Tropical Health Matters

In many parts of the tropical world malaria is seasonal, depending in large part upon rains.  If taken into account, seasonality can allow malaria program managers to plan better to serve different areas of their countries.  There are areas where a dry season or colder weather may appear to put a stop to transmission completely, but often minimal transmission manages to take place.

When we know that some areas have more intense malaria transmission during certain times of year, we can ensure that our interventions are in place well in advance of major rains.  Knowledge of seasonality can guide vector control efforts and help plan for increased stocks of medicines and diagnostic tests in clinics, for example.  Several examples of the need for such preparations have been in the news this weekend.

Malaria’s Day in Court

In India the Kolkata Municipal Corporation is apparently under legal investigation for inadequate supplies of malaria medicines in clinics in Bhowanipore, which is a malaria-prone area.  In a bid to find out what he needed to do, a medical officer unknowingly broke protocol and visited the judge hearing the case to get advice on how better to serve the people of the area.

Fortunately he was not reprimanded for his efforts to get ahead of impending malaria outbreaks.

Awaiting the Storm

Adding to Haiti’s existing medical chaos and suffering is the season of increasing rains.  People are still living in makeshift tents that given no protection when it comes to mosquitoes and malaria.

The Boston Globe reports that, “Some rain typically falls every month in Haiti, meteorologists say, but heavy downpours could begin as early as this month.”  As seen in the satellite photo from NOAA, Haiti was in the path of several major hurricanes and tropical storms in 2008 – so rains from these storms kill people directly through flooding, and those who survive can expect to be threatened with malaria.

Interfaith Preparation

Nigeria accounts for at least one-fourth of the malaria deaths in Africa, according to AFP.  A major national net distribution is underway, which will hopefully make major inroads before the heavy rains start.

Planning is the key – we must understand the malaria transmission patterns in our countries and plan to get the material and human resources in place in a timely manner so that they will be effective in bringing down malaria morbidity and mortality.

Women and men have different health and disease experiences according to an article this morning in the Baltimore Sun. The article stresses that, “A rapidly growing body of research shows men and women are biologically different in ways that have nothing to do with the obvious physical features and lots to do with which diseases strike and how successfully or not the body fights them off.”

Some of the highlighted examples include …

• Women’s bodies have been shown to generate a stronger antibody response to the H1N1 vaccine than men’s
• Autism is four times more common in males
• Lupus and irritable bowel syndrome predominantly afflict females

The Sun article states that like many innovative thoughts and practices, “… for the most part, the idea that males and females are very different patients hasn’t made its way into the doctor’s office.” Fortunately the Society for Women’s Health Research is trying to address these issues.

We might ask, is there evidence that malaria affects men and women differently? Such differences may be biological – sex-related; while other differences may be social – gender-related.

Among travelers, Schlagenhauf and colleagues found that, “Women are proportionately less likely to have febrile illnesses (OR, 0.15; 95% CI, 0.10-0.21) [and] vector-borne diseases, such as malaria (OR, 0.46; 95% CI, 0.41-0.51).”  Munga and Gideon learned that a greater proportion of women in rural Tanzania reported malaria episodes compared to men, while the opposite was true in urban areas. They surmise that social or gender roles may actually increase the exposure to mosquitoes in each setting.

In Yemen El-Taiar and colleagues observed that women were less likely to associate malaria with mosquitoes and that “different beliefs and roles identified between men and women need to be taken into account in health promotion messages.” In many places women have less access to formal education than men.

“Some research suggests that gender may influence the use of ITNs within households, as different roles dictate different sleeping patterns for men and women,” as Toe and colleagues summarized from the literature. Ahmed et al. in Bangladesh observed a “gender divide in knowledge and health-seeking behaviour was observed disfavouring women,” with malaria-like symptoms.

Other studies have shown that pregnant women attract more malaria-bearing mosquitoes, a biological issue in Sudan and The Gambia. Intra-household gender issues have been found to influence equitable use of bednets.

We welcome readers to contribute other examples of the gender and human biological factors that may influence malaria and its control. The key lesson is that unless we plan for both sets of influences, our tools may not be fully effective or equitably utilized in order to achieve universal coverage and mortality reduction.

Thirty-four centuries ago, when preparing the body of the 20-year old Egyptian king for the afterlife, the embalmers probably could not imagine the later worldwide interest and curiosity in this young royal – a life after death that has been in the spotlight since 1922. Much speculation and research has centered King Tutankhamun’s death.

Archaeology Magazine reports that, “new evidence of Tutankhamun’s reign has emerged that shows he was much more active than was thought, and may have led military campaigns against the Syrians and Nubians before he died,” as exemplified to the left where Archaeology Magazine shows Tutankhamun as a sphinx, trampling Egypt’s traditional foes, a Syrian or Asiatic and a Nubian (picture by Araldo De Luca).

