MALARIA: in pregnancy

The intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) has been a key component of the focused antenatal care package for nearly a decade, reducing the burden of low birthweight attributable to malaria in sub-Saharan Africa. However, SP has lost parasite sensitivity in many sub-Saharan locations during the same period, rendering its beneficial effect in IPTp debatable. Malaria transmission has also declined in some epidemiological settings. There is no evidence to suggest, however, that the risk of malaria in pregnancy without preventive measures has declined in the same locations. Thus, the urgency to identify efficacious drugs and/or new strategies to prevent malaria in pregnancy remains as great as ever. We summarise the results of recently published SP-IPTp studies from areas of high drug resistance and/or low malaria transmission. We also present the evidence for mefloquine and azithromycin-based combinations (ABCs), two leading drug options to replace SP in IPTp. We discuss optimal dosing for ABCs and their likely protection against several sexually transmitted and reproductive tract infections. We also summarise data from a diagnosis-based alternative to IPTp known as the intermittent screening and treatment (IST) for malaria. Clinical and operational research is urgently needed to compare birth outcomes achieved by IPTp with ABCs vs. IST using an efficacious antimalarial therapy



http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2011.02765.x/abstract

MALARIA: mefloquine as a 21st century malaria chemoprophylaxis

Patricia Schlagenhauf , Miriam Adamcova , Loredana Regep , Martin T Schaerer and Hans Georg Rhein
Malaria Journal 2010, Published: 9 December 2010

Background
Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis.

Methods
A literature search to update the status of mefloquine as a malaria chemoprophylaxis.

Results
Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerarability of mefloquine and the use of this medication by groups at high risk of malaria.

Discussion
Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors.

Conclusion
The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline.

http://www.malariajournal.com/content/9/1/357

MALARIA: Malaria in the Military

 Bill Brieger

11 Nov 2010



November 11th is Veteran’s Day in the United States. Over the years soldiers have been vulnerable to malaria. During the U.S. Civil War 150 years ago over 14,000 Union troops are estimated to have died from malaria. While death estimates were not available for the Confederates, it was thought that over 40,000 malaria cases occurred in an 18-month period in the middle of the war.

Today places like Afghanistan and the Horn of Africa pose a malaria threat to troops, so there is malaria prophylaxis for soldiers. Sometimes the prevention itself poses problems. “The Army has dropped Lariam — the drug linked to side effects including suicidal tendencies, anxiety, aggression and paranoia,” and now prefers doxycycline for people who may react to mefloquine.
The military takes malaria seriously now. The Walter Reed Army Institute of Research (WRAIR) puts a priority on malaria research since, “Malaria remains highly relevant to the military because of its prevalence, variety (there are four species that infect humans), debilitating nature, potential lethality, and tendency to become resistant to drugs. No organization in the world has WRAIR’s experience in the complete spectrum of malaria research.”
WRAIR’s “Work on a vaccine is also progressing. Advanced molecular, genetic, and biomedical technologies are now being employed to produce candidate malaria vaccines. Field trials of these candidate pharmaceuticals are an essential part of the program and are underway in Thailand and Kenya.”
The military of all nations are at risk when they serve in malaria endemic areas. For example, a Philippine soldier “succumbed to malaria on 23 October 2008 while serving as a military observer with the U.N. Mission in Sudan.”
Another concern of malaria in the military is the potential for soldiers who contract malaria for spreading it to other countries or bringing it home. It was reported that Soviet soldiers serving in Afghanistan some years ago brought the disease back to republics in the Caucasus and Central Asia. Though this particular spread could be controlled, not all situations may be so fortunate.
Today a variety of injury and mental health problems may overwhelm the effects of malaria on soldiers. Still, soldiers are at risk. For example in 2002, “38 cases of malaria were identifiedin a 725-man Ranger Task Force that deployed to eastern Afghanistan.” Also over a 6-year span the Defense Medical Surveillance System reported 423 cases of malaria including Plasmodium vivax, P. falciparum, P. ovale, and P. malaria. A big challenge is the inability of health systems in non-endemic countries to treat and save lives of soldiers who return home with the disease.
There are basically two lessons from this issue. First malaria control must recognize that soldiers who may not be immune when they enter a malaria endemic war zone are at risk of malaria death. Secondly, as a mobile population soldiers have the potential for reintroducing malaria to areas where it may have been eliminated. War kills people; malaria kills people - when soldiers are infected a double dose of death potentially occurs
http://www.malariafreefuture.org/blog/?p=1080

