Posts or Comments 07 March 2021

Monthly Archive for "July 2009"

Advocacy &Funding Bill Brieger | 31 Jul 2009

Malaria funding – how can we fill the gaps

Nigeria is getting close to final signing of its Global Fund Round 8 Malaria Grant.  The amount approved over five years is roughly two-thirds of the original estimated need to cover those areas of the country not already served by donor support. Part of this reduction was judicious pruning, but the bulk reflects how economic hard times are hitting GFATM.

Aidspan’s Global Fund Observer notes that, “the economic slowdown has dampened expectations concerning how much money the Global Fund may be able to raise over at least the next year or two.”  And although funds requested for proposals in Round 9 are on average greater that those in Rounds 1-7, “The average two-year cost of the proposals submitted in Round 9 was $29 million, less than the $35 million average for Round 8.”  Although the number of malaria proposals in Round 9 is higher than for Round 8, their estimated funding requests are about two-thirds of those submitted for Round 9.

An important irony is becoming apparent with Round 8 malaria funding. Of the 23 approved R8 grants, only 3 are listed as having signed the grant agreement that allows funds to flow.  In these hard economic times, one wonders why 8 months have passed without efforts by countries to get their money.

from-approval-to-signing.jpgGrant agreement signing depends on a country presenting a work plan and budget for the first year.  RBM partners have taken a special interest in grant signing in recent years, recognizing it is not enough to provide technical assistance needed to write a winning grant.  This may say something about country level capacity to manage grant funds or the level of political will and seriousness applied to the problem of malaria in endemic countries.  Whatever the reason for delays, we must recognize that 2010 is fast approaching, thus imperiling universal coverage.

Malaria in Pregnancy Bill Brieger | 30 Jul 2009

Malaria in pregnancy … and beyond

Roll Back Malaria reminds us that, ” In areas of Africa with stable malaria transmission, P. falciparum infection during pregnancy is estimated to cause as many as 10,000 maternal deaths each year,” many of which are associated with “malaria-related anaemia.”  We also know that the effects malaria in pregnancy (MIP) go beyond the birth of the child. The presence of parasites in the placenta leads to fetal growth retardation such that, “8% to 14% of all low birth weight babies, and 3% to 8% of all infant deaths” are due to MIP.

Now Malhotra and colleagues have provided new insight into additional ways that MIP can harm the newborn. Their research identified three groups of newborns based on maternal experience with malaria infection:

  1. sensitized (and thus exposed)
  2. exposed not sensitized
  3. not exposed” based on evidence of malaria parasites in the mother and cord blood.

The authors concluded that Group 1 “children exposed to malaria in utero acquire a tolerant phenotype to blood-stage antigens that persists into childhood and is associated with an increased susceptibility to malaria infection and anemia.” Group 1 children had more malaria during follow-up and were more anemic.

An accompanying editorial in PLoS Medicine pointed out that, “However, the prevalence of placental infection peaks in the second trimester, and undoubtedly many infections with the potential to affect the immune system of the fetus have been resolved well before delivery.” Thus, the reported results do not account for the overall history of MIP in a woman – an area for further research.

anc-health-education.jpgEven so, based on this research and what is already known about the dangers of MIP, there is increasing need to protect pregnant women from malaria for their own sake and that of the unborn child. Unfortunately MIP programming may be the weakest link in our efforts to roll back malaria.

The campaign approach to distribution of long lasting insecticide-treated nets (LLINs) can easily bypass pregnant women.  Even efforts at universal coverage of nets that aim to place two nets in a household or one net per two people in a community does not guarantee that pregnant women will actually have access to and use of a LLIN.  Family power dynamics and weaknesses in follow-up health education on net use are problematic.

Also many countries do not take intermittent preventive treatment in pregnancy (IPTp) seriously.  Drug regulatory agencies allow the main drug for IPTp – sulphadoxine pyrimethamine (SP) – to be sold on the open market for treatment of the general public. This drug has obviously been experiencing problems of developing parasite resistance, and continued use for general treatment will only speed up that process.

Antenatal clinics should be the only place where SP is stocked and dispensed only to pregnant women. LLIN supplies in ANC clinics should be adequate to cover all pregnant women in a community – how else will the keep up component of LLIN interventions be maintained? RDTs and ACTs also need to be accessible to ANC clients.  When will we be ready to make a serious commitment to protecting pregnant women from malaria?

