Articles tagged as "Malawi"

Disease-specific Global Fund grants may be preventing the realisation of system-wide synergies for increased human resources for health

Global Fund investments in human resources for health: innovation and missed opportunities for health systems strengthening.

Bowser D, Sparkes SP, Mitchell A, Bossert TJ, Bärnighausen T, Gedik G, Atun R. Health Policy Plan. 2014 Dec;29(8):986-97. doi: 10.1093/heapol/czt080. Epub 2013 Nov 6.

Background: Since the early 2000s, there have been large increases in donor financing of human resources for health (HRH), yet few studies have examined their effects on health systems.

Objective: To determine the scope and impact of investments in HRH by the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), the largest investor in HRH outside national governments.

Methods: We used mixed research methodology to analyse budget allocations and expenditures for HRH, including training, for 138 countries receiving money from the Global Fund during funding rounds 1-7. From these aggregate figures, we then identified 27 countries with the largest funding for human resources and training and examined all HRH-related performance indicators tracked in Global Fund grant reports. We used the results of these quantitative analyses to select six countries with substantial funding and varied characteristics-representing different regions and income levels for further in-depth study: Bangladesh (South and West Asia, low income), Ethiopia (Eastern Africa, low income), Honduras (Latin America, lower-middle income), Indonesia (South and West Asia, lower-middle income), Malawi (Southern Africa, low income) and Ukraine (Eastern Europe and Central Asia, upper-middle income). We used qualitative methods to gather information in each of the six countries through 159 interviews with key informants from 83 organizations. Using comparative case-study analysis, we examined Global Fund's interactions with other donors, as well as its HRH support and co-ordination within national health systems.

Results: Around US$1.4 billion (23% of total US$5.1 billion) of grant funding was allocated to HRH by the 138 Global Fund recipient countries. In funding rounds 1-7, the six countries we studied in detail were awarded a total of 47 grants amounting to US$1.2 billion and HRH budgets of US$276 million, of which approximately half were invested in disease-focused in-service and short-term training activities. Countries employed a variety of mechanisms including salary top-ups, performance incentives, extra compensation and contracting of workers for part-time work, to pay health workers using Global Fund financing. Global Fund support for training and salary support was not co-ordinated with national strategic plans and there were major deficiencies in the data collected by the Global Fund to track HRH financing and to provide meaningful assessments of health system performance.

Conclusion: The narrow disease focus and lack of co-ordination with national governments call into question the efficiency of funding and sustainability of Global Fund investments in HRH and their effectiveness in strengthening recipient countries' health systems. The lessons that emerge from this analysis can be used by both the Global Fund and other donors to improve co-ordination of investments and the effectiveness of programmes in recipient countries.

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Editor’s notes: This study describes Global Fund’s budget allocations, expenditures and specific activities on human resources for health (HRH) from 2002 to 2010. The authors were particularly interested in exploring whether and how these investments contributed to health system strengthening through a more detailed qualitative analysis of six geographically and programmatically different countries.  

They find that the 27 countries with the largest budgeted HRH expenditures allocated some 29.6% to HRH, and had a ratio of 1.35 health workers trained in comparison to the total national health workforce, suggesting duplication of training activities and programme inefficiency. This reflects the confirmed lack of coordination with national HRH training programmes that the authors documented, particularly in Ethiopia, Bangladesh and Malawi. In terms of coordinating HRH salary support and financing plans, only Honduras and Malawi had developed plans for absorbing some of the health workers that were being covered by Global Fund grants. In other countries, the top-ups and monetary compensation/ incentives funded through Global Fund grants to increase retention and motivation, were considered short-term and would not be sustained. Of the six country case studies, it is only in Malawi that the Global Fund coordinated its efforts with the national HRH strategy and other donor programmes.

The study highlights the need for a paradigm shift away from disease-focused grants to co-investments in HIV, tuberculosis and malaria that would allow the realisation of remarkable synergies and efficiency gains.

Africa, Asia, Europe, Latin America
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Can community based health care form part of a wider primary health care strategy in sub-Saharan Africa?

Integration of community home based care programmes within national primary health care revitalisation strategies in Ethiopia, Malawi, South-Africa and Zambia: a comparative assessment.

