Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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The Agony of Second Class Treatment for the Global Poor
- Daniel J Kiely (13 August 2005)
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Malaria - the many headed monster
- Dr. Chandrakant Madgaonkar (19 August 2005)
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Malaria and severe anemia in children
- Stephen J. Gerrish (29 August 2005)
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Proposed Guidelines
- Timothy D. Planche, Mike Sharland, Peter Kremsner, Sanjeev Krishna (30 August 2005)
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Proposed guidelines for severe imported malaria in children: the need for more evidence
- Shamez Ladhani, Delane Shingadia, F. Andrew I. Riordan (21 September 2005)
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Severe Malaria is COMPLICATED MALARIA!
- Navneet Singh (30 September 2005)
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oral quinine in management of M. falciparum infection
- jeewan rawal, Dr G. Subramanian ,Dr Bikash Bhojanagarwala, Dr Ashwani Peshen (14 October 2005)
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Daniel J Kiely, Medical Student McGill University
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I sometimes wish (respectfully) that sentences like this: "the safe use of anticonvulsants in the setting of a modern paediatric intensive care setting is likely to differ greatly from that in African centres where ventilatory support is unavailable and should follow the standard algorithm" will one day continue to say something like, "at least until intensive global efforts to make that ventilatory support available to all children are successful". I hope (and I do not think I am unreasonable) that one day all children will have access to the same excellent level of medical care just as all children have the same human right to health. As such, I cannnot agree with the statement that sub-Saharan Africans are "a population for whom use of and access to modern inensive care facilities are not possible". Competing interests: None declared |
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Dr. Chandrakant Madgaonkar, Family Physician J C Nagar; Hubli-580020; India
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The article “Management of severe malaria in children: proposed guidelines for the United Kingdom ” in BMJ 2005; 331:337-343 (6 August), once again emphasizes two important facts; one – epidemiological – that malaria is back with a vengeance; and two – clinical – that Malaria - the many headed monster – can present with a wide range of symptoms and signs, none of them diagnostic, its prudent that clinician should consider malaria in the dirrerential diagnosis in any acute febrile illness until it can be excluded by a definite lack of exposure, by repeated examination of blood smears, or, if the patient is seriously ill, by a therapeutic trail of anti-malarial chemotherapy. As "most deaths (due to falciparum malaria) occur within hours of admission, principally because the clinician fails to recognize impending circulatory collapse or respiratory compromise”(1), its essential on the clinicians part to avoid errors in the management of falciparum malaria. These could be enumerated as follows: 1 – delay in starting anti-malarial therapy
Further, it should be emphasized that “malaria in children” includes “congenital and neonatal” malaria. Most evidence from malarious part of the world indicates that congenital malaria is extremely rare, due to the protection given by the placental barrier and the protection provided by immunoglobulins from the immune mother, which crosses the plasenta. Congenital malaria is, however, much common in infants born to non-immune mothers. Clinical features include fever, irritability, feeding problems, anemia, hepatosplenomegaly and jaundice. Unless parasites are found in the smear from a heel prick or cord blood, the newborn may be misdiagnosed as having rhesus incompatibility or another congenital infection such as cytomegalovirus, herpes simplex, rubella, toxoplasmosis, or syphilis. Hence, an update / guidelines in neonatal malaria is a necessity, Ref: 1 - BMJ 2005; 331:337-343 (6 August), Competing interests: None declared |
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Stephen J. Gerrish, physician with ARV program Kara Counselling, Box 37559, Lusaka, Zambia 00000
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The Clinical Review article by Maitland, et. al., on the Management of Severe Malaria in Children, described a clinical picture quite different than that experienced by myself while working several years in a rural Zambian hospital. Our patients, from the Zambezi floodplain, were constantly exposed to malaria from birth, with chronic splenomegally and recurrent year round infections. In the review article, hypovolaemic shock, metabolic distorders, and cerebral symptoms are emphasized, while severe anemia is only briefly discussed, saying, "...most do not require transfusion." While this clinical picture was seen at our hospital, the large majority of severely ill children had severe anemia, under 50 gms/L, and often under 30 gms/L. These patients, who would literally die in the waiting room or while trying to obtain IV access, only responded to emergent blood transfusion, which if given in time, often resulted in remarkable recovery. Isotonic fluids