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Estimating the impact of expanded access to antiretroviral therapy on maternal, paternal and double orphans… Anema, Aranka; Au-Yeung, Christopher G; Joffres, Michel; Kaida, Angela; Vasarhelyi, Krisztina; Kanters, Steve; Montaner, Julio S; Hogg, Robert S Mar 7, 2011

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RESEARCH Open AccessEstimating the impact of expanded access toantiretroviral therapy on maternal, paternal anddouble orphans in sub-Saharan Africa, 2009-2020Aranka Anema1,2*, Christopher G Au-Yeung1, Michel Joffres3, Angela Kaida3, Krisztina Vasarhelyi3,4, Steve Kanters1,3,Julio SG Montaner1,2, Robert S Hogg1,3AbstractBackground: HIV/AIDS has orphaned 11.6 million children in sub-Saharan Africa. Expanded antiretroviral therapy(ART) use may reduce AIDS orphanhood by decreasing adult mortality and population-level HIV transmission.Methods: We modeled two scenarios to measure the impact of adult ART use on the incidence of orphanhood in10 sub-Saharan African countries, from 2009 to 2020. Demographic model data inputs were obtained from cohortstudies, UNAIDS, UN Population Division, WHO and the US Census Bureau.Results: Compared to current rates of ART uptake, universal ART access averted 4.37 million more AIDS orphans byyear 2020, including 3.15 million maternal, 1.89 million paternal and 0.75 million double orphans. The number ofAIDS orphans averted was highest in South Africa (901.71 thousand) and Nigeria (839.01 thousand), and lowest inZimbabwe (86.96 thousand) and Côte d’Ivoire (109.12 thousand).Conclusion: Universal ART use may significantly reduce orphanhood in sub-Saharan Africa.IntroductionAn estimated 11.6 million children (aged 0 to 17 years)in sub-Saharan Africa have lost one or both parents dueto human immunodeficiency virus/acquired immunedeficiency syndrome (HIV/AIDS) since the beginning ofthe epidemic [1]. Studies suggest that orphans in sub-Saharan Africa may have poor quality of life and health,including reduced access to basic material goods andretention in education [2], and elevated psychologicaldistress and symptoms of depression [3,4]. Orphans maybe at heightened risk of acquiring HIV due to engage-ment in early and unprotected sex, and in multiple sex-ual relationships [5,6]. HIV-infected orphans haveshown to have delayed access to HIV treatment andcare, reduced adherence to HIV treatment, and poornutritional status [7-9].Antiretroviral therapy (ART) has substantially reducedHIV-related morbidity and mortality worldwide [10].A growing body of empirical evidence and mathematicalmodeling suggests that expanded ART use may also pre-vent population-level transmission of HIV [11-14]. Insub-Saharan Africa, 44% (2.925 million) of people clini-cally eligible for treatment were receiving it at the end of2008 [15]. Several studies have evaluated the impact ofthe AIDS epidemic on orphanhood [15,16]. However,none to date have examined this in the context of effortsto expand ART access. We sought to determine to whatextent the varying rates of ART uptake among adultswould prevent the incidence of paternal, maternal anddual orphans in sub-Saharan Africa, from 2009 to 2020.MethodsWe projected the impact of ART expansion to adults(15-49 years) on the incidence of paternal, maternal anddual orphans in 10 sub-Saharan African countries, from2009 to 2020. We included 10 sub-Saharan Africancountries with the highest number of AIDS orphans liv-ing in 2007: Cote D’Ivoire, Ethiopia, Kenya, Malawi,Nigeria, South Africa, Uganda, United Republic ofTanzania, Zambia, and Zimbabwe [1].* Correspondence: aanema@cfenet.ubc.ca1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital,Vancouver, British Columbia, CanadaFull list of author information is available at the end of the articleAnema et al. AIDS Research and Therapy 2011, 8:13http://www.aidsrestherapy.com/content/8/1/13© 2011 Anema et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.In order to explore the impact of expanded ART useon orphanhood, we modeled two scenarios. Scenario 1theoretically assumed that all (100%) HIV infectedadults in the countries under study would receive ARTimmediately after year 2008, irrespective of CD4+ cellcount or clinical stage. Scenario 2 assumed that thenumber of adults receiving ART remained constant fol-lowing year 2008, reflecting country-specific rates ofART uptake and clinical