Gamble CL, Ekwaru JP, ter Kuile FO
In endemic areas, malaria in pregnancy is a major public health problem. It contributes to severe anaemia in the mother and low birth weight for babies, which are associated with poor infant health and early infant death. Also the unborn child and the pregnant woman may die from malaria in pregnancy. Protection with insecticide-treated bednets (ITNs) during pregnancy is widely advocated, but evidence of their benefit has been inconsistent. This review found five trials of ITNs in pregnant women. The four trials in sub-Saharan Africa compared ITNs with no nets and showed a benefit from ITNs in terms of fewer malaria infections, low birthweight babies, and fewer babies died before delivery. The effects on severe anaemia in the mothers were inconclusive. The one trial from Asia compared ITNs with untreated nets and showed a beneficial effect on anaemia in women and fewer babies died before delivery, but it had no impact on other outcomes. ITNs have been shown to be beneficial and should be included in strategies to try to reduce the adverse effects of malaria in pregnant women in endemic areas of the world.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2009 Issue 1, Copyright © 2009 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Gamble C, Ekwaru JP, ter Kuile FO. Insecticide-treated nets for preventing malaria in pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003755. DOI: 10.1002/14651858.CD003755.pub2.
Malaria in pregnancy is associated with adverse consequences for mother and fetus. Protection with insecticide-treated nets (ITNs) during pregnancy is widely advocated, but evidence of their benefit has been inconsistent.
To compare the impact of ITNs with no nets or untreated nets on preventing malaria in pregnancy.
We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to January 2006), EMBASE (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted researchers working in the field.
Individual and cluster randomized controlled trials of ITNs in pregnant women.
Three authors independently assessed the risk of bias in the trials and extracted data. Data were combined using the generic inverse variance method.
Six randomized controlled trials were identified, five of which met the inclusion criteria: four trials from sub-Saharan Africa compared ITNs with no nets, and one trial from Asia compared ITNs with untreated nets. Two trials randomized individual women and three trials randomized communities. In Africa, ITNs, compared with no nets, reduced placental malaria in all pregnancies (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.63 to 0.98). They also reduced low birthweight (RR 0.77, 95% CI 0.61 to 0.98) and fetal loss in the first to fourth pregnancy (RR 0.67, 95% CI 0.47 to 0.97), but not in women with more than four previous pregnancies. For anaemia and clinical malaria, results tended to favour ITNs, but the effects were not significant. In Thailand, one trial randomizing individuals to ITNs or untreated nets showed a significant reduction in anaemia and fetal loss in all pregnancies but not for clinical malaria or low birthweight.
ITNs have a beneficial impact on pregnancy outcome in malaria-endemic regions of Africa when used by communities or by individual women. No further trials of ITNs in pregnancy are required in sub-Saharan Africa. Further evaluation of the potential impact of ITNs is required in areas with less intense and Plasmodium vivax transmission in Asia and Latin America.
2) CENTENARY OF CHAGAS' DISCOVERY OF CHAGAS DISEASE
It was in April 1909 that the Brazilian researcher Carlos Chagas, aged 29, made discoveries of the yet unidentified Chagas' disease in a two-year-old girl. He named the causative agent of the disease Trypanosoma cruzei, after Oswaldo Cruz. The homepage of the Oswaldo Cruz Institute (see full text below) tells the story.
‘After several tests in human beings and animals, he found a cat with parasite in the bloodstream. Two or three weeks later (April 14, 1909), he was asked to investigate on the possibility of an acute malarial episode in a 2 years old girl (Berenice) living in the same house where this feline was found. He had previously examined this girl and no parasite could be observed before. However, several parasites could be detected this time.
Therefore, he suggested the possibility of an acute phase of a disease yet to be described. Several examinations showed the disappearance of flagellates in the bloodstream as the symptoms vanished, thus raising the possibility of a chronic phase of this new disease. On April 23rd, Oswaldo Cruz announced Carlos Chagas' discovery at a session of the Brazilian National Academy of Medicine.’
For more detail on this extraordinary man, go to the biography at http://en.wikipedia.org/wiki/Carlos_Chagas
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By: Silvano Wendel and Zigman Brener (in: Chagas Disease - American Trypanosomiasis: its impact on transfusion and clinical medicine. S. Wendel, Z. Brener, M.E. Camargo, A. Rassi (Edt.). ISBT BRAZIL'92, SAO PAULO,
Carlos Justiniano Ribeiro Chagas was born on July 9th , 1879 in Oliveira, in a coffee farm in the State of Minas Gerais. His father (Jose Justiniano das Chagas) died when he was only 4 years old, leaving his mother (Mariana Candida Chagas) the difficult task to raise four young children.
In 1896, under the influence of his uncle (Carlos Ribeiro de Castro) he decided to study medicine in Rio de Janeiro. In 1900 he became assistant to Prof. Francisco Fajardo, dedicating his initial efforts to the control of malaria. In fact, his mentor convinced him to focus his graduating thesis on "Hematological Aspects of Malaria". He was also responsible for introducing Carlos Chagas to Oswaldo Cruz, who, at the time was in charge to develop his great work on Malaria and Yellow Fever eradication in Rio de Janeiro. These diseases were responsible for a great devastation of the local population.
