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INTEGRATED ACTIVITY FLAG:

This activity relates to National Institute of Communicable activities in Laboratory Infrastructure (#7391), SI (#7390) and PMTCT (#7917). This partner may benefit from the Partnership for Supply Chain Management ARV Drugs activity (#7935), which will explore current pain and symptom management practices, drug availability and cost, and provide recommendations.

SUMMARY:

This activity supports screening people living with HIV for sexually transmitted infections (STI), and help to improve the health of sex workers (SWs) living with HIV through cervical screening. The major emphasis area is policy/guidelines, with minor emphasis on needs assessment, and training. Target populations will be people living with HIV and partners in general population, HIV-infected sex workers (SWs), nurses and other healthcare workers (HCWs).

BACKGROUND:

FY 2007 funds will be used to continue STI screening of HIV-infected individuals attending an HIV treatment clinic. STIs are strongly linked to HIV transmission and can further complicate the clinical care of the HIV-infected patient. Screening and treating HIV-infected individuals for STIs identified will result in better palliative care services, will reduce the likelihood of HIV and STI transmission to their partners and will identify those HIV-infected individuals that could potentially benefit from additional prevention/risk reduction services. Currently the South African Government operates all public health clinics, including ARV sites, using a syndromic management model for STI treatment. Therefore asymptomatic individuals go undetected and untreated, unless such patients present as contacts of other symptomatic STI-infected patients. The prime partner, The Sexually Transmitted Infections Reference Centre (STIRC) carrying out this project is part of the South African National Institute for Communicable Diseases (NICD). NICD is organized as a parastatal, with accountability to the National Department of Heath through a Board of Directors.

Activity 2 is an expansion with FY 2007 funds which involves providing a new cervical screening service for HIV-infected SWs and other women at high risk of STIs who attend a mobile clinic service in the Carletonville area. These HIV-infected women will be also tested for high risk types of human papillomavirus (HPV) infection to determine those most at risk of developing cervical cancer. There is little South African data on HPV infection/cervical dysplasia in HIV-infected SWs, so given the presence of the new HPV vaccine, this activity will also provide baseline data on the prevalence of abnormal Pap smears and the distribution and burden of HPV subtypes among these women.

STIRC will implement both activities in collaboration with CDC's Division of STD Prevention, an HIV clinic in Johannesburg and the Mothusimpilo NGO which provides outreach services to SWs.

ACTIVITIES AND EXPECTED RESULTS:

ACTIVITY 1: Screening

The proposed activities will be carried out in the South African Government's largest Johannesburg hospital-based ARV site. People living with HIV will be screened for asymptomatic STIs. Since these activities will take place in a public ARV clinic, medicines needed to treat the STIs diagnosed will be provided by the South African Government, and not purchased with PEPFAR funds. Those with STIs will be counseled regarding enhanced risk of HIV transmission in the presence of STIs. Partner notification and counseling of those infected will result in the referral of sex partners for STI diagnosis and treatment as well as HIV counseling and testing. Couples counseling will be encouraged for discordant couples. Data on the prevalence and etiology of the STIs identified will be gathered to inform policy on the burden of asymptomatic STI in the HIV population.

ACTIVITY 2: HIV testing

SWs will be tested for HIV infection using rapid tests in informal settlements. The SWs will be screened with cervical Pap smears to detect either dyskaryosis or cervical cancer as well as undergo HPV screening/typing. HIV-infected SWs with abnormal smears will be referred to gynecologists for further assessment and treatment.

Total staffing for both activities includes two nurses and two counselors, who will deliver the clinical service to those with STIs and their partners as well as to SWs; one clerk will enter data. STI screening results and the importance of the STI-HIV link will be disseminated through training and building of human capacity of healthcare workers. Treating STIs will reduce on-going HIV transmission from index HIV clients. Partners in Activity 1 will receive epidemiological treatment for STIs as contacts and be offered HIV testing. Early treatment of cervical dysplasia in Activity 2 will prevent cervical cancer in SWs. Activity 2 will involve training in the taking of cervical smears by the NGO project nurses as well as raise awareness about cervical cancer among SWs attending the service. Findings from both activities will be used by STIRC to influence local and national health policy and guidelines which will enhance sustainability of each activity.

