In the ten years since its initiation, the international effort to eliminate lymphatic filariasis (LF) has made a large impact towards ridding the world of one of its most debilitating diseases. A new analysis finds that the LF elimination programme has prevented 6.6 million children from acquiring LF and stopped another 9.5 million people already infected with the disease from progressing to more debilitating stages. These efforts are the result of the most rapid scale-up of a drug administration programme in public health history, delivering what the study calls a “best buy in public health”. The paper assesses the impact of the World Health Organization-sponsored Global Programme to Eliminate Lymphatic Filariasis. These data illustrate that with the right partnerships, it is possible to make an extraordinary impact on the health of hundreds of millions of people at minimal cost. Workers are on track to accomplish our goal of elimination by 2020. When they do, this programme will be a leading case study for how to scale up disease elimination programmes globally.
Lymphatic filariasis, often called elephantiasis, is a parasitic infection spread by mosquitoes that causes grotesque, painful swelling of the limbs, breasts, and genitals. Considered a neglected tropical disease, LF almost exclusively affects the world’s poorest people. Approximately one-fifth of the world’s population (1.3 billion people) is at risk of contracting LF, and approximately 120 million people in 83 countries are currently infected. The Global Programme to Eliminate LF has already become the most rapidly scaled-up drug administration programme in public health history, and is on track to becoming the largest such programme in history. The new study found that since drug administrations began in 2000, the programme has administered more than 1.9 billion treatments to over 570 million people in 48 of the 83 countries with endemic LF. The LF elimination treatment programme utilises a combination of two anti-parasitic drugs, administered once yearly to everyone in an at-risk area. When given for a minimum of five consecutive years, these drugs have proven to effectively stop transmission of LF. The drugs used to eliminate LF are the same medications used to treat a number of intestinal worms and parasitic skin diseases, which infect hundreds of millions of people in developing countries and are major contributors to malnutrition, disability, delayed development, and problems during pregnancy.
The benefits of this programme go far beyond simply preventing LF infections. Because of the LF programme, at least 56.6 million children and 44.5 million women of childbearing age have been treated for intestinal worms, most multiple times. The drugs have also treated millions more in Africa for skin diseases. These data confirm what some public health officials have long asserted: that the LF programme is a “best buy” in public health, providing benefits that far outweigh its costs. The total cost per patient over the first eight years of the programme is estimated to be less than US $0.50. This low cost is made possible in part by the donation of albendazole and Mectizan from the programme’s two key pharmaceutical partners, GlaxoSmithKline and Merck & Co., Inc. The cost-efficiency combined with the programme’s achievements has prompted officials to call for the development of a dedicated fund for the treatment and elimination of other neglected tropical diseases. Future public-private partnerships will look to the global LF elimination effort as a standout example of how groups can come together to solve a major public health issue. We must take the lessons we have learned from the LF model and apply them toward the treatment and elimination of other neglected tropical diseases.
The Global Programme to Eliminate Lymphatic Filariasis: Health Impact after 8 Years. 2008 PLoS Negl Trop Dis 2(10): e317
In its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) achieved an unprecedentedly rapid scale-up. 1.9 billion treatments with anti-filarial drugs (albendazole, ivermectin, and diethylcarbamazine) were provided via yearly mass drug administration (MDA) to a minimum of 570 million individuals living in 48 of the 83 initially identified LF-endemic countries. To assess the health impact that this massive global effort has had, we analyzed the benefits accrued first from preventing or stopping the progression of LF disease, and then from the broader anti-parasite effects (‘beyond-LF’ benefits) attributable to the use of albendazole and ivermectin. Projections were based on demographic and disease prevalence data from publications of the Population Reference Bureau, The World Bank, and the World Health Organization. Between 2000 and 2007, the GPELF prevented LF disease in an estimated 6.6 million newborns who would otherwise have acquired LF, thus averting in their lifetimes nearly 1.4 million cases of hydrocele, 800,000 cases of lymphedema and 4.4 million cases of subclinical disease. Similarly, 9.5 million individuals – previously infected but without overt manifestations of disease – were protected from developing hydrocele (6.0 million) or lymphedema (3.5 million). These LF-related benefits, by themselves, translate into 32 million DALYs (Disability Adjusted Life Years) averted. Ancillary, ‘beyond-LF’ benefits from the 1.9 billion treatments delivered by the GPELF were also enormous, especially because of the 310 million treatments to the children and women of childbearing age who received albendazole with/without ivermectin (effectively treating intestinal helminths, onchocerciasis, lice, scabies, and other conditions). These benefits can be described but remain difficult to quantify, largely because of the poorly defined epidemiology of these latter infections. The GPELF has earlier been described as a best buy in global health; this present tally of attributable health benefits from its first 8 years strengthens this notion considerably.