Furthermore, many ships from Europe and North America refused to dock in Rio de Janeiro harbor, jeopardizing the financial economy of the Brazilian capital at the turn of the century. Oswaldo Cruz became the founder of Manguinhos Institute (now named after his founder: Instituto Oswaldo Cruz), heading to major contributions for the development of Preventive and Sanitary Medicine in Brazil.
Despite a strong friendship between Carlos Chagas and Oswaldo Cruz, Chagas decided not to follow his friend to Manguinhos. After a short working period as a general practitioner in Jurujuba, he was asked to eradicate the malaria epidemic which was devastating the city of Santos (1905). There, the Santos Docks Company was building port facilities to server the city of São Paulo, especially for coffee exportation. Although no long-lasting insecticides
(e.g.DDT) were available at that time, Chagas focused his efforts in destroying anophelines mosquitoes inside homes; this became the first well succeeded Campaign for malaria eradication achieved in Brazil. He, then, returned to Rio de Janeiro, in order to fight malaria along the Xerem River banks, in the outskirts of Rio de Janeiro. He became a member of the Manguinhos Institute, where he joined famous foreign microbiologists such as Prowazeck and Max Hartmann.
In 1908, the Brazilian Government was trying to connect Belem (in the Amazon Basin) to Rio de Janeiro, but construction had to be halted in Minas Gerais due to a severe malaria attack suffered by the railroad workers, near the Velhas River Valley. Oswaldo Cruz commissioned Carlos Chagas and Belisario Pena to that region, where they settled in Lassance their headquarters inside a railroad car, which served as consultation room, laboratory and sleeping quarters.
After one year of exhausting work, Carlos Chagas was advised by a railroad engineer, Cantarino Mota and by Belisario Pena about the existence of a hematophagus bugs which, due to their typical behavior of biting human beings (while sleeping at night) on the uncovered face, were known as "barbeiros" (barbers) or "kissing bugs". As C. Chagas candidly described "We spent more than one year in that area, without having any notice on the existence of a hematophagic insect in the huts, currently known as barbeiro, chupão or chupança". What would have happened if Chagas had left this region after the malaria eradication without meeting with Cantarino Mota, could only be predicted by the Gods of Science.
Chagas became interested in researching the possibility of this bug transmitting any kind of parasite to human or other vertebrates. Soon he detected flagellates resembling crithidiae in the hindgut of this bug. Intrigued by the possibility that this parasite could represent an evaluative stage of Trypanosoma minasense, which he had previously described in 1908, infesting marmosets (Callithrix), he sent some bugs to Manguinhos to be fed in primates free of infection. After some weeks, the same flagellates were recovered in the blood stream of those animals and he recognized a new species, different from T. minasense or "any other species of the same genus". The parasite was first named as Schyzotrypanum cruzi (in honor of Oswaldo Cruz); subsequently it was renamed as Trypanosoma cruzi.
Carlos Chagas returned to Lassance looking for the presence of vertebrate hosts of this newly discovered parasite. After several tests in human beings and animals, he found a cat with parasite in the bloodstream. Two or three weeks later (April 14, 1909), he was asked to investigate on the possibility of an acute malarial episode in a 2 years old girl (Berenice) living in the same house where this feline was found. He had previously examined this girl and no parasite could be observed before. However, several parasites could be detected this time. Therefore, he suggested the possibility of an acute phase of a disease yet to be described. Several examinations showed the disappearance of flagellates in the bloodstream as the symptoms vanished, thus raising the possibility of a chronic phase of this new disease. On April 23rd, Oswaldo Cruz announced Carlos Chagas' discovery at a session of the Brazilian National Academy of Medicine. His findings were also reported as previous notes in "Brazil Medico" and "Archive für Schiffs und Tropen Hygiene". In August he published in the first volume of "Memórias do Instituto Oswaldo Cruz" his classical paper about a "New Human Trypanosomiasis". In this paper he described the human infection, parasite
morphology in bloodstream, cycle in the digestive trait of invertebrate vector, cultivation in agar-blood and transmission to vertebrates of flagellates from infected triatomines. Although some slight errors were committed in relation to the parasite life cycle, the great contribution of this work clearly surpassed some minor mistakes.
After these first observations, he returned to endemic zones to study the clinical stages of this disease. he described the effects on heart and gastrointestinal systems. Furthermore, the neurological manifestations were also observed by the findings of meningoencephalitis in a mortal case.
Additional studies showed that the initial findings on the thyroid gland could not be corroborates by clinical facts and that all the wide range of neurological cases observed in the region could not be explained by this disease. He described the main cardiac disturbances such as those related to the degeneration of the Hiss bundle, premature beats, atrio-ventricular blockade, Stoke-Adams syndrome, bradicardia and congestive heart failure.
In 1911, he presented at the National Academy of Medicine (Rio de Janeiro) the first case of a congenital case and in 1912 the possibility of a sylvatic cycle in armadillos.
