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.

The recently concluded climate change summit on Copenhagen did not stress health, let alone malaria, as much as other consequences of climate change.  The Inter-governmental Panel on Climate Change has let us know a reason why attention to malaria in the climate debate may be somewhat confused:

Climate change may “have mixed effects on malaria; in some places the geographical range will contract, elsewhere the geographical range will expand and the transmission season may be changed.”

Kenya is one of those areas that has been reporting increases in the geographical range of malaria – particularly into the highlands.

Li and colleagues have been examining the Western Highlands over the period 2003-05 and documented variability of mosquito breeding sites by season and year.  Their findings point to ways to improve larval habitat modifications as an important part of integrated vector management in such areas of seasonal and focal mosquito breeding.

An integrated approach to malaria control also is credited for a “pronounced reduction and possible interruption of malaria transmission in 2 highland areas of Kenya for a 1-year period and provides evidence that interruption of transmission was related to widespread annual IRS insecticide treatment and use of ACT as first-line treatment for uncomplicated malaria. Although both areas remain at risk for recurrence of malaria epidemics, our study provides evidence that interruption and eventual elimination of malaria in areas of unstable transmission may be achievable.”

The Mount Kenya highlands have been studied by Chen et al. who were concerned about possible increases in malaria cases reported over the past 10-20 years there. They found that, “Local malaria transmission on the Mount Kenya highlands is possible due to the presence of An. arabiensis. Land use pattern and land cover might be the key factors affecting the vector population dynamics and the highland malaria transmission in the region.” Human factors appear to play an important role –

On the Mount Kenyan highlands, the population has increased at least 25% over the past 20 years. Population density in Karatina and Naro Moru areas is estimated at 530 persons per square km, much higher than those in the further north areas, e.g., only 81 persons per square km in Nanyuki. With the increasing population on the highlands, enhanced human activities including deforestation, farming and livestock rearing could create more vector habitats. For example, at the site northwest to Karatina, hundreds of anopheline larvae were found in ditches holding spring water for crops in a field. The vectors emerging from this kind of habitat can play an important role in local malaria transmission.

More recently researchers from the Kenya Medical Research Institute with support from DfID “found that the average temperature in the Kenyan Central Highlands had risen from 17C in 1989 to 19C today.” Specifically the group reported that …

Before the 1990s malaria was absent from the region because the parasite that causes it can mature only above 18C. However, malaria epidemics began among the population as average temperatures went over the 18C tipping point. The number of people contracting malaria during these epidemics has increased seven-fold in the past decade. In 2005, malaria-carrying anopheles mosquitoes were discovered in Naru Moro, more than 6,175ft (1,900m) above sea level.

Climate change may partly explain malaria increases in Kenya’s highlands, as may more local human activities. The important lesson is that such epidemic-prone areas need to be closely monitored. A timely mix of control interventions can then be judiciously applied. As Noor and colleagues recommend:

As malaria interventions go to scale effectively tracking epidemiological changes of risk demands a rigorous effort to document infection prevalence intime and space to remodel risks and redefine intervention priorities over the next 10-15 years .

Mobile population importation of drug-resistant infections and diseases is a focus of the November 2009 issue of Emerging Infectious Diseases. In that issue, MacPherson and colleagues cite, “Many examples of imported multidrug-resistant (MDR) infectious diseases are associated with migrant populations, e.g., MDR Plasmodium falciparum malaria in immigrants, tourists, and returned foreign-born travelers.”

Parasites travel –

• According to Monge-Maillo, malaria accounted for nearly 10% “of 2,198 immigrants referred to the Tropical Medicine Unit of Ramón y Cajal Hospital over a 20-year period” in Spain.
• “CDC received reports of 1,324 cases of malaria, including four fatal cases, with an onset of symptoms in 2004 among persons in the United States or one of its territories. This number represents an increase of 3.6% from the 1,278 cases reported for 2003,” as reported in MMWR by Skarbinski and colleagues.
• In the Netherlands 5043 laboratory cases of imported malaria were confirmed between 2000 and 2003 according to Klein and Bosman.

The problem is worse when drug-resistant parasites travel. Chan and co-researchers have been examining archival human sera “to explore the origin and evolution of Plasmodium falciparum chloroquine resistance in the Pacific.”