These activities contribute to PEPFAR goal of 10 million people in care by improving the palliative care provided to HIV-infected individuals presenting at ARV sites through the diagnosis and treatment of their asymptomatic STIs. These activities further contribute to the 2 and 7 portions of the PEPFAR goals through the referral, testing and treatment of the sex partners of HIV-infected patients and by identifying those HIV-infected patients that may benefit from further risk reduction and prevention counseling.

SUMMARY Activities will be carried out to strengthen the current TB laboratory infrastructure and capacity under the NHLS with direct support from NICD. With significant increases in MDR and XTR-TB cases within South Africa, and recognizing the limited laboratory capacity to capture and report cases within NHLS and the NTP, there is an immediate need to provide increased access of TB culture and referral services, investigations into creative approaches to increasing laboratory through-put of sputum specimens to meet increased demand, expansion and refinement of information management and dissemination methods of TB diagnostic results, as well as strengthening NHLS ability to improve MDR and XTR-TB reporting and surveillance activities.

BACKGROUND NHLS is a public laboratory network that provides services within all 9 provinces. NHLS is composed of close to 300 laboratories located in both rural and urban settings, and provides diagnostic services to almost 85 percent of general population. NHLS is a parastatal organization, with NICD residing within the NHLS organizational structure.

Activity 1: Integrated HIV/TB technologist training program (co support in HLAB). Funds are requested to respond to technical assistance requests from NHLS to assist in the development of an integrated HIV/TB technologist training program. It is apparent that many of the rural NHLS laboratory staffing needs fall short of the human resource requirements needed to maintain and sustain viable HIV and TB diagnostic services. In light of this shortcoming, NICD/NHLS has proposed an integrated training program that would encompass the needs of understaffed testing sites. The objectives of the training curriculum would address technical HIV testing methodologies and practical hands on training to meet the increased technical demands of HIV testing services, as well as the need to improve TB smear microscopy and AFB culture techniques. The proposed 1 year training curriculum would include didactic sessions, but more importantly on-site laboratory practicums. Funding would be used to assist in curriculum development and technical content review, as well as training implementation and oversight. Efforts will be coordinated with SA Health Care Professionals Association to ensure course accreditation

Activity 2: Automated NALC decontamination With the current number of sputum samples submitted for laboratory smear microscopy and culture already at an all time high and continuing to increase, it is recognized that one of the most significant rate determining factors directly impacting laboratory through-put is that of the NALC decontamination process, a labor intensive processes of sputum concentration and decontamination. In order to streamline this process and to increase overall laboratory through-put of sputum specimens to meet the increased demand and lack of available staff to process such specimens, alternate or automated measures should be investigated. Currently, NICD has vested time in investigating possible automated methods that could significantly reduce and provide standardized decontamination processes. The currently proposed funds would be used, in partnership and through co-funding with NHLS, for the development of automated NALC decontamination instrumentation and technologies.

Activity 3: Expansion and refinement of information management processes Information management and dissemination of TB/HIV diagnostic results is a continuing issue that needs to be addressed. Current laboratory reporting mechanisms, as well as patient enrollment systems into DOTs treatment programs need IT support and information bridges that currently do not exist. Currently, NICD has vested time in investigating logistic support mechanism for strengthening the current system. A draft proposal has been submitted by LTS, an engineering firm within South Africa, to address this problem. The currently proposed system will utilize biometric enrollment systems as confirmation of patient identification and incorporates the existing NHLS data warehouse as a source of laboratory information that can be used to increase the efficacy and use of the existing systems for diagnostic and treatment purposes. CDC proposes a modular approach to address the overarching system needs. The currently proposed funds would be used, in partnership and through co-funding with NHLS, for the development of modular logistical and information management support systems as a means to address the current integration issues associated with the existing system.