“The recent reexamination of Tutankhamun’s body suggests that his death was the result of an accident that injured his leg, leading to a fatal infection.” Coinciding with this report is publication of medical evidence that King Tut’s death may have been more complicated.

The Journal of the American Medical Association reports that for the past two years “royal mummies underwent detailed anthropological, radiological, and genetic studies as part of the King Tutankhamun Family Project.” Hawass and colleagues found that …

These results suggest avascular bone necrosis in conjunction with the malarial infection as the most likely cause of death in Tutankhamun. Walking impairment and malarial disease sustained by Tutankhamun is supported by the discovery of canes and an afterlife pharmacy in his tomb.

The researchers discovered “genes specific for Plasmodium falciparum” in several of the mummies. Over 3,000 years later, Egypt is almost free from malaria. Dahesh and colleagues discuss that, “remnant residual foci are still localized in two districts; Sinnuris and Faiyoum, Faiyoum Governorate.”

The herbal apothecary found in King Tut’s tomb also suggest treatment for malaria. Whether malaria itself was the ultimate cause of demise has been questioned. Mark Rose of Archaeology.org says, “I suspect that they are overdoing it a bit” when researchers portray the king as a weakling who was finally knocked out by malaria. We need to know more about malaria transmission and ecology in the area many years ago to give a better conclusion.

If the king’s domain was in an area of stable transmission, it would be unusual for an adult to succumb to malaria, having developed some immunity over the years.  Had the area been one of seasonal or epidemic malaria, a bout of the disease could have been the final blow.

Transmission may have been seasonal following the annual floods. Bernard Ziskind observes that ancient texts show the Nile valley to be particularly susceptible to malaria. He quoted Herodotus who reported around 430 BC that Egyptians living in marshy areas used nets for fishing by day and protection from mosquitoes by night.

More than three thousand years of malaria transmission is a sobering thought. We have been trying to eradicate it for less that 100 years.  We have more tools to fight the disease than the herbs and fishnets of ancient times, but King Tut’s new diagnosis should remind us that this ancient disease will not go quietly.

If mosquitoes could read, they would know from two recent announcements that their way of life is threatened. Neither of the innovations is ready to go to scale, but both demonstrate the need for continuing research and new tools if malaria is eventually to be eliminated.

The attention grabber among these two tools is a laser gun that shoots down mosquitoes. At the annual TED Conference “Former Microsoft CTO Nathan Myhrvold says his company, Intellectual Ventures, can assemble electronic parts from readily available devices — printers, digital cameras, projectors — to make ground-to-air lasers that can take out mosquitoes.”

According to the New York Times, “Mr. Myhrvold said the software detects the speed and size of the image before deciding whether to shoot. It would reject a butterfly or a human, for example, and more powerful laser blasts could be used for locusts. In regions afflicted by malaria, the lasers could be used to create protective fences around clinics, homes, or even agricultural fields as a substitute for pesticides.”

A video shows the laser in action shearing off the wings of mosquitoes. SmartPlanet.com reports that, “Altogether, the device could cost as little as $50, depending on volume. For now, it’s merely a proof-of-concept device.”  In addition to bring down the price, the inventors must ensure a battery operated model is available in endemic rural communities.

A second innovation is “A new insecticide against malaria mosquitoes has proved safe and effective as an alternative to DDT in an experimental trial in Benin, West Africa.” The chemical is the long-lasting insecticide, chlorpyrifos-methyl. N’Geussan and colleagues found that this insecticide, “killed 95% of An. gambiae that entered the hut as compared to 31% with lambdacyhalothrin and 50% with DDT.”

The challenge with chlorpyrifos-methyl was that it did not have the repellent power of the other insecticides and therefore may allow resistance to develop faster.  Still, this compound might be used in combination with other insecticides for greater effect.

The important lesson to come out of the insecticide research is that, “The remarkable residual activity indicates that cost-effective alternatives to DDT are feasible through modern formulation technology.”

So while neither of these innovations is ready for prime time, they represent a much needed inquiry into multiple ways that malaria can be controlled.  A recurrent theme at last year’s 5th MIM Pan-African Malaria Conference was advocacy for continued and increased malaria research support.  This is the only way to guarantee appropriate and effective malaria control tools are available when needed.

Kenya’s Saturday Nation reports that the country lost out on appeal for its Global Fund Round 9 malaria and HIV application rejection. “Late last year, Kenya’s (original) application for funding from the Global Fund on Aids, TB and malaria for $270 million was rejected on technicalities and the country’s poor record with the organisation.”

Apparently the rejection of the appeal was two pronged – proposal quality and past performance. First the Nation reports that, “On Kenya’s appeal for malaria funding for example, the panel upholds that the decision made initially by the technical team was sound and saw no need to reverse it.” Then the Nation quotes a Ministry official as saying, “Our under-performance has been the main undoing.”