Environment &Epidemiology Bill Brieger | 26 Jul 2009

Sharing Diseases – HIV, malaria, humans, monkeys

The Los Angeles Times has reported on “Scientists have discovered that chimpanzees in Tanzania are falling ill and dying from an AIDS-like disease.” Researchers have known of simian immunodeficiency virus (SIV) for some time now, but had discounted its virulence.  The group in Tanzania has changed that by finding that chimps with SIV “died 10 to 16 times more frequently than uninfected chimps during a nine-year study.”

Not only are the researchers looking “into the origins of HIV and how it jumped from chimps to humans.”  They are also exploring the implications for HIV therapy and vaccines for humans.  A pathologist who examined the tissue in one dead chimp said it “looked just like a sample from a human patient who has died of AIDS.”

Reports are of shared malaria parasites between simians and humans are also becoming more common.  Here are some of the recent findings.

  • Researchers at Duke University found some similarity in genetic response to P. vivax between yellow baboons in Kenya’s Amboseli National Park and humans
  • Researchers based in Gabon and France report the discovery of a new malaria agent infecting chimpanzees in Central Africa. This new species, named Plasmodium gaboni, is a close relative of the most virulent human agent P. falciparum
  • Ulf Bronner and colleagues document a human case of P. Knowlesi in a Swedish traveler returning from Malarian Borneo, while readers of Mayo Clinic Proceedings are reminded to “keep in mind a broad differential diagnosis. P knowlesi is transmitted from human to human or from the macaque monkeys.” in Southeast Asia
  • In Brazil Ana Maria Ribeiro de Castro Duartea and colleagues explored the possibility arising from the parasitological prevalence of P. vivax and P. malariae in wild monkeys from Atlantic forest that monkeys could be a potential reservoir of these parasites for humans

In our efforts to control both HIV and malaria we must look at the broader environment and consider direct and indirect human interaction with wildlife.  It will not be enough to reduce and eliminate disease transmission among humans, if an animal reservoir remains.

Drug Quality Bill Brieger | 25 Jul 2009

Vigilance for the malaria drug supply – never ending

Malaria drug supplies provided by or purchased through major donor programs like the Global Fund, World Bank Booster, and the US President’s Malaria Initiative are safe and of high quality, at least upon arrival at ports in endemic countries. We still need to monitor storage conditions and shelf life. While these sources of malaria medicine are substantial, especially in providing for the public sector, there are huge variations of drug type, formulation and quality available to the average consumer in endemic countries.

Major donors rely on efforts to screen the mass of medicines available for malaria by the World Health Organization that has a medicine ‘prequalification’ program with the following mission:

In close cooperation with national regulatory agencies and partner organizations, the Prequalification Programme aims to make quality priority medicines available for the benefit of those in need. This is achieved through its evaluation and inspection activities, and by building national capacity for sustainable manufacturing and monitoring of quality medicines.

At present there are three prequalified providers of the popular artemether-lumafantrine (AL) combination: Novartis Pharma  of Beijing, China and Suffern, USA, Ajanta Pharma Ltd of Paithan, Aurangabad, Maharashtra, India, Cipla Ltd of Patalganga, India.  The National Agency for Food and Drug Administration in Nigeria has approved AL from twelve pharmaceutical companies, only two of which is prequalified.

One can see that the market for anti-malarial drugs is huge, and not even government approval can always solve the quality problem. Recently Gatonye Gathura and Mike Mwaniki of the Daily Nation reported that in Kenya , “A number of children’s malaria medicines on the Kenyan local market contain organisms that cause disease. Seven of about a dozen anti-malaria  suspensions on sale in Nairobi and registered with the Pharmacy and Poisons Board also dissolve poorly in water. A study published in Malaria Journal says that although dry powder suspensions are few because the active ingredient artemisinin is not stable in solution form, those available are of poor quality.”

Suspensions are easier to administer to children. Unfortunately the Kenyan researchers also found that, “paediatric antimalarial dry powder formulations on the market may contain ineffective or incorrect amounts of preservatives. This is a potential risk to the patient.”

News reports from Cambodia show that the malaria drug problem is a world-wide concern. “Many of the drugs are cheaply made and don’t contain the right chemistry, or are stored at incorrect temperatures, while others are deliberate fakes that have authentic-looking pills and packaging but contain only a small percentage of the active ingredient in each pill,” according to Talea Miller of Online NewsHour.

We cannot allow the caveat “Let the buyer beware” serve the global malaria control effort.  Maybe as donor contributions of quality drugs flood the market, the unsafe and ineffective formulations will be driven out. But unless national food and drug boards take their role more seriously and collaborate with the malaria community, the threat of fake and substandard drugs will continue to threaten lives now and stimulate drug resistance that threatens future generations.