eligibility of people living withHIV/AIDS in that year [15].These scenarios were developed using DemProj andAIM programs within the Spectrum Policy ModelingSystem (Futures Group International) software package,Version 3.34. These programs are designed to produceinformation that is useful for policy formulation andprogram planning, and have been used by UNAIDS,UNICEF, USAID and the US Census Bureau to estimateorphanhood. Detailed descriptions of how Spectrummodels the impact of HIV/AIDS on demographic para-meters, including background mathematical methodol-ogy and parameter estimates, are described elsewhere[17-26]. We followed the prescribed steps for makingHIV/AIDS and orphanhood projections, as outlined inthe USAID Health Policy Initiative’s recent guidelines[21,23]Country-specific demographic and epidemiologicalmodel inputs are described in Table 1. All inputs andparameters used default values in the Spectrum programdeveloped by the UNAIDS References Group on Esti-mates, Model and Projections [23]. Where possible,default values were exchanged with more recent empiri-cal data, as described below.Non-HIV demographic inputsAs a first step to developing our AIDS orphanhood pro-jection model, we conducted a demographic projection.This involved inputting non-HIV country-specific demo-graphic estimates, such as population size, fertility andlife expectancy, into the Spectrum Policy Modeling Sys-tem’s DemProj Program.Population estimatesCountry and age-specific population estimates for eachyear were obtained from the United Nations PopulationDivision. In order to ensure consistency between popula-tion sizes from our demographic projections and coun-try-specific census estimates, some of our demographicinputs were obtained from the US Census Bureau insteadof the United Nations Population Division [27]. This pro-cess of matching current population estimates with pro-jection outputs is described elsewhere [23,28,29].Fertility estimatesWe obtained country- and age-specific total fertilityrates (TFR) from the US Census Bureau’s World Popu-lation Profile [30]. The age distribution of fertility wasestimated using the United Nations Sub-Saharan Africamodel fertility table as outlined by Spectrum.Mortality estimatesFor non-HIV infected individuals, we inputted age-specificdistributions of life expectancy at birth for non-AIDS-related mortality using the DemProj feature of Spectrum.HIV-specific inputsHIV-specific fertilityA review and meta-analysis of 19 studies examining thepopulation-level impact of HIV on fertility in sub-SaharanTable 1 Country-specific projection model inputsNumber of singleand dual AIDSorphans (0-17 yrs),2007 [44]HIVprevalence,adults 15-49yrs, 2007 (%)[44]Estimated annualincrease in number ofpeople receiving ART,2008 [15]ReportedNumberHIV+ peoplereceivingART, 2008[15]Number of HIV+pregnant womenreceiving ART forPMTCT, 2008 [15]Estimated Number ofHIV+ pregnantwomen who needART, 2008[15]SouthAfrica1,400,000 18.1 192,840 700,500 149,118 200,000Uganda 1,200,000 5.4 42,492 153,718 41,598 82,000Nigeria 1,200,000 3.1 68,544 238,659 19,804 210,000Kenya 1,195,000 7.8 65,880 242,881 59,601 110,000Zimbabwe 1,000,000 15.3 50,112 147,804 18,756 53,000UnitedRep. ofTanzania970,000 6.2 18,768 154,468 70,944 85,000Ethiopia 650,000 2.1 42 168 132,379 6,354 36,000Zambia 600,000 15.2 74,436 225,634 41,286 70,000Malawi 560,000 11.9 46,008 146,657 33,838 57,000Coted’Ivoire420,000 3.9 13,608 51,833 9,296 22,000Anema et al. AIDS Research and Therapy 2011, 8:13http://www.aidsrestherapy.com/content/8/1/13Page 2 of 8Africa reported that HIV-positive women not receivingART have substantially lower TFR compared to HIV-negative women. This fertility differential resulted in a0.37% decrease in population-attributable fertility for eachpercentage point of HIV prevalence within a country [31].In order to incorporate this reduction in TFR in HIV-infected women into our projections, we used the defaultTFR reduction feature in AIM, which inputs age-specificratios of fertility for HIV infected women compared to fer-tility in uninfected women.HIV incidenceCountry-specific HIV incidence inputs for adults (15-49years) for years 1985 to 2008 were obtained using theUNAIDS-developed Estimation and Projection Package(EPP) software, and were converted into percentagesbefore being inputted into the AIM program [32]. Weassumed HIV was transmitted vertically and