To date Kenya has received only two malaria grants from the Global Fund – Rounds 2 and 4. Only 17% of the Round 2 funds were ever disbursed for the $27 million grant after start-up in 2003, and apparently the grant ground to a halt after about 3 years, never entering Phase 2.

So far 63% of the $162 million Round 4 grant have been disbursed since inception in 2006. Expenditures are only 60% of disbursement. On last review in November 2009 the grant scored a B2, meaning inadequate performance but potential demonstrated.  The difficulties in performance and new grant success seem ironic since Kenya has recently made major strides in updating its malaria strategy and action plans to better reflect the country’s epidemiological and transmission profiles.

On top of these problems were reports from Kenya early last year that “the Government appointed a taskforce to trace the missing Sh13 billion grant from the Global Fund to fight Aids, tuberculosis and malaria.”

Once grants have been made, the Global Fund’s Office of the Inspector General has a role in monitoring implementation and colating lessons learned to improve GFATM functioning. The most recent report notes that of 17 recommendations made to Kenya to improve the functioning of its grants, none were implemented. General problems across several countries included among others …

• Conflicts of interest with PRs and SRs sitting on CCMs
• CCMs micromanaging grants instead of overseeing them
• PRs not complying with grant agreement clauses
• Procurement not executed in line with best practices
• Weak financial management and internal control of PRs
• Unworkable monitoring/evaluation systems because of unattainable targets and poor data collection procedures (feature attributed to countring including Kenya)

None of the foregoing problems are secret, and yet countries like Kenya cannot seem to get out of the viscious cycle of poor performance leading to new grant rejection leading to funding shortages that lead to more poor performance in their malaria control efforts.  Back in 2008 Kenya went through major efforts to democratize and improve the functioning of its Global Fund governance mechanisms.  Maybe the malaria partnership has not help Kenya accountable for the promises it made?

PS – the Global Fund is not Kenya’s only weak area for international assistance. According to the Nation yesterday, “Kenya has failed the eligibility test for (US) Millennium Challenge aid in each of the past five years because it falls short on governance standards.”

Yesterday we presented some of the findings from the malaria drug studies conducted by US Pharmacopeia (USP) in Madagascar, Uganda and Senegal.  We conjectured that the problem may be less in the public sector since it is often guided by WHO drug pre-qualification approvals – especially if the drugs are purchased through major donor programs like Global Fund, World Bank or PMI. At times the US Food and Drug Administration may be involved.

After reviewing the whole report from USP our faith in the public sector is somewhat shaken.  While the chart at the right shows that the informal and private sectors have the greatest proportion of substandard malaria drugs, the public sector is not without problems – 23% of SP products tested 14% of ACTs in the public sector were not up to standard.

An interesting finding is that the problem of substandard drugs rests in inadequate amounts of active ingredients or the presence of impurities in the product – not specifically the issue of counterfeit/fake medications.

Problems in the public sector may arise in the procurement processes. In some cases there are central procurement agencies in the national health ministry. In some countries states/provinces and local governments/districts can do their own tendering and procurement. This opens the door to a variety of medications entering the public sector, not just the few recommended prequalified products.

As mentioned in yesterday’s post, it is often necessary to back to the manufacturer to correct problems.  The USP report had the following observations about common brands that may find their way into public procurement processes:

The results were similar for the ACT products, that is, samples of most of the brands either all passed or all failed the QC test requirements, with only a few exceptions. One example is the Larimal brand, sampled from both Uganda and Senegal. All six Larimal samples tested failed the QC test requirements. Coartem and Duo-Cotecxin brands, on the other hand, were found in all three countries, and all samples of these brands passed the testing requirements. Also, all samples of the Lonart brand sampled from Uganda passed the QC test requirements.

This type of information should inform both donors and national malaria control programs. We look forward to reports from the seven other countries in the study.

While research for new malaria drugs continues, supplies of existing drugs are threatened by poor quality, parasite resistance and counterfeiting.

With USAID support, US Pharmacopeia (USP) has been studying malaria drug supplies in 10 Sub0Saharan Africa countries, and has recently issued a press release on its findings in three locations. USP found that, “a high percentage of medicines circulating on national markets are of substandard quality and thus may contribute to the growth of drug-resistant strains of Plasmodium falciparum, the most virulent form of malaria.”

Reports on the first three countries, Madagascar, Senegal and Uganda, looked at the recommended first line case management drugs, artemisinin-based combination therapy (ACT), and sulfadoxine-pyrimethamine (SP), which is used to prevent malaria in pregnancy. Between 26% and 44% of the drugs that were tested were sub-standard, that is they …

• do not contain the correct amount of the active ingredient(s)
• do not dissolve properly in the body or
• include unacceptable levels of potentially harmful impurities.

