Articles tagged as "Epidemiology"

Antiretroviral therapy alone not enough to reduce TB incidence where HIV- and TB- prevalence is high

Incidence of HIV-associated tuberculosis among individuals taking combination antiretroviral therapy: a systematic review and meta-analysis.

Kufa T, Mabuto T, Muchiri E, Charalambous S, Rosillon D, Churchyard G, Harris RC. PLoS One. 2014 Nov 13;9(11):e111209. doi: 10.1371/journal.pone.0111209. eCollection 2014.

Background: Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.

Methods: Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy.

Results: From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39-5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23-0.69 per 100 person-years]) with significant heterogeneity observed between the studies.

Conclusions: Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.

Abstract Full-text [free] access

Editor’s notes: This systematic review and meta-analysis looks at tuberculosis (TB) incidence rates among adults living with HIV on antiretroviral treatment (ART). The review reinforces and quantifies what we already know about the disparities between low-burden and high-burden settings. TB incidence rates in high and intermediate burden settings are ten times higher than those in low burden settings.

The authors draw attention to the need for implementation of programmes that address the social determinants of TB. Low socio-economic conditions are associated with higher TB incidence rates in individuals on ART. Interestingly, the meta-analysis found that TB incidence rates were higher among individuals on ART who had a previous history of TB, than individuals who did not have a history of previous TB. The epidemiological association between previous TB treatment and active TB was one of the foundations for the emphasis on case retention and cure rates with the Directly Observed Treatment, Short-Course (DOTS) strategy. Yet prevalence surveys conducted in Zimbabwe, South Africa and Zambia in the pre-ART and early ART era did not find an association between a history of previous TB and prevalent active undiagnosed TB in individuals living with HIV. The finding from this meta-analysis suggests that individuals on ART are now surviving long enough to develop recurrent TB disease.

The overall message of the study is that ART alone is not sufficient to reduce TB incidence in high HIV prevalence settings. Additional strategies are required to prevent TB focussing on individuals with low CD4 counts, a history of previous TB disease and people who have recently initiated ART.

Avoid TB deaths
Africa, Asia, Europe, Northern America
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Reduction in the incidence of invasive pneumococcal disease following vaccination

Effects of vaccination on invasive pneumococcal disease in South Africa.

von Gottberg A, de Gouveia L, Tempia S, Quan V, Meiring S, von Mollendorf C, Madhi SA, Zell ER, Verani JR, O'Brien KL, Whitney CG, Klugman KP, Cohen C; GERMS-SA Investigators. N Engl J Med. 2014 Nov 13;371(20):1889-99. doi: 10.1056/NEJMoa1401914. Epub 2014 Nov 11.

Background: In South Africa, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 with a three-dose schedule for infants at 6, 14, and 36 weeks of age; a 13-valent vaccine (PCV13) replaced PCV7 in 2011. In 2012, it was estimated that 81% of 12-month-old children had received three doses of vaccine. We assessed the effect of vaccination on invasive pneumococcal disease.

Methods: We conducted national, active, laboratory-based surveillance for invasive pneumococcal disease. We calculated the change in the incidence of the disease from a prevaccine (baseline) period (2005 through 2008) to postvaccine years 2011 and 2012, with a focus on high-risk age groups.

Results: Surveillance identified 35 192 cases of invasive pneumococcal disease. The rates among children younger than 2 years of age declined from 54.8 to 17.0 cases per 100 000 person-years from the baseline period to 2012, including a decline from 32.1 to 3.4 cases per 100 000 person-years in disease caused by PCV7 serotypes (-89%; 95% confidence interval [CI], -92 to -86). Among children not infected with the human immunodeficiency virus (HIV), the estimated incidence of invasive pneumococcal disease caused by PCV7 serotypes decreased by 85% (95% CI, -89 to -79), whereas disease caused by nonvaccine serotypes increased by 33% (95% CI, 15 to 48). Among adults 25 to 44 years of age, the rate of PCV7-serotype disease declined by 57% (95% CI, -63 to -50), from 3.7 to 1.6 cases per 100 000 person-years.

