Ronald C. Ballard

Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection.

Background and Objectives: While genital ulcers are a risk factor in HIV infection, the association of specific agents of genital ulcer disease (GUD) with HIV infection may vary. Goal: To determine the etiology of GUD in HIV‐infected and HIV‐uninfected men attending sexually transmitted disease (STD) clinics in Durban, Johannesburg, and Cape Town, South Africa, and the association of previous and current sexually transmitted infections with HIV infection in men with ulcerative and nonulcerative STDs. Study Design: A cross‐sectional study of 558 men with genital ulcers and 602 men with urethritis. Results: Patients with GUD were more likely to be infected with HIV than patients with urethritis (39.4% versus 21.4%, P ≤ 0.001). Herpes simplex virus 2 (HSV‐2) was the most common agent identified in ulcer specimens (35.9%), and was detected in a significantly higher proportion of ulcer specimens from HIV‐infected patients than in specimens from HIV‐uninfected patients (47.4% versus 28.2%, P ≤ 0.001). Patients infected with HIV‐1 were significantly more likely to have HSV‐2 infection, as measured by the presence of the antibody to glycoprotein G‐2, than patients not infected with HIV (63.1% versus 38.5%, P ≤ 0.001). Patients infected with HIV‐1 were also significantly more likely to have initial HSV‐2 infection than HIV‐uninfected patients with GUD (50.0% versus 31.6%, P = 0.007). Haemophilus ducreyi was detected in 31.7% of ulcer specimens; prevalence did not vary by HIV‐infection status. Treponema pallidum DNA was detected significantly less frequently in ulcer specimens from patients infected with HIV than in specimens from patients not infected with HIV (10.2% versus 26%, P ≤ 0.001); no association was found between HIV‐infection status and fluorescent treponemal antibody absorption test seroreactivity, even when men with M‐PCR‐positive syphilis lesions were excluded from the analyses. Conclusion: The authors found that HSV‐2 is a more common etiology of GUD than has been suggested by previous studies conducted in South Africa; serologic evidence of HSV‐2 infection and current cases of genital herpes are strongly associated with HIV infection among men who present to STD clinics with GUD or urethritis.

Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests for syphilis

Objectives: To evaluate prospectively four rapid, point-of-care serological tests for syphilis in prenatal or high risk populations in four countries. Methods: Tests were performed on consecutive clinic attenders, using whole blood in the clinic, and whole blood and serum in the laboratory. The sensitivity and specificity of each test was evaluated, using a standard treponemal test (Treponema pallidum haemagglutination assay (TPHA) or fluorescent treponemal antibody, absorbed (FTA-ABS) as gold standard. Non-treponemal tests (rapid plasma reagin (RPR) or venereal diseases research laboratory (VDRL) tests) were also performed on all subjects at three sites. Results: The specificity of each rapid test was >95% at each site. Sensitivities varied from 64–100% and, in most cases, were lower when whole blood was used rather than serum. Conclusions: Rapid serological tests for syphilis are an acceptable alternative to conventional laboratory tests. Since they do not require equipment or electricity, they could increase coverage of syphilis screening, and enable treatment to be given at the first clinic visit.

A Multi-centre Evaluation of Nine Rapid Point of Care Syphilis Tests Using Archived Sera

Objectives: To evaluate nine rapid syphilis tests at eight geographically diverse laboratory sites for their performance and operational characteristics. Methods: Tests were compared “head to head” using locally assembled panels of 100 archived (50 positive and 50 negative) sera at each site using as reference standards the Treponema pallidum haemagglutination or the T pallidum particle agglutination test. In addition inter-site variation, result stability, test reproducibility and test operational characteristics were assessed. Results: All nine tests gave good performance relative to the reference standard with sensitivities ranging from 84.5–97.7% and specificities from 84.5–98%. Result stability was variable if result reading was delayed past the recommended period. All the tests were found to be easy to use, especially the lateral flow tests. Conclusions: All the tests evaluated have acceptable performance characteristics and could make an impact on the control of syphilis. Tests that can use whole blood and do not require refrigeration were selected for further evaluation in field settings.

Changes in the etiology of sexually transmitted diseases in Botswana between 1993 and 2002: implications for the clinical management of genital ulcer disease

BACKGROUND In recent years, increasing evidence has accumulated that suggests the majority of cases of genital ulcer disease in sub-Saharan Africa are due to viral and not bacterial infections. Although many cross-sectional studies support such a trend, few serial cross-sectional data are available to show the evolution of genital ulcer disease over time. METHODS We surveyed the prevalence of sexually transmitted diseases (STDs) among patients with STD symptoms and women recruited from family planning clinics in 3 cities in Botswana in 2002 and compared our findings with those from a survey of a similar population conducted in 1993. RESULTS The observed proportion of cases of genital ulcer disease due to chancroid decreased from 25% in 1993 to 1% in 2002, whereas the proportion of ulcers due to herpes simplex virus increased from 23% in 1993 to 58% in 2002. Although the proportion of ulcers due to syphilis was similar for both surveys, the rate of positive serologic test results for syphilis among patients with genital ulcer disease decreased from 52% in 1993 to 5% in 2002. During this period, decreases in the prevalence of gonorrhea, syphilis-reactive serologic findings, chlamydial infection, and trichomoniasis were also detected among patients with STDs and women from family planning clinics. These changes remained significant after estimates were adjusted for the sensitivity and specificity of diagnostic tests. CONCLUSIONS Our findings suggest a decrease in the prevalence of bacterial STDs and trichomoniasis, a reduction in the proportion of ulcers due to bacterial causes, and an increase in the proportion of ulcers due to herpes simplex virus during the period 1993-2002. These changes should be taken into consideration when defining new guidelines for the syndromic management of genital ulcer disease.

