[Show abstract][Hide abstract] ABSTRACT: Background: Several circumcision devices have been evaluated for a safe and simplified male circumcision among adults. The PrePex device was prequalified for voluntary male medical circumcision (VMMC) in May 2013 by the World Health Organization and is expected to simplify the procedure safely while reducing cost. South Africa is scaling up VMMC. Objective: To evaluate the overall unit cost of VMMC at a mixed site vs. a hypothetical PrePex-only site in South Africa. Design: We evaluated the overall unit cost of VMMC at a mixed site where PrePex VMMC procedure was added to routine forceps-guided scalpel-based VMMC in Soweto, South Africa. We abstracted costs and then modeled these costs for a hypothetical PrePex-only site, at which 9,600 PrePex circumcisions per year could be done. We examined cost drivers and modeled costs, varying the price of the PrePex device. The healthcare system perspective was used. Results: In both sites, the main contributors of cost were personnel and consumables. If 10% of all VMMC were by PrePex at the mixed site, the overall costs of the surgical method and PrePex were similar -US$59.62 and $59.53, respectively. At the hypothetical PrePex-only site, the unit cost was US$51.10 with PrePex circumcisions having markedly lower personnel and biohazardous waste management costs. In sensitivity analysis with the cost of PrePex kit reduced to US$10 and $2, the cost of VMMC was further reduced. Conclusions: Adding PrePex to an existing site did not necessarily reduce the overall costs of VMMC. However, starting a new PrePex-only site is feasible and may significantly reduce the overall cost by lowering both personnel and capital costs, thus being cost-effective in the long term. Achieving a lower cost for PrePex will be an important contributor to the scale-up of VMMC.
Full-text · Article · Dec 2015 · Global Health Action
[Show abstract][Hide abstract] ABSTRACT: Effective treatment of tuberculosis during pregnancy is essential to prevent maternal and fetal mortality, but little is known about the effects of pregnancy on disposition of anti-tuberculosis drugs. We explored the effects of pregnancy on pharmacokinetics of rifampicin, the key sterilizing drug in tuberculosis treatment, in Tshepiso, a prospective cohort study involving pregnant HIV-infected women with or without tuberculosis in Soweto, South Africa. Participants taking standard first-line tuberculosis treatment underwent sparse sampling for rifampicin at 37 weeks' gestation or delivery, then postpartum. Cord blood was collected when possible. A population pharmacokinetic model was developed to investigate the effects of pregnancy on rifampicin pharmacokinetics.
Among 48 participants, median age and weight were 28 years and 67 kg. A one-compartment model with first-order elimination, transit compartment absorption, and allometric scaling described the data well. Pregnancy reduced rifampicin clearance by 14%. The median (interquartile range) model-estimated rifampicin area under the concentration-time curve (AUC
) during pregnancy or intra-partum was 40.8 h⋅mg/L (27.1-54.2), compared to 37.4 (26.8-50.3) postpartum. Maximum concentrations were similar during pregnancy and postpartum. Rifampicin was detectable in 36% (8/22) of cord blood samples. 88% (42/48) of women had successful treatment outcomes. There was one case of perinatal TB.
In conclusion, rifampicin clearance is modestly reduced during the last trimester of pregnancy. Exposures are only slightly increased, so dose adjustment during pregnancy is not needed. Rifampicin was detected in cord blood samples when delivery occurred soon after dosing. Consequences of exposure to this potent inducer of metabolizing enzymes among HIV-exposed infants are unclear.
No preview · Article · Dec 2015 · Antimicrobial Agents and Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: This is a cross-sectional study to estimate the prevalence of latent tuberculous infection (LTBI) and the annual risk of tuberculous infection (ARTI) among a sample of children aged 5 and 7 years in Matlosana, South Africa. LTBI prevalence was significantly higher in children aged 7 years (n = 704) (19.7%, 95%CI 16.75-22.65) than in those aged 5 years (212/1401, 15.1%, 95%CI 13.23- 16.97) (P=0.0075).TheARIwas 2.9%(95%CI 2.2-3.6).