Aantjes C, Quinlan T, Bunders J. Global Health. 2014 Dec 11;10(1):85. [Epub ahead of print]

Background: In 2008, the WHO facilitated the primary health care (PHC) revitalisation agenda. The purpose was to strengthen African health systems in order to address communicable and non-communicable diseases. Our aim was to assess the position of civil society-led community home based care programmes (CHBC), which serve the needs of patients with HIV, within this agenda. We examined how their roles and place in health systems evolved, and the prospects for these programmes in national policies and strategies to revitalise PHC, as new health care demands arise.

Methods: The study was conducted in Ethiopia, Malawi, South Africa and Zambia and used an historical, comparative research design. We used purposive sampling in the selection of countries and case studies of CHBC programmes. Qualitative methods included semi-structured interviews, focus group discussions, service observation and community mapping exercises. Quantitative methods included questionnaire surveys.

Results: The capacity of PHC services increased rapidly in the mid-to-late 2000s via CHBC programme facilitation of community mobilisation and participation in primary care services and the exceptional investments for HIV/AIDS. CHBC programmes diversified their services in response to the changing health and social care needs of patients on lifelong anti-retroviral therapy and there is a general trend to extend service delivery beyond HIV-infected patients. We observed similarities in the way the governments of South Africa, Malawi and Zambia are integrating CHBC programmes into PHC by making PHC facilities the focal point for management and state-paid community health workers responsible for the supervision of community-based activities. Contextual differences were found between Ethiopia, South Africa, Malawi and Zambia, whereby the policy direction of the latter two countries is to have in place structures and mechanisms that actively connect health and social welfare interventions from governmental and non-governmental actors.

Conclusions: Countries may differ in the means to integrate and co-ordinate government and civil society agencies but the net result is expanded PHC capacity. In a context of changing health care demands, CHBC programmes are a vital mechanism for the delivery of primary health and social welfare services.

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Editor’s notes: This paper presents a comprehensive overview of the integration of community home based care (CHBC) with primary health care (PHC) strategies in four countries in sub-Saharan Africa. It emphasises the co-ordination of efforts between government and civil society. Using a multi method approach drawing on surveys, key informant interviews, focus group discussions and in-depth interviews the authors sought to gain an historical perspective on the changing form and content of CHBC and PHC in Ethiopia, Malawi, South Africa and Zambia. They focused on programmes that had been active for more than 10 years, were nationally representative and offered diversity of care. Their findings reveal a commitment to integration of care within PHC strategies in all the countries. This reflects the recent call by WHO to revitalise primary health care approaches in developing countries. The authors identified similarities across the countries, especially government commitment to revitalise PHC, a strong presence of actors providing CHBC, and the extension of focus beyond one disease such as HIV to the care and support for people with chronic conditions. They also identified three different approaches taken. These included supervision by the government (Malawi, Zambia), contracting (South Africa) and referral (Ethiopia). This reveals that approaches to integration need to be context-driven. This is a very useful paper to understand how HIV care is now being integrated into broader medical and social care and lessons learned from innovative HIV care are being applied more widely and in a more coordinated way.

Africa
Ethiopia, Malawi, South Africa, Zambia
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Facility-level costs for antiretroviral therapy are much lower than previously understood

Multi-country analysis of treatment costs for HIV/AIDS (MATCH): facility-level ART unit cost analysis in Ethiopia, Malawi, Rwanda, South Africa and Zambia.

Tagar E, Sundaram M, Condliffe K, Matatiyo B, Chimbwandira F, Chilima B, Mwanamanga R, Moyo C, Chitah BM, Nyemazi JP, Assefa Y, Pillay Y, Mayer S, Shear L, Dain M, Hurley R, Kumar R, McCarthy T, Batra P, Gwinnell D, Diamond S, Over M. PLoS One. 2014 Nov 12;9(11):e108304. doi: 10.1371/journal.pone.0108304. eCollection 2014.

Background: Today's uncertain HIV funding landscape threatens to slow progress towards treatment goals. Understanding the costs of antiretroviral therapy (ART) will be essential for governments to make informed policy decisions about the pace of scale-up under the 2013 WHO HIV Treatment Guidelines, which increase the number of people eligible for treatment from 17.6 million to 28.6 million. The study presented here is one of the largest of its kind and the first to describe the facility-level cost of ART in a random sample of facilities in Ethiopia, Malawi, Rwanda, South Africa and Zambia.