Conclusions: Rates of invasive pneumococcal disease among children in South Africa fell substantially by 2012. Reductions in the rates of disease caused by PCV7 serotypes among both children and adults most likely reflect the direct and indirect effects of vaccination.

Abstract Full-text [free] access

Editor’s notes: There has been a marked reduction in invasive pneumococcal disease in high-income settings following the roll-out of pneumococcal conjugate vaccine. The reduction in incidence of pneumococcal disease has been observed not just among vaccinated infants but also among older children and adults, indicating herd immunity. This study is the first to report on the population impact of pneumococcal vaccination given at six weeks, 14 weeks and nine months of age in an African setting with a high prevalence of HIV and high antiretroviral therapy coverage. Following the introduction of infant pneumococcal vaccination in 2009, the incidence of laboratory reported invasive pneumococcal disease (defined as hospitalised person with positive cultures from sterile sites) declined by 89% for pneumococcal conjugate vaccine -7 (PCV-7) serotypes. A reduction in the incidence of non-vaccine serotypes of 20% indicates that some, but not all of this reduction may be due to improvements in HIV care and increasing antiretroviral therapy coverage. As observed in high-income settings the benefits were seen not just in infants but also in older children and adults. Reassuringly, a reduced incidence of pneumococcal disease was found in individuals living with HIV and in people who did not have the disease. While there was some indication that serotype replacement may become a future problem (small increase in invasive diseases caused by non-vaccine serotypes in HIV negative infants) longer follow-up data is required to fully explore this issue.

Avoid TB deaths
Africa
South Africa
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More, older people living with HIV, but how many more?

Increasing trends in HIV prevalence among people aged 50 years and older: evidence from estimates and survey data.

Mahy M, Autenrieth CS, Stanecki K, Wynd S. AIDS. 2014 Sep 12. [Epub ahead of print]

Objective: To present the most recent 2013 UNAIDS estimates of HIV prevalence among people aged 50 years and older, and to validate these estimates using data from national household surveys.

Design: Modelled estimates of HIV prevalence were validated against nationally representative household survey measures of HIV prevalence.

Methods: The UNAIDS 2013 HIV estimates were used to compute HIV prevalence and number of people living with HIV aged 50 years and older. Sex-specific HIV-prevalence rates by 5-year age groups were calculated from nationally representative household surveys conducted between 2003 and 2013, and were compared to prevalence rates from the modelled estimates. The ratios of the prevalence rates from the two sources were analysed.

Results: In 2013, an estimated 4.2 million (4.0-4.5 million) people aged 50 years and older were living with HIV. The global HIV prevalence among older individuals more than doubled in almost all the 5-year age groups since 1995. There was a relatively good agreement between the modelled HIV-prevalence rates and the survey-based rates among men and women aged 50-54 years (0.90 and 0.98 median ratio, respectively), whereas for 55-59-year-olds, the differences were more notable (ratios of 0.63 for men and 0.9 for women).

Conclusion: Both data sources suggest HIV-prevalence rates among people aged over 50 have increased steadily in recent years. Care and treatment services need to address the specific needs of older people living with HIV. Action is needed to incorporate older age groups into HIV surveillance systems.

Abstract access 

Editor’s notes: According to the most recent estimates, the global number of people above age 50 years and living with HIV, has more than doubled since the mid-1990s. In southern Africa, it has more than tripled. These numbers are expected to increase further as treatment programmes continue to expand. This study by the UNAIDS secretariat, underscores the numeric importance of this population subgroup. Above all, it highlights how little we know about the epidemic in older adults. The authors compare UNAIDS (modelled) HIV prevalence estimates with those from nationally representative surveys. They find good correspondence among 50-54 year-old men and women. The discrepancy between the two sources are more pronounced above age 54 years where the UNAIDS figures tend to fall short of the empirical estimates. This is particularly the case for men. HIV prevalence estimates among older women are rather scarce as surveys and data collection at antenatal clinics typically focus on women of reproductive age. Longer than expected survival of people living with HIV and higher than anticipated HIV incidence at older ages, could explain the discrepancy between the estimates. But we need more and better data about these age groups to be in a position to adjudicate between these explanations.