No preview · Article · Nov 2015 · The International Journal of Tuberculosis and Lung Disease
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: A high proportion of deaths in Africa occur at home, where cause of death (CoD) is often unknown. We ascertained undiagnosed pulmonary tuberculosis (TB) by performing limited autopsies in adults dying at home in whom there was no apparent CoD. METHODS : Mortuaries in Matlosana, South Africa, identified potentially eligible adults with no antemortem diagnosis and/or no recent hospital admission. A questionnaire was administered to family members. Bilateral lung core biopsies and modified bronchoalveolar lavage (BAL) were performed. The biopsies were examined histologically and submitted with BAL aspirates for mycobacterial culture (MGIT™) and Xpert® MTB/RIF testing. Human immunodeficiency virus (HIV) testing was not performed. RESULT S : Of 162 families approached, 28 refused and 29 of the deceased were on or had recently stopped antituberculosis treatment; 85 were included. All were Black and 53% were men. The median age was 57 years (interquartile range [IQR] 44-66) and median symptom duration (mainly cough) was 63 days (IQR 14-112). Laboratory evidence of TB was found in 27 (31.8%); 21 were Xpert-positive, 23 were MGIT-positive and 14 had histological evidence consistent with active TB. CONCLUS ION: In this high HIV prevalence setting, a quarter of the home deaths had evidence of undiagnosed, likely infectious TB, suggesting that TB-related mortality is under-ascertained and under-reported, with serious implications for TB control in high TB burden settings.
No preview · Article · Nov 2015 · The International Journal of Tuberculosis and Lung Disease
[Show abstract][Hide abstract] ABSTRACT: The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a crucial opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programmes focusing on single strategies rather than comprehensive programmes that deliver an integrated arsenal for tuberculosis control might continue to struggle. Tuberculosis preventive therapy is a poorly used method that is essential for controlling the reservoirs of disease that drive the epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission, and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. In this Series paper we outline challenges to implementation of preventive therapy and provide pragmatic suggestions for overcoming them. We further advocate for tuberculosis preventive therapy as the core of a renewed worldwide focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems and community engagement, and enhance sustainable large scale implementation of preventive therapy programmes.
[Show abstract][Hide abstract] ABSTRACT: Background:
Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.
Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts.
Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART.
In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings-integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The household is important in influenza transmission due to intensity of contact. Previous studies reported secondary attack rates (SAR) of 4-10% for laboratory-confirmed influenza in the household. Few have been conducted in middle-income countries.
We performed a case-ascertained household transmission study during May-October 2013. Index cases were patients with influenza like illness(cough and self-reported or measured fever (≥38°C)) with onset in the last 3 days and no sick household contacts, at clinics in South Africa. Household contacts of index cases with laboratory-confirmed influenza were followed for 12 days.
Thirty index cases in 30 households and 107/110 (97%) eligible household contacts were enrolled. Assuming those not enrolled were influenza negative, 21/110 household contacts had laboratory-confirmed influenza (SAR 19%); the mean serial interval was 2.1 days (SD = 0.35, range 2-3 days). Most (62/82; 76%) household contacts who completed the risk factor questionnaire never avoided contact and 43/82 (52%) continued to share a bed with the index case after illness onset.
SAR for laboratory-confirmed influenza in South Africa was higher than previously reported SARs. Household contacts did not report changing behaviors to prevent transmission. These results can be used to understand and predict influenza transmission in similar middle-income settings.
No preview · Article · Sep 2015 · The Journal of infection
[Show abstract][Hide abstract] ABSTRACT: T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naïve T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Δ32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Δ32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (≥800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes.
Full-text · Article · Aug 2015 · Proceedings of the National Academy of Sciences
[Show abstract][Hide abstract] ABSTRACT: We assessed HIV RNA suppression, resistance, and CD4 T-cell count 12 months post-partum among pregnant women retained in care in an observational cohort study.
We prospectively followed two groups of HIV-infected pregnant women - with or without tuberculosis - recruited from pre-natal clinics in South Africa. Women who received antiretroviral therapy during pregnancy and reported being on therapy 12 months post-partum were included. Serum samples from women with HIV viremia 12 months post-partum were tested for drug resistance.