Methods & Findings: In 2010-2011, comprehensive data on one year of facility-level ART costs and patient outcomes were collected from 161 facilities, selected using stratified random sampling. Overall, facility-level ART costs were significantly lower than expected in four of the five countries, with a simple average of $208 per patient-year (ppy) across Ethiopia, Malawi, Rwanda and Zambia. Costs were higher in South Africa, at $682 ppy. This included medications, laboratory services, direct and indirect personnel, patient support, equipment and administrative services. Facilities demonstrated the ability to retain patients alive and on treatment at these costs, although outcomes for established patients (2-8% annual loss to follow-up or death) were better than outcomes for new patients in their first year of ART (77-95% alive and on treatment).

Conclusions: This study illustrated that the facility-level costs of ART are lower than previously understood in these five countries. While limitations must be considered, and costs will vary across countries, this suggests that expanded treatment coverage may be affordable. Further research is needed to understand investment costs of treatment scale-up, non-facility costs and opportunities for more efficient resource allocation.

Abstract Full-text [free] access

Editor’s notes: This paper describes the facility-level costs for antiretroviral therapy (ART) delivery in 161 facilities across five countries. The scale of this study is impressive. At 161 facilities, it is one of the largest existing evaluations of facility-level costs for delivering ART. Collecting detailed cost data is a time- and resource-intensive process, and there is remarkable value in this quantity of cost data being made available.

The results are also surprising. The average cost for ART at the facility level in four of five countries ($208 per person per year) is consistently much lower than previously understood. Primary costing studies in low- and middle-income settings typically find some level of inconsistency between facilities, reflecting room to improve efficiency. This study found more variation in South Africa than in other settings, but relatively little variation overall. It would be interesting to find out in more detail whether this was a function of missing data, or whether the facilities included in the analysis were consistently efficient. If the latter, this may be an indication of improving efficiency in delivery of HIV treatment services.

The most exciting outcome from this study is the low costs found across settings. A number of existing studies of ART costs, all published between 2004-2008, find average facility costs ranging from $650 to $1000 per person, per year. The authors explain their lower costs as a reflection of reduced ART drug prices over the last ten years. Such a dramatic drop in costs is encouraging, particularly in the context of current efforts to expand access to ART.

Africa
Ethiopia, Malawi, Rwanda, South Africa, Zambia
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Why pregnant women and mothers living with HIV do not access, or do not stay in care

A systematic review of individual and contextual factors affecting ART initiation, adherence, and retention for HIV-infected pregnant and postpartum women.

Hodgson I, Plummer ML, Konopka SN, Colvin CJ, Jonas E, Albertini J, Amzel A, Fogg KP. PLoS One. 2014 Nov 5;9(11):e111421. doi: 10.1371/journal.pone.0111421. eCollection 2014.

Background: Despite progress reducing maternal mortality, HIV-related maternal deaths remain high, accounting, for example, for up to 24 percent of all pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART) is effective in improving outcomes among HIV-infected pregnant and postpartum women, yet rates of initiation, adherence, and retention remain low. This systematic literature review synthesized evidence about individual and contextual factors affecting ART use among HIV-infected pregnant and postpartum women.

Methods: Searches were conducted for studies addressing the population (HIV-infected pregnant and postpartum women), intervention (ART), and outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. Individual and contextual enablers and barriers to ART use were extracted and organized thematically within a framework of individual, interpersonal, community, and structural categories.

Results: Thirty-four studies were included in the review. Individual-level factors included both those within and outside a woman's awareness and control (e.g., commitment to child's health or age). Individual-level barriers included poor understanding of HIV, ART, and prevention of mother-to-child transmission, and difficulty managing practical demands of ART. At an interpersonal level, disclosure to a spouse and spousal involvement in treatment were associated with improved initiation, adherence, and retention. Fear of negative consequences was a barrier to disclosure. At a community level, stigma was a major barrier. Key structural barriers and enablers were related to health system use and engagement, including access to services and health worker attitudes.