Epidemiology
Africa
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Mother’s HIV status has a major impact on child, but not neonatal mortality

Maternal HIV status associated with under-five mortality in rural northern Malawi: A prospective cohort study

Chihana ML, Price A, Floyd S, Mboma S, Mvula H, Branson K, Saul J, Zaba B, French N, Crampin AC, Glynn JR. J Acquir Immune Defic Syndr. 2014 Oct 15. [Epub ahead of print]

Background: Under-five mortality is decreasing but with little change in neonatal mortality rates. We examined the effect of maternal HIV-status on under-five mortality and cause of death since widespread availability of antiretroviral therapy in rural Malawi.

Methods: Children born in 2006-2011 in the Karonga demographic surveillance area were included. Maternal HIV-status was available from HIV sero-surveys. Age-specific mortality rate ratios for children born to HIV-positive and HIV-negative mothers were obtained by fitting a Poisson model accounting for child clustering by mother and adjusting for potential confounders. Cause of death was ascertained by verbal autopsy.

Findings: There were 352 deaths among 6913 under-five singleton children followed for 20 754 person-years (py), giving a mortality rate of 17.0/1000py overall, 218/1000py (16.5/1000 live births) in neonates, 20/1000py (17.4/1000 live births) in post-neonatal infants and 8/1000py in 1-4 year-olds. Comparing those born to HIV-positive and HIV-negative mothers, the rate ratio, adjusted for child age, sex, maternal age, parity and drinking water source was 1.5 (95%CI 0.6-3.7) in neonates, 11.5 (95%CI 7.2-18.5) in post-neonatal infants and 4.6 (95%CI 2.7-7.9) in 1-4 year-olds. Birth injury/asphyxia, neonatal sepsis and prematurity contributed >70% of neonatal deaths, while acute infections, malaria, diarrhoea and pneumonia accounted for most deaths in older children.

Conclusions: Maternal HIV status had little effect on neonatal mortality but was associated with much higher mortality in the post-neonatal period and among older children. Greater attention to HIV care in pregnant women and mothers should help improve child survival but broader interventions are needed to reduce neonatal mortality.

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Editor’s notes: Child mortality remains a major public health problem in sub-Saharan Africa. A substantial proportion of under-five deaths are attributable to HIV in some countries, estimated as 13% in Malawi, where HIV prevalence is 10-14%.  Child mortality has declined in Malawi, and this large population-based study looked at causes of death from 2006-2012 when antiretroviral therapy (ART) was widely available.  Overall, child mortality was higher in children born to women living with HIV than women without HIV, but this effect was only seen after the neonatal period.  As expected, there were clear differences in causes of death by age. About half of the neonatal deaths were due to infections or prematurity, where HIV status may play a role. Therefore the small effect of the mother’s HIV status in this age group is interesting, although in line with other studies from sub-Saharan Africa.  Older children tended to die from acute infections such as pneumonia, diarrhoea and acute febrile diseases. Maternal HIV positive status was estimated to account for most of these deaths. Strengths of this study are the large number of children included and the length of follow up. The study was not designed to define the mechanisms underlying the excess mortality, and did not include data on child HIV status and other programmes such as vitamin supplementation, vaccination and duration of breast feeding. Optimisation of Option B+ will prevent further children from acquiring HIV and maintain the health of their mothers, but this study illustrates the need for a continued focus on other causes of neonatal mortality.

Africa
Malawi
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Increase in pregnancy rates in west Africa after initiation of antiretroviral therapy

Incidence of pregnancy after antiretroviral therapy initiation and associated factors in 8 West African countries.

Burgos-Soto J, Balestre E, Minga A, Ajayi S, Sawadogo A, Zannou MD, Leroy V, Ekouevi DK, Dabis F, Becquet R, IeDEA West Africa Collaboration. J Acquir Immune Defic Syndr. 2014 Oct 1;67(2):e45-54. doi: 10.1097/QAI.0000000000000279.

Introduction: This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in 8 West African countries over a 10-year period.