According to a new analysis, neglected tropical diseases (NTDs) as a group may have surpassed HIV/AIDS, tuberculosis and malaria as the most prevalent infectious diseases in Latin America and the Caribbean. The work found that NTDs are the most common infections of approximately 200 million of the poorest people in the region. They include tens of millions of cases of intestinal worm infections, and almost 10 million cases of Chagas disease, as well as schistosomiasis, trachoma, dengue fever, leishmaniasis, lymphatic filariasis (LF), and onchocerciasis. NTDs produce extreme poverty by adversely impacting child development, pregnancy outcomes and worker productivity. In some cases in Latin America and the Caribbean, NTDs also represent a living legacy of slavery, because they were first introduced into the region through the global slave trade, and even today they predominantly affect people of African descent and indigenous groups, as well as other vulnerable groups such as women and children.
In the coming years, schistosomiasis transmission could be eliminated in the Caribbean, and that transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America and the Caribbean with proven successful, cost effective and low-cost treatments. The most burdensome NTDs, such as Chagas disease, intestinal worm infections, and schistosomiasis may first require scale-up of existing resources and/or the development of new tools in order to achieve wider control and/or elimination. Ultimately, successful wide-scale efforts for NTD elimination will require an inter-sectoral approach that bridges public health with social services and environmental interventions.
Neglected diseases impose a huge burden on developing countries, constituting a serious obstacle for socioeconomic development and quality of life. They mostly affect people living either in shantytowns, indigenous communities or poor rural and agricultural areas. Last week, UK government officials announced that they will be contributing £50 million over the next five years toward the control and elimination of NTDs, including Guinea worm. In addition, the World Health Organziation announced that in 2007 alone, 546 million of the world’s poorest people received treatment for lymphatic filariasis at a cost of 10 cents per person, enabling them to live healthier more productive lives. After rainfall-induced disasters like Hurricane Ike, respiratory and intestinal infections usually increase and there is increased risk of breeding of the mosquito that transmits lymphatic filarisis in Haiti. While around three million people will be treated in Haiti in 2008 for lymphatic filariasis, additional resources are needed to step up and maintain treatment coverage in Haiti with its population of 9.5 million people, particularly in the wake of the Hurricane.
Between a quarter and a third of pregnant women in sub-Saharan Africa, almost 7 million, are infected with hookworms and at increased risk of developing anaemia. Hookworms are parasitic worms which live in the intestine and can cause anaemia (lower than normal number of red blood cells in the blood). Their importance in causing anaemia during pregnancy has been poorly understood, and this has hampered effective lobbying for the inclusion of deworming drugs in maternal health care packages. By carrying out a systematic search of medical databases, reference lists, and unpublished data, the team was able to compare levels of haemoglobin (the oxygen-carrying part of red blood cells) according to the intensity of hookworm infection among the women studied. They found that increasing intensity of infection was associated with lower levels of haemoglobin. The authors estimate that 37.7 million women of reproductive age and 6.9 million pregnant women in sub-Saharan Africa were infected with hookworm in 2005, and were therefore at risk of anaemia. In many developing countries it is policy that pregnant women receive deworming treatment, but in practice coverage rates are often unacceptably low.