Urban Bill Brieger | 16 Jul 2009

Urban Malaria – where can we find it?

In Nairobi’s Korogocho slum Yazoume Ye and colleagues looked for evidence of malaria parasites among 1,069 residents. Among those with data, 16.9% had a recent fever episode. Half were treated, primarily with sulphadoxine-pyrimethamine or amodiaquine, while four received artemether-lumefantrine. Ironically, “Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence.”

These results were similar to a study we did in low income neighborhoods of Lagos in 1998 screening only children between 6 months and 5 years of age [Afr. J. Med. med Sci (2001) 30, suppl. 7-15].  Blood film investigation of 916 children yielded a parasite prevalence of 0.9%.  Knockdown and night landing collections of mosquitoes in houses in these neighborhoods found no anopheles species. Very low densities of A. gambiae larvae were found in breeding sites.

urban-ag-dscn4842.JPGThese findings should not have surprised us since as far back as 1946, researchers had found that urban Lagos was too dirty to host the more finicky anopheles (Muirhead Thomson RC. Studies on Anopheles gambiae and A. melas in and around Lagos. Bulletin of Entomological Research. 1946; 38: 527-558).  Those cases we did find may have resulted from Lagosians visiting their relatives in the village during a recent wedding or funeral ceremony.

We do know that urban environments are not free from malaria, but one needs to identify anopheles-friendly sites and then look for focal transmission sites around those.  Urban agriculture (see photo from Bamako), flower gardens in higher income areas and some of the less dense urban peripheral settlements might be places to look.  This shows the need to plan urban malaria control with full understanding of the micro-ecologies of an urban setting.

Eradication Bill Brieger | 13 Jul 2009

Eradication – lessons from the Nigerian guinea worm program

Guinea worm is an ancient disease technically known as Dracunculiasis medinensis – or medina dragon.  While some assume that the ‘M’ in medina should be capitalized as in the Saudi Arabian city, the name also comes from the smaller case medina that means town or city, for it was in such urban populations where the worm could best spread.

guinea-worm-nigeria-1988-2008.jpgA 1986 World Health Assembly resolution marked the start of eradication for this thread-like subcutaneous parasite that is well known for disabling productive populations and causing great economic hardship. In Nigeria the first national conference on the disease in 1987 presented the first systematically collected data that showed the extent of the worm in almost every state.  This led to the first national case search that documented over 600,000 cases nationwide.  The race began to eliminate the disease by 1995 in line with overall global eradication targets.

The Nigeria Guinea Worm Eradication Program (NIGEP) was launched in 1988 and used multiple strategies to contain the disease.  Strong efforts were made to get all government and donor water supply programs to site wells in guinea worm endemic villages. Filter cloths were produced to remove the ‘vector’, a species of water flea/crustacean known as cyclops, from local pond water. The chemical abate was applied in some cases to ponds.  Villagers were taught not to enter water sources if they had an open ulcer where the guinea worm was protruding to lay its larvae in the ponds.

As we can see from the attached chart, the number of guinea worm cases in 1995, the target date for elimination, was only 2.5% of the 1988 baseline, but the disease was still resistant to human control.  Improved water supply interventions were harder to organize than previously thought, and use of filters was not an easy behavior to adopt in all communities. A case containment strategy was then adopted that required prompt reporting of emergent worms by volunteer village guinea worm scouts and hopefully a quick response by the local health department to ensure everyone had a filter and that the affected person did not enter the water source/pond.

NIGEP reports no new guinea worm cases so far in 2009, and hope this spells the end of the disease in Nigeria. The chart shows slow but steady progress, with a few blips, but clearly, elimination was not easy even though people were prone to say it was an easy disease to eliminate since the cyclops could not move from their ponds and people could be taught to avoid or treat the pond water.  In real life nothing is simple, and now, nearly twenty years after efforts began in Nigeria, elimination might be possible.

With malaria, like guinea worm, any case is a cause for concern and a potential for further transmission.  If a ‘simple’ disease like guinea worm has taken 20 years to conquer in Nigeria, how much longer for malaria?  Mosquitoes don’t stay put. People have medicine but not always access or proper adherence attitudes.  Commodities like nets are eventually delivered in countries, but how long does it take to distribute them to the people in need?  Even then, like the guinea worm filters, will the nets be used properly.