Of 103 women in the study, median age and CD4 T-cell count at enrollment were 29 years [interquartile range (IQR): 26, 32] and 317 cells/mm (IQR: 218, 385), respectively; 43 (42%) had tuberculosis at baseline. During pregnancy, 87% of the women achieved an HIV RNA <400 c/mL compared to 71% at 12 months post-partum (p<0.001). Factors independently associated with an HIV RNA <400 c/mL at 12 months were age ≥30 years, detectable plasma efavirenz concentration, and HIV RNA <400 c/mL while pregnant; there was a trend toward both a detectable viral load and peripartum depression. HIV drug resistance results were available from 25 women, 12 (48%) had major drug resistance mutations. CD4 T-cell count declined a median of 13 cells/mm (IQR: -66, 140) from delivery to 12 months in women with viremia at 12 months CONCLUSIONS:: Success with maintaining virologic control declined post-partum among HIV-infected women who remained in care and on ART, and CD4 T-cell count decline and drug resistance was common.
Full-text · Article · Aug 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis is the leading cause of death among adults infected with human immunodeficiency virus (HIV), and rates of tuberculosis
remain high even after preventive therapy. Among 908 HIV-infected adults in a trial of preventive treatment, we found self-reported
alcohol consumption, low baseline CD4 count, high baseline viral load, and tuberculin skin test size >15 mm as independent
risk factors for incident tuberculosis.
Preview · Article · Dec 2014 · Open Forum Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Scaling up services to achieve HIV targets will require that countries optimize the use of available funding. Robust unit cost estimates are essential for the better use of resources, and information on the heterogeneity in the unit cost of delivering HIV services across facilities - both within and across countries - is critical to identifying and addressing inefficiencies. There is limited information on the unit cost of HIV prevention services in sub-Saharan Africa and information on the heterogeneity within and across countries and determinants of this variation is even more scarce. The "Optimizing the Response in Prevention: HIV Efficiency in Africa" (ORPHEA) study aims to add to the empirical body of knowledge on the cost and technical efficiency of HIV prevention services that decision makers can use to inform policy and planning.
ORPHEA is a cross-sectional observational study conducted in 304 service delivery sites in Kenya, Rwanda, South Africa, and Zambia to assess the cost, cost structure, cost variability, and the determinants of efficiency for four HIV interventions: HIV testing and counselling (HTC), prevention of mother-to-child transmission (PMTCT), voluntary medical male circumcision (VMMC), and HIV prevention for sex workers. ORPHEA collected information at three levels (district, facility, and individual) on inputs to HIV prevention service production and their prices, outputs produced along the cascade of services, facility-level characteristics and contextual factors, district-level factors likely to influence the performance of facilities as well as the demand for HIV prevention services, and information on process quality for HTC, PMTCT, and VMMC services.
ORPHEA is one of the most comprehensive studies on the cost and technical efficiency of HIV prevention interventions to date. The study applied a robust methodological design to collect comparable information to estimate the cost of HTC, PMTCT, VMMC, and sex worker prevention services in Kenya, Rwanda, South Africa, and Zambia, the level of efficiency in the current delivery of these services, and the key determinants of efficiency. The results of the study will be important to decision makers in the study countries as well as those in countries facing similar circumstances and contexts.
Full-text · Article · Nov 2014 · BMC Health Services Research
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION
Evidence on the efficiency of HIV prevention interventions is limited. ORPHEA project aimed to estimate average costs and analyse their heterogeneity for three HIV prevention interventions: prevention of mother-to-child transmission (PMTCT), voluntary medical male-circumcision (VMMC), and HIV-testing and counseling (HTC), in Kenya, Zambia, Rwanda and South-Africa.
Sample comprises of 60-80 clinics per country. Micro-costing was performed and relevant costs (personnel, supplies, utilities, equipment and property) and intervention-output data were collected retrospectively for 2011/2012. Information on time-allocation, building-space-used and time-motion is also collected . Quality is captured by measuring the facility’s attrition rate at each stage along the service delivery, using provider-vignettes and patient-exit-interviews. We estimated average-cost per each HIV prevention intervention.