While USP called on local drug regulatory authorities to step up to the challenge of testing and enforcement, but also recognized that the problem traces back to the manufacturer. “The results also showed that, as a general rule, when a brand passed or failed in one country, it would also pass or fail in other countries. This indicates that the problem of quality is created at the source, rather than during passage through the distribution chain.”

Other countries included in USP the study are Cameroon, Ethiopia, Ghana, Kenya, Malawi, Nigeria and Tanzania. In a smaller scale study two years ago, Roger Bate and colleagues reported similar poor quality in 35% of malaria drugs sampled in 6 countries, five of which overlap with the USP work.

Last July VOA reported that fake pharmaceuticals are a bigger threat to West Africa than drug trafficking. At that time “The UN estimate(d) that more than half of anti-malaria medication available in West Africa is of sub-standard quality.”  A seminal study on drug quality in Nigeria in The Lancet supports the USP’s conclusions that the problem often lies at the source – “the main reason for such products not complying with pharmacopoeial limits is poor quality control and quality assurance during manufacture.”

We hope that the malaria medicines used by national control programs and purchased with WHO’s pre-qualification recommendations in mind, are safe, but the private market for antimalarials is wide. It may be unreasonable to expect that each country’s drug regulatory authority take full responsibility for guaranteeing drug quality when we could go to the source – the manufacturers, or at least the importers – and prevent the problem from even entering endemic countries.

Is the international community living up to its responsibilities to protect the quality of malaria drugs and thus save lives?

VOA reports that, “the U.S. isn’t backing off its commitment to aid other nations. In fact, the President has asked for increased funding for global development programs to provide humanitarian and economic assistance around the world.”

While the President’s Emergency Plan for AIDS Relief (PEPFAR) and the President’s Malaria Initiative (PMI) are continuing, they are doing so in the context of a new perspective – global public health.  VOA further notes that …

As part of a new emphasis on global health, the President’s budget will also devote new funding to reduce the number of mothers and infants who die each year from complications of childbirth or pregnancy, poor nutrition, and malaria, tuberculosis, pneumonia and polio. These are treatable diseases, yet they kill millions every year. And rather than the U.S. delivering aid services on its own, it will continue to work with its partner countries to build their capacity to deliver services through strong and accountable institutions. 

A key issue in this approach is health systems strengthening.  It is one thing to provide needed malaria (or HIV) commodities to endemic countries, and quite another for that country to be able to distribute those to people in need, promote proper use and monitor and report back to improve programming. The emphasis on health systems is most welcome and an important evolution in the life PEPFAR and PMI.

The potential for integration with maternal and child health services is an essential part of systems strengthening.  Too often, malaria in pregnancy program coverage has been low because of weak linkages between MCH and Malaria programs.

This pledge to expanding work on global public health should serve as a positive example to other donor countries.  We are still a long way from achieving the annual financial commitments needed to move from malaria control to elimination.

Nigeria’s Daily Champion Newspaper reports that, “CHIEF Executive Officer of Friends of the Global Fund Africa (Friend Africa)- an advocacy and fund raising organization, Akudo Anyanwu Ikemba has canvassed the need for institutionalize workplace policies to ensure the protection of health and right of workers.”

Participants at the 2-day Workplace Policy Workshop recognized that, “The HIV/AIDS scourge, tuberculosis and malaria are impending threats to productivity that could have negative economic impact on the workforce if not properly tackled.”  Akudo Ikemba also explained that “there is need for Small and Medium Enterprises (SMEs) to embark on deliberate workplace policies.”

In reality ‘small’ enterprises does not begin to describe the work setting for the majority of people in Nigeria and Africa generally. “This sector may be invisible, irregular, parallel, non-structured, backyard, under ground, subterranean, unobserved or residual.” It is hard to imagine members of this sector setting workplace health policies.

Their numbers are substantial. Geoffrey Nwaka estimates that the sector accounts for between 45% and 60% of the urban labor force.  The proportion is probably even greater in rural communities wheremost people work in subsistence agriculture.

Onyenechere reminds us that just because health services are available, it does not mean that the poorer people in the informal sector can access these. People in the informal sector have their own informal ways of raising money for health care. Yusuf and colleagues found that rotational credit/savings schemes have been used to finance health services, thus increasing access to a social service that many could not easily afford.

So how do people in the informal sector get malaria control services? The local butcher, carpenter or seamstress certainly does not keep a medical clinic on retainer. Most people in both rural and urban settings rely on the patent medicine seller or pharmacy shops.

A healthy and productive workplace is essential for national, community and individual development.  We need to be a bit more creative in ensuring that the informal sector and its employees have the same access to malaria prevention and treatment services as those working in the larger commercial and industrial sectors.