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 PSI STI Treatment Kits Health Impact
Estimation Model
Hongmei Yang Research & Metrics, Population Services International December 2010 This document may be freely reviewed, quoted, reproduced or translated, in part or in full, provided the source is acknowledged: Yang H (2010). PSI STI Treatment Kits Health Impact Estimation Model. Washington, DC: Population Services International. Available at: http://www.psi.org/resources/publications. PSI shares its models with all interested individuals or organizations. Please note that the models are updated periodically based on the latest available epidemiological, demographic, intervention effectiveness, and utilization data. As a result, numbers used in this document should be considered illustrative only. They show how the model works, but they are likely to have changed since the time of writing. For more information or the latest model updates, contact Hongmei Yang at [email protected]. © Population Services International, 2010 P S I ■■ | 2 Contents
Background ............................................................................................................................................................................. 4 Section 1 Structure of the Model ............................................................................................................................................ 7 1.1 Parts of the syndrome model ....................................................................................................................................... 7 Section 2 Estimating Disease Burden ...................................................................................................................................... 9 Section 3 Estimating the Impact of Interventions ................................................................................................................ 11 3.1 Impact of syndromic management in the ideal situation (i.e., the person being treated with the STI kit is actually infected with the STI(s)) .................................................................................................................................................... 11 3.2 Impact of STI treatment kits ....................................................................................................................................... 11 References ............................................................................................................................................................................ 14 Appendix A: Tables A.1 – A.5 ................................................................................................................................................ 16 P S I ■■ | 3 STI Treatment Kits DALY Model
Background
Population Services International (PSI) is a social marketing organization that promotes healthy behaviors in low‐income and vulnerable populations. PSI has programs in 65 countries (www.psi.org) and covers a wide range of health areas including prevention of sexually transmitted infections (STIs). PSI uses the disability‐adjusted life year (DALY) as the metric for measuring the health impact of interventions. A DALY model has been developed for each of PSI’s products/services and behavior change communication (BCC) interventions. The DALY model presented here is the STI treatment kits DALY model. Specific to STI prevention, PSI implements social marketing programs that distribute pre‐packaged STI treatment kits to end‐users for treatment of existing STIs and to prevent the spread of STIs and HIV. These programs are implemented in nine platforms worldwide, four in sub‐Saharan Africa (Côte d’Iviore, Ethiopia, Madagascar and Swaziland) and five in Asia (Cambodia, India, Lao, Myanmar, and Pakistan). The contents of the STI kits vary by country. For example, the antibiotics in kits may vary because they are targeting different STI syndromes and populations. Currently, kits have been designed for the following six STI syndromes: urethritis/ cervicitis, nonherpetic genital ulcer, herpetic genital ulcer, vaginitis, lower abdominal pain, and inguinal bubo. Kits are distributed to individuals through doctors or pharmacies, based on symptoms and signs, following WHO guidelines on syndromic management of STI syndromes. Detailed information about the kits is presented in Table 1 (below) by country. A DALY model has been developed for each syndrome that the kits are designed to treat and DALYs averted per unit consumed (i.e., DALY coefficient) is estimated for each STI kit. Sexually transmitted infections (STIs) are prevalent in all parts of the world; more than 30 pathogens are known to cause STIs. The World Health Organization estimates that each year gonorrhea, chlamydia, syphilis, and trichomoniasis (the four main curable STIs) account for more than 340 million new infections (WHO, 2007; WHO, 2001). While some STIs are self‐limiting, the symptoms affect a person’s quality of life and, if left untreated, may lead to severe complications, particularly in women of reproductive age. In addition, evidence indicates that STIs may facilitate the transmission of HIV (Buchacz et al., 2006; Cohen and Hoffman, 1998; Cowan et al., 2006; Hayes et al., 1995; Laga et al., 1993; Sadiq et al., 2005; Wawer et al., 1999; Weiss et al., 2001). Therefore, effective treatment of STIs is important not only at the individual level (to cure and/or shorten the duration of the STI) but also at the population level (to slow the potential spread of HIV in the population). [Note: The debate continues whether curing STIs leads to reduced risk of HIV infection (See Gray and Wawer, 2008).] P S I ■■ | 4 Table 1: PSI STI treatment kits, by country Country Ethiopia STI kit AddisCure Genicure Madagascar Cura‐7 URET‐P Côte d’Ivoire URET‐S LEUCO‐P LEUCO‐S SALPIN‐P SALPIN‐S ULGEN Swaziland India Kit1 (ACT‐