were usually of limited use. The article's management guidelines certainly apply to non-immune patients, such as those seen in the UK, or to patients in Africa who live in areas of occasional malaria, such as urban areas. These patients, when visiting our area, would present as described in the article . However, it would be useful to include more on the clinical presentation and treatment of children who are exposed to malaria "daily," and who are more typical of the patients I experienced. Regarding diagnosis and specimen collection, it is recommended that blood slides made from blood collected in EDTA tubes be done so within one hour, and that non-anticoagulated blood (direct slides from capillary blood) might offer a better alternative. (1) As most labs in the "west" have little experience with malaria smears, this would be espeically true. And since the BMJ is read in the US, it would be prudent to mention the lack of FDA approved artemether drugs or parenteral quinine in the US, with parenteral quinidine being the only, and hard to find, option. (2) Finally, based on personal experience, children raised on "bitter" chloroquine prophylaxis, still an option in some circumstances, will take oral quinine without complaint! Stephen Gerrish, M.D. Lusaka, Zambia "gerrish@zamnet.zm" (1) Cheesborough, M. Medical Laboratory Manual for Tropical Countries, Vol. 1, 2nd Ed., p. 240. (2) Magill, Making Antimalarials Agents Available in the United States, NEJM; 353:335 Competing interests: None declared |
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Timothy D. Planche, SpR Department of Infectious Diseases, St. George's Hospital, London, SW17 0RE, Mike Sharland, Peter Kremsner, Sanjeev Krishna
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Dear Editor, The proposed guidelines for the management of severe imported malaria in children (1) may be useful for some physicians, as there are about 160 cases per year in the UK of childhood falciparum malaria (2), and between 2 to 16 cases of severe or complicated disease. As the authors of these proposed guidelines state, there are few trial data from studies on malaria in the UK (2). Clearly, guidelines must also rely on the wealth of accumulated experience in Africa. These proposed guidelines invite consultation and we therefore make the following comments consistent with recommended good practice for guidelines (3). Both within and between sub-Saharan countries, the clinical manifestations and complications of malaria vary, suggesting that as wide an experience as possible should be sought in formulating management options. For example, treating hypoglycaemia is one of the less controversial and most important aspects of the care children with severe malaria, and a recommended rate for glucose infusions (missing at present apart from rather general statements) can be derived from available kinetic data (4), and other experience from large, prospective studies. Other more controversial areas such as the possible requirements for aggressive fluid therapy are discussed in more detail, although the evidence base for some recommendations remains slender and a recent opinion article from these investigators suggested further studies are needed. However, these suggestions should also be interpreted in light of an alternative view that hypovolaemia may not be of primary importance in the pathogenesis of metabolic acidosis in childhood malaria as summarised in recent reviews (5). A further concern is that these proposed guidelines may be applied de facto in African contexts, where wider consultation and resolution of controversial areas is urgently needed, perhaps through involvement of experienced groups such as the clinical guidelines committee of the RCPCH. 1. Maitland K, Nadel S, Pollard AJ, Williams TN, Newton CR, Levin M. Management of severe malaria in children: proposed guidelines for the United Kingdom. Bmj 2005;331(7512):337-43. 2. Williams JP, Chitre M, Sharland M. Increasing Plasmodium falciparum malaria in southwest London: a 25 year observational study. Arch Dis Child 2002;86(6):428-30. 3. Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. Bmj 1999;318(7183):593-6. 4. Agbenyega T, Angus BJ, Bedu-Addo G, Baffoe-Bonnie B, Guyton T,Stacpoole PW, et al. Glucose and lactate kinetics in children with severe malaria. J Clin Endocrinol Metab 2000;85(4):1569-76. 5. Planche T, Krishna S. The relevance of malaria pathophysiology to strategies of clinical management. Current Opinions in Infectious Diseases 2005; In press. Competing interests: None declared |
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Shamez Ladhani, Research Fellow, Paediatric Infectious Diseases Academic Centre for Child Health, Royal London Hospital, 38 New Road, London El 2AX., Delane Shingadia, F. Andrew I. Riordan