Onsite Rapid Antenatal Syphilis Screening With an Immunochromatographic Strip Improves Case Detection and Treatment in Rural South African Clinics

Objectives: Congenital syphilis is a significant cause of adverse pregnancy outcomes. In South Africa, rural clinics perform antenatal screening offsite, but unreliable transport and poor client follow up impede effective treatment. We compared 3 syphilis screening strategies at rural clinics: onsite rapid plasma reagin (RPR), onsite treponemal immunochromatographic strip (ICS) test, and the standard practice offsite RPR with Treponema pallidum hemagglutination assay (RPR/TPHA). Methods: Eight rural clinics performed the onsite RPR and ICS tests and provided immediate treatment. Results were compared with RPR/TPHA at a reference laboratory. Chart reviews at 8 standard practice clinics established diagnosis and treatment rates for offsite RPR/TPHA. Findings: Seventy-nine (6.3%) of 1,250 women screened onsite had active syphilis according to the reference laboratory. The onsite ICS resulted in the highest percentage of pregnant women correctly diagnosed and treated for syphilis (89.4% ICS, 63.9% onsite RPR, 60.8% offsite RPR/TPHA). The onsite RPR had low sensitivity (71.4% for high-titer syphilis). The offsite approach suffered from poor client return rates. One percent of women screened with the ICS may have received penicillin unnecessarily. There were no adverse treatment outcomes. Conclusions: The onsite ICS test can reduce syphilis-related adverse outcomes of pregnancy through accurate diagnosis and immediate treatment of pregnant women with syphilis.

Novel Point-of-Care Test for Simultaneous Detection of Nontreponemal and Treponemal Antibodies in Patients with Syphilis

ABSTRACT We describe a point-of-care immunochromatographic test for the simultaneous detection of both nontreponemal and treponemal antibodies in the sera of patients with syphilis that acts as both a screening and a confirmatory test. A total of 1,601 banked serum samples were examined by the dual test, and the results were compared to those obtained using a quantitative rapid plasma reagin (RPR) test and the Treponema pallidum passive particle agglutination (TP-PA) assay. Compared to the RPR test, the reactive concordance of the dual test nontreponemal line was 98.4% when the RPR titers of sera were ≥1:2 and the nonreactive concordance was 98.6%. Compared to the TP-PA assay, the reactive and nonreactive concordances of the treponemal line were 96.5% and 95.5%, respectively. These results indicate that the dual test could be used for the serological diagnosis of syphilis in primary health care clinics or resource-poor settings and therefore improve rates of treatment where patients may fail to return for their laboratory results.

Serologic testing for syphilis in the United States: a cost-effectiveness analysis of two screening algorithms.

Background: The introduction of automated treponemal enzyme immunoassays and chemiluminescence assays (EIA/CA) tests has led some laboratories in the United States to use new syphilis screening algorithms that start with a treponemal test. We compared the economic and health outcomes of this new algorithm with the standard algorithm from the perspective of the United States health system. Methods: We used a cohort decision analysis to estimate the expected costs and effects (including follow-ups and overtreatment) of the 2 algorithms from a health-care system perspective. In the standard algorithm, rapid plasma reagin (RPR) is followed (if reactive) by EIA/CA (Nontreponemal-First). In the new algorithm, EIA/CA is followed (if reactive) by RPR. If the RPR is negative, Treponema pallidum passive particle agglutination assay (TP-PA) test is used (Treponemal-First). Results: For a cohort of 200,000 individuals (1000 current infections and 10,000 previous infections), the net costs were

The epidemiology of HIV-1 infection in northern Tanzania: results from a community-based study.

1.6 m (Treponemal-First) and

Molecular Typing of Treponema pallidum in South Africa: Cross-Sectional Studies

1.4 m (Nontreponemal-First). The Treponemal-First option treated 118 more cases (986 vs. 868) but resulted in a substantially higher number of follow-ups (11,450 vs. 3756) and overtreatment (964 vs. 38). Treating the additional 118 cases might prevent 1 case of tertiary syphilis. The estimated cost-effectiveness ratios were

The molecular diagnosis of lymphogranuloma venereum: evaluation of a real-time multiplex polymerase chain reaction test using rectal and urethral specimens.

1671 (Treponemal-First) and