1) Kit2 Kit4 Kit5 Kit6 Kit7 P S I ■■ | 5 Targeted STI syndrome Urethral discharge Antibiotics (dosage & tablets) Doxycycline: 100mg x 14, Ciprofloxacin: 500mg x 1 Nonherpetic genital ulcer Ciprofloxacin: 500mg x 6, Penicillin: 15cc vials Urethritis Doxycycline: 100mg x 14, Ciprofloxacin: 500mg x 1 Urethral discharge (men & Ciprofloxacin: 500mg x 1, SWs) Doxycycline: 100mg x 14 Chlamydia & trichomona Doxycycline: 100mg x 28, Metronidazole: 500mg x 4 Vaginitis Metronidazole: 500mg x 20, Butoconazole: 100mg x 6 Cervicitis Doxycycline: 100mg x 42, Ciprofloxacine: 500mg x 1 Lower abdominal pain Amoxicilline: 200mg x 4, Pefloxacine: 400mg x 4 Lower abdominal pain Doxycycline: 100mg x 42, Ketoprofene or Diclofenac: x 20, Metronidazole: 250mg x 20 Nonhepatic genital ulcer Cefriaxone: 250 mg (1 vial), Benzathine penicillin: 2.4mµ X 2 Urethral discharge (men) Doxycycline: 100mg x 14 Ciprofloxacin: 500mg x 1 Urethral discharge (women): Doxycycline: 100mg x 2 x 14 (Chlamydia, Gonorrhea, Ciprofloxacin: 500mg x 1 Trichomona) Metronidazole: 200mg x 10 Genital ulcer syndrome Benzathine penicillin: 2.4mµ (Herpes, Syphillis, Chancroid) Ciprofloxacin: 500mg x 1 Acyclovir: 200mg x 35 Genital Herpes Acyclovir: 200mg x 5 x 7 Inguinal bubo: (Chancroid, Doxycycline: 100mg tabs x 2 x 7 Lymphogranuloma Ciprofloxacin: 500mg x 1 x1 Venerium) Urethral discharge Azithromycin: 1g x 1, Cefixime: 400mg x 1 Vaginitis Secnidazole: 2g x 1, Fluconazole: 150mg x 1 Nonherpetic genital ulcer Doxycycline: 100mg x 30, Azithromycin: 1g x 1 Herpetic genital ulcer Acyclovir: 400mg x 21 Lower abdominal pain Cefixime: 400mg x 1, Metronidazole: 400mg x 28, Doxycycline: 200mg x 28 Inguinal bubo Doxycycline: 100mg x 42, Azithromycin: 1g x 1 Number of condoms included 4 7 7 4 Pakistan Myanmar Cambodia Laos Clear‐7 Urethritis & cervicitis CureU Urethritis & cervicitis CureU Nonherpetic genital ulcer STOP‐Z Urethral discharge 1‐Stop Urethritis & cervicitis Ciprofloxacin: 500mg x 1, Doxycycline: 100mg x 14 Cefixime: 400mg x 1, Azithromycin: 1g x 1 Azithromycin: 1g x 1, Benzathine benzyl penicillin: 2.4mµ Azithromycin: 1g x 1, Cefixime: 400mg x 1 Azithromycin: 1g x 1, Cefixime: 400mg x 1 7 4 4 Accurate diagnosis of STIs is not easy, especially in resource‐poor countries where laboratory procedures for diagnosis are not readily available. To identify and treat STI cases in such settings WHO recommends the use of syndromic case management (WHO, 2005). Syndromic management relies on the patient’s symptoms and clinical signs for identification of the specific syndrome; then all causes of the syndrome are treated. WHO further recommends that persons with STIs receive counseling from a health professional. The content of the counseling should emphasize the following: •
•
•
Consistent use of condoms during treatment of the STI, Completing the full course of STI medication, and Ensuring that all sexual partners receive STI treatment. Syndromic management can be used to identify a range of STI syndromes in both women and men, although the sensitivity and specificity of the approach in detecting cervical infections in women is not considered satisfactory (Dallabetta et al., 1998; WHO, 2002). A major drawback of reliance on syndromic management of STIs is that many people with STIs do not go to clinics or hospitals for diagnosis and treatment. The reasons for this are typically concern about the cost of treatment and fear of the stigma associated with having an STI (Crabbe et al., 1996; Khamboonruang et al., 1996; Van der Geest, 1987). Such people usually end up self‐treating with drugs purchased at a pharmacy or drug store. The result can be inappropriate treatment (e.g., using antibiotics when an STI is not present), undertreatment (e.g., not taking the full course of medication), or overtreatment (e.g., using multiple medications when just one is recommended). PSI prepackaged STI treatment kits are effective in both the clinical and the nonclinical setting (Crabbe et al., 1998; Kambugu et al., 2000; Wilkinson et al., 1999). The typical PSI prepackaged STI treatment kit contains the following: •
•
•
•
Blister‐packed antibiotics ‐ a full regimen of pills to treat the pathogens causing the syndrome. The antibiotics are selected according to WHO guidance on syndromic management, taking into consideration local information on possible antibiotic resistance. Condoms ‐ a supply of condoms for use during the period of STI treatment; Partner referral cards ‐ cards to be given to all sexual partners, notifying them of the STI risk and referring them for treatment; and STI and product information leaflet – specific instructions on 1) treating the STI, 2) use of condoms to prevent the spread of STIs, and 3) notifying sexual partners about STI treatment. With all the STI treatment and prevention essentials together in one package, there is greater likelihood that the person with the STI will 1) adhere to the full course of treatment, 2) use protected sex to prevent the spread of the STI, and 3) notify sexual partners that they need to seek STI treatment. In most cases, PSI STI treatment kits are distributed to P S I ■■ | 6 patients by clinical physicians; however, they may also be sold in pharmacies, drug stores, and neighborhood retail outlets. The purpose of this write‐up is 1) to describe the structure and principles of a simple deterministic model (in Excel) that estimates the health impact of STI treatment kits measured in DALYs averted per STI kit distributed, and 2) to identify the parameters and assumptions used in the model. Section 1 Structure of the Model
The model for the STI treatment kits is designed to estimate both the burden of disease (BOD) of STIs and the health impact of the PSI STI treatment kit program. Calculating the burden of disease tests the reliability of the model by comparing the BOD obtained with those reported by other international organizations (e.g., UNAIDS). The burden of disease is measured by the number of new infections, deaths, and disability‐adjusted life years (DALYs). The health impact of a program’s products and services is usually measured by the number of new infections averted, deaths averted, and DALYs averted. However, because STI treatment kits are used by persons who already have STI infections, the health impact of these products is measured solely by deaths averted and DALYs averted. The six STI syndromes included in the DALY model differ substantially from each other; therefore, separate models and treatment kits were developed for each of the syndromes: •
