Intermittent preventive therapy or intermittent preventive treatment (IPT) is a public health intervention aimed at treating and preventing malaria episodes in infants (IPTi), children (IPTc), schoolchildren (IPTsc) and pregnant women (IPTp). The intervention builds on two tested malaria control strategies to clear existing parasites (treatment effect seen in mass drug administrations) and to prevent new infections (prophylaxis).[ citation needed ]
IPTi using the antimalarial drug sulfadoxine/pyrimethamine (S/P) was pioneered in Ifakara, Tanzania in 1999. [1] Infants received S/P at ages 3, 6, and 9 months in combination with their routine childhood (EPI) vaccinations. IPTi reduced clinical attacks of malaria by 59% (95% CI, 41%–72%) in Ifakara. Remarkably, protection persisted throughout the second year of life, long after SP had disappeared from circulation. [2] A trial conducted in northern Tanzania using the antimalarial drug amodiaquine instead of S/P was similarly successful. [3] Six subsequent trials showed less encouraging results. [4] [5] [6] [7] [8]
The latest and so far largest IPTi study was an effectiveness study conducted in the South East of Tanzania. [9] A study area of approximately 250x180km2 with a population of about 900,000 people was subdivided into 24 similar clusters. Half of the 23,400 infants, those residing in 12 of 24 randomly selected clusters were invited in 2005 to receive IPTi. Between 47 and 76% of the eligible infants in each of the 12 selected clusters received IPT-SP. In the following year, 2006, the effect of IPTi on malaria and anaemia was assessed in a representative sample of 600 infants. An intention to treat analysis, which includes all eligible infants did not show a statistically significant benefit of IPTi-SP. Parasitaemia prevalence was 31% in the intervention and 38% in the comparison areas (p=0.06). In a ‘per protocol’ analysis, which only included infants who actually received IPTi there was a significant benefit: parasite prevalence was 22%, 19 percentage points lower than comparison children in the control group (p=0.01). This trial showed that IPTi has a protective effect at the individual level but is not effective at the community level. The study had followed up children for two years until 2007 but the findings from the surveillance in 2007 have not been reported.[ citation needed ]
Treating children with S/P and artesunate in Senegal where malaria is highly seasonal repeatedly during the malaria season reduced malaria attacks by 86% (95% CI 80-90)9. [10] A subsequent trial in Mali showed a protective efficacy of 43% [95% CI 29–54%]. [11]
Treating schoolchildren in Kenya with S/P and amodiaquine significantly improved anaemia (RR 0.52, 95% CI 0.29-0.93). [12]
IPTp consists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy – regardless whether or not the woman is infected. The drug is administered under supervision during antenatal care (ANC) visits. Sulfadoxine-pyrimethamine is the drug currently recommended by the WHO because of its safety and efficacy in pregnancy. [13] Several studies have shown the high efficacy of IPTp with SP, compared to placebo or CQ prophylaxis, on placental infection, LBW and/or severe maternal anaemia. [14] [15] [16] [17] [18] [19] [20] [21] [ excessive citations ] More recent findings from Tanzania also suggest that IPTp using S/P has reached the end of its lifecycle. [22] The authors found that the "use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance". As for infants, there is no simple readily available replacement of S/P for malaria in pregnancy. Indeed, the fear of teratogenic effects add a layer of complexity how this intervention will evolve.[ citation needed ]
While some controversial aspects e.g. the drug of choice are shared by all forms of intermittent preventive therapy, the controversy has been reported in greatest detail for IPTi (see also politics below). The reasons which make the large scale introduction of IPTi highly controversial include: [23]
An added theoretical concern is that the widespread use of antimalarial drugs for prophylaxis will add to the already considerable drug pressure and will facilitate the emergence and spread of drug resistance. McGready summarised IPTi as an intervention which uses the wrong drug, probably in the wrong dose in the wrong age group. [25]
The politics of IPTi are well documented and illustrate the working of contemporary international health politics. The promising results of the first two IPTi studies led to the creation of the IPTi Consortium, whose brief is to determine the efficacy, safety, relation of efficacy to drug sensitivity, cost-effectiveness, and acceptability of this intervention. [26] The IPTi Consortium received approximately US$28 million from the Bill & Melinda Gates Foundation (BMGF). A WHO technical advisory group reviewed the evidence relevant for the widespread introduction of IPTi available in 2008, and came to the conclusion that the available evidence was not sufficient to recommend the widespread introduction of IPTi -SP. Program officers of the BMGF as well as scientists funded by the BMGF criticised the WHO conclusions. The criticism from the BMGF in turn triggered a memorandum of the WHO malaria chief Dr. Akira Kochi to the director general of the WHO which was leaked to The New York Times. [27]
Dr. Kochi wrote, although it was less and less straightforward that the health agency should recommend IPTi, the agency's objections were met with intense and aggressive opposition from Gates-backed scientists and the foundation. The W.H.O., he wrote, needs to stand up to such pressures and ensure that the review of evidence is rigorously independent of vested interests.