Hookworm-Related Anaemia among Pregnant Women: A Systematic Review. 2008 PLoS Negl Trop Dis 2(9): e291
Hookworm infection is among the major causes of anaemia in poor communities, but its importance in causing maternal anaemia is poorly understood, and this has hampered effective lobbying for the inclusion of anthelmintic treatment in maternal health packages. We sought to review existing evidence on the role of hookworm as a risk factor for anaemia among pregnant women. We also estimate the number of hookworm infections in pregnant women in sub-Saharan Africa (SSA). Structured searches using MEDLINE and EMBASE as well as manual searches of reference lists were conducted, and unpublished data were obtained by contacting authors. Papers were independently reviewed by two authors, and relevant data were extracted. We compared haemoglobin concentration (Hb) according to intensity of hookworm infection and calculated standardised mean differences and 95% confidence intervals. To estimate the number of pregnant women, we used population surfaces and a spatial model of hookworm prevalence. One hundred and five reports were screened and 19 were eligible for inclusion: 13 cross-sectional studies, 2 randomised controlled trials, 2 non-randomised treatment trials and 2 observational studies. Comparing uninfected women and women lightly (1 1,999 eggs/gram [epg]) infected with hookworm, the standardised mean difference (SMD) was 0.24 (95% CI: 0.36 to 0.13). The SMD between women heavily (4000+ epg) infected and those lightly infected was 0.57 (95% CI: 0.87 to 0.26). All identified intervention studies showed a benefit of deworming for maternal or child health, but since a variety of outcomes measures were employed, quantitative evaluation was not possible. We estimate that 37.7 million women of reproductive age in SSA are infected with hookworm in 2005 and that approximately 6.9 million pregnant women are infected. Evidence indicates that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women in poor countries. There are insufficient data to quantify the benefits of deworming, and further studies are warranted. Given that between a quarter and a third of pregnant women in SSA are infected with hookworm and at risk of preventable hookworm-related anaemia, efforts should be made to increase the coverage of anthelmintic treatment among pregnant women.
Trichomonas vaginalis is a flagellated protozoan parasite, 10-30 µm in diameter, and is responsible for one of the most widespread sexually transmitted diseases worldwide, trichomoniasis or “trich”. The WHO has estimated that 180 million infections are acquired annually worldwide. The main signs of a Trichomonas infection in women are abdominal pain, itching, and presence of a foul-smelling discharge with abundant leukocytes, while in men the infection is mostly asymptomatic, although it can sometimes lead to urethritis, prostatitis, and epididymitis. Infection with this organism is also associated with severe complications, such as infertility and enhanced predisposition to cervical tumours.
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Diagnosis depends on finding trophozoites in secretions of the genital tract from men or women. In cases where the numbers of organisms are very low, the trophozoites can be cultured to increase their numbers. There is no cyst in the parasite life cycle, so transmission occurs via the trophozoite stage. These motile cells have four flagella (visible in this video if you look carefully) and single nucleus. There is also a median rod called the axostyle which is characteristic of the trichomonads. However, this is not clearly visible without staining the cells.
The pathogenesis of Trichomonas infections occurs through cytopathogenicity of the organism for vaginal epithelial cells. Adhesion of the parasite to the target cell is essential for the maintenance of infection and for cytopathogenicity. Flattened, adherent forms can be seen in the last two clips in this video.
People infected with schistosomes, and possibly other parasitic worm infections, may be more likely to become infected with HIV than persons without worm infections, according to a new study. Researchers at the U.S. Centers for Disease Control and Prevention and the Dana-Farber Cancer Institute and Harvard Medical School found that the infectious dose of an HIV-like virus necessary to infect rhesus macaques was 17-fold lower in animals with acute schistosomiasis than in controls. The study represents a novel in vivo demonstration that parasitic worms increase a host’s susceptibility to becoming infected with an AIDS-causing virus. The macaques co-infected with Schistosoma mansoni also demonstrated higher peak viral loads and higher memory cell concentrations of virus, both predictors of more rapid progression to AIDS. These findings are consistent with the hypothesis that persons living in areas highly endemic for parasitic worms may also have a higher risk of acquiring HIV/AIDS. Previous studies by this and other research groups have demonstrated that presence of schistosome infections increases viral replication in animal or human hosts with established immunodeficiency virus infections. The earlier findings, combined with the increased susceptibility to AIDS virus transmission shown in this study, may have profound public health implications for areas of the world where both parasitic worms and HIV-1 are endemic.
Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure. PLoS Negl Trop Dis 2(7): e265
Individuals living in sub-Saharan Africa represent 10% of the world’s population but almost 2/3 of all HIV-1/ AIDS cases. The disproportionate HIV-1 infection rates in this region may be linked to helminthic parasite infections that affect many individuals in the developing world. However, the hypothesis that parasite infection increases an individual’s susceptibility to HIV-1 has never been prospectively tested in a relevant in vivo model. We measured whether pre-existing infection of rhesus monkeys with a parasitic worm would facilitate systemic infection after mucosal AIDS virus exposure. Two groups of animals, one consisting of normal monkeys and the other harboring Schistosoma mansoni, were challenged intrarectally with decreasing doses of R5-tropic clade C simian-human immunodeficiency virus (SHIV-C). Systemic infection occurred in parasitized monkeys at viral doses that remained sub-infectious in normal hosts. In fact, the 50% animal infectious (AID50) SHIV-C dose was 17-fold lower in parasitized animals compared to controls (P,0.001). Coinfected animals also had significantly higher peak viral RNA loads than controls (P,0.001), as well as increased viral replication in CD4+ central memory cells (P = 0.03). Our data provide the first direct evidence that acute schistosomiasis significantly increases the risk of de novo AIDS virus acquisition, and the magnitude of the effect suggests that control of helminth infections may be a useful public health intervention to help decrease the spread of HIV-1.
Resistance to ciprofloxacin, a member of one of the most commonly used groups of antibiotics in the world, has been discovered by a team of Canadian researchers among people in remote South American villages who are believed to have never taken this medication. The researchers found high levels of ciprofloxacin resistance in Escherichia coli in Amerindians from the Guyanese rainforest. These individuals are reported as never having received treatment with ciprofloxacin or related fluoroquinolone antibiotics. The Amerindians had however received frequent treatment for malaria (which is a eukaryotic parasite and not a bacterium) with chloroquine. Chloroquine is used widely around the world to combat malaria, and it also is a close chemical cousin of the fluoroquinolones. Fluoroquinolones began widespread use in the late 1980s and now are among the most commonly used antibiotics in North America and Europe. Because the bacteria carried by the Guyanese Amerindians were resistant to ciprofloxacin, the researchers suggest that it is possible that exposure to chloroquine may make the bacteria that people carry in their intestines resistant to fluoroquinolones – a theory that, if corroborated by further research, could have important public health implications in developing countries and in the developed world. They also found resistance in many other species of bacteria – including Salmonella – that are found in rectal swabs. This means that chloroquine use for malaria may make the fluoroquinolones less effective for many common tropical diseases such as typhoid fever, diarrheal illnesses, and possibly also tuberculosis and pneumonia in the developing world.
Plans are being considered by major global health-promotion organizations to launch a campaign of widespread use in Africa and South America of a new anti-malarial treatment regimen called Artemesinin combination therapy (ACT). ACT usually includes quinoline drugs similar to chloroquine. These drugs are closely related to both chloroquine and fluoroquinolones. The researchers plan to carry out further studies to identify whether some quinolines may be less likely to induce quinolone resistance than others, and thus may be safer for malaria control programs. Dr Mike Silverman and 19 other volunteer health care professionals traveled by airplane from Bartica, a town that serves as the gateway to the interior of the Guyanese rainforest, to a handful of remote villages as part of annual humanitarian medical missions between 2002 and 2005. They took rectal swabs from 535 people in Bartica and the remote villages. They also asked the local inhabitants about whether they had ever been exposed to chloroquine or fluoroquinolones, and took water samples. They took the samples home and analyzed them. The team found that 5.4% of the rectal-swab samples contained ciprofloxacin-resistant Escherichia coli, with a 4.8% resistance rate among the remote-village samples. This is a very high rate – particularly when compared to the 4% rate found in a recent study of ciprofloxacin resistance in American intensive care units where fluroquinolones are very intensively used. It is also particularly remarkable because fluoroquinolones had never been available in these communities.