•
•
•
•
•
urethritic/ cervicitis, nonherpetic genital ulcer, herpetic genital ulcer, vaginitis, lower abdominal pain, and inguinal bubo. Because males and females differ in the incidence of STIs, clinical presentation of STIs, disease progression of STIs, and treatment‐seeking behavior, the model maintains this dichotomy throughout. 1.1 Parts of the syndrome model
The model for each of the six syndromes has four parts. Parts 1 and 2 estimate the burden of disease (BOD) of STIs; parts 3 and 4 estimate the health impact of the STI treatment kits. The four parts are described below: Part 1 presents the epidemic and infection/complication information. The information includes epidemic parameters (incidence/death rates), severity of the infection (disability weight), progression of infection, and complications of the infection (see Table 2 below). Epidemic parameters can be country‐specific or region‐specific when country‐level data are not available. Although a person’s HIV/AIDS status and nutritional status may influence the progression and severity of STDs, they are not considered in the modeling. Data on disease progression and severity when left untreated is assumed to be the same for all PSI platforms. Part 2 calculates the burden of disease (BOD) of STIs. Calculating the burden of disease of STIs follows the method developed by the World Health Organization (World Bank/WHO, 2006). P S I ■■ | 7 Table 2: Disease‐related parameters STI infection Gonorrhea Chlamydia Syphilis Chancroid Herpes episode Trichomoniasis Vulvovaginal candidiasis Sequelae/complication Urethritis (M) Epididymitis (M) Cervicitis (F) PID episode (F) Infertility (F) Ophthalmia neonatorum Newborn blindness Newborn low vision Urethritis (M) Epididymitis (M) Cervicities (F) PID episode (F) Infertility (F) Ophthalmia neonatorum
Neonatal pneumonia
Primary syphilis (M&F)
2nd syphilis (M&F) 3rd syphilis (M) 3rd syphilis (F) Congenital syphilis Genital ulcer Herpetic genital ulcer
Vaginitis Vaginitis Duration
(years) 0.5
0.12
0.5
0.12
28.38
0.1
81.15
81.15
1.25
0.12
1.25
0.12
27.63
0.17
0.12
0.09
1
22.97
44
71.62
0.17
0.08
1.5
1.5
Disability
weight 0.067
0.167
0.049
0.169
0.18
0.18
0.6
0.233
0.067
0.167
0.049
0.327
0.18
0.18
0.28
0.015
0.048
0.283
0.283
0.315
0.05
0.1
0.015
0.015
Source (for duration): Refer to the Excel model sheets for the source of each individual parameter. Source (for most of the disability weights): World Bank. Global burden of disease and risk factors, by Lopez AD, Mathers CD, Ezzati M, Jamison DT, & Murray CJL. Oxford University Press, 2006. Part 3 presents the health impact, measured as STI deaths and DALYs averted, when an infected symptomatic person is treated effectively through syndromic management. This part of the model estimates the health impact of syndromic management measured by STI deaths averted and DALYs averted when an infected symptomatic patient is treated effectively through syndromic management. With curable STIs (e.g., gonorrhea, chlamydia, syphilis, chancroid, trichomoniasis, vulvovaginal candidiasis), the heath impact results from curing the infection, preventing severe complications, and, in the case of pregnant women, preventing a negative impact on the newborn. When the STI is not curable (e.g., genital herpes), the health impact results from shortening the duration of each episode and reducing the severity of the episode. P S I ■■ | 8 Part 4 presents the health impact, measured as STI deaths and DALYs averted per unit of STI treatment kit consumed (i.e., DALY coefficient). This part of the model estimates the health impact of STI treatment kits as measured by STI deaths and DALYs averted per STI kit consumed. It includes linking the STI kit to the health impact obtained in Part 3 and takes into consideration inappropriate treatment or overtreatment (i.e., wastage or 1‐ positive predictive value). Additionally, the following benefits are considered in the model: •
•
Preventing heterosexual transmission of HIV because STI was cured or the duration of the STI was shortened, and Preventing heterosexual transmission of HIV through use of condoms enclosed in the STI treatment kits. The model does not factor in the potential effect of the STI referral cards included in most of the STI treatment kits. PSI’s pilot studies found that the number of cards collected at the clinics involved was negligible. They concluded that it was difficult to measure both the utility of the STI referral cards and their impact (PSI, 2001). Section 2 Estimating Disease Burden
To estimate the burden of disease (BOD) of STIs the main causes of each syndrome are considered. For example, in the model for nonherpetic genital ulcer, syphilis and chancroid are the main causes of the syndrome and their burden of disease is estimated. In addition, the key sequelae/complications and their effects on newborns (if applicable) are considered. The relationship between infections, sequelae, and complications for each syndrome are shown in Figure 1 (see below). STI syndromes (cont.)
Vaginitis (F)
Lower abdominal
Pain (F)
Inguinal
bubo (M & F)
Pathogens
Trichomonas
Vaginalis
Candida
albicans
Nesseiria
gonorrhoeae
Chlamydia
trachomatis
Chlamydia
trachomatis
L types
Haemophilus
ducreyi
Inguinal &
femoral bubo
Inguinal &
femoral bubo
Infection/
sequelae/
complication
Vaginitis
Vaginitis
Lower abdominal pain
(PID episode)
Infertility
Lower abdominal pain
(PID episode)
infertility
Source: 1. WHO. Sexually transmitted and other reproductive tract infections - A guide to essential practice. WHO, Geneva, 2005.