MALARIA: An Outbreak of Plasmodium falciparum Malaria in U.S. Marines Deployed to Liberia

In 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or presumed Plasmodium falciparum malaria. An outbreak investigation showed that only 19 (45%) used insect repellent, 5 (12%) used permethrin-treated clothing, and none used bed netting. Adherence with weekly mefloquine (MQ) was reported by 23 (55%). However, only 4 (10%) had serum MQ levels high enough to correlate with protection (> 794 ng/mL), and 9 (22%) had evidence of steady-state kinetics (MQ carboxy metabolite/MQ > 3.79). Tablets collected from Marines met USP identity and dissolution specifications for MQ. Testing failed to identify P. falciparum isolates with MQ resistance. This outbreak resulted from under use of personal protective measures and inadequate adherence with chemophrophylaxis. It is essential that all international travelers make malaria prevention measures a priority, especially when embarking to regions of the world with high transmission intensity such as west Africa.

"Good doctors are of no use without good discipline. More than half the battle against disease is not fought by doctors, but by regimental officers. It is they who see that the daily dose of mepacrine (anti-malarial chemoprophylactic drug used in WW II) is taken...if mepacrine was not taken, I sacked the commander. I only had to sack three; by then the rest had got my meaning."
—Lieutenant General William Slim (1891–1970), Burma Campaign, 1943
http://www.ajtmh.org/cgi/content/abstract/83/2/258?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=malaria&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