Estimated weighted-average costs were US$18.1 per HTC client, US$50.1 per women tested in PMTCT services, US$93.4 per MC client. Staff costs account for more than 80% of the average costs in each prevention intervention. Variation in average cost for HTC and PMTCT by facility type is limited, except for faith-based hospitals. VMMC costs show important variations among different type of facilities, resulting cheaper to perform VMMC intervention in health centres.
Results suggest that there is a large potential to increase efficiency within the current financial and structural constraints of the health system in some countries in Africa. Staff accounts for the larger proportion of average-costs and offer the highest potential to implement actions to increase efficiency and quality. There is also need to explore different types of service delivery-models and their impacts on efficiency.
[Show abstract][Hide abstract] ABSTRACT: Background: While healthcare services become increasingly available in developing countries, there is heterogeneity in the quality of service delivery across health providers. As part of a cost-efficiency project (ORPHEA) conducted in Kenya, Zambia, South Africa and Rwanda, we assessed the quality of three HIV prevention interventions: Voluntary Medical Male Circumcision (VMMC), Prevention of Mother-to-Child Transmission (PMTCT), and HIV Testing and Counseling (HTC).
Description: We used multistage sampling techniques to select 60-80 health facilities per country stratifying by facility location, size and type. We conducted cross-sectional provider vignettes and patient exit interviews (PEI) to assess service quality measures by estimating provider competence and performance scores. Provider competence scores were compared with average scores for provider performance at the facility level to estimate potential performance.
Results: Results are currently available for two (Kenya, Zambia) of the four countries*, where we surveyed 799 providers and 1,161 clients. On average, HTC healthcare providers had a vignette score of 59% and a PEI score of 26%; PMTCT providers had a vignette score of 56% and a PEI score of 32%; and VMMC providers had a vignette score of 67% and received a score of 48% from PEI.
Conclusions: We found, there is significant opportunity to increase quality of services without additional health resources but rather by reallocating labor resources. There is therefore need to investigate how different service delivery models could be implemented to reach full performance.
* Results from the remaining two countries may be available by the time of the conference.
Learning Areas: Biostatistics, economics
Conduct evaluation related to programs, research, and other areas of practice
Provision of health care to the public
Public health or related research
Social and behavioral sciences
Assess the quality of three HIV prevention interventions in Kenya, Rwanda, South Africa and Zambia.
Keywords: HIV Interventions, Quality of Care
Presenting author's disclosure statement:
Qualified on the content I am responsible for because: I am a researcher at the Center for Health Systems Research at the Mexico National Institute of Public Health (INSP) where I have been involved in multi-country economic, impact, and efficiency evaluations in in low- and middle-income countries. I hold a master's degree in economics.
Any relevant financial relationships? No
I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.
Back to: 4330.0: HIV/AIDS in International Settings
[Show abstract][Hide abstract] ABSTRACT: Introduction: Staff costs comprise the largest share of average facility costs to provide HIV prevention services. Evidence has shown that greater scale of production reduces average costs of these interventions. Little is known about the optimal combination of staff and quality that predict technical efficiency, as to increase value-for-money of HIV spending.
Methods: A cost analysis was implemented at 92 facilities offering HTC in Kenya, Zambia, Rwanda and South Africa in 2011-2012. Staff costs were allocated to interventions using time-motion data. Standardized vignettes were administered to score technical proficiency. We estimated average staff cost by dividing total prorated staff costs by the number of HTC clients in each facility. We created quantiles of operation scale and quality, to analyze its tradeoff and explore costs efficiency of HTC delivery.
Results: Mean staff costs per client tested were 18.8 USD (IQR: 0.5;18.1), with heterogeneity by facility type. Independent of health providers' competence score, operation scale negatively correlated with average costs: Moving from the first quartile of scale towards the upper quartile yielded a 90% reduction in staff costs. Among the subset of facilities in the uppermost quartile of scale, we found a mean difference in staff costs between the lower and upper quartiles of providers’ competence of 1.2 USD.
Conclusions: These results demonstrate the need to understand the mechanisms that curb efficiency in the provision of HIV prevention interventions. We provide evidence of the possibility to achieve higher quality of care without escalating the budget, provided that service utilization is increased.