Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa ...where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment.
Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination.
The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.
Mali is endemic for all five targeted major neglected tropical diseases (NTDs). As one of the five 'fast-track' countries supported with the United States Agency for International Development (USAID) ...funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned.
The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76-97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported.
Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons learned in Mali can be valuable assets to other countries starting up their own integrated national NTD control programs.
Mass treatment with ivermectin is a proven strategy for controlling onchocerciasis as a public health problem, but it is not known if it can also interrupt transmission and eliminate the parasite in ...endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission and test whether ivermectin treatment could be safely stopped in the study areas.
Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000.
This study has provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other endemic areas in Africa, the principle of elimination has been established. The African Programme for Onchocerciasis Control has adopted an additional objective to assess progress towards elimination endpoints in all onchocerciasis control projects and to guide countries on cessation of treatment where feasible.
Highlights • Onchocerciasis is earmarked for elimination in some African countries by 2020/2025. • 15+ years of ivermectin treatment drove infection prevalence to zero in areas of Mali & Senegal. • ...Data-driven model projections are used to evaluate the risk of infection resurgence. • Latent infections can initiate slow resurgence in communities with high transmission propensity. • Highly sensitive and long-term surveillance will be necessary to verify elimination.
To assess clinic- and community-based trends in demographic and behavioral characteristics and clinic-based trends in HIV infection and other sexually transmitted diseases (STD) in female sex workers ...in Abidjan, Côte d'Ivoire.
Multiyear cross-sectional study of first-time attenders in Clinique de Confiance, a confidential STD clinic; biannual community-based behavioral surveys.
From 1992 to 1998, female sex workers were invited to attend Clinique de Confiance, where they were counseled, interviewed, clinically examined during their first visit and tested for STD and HIV infection. Community-based surveys, conducted in 1991, 1993, 1995, and 1997, interviewed women regarding socio-demographic characteristics and HIV/STD-related knowledge, attitudes and behavior.
Among female sex workers in Abidjan, there was a trend toward shorter duration of sex work, higher prices, and more condom use. Among sex workers attending Clinique de Confiance for the first time, significant declines were found in the prevalence of HIV infection (from 89 to 32%), gonorrhoea (from 33 to 11%), genital ulcers (from 21 to 4%), and syphilis (from 21 to 2%). In a logistic regression model that controlled for socio-demographic and behavioral changes, the year of screening remained significantly associated with HIV infection.
The increase in condom use and the decline in prevalence of HIV infection and other STD may well have resulted from the prevention campaign for female sex workers, and such campaigns should therefore be continued, strengthened, and expanded.
Antibodies to human immunodeficiency virus (HIV) of the IgA, IgG, and IgM isotypes and high levels of the HIV suppressive β-chemokine RANTES (regulated on activation, normally T cell expressed and ...secreted) were found in the cervicovaginal secretions (CVSs) of 7.5% of 342 multiply and repeatedly exposed African HIV-seronegative female sex workers. The antibodies are part of a local compartmentalized secretory immune response to HIV, since they are present in vaginal fluids that are free of contaminating semen. Cervicovaginal antibodies showed a reproducible pattern of reactivity restricted to gp160 and p24. Locally produced anti-env antibodies exhibit reactivity toward the neutralizing ELDKWA epitope of gp41. Study results show that antibodies purified from CVSs block the transcytosis of cell-associated HIV through a tight epithelial monolayer in vitro. These findings suggest that genital resistance to HIV may involve HIV-specific cervicovaginal antibody responses in a minority of highly exposed HIV-seronegative women in association with other protecting factors, such as local production of HIV-suppressive chemokines
To compare the seroincidence of HIV infection among female sex workers in Abidjan, Côte d'Ivoire before and during an intervention study to control sexually transmitted diseases (STD) and to study ...the effect of two STD diagnosis and treatment strategies on the prevalence of STD and on the seroincidence of HIV infection.
A screening facility for STD and HIV had been available since October 1992 for female sex workers. From June 1994, women who were HIV seronegative or HIV-2 positive during the screening could enroll in the intervention study in which participants reported once a month to a confidential clinic where they received health education, condoms and STD treatment if indicated. Women in the study were randomized either to a basic STD diagnosis and treatment strategy, which included a gynecologic examination when symptomatic, or to an intensive strategy that included a gynecologic examination regardless of symptoms. An outcome assessment every 6 months included a gynecologic examination, HIV serology and laboratory tests for STD.