2. World Bank. Global Burden of Disease & Risk Factors, by Lopez AD, Mathers CD, Ezzati M, Jamison DT, & Murray CJL.
Oxford University Press, 2006.
Fig. 1 Sexually transmitted infections and their sequelae (cont.)
P S I ■■ | 9 STI syndromes
Non-herpetic
genital ulcer (M&F)
Urethritis (M)/
Cervicitis (F)
Herpetic
genital
ulcer (M&F)
Pathogens
Nesseiria
gonorrhoeae
Chlamydia
trachomatis
Treponema
pallidum
Haemophilus
ducreyi
HSV-2
Genital ulcer
2nd syphilis
3rd syphilis
Genital
ulcer
Herpetic
ulcer
Infection/
sequelae/
complication
Urethritis (M)
Epididymitis (M)
Cervicitis (F)
PID episode (F)
Inf ertility (F)
Urethritis (M)
Epididymitis (M)
Cervicitis (F)
PID episode (F)
Infertility (F)
Influence
Ophthalmia neonatorum
Newborn blindness
on newborns
Newborn low vision
Death
Ophthalmia neonatorum
Neonatal pneumonia
Congenital
syphilis
yes
Source: 1. WHO. Sexually transmitted and other reproductive tract infections - A guide to essential practice. WHO, Geneva, 2005.
2. World Bank. Global Burden of Disease & Risk Factors, by Lopez AD, Mathers CD, Ezzati M, Jamison DT, & Murray CJL.
Oxf ord University Press, 2006.
Fig. 1 Sexually transmitted infections and their sequelae
The burden of disease (BOD) of each STI infection (including its progression) is estimated using the following formula developed by the World Health Organization: BOD = population size * incidence rate * YLD + population size * death rate * YLL Where, YLD (years lost due to disability) = duration of each condition * disability weight of each condition, discounted at 3% for future years, and YLL (years of life lost) = life expectancy – age at death, discounted at 3% for future years. The incidence rate and death rate are used to calculate the number of infections and deaths in a year. The number of cases with sequelae/complications is calculated by multiplying the number of infections by the disease progression rates. The duration and disability weight of each condition (infection/sequelae/complication) when left untreated is disease‐
specific and values are assumed to be the same for all the platforms. However, STI morbidity and mortality data (including age at death) vary from country to country. Ideally, such data should be country‐specific, but because STI information is not readily available for most developing countries, the decision was made to use regional epidemic data in the model. The regional incidence data on common STIs included in the STI treatment model are from 2001 (WHO, 2001); the World Health Organization scheduled an update for 2007 but it has not yet been published. Mortality data for the STI treatment model is from World Bank information on the global burden of diseases and risk factors (World Bank, 2006). It should be noted that some countries are included in different regions in the WHO and World Bank reports. For example, India and Pakistan are grouped under South Asia in the World Bank report and grouped under the South East Asia Region in the WHO report. Appendix Table A.1 (STI incidence rate by sex and region) and A.2 (syphilis death rate and age at death by sex and region) have detailed footnotes explaining the differences in regional classification of countries. P S I ■■ | 10 Because there is limited epidemic data on lymphogranuloma venereum (LGV) and the STI treatment kit for LGV‐
associated inguinal bubo is marketed only in India, the epidemic data for LGV covers India only and is based on the results of two studies in different settings (Parashar et al., 2006; Sharma and Gupta, 2009). Section 3 Estimating the Impact of Interventions
In the STI treatment model the health impacts of interventions are measured two ways. First, the health impact resulting from curing an infected symptomatic person effectively (or shortening the STI episode) through syndromic management is estimated in deaths and DALYs averted (Part 3). Second, the health impact resulting from the distribution/consumption of STI treatment kits is estimated according to deaths and DALYs averted (Part 4). 3.1 Impact of syndromic management in the ideal situation (i.e., the person being treated with the STI kit is
actually infected with the STI(s))
For curable STIs (e.g., gonorrhea), the probability of being cured is estimated by multiplying the likelihood of an infected symptomatic person being adequately treated by the clinical efficacy of the treatment. Deaths averted and then DALYs averted are calculated using case fatality rate data for the situation when infected symptomatic persons are treated effectively by syndromic management. For noncurable STIs (e.g., herpes), the duration of symptoms after treatment and the disability weight after treatment are used to estimate DALYs averted when an infected symptomatic person is treated effectively by syndromic management. Treatment‐related parameters are shown in Appendix Tables A.3 and A.4 for curable and noncurable STIs, respectively. For inguinal bubo associated with lymphogranuloma venereum (LGV), although clinical observations have reported treatment success using tetracycline, minocycline, and rifampicin (Sowmini et al., 1976; CDC, 1993), no controlled double‐blind treatment trials have been published on effective management of LGV. One comparative trial published in 1957 reported that the duration of buboes was shortened significantly in patients receiving tetracycline, sulfadiazine, or chloramphenicol, compared with patients receiving symptomatic treatment (pain killer) (Greaves et al., 1957). The STI treatment model applied the approach for noncurable STIs (i.e., shorten the duration) to LGV (see Appendix Table A.4). The health impact of STI treatment kits treating LGV is shown in Appendix Table A.5. 3.2 Impact of STI treatment kits
To estimate DALYs averted per STI treatment kit consumed (i.e., DALY coefficient), three components are considered in the model: 1) curing the STI infection if it is curable or shortening the duration of the episode if it is not curable, 2) preventing HIV heterosexual transmission by curing STI or shortening the duration of the episode if it is not curable, and 3) preventing HIV heterosexual transmission through use of condoms. Curing the STI infection if it is curable or shortening the duration of the episode if it is not curable. In this component the health impact of an STI treatment kit is estimated to better reflect the reality of the situation. Because STI treatment kits can be obtained without a prescription/diagnosis, and many cases presenting with symptoms may not be STI cases, positive predictive value (i.e., percentage of the syndrome caused by key pathogens) was taken into account for potential wastage due to inappropriate treatment or overtreatment. Figure 2 (below) uses curable STI syndromes as an example and presents the operational model of the STI treatment kit in curable STI syndromic management. P S I ■■ | 11 Is the symptom
caused by
key STI pathogens
associated with it?