In 2002 Afghan refugees brought malaria into northwestern Pakistan. They experienced a 28% treatment failure rate when chemically substandard locally manufactured sulfadoxine-pyrimethamine was used for routine treatment. This is a potential way of producing drug resistance that could be carried back home by returning refugees

MacPherson and colleagues demand what they call, “Pharmaceutical security systems for standard and quality medicines,” in an effort to combat “commonly substandard or counterfeit” drugs in endemic countries.  Progress in eliminating malaria in Zanzibar, Rwanda and Zambia can easily be threatened if resistant parasites cross their borders. These parasites don’t need passports and visas.

A consensus has evolved that as malaria interventions become more widespread and successful, the need for Artemisinin-based Combination Therapy (ACT) medicines will decrease in endemic countries.  As a case in point, The RBM Needs Assessment produced by Burkina Faso in 2008 and used as a base for planning the Round 8 GFATM proposal projected a decline in the number of P. falciparum malaria cases and hence, a decrease in the need for ACT supplies.

While the attached chart shows a projected decrease in malaria cases starting in 2009, there is little evidence that LLIN distribution and use are adequate enough at present to produce such a drop.  Burkina Faso’s RBM Road Map shows that the most recent coverage is LLINs is 24% for children below 5 years of age and 28% for pregnant women.

Furthermore, the major distribution campaign to achieve universal coverage of LLINs in Burkina Faso is not slated to take off until July 2010 at the earliest.

Specifically, the Global Fund reports that, “The Global Fund has shown that where distribution of insecticide-treated bed nets (ITNs), spraying and treatment are scaled up to national population coverage, malaria cases and child mortality can be reduced by up to 50 percent.” It appears that in the countries cited, less than 80% coverage was able to achieve up to 50% reduction in cases over a couple years.

The major challenge though is how to ensure coverage/use after a big campaign, since actual use if often much less than proportions of households possessing nets. Then too, there is the challenge of promoting continued use. Lea Pare Toe and colleagues recently reported research findings on decreased motivation to use ITNs in Burkina Faso. Factors included –

• Acceptance was moderated by the fact that mosquitoes not seen as only cause of malaria
• Use of ITNs adversely affected by functional organization of the houses: e.g. if also cook in sleeping areas, see nets as fire hazard
• Bednets not used when perceived benefits of reduction in mosquito nuisance and of malaria were considered not to be worth the inconvenience of daily use

Universal coverage is not a one-time event. It must be maintained for many years. There must be continuous supplies of nets for new people and to replace old nets.  If after 3-4 years coverage falls, severe cases and mortality will rise as populations would have lost immunity.

And finally, any reduction in ACT need and use depends on use and acceptance of RDTs.  As the chart above shows, we will have no shortage of fever illness episodes even as malaria reduces.  Unless we couple diagnosis AND treatment, ACTs will be wasted and shortages will arise, especially if we reduce our orders of ACTs before we are sure that universal net coverage effects have really begun.

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.

The American Journal of Tropical Medicine and Hygiene is announcing as ‘good news’ the ‘remarkable malaria control progress and benefits on the island of Bioko in Equatorial Guinea over the last 4 years.’  Kleinschmidt and colleagues report –

• spraying IRS every 6 months in typically > 80% of households
• achieving 73% LLIN use (not just ownership) in households through house-to-house distribution with instruction and education
• achieving significant reductions in parasite prevalence, anemia and fever
• falling under five mortality from 152 per 1,000 births to 55 per 1,000

Steketee commends the strong public-private partnership that enabled this progress and recommends case containment and other strategies to solidify and sustain the gains toward elimination from the island.

Only one key component of the control strategy did not show progress – by 2008 coverage of pregnant women with two doses of intermittent preventive treatment (IPTp) was only 19%.  This component is not campaign based and requires strengthening the basic MCH services – so one wonders is the program to date has really strengthened the local health system to maintain the achievements. Then there is the Equatorial Guinea mainland to consider

Bioku Island is in the middle of the off shore oil fields, headquarters for the oil companies and an important tourist destination.  the benefits of controlling malaria in this powerful setting definitely have international economic ramifications for the local economy.

Apparently the poor people on the mainland are not being forgotten – in “2006, the partners secured Global Fund resources to expand the work to mainland Equitorial Guinea.”  The mainland is still a relatively small territory – and if Rwanda as a nation can make and achieve a commitment to control malaria, an oil rich nation like Equatorial Guinea should be up to the task of helping all its population.

