Malaria Deaths 2x Greater than Previously Reported

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Malaria is killing more people worldwide than previously thought, but the number of deaths has fallen rapidly as efforts to combat the disease have ramped up, according to new research from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington.
More than 1.2 million people died from malaria worldwide in 2010, twice the number found in the most recent comprehensive study of the disease. IHME researchers say that deaths from malaria have been missed by previous studies because of the assumption that the disease mainly kills children under 5. IHME found that more than 78,000 children aged 5 to 14 and more than 445,000 people aged 15 and older died from malaria in 2010, meaning that 42% of all malaria deaths were in people aged 5 and older.
“You learn in medical school that people exposed to malaria as children develop immunity and rarely die from malaria as adults,” said Dr. Christopher Murray, IHME Director and the study’s lead author. “What we have found in hospital records, death records, surveys, and other sources shows that just is not the case.”
The study also found that while the overall number of malaria deaths is higher than earlier reports, the trend in malaria deaths followed a similar downward pattern. Starting in 1985, malaria deaths grew every year before peaking in 2004 at 1.8 million deaths worldwide. Since then, the number of deaths fell annually, and between 2007 and 2010, the decline in deaths was more than 7% each year.
The new findings are being published today in The Lancet in “Global malaria mortality between 1980 and 2010: a systematic analysis.” The work is part of the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. Other research from this study, global trends in child mortality, maternal mortality, breast cancer, and cervical cancer, were released last year, and more trends will be released in the coming months.
Researchers say the biggest drivers of the decline in malaria deaths have been the scale-up of insecticide-treated bed nets and artemisinin-combination treatments (ACTs). This has been accomplished through the advent of the Global Fund to Fight AIDS, Tuberculosis and Malaria in 2001 and the creation of organizations focused on fighting malaria, such as the World Health Organization’s Roll Back Malaria, Malaria No More, and Nothing But Nets. Overall funding for malaria efforts grew from less than $0.25 billion annually in 2001 to more than $2 billion in 2009, according to IHME’s latest estimates. IHME reported in September 2011 that homes owning at least one bed net were associated with a 23% reduction in child mortality.
“We have seen a huge increase both in funding and in policy attention given to malaria over the past decade, and it’s having a real impact,” said Dr. Alan Lopez, Head of the School of Population Health at the University of Queensland and one of the study’s co-authors. “Reliably demonstrating just how big an impact is important to drive further investments in malaria control programs. This makes it even more critical for us to generate accurate estimates for all deaths, not just in young children and not just in sub-Saharan Africa.”
One of the most important factors in identifying the new malaria estimates was the use of verbal autopsy data. In a verbal autopsy, researchers interview the relatives of someone who has recently died to identify the cause of death. IHME and collaborators around the world published a series of articles in a special edition of Population Health Metrics in August 2011 focused on advancing the science of verbal autopsy. Verbal autopsy data were especially important in India, where malaria deaths have been vastly undercounted in both children and adults. IHME found that more than 37,000 people over the age of 15 in India died from malaria in 2010, and the chances of someone dying from malaria in India have fallen rapidly since 1980.
Progress in fighting malaria can be seen everywhere. Countries such as Zambia and Tanzania saw malaria deaths fall by more than 30% between 2004 and 2010. The progress being seen in Africa is especially significant, given that malaria deaths there accounted for a quarter of all deaths in children under 5 in 2010.
But the researchers warn that those gains could be reversed if global economic troubles continue to stifle funding efforts. IHME reported in December that growth in development assistance for health slowed greatly between 2009 and 2011. The announcement by the Global Fund in November that it would cancel its next round of funding casts a cloud over the future of malaria programs, the researchers say.
“If the Global Fund is weakened, the world could lose 40% of all the funding dedicated to fighting malaria,” said Dr. Stephen Lim, Associate Professor of Global Health at IHME and a co-author on the study. “That kind of loss of funding poses a definite threat to the health of people in countries with a high malaria burden, which in many cases are some of the poorest countries in the world. We need to think of ways to fill funding deficits in order to ensure continued progress on malaria mortality.”

Source: IHME

The “E” word and the “V” word: Two Holy Grails of Malaria Control

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The Roll Back Malaria Partnership talks confidently of elimination—many others question if this is possible without new interventions. The recent publication of the first Phase 3 clinical trial for a malaria vaccine shows promise, but is it actually good enough?

REVIEW OF:

  • Roll Back Malaria Partnership, “Eliminating Malaria: Learning from the Past, Looking Ahead”, Progress & Impact Series, vol 8, October 17th, 2011
  • RTS,S Clinical Trials Partnership, “First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children”, New England Journal of Medicine, October 18th, 2011

This past week has been a busy one in the world of malaria research and control. On Monday, the Roll Back Malaria Partnership (a joint enterprise between the World Health Organisation, UNICEF, UNDP and the World Bank) released the 8th volume in its Progress & Impact Series, entitled, “Eliminating Malaria: Learning from the Past, Looking Ahead”. The report summarizes RBM’s malaria eradication and elimination efforts to date, and outlines action plans and on-going progress in all malaria-endemic countries around the world. The overall tone of the document is highly positive, emphasizing the various success stories of countries achieving or nearing elimination of malaria in different parts of the world.