At the request of Dr. Brandling-Bennett of the BMGF and with funding from the BMGF, the Institute of Medicine (IOM) convened an expert committee to evaluate the evidence concerning IPTi - SP and provide guidance on the value of continued investment in IPTi-SP. The committee was chaired by Myron M. Levine who has been funded and is currently funded by the BMGF. The committee concluded "… that an intervention with results of this magnitude is worthy of further investment as part of a public health strategy to decrease morbidity from malaria infections in infants." [28] The WHO technical expert group responded to the IOM report "WHO is committed to review the available information each year." Dr. Kochi was ultimately replaced by one of the members of the IPTi consortium, Dr. Robert Newman. In March 2010, i.e. after Dr. Kochi had been replaced, the WHO recommended the co-administration of the antimalarial drug sulfadoxine pyrimethamine with routine childhood vaccinations (DTP2, DTP3 and measles immunization) in sub-Saharan Africa. [29] The recommendation applies only for areas with high malaria transmission and low resistance against SP, both measures are not free of controversy and only available for few spots in Africa. With the recent drop of malaria transmission in wide stretches of Africa [30] [31] and a steady increase in SP resistance [32] [33] few malaria control programs will hurry to implement this intervention.
Malaria is a mosquito-borne infectious disease that affects humans and other vertebrates. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.
Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.
Artemisia annua, also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood, is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North America.
Artemisinin and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to Plasmodium falciparum. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her discovery. Artemisinin-based combination therapies (ACTs) are now standard treatment worldwide for P. falciparum malaria as well as malaria due to other species of Plasmodium. Artemisinin is extracted from the plant Artemisia annua a herb employed in Chinese traditional medicine. A precursor compound can be produced using a genetically engineered yeast, which is much more efficient than using the plant.
Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, by mouth, and by rectum.
Artemether/lumefantrine, sold under the trade name Coartem among others, is a combination of the two medications artemether and lumefantrine. It is used to treat malaria caused by Plasmodium falciparum that is not treatable with chloroquine. It is not typically used to prevent malaria. It is taken by mouth.
Artesunate suppositories are used for the treatment of malaria. Artesunate is an antimalarial water-soluble derivative of dihydroartemisinin. Artemisinins are sesquiterpene lactones isolated from Artemisia annua, a Chinese traditional medicine. These suppositories are given rectally due to the risk of death from severe malaria, as described below.
Malaria prophylaxis is the preventive treatment of malaria. Several malaria vaccines are under development.
Amodiaquine (ADQ) is a medication used to treat malaria, including Plasmodium falciparum malaria when uncomplicated. It is recommended to be given with artesunate to reduce the risk of resistance. Due to the risk of rare but serious side effects, it is not generally recommended to prevent malaria. Though, the WHO in 2013 recommended use for seasonal preventive in children at high risk in combination with sulfadoxine and pyrimethamine.
Sulfadoxine is an ultra-long-lasting sulfonamide used in combination with pyrimethamine to treat malaria.
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Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination medication used to treat malaria. It contains sulfadoxine and pyrimethamine. For the treatment of malaria it is typically used along with other antimalarial medication such as artesunate. In areas of Africa with moderate to high rates of malaria, three doses are recommended during the second and third trimester of pregnancy.
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