438. 10.1086/600103.PubMedPubMed CentralView ArticleGoogle Scholar
- Brayfield BP, Phiri S, Kankasa C, Muyanga J, Mantina H, Kwenda G, West JT, Bhat G, Marx DB, Klaskala W, Mitchell CD, Wood C: Postnatal human herpesvirus 8 and human immunodeficiency virus type 1 infection in mothers and infants from Zambia. J Infect Dis. 2003, 187: 559-568. 10.1086/367985.PubMedView ArticleGoogle Scholar
- de Sanjose S, Mbisa G, Perez-Alvarez S, Benavente Y, Sukvirach S, Hieu NT, Shin HR, Anh PT, Thomas J, Lazcano E, Matos E, Herrero R, Munoz N, Molano M, Franceschi S, Whitby D: Geographic variation in the prevalence of Kaposi sarcoma-associated herpesvirus and risk factors for transmission. J Infect Dis. 2009, 199: 1449-1456. 10.1086/598523.PubMedView ArticleGoogle Scholar
- Newton R, Ziegler J, Bourboulia D, Casabonne D, Beral V, Mbidde E, Carpenter L, Reeves G, Parkin DM, Wabinga H, Mbulaiteye S, Jaffe H, Weiss R, Boshoff C: The sero-epidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in adults with cancer in Uganda. Int J Cancer. 2003, 103: 226-232. 10.1002/ijc.10817.PubMedView ArticleGoogle Scholar
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