This is nowhere more obvious than in Chapter V’s regional summary of the WHO African Region, where no mention is made of the countries that are struggling the most with malaria control, but instead the focus is entirely on congratulating the 4 countries that have already achieved elimination, and praising those 12 countries with existing or imminent plans to move towards elimination. The document as a whole is a comprehensive overview of the status of malaria control, although somewhat light on epidemiological specifics. I was also dismayed to see at least two large photographs of fingerprick blood samples being taken without protective gloves being worn, against all standard diagnostic protocol!

But that’s an aside. In their conclusion, the authors primarily support “existing interventions”, and caution against waiting for “better options” to become available, given the measurable successes already being achieved in many settings using already-available control strategies such as bednet distribution, improved access to diagnosis and treatment and vector control.

It is not perhaps without a touch of irony then that on Tuesday, the first comprehensive analysis of an on-going Phase 3 clinical trial for one of the most promising malaria vaccine candidates was published, in the New England Journal of Medicine. The quest for a malaria vaccine has been protracted, expensive and, thus far, basically unsuccessful, yet to many, global elimination of malaria will not succeed without an intervention that gives lasting protection against re-infection, given the extraordinarily high rates of transmission of malaria in some parts of the world.

The paper reports a reduction of clinical malaria and severe malaria by 56% and 47% respectively, although protection seemed to decay over time; further evaluations will be analysed in 2012 and at the conclusion of the trial in 2014. The authors of the paper are careful to note that the trial was conducted in a cohort with generally good access to medical care, well-supplied health facilities and widespread usage of bednets and other control interventions. As such, mortality from malaria was low even in the control group, and so conclusions about the impact of the vaccine on malaria-related deaths may be difficult to draw.

Moreover, the paper did not directly analyse the relationship between the antibody titers (levels of immune protection to malaria in the blood) conferred by the vaccine and if the patient got malaria or not. In previous studies (for example, Bejon et al.’s 2008 paper also in the NEJM), this relationship was weak, suggesting that the vaccine itself was not contributing strongly to levels of protection against infection, and that other factors were at play. One suggestion is that the adjuvant, a non-specific immune-response enhancer included in the vaccine, may itself play a role, and given that the control groups received vaccines with a different adjuvant, this may partially account for the variations in malaria prevalence seen between the children studied. However, these early data still show potential at least for reducing clinical cases of malaria in a highly-endemic African setting.

It should be noted that these findings do not come entirely as a surprise; there were early signs of potential, at least partial, protection from this vaccine (the results of the Phase 2b trials were published in The Lancet back in 2004). Despite this, the word “vaccine” is mentioned but twice in the latest RBM report. I have a deep admiration for the RBM and all that the partnership has achieved thus far in the struggle to control malaria throughout the world. Without a doubt, the scale of the problem is immense, and they are right to emphasise the enormous achievements many countries have realized, and particularly in reducing malaria mortality in the last 10 years. Nor would I advocate for countries to latch onto the promise of a vaccine too quickly; clearly more research is needed to evaluate the long-term efficacy of the vaccine, as well as its impacts specifically on mortality as opposed to morbidity; hopefully we will have some of these answers in a year, at the conclusion of the Phase 3 trial.

However, in the meantime, there is clearly a huge opportunity for using these preliminary findings to determine what role there might be, if any, for the vaccine in its existing form as part of new and improved control strategies. For example, if the vaccine is not fully protective, might it, perhaps counter-intuitively, actually be more effective in areas which are already well on their way to successful control, by reducing transmission below that which is viable for the persistence of malaria? Or will its role in reducing incidence of severe disease be equally well utilized in extremely high prevalence and low health infrastructure areas, where access to diagnosis and treatment is the limiting step in effecting control? To its credit, RBM has acknowledged this since the publication of the vaccine trial results, with the following statement from the CDC: “These promising vaccine trial results add to the hope that adding an effective vaccine to current malaria interventions will move us closer to that goal.” Perhaps the “better option” wasn’t so long in coming after all.

 

Malaria Survey in Mumbai, India

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QUESTION:

I want the past year’s malaria survey in Mumbai and other states.

ANSWER:

The Lancet, one of the world’s leading medical journals, recently published an article summarising the mortality of malaria in India. The citation for the article is as follows:

Dhingra, Jha, Sharma, Cohen, Jotkar, Rodriguez, Bassani, Suraweera, Laxminarayan and Peto (2010), ‘Adult and child mortality in India: a nationally representative mortality survey’, The Lancet, 376: 1768-1774.

A slightly older article (from 2007) discusses the burden of malaria in India:

Kumar, Valecha, Jain and Dash (2007), ‘Burden of malaria in India: A retrospective and prospective view’, American Journal of Tropical Medicine and Hygiene, 77: 69-78.