throughheterosexual contact. We assumed individuals receivingART were on triple combination therapy, or ART. InScenario 1, we assumed that individuals receiving ARThad suppressed HIV plasma viral load [14]. Based onempirical results from a study in Rakai, Uganda, weassumed that no cases of HIV transmission occurredamong discordant contacts [33], and assumed HIV inci-dence was zero for every year subsequent to 2008. InScenario 2, we assumed HIV incidence remained at thecountry-specific rate for 2008, reflecting current rates ofART uptake [15].HIV disease progression and survivalWe inputted varying disease progression data for Sce-narios 1 and 2. In Scenario 1, we assumed that all HIVinfected individuals were clinically eligible to receiveART from end 2008 onward [15]. In Scenario 2, weassumed that individuals were clinical eligible for ART ifthey had CD4 cell count under 350, and that time fromHIV infection to ART eligibility was 3.2 years [23].For individuals not receiving ART, we assumedthat the median time from HIV infection to AIDSdeath, without treatment, was 10.5 years for men and11.5 years for women [23]. These assumptions werebased on findings from a large multi-country cohortstudy in low-resource settings [34]. For adults on ART,we assumed a survival rate of 0.86 for the first year onART. This figure was derived from longitudinal cohortstudies and systematic review of ART patients in low-incomes settings, and are recommended for use by theAIM projection model guidelines [23]. The survival rateof individuals receiving ART gradually increased over a5-year period, and remained constant at 0.94 for theduration of the study period, based on a multi-countryprospective cohort across low-income settings [35].However, due to limitations in Spectrum, the survivalrate for adults on ART was capped at 0.93 in sub-sequent years.ART and PMTCT uptakeIn Scenario 1, we assumed that all HIV-positive indivi-duals were receiving ART as of year 2009. In Scenario 2,we inputted country-specific estimates for annual ARTuptake, based on UNAIDS 2008 figures [15]. Weassumed that antiretroviral (ARV) prophylaxis was una-vailable to HIV-positive pregnant women in our coun-tries of interest prior to the year 2004 and that it wasentirely triple ARV prophylaxis. For Scenario 1, weassumed that all HIV-positive pregnant women receivedARV prophylaxis for prevention of mother-to-child-transmission (PMTCT) from year 2009 onward. ForScenario 2, we inputted the percentage of HIV-positivepregnant women receiving PMTCT between the years2004 and 2008 obtained from UNAIDS country-specificepidemiological fact sheets [15,36]. Other inputs underthe Mother to Child Transmission section of AIM wereunaltered.Outcomes variablesOur primary outcomes were the number of maternal,paternal and dual AIDS orphans in each country at year2020 following varying scenarios of ART uptake. Mater-nal and paternal AIDS orphans were defined as childrenunder the age of 17 who have lost either their motheror father to AIDS. Dual orphans are children who havelost both parents to AIDS [23].Projection and Calibration of ModelWe ran each country’s DemProj and AIM input datatogether from Spectrum to project the number of AIDSorphans incurred in each year. In order to calibrate ourmodel, we ran DemProj and AIM programs for eachcountry, using the above inputted data and parameters,from 1985 to end 2007. We verified the accuracy of ourAIDS orphans projections by comparing our results for2007 to the 2007 AIDS orphan estimate published inUNAIDS country-specific epidemiological fact sheets[36]. In order to identify the best fit for our model, asdescribed in previous sections, we modified assumptionsregarding population size and HIV survival rates usingpublished ranges for census [23,27-29] and empiricalcohort [23,34,35] data.ResultsTable 2 presents the projected number of maternal,paternal, double and total AIDS orphans averted, persub-Saharan African country, by varying levels of ARTuptake at year 2020. Scenario 1, in which adults had uni-versal ART access, averted a cumulative total of 4.37 mil-lion more AIDS orphans by year 2020 than Scenario 2,where ART access was expanded gradually. This includedan estimated 3.15 million maternal orphans, 1.89 millionpaternal orphans and 748,320 double orphans.Anema et al. AIDS Research and Therapy 2011, 8:13http://www.aidsrestherapy.com/content/8/1/13Page 3 of 8Countries