Proportion of
key
pathogens?
Adequately
treated?
Yes
(or clinical efficacy)
No
(or treatment
failure)
Pathogen 1
Yes
Effectively
treated?
Yes
No
(or PPV)
(or undertreated)
……
An STI kit is
used by an
individual
w symptoms
Pathogen n
No
(or mistreated)
Fig. 2 Operational model of STI kit program in curable STI syndromic
management
Some STI treatment kits target males, some target females, and some target both males and females. Because disease progression (infection/sequelae/complication) can vary by gender the health impact of treating some STIs can also vary by gender. Therefore, in the model, when an STI treatment kit is designed for use by both genders, it is important to know how likely it is that the kit will be used by a man versus a woman. The information is estimated through a function that includes: • STI incidence rate by sex, • Percentage of infected men and/or women who present with symptoms, and • Percentage of symptomatic men and women seeking and receiving treatment. When a syndrome is related to more than one key pathogen and different pathogens cause different infections/sequelae/complications, the proportion of etiological agents is considered for a better estimate of the health impact of the STI treatment kit. Data on positive predictive value and etiological agents is presented in Appendix Table A.5. Preventing sexual transmission of HIV by curing the STI or shortening the duration of the episode if it is not curable. To estimate the health impact of the second component (i.e., preventing sexual transmission of HIV by curing the STIs or shortening its duration), the model groups STIs into two large categories, ulcerative and nonulcerative STIs. Although different STI infections may have different effects on sexual transmission of HIV, the literature suggests that ulcerative STIs generally have greater effect on HIV transmission than nonulcerative STIs. It has been estimated that the per‐act cofactor effect of genital ulcers on HIV infection ranges from 3 to 300 (Hayes et al., 1995); for nonulcerative STIs, a relative risk of 2 to 5 has often been used in models of HIV transmission (Schmid et al., 2000); and a per‐act cofactor effect of 3 has been used by other researchers (White et al., 2008). In the STI treatment model a cofactor effect of 7 was assumed for ulcerative STIs and a cofactor effect of 2 was assumed for nonulcerative STIs. P S I ■■ | 12 The PSI HIV DALY model currently in use is adopted and the effect of STI treatment on HIV transmission is factored in while calculating the probability of infection at follow‐up (i.e., after the STI treatment kit intervention). [Note: For purposes of external review, please refer to the spreadsheet “DALYs via reducing HIV transmission.”] The outputs (i.e., deaths averted and DALYs averted in a year if a person with an ulcerative or nonulcerative STI is treated effectively) from the spreadsheet are analyzed for one year. Because the duration of most STIs is not exactly a year, the duration of each STI when left untreated is used to adjust the impact (see formula below). Preventing heterosexual transmission of HIV through use of condoms. To estimate the health impact of the third component (i.e., preventing heterosexual transmission of HIV through use of condoms), the condom death coefficient (number of deaths averted per condom used) and the condom DALY coefficient (number of DALYs averted per condom used) obtained from the PSI HIV DALY model currently in use are multiplied by the number of condoms in the STI treatment kit. P S I ■■ | 13 References
Buchacz K, Patel P, Taylor M et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV‐infected patients with new syphilis infections. AIDS 2006; 20: 305‐306. Centers for Disease Control and Prevention (CDC). Recommendations for the prevention and management of Chlamydia trachomatis infections. MMWR 1993; 42(RR‐12): 1‐39. Cohen MS, Hoffman I. Sexually transmitted diseases enhance transmission of HIV; no longer a hypothesis. Lancet 1998; 351: 5‐7. Cowan FF, Pascoe SJ, Barlow KL et al. Association of genital shedding of herpes simplex virus type 2 and HIV‐1 among sex workers in rural Zimbabwe. AIDS 2006; 20: 261‐267. Crabbe F, Carsauw H, Buve A, Laga M, Tchupo J‐P, Trebucq A. Why do men with urethritis in Cameroon prefer to seek care in the informal health sector? Genitourin Med 1996; 72: 220‐222. Crabbe F, Tchupo J‐P, Manchester T et al. Prepackaged therapy for urethritis: the “MSTOP” experience in Cameroon. Sex Transm Infect 1998; 74: 249‐252. Dallabetta GA, Gerbase AC, Holmes KK. Problems, solutions, and challenges in syndromic management of sexually transmitted diseases. Sex Transm Infect 1998; 74 (Suppl 1): S1–11. Hayes RJ, Schulz KF, Plummer FA The cofactor effect of genital ulcers on the per‐exposure risk of HIV transmission in sub‐