Of 542 women enrolled in the study, 225 (42%) had at least one outcome assessment. The HIV-1 seroincidence rate during the intervention study was significantly lower than before the study (6.5 versus 16.3 per 100 person-years; P = 0.02). During the study, the HIV-1 seroincidence rate was slightly lower in the intensive than in the basic strategy (5.3 versus 7.6 per 100 person-years; P = 0.5).
National AIDS control programs should consider adopting as policy the type of integrated approach used in this intervention study for HIV prevention in female sex workers.
To detect anti-HIV antibodies in cervicovaginal secretions of HIV-seronegative female sex workers and to evaluate whether the presence of these antibodies is associated with increased sexual ...exposure.
A cross-sectional study was carried out at a confidential clinic for female sex workers in Abidjan, Côte d'Ivoire. The participants were 342 HIV-seronegative female sex workers in whom a cervicovaginal lavage was collected. The main outcome measures were the detection of antibodies to HIV-1 in cervicovaginal lavages using an in-house and a commercial (Seradyn Sentinel; Calypte Biomedical Corporation, Berkeley, California, USA) enzyme immunoassay; the detection of semen in cervicovaginal lavages; and the assessment of epidemiological and biological markers of sexual exposure to HIV.
Cervicovaginal anti-HIV antibodies were detected in 7.3 and 29.8% of women using in-house enzyme-linked immunosorbent assay (ELISA) and Seradyn Sentinel respectively. All cervicovaginal secretions found to be positive by in-house ELISA were also positive by Seradyn Sentinel. In a minority of women, ranging from 2.9% by in-house ELISA to 12.3% by Seradyn Sentinel, the anti-HIV antibodies were present in vaginal fluids that did not contain semen. Sexual exposure to HIV was similar in women with anti-HIV antibodies in their semen-free cervicovaginal secretions compared with women without anti-HIV antibodies in their cervicovaginal secretions.
Cervicovaginal HIV-specific antibodies were detected in a minority of sexually exposed HIV-seronegative female sex workers in Abidjan. The lack of association between increased sexual exposure to HIV and presence of cervicovaginal HIV-specific antibodies suggests that the production of genital HIV-specific antibodies in exposed seronegative women depends on the ability of individual women to mount specific mucosal immunity to HIV antigens, the determinants of which are currently unknown.
To measure the frequency and associated factors of cervicovaginal HIV shedding and to determine the impact of sexually transmitted disease (STD) treatment on HIV shedding.
Cross-sectional study with ...1-week follow-up.
Confidential clinic for female sex workers in Abidjan, Côte d'Ivoire.
A total of 1201 female sex workers.
STD treatment based on clinical signs.
HIV serostatus; cervicovaginal HIV shedding at enrollment and at 1-week follow-up; STD status at enrollment and at 1-week follow-up.
Cervicovaginal shedding of HIV-1 in HIV-1-seropositive women was more frequent (96 out of 404, 24%) than shedding of HIV-2 in HIV-2-seropositive women one out of 21, 5%; odds ratio (OR), 6.2; 95% confidence interval (CI), 1.0-261. Among 609 HIV-1-seropositive or dually seroreactive women, HIV-1 shedding was significantly more frequent in immunosuppressed women adjusted OR (AOR), 6.3; 95% CI, 3.4-11.9; and AOR, 2.9; 95% CI, 1.6-5.0 for CD4 < 14% and CD4 14-28%, respectively, versus CD4 > 28%, and in women with Neisseria gonorrhoeae (AOR, 1.9; 95% CI, 1.2-3.0), those with Chlamydia trachomatis (AOR, 2.5; 95% CI, 1.1-5.8), and with a cervical or vaginal ulcer (AOR, 3.9; 95% CI, 2.1-7.4). HIV-1 shedding decreased from 42 to 21% (P < 0.005) in women whose STD were cured.
These data help to explain the difference in transmissibility between HIV-1 and HIV-2 and the increased infectiousness of HIV in the presence of immunosuppression and STD. In addition, they lend biological plausibility to arguments for making STD control an integral part of HIV prevention strategies in Africa.
Background Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci ...in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment. Methodology/Principal Findings Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination. Conclusion/Significance The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.
PDF