Methods: A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged <50 years and starting ART for their own health between 1998 and 2011 were eligible. Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, hemoglobin, age, first ART regimen, and calendar year.

Results: Overall, 29 425 HIV-infected women aged 33 years in median (interquartile range, 28-38) contributed for 84 870 woman-years of follow-up to this analysis. The crude incidence of first pregnancy (2304 events) was 2.9 per 100 woman-years [95% confidence interval (CI): 2.7 to 3.0], the highest rate being reported among women aged 25-29 years: 4.7 per 100 woman-years; 95% CI: 4.3 to 5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4 to 11.4) and as high as 28.4% (95% CI: 26.3 to 30.6) among women aged 20-29 years at ART initiation.

Conclusions: The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world.

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Editor’s notes: Women of reproductive age are the largest population affected by HIV infection in sub-Saharan Africa. The wide availability of antiretroviral therapy (ART) has considerably decreased morbidity and mortality among women living with HIV. In addition, the risk of mother-to-child transmission of HIV has also been reduced. The authors hypothesised that the improvement in life expectancy is positively associated with procreation desires and fertility rates observed after ART initiation in several other settings. To test this hypothesis, they conducted a retrospective analysis using data from the International epidemiological Database to Evaluate AIDS (IeDEA). They found that the incidence of pregnancy was high after ART initiation among women living with HIV, although it was lower than among women without HIV in the same countries (four to six livebirths per 100 woman-years). The incidence rate of pregnancy increased slightly but progressively throughout years on ART, suggesting a positive effect of ART on fertility among women of reproductive age, particularly among young women. The authors suggest some biological mechanisms for the effect of ART on fertility. Further research in this area would be useful. Further, there is a large unmet need for family planning among women in west Africa, resulting in high rates of unintended pregnancies. This study highlights the need to understand the dynamics of fertility among women on ART, which is key to informing strategies integrating family planning into HIV care.

 
Africa
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Does pregnancy accelerate HIV progression?

Pregnancy and HIV disease progression: a systematic review and meta-analysis.

Calvert C, Ronsmans C. Trop Med Int Health. 2014 Oct 31. doi: 10.1111/tmi.12412. [Epub ahead of print]

Objective: To assess whether pregnancy accelerates HIV disease progression.

Methods: Studies comparing progression to HIV-related illness, low CD4 count, AIDS-defining illness, HIV-related death, or any death in HIV-infected pregnant and non-pregnant women were included. Relative risks (RR) for each outcome were combined using random effects meta-analysis and were stratified by antiretroviral therapy (ART) availability.

Results: 15 studies met the inclusion criteria. Pregnancy was not associated with progression to HIV-related illness [summary RR: 1.32, 95% confidence interval (CI): 0.66-2.61], AIDS-defining illness (summary RR: 0.97, 95%CI: 0.74-1.25) or mortality (summary RR: 0.97, 95%CI: 0.62-1.53), but there was an association with low CD4 counts (summary RR: 1.41, 95%CI: 0.99-2.02) and HIV-related death (summary RR: 1.65, 95%CI: 1.06-2.57). In settings where ART was available, there was no evidence that pregnancy accelerated progress to HIV/AIDS-defining illnesses, death and drop in CD4 count. In settings without ART availability, effect estimates were consistent with pregnancy increasing the risk of progression to HIV/AIDS-defining illnesses and HIV-related or all-cause mortality, but there were too few studies to draw meaningful conclusions.

Conclusions: In the absence of ART, pregnancy is associated with small but appreciable increases in the risk of several negative HIV outcomes, but the evidence is too weak to draw firm conclusions. When ART is available, the effects of pregnancy on HIV disease progression are attenuated and there is little reason to discourage healthy HIV-infected women who desire to become pregnant from doing so.

