HerpeZ

Diagnostics Research & Training in Zambia

Starting with KSHV

Herpesvirus research in Zambia began in 1976 when the Indian Journal of Cancer published a histopathological study of Kaposi’s Sarcoma in Zambian patients (Naik 1976). In the early 1980s early work on the characterization of atypical Kaposi’s Sarcoma (Bayley 1984) and AIDS was undertaken in Zambia by Anne C. Bayley FRCS OBE, who was professor of surgery at the University of Zambia (Reynolds and Tansey 2001). Work on serum collected from Zambian Kaposi’s Sarcoma and AIDS patients was then instrumental in the search for the causative agent of AIDS (Bayley, Downing et al. 1985). Both HIV associated and childhood endemic forms of KSHV probably account for half of all herpesvirus research done in Zambia. Over the last decade this work has been lead by Prof Charles Wood and his team at the Nebraska Centre for Virology, University of Nebraska-Lincoln, who have established a dedicated KSHV lab in the department of paediatrics at University Teaching Hospital in Zambia. This group are particularly interested in transmission routes for early infant KSHV infections and correlates with infant and maternal HIV-1 infection (Minhas, Crabtree et al. 2008). Recently they have used molecular analysis of KSHV genotypes to show that infant primary infections may arise from family and non-family contacts (Olp, Shea et al. 2013).

HIV and HSV-2

The second most studied herpesvirus in Zambia is HSV-2. The Study Group on the Heterogeneity of HIV Epidemics in African Cities (one of which was Ndola in Zambia) was set up to answer a set of key epidemiological questions with respect to the HIV epidemic in African cities with higher and lower HIV prevalence.  HSV-2 and lack-of-circumcision were shown to be risk factors HIV infection (Auvert, Buve et al. 2001). More recent studies have looked at acyclovir efficacy for genital ulcers (Corbell, Stergachis et al. 2010; Lu, Celum et al. 2012)

The rise of the Betas

The Betaherpesviruses, HCMV, HHV-6A, HHV-6B and HHV-7, have recently emerged as very interesting topics of study in Zambia and regionally. A seminal paediatric autopsy study from Zambia published by the Lancet in 2002, demonstrated for the first time, that HCMV pneumonia was a highly prevalent cause of death in HIV-infected children (Chintu et al. 2002). Subsequent molecular analysis suggested active HCMV infections might be even more prevalent and demonstrated that distribution of HCMV genotypes was similar ot that seen elsewhere (Bates et al. 2008). More recent HCMV studies have presented evidence for links between highly prevalent infant HCMV infections and developmental defects (Gompels et al. 2012). We have recently shown that congenital HCMV infections are highly prevalent among admitted neonates born to HIV-infected mothers (Mwaanza et al... 2014), with others recently publishing supporting data showing an inverse correlation between maternal CD4 count and CMV viral loads in neonates (Maniklal et al...2014). CMV DNAemia in admitted Zambian children under 2 years of age, is associated with HIV infection, being underweight and and meningitis (Tembo et al... 2015). See our recent review which succinctly summarises the current knowledge and potential impact of congenital CMV in sub-Saharan Africa (Bates et al...2014). Work has also been published on HHV-6, with the very surprising finding that HHV-6A is endemic in Zambian children (Bates et al. 2009). HerpeZ is engaged in ongoing prevalence and clinical-impact studies to characterise this finding further. Together these few findings suggest that in high HIV burden communities in sub-Saharan Africa, betaherpesviruses have a unique epidemiology, with linked disease presentations, such as paediatric HIV-associated HCMV pneumonia, which are not present in Western countries, although there may be useful parallels in the transplant setting from which we can learn, particularly in regards to treatment and control of betaherpevirus infections. 

References

  • Auvert, B., A. Buve, et al. (2001). "Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection." AIDS 15 Suppl 4: S15-30.
  • Bates, M., M. Monze, et al. (2009). "Predominant human herpesvirus 6 variant A infant infections in an HIV-1 endemic region of Sub-Saharan Africa." J Med Virol 81(5): 779-789.
  • Bates, M., M. Monze, et al. (2008). "High human cytomegalovirus loads and diverse linked variable genotypes in both HIV-1 infected and exposed, but uninfected, children in Africa." Virology 382(1): 28-36.
  • Bates M, Tembo J, Zumla A. (2014) Congenital cytomegalovirus infections in sub-Saharan Africa - a neglected and growing problem. Trop Med Int Health. Apr 10.

  • Bayley, A. C. (1984). "Aggressive Kaposi's sarcoma in Zambia, 1983." Lancet 1(8390): 1318-1320.
  • Bayley, A. C., R. G. Downing, et al. (1985). "HTLV-III serology distinguishes atypical and endemic Kaposi's sarcoma in Africa." Lancet 1(8425): 359-361.
  • Corbell, C., A. Stergachis, et al. (2010). "Genital ulcer disease treatment policies and access to acyclovir in eight sub-Saharan African countries." Sex Transm Dis 37(8): 488-493.
  • Gompels, U. A., N. Larke, et al. (2012). "Human cytomegalovirus infant infection adversely affects growth and development in maternally HIV-exposed and unexposed infants in Zambia." Clin Infect Dis 54(3): 434-442.
  • Lu, Y., C. Celum, et al. (2012). "Acyclovir achieves a lower concentration in African HIV-seronegative, herpes simplex virus 2-seropositive women than in non-African populations." Antimicrob Agents Chemother 56(5): 2777-2779.
  • Manicklal S, van Niekerk AM, Kroon SM, Hutto C, Novak Z, Pati SK, Chowdhury N, Hsiao NY, Boppana SB. Birth prevalence of congenital cytomegalovirus among infants of HIV-infected women on prenatal antiretroviral prophylaxis in South Africa. Clin Infect Dis. 2014 May;58(10):1467-72.

  • Minhas, V., K. L. Crabtree, et al. (2008). "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 168(3): 311-320.
  • Mwaanza N, Chilukutu L, Tembo J, Kabwe M, Musonda K, Kapasa M, Chabala C, Sinyangwe S, Mwaba P, Zumla A, Bates M. (2014). High Rates of Congenital Cytomegalovirus Infection Linked With Maternal HIV Infection Among Neonatal Admissions at a Large Referral Center in Sub-Saharan Africa.  Clin Infect Dis. 2014 Mar;58(5):728-35. 
  • Naik, K. G. (1976). "Kaposi's sarcoma in Zambia a histopathological study." Indian J Cancer 13(2): 132-142.
  • Olp, L. N., D. M. Shea, et al. (2013). "Early childhood infection of Kaposi's sarcoma-associated herpesvirus in Zambian households: A molecular analysis." Int J Cancer 132(5): 1182-1190.
  • Reynolds, L. A. and E. M. Tansey (2001). British Contributions to Medical Research and Education in Africa after the Second World War. Wellcome Witnesses to Twentieth Century Medicine, vol. 10. London: Wellcome Trust Centre for the History of Medicine at UCL. . Wellcome Trust Witness Seminars, London, Wellcome Trust Centre.
  • Tembo J, Kabwe M, Chilukutu L, Chilufya M, Mwaanza N, Chabala C, Zumla A, Bates M. Prevalence and risk factors for betaherpesvirus DNAemia in infants aged between 3 weeks and 2 years of age, admitted to a large referral hospital in sub-Saharan Africa. Clin Infect Dis. 2014 Oct 28. ICSW