with the largest number of AIDS orphansaverted over the study period included South Africa(901,705), Nigeria (839,014), and Kenya (717,382).Countries with the least number of AIDS orphansaverted were Zimbabwe (86,961), Malawi (262,428) andCôte d’Ivoire (109,121). The number of maternalorphans averted was higher than the number of paternalorphans averted in all countries: South Africa (879,336versus 361,599), Uganda (188,307 versus 143,526),Nigeria (525,277 versus 336,117), Kenya (484, 738 versus324,532), Zimbabwe (75,518 versus 23,108), Tanzania(334,028 versus 273,870), Ethiopia (180,877 versus125,483), Zambia (228,301 versus 128,468), Malawi(179,246 versus 125,327), and Cote d’Ivoire (72,609versus 46,269)Figure 1 describes the number of maternal, paternal,and double AIDS orphans averted at year 2020, bycountry, due to universal ART access. It shows that thenumber of total AIDS orphans averted by increasingART access would be highest in South Africa (901,705)and lowest in Zimbabwe (86,961).Figure 2 shows the number of orphans incurred inScenario 1 and Scenario 2 for each of the 10 sub-Saharan African countries.DiscussionResults of this study highlight the positive impact thatexpanded ART may have in sub-Saharan African coun-tries already burdened with high numbers of AIDSorphans. We found that achieving universal ART uptakeamong adults may avert over 4 million maternal, pater-nal and double AIDS orphans over the next 10 years.These findings underscore the critical role of ART forreducing harms associated with AIDS orphanhood incountries such as South Africa and Nigeria, whereannual rates of ART uptake were projected to have thegreatest impact. They also draw attention to the needfor accelerated ART expansion in countries, such asZimbabwe and Uganda, where low annual rates of ARTexpansion will have a comparatively reduced impact onorphanhood averted.These results have important implications for thehealth and quality of life of children in sub-SaharanAfrica and other HIV-endemic areas. Studies inZimbabwe and Namibia have found that orphans experi-ence elevated psychological distress, including symptomsof depression [3,4] Across Africa, orphans appear tohave limited access to basic material goods and educa-tion, and tend to drop out of school more than non-orphans [1]. Studies in Zimbabwe have found thatorphans, and particularly maternal orphans, are at ele-vated risk of acquiring HIV since they engage in earlyand unprotected sex, and have multiple sexual partners[5,6]. HIV-positive orphans have shown to have delayedaccess to HIV treatment and care in Uganda, reducedadherence to ART in Kenya, and poor nutritional statusin Thailand [7-9]. We found that universal ART accesswould have a particularly positive impact on reducingTable 2 Projected number of maternal, paternal, and double AIDS orphans incurred and averted, per sub-SaharanAfrican country, at year 2020SouthAfricaUganda Nigeria Kenya Zimbabwe Tanzania Ethiopia Zambia Malawi Coted’IvoireOrphans incurred with universal ARTaccessMaternal 1,379,420 379,000 887,810 691,022 286,624 549,876 316,258 413,474 312,314 151,461Paternal 1,452,297 592,386 1,165,760 913,492 410,784 735,112 421,703 535,465 432,220 241,890Double 688,762 151,493 201,155 378,776 171,243 233,989 77,547 224,763 126,391 77,932All 2,258,756 857,842 1,982,969 1,288,338 561,259 1,096,206 693,419 769,052 632,518 325,891Orphans incurred by sustainingcurrent ART accessMaternal 2,258,756 567,307 1,413,087 1,175,760 362,142 883,904 497,135 641,775 491,560 224,070Paternal 1,813,896 735,912 1,501,877 1,238,024 433,892 1,008,982 547,186 663,933 557,547 288,159Double 940,552 192,112 282,339 503,190 188,051 318,425 98,724 290,848 174,617 91,513All 3,160,461 1,163,017 2,821,983 2,005,720 648,220 1,641,721 994,221 1,075,967 894,946 435,012Orphans averted with universal ARTaccessMaternal 879,336 188,307 525,277 484,738 75,518 334,028 180,877 228,301 179,246 72,609Paternal 361,599 143,526 336,117 324,532 23,108 273,870 125,483 128,468 125,327 46,269Double 251,790 40,619 81,184 124,414 16,808 84,436 21,177 66,085 48,226 13,581All 901,705 305,175 839,014 717,382 86,961 545,515 300,802 306,915 262,428 109,121Anema et al. AIDS Research and Therapy 2011, 8:13http://www.aidsrestherapy.com/content/8/1/13Page 4 of 8the number o maternal AIDS orphans in sub-SaharanAfrica. Several studies have evaluated the impact ofAIDS-specific maternal mortality