Studies on genital ulcer disease in Tanzania. Aetiology with special reference to Haemophilus ducreyi, association with human immunodeficiecy virus infection, and human papilloma virus

Abstract

Genital ulcer diseases (GUD) caused by Haemophilus ducreyi, Treponema pallidum and herpessimplex type 2 (HSV-2) are an important health problem in many developing countries. Ulcerativesexually transmitted infections (STIs) have been associated with increased acquisition andtransmission of human immunodeficiency virus type 1 (HIV-1). Thus, the recognition and controlof GUD is important for the prevention of HIV-1.In the present thesis the aetiology of GUD with special reference to Haemophilus ducreyicausing chancroid, was investigated. Presence of antibodies to H. ducreyi cytolethal distendingtoxin (HdCDT) as a tool for the diagnosis of chancroid was determined. The seroprevalence of HIVand to human papilloma virus (HPV) infections was evaluated among patients with GUD andindividuals from the general population of urban Tanzania.Three hundred and two patients with GUD from two Tanzanian cities, representing high-riskgroups, were recruited in 1999 and in 2001 into the study. The sera from pregnant women and maleblood donors were used as a controls and represented individuals from the general population ofTanzania. We used a multiplex PCR to determine the aetiological agents, H. ducreyi, T. pallidumand HSV-2 in ulcer specimens. H. ducreyi was also cultured from the specimens. A randomamplified polymorphic DNA (RAPD) method with two primers was adapted to characterize 43 H.ducreyi isolates from Tanzania, Senegal, South East Asia, Europe and North America. An enzymeimmunosorbent assay (ELISA) was used to detect antibodies to HdCDT, HIV-1 and HPV in serafrom GUD patients, from pregnant women and from male blood donors.HSV-2 was the most common identified agent (49%), followed by H. ducreyi bacterium(12%) in the genital ulcer specimens. The RAPD method generated nine different banding profilesand the majority of African strains were clustered into two patterns for both primers.HIV-1 antibodies were detected in 49% of the GUD sera collected in 1999 and 62% inpatients recruited in 2001.The majority of patients with chancroid and blood donors had low levels of antibodies to HdCDT.However, 32 % of the chancroid patients had significantly higher levels of antibodies to the toxin ascompared to levels in sera from Tanzanian blood donors (4%) (p=0.001).The seroprevalence of HPV types 11, 16, 18, 31, 33, 35, 51 and 52 among the 200 GUD patientswas 11%, 58%, 28% 0%, 3%, 10%, 18% and 62%, respectively. For the pregnant women thehighest prevalence of antibodies was detected to HPV16 (40%) followed by HPV52 (38%) and forthe blood donors HPV16 (10%).To identify the causative agents of GUD is important, since treatment of each of thepathogen differs. The present study revealed that HSV-2 is the most common cause of GUD,followed by H. ducreyi and that the prevalence of HIV-1 is high among patients with STI. Thesefindings suggest the need for integrating diagnosis and HSV-2 treatment in the syndromicmanagement of GUD in Tanzania, in addition to other intervention measures. Treatment of STI,including HSV-2 could also play a role in preventing HIV-1 infection. The diagnosis of chancroidby culture is difficult and PCR method is a good alternative. The study showed a high prevalence ofoncogenic HPV types, 16, 18, 51 and 52 among high-risk group of STI as well as in women fromthe general population of Tanzania. The overload of STIs in high risk-group in Tanzania reinforcesthe need for appropriate strategy to control these infections.