The ciprofloxacin-resistant E. coli samples were also all found to be highly resistant to chloroquine, and to have characteristics that would confer resistance to all fluoroquinolones including the newer drugs levofloxacin and moxifloxacin. Furthermore, the team found that one of the water samples they took in 2004 contained ciprofloxacin-resistant E. coli and another contained a small amount of chloroquine, probably from human waste contamination. Because of a widespread malaria outbreak in rural Guyana in late 2002, 30% of the villagers tested by the Canadian team in 2003 said they had been given chloroquine within the past six months, and in 2005 86% said they had used chloroquine within the past two years. The rates of chloroquine use may in fact have been much higher the investigators believe. This is because patient reports are not always reliable, and because of the very extensive treatment with chloroquine during the late-2002 malaria epidemic. The data also showed that community-wide fluoroquinolone resistance rose dramatically shortly after the malaria outbreak, further suggesting a link between chloroquine use for malaria and bacterial resistance to fluoroquinolones. Together, these data suggest that we must focus our efforts on prevention of malaria using mosquito-control measures such as bednets and by developing vaccines. For the short term, however, we still will have no choice but to use these lifesaving antimalarial drugs. However we need to investigate which of the antimalarials can be used in the future with the least impact on bacterial drug resistance.
Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America. PLoS ONE 3(7): e2727
Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant Gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations. In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p 0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.
An international research team has found the first clear example of how climate extremes, such as increased frequency of droughts and floods expected with global warming, can create conditions in which diseases that are tolerated one at a time may converge and cause mass die-offs of livestock or wildlife. The study suggests that extreme climatic conditions are capable of altering normal host-pathogen relationships and causing a “perfect storm” of multiple infectious outbreaks that could trigger epidemics with catastrophic mortality. Led by scientists at the University of California, Davis, the University of Illinois, and the University of Minnesota, the research team examined outbreaks of canine distemper virus (CDV) in 1994 and 2001 that resulted in unusually high mortality of lions of Tanzania’s Serengeti National Park and Ngorongoro Crater. CDV cycles periodically within these ecosystems; numerous epidemics have occurred without decreasing lion populations. But the virus outbreaks of 1994 and 2001 were both preceded by extreme drought conditions, which led to debilitated populations of Cape buffalo, a major prey of lions. After the rains returned, the buffalo suffered heavy tick infestations, resulting in high levels of a tick-borne blood parasite in the lion population. (The parasites are normally present in lions at harmless levels.) The canine distemper virus further suppressed the lions’ immunity, which was already challenged by the high level of blood parasites. This allowed the tick-borne disease to reach fatally high levels, leading to mass die-offs of lions. In 1994, the number of lions in the Serengeti study area dropped by over 35 percent after the double infection. Similar losses occurred in the Crater die-off in 2001. Lion populations recovered quickly – within years after each event, but most climate change models predict increasing frequency of droughts in East Africa. The study illustrates how ecological factors can produce unprecedented mortality events and suggests that co-infections may lie at the heart of many of the most serious die-offs in nature.
Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions. PLoS ONE 2008 3(6): e2545
Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five “silent” CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative realtime PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts.
Antigenic variation is one of the most elegant systems that have evolved to evade host immune defenses. The surface of Trypanosoma brucei, a unicellular parasite that lives in the bloodstream of its mammalian host, is coated with glycoprotein (VSGs) molecules. To evade elimination by the immune system, this parasite replaces its coat with one tailored from another glycoprotein variant. Even though there are hundreds of VSG genes in the genome, this process, called antigenic variation, works because all are silenced except for the one that encodes the current coat. In this week’s issue of PLoS Biology, new research shows show that the chromatin modifying enzyme DOT1B helps to epigenetically regulate the number of VSGs each parasite can have at a time and how fast each parasite can switch from one coat to another. Post-transcriptional histone modifications play important roles in the regulation of chromatin structure and gene expression. Unlike acetylation, which is in general associated with transcription activation, histone methylation can activate or repress transcription depending upon the genomic location and the position of the modified amino acid in the histone chain. In cells lacking DOT1B, silent VSG genes become partially active and the switch from one VSG to another slows down, allowing two different VSGs to appear on the surface of an individual parasite at the same time. This study reveals the importance of epigenetics in regulating VSG genes and provide new insights toward the understanding of this unique survival device.