INTEGRATED ACTIVITY FLAG: This National Institute of Communicable Diseases (NICD) activity also relates to activities in PMTCT (#7917), SI (#7390) and Basic Health Care and Support (#7393). BACKGROUND: As the burden of TB increases, the need for a NTBRL is increasingly important. The National Health Laboratory Service (NHLS) is overburdened with routine diagnostic testing, affecting standards and turnaround times for specimen processing. The NTBRL will play a pivotal role in improving routine TB lab services and drug-resistance surveillance. As HIV rapid test use increases, it is critical to ensure quality assurance and quality control (QA/QC) mechanisms and review of rapid test kits for efficacy. QA mechanisms must be equivalent to those in place in diagnostic labs. The proposed quality management system (QMS) will identify and remedy any deficiencies in CT centers. There are also quality concerns with routine use of nucleic acid testing including assay sensitivity and specificity, contamination, clinical significance, variable isolation/amplification procedures, lack of robustness and standardization, lack of appropriate control material and regulations and policies. To help detect weak spots in performance and improve reliability and confidence when reporting results, an EQA (proficiency testing (PT)) and internal quality control (IQC) program (as part of the QMS) will allow comparison and benchmarking, education in good lab practice and method utility. The activity is integrated as part of the program to increase access to testing. The development of improved practical methods for early infant HIV diagnosis is important for effective PMTCT interventions and to improve clinical management of HIV-exposed infants. NICD will help develop program guidance, technical support and in-country and regional evaluations to implement an operational plan to scale up HIV diagnosis in infants. Progress includes automation for an infant diagnosis program at NHLS. The NICD supports the Lesotho Ministry of Health in testing infants and has produced a publication of usefulness of testing at 3 months of age versus later time points using standard methods in FY 2005.

ACTIVITES AND EXPECTED RESULTS: ACTIVITY 1: The NTBRL will be integrated with NHLS service provision. Renovation of an existing laboratory will begin in 2007.. The NTBRL will: develop a quality assurance program for TB laboratories, including PT and a nationwide re-screening program as part of the National TB Control Program; characterize the mechanisms of drug resistance found in South African isolates; and conduct laboratory investigations of drug-resistant outbreaks using molecular methods. The NTBRL will enhance the SAG's ability to respond to the growing TB epidemic among the HIV-infected by quality assuring routine testing to ensure that TB cases are properly identified. This will also ensure that high quality surveillance systems are in place. The NTBRL will work with the Medical Research Council, WHO, CDC and other partners to implement rapid drug-resistance surveys to help characterize the extent of drug-resistance including XDR-TB. ACTIVITY 2: NICD will continue to evaluate the performance of rapid test kits and testing algorithms in the field and in the lab. In Phase 1, individual rapid test kits - and combinations of kits -- are evaluated for sensitivity, specificity, positive predictive valueand negative predictive value. Phase 2 assesses the field performance of rapid kits to inform scale-up. In FY 2006, NICD evaluated 15 rapid HIV test kits, and conducted field testing of three kits and an evaluation at one clinical site. In addition, an assessment and quality control program will be expanded as part of the national strategy for quality control of HIV testing. Well-characterized panels will be sent to participating labs on a quarterly basis. The approach has been successfully tested in participating labs in the national antenatal survey, in 210 NHLS labs and 60 non-NHLS sites, including NGO/Vaccine sites. For CT sites that utilize the rapid HIV-1 kits, the dried blood spot (DBS) is proposed as a proficiency-testing tool. ACTIVITY 3: A CT QMS will be established by first defining aspects required for such a system (i.e., proficiency panels, standard operating procedures (SOPs), safety, piloting ELISA testing from DBS) and then establishing lab and training capacity to implement it. Expected outcomes are to train public health sector and NGO counselors that perform rapid HIV testing to implement quality management of testing. The NICD and CDC have engaged key organizations including the NDOH and NGOs in the demonstration of the WHO/CDC training curriculum. The curriculum has been revised and is ready for piloting for 2006 and rollout in 2007. ACTIVITY 4: An EQA program will be implemented to monitor lab performance related to the ART program, including performance of the viral load assay as well as DNA PCR (standard and DBS) important for infant diagnosis. Currently 11 labs perform viral load testing, 5 provide DNA testing for infants and 45 labs are equipped CD4 testing. The ART