Malaria is a complicated disease – eradication, let along elimination from any particular endemic country – is a looooong term goal.  With guinea worm, the first step was made with a commitment by the countries of the world in 1986. That commitment is eventually bearing fruit – commitment, patience and persistence are needed for malaria eradication to succed, too.

Funding Bill Brieger | 04 Jul 2009

Malaria funding shortfall

The Reuters agency shares a press release from the Global Fund that worries that, “The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) is facing a budget hole of about $3 billion as the recession dries up foreign aid.” This includes commitments to existing grants as well as new ones planned for the upcoming year.  Through the end of 2008, GFATM “distributed 70 million insecticide-treated bed nets worldwide to prevent malaria infections,” but continued progress may be threatened.

The report notes that the US and Japan, who have respectively pledged $4.4 billion and $1 billion since GFATM started, are both facing a major credit crunch as well as commitments to domestic stimulus packages.  This does not preclude the US from continuing its controbutions.  In April the US Ambassador to the United Nations relayed that, “President Barack Obama is committed to making the United States a global leader in ending the nearly 1 million deaths annually from malaria by 2015.”

The problem may not even be a US one per se. The US is constrained by law to fund no more that 25% of GFATM activities.  If other donors reduce their contributions, the US cannot make up the difference to the GFATM.  Does this mean that the US would increase support to endemic countries through the US President’s Malaria Initiative and other USAID country projects (since PMI covers only 15 countries)? What about the G8 commitments made over the years?

african-money-sm.jpgWe thus must revisit the question – a particularly difficult one in this harsh economic climate – when and to what extent will malaria endemic countries begin to take on more responsibility for eliminating the disease within their borders and in their regions?  Since national health account studies in endemic countries show that the bulk of health expenditures often come from out-of-pocket expenditures by the same poor people who need protection from malaria, the idea of sustaining malaria control efforts for another 20-30 years to reach elimination is challenging to say the least.

In the US state and local governments annually spend millions of dollars on mosquito control.  Will the US and other industrialized nations continue to direct greater sums of money to other parts of the world where mosquitoes lead to millions of malaria deaths?

PS – While we worry about the need to continue malaria control support in highly endemic countries, we must not forget support in low or formerly endemic areas if we are to reach goals of malaria elimination.  A study of the Caribbean by Rawlins and colleagues is sobering:  All the essential malaria transmission conditions–vector, imported malaria organism and susceptible human host–now exist in most CMCs (Caribbean Epidemiology Centre [CAREC] Member Countries). A call is now made for enhanced surveillance, vector control and anti-malaria skills to be established in CMCs, in particular in: Recognizing the possible impact of climate change on the spread of anopheles and malaria transmission. Improving vector control skills for anopheles in CMCs.

ITNs &Private Sector Bill Brieger | 02 Jul 2009

Net Channels – are we losing the private sector?

at-nung-ette-sm.jpgThe New Vision reports that, “ALL Ugandans will be given free insecticide-treated mosquito nets, the health ministry has said, adding that their distribution will start in September,” according to government officials. The is is keeping with the United Nations drive to achieve universal net coverage by 2010.  Could this approach have any downsides?

Karen Grepin has observed that after free net distribution in Ethiopia, “the private distribution channels that existed before this distribution programs suffered major set backs. No one needed to buy a net anymore, so no one did. Importers stopped importing nets, distributors stopped distributing nets, and retailers stopped selling nets. Selling bed nets was no longer good business.”

Karen is not suggesting that nets should not be provided free, she does feel that, “donor funds (could have) been used to purchase some of the nets from local distributors, using local channels, than the networks might have been saved – even rewarded for their efforts.”  Without these local sources, Karen asks how people will buy additional and replacement nets.

This problem gets at the heart of the challenge of undertaking both catch-up and keep-up net distribution strategies.  Without alternative sources of net supplies, we may not be able to keep up with need in case donor program money does not flow continuously.

Up until recently net delivery strategies in Africa are categorised as public, private or mixed. Voucher schemes that include a public sector subsidy and private sector distribution are a good example of the mixed.  Voucher schemes have never been touted as a solution to universal coverage, but now they are being made redundant by mass or universal distribution.

Campaigns are needed, especially if they can guarantee that people actually use the insecticide-treated nets they receive, but if they kill local business as well as mosquitoes, we have cause to worry.  Malaria itself created economic burdens, and we don’t want malaria control to add to the burden.  Local net production can benefit from campaigns if governments buy and distribute these local ITNs.  Keeping local net production and sales alive can benefit the keep-up strategies, especially in these days of unxcertain economic and donor vitality.