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Editor’s notes: The suppression of cell-mediated immunity during pregnancy is associated with increased susceptibility to and/or severity of many infections. Therefore the question of whether pregnancy accelerates HIV disease progression in HIV-positive women is pertinent. A previous systematic review published in the late 1990s found weak evidence that the odds of acquiring an AIDS-defining illness or death were higher among HIV-positive pregnant women than HIV-positive non-pregnant women. The findings from this meta-analysis also suggest that in the absence of antiretroviral therapy (ART), pregnancy is associated with an increase in the risk of several negative HIV outcomes. Fortunately ART appears to diminish the effects of pregnancy on HIV progression.  The authors also draw attention to the methodological weaknesses of the studies included and highlight the need for better quality data, examining whether pregnancy aggravates HIV progression.

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Problematic risk perception: half of women acquiring HIV reported that they were not at risk

A descriptive analysis of perceptions of HIV risk and worry about acquiring HIV among FEM-PrEP participants who seroconverted in Bondo, Kenya, and Pretoria, South Africa.

Corneli AL, McKenna K, Headley J, Ahmed K, Odhiambo J, Skhosana J, Wang M, Agot K. J Int AIDS Soc. 2014 Sep 8;17(3 Suppl 2):19152. doi: 10.7448/IAS.17.3.19152. eCollection 2014.

Methods: FEM-PrEP was a phase III clinical trial of once-daily, oral emtricitabine and tenofovir disoproxil fumarate for HIV prevention among women in sub-Saharan Africa. We asked all participants about their perceived HIV risk in the next four weeks, prior to HIV testing, during a quantitative face-to-face interview at enrolment and at quarterly follow-up visits. Among participants who seroconverted, we calculated the frequencies of their responses from the visit conducted closest to, but before, HIV acquisition. Also among women who seroconverted, we conducted qualitative, semi-structured interviews (SSIs) at weeks 1, 4 and 8 after participants' HIV diagnosis visit to retrospectively explore feelings of HIV worry. Applied thematic analysis was used to analyse the SSI data.

Results: Among participants who seroconverted in Bondo and Pretoria, 52% reported in the quantitative interview that they had no chance of acquiring HIV in the next four weeks. We identified four processes of risk rationalization from the SSI narratives. In "protective behaviour," participants described at least one risk reduction behaviour they used to reduce their HIV risk; these actions made them feel not vulnerable to HIV, and therefore they did not worry about acquiring the virus. In "protective reasoning," participants considered their HIV risk but rationalized, based on certain events or beliefs, that they were not vulnerable and therefore did not worry about getting HIV. In "recognition of vulnerability," participants described reasons for being worried about getting HIV but said no or limited action was taken to reduce their perceived vulnerability. Participants with "no rationalization or action" did not describe any HIV worry or did not engage in HIV risk reduction behaviours.

Conclusions: Women who are at substantial risk of acquiring HIV may underestimate their actual risk. Yet, others who accurately understand their HIV risk may be unable to act on their concerns. Perceived HIV risk and risk rationalization are important concepts to explore in risk reduction counselling to increase the use of HIV prevention strategies among women at risk of HIV.

Abstract  Full-text [free] access

Editor’s notes: Risk perception has been thought to be a significant driver of accessing and using HIV prevention methods. However, over the years, researchers have struggled to present a definitive argument as to the role risk perception plays in HIV prevention. While the FemPrEP study failed to show efficacy, or rather effectiveness of oral pre-exposure prophylaxis (PrEP) in preventing HIV acquisition in women in several sites in Africa, valuable data have been collected relating to risk perception. About half of the women who seroconverted to HIV during the trial and were interviewed, indicated that they did not perceive themselves to be at risk of contracting HIV. Interviews revealed different cognitive mechanisms by which women rationalised their perceptions and/or behaviours, some of which were outside their immediate control. A key finding was that women who were actually at significant risk of acquiring HIV did not accurately perceive their risk. While this analysis focused on risk perception, the narratives from some participants suggest that risk perception is only a small piece of the puzzle in understanding how and why women may access and use HIV prevention methods. While this study demonstrates that risk perception clearly plays an important role, it would be valuable to understand further the context within which the women are living and making decisions to fully comprehend HIV access and use. 

Africa
Kenya, South Africa
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Low CD4 counts among alcohol-dependent people on antiretroviral therapy – not due to poor adherence

Alcohol dependence and CD4 cell count: is there a relationship?

