HIV/AIDS AND THE KNOWLEDGE GAP: FAILURE OF PRE-PANDEMIC RESEARCH TO AVERT DISASTER IN PARTS OF AFRICA Christopher K. Williams College of Medicine, University of Ibadan, and University College Hospital, Ibadan, Nigeria, Nanaimo General Hospital, and University of British Columbia, Nanaimo and Vancouver, BC, Canada

Abstract 504 The current high seroprevalence rate (SPR) for HIV in Subsaharan Africa stands in striking contrast with the low rates, even in individuals of high-risk lifestyle, observed in surveys of pre-pandemic period in certain locales. Human retroviral research in Nigeria dates back to 1983 with the description of the index case of adult T-cell leukaemia/lymphoma. Subsequent screening of normal blood donors, school children and patients with haematological disorders with first-generation ELISA and lymphocyte immunophenotyping techniques revealed HTLV-I SPR of 6.4%, 0.0% and 0.0%-13% respectively, as well as unexplained fatal cases of immunodeficiency and lymphadenopathy/dermatitis. A WHO sponsored survey of risk factors of retroviral infection carried out in parts of Nigeria from 1985 to 1986 involved assessment of lifestyle of members of 5 population groups by a detailed questionnaire. They included 237 normal blood donors (NBD), 46 female commercial sex workers (FCSW), 54 male-, 17 female celibates (MC/FC) and 42 sexually transmitted diseases (STD) clinic patients (STDCP), who were screened for HTLVs and HIVs by ELISA and Western blot (WB). HTLV-I SPR for NBD, FCSW, MC, FC and STDCP were 4.6%, 13%, 16.7%, 1.85% and 11.8%. Multivariate analysis revealed eastern Nigerian origin (ENO) (p=0.0000095), female sex (p=0.037) and female sex of ENO (p=0.0006) but not ethnicity (p=0.215) or polygamy (p=0.43) as risk factors for HTLV-I infection. Confirmation of HIV-1/2 SPR in the study group was not possible until the development in the 1990's of the recombinant enhanced "Singapore" HIV-1/2 WB, which identified 2 HIV-1, but 0 HIV-2 cases, thus yielding HIV-1 SPR of 0% for FCSW, MC, FC, STDCP, and ≈0.5%-1.0% in NBD nationally. Retrospective estimates indicates expected ≈2400-4800 AIDS deaths in 1985/6 at the University College Hospital, the main health care unit of the region, ≈5 of which were clinically diagnosed. In addition to the educational challenges resulting in the knowledge gap (vis-à-vis the situation in developed countries) about HIV/AIDS, cultural and infrastructural challenges probably also contributed to the failure of averting the disastrous progression of the pandemic in areas where timely intervention might have been effective. Senegal was another locale where retroviral research program was in place prior to the HIV/AIDS crisis. The low Senegalese HIV SPR probably resulted from early recognition of the dangers of the new disease and the prevailing cultural millieu, in contrast to other West African locales. Recent Ugandan experiences indicate that a reversal of the pandemic is possible in Subsaharan Africa. Lessons learnt from failure to control HIV/AIDS could help in confronting emerging new health challenges, including AIDS associated malignancies, breast and lung cancer as well as other diseases of "westernization" and changing lifestyles in Africa.

HTLV- I INFECTION IN NIGERIA – THE INDEX CASE The picture of a 19-year old Nigerian boy whom we studied 10 years and diagnosed as having ATL. He was the first of the disease to be observed in an African. We were able to show that he had clinical and laboratory features of ATL and had antibodies to HTLV-I. We subsequently initiated a series of studies in collaboration with Dr Gallo's lab. at the NCI in Bethesda, MD, as well as with the NCI's Viral Epidemiology Section through its Chief, Dr W A Blattner. Describe SLIDE 13: In analysing the results of the K study, we observed that HTLV-I seropositivity occured in all 4 patients who were diagnosed to have ATL on clinical grounds. Lower seroprevalence rates were observed in other hematologic malignancies. Seroprevalence rates in healthy adult blood donors and school children were 11% and 21% respectively (but with very wide 95% confidence intervals). We concluded that HTLV-I was endemic in Nigeria at about the same seroprevalence rates as in Japan and the West Indies, but that the frequency of ATL was unexplainably lower in Nigerians compared to the other endemic areas. 19-yr old Nigerian with ATL diagnosed in early 1980’s, believed to be the first such patient to be appropriately documented on the African continent

23 yr old Nigerian woman with features of AIDS, 1983 (case 2)    