MALARIA: personal experience and review

To watch children slip into the potentially fatal clutches of malaria is terrifying. It's the speed of the descent from good health to serious illness that is so frightening: at dawn they are fine, by dusk they could be in a coma, from which they might never wake. I know this because several years ago I was there – panic-stricken – watching my then eight-year old son, his mind drowning in delirium and his young body teetering on the brink of collapse.
He begged me to 'Just let me close my eyes for a bit, mum', and, desperate, I pleaded with him to stay awake. His decline took less than six hours. In the end he was fine – it meant an emergency airlift, an admission to hospital where he was administered artemisinin (a drug derived from the plant Artemesia annua) intravenously, and four long recuperative weeks out of school, but he did make a full recovery. We were lucky, luckier than the parents of the estimated 5,000 children that die from malaria every day.
Malaria is the world's biggest killer. It affects almost 500 million people a year and takes the lives of nearly 3 million – mostly in Africa, where a child is estimated to die from the disease every 30 seconds, at an estimated cost to the economy of more than £6bn a year.
Despite its much publicised Roll Back Malaria Partnership, the World Health Organisation has had limited success in 20 years. The only real impact the programme has had on the disease is through the introduction of insecticide-treated nets (ITNs), which are an effective prophylactic, particularly for children, when used correctly (but which remain heavily taxed in much of Africa).
Most of the world's millions of malaria sufferers are still not benefiting from life-saving drugs nearly five years after the WHO urged their widespread use. Since 2001, the UN health agency has recommended countries switch to artemisinin-based combination drugs (or ACTs) to treat malaria, which has become resistant to conventional medicines, like chloroquine.
The majority of sufferers understand very little about the disease or how it is transmitted (by the female mosquito, which must be pregnant, and which only bites between dusk and dawn).
Ronald Ross, a British doctor born in India, discovered it was the mosquito that transmitted malaria. Until then the popular theory was that foul-smelling gases emitted from swampy soils caused the disease – the word 'malaria' comes from the Italian, 'bad air'. The mortality rate at the time – over a million deaths a year – was reduced to less than 10,000 during the 1950s as a direct result of education and the eradication schemes initiated by Ross. Since the 60s, though, the disease has been on the increase – in 1960 only 10% of the world's population was at risk; that figure now stands at over 40%.
Today, as a result of poor vector control, global warming and intercontinental travel, malaria infects one in 10 of the world's population. It is present in over 100 countries (including eastern Europe, Russia and Turkey), visited by more than 125 million tourists every year, up to 30,000 of whom fall ill when they get home. Last year 1,754 Britons contracted malaria abroad – 1,300 of them the deadliest strain, Plasmodium falciparum (or cerebral malaria). Eleven of them died.
Poverty and poor education compound the problem of malaria in third-world countries, elevating mortality rates. Astonishingly, ignorance of the disease – despite the press coverage it receives and the access to world-class medicine – is a factor in first-world infection, too. Most British travellers who were infected with malaria last year admitted to failing to take correctly – or at all – oral malarial prophylaxis when visiting areas where the disease is endemic.
An investigation conducted earlier this year in the UK found that travellers who sought advice from alternative health centres (complaining that drugs prescribed by their GPs made them feel nauseous) were being offered 'dangerous' advice on malaria prevention and given unproven homoeopathic remedies. Conventional drugs prescribed by GPs are a combination of chloroquine and proguanil, mefloquine (Lariam), doxycycline and Malarone.
As a resident in Africa, I questioned my own doctor about the efficacy and side effects of these drugs. He dismissed chloroquine and proguanil as almost useless, since the parasite has been shown – in this region anyway – to have developed significant resistance to the combination. Lariam, he said, can cause serious neurological disturbances in as many as one in 10 people. Doxycycline increases photosensitivity, which means patients must be prepared to stay out of the sun. It can also interfere with the potency of oral contraception. Malarone, the most recent anti-malarial to be registered, is considered both effective and relatively easily tolerated, but expensive.
Without exception, all short-term visitors to a malarious area should seek advice from the experts (which include the London School of Hygiene and Tropical Medicine, the WHO and the Health Protection Agency) on malarial prophylaxis beforehand. The situation, however, is more complicated for expatriates living in endemic areas, partly because of the risk associated with long-term use of chemoprophylaxis and partly because there is limited data available on the sustained use of some drugs.
The Health Protection Agency suggests that 'the risk of serious side effects associated with long-term prophylactic use of chloroquine and proguanil is low. However, anyone who has taken chloroquine regularly for over five years and requires further prophylaxis should be screened twice-yearly for early retinal changes'. Even before these changes become apparent, there could be other intolerable side effects: my husband, for example, is unable to take proguanil (Paludrine) as it gives him appallingly bad mouth ulcers, which render him unable to eat.
Research suggests there is no increased risk of serious side effects with long-term use of mefloquine (Larium), assuming a person can tolerate it in the short term. Experience of doxycycline in long-term use is limited, though the available data is reassuring (however, like mefloquine, it must be avoided during pregnancy). In many parts of the world, oral prophylaxis is not a guaranteed form of protection; Plasmodium falciparum is increasingly resistant to various antimalarial drugs (indeed my son was on a chloraquine/proguanil combination when he contracted this particularly virulent strain of the disease). As the WHO warns, no antimalarial prophylactic regimen gives complete protection.
Those travelling to malarious areas for extended periods of time (over six months) – or living there (particularly in the case of women, who may become pregnant, and young children) – need to balance the risk of infection against the benefits and side effects of oral prophylaxis; sometimes taking a pill daily gives a false sense of security and might result in laziness when it comes to other prophylactic measures – sleeping under nets, for example, spraying rooms or burning mosquito coils at night.
http://www.guardian.co.uk/money/2008/mar/19/expat-finance-malaria-prevention