on orphanhood[16,21]. However, none have explored this within thecontext of the expansion of ART access.Strengths and limitations of our model pertain to theSpectrum program used. Spectrum is used by UNAIDSto estimate HIV-prevalence, mortality, ART needs andorphanhood. One strength of this software is that itenables the inputting of country, age and sex-specificFigure 1 Maternal, paternal, and double AIDS orphans averted due to universal antiretroviral uptake in ten Sub-Saharan Africancountries by year 2020.Figure 2 Total number of AIDS orphans incurred in Scenario 1 (Universal ART uptake) and Scenario 2 (Sustaining current rate of ARTaccess) in 10 Sub-Saharan African countries by year 2020.Anema et al. AIDS Research and Therapy 2011, 8:13http://www.aidsrestherapy.com/content/8/1/13Page 5 of 8HIV prevalence values. In doing so, it allows modellersto consider the heterogeneity of HIV prevalence, bothbetween and within, countries under study. However,we assumed that HIV prevalence for each countrywould remain constant after year 2008 due to the lackof UNAIDS data beyond that year. Since high HIV pre-valence is correlated with high orphanhood, and sinceprevalence is declining in many sub-Saharan Africancountries, this assumption about a stable HIV preva-lence after year 2008 may led to an overestimation ofAIDS orphanhood. Use of the Estimation and ProjectionPackage (EPP) in conjunction with Spectrum may haverectified this issue. Developers of Spectrum previouslytested and validated the age and sex-specific HIV preva-lence values for several countries included in our analy-sis (e.g. Kenya, Tanzania and Zambia) [17]. Theverification of country-specific projection estimatesagainst demographic health survey findings allowed forthe generation of prevalence values that are as close aspossible to actual epidemiological trends.Program limitations relate to the detailed methodologyfor calculating AIDS orphans in the presence andabsence of ART. For instance, there is little quantitativeinformation regarding the effect of ART on female ferti-lity and its effect on orphanhood. While there is aninput for adult and child survival on ART, these valuesare fixed, and are based on a single study [19]. Anotherorphan modeling study assumed that women receivingARVs had a fertility rate 50% lower than women notreceiving treatment [37]. They also assumed that indivi-duals initiating ART had a median survival 50% higherthan those not on therapy. Yet, these assumptions havelittle empirical evidence that lend support. However,when comparing their results, the number of maternalorphans incurred in South Africa with ART interventionwas similar to our findings, indicating that their metho-dology paralleled our own.Discrepancies between Spectrum-based and empiricalhousehold survey estimates of orphanhood have beenpreviously identified. Projected estimates of orphanhoodhave tended to be higher than empirical approximates[28,29]. This may be due either to several factors includ-ing under-reporting of deaths in household surveys,erroneously high non-AIDS related mortality rates inprojection models, or the fact that foster parents some-times claim adopted children as their natural children[28,29]. Given these reported discrepancies, it is possiblethat our projection model may have also over-estimatedthe number of orphans incurred and averted in the sub-Saharan African countries under study.This study only indirectly considered the impact ofnon-adherence on HIV outcomes by means of inputtingempirically obtained mortality rates. A closer examina-tion of adherence would have been valuable given theassociation between adherence and mortality [38].A systematic review of 33 cohort studies in sub-SaharanAfrica found that on average one-year patient retentionin ART programs was 75%, with patient attrition causedby loss to follow-up or death [39]. A more recent cohortstudy of 48,338 Médecins Sans Frontières patients foundmedian patient retention to be 86% at one year [40].These empirical studies suggest adult survival rates maybe lower than what we inputted in our model, and thatthe projected number of orphans averted may also beslightly lower.Another potential limitation of our analysis relates toour assumption that the TFR of women on ART wouldbe comparable with that of the general population,while the TFR of women not on ART is depressed[41,42]. A recent study from Uganda