program will expand to 16 NHLS labs in 2007 for viral load testing and 11 NHLS labs for DNA testing. The CD4 testing sites will expand to 58 sites. The NICD will monitor HIV testing performance and provide training in EQA/IQC management. ACTIVITY 5: NICD will provide technical support to CDC to develop expert guidance on simplified early diagnosis tools and the use of DBS PCR testing. Specific activities include: provide expert lab consultation and participate in a CDC-organized early diagnosis workgroup; develop simplified lab SOPs for standardized field application in resource-poor settings; test available specimens for test validation and optimization; provide training to selected labs and PEPFAR partners; and help develop and support a plan for implementation of improved methods for early diagnosis. By scaling up access to advanced PCR-based HIV testing assays for infants born to HIV-infected women, the NICD will improve the ability of pediatricians to assess and prescribe ART to prevent or treat infection in exposed infants. ACTIVITY 6: Strengthen the current NHLS HIV-related testing capacity. Assistance will include funding to expand and improve current drug resistance testing, real time PCR for infant diagnosis, implementation of new and monitoring of existing EQA programs, investigating viable and sustainable communication systems to provide rural clinics with patient results, as well as providing temporary structures to house laboratory equipment in space limited settings and/or rural areas with limited laboratory services. ACTIVITY 7: Assist NHLS in the development of an integrated HIV/TB technologist training program. (co supported in HVTB) to maintain and sustain viable HIV and TB diagnostic services. The training curriculum would address technical HIV-testing methodologies and provide practical hands-on training to meet the increased technical demands of HIV testing services, as well as the need to improve TB smear microscopy and AFB culture techniques. Efforts will be coordinated with SA Health Care Professionals Association to ensure course accreditation. ACTIVITY 8: Expand TB culture and drug sensitivity testing (DST) services. 4 TB laboratories will be renovated and equipped to meet current demands: 2 in the midlands and northern provincial KZN region and 2 sites in Limpopo and Mpumalanga provinces. Proposed sites would improve overall performance and TB diagnostic capacity within the region.

INTEGRATED ACTIVITY FLAG: This National Institute of Communicable Diseases (NICD) activity also relates to activities in PMTCT (#7917), Laboratory Infrastructure (#7391) and Basic Health Care and Support (#7393). SUMMARY: The NICD will use PEPFAR funds to: 1) Enhance existing national and provincial surveillance by extending sentinel surveillance of opportunistic bacterial and fungal pathogens in HIV-infected individuals; 2) Conduct microbiological, etiological and antimicrobial resistance surveillance for sexually transmitted infections (STIs) in five population groups in Gauteng province; 3) Develop a program to assist national efforts in communicable disease surveillance by providing appropriate training for epidemiologists and laboratory workers; 4) Collect trend data for HIV incidence in the evaluation of the BED assay and the validation of the assay in general populations; and 5) Conduct HIV-1 drug resistance testing in drug-naive and drug-treated persons. Major emphasis areas are HIV surveillance and facility surveys. Target populations include infants and children, adults, pregnant women, clients and sex partners of sex workers, volunteers, members of the National AIDS Control Program, public healthcare workers and country coordinating mechanisms. BACKGROUND: HIV opportunistic infection (OI) surveillance was initially enhanced with CDC funding in FY 2003 by establishing population-based incidence rates of Cryptococcus in Gauteng province. PEPFAR funding in FY 2006 was used to expand cryptococcal surveillance to all nine provinces. This system will document the effect that the introduction of antiretroviral treatment (ART) has on the incidence of opportunistic diseases. STIs remain a major co-factor for acquiring and transmitting HIV infection. An ongoing surveillance program for STIs is essential to provide appropriate management information at various levels of the health service. These data are critical for monitoring the effectiveness of syndromic management algorithms and for measuring the impact of STI interventions on HIV prevention. However, syndromic management of STIs does not allow for surveillance of either disease etiology or of antimicrobial resistance. Rising levels of antimicrobial resistance in gonococci and the high prevalence of herpes as a cause of genital ulceration are cause for concern and may accelerate HIV transmission. Microbiological surveillance activities will focus on STI microbiological surveillance in Gauteng. Data from these projects will inform national and local HIV and STI policy development. ACTIVITIES AND EXPECTED RESULTS: ACTIVITY 1: Training in integrated public health practice There is an increasing need for public health professionals to receive training in integrated public health practice. The Field Epidemiology and Laboratory Training Program (FELTP), modeled after the CDC's Epidemic Intelligence Service, is a training and service program intended to build capacity in applied epidemiology and public health practice. The NICD is working with the National Department of Health, the University of Pretoria and the CDC to develop a FELTP in South Africa. FELTP training will include: situational analyses to identify management skills and performance gaps; creating an action plan for faculty and curriculum development; and training in epidemiology, laboratory and public health practice. To date, FELTP activities include joint introductory short courses for surveillance/epidemiologists (n=9) and lab technologists (n=9) and project feedback is scheduled for October 2006. The FELTP, National Health Laboratory Systems (NHLS) and CDC provided a short course (3 days, n=34) on laboratory quality management systems that serves to segue on specific courses centered on HIV, OI and TB to promote laboratory quality systems for NHLS business managers and laboratories that provide support to the antiretroviral program. Training segues with Laboratory Information programs. ACTIVITY 2: Incidence testing Incidence testing is critical for targeted planning and to measure the effect of HIV prevention programs. HIV incidence measures are needed to understand the dynamics of the epidemic and to make decisions about interventions to prevent infections. Measuring incidence in cross-sectional population surveys can avoid the complexities associated with surveillance systems or with inferring incidence from prevalence. In the context of expanding ART programs it will become more complex to interpret HIV prevalence survey data, and more valuable to have HIV incidence estimates as an additional data source. The BED assay will be used to evaluate specimens from the 2005 and 2006 antenatal care seroprevalence surveys. The NICD will also measure the specificity of the BED, estimate the sensitivity of the BED and determine HIV-1 incidence in different general populations.