The most recent Global Fund Malaria Grant performance information (April 2009) shows the Equatorial Guinea project performing at the B2 level.  This is at the bottom rung of acceptable performance.  There is mixed achievement on indicators as seen in the chart – IPTp seems better than on Bioku, but not everyone is sleeping under distributed nets. ACT case management training has started but no data are available to show if people have been treated. According to the Global Fund, “The program has faced significant delays due to long procurement process and treatment protocol approval but is now on track as drugs have been delivered.”

The Global Fund project has two more years to go – hopefully all partners – public, private, NGO, etc. – will pull together and help the mainland just as they have been willing to protect their interersts on the island.

The Malaria Atlas Project (MAP) has been working hard over the past several years to assemble what is known – published and unpublished – about the distribution of malaria around the world.  A press release notes that now, “The most detailed map ever created of malaria risk worldwide is published today by an international team of researchers funded by the Wellcome Trust. The Malaria Atlas Project (MAP) will be a powerful tool for helping target malaria control programmes and suggests that elimination of malaria in three-quarters of the world’s at-risk areas might be less difficult than previously thought.”

The Executive Director of the Global Fund has stressed the importance of MAP in helping donors like GFATM measure and count progress of their investments: “We need to increase the information available to us and to our donors to demonstrate that investing in malaria control does indeed reduce the numbers of people at risk worldwide. With this kind of information, we can reassure donors by graphically showing progress and highlight where further investments are most needed.”

While the publication of the 2007 MAP in this month’s PLoS Medicine marks a culmination in efforts to locate Plasmodium falciparum in the world, it is also a baseline for future updating.  The team now wants to map vivax malaria, too. In addition, the team has been publishing findings in over 30 scientific articles since 2004.

A particularly instructive publication concerned comparison of ITN coverage compared with levels of malaria endemicity and poverty. They documented that areas with some of the highest levels of malaria as well as largest burden of disease have some of the lowest levels of net coverage.  Nigeria was a case in point where its large population accounts for 25% of the children at risk in stable transmission areas of Africa and yet its net coverage was projected at 4% for 2007.

Another important finding from the net study was the clear indication that net distribution mechanism affected coverage.  The best coverage was achieved where nets were free, followed by areas with subsidies. The lowest coverage figures were found in areas where nets were made available through the commercial sector.  Such information about distribution strategies and coverage can help national program planners.

The continued success of MAP depends on researchers and program managers in endemic countries.  Data need to be shared on a regular basis so that the malaria maps can be updated and national and international partners can better target their interventions.  Researchers and program managers with up-to-date malaria information are encouraged to share their results with the MAP team at map@zoo.ox.ac.uk.

We know at the global level that malaria currently clusters in countries that are relatively closer to the equator rather than in temperate or colder regions.  A study out of Papua New Guinea (PNG) emphasizes the need to learn about local variations in malaria distribution as an aid to proper planning and intervention.

Meyers and colleagues found that, “malarial infection is significantly and independently associated with lower elevation and greater distance from administrative centre in a rural area in PNG.” They considered that higher elevations would be hillier with less opportunity for water collection, and locations on the outskirts of villagers may be closer to swampy or agricultural lands where mosquito breeding would be greater.

Local geography also plays a role in the distribution of urban malaria. A recent study in Ouagadougou, Burkina Faso found that malaria was “focused in areas which are irregularly or sparsely built-up or near the hydrographic network” such as urban gardens as well as in poorer neighborhoods. The solutions to urban areas are multi-sectoral according to Donnelly et al. : “Urban malaria is uniquely amenable to prevention and control as the existing health, urban planning, agricultural and governance structures present opportunities for collaborative approaches that can include both the community and the substantial private sector.”

The East African Highlands are another example of geographical variations of malaria distribution in a country.  These are areas where malaria is seasonal.  Recent investigation has shown how climate change may actually be changing the seasonal distribution of rain, vector and thus malaria. Deforestation can also create geographical variations in malaria distribution.

Natural and man-made variations in geography within countries and even communities have important implications for the planning, targeting and timing of malaria control activities.  Clinics in certain areas may need more stocks of ACTs. Supplies of drugs, nets and spray should be timed in advance of known seasonal onset of malaria in other areas.  As elimination comes closer to reality this micro-planning for micro-geographical areas will be the only way to keep the disease under control. It will also require a multi-sector approach.