has shown, how-ever, that women on ART were 44% less likely tobecome pregnant and 70% less likely to give birth thanHIV-positive women not on ART in the three yearsprior to the study [43]. It remains to be determined ifthis fertility differential remains constant over the courseof the reproductive lifespan. In this case, our assumptionwill have slightly overestimated the TFR of women onART, thereby overestimating the number of orphansaverted through expanded access to ART. Nevertheless,as shown in the case of South Africa, even when theTFR is low, high HIV prevalence and high rates of ARTuse still result in a high number of maternal orphansaverted. Other potential limitations in our study includeour assumption that adult and child ART survival wasthe same for all countries may not be reflective of actualcountry rates.ConclusionOur projection model strongly argues that expandedaccess to HIV treatment will have immediate preventiveimpact on the health and welfare of children in sub-Saharan Africa. If we are to make important gains inlivelihood for future generations in Africa, expandingaccess to ART should be of paramount importance.Abbreviations(AIDS): Acquired immune deficiency syndrome; (ART): antiretroviral therapy;(HIV): human immunodeficiency virus; (MTCT): mother-to-child transmission;(PMTCT): prevention of mother-to-child transmission; (TFR): total fertility rate;HIV/AIDS (UNAIDS): Joint United Nations Programme on HIV/AIDS; (UNICEF):United Nations Children’s Fund; (USAID): United States Agency forInternational Development; (WHO): World Health Organization.AcknowledgementsA Anema and A. Kaida have received funding from the Canadian Institutesfor Health Research. RS Hogg has held grant funding from the NationalInstitutes of Health, Canadian Institutes of Health Research National HealthResearch Development Program, and Health Canada. He has also receivedfunding from Agouron Pharmaceuticals Inc, Boehringer IngelheimPharmaceuticals Inc, Bristol-Myers Squibb, GlaxoSmithKline, and Merck FrosstLaboratories for participating in continued medical education programmes.Anema et al. AIDS Research and Therapy 2011, 8:13http://www.aidsrestherapy.com/content/8/1/13Page 6 of 8JSG Montaner has received grants from, served as an ad hoc advisor to, orspoken at various events sponsored by Abbott, Argos Therapeutics, BiojectInc, Boehringer Ingelheim, BMS, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Janssen-Ortho, Merck Frosst, Pfizer, Schering, Serono Inc,TheraTechnologies, Tibotec, Trimeris. He has also held grant funding fromthe Canadian Institutes of Health Research and National Institutes of Health.He has also received funding for research and continuing medical educationprograms from a number of pharmaceutical companies including Abbott,Boehringer Ingelheim, and GlaxoSmithKline.Author details1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital,Vancouver, British Columbia, Canada. 2Faculty of Medicine, University ofBritish Columbia, Vancouver, British Columbia, Canada. 3Faculty of HealthSciences, Simon Fraser University, Burnaby, British Columbia, Canada. 4Inter-disciplinary Research for Mathematical and Computational Sciences(IRMACS), Simon Fraser University, Burnaby, British Columbia, Canada.Authors’ contributionsAA conceived the study design, contributed to the demographic modelingmethods, and wrote the first draft of the manuscript. CA and MJ ran thedemographic projection software and contributed to the first draft of thepaper. AK contributed to specialized knowledge on reproductive healthissues specific countries under investigation. SK, KV, JSGM and BRSHprovided critical feedback on study design and manuscript draft. All authorsread and approved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 26 August 2010 Accepted: 7 March 2011Published: 7 March 2011References1. United Nations Children’s Fund (UNICEF): State of the World’s Children:Maternal and Newborn Health. 2009 [http://www.unicef.org/sowc09/].2. Monasch R, Boerma JT: Orphanhood and childcare patterns in sub-Saharan Africa: an analysis of national surveys from 40 countries. AIDS2004, 18(Suppl 2):S55-65.3. Ruiz-Casares M, Thombs BD, Rousseau C: The association of single anddouble orphanhood with symptoms of depression among children andadolescents in Namibia. Eur Child Adolesc Psychiatry 2009, 18(6):369-76.4. 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