Conclusions: To be successful, programs seeking to expand access to and continued use of ART by integrating maternal health and HIV services must identify and address the relevant barriers and enablers in their own context that are described in this review. Further research on this population, including those who drop out of or never access health services, is needed to inform effective implementation.

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Editor’s notes: This systematic review is one of three by the same team, related to HIV and maternal mortality. The review findings illustrate that the individual and contextual factors which affect antiretroviral therapy (ART) initiation, adherence and retention for pregnant/postpartum women living with HIV are numerous. Fears over disclosure, and consequent stigma and discrimination feature in many of the studies reviewed. Practical barriers might be overcome, by making services more accessible. The lack of knowledge about HIV and treatment among some women may be addressed through information campaigns. However, the fear of negative consequences as a result of disclosure, even to health workers, presents significant barriers to care. This is something that is of particular note as Option B+ is rolled out. An important strength of this review is the combination of qualitative and quantitative studies. The meticulous description of the approach to the review is also welcome. The authors’ call for ‘consistent, standardised and appropriate measures of adherence and retention’ with a ‘longitudinal component’, is a valuable suggestion as the performance of countries in providing Option B+ begins to be compared.

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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.

Abstract access 

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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`Real men’ do not need healthcare: men and treatment seeking in Malawi

Control, struggle, and emergent masculinities: a qualitative study of men's care-seeking determinants for chronic cough and tuberculosis symptoms in Blantyre, Malawi.

Chikovore J, Hart G, Kumwenda M, Chipungu GA, Desmond N, Corbett L.BMC Public Health. 2014 Oct 9;14:1053. doi: 10.1186/1471-2458-14-1053.

Background: Men's healthcare-seeking delay results in higher mortality while on HIV or tuberculosis (TB) treatment, and implies contribution to ongoing community-level TB transmission before initiating treatment. We investigated masculinity's role in healthcare-seeking delay for men with TB-suggestive symptoms, with a view to developing potential interventions for men.

Methods: Data were collected during March 2011 - March 2012 in three high-density suburbs in urban Blantyre. Ten focus group discussions were carried out of which eight (mixed sex = two; female only = three; male only = three) were with 74 ordinary community members, and two (both mixed sex) were with 20 health workers. Individual interviews were done with 20 TB patients (female =14) and 20 un-investigated chronic coughers (female = eight), and a three-day workshop was held with 27 health stakeholder representatives.

Results: An expectation to provide for and lead their families, and to control various aspects of their lives while facing limited employment opportunities and small incomes leaves men feeling inadequate, devoid of control, and anxious about being marginalised as men. Men were fearful about being looked at as less than men, and about their wives engaging in extramarital sex without ability to detect or monitor them. Control was a key defining feature of adequate manhood, and efforts to achieve it also led men into side-lining their health. Articulate and consistent concepts of men's bodily strength or appropriate illness responses were absent from the accounts.

Conclusions: Facilitating men to seek care early is an urgent public health imperative, given the contexts of high HIV/AIDS prevalence but increasingly available treatment, and the role of care-seeking delay in TB transmission. Men's struggles trying to achieve ideal images seem to influence their engagement with their health. Ambiguous views regarding some key masculinity representations and the embrace of less harmful masculinities raise questions about some common assumptions that guide work with men. Apparent 'emergent masculinities' might be a useful platform from which to support the transformation of harmful masculinity. Finally, the complex manifestations of masculinity indicate the need for interventions targeting men in health and TB control to assume supportive, multidimensional and long-term outlooks.

Abstract  Full-text [free] access

Editor’s notes: The differences between men and women’s willingness to seek healthcare have been described in many different settings. This paper sets out the detailed results from a cross-sectional qualitative study looking at men’s care seeking practices for tuberculosis/chronic cough in Malawi. As well as describing perceptions of how a man should behave in society, and what this means for managing health, the authors examine how masculinity influences ill-health responses. Some men delay treatment seeking, because it is not manly to give in to symptoms. Men should publicly show an ability to put up with poor health or employ alcohol or exercise to chase away sickness. While the focus of this paper is on treatment seeking for tuberculosis, the authors draw parallels with the emerging literature on masculinity and HIV-treatment access. Making treatment available will not be enough; efforts have to be made to develop programmes to support and sustain men on treatment.