Saharan Africa. J Trop Med Hygiene 1995; 98: 1‐8. Gray RH & Wawer M. Reassessing the hypothesis on STI control for HIV prevention. Lancet 2008; 371: 2064‐2065. Greaves AB, Hilleman MR, Taggart SR, Bankhead AB, Feld M. Chemotherapy in bubonic lymphogranuloma venereum: a clinical and serological evaluation. Bull World Health Org 1957; 16: 277‐289. Kambugu et al. Evaluation of a socially marketed pre‐packaged treatment kit for men with urethral discharge in Uganda. XIIIth International AIDS Conference, Durban, July 2000, Abstract ThOrC765. Khamboonruang C, Beyer C, Natpratan C et al. Human immunodeficiency virus infection and self‐treatment for sexually transmitted diseases among northern Thai men. Sex Transm Dis 1996; 23: 264‐269. Laga M, Manoka A, Kivuvu M et al. Non‐ulcerative sexually transmitted diseases as risk factors for HIV‐1 transmission in women: results from a cohort study. AIDS 1993; 7: 95‐102. Parashar A, Gupta BP, Bhardwaj AK, Sarin R. Prevalence of RTI's Among Women of Reproductive Age Group in Shimla City. Indian Journal of Community Medicine 2006; 31(1). Available at http://www.indmedica.com/journals.php?journalid=7&issueid=80&articleid=1061&action=article PSI. Sexually transmitted infections in Sub‐Saharan Africa – the use and effectiveness of treatment kits. 2001. Sadiq T, McSorley J, Copas AJ et al. The effects of early syphilis on CD4 counts and HIV‐1 RNA viral loads in blood and semen. Sexually Transmitted Infections 2005; 5: 380‐385. P S I ■■ | 14 Schmid G, Markowitz L, Joesoef R and Koumans E. Bacterial vaginosis and HIV infection. Sexually Transmitted Infections 2000; 76: 3‐4. Sharma S and Gupta BP. The prevalence of reproductive tract infections and sexually transmitted diseases among married women in the reproductive age group in a rural area. Indian Journal of Community Medicine 2009; 34(1): 62‐64. Sowmini CN, Gopalan KN, Rao GC. Minocycline in the treatment of lymphogranuloma venereum. J Am Vener Dis Assoc 1976; 2(4): 19‐22. Van der Geest S. Self‐care and the informal sale of drugs in South Cameroon. Social Sci Med 1987; 25: 293‐305. Wawer J, Gray RH, Sewankambo NK et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Lancet 1999; 353: 525‐535. Weiss HA, Buve A, Robinson NJ et al. The epidemiology of HSV‐2 infection and its association with HIV infection in four urban African populations. Study Group on Heterogeneity of HIV Epidemics in African Cities. AIDS 2001; 15 (Suppl 4) S97‐
108. White RG, Orroth KK, Glynn JR, Freeman EE, Bakker R, Habbema DF, Terris‐Prestholt F, Kumaranayake L, Buve A, and Hayes RJ. Treating curable sexually transmitted infections to prevent HIV in Africa ‐ still an effective control strategy? Journal of Acquired Immune Deficiency Syndrome 2008; 47(3): 346‐353. WHO. Global prevalence and incidence of selected curable sexually transmitted infections ‐ overview and estimates. WHO, Geneva, 2001. WHO. Estimation of the incidence and prevalence of sexually transmitted tnfections. WHO, Geneva, 2002. WHO. Sexually transmitted and other reproductive tract infections ‐ a guide to essential practice. WHO, Geneva, 2005. WHO. Global strategy for the prevention and control of sexually transmitted infections : 2006‐2015 : breaking the chain of transmission. WHO, Geneva, 2007. World Bank. Global burden of disease and risk factors, by Lopez AD, Mathers CD, Ezzati M, Jamison DT, and Murray CJL. Oxford University Press, 2006. Wilkinson D, Harrison A, Lurie M, and Abdool Karim SS. STD syndrome packets: improving syndromic management of sexually transmitted diseases in developing countries. Sex Transm Dis 1999; 26: 152‐156
P S I ■■ | 15 Appendix A: Tables A.1 – A.5
Table A.1: STI incidence rate by sex and region STI infection Gonorrhea Chlamydia Syphilis Chancroid Herpes Trichomoniasis Vulvovaginal candidiasis Sex M F M F M F M F M F F F South East Asia 0.025382 0.031602 0.039644 0.050178 0.004580 0.003876 0.006870 0.005815 0.014313 0.012114 0.083895 0.194757 Eastern Europe & Central Asia 0.014634 0.017659 0.026537 0.031707 0.000507 0.000517 0.000761 0.000776 0.001585 0.001616 0.062049 0.144042 East Asia 0.003902 0.004123 0.006282 0.006724 0.000324 0.000275 0.000486 0.000412 0.001012 0.000859 0.012049 0.027971 Latin America & Caribbean 0.025077 0.030846 0.032231 0.039385 0.012569 0.009954 0.018854 0.014931 0.039279 0.031106 0.067615 0.156964 Sub‐Saharan Africa 0.060892 0.065725 0.056877 0.061264 0.015941 0.012513 0.023911 0.018770 0.049814 0.039103 0.118439 0.274947 South East Asia includes: Afghanistan, Cambodia, India, Lao, Myanmar, Nepal, Pakistan, Philippines, Thailand, and Vietnam. (Countries in orange are PSI platforms with STI kit program.) Eastern Europe & Central Asia include: Armenia, Azerbaijan, Belarus, Bosnia, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Kazakstan, Kyrgyzstan, Latvia, Lithuania, Poland, Republic of Moldava, Romania, Russia, Slovakia, Tajikistan, Turkmenistan, Ukraine, and Uzbekistan. East Asia includes: China, Papua New Guinea, and other East Asian countries. Latin America & Caribbean include: Argentina, Bahamas, Barbados, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guadaloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico, Netherlands, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Suriname, Trinidad and Tobago, Uruguay, and Venezuela. P S I ■■ | 16 Sub‐Saharan Africa includes: Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Cote d’Ivoire, Djibouti, Qquatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea‐Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Reunion, Rwanda, Senegal, Sierra Leone, Somalia, South Africa, Swaziland, Togo, Uganda, United Rep. of Tanzania, Zaire, Zambia, and Zimbabwe. Source for gonorrhea, chlamydia, syphilis, and trichomoniasis: Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections‐Overview and Estimates, "WHO 2001. Tables 1, 2, 3, 4, and 5. Source for chancroid, herpes, and candidiasis: "Establishing STI Surveillance ‐‐ Basic Data Needs, Methodology, Indicators," Surveillance, Research, Monitoring & Evaluation, Department of HIV/AIDS, WHO. Slide 15. P S I ■■ | 17 Table A.2: Syphilis death rate and age at death by sex and region Male Age at death East Asia 0.002915 70 Central Asia 0 LAC 0 South Asia 0.038877 65.97 SSA 0.164835 48.25 Region Death rate Female Death rate Age at death 0 0 0 0.011468 0.153439 81.25 72 37.59 East Asia includes: American Samoa, Cambodia, China, Fiji, Indonesia, Kiribati, Republic of Korea, Lao, Malaysia, Marshall Islands, Micronesia, Mongolia, Myanmar, Palau, Papua New Guinea, Philippines, Samoa, Solomon Islands, Thailand, Tonga, Vanuatu, and Vietnam. (Countries in orange are PSI platforms with STI kit program.)
Europe & Central Asia include: Albania, Armenia, Azerbaijan, Belarus, Bosnia & Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Isle of Man, Kazakhstan, Kyrgyz Republic, Latvia, Lithuania, Macedonia, Moldova, Poland, Romania, Russia, Serbia and Montenegro, Slovak Republic, Tajikistan, Turkey, Turkmenistan, Ukraine, and Uzbekistan.
South Asia includes: Afghanistan, Bangladesh, Bhutan. India, Maldives, Nepal, Pakistan, and Sri Lanka. (Countries in orange are PSI platforms with STI kit program.) Sub‐Saharan Africa includes: Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Cote d’Ivoire, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea‐Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, Somalia, South Africa, Sudan, Swaziland, Tanzania, Togo, Uganda, Zambia, and Zimbabwe. Latin America & the Caribbean include: Antigua & Barbuda, Argentina, Barbados, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Dominica, Dominican Republic, Ecuador, El Salvador, Grenada, Guatemala, Guyana, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, St. Kitts and Nevis, St. Lucia, Suriname, Trinidad and Tobago, Uruguay, and Venezuela. Source: World Bank. Global Burden of Disease and Risk Factors, by Lopez AD, Mathers CD, Ezzati M, Jamison DT, and Murray CJL. Oxford University Press, 2006. P S I ■■ | 18 Table A.3: Treatment‐related parameters for curable STIs STIs Gonorrhea Chlamydia Syphilis Chancroid Trichomoniasis Vulvovaginal candidiasis Percentage of symptomatic infections Male Female 90a 20a 75a 27.5a 100 100 100b 86b ‐ ‐ c ‐ ‐ c Percentage of persons with symptomatic infections adequately treated Male Female 35d 25d 35d 25d 35d 25d 35d 25d ‐ 25d ‐ 25d Clinical efficacy of syndromic management 0.97e 0.97e 0.99f 0.98g 0.92h 0.90i Case fatality rate 0 0 0.1j 0 0 0 Source: a. "Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections‐Overview and Estimates," WHO 2001. b. Available at http://www.cdc.gov/mmwR/preview/mmwrhtml/00000643.htm and http://www.idph.state.il.us/public/hb/hbchancroid.htm c. don’t need such data since that the data is needed for the purpose of calculating the proportion of products used by male versus female and that the STI kits for vaginitis are consumed by females only. d. "Estimation of the Incidence and Prevalence of Sexually Transmitted Infections," WHO 2002. Because the assumption may not reflect the situation in many PSI platforms, we are open to evidence‐based data from platforms (e.g., published reports by well‐recognized organizations, published studies, etc). e. MMWR CDC STI Treatment Guideline 2006 f. available at http://www.cdc.gov/std/syphilis/STDFact‐Syphilis.htm g. Solorzano R. International Conference on AIDS. 1992 Jul 19‐24; 8: We54 (abstract no. WeB 1050). Guatemala, City. and Martin DH. Clin Infect Dis, 1995; 21(2): 409‐14. h. MMWRCDC STD treatment guidline.pdf, page 53 & http://emedicine.medscape.com/article/787722‐treatment i. available at http://en.wikipedia.org/wiki/Candidiasis j. Zajdowicz T. Syphilis – Clinical Aspects of Secondary Syphilis. Available at www.bibalex.org/supercourse/supercourseppt/13011.../13491.ppt P S I ■■ | 19 Table A.4: Treatment‐related parameters for non‐curable STIs STIs Genital herpes lymphogranuloma venereum Percentage of symptomatic infections Male Female a