The assay will be applied to a large population-based HIV surveillance program conducted by the Africa Centre (which is located in KwaZulu-Natal and is also a PEPFAR partner). Additional incidence tests and empirically-derived correction factors will be applied to determine the suitability of the BED assay. ACTIVITY 3: HIV drug resistance project The HIV drug resistance project started in 2003 will continue to watch for the emergence of drug resistance in the community (transmitted resistance) as part of South African Treatment and Resistance Network (SATuRN). This is key to determine the choice of regimen and to identify high levels of resistance for further investigation. HIV drug resistance testing will be performed on newly diagnosed patients to determine potential transmitted resistance. It will also be performed on those receiving treatment to determine resistance to drug regimens. Other methodologies for resistance surveillance will also be evaluated, including assays for measuring phenotypic drug resistance. ACTIVITY 4: OI surveillance OI surveillance will be performed by capturing case data at sentinel site hospitals; analyzing clinical data centrally, and gathering details about pathogens with regard to susceptibility, serotypes/groups, subspecies and other relevant data; providing training and site visits for feedback to clinical and laboratory staff; establishing provincial and national laboratory networks; conducting annual meetings for principal collaborators to discuss results, surveillance objectives, and the inclusion of new diseases/syndromes as national priorities change. Microbiological STI surveillance will take place among five population groups: township youth, HIV-infected symptomatic patients, pregnant women living with HIV, STI patients attending private health providers and STI patients attending public healthcare facilities. Youth and STI clinic attendees will be encouraged to test for HIV using VCT delivered at the same time as STI testing. STIs are strongly linked to HIV transmission and effective STI management reduces HIV transmission. NICD will implement the project in collaboration with local health departments (STI medicines) Mothusimpilo NGO (youth), treatment and antenatal clinics for people living with HIV, primary healthcare and private practitioner clinics in Johannesburg and Carletonville. STI screening results will be used to determine prevalence of STIs in each population, to inform STI syndromic management guidelines through provision of information on syndrome etiology and resistance of gonorrhea to current first-line antimicrobial therapy. Thirty healthcare workers will be trained on the importance of STI management to prevent HIV transmission. By improving surveillance and building capacity to inform policy and facilitate program management, these activities will contribute to the PEPFAR's goals of preventing 7 million new infections and treating 2 million people. These activities also support the prevention and treatment goals in the USG Strategy for South Africa.