Avoid TB deaths
Africa
Malawi
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Prednisolone does not reduce poor outcomes in TB pericarditis

Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

Mayosi BM, Ntsekhe M, Bosch J, Pandie S, Jung H, Gumedze F, Pogue J, Thabane L, Smieja M, Francis V, Joldersma L, Thomas KM, Thomas B, Awotedu AA, Magula NP, Naidoo DP, Damasceno A, Chitsa Banda A, Brown B, Manga P, Kirenga B, Mondo C, Mntla P, Tsitsi JM, Peters F, Essop MR, Russell JB, Hakim J, Matenga J, Barasa AF, Sani MU, Olunuga T, Ogah O, Ansa V, Aje A, Danbauchi S, Ojji D, Yusuf S; IMPI Trial Investigators. N Engl J Med. 2014 Sep 18;371(12):1121-30. doi: 10.1056/NEJMoa1407380. Epub 2014 Sep 1.

Background: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis.

Methods: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.

Results: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer.

Conclusions: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.

Abstract  Full-text [free] access

Editor’s notes: Tuberculous pericarditis remains an important and serious complication of HIV disease. Previous studies have suggested that treatment with steroids, in addition to standard TB treatment, reduces the risk of serious complications such as constrictive pericarditis. However, previous studies have been small, and have included few HIV-positive people.

This randomised controlled trial across eight countries in Africa tested two treatments for people with either definite or probable TB pericarditis. These included high dose steroid treatment, and injections of Mycobacterium indicus pranii. Mycobacterium indicus pranii is an environmental mycobacterium suggested to have a possible effect to reduce inflammation among people with TB. Two-thirds of the 1400 study participants were HIV-positive, most of whom were not taking antiretroviral therapy at the time of enrolment. The median CD4 count at enrolment was around 150 cells/µl. The primary outcome of the study was a composite of death, cardiac tamponade requiring drainage, and constrictive pericarditis. 

The death rate overall was high at 18%, and the main causes of death were considered to be pericarditis, TB, and HIV disease. Immunotherapy with Mycobacterium indicus pranii had no beneficial effects on any outcome. There was no overall difference in the composite primary outcome among people receiving prednisolone compared to placebo. However, people receiving prednisolone were less likely to develop constrictive pericarditis or to be hospitalised. There were more cancers (primarily Kaposi’s sarcoma among HIV-positive people) in people receiving either prednisolone or Mycobacterium indicus pranii, although the absolute rate was low. This is in keeping with previous observations.

Limitations of the study include that most people did not have microbiological confirmation of their TB diagnosis, so could potentially have had other causes of pericarditis for which prednisolone would not be expected to improve outcomes.

The results of this trial suggest that guidelines concerning use of prednisolone for TB pericarditis should be reviewed, particularly for people living with HIV. The poor outcomes among this group of people with TB and advanced HIV disease highlight the need for earlier HIV diagnosis, initiation of antiretroviral therapy, and TB preventive therapy.

Avoid TB deaths
Comorbidity, HIV Treatment
Africa
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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.

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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
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Cotrimoxazole appears safe in pregnant women living with HIV, despite poor quality evidence

Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis.

Ford N, Shubber Z, Jao J, Abrams EJ, Frigati L, Mofenson L. J Acquir Immune Defic Syndr. 2014 Aug 15;66(5):512-21. doi: 10.1097/QAI.0000000000000211.

Introduction: Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy.

Methods: Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.

Results: Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4 196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; τ² = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low.

Conclusions: The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.

Abstract access 

Editor’s notes: Cotrimoxazole significantly reduces morbidity and increases survival in people living with HIV (including people on antiretroviral therapy) in resource-limited settings.  However, there is some concern of potential human foetal risk when cotrimoxazole is taken during pregnancy. This systematic review found very limited evaluable data on maternal and infant outcomes associated with cotrimoxazole exposure during pregnancy. Cotrimoxazole is likely to be of most benefit in high HIV burden, low-income settings. In this context, the known benefit of treatment outweighs the potential risk to the foetus, in HIV-positive pregnant women.  Importantly, this paper highlights the need for better pregnancy outcome surveillance in women living with HIV, in resource-poor settings, which includes evaluation of exposure to cotrimoxazole and antiretroviral treatment.  

Africa, Asia, Europe, Northern America, Oceania
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