In 1916, he firstly raised that the digestive system could also be involved, especially the related to megaesophagus and dysphagia ("Mal do Engasgo" or "Swallow disease"), which had been regionally known for over a hundred years.
The genius of Carlos Chagas enabled him to describe, when he was only 29 years old, the agent, vectors, clinical signs in human beings, animals and the existence of animal reservoirs of a new disease which was now known as Chagas disease (a name suggested by Miguel Couto, one of his former teachers) or American Trypanosomiasis. Additionally, he influenced other fellow researchers in Manguinhos. Gaspar Vianna, described in 1911 the intracellular cycle (in a necropsied child who died in the acute phase) as "successive binary division as leishmanias with subsequent transformation to trypanosomes inside the cells and the evasion of this parasite to other cells". Arthur Neiva became very interested to study the insects and soon he became the best specialist in triatomines of his time. Also, Guerreiro and Machado introduced the method of Bordet and Gengou (Complement Fixation) for serological diagnosis.
Chagas was declared "Extraordinary Member" of Brazilian Academy of Medicine and also received the Schaudinn Prize, which was awarded every four years to the best work in Parasitology and Tropical Medicine in the world. He was also conceded honorary degrees from the Universities of Buenos Aires, Lima, Harvard, Brussels, Hamburg, Paris and memberships in several medical societies. Additionally, he was granted the Great Prize of the Pasteur Centenary Commemorative Exposition in Strasbourg (1922).
Chagas was also commissioned to control malaria in the Amazon, a task which clearly had a strong influence in his life when developing Preventive Medicine in Brazil.
After the death of Oswaldo Cruz in 1917, he replaced him as director of the Manguinhos Institute, a position he held until his death in 1934 , with the difficult task of controlling the Spanish Fever in Rio de Janeiro. He died on November 8th, 1934 at the age of 55. His lifelong work was followed by several scientists in the Manguinhos Institute.
His great success naturally provoked some opposition. In 1916, during the 1st Panamerican Congress in Buenos Aires (Argentina), Krause, one of the most prominent German microbiologists clearly denied his findings, since he was unable to find cases of Chagas disease in areas such as the Argentine Chaco. Unfortunately, he also had opponents in the National Academy of Medicine and Chagas disease was forgotten for almost 20 years.
From 1931 to 1936, Johnson and Rivas collected 19 cases of Chagas disease in Panama and Mazza in Argentina, described after 1934 more than a thousand cases, particularly in regions where Krause had been 20 years before and led him to deny the existence of American Trypanosomiasis.
It is interesting to know that Berenice, the young girl who enabled Chagas to describe the first acute case, was found alive in 1961 at the age of 53 and extensively studied in Belo Horizonte, clearly demonstrating that Chagas disease may remain for more than 50 years as a chronic human disease. At that time she only had a positive Complement Fixation Test and T. cruzi could be isolated from the bloodstream by xenodiagnosis, though no cardiac, digestive or other clinical manifestations could be found.
The possibility of Transfusion Transmitted Chagas disease (TxCD) was first raised by Mazza in 1936, followed by Dias I Brazil (1945), Bacigalupo in Argentina (1945) and Talice in Uruguay (1947).
In the 40's, the Argentine Sanitary code stated that donors who "could suffer from Syphilis, Recurrent Fever, infectious jaundice, Tuberculosis, Leprosy, Nicholas-Favre, Malaria, Leishmaniasis, Trypanosomiasis or any other diseases whose agent lives or circulates in the bloodstream, should be rejected, showing how long TxCD has been a major concern.
Blood donors found to be reactive by Complement Fixation Tests were first described in 1949 in Belo Horizonte (Brazil), followed in São Paulo in 1951.
The first reported cases of TxCD were in São Paulo, in 1952 by Pedreira de Freitas. At the same time this author started to work on chemoprophylaxis of whole blood, which led to the description of Gentian Violet as an useful agent by Nussenzweig (1953). Further cases of TxCD were described in Brazil, Argentina, Venezuela, Chile, Bolivia and gradually in all Latin American countries. Recently, three cases have been reported in North America, one in
Canada and two in USA.
Although complement fixation tests were described for Chagas disease since 1913, and xenodiagnosis in 1914, a great development in serodiagnosis of Chagas disease occurred after 1970 (see chapter 10).
In Brazil (where the majority of cases of TxCD were described), paid donors were progressively abandoned since 1980. Additionally, two main events led to a positive effect on blood transfusion: the setting of a National Policy on Blood Products and the newly described disease - AIDS - which promptly changed Blood Transfusion scenario in Brazil. Although many things remain to be done in this vast area of Latin America, including Brazil, there are no
doubts that Blood Transfusion is now facing a major development.
However, the economical and political turmoil which faced (and in certain areas are still facing) the majority of Latin American countries led to a great emigration to developed countries. What will occur in these countries which are not used to handle this relatively "old disease" will be definitively answered as time goes by. We will try to give some of these answers in the following chapters of this book.