Malbergier A, Amaral RA, Cardoso LD. AIDS Care. 2014 Sep 1:1-5. [Epub ahead of print]

Alcohol and other drugs use seem to be common among people infected with HIV on antiretroviral treatment (ART). Their effects on HIV progression is still in debate. This study aimed to assess the association between alcohol and drug use and an HIV disease progression biomarker (CD4 cell count) among patients on ART. A cross-sectional study was carried out at an HIV treatment center affiliated with Medical School of the University of Sao Paulo, Brazil. Four hundred and thirty-eight HIV-positive patients on ART were interviewed by trained psychiatrists and psychologists using the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Alcohol Use Disorders Identification Test (AUDIT), 17-item Hamilton Rating Scale for Depression, and the Simplified Medication Adherence Questionnaire (SMAQ). In the previous month, 219 (50%) and 41 (9.3%) patients reported use of alcohol and illicit drugs, respectively. Fifty patients (12.6%) were classified as having harmful alcohol use by AUDIT. According to SCID-I, 80 patients (18.3%) were alcohol abusers, 24 (5.5%) alcohol dependents, and 21 (4.2%) had a current depressive disorder. Almost 73% (n = 319-72.8%) of the patients were adherent to ART. Alcohol dependents were nine times (p < 0.01) more likely to have CD4 cell count ≤200/mm3, and this association was independent of ART adherence. In conclusion, alcohol dependence seems to be associated with low CD4 cell count in HIV-positive patients. Based on these data, HIV health care workers should always assess alcohol consumption in the treatment setting, and patients should be advised that alcohol dependence may be linked to low CD4.

Abstract access 

Editor’s notes: The prognosis for people living with HIV who initiate antiretroviral therapy (ART) depends not only on their adherence to ART, but also the presence of co-morbid health conditions. There is now increasing focus on the role mental health disorders have on HIV-related outcomes. In this study of 438 HIV positive people on ART in Brazil, nearly 20% of individuals were found to be abusing alcohol, and five percent were diagnosed as being alcohol dependent. The people who were alcohol dependent were nine times more likely to have CD4 count <200/mm3, an association which was independent of ART adherence, HIV viral load and illicit substance use. As the availability of mental health care in low- and middle-income countries continues to expand, people living with HIV will comprise a key population for these services. Future research must confirm whether the relationship between alcohol dependence and CD4 count persists over time, and how alcohol dependence services can be integrated with HIV care services.

Latin America
Brazil
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Counting and classifying global deaths

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Murray CJ, Ortblad KF, Guinovart C, et al. Lancet. 2014 Sep 13;384(9947):1005-70. doi: 10.1016/S0140-6736(14)60844-8. Epub 2014 Jul 22.

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration.

Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

Findings: Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3 million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.1 million life-years (16.6 million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$ 4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6 million to 12.2 million), and number of deaths was 1.4 million (1.3 million to 1.5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3 million), prevalence was 11.2 million (10.8 million to 11.6 million), and number of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2 million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

Interpretation: Our estimates of the number of people living with HIV are 18.7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

Abstract  Full-text [free] access

Editor’s notes: The Global Burden of Disease (GBD) study uses standard methods to compare and track over time national distributions of deaths by cause, and the prevalence of disease and disability.  This detailed report focuses on HIV, TB and Malaria. It presents regional summaries of incidence, prevalence and mortality rates, and national estimates of the number of male and female deaths and new infections. Point estimates are shown for 2013, and annualised rates of change for 1990-2000 and 2000-2013. These highlight the contrasting trends in disease impact before and after the formulation of the Millennium Development Goal to combat these diseases.  The global peak of HIV mortality occurred in 2005, but regional annualised rates of change for 2000-2013 indicate that HIV deaths are still increasing significantly in east Asia, southern Africa, and most rapidly in eastern Europe.