40 40a 90b 25b Percentage of persons with symptomatic infections adequately treated Male Female c
35 25c 35c 25c Duration of infection after treatment (year) Disability weight after treatment Case fatality rate 0.02d 0.05d 0 0.12e 0.025d 0 Source: a. http://www.ihmf.org/general/resources03.asp b. Personal communication with Chattarpal Chauhan (PSI/India staff) c. "Estimation of the Incidence and Prevalence of Sexually Transmitted Infections,” WHO 2002 d. Assumes that duration and disability weight after treatment will be half duration and disability weight when STI left untreated e. Greaves AB, Hillieman MR, Taggart SR, Bankhead AB, Feld M. Chemotherapy in bubonic lymphogranuloma venereum: a clinical and serological evaluation. Bull World Health Organ. 1957; 16(2):277‐89. P S I ■■ | 20 Table A.5: Positive predictive value (PPV) and proportion of etiologic agents Syndrome/ infection PPV (range)*** Etiological agents Urethritis/ gonorrhea and/or chlamydia 55% (38%‐75%) Cervicitis/ gonorrhea and/or chlamydia 30% (4%‐67%) a3,b1,b2 Genital ulcer/ syphilis and/or chancroid Genital ulcer/ HSV‐2 Vaginitis/ trichomoniasis and/or candida Lower abdominal pain/ gonorrhea and/or Chlamydia and/or anaerobic Inguinal bubo/ LGV Inguinal bubo/ chancroid a1‐a3
40% (24%‐60%) b2,c1,c2 41% b2 34% (34%‐47%) b1, d1,d2 28% e 10% f1‐f3 21.8% f1‐f3 Gonorrhea Chlamydia Both Gonorrhea Chlamydia Both Syphilis Chancroid Trichomoniasis Candida albicans Many cases are polymicrobial in etiology Proportion (%) of etiological agent in male 68.3g 25.7 6.0 16h 24 Proportion (%) of etiological agent in femaleh 33.3 31.2 45.5 16 24 28 65 ***PPV: positive predictive value. Currently, we obtain this value from literature and use a point estimate for all PSI countries and populations due to limited available country‐specific or population‐specific epidemic data. Whenever possible, we will update our PPV value by using a formula in which PPV is a function of sensitivity, specificity and prevalence. Source: a1. El‐Gamal AF, Al‐Otaibi SR, Alshamali A, Abdulrazzaq A, Najem N, Al. Fouzan A. Polymerase chain reaction is no better than Gram stain for diagnosis of gonococcal urethritis. Indian J Dermatol Venereol Leprol 2009; 75:101 a2. Cohen MS. STDs and HIV: Deadly Synergy. http://cme.medscape.com/viewarticle/419908 a3. Pettifor A, Walsh J, Wilkins V, Raghunathan P. How Effective Is Syndromic Management of STDs?: A Review of Current Studies. Sexually Transmitted Diseases: August 2000 ‐ Volume 27 ‐ Issue 7 ‐ pp 371‐385. b1. Rahman S, Bogaerts J, Rahman M, Razzak R, Nessa K, Reza M. Validity assessment of flowcharts for syndromic management of vaginal discharge [WP158, 2003] b2. Wang Q, Yang P, Zhong M, Wang G. Validation of diagnostic algorithms for syndromic management of sexually transmitted diseases. Chin Med J (Engl). 2003 Feb; 116(2):181‐6
P S I ■■ | 21 c1. Sanchez J, Volquez C, Totten PA, Campos PE, Ryan C, Catlin M, Hasbun J, Rosado De Quiñones M, Sanchez C, De Lister MB, Weiss JB, Ashley R, Holmes KK. The etiology and management of genital ulcers in the Dominican Republic and Peru. Sex Transm Dis. 2002 Oct; 29(10):559‐67 c2. DiCarlo RP and Martin DH. The Clinical Diagnosis of Genital Ulcer Disease in Men. Clinical Infectious Diseases 1997; 25:292–8 d1. H Swygard, A C Seña, M M Hobbs and M S Cohen. Trichomoniasis: clinical manifestations, diagnosis and management. Sexually Transmitted Infections 2004; 80:91‐95. d2. Cucuzza L. Vaginal Discharge Syndromic Management in Family Planning Programs: A Review of the Literature. e. Data reported in “MMWE CDC STD treatment guidance.pdf” indicates that a clinical diagnosis of symptomatic PID has a positive predictive value (PPV) for salpingitis of 65%–90% compared with laparoscopy. But, I could not find any data on the percentage of lower abdominal pain that is caused by PID (diagnosed clinically). We are planning to collect such data in Lesotho by asking symptoms and doing physical exam among female patients complaining lower abdominal pain. At present, we assume 40% of lower abdominal pain is caused by STI infections. So, 40% * 70%=28%. f1. Mohammed KN. Inguinal bubo: problems in diagnosis. Singapore Med J 1992; vol 33: 600‐602. f2. World Health Organization. 2003. Guidelines for the management of sexually transmitted infections. http://www.emro.who.int/aiecf/web79.pdf f3. Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm Infect. 2002 Apr; 78(2):90‐2. g. El‐Gamal AF, Al‐Otaibi SR, Alshamali A, Abdulrazzaq A, Najem N, Al. Fouzan A. Polymerase chain reaction is no better than Gram stain for diagnosis of gonococcal urethritis. Indian J Dermatol Venereol Leprol 2009; 75:101. h. "Establishing STI Surveillance ‐‐ Basic Data Needs, Methodology, Indicators," Surveillance, Research, Monitoring & Evaluation, Department of HIV/AIDS, WHO. Slide 15. P S I ■■ | 22 1120 19th Street, NW | Suite 600 Washington, DC 20036 psi.org | Twitter: @PSIHealthyLives | blog: psihealthylives.com