A histone methyltransferase modulates antigenic variation in African trypanosomes. 2008 PLoS Biol 6(7): e161
To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evasion relies on two important features: exposing a single type of VSG at the cell surface and periodically and very rapidly switching the expressed VSG. Transcriptional switching between resident telomeric VSG genes does not involve DNA rearrangements, and regulation is probably epigenetic. The histone methyltransferase DOT1B is a nonessential protein that trimethylates lysine 76 of histone H3 in Trypanosoma brucei. Here we report that transcriptionally silent telomeric VSGs become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected. DOT1B also is involved in the kinetics of VSG switching: in DDOT1B cells, the transcriptional switch is so slow that cells expressing two VSGs persist for several weeks, indicating that monoallelic transcription is compromised. We conclude that DOT1B is required to maintain strict VSG silencing and to ensure rapid transcriptional VSG switching, demonstrating that epigenetics plays an important role in regulating antigenic variation in T. brucei.
Leishmaniasis is an antropozoonotic disease with a wide range of clinical manifestations. In humans, signs of disease vary from skin and mucosal ulcers to enlargement of internal organs such as the liver and spleen. The unicellular parasite Leishmania amazonensis is able to infect humans and cause localized or diffuse skin lesions. The treatment for this disease is difficult, as it requires prolonged and painful applications of toxic drugs that are poorly tolerated. Therefore, a key area in leishmaniasis research is the study of new therapeutic schemes and less toxic drugs.
Researchers from the University of Sao Paulo, Brazil, have shown the efficacy of tamoxifen against L. amazonensis, one of the species that causes cutaneous leishmaniasis in South America. The paper explains how tamoxifen, a medication widely used in the treatment and prevention of breast cancer, fights the parasitic disease in experimentally infected mice. Unicellular parasites of Leishmania genus are the causative agents of leishmaniasis. Treatment of leishmaniasis requires the administration of toxic and poorly tolerated drugs. Having previously demonstrated that tamoxifen was active against parasites in vitro, the authors now show its efficacy in a rodent model of infection with L. amazonensis. The Brazilian group observed that infected mice treated with tamoxifen for two weeks showed a significant reduction in parasite burden. Researchers also detected a notable delay in the development of skin ulcers, a typical symptom of the disease caused by L. amazonensis. The promising results presented in this study, coupled with the fact that tamoxifen’s safety and pharmacological profiles in humans are well established (the compound that has been in clinical use since the 1970s for the treatment of breast cancer), point to a new alternative in the treatment of leishmaniasis. Further trials will be necessary in other experimental models of infection before the drug is tested in humans.
Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice. PLoS Negl Trop Dis 2008 2(6): e249
Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America. Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.
In the ten years since its initiation, the international effort to eliminate lymphatic filariasis (LF) has made a large impact towards ridding the world of one of its most debilitating diseases. A new analysis finds that the LF elimination programme has prevented 6.6 million children from acquiring LF and stopped another 9.5 million people already infected with the disease from progressing to more debilitating stages. These efforts are the result of the most rapid scale-up of a drug administration programme in public health history, delivering what the study calls a “best buy in public health”. The paper assesses the impact of the World Health Organization-sponsored Global Programme to Eliminate Lymphatic Filariasis. These data illustrate that with the right partnerships, it is possible to make an extraordinary impact on the health of hundreds of millions of people at minimal cost. Workers are on track to accomplish our goal of elimination by 2020. When they do, this programme will be a leading case study for how to scale up disease elimination programmes globally.