The GBD 2013 global estimates of new infections and deaths agree closely with the corresponding estimates made by UNAIDS. But there are significant differences in the respective estimates of the number of people currently living with HIV (UNAIDS estimates are some 18% higher), and historical trends in AIDS deaths, with UNAIDS judging that the recent fall has been steeper. These differences are attributed primarily to methods used in the GBD study to ensure that the sum of deaths from specific causes fits the estimated all cause total, and to varying assumptions about historical survival patterns following HIV infection. 

It may be worthwhile to look at a comment by Michel Sidibé, Mark Dybul, and Deborah Birx in the Lancet on MDG 6 and beyond: from halting and reversing AIDS to ending the epidemic which refers to this study.

Epidemiology
Afghanistan, Albania, Algeria, Andorra, Angola, Antigua and Barbuda, Argentina, Australia, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Bosnia and Herzegovina, Botswana, Brazil, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, Chad, Chile, China, Colombia, Comoros, Congo, Costa Rica, Côte d'Ivoire, Croatia, Cuba, Cyprus, Czech Republic, Democratic People's Republic of Korea, Democratic Republic of the Congo, Democratic Republic of Timor-Leste, Denmark, Djibouti, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, Fiji, Finland, France, Gabon, Gambia, Germany, Ghana, Greece, Grenada, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, Hungary, Iceland, India, Indonesia, Iran (Islamic Republic of), Iraq, Ireland, Israel, Italy, Jamaica, Jordan, Kazakhstan, Kenya, Kiribati, Kuwait, Kyrgyzstan, Lao People's Democratic Republic, Latvia, Lebanon, Lesotho, Liberia, Libyan Arab Jamahiriya, Lithuania, Luxembourg, Madagascar, Malawi, Malaysia, Maldives, Mali, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia (Federated States of), Monaco, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Niger, Nigeria, Norway, Oman, Pakistan, Palestinian Territory, Occupied, Panama, Papua New Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Qatar, Romania, Russian Federation, Rwanda, Saint Lucia, Saint Vincent and the Grenadines, Samoa, Sao Tome and Principe, Saudi Arabia, Senegal, Serbia and Montenegro, Seychelles, Sierra Leone, Slovakia, Slovenia, Solomon Islands, Somalia, South Africa, Spain, Sri Lanka, Sudan, Suriname, Swaziland, Sweden, Switzerland, Syrian Arab Republic, Taiwan, Tajikistan, Thailand, Togo, Tonga, Trinidad and Tobago, Tunisia, Turkey, Turkmenistan, Uganda, Ukraine, United States of America, Uruguay, Uzbekistan, Vanuatu, Venezuela, Viet Nam, Yemen, Zimbabwe
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Model estimates large global burden of childhood tuberculosis infection and potentially preventable future tuberculosis disease

Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.

Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Lancet Glob Health. 2014 Aug;2(8):e453-9. doi: 10.1016/S2214-109X(14)70245-1. Epub 2014 Jul 8.

Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.

Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.

Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15 319 701 (IQR 13 766 297-17 061 821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7 591 759 (5 800 053-9 969 780), and 650 977 children (424 871-983 118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53 234 854 (41 111 669-68 959 804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.

Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.

Abstract  Full-text [free] access 

Editor’s notes: Estimating the burden of childhood tuberculosis has been largely neglected until recently. Children with tuberculosis rarely transmit and therefore from a control perspective, childhood tuberculosis does not notably contribute to the continuation of the tuberculosis epidemic. This modelling paper attempts to estimate the global burden of childhood tuberculosis infection and disease. Incidence estimates are made by using adult tuberculosis prevalence data to tackle the known limitations of using paediatric notification data. A second model estimates the prevalence of infection in children and household exposure, ignoring exposure outside of the household.  As with all mathematical model predictions, precision of estimates are dependent on the data used as inputs in the model. Despite these limitations, the paper draws attention to the fact that the burden of childhood tuberculosis infection and disease is significant and reflects failure of tuberculosis control in the 22 high-burden countries. The paper also highlights the fact that household contact tracing and preventive therapy in tuberculosis-exposed children could substantially reduce future tuberculosis-related morbidity.

Avoid TB deaths
Comorbidity, Epidemiology
Africa, Asia, Latin America
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