Survey of Risk Factors For Retroviral Infection in Nigerians sponsored by the World Health Organization; Purpose of the study: To evaluate the role of sexual behavior in the transmission of human retroviruses among Nigerians Methods: enzyme-linked immunoabsorbent assay (ELISA) and an investigational Western blot, A small survey of the seroprevalence of HTLV-I and HIV was conducted in 1985/86 sponsored by the World Health Organization; Purpose of the study: To evaluate the role of sexual behavior in the transmission of human retroviruses among Nigerians Methods: Using enzyme-linked immunoabsorbent assay (ELISA) and an investigational Western blot, a small survey of the seroprevalence of HTLV-I and HIV was conducted in 1985/86 among 5 population groups with differing lifestyles and sexual behavior as assessed by a detailed questionnaire . They included normal blood donors, female prostitutes, patients attending a sexually transmitted diseases (STD) clinic, and young men and women who were required to be celibate for religious reasons.

5 population groups with differing lifestyles and sexual behavior as assessed by a detailed questionnaire Normal blood donors; female commercial sex workers; patients attending a sexually transmitted diseases (STD clinic); Seminarians and Nuns (celibate for religious reasons).

Dear Chris - Among 204 subjects in the HIV database under our study code WLL (Williams), we found two subjects (# 200042 and 105780) who were scored as positive for HIV-1 (negative for HIV-2) with a recombinant enhanced "Singapore" HIV-1/2 Western blot. All of the HIV serology data for these two subjects are in the attached Word file. Subject 200042 was very weakly reactive in only one EIA; subject 105780 was weakly reactive in two EIAs. I could get the specific Western blot band patterns if you like, but I can predict that they had at least three bands, all of which were weak but discernable (which we score as a minimum density of 2 on an 11-point scale from pure white to pure black). The blots were done in August 1994.

WHO Survey: HIV- I Seroprevalence 1985 - 1986 SSTUDY=WLL STUDY NAME=WILLIAMS - HTLV/NIGERIA,U OF IB SUBJECT SAMPLE VIRUS TEST ID ID TYPE ASSAY RESULT DATE -------------------------------------------------------------------------------------------------------------------- 200042 L 9191 HIV-1 ANTI P24 - 0.00 31OCT88 HIV-1 ANTI 120 - 0.00 31OCT88 HIV-1 ENI WV - 1.84 31OCT88 HIV-1 GEN EIA - 1.10 15DEC94 HIV-1 GN PEP E - 1.00 15DEC94 HIV-2 GEN EIA + 1.30 06JAN88 HIV-2 GEN EIA - 1.10 15DEC94 HIV-2 GN PEP E - 1.00 15DEC94 HIVI&II SNG BLOT +,0 29AUG94 105780 L 9289 HIV-1 ANTI P24 - 0.00 31OCT88 HIV-1 ANTI 120 - 0.01 31OCT88 HIV-1 ENI WV - 0.94 31OCT88 HIV-1 GEN EIA + 3.00 15DEC94 HIV-1 GN PEP E - 1.00 15DEC94 HIV-2 GEN EIA + 1.80 06JAN88 HIV-2 GEN EIA - 1.20 15DEC94 HIV-2 GN PEP E - 1.00 15DEC94 HIVI&II SNG BLOT +,0 25AUG94

HIV SEROPREVALENCE IN NIGERIA 1985 – 1986 only 202 of 394 samples collected from various parts of Nigeria re-studied in 1994 for HIV seropositivity; 2/202 (1.0%) seropositive; The two confirmed cases represented: 1/100 (1%) Ibadan blood donors; 1/53 (1.9%) GOPD patients in Calabar; 1/184 (0.54%) Ibadan+Zaria blood donors; 2/237 (0.84%) Nigerians of no known high-risk sexual behavior; Estimated Seroprevalence Rate: ~0.5%-1%

~12,000-24,000 AIDS deaths in Nigeria in 1985 -1986 Population of adult Nigerians in the period: about 48 million ~240,000 -480,000 HIV seropositive adult Nigerians in 1985-1986; Assuming that the estimate of 1 AIDS death for every 20 HIV seropositive cases, there could have been ~12,000-24,000 AIDS deaths in Nigeria in 1985 -1986

Reasons for detection failure: UCH, Nigeria’s pre-eminent medical facility, had a catchment population of at least 20% of Nigeria (20 million) in 1985-1986; expected AIDS deaths: 2,400-4,800 observed cases with clinical features of AIDS: ~ 5. Reasons for detection failure: technological and infrastructure underdevelopment; ineffective surveillance.

Conclusion Knowledge gap and cultural missteps probably contributed to failure of early control of HIV/AIDS in parts of Africa Lessons learnt from the disaster could help in confronting emerging health challenges, including cancers (breast, lung etc) and other diseases of changing lifestyles in Africa.