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Dear Editor, We read with interest the proposed guidelines by Maitland and colleagues for the management of severe malaria in children in the United Kingdom [1]. Their definition for children at immediate risk of dying (the high risk group) would encompass a very small proportion of children with imported malaria – only 6/211 cases (2.8%) over a 6-year period in 3 East London hospitals [2]. We think this is an excellent attempt to improve the care of children with severe malaria in the UK. However, we were concerned about: 1. Use of parenteral antibiotics. In the UK, a child presenting with features defining the high risk group is significantly more likely to have bacterial septic shock and/or meningitis, even with a history of foreign travel. Furthermore, it is impossible to differentiate between cerebral malaria and bacterial meningitis [3], nor between shock due to malaria and bacterial septicaemia [4]. We would, therefore, suggest that the management algorithm (Figure 1) should emphasise the importance of starting early empiric broad-spectrum antibiotics in children presenting with features defining the high risk group until bacterial infection can safely be excluded through lumbar puncture and blood/cerebrospinal fluid cultures [5]. 2. Transfusion. The authors propose that children with haemoglobin <100 g/l should be managed in a high dependency unit and be transfused. A Cochrane review found no significant difference in mortality between initial and expectant blood transfusion among children with malarial anaemia (with no respiratory distress or cardiac failure), but found that adverse events were more common with initial blood transfusion [6]. In east London, 65/211 (31%) presented with haemoglobin levels between 50-100 g/l and none developed complications despite being managed conservatively [2,5]. The recommendation to transfuse these children should be reconsidered, especially given the current moves to decrease transfusions in the UK. 3. Oral Quinine. The authors recommend that children should “never” be given oral quinine because it is unpalatable. However, the BNF states it is “well tolerated by children” [7]. In east London, only 1/192 children receiving quinine (0.5%) relapsed [2,5]. Oral quinine is currently the mainstay treatment for childhood falciparum malaria because it remains highly effective and is significantly cheaper than other recommended antimalarials. In addition, mefloquine should be rarely used for treatment because of concerns about resistance [7]. Further studies are necessary before recommending newer antimalarials. Finally, the proposed guidelines really only apply to Plasmodium falciparum malaria. This leads to some confusion about children with non- falciparum malaria. These children are extremely unlikely to develop severe malaria and the suggested treatment for “Uncomplicated Malaria” would be inappropriate and much more costly than the currently recommended chloroquine [7]. A 12-month surveillance study of imported malaria in Great Britain through the British Paediatric Surveillance Unit (BPSU) will begin later this year (http://bpsu.inopsu.com). We will aim to collect comprehensive epidemiological, clinical and laboratory information about children with imported malaria and hope that this and similar studies will provide objective data to support future recommendations for the management of uncomplicated and severe imported malaria. References 1. Maitland K, Nadel S, Pollard AJ, Williams TN, Newton CR, Levin M. Management of severe malaria in children: proposed guidelines for the United Kingdom. BMJ. 2005; 331(7512):337-43. 2. Ladhani S, El Bashir H, Patel VS, Shingadia D. Childhood malaria in East London. Pediatr Infect Dis J. 2003; 22(9):814-9. 3. Berkley JA, Mwangi I, Mellington F, Mwarumba S, Marsh K. Cerebral malaria versus bacterial meningitis in children with impaired consciousness. QJM. 1999; 92(3):151-7. 4. Berkley J, Mwarumba S, Bramham K, Lowe B, Marsh K. Bacteraemia complicating severe malaria in children. Trans R Soc Trop Med Hyg. 1999; 93(3):283-6. 5. Ladhani S, Patel VS, El Bashir H, Shingadia D. Changes in laboratory features of 192 children with imported falciparum malaria treated with quinine. Pediatr Infect Dis J. 2005: In press. 6. Meremikwu M, Smith HJ. Blood transfusion for treating malarial anaemia. In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software 7. British National Formulary 50 (SEPTEMBER 2005). British Medical Association, London, 2005 (http://www.bnf.org/bnf/bnf/50/openat/16012.htm?q=%22malaria%22) Competing interests: None declared |
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Navneet Singh, Senior Resident Department of Pulmonary Medicine, PGIMER, Chandigarh, India - 160012
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Randomized Controlled Trials have ushered in the era of modern (evidence based) medicine. This evidence base has helped in the formulation of guidelines for clinical practice. Maitland and colleagues have recently proposed guidelines for the management of severe malaria in children including an algorithm for initial triage.1 Severe or complicated malaria carries a 200 fold higher mortality than uncomplicated malaria.2 It is characterized by the presence of multi organ dysfunction, criteria for which have been laid down by the World Health Organization.3 Newer drugs like artesunate, that have till now been considered, at best, as effective as traditional drugs like quinine, may infact be superior as has been demonstrated in a recent study.4 Appropriate antimalarial treatment needs to be supplemented by early and optimal management of organ dysfunction, a usual accompaniment of severe malaria, in order to improve patient outcomes and minimize morbidity as well as mortality. However, management of a disease entity can be initiated only if it is recognized. In developing countries like ours not only is the burden of malaria high, access to good health care (including referral of complicated cases to tertiary level institutes that are capable of handling such cases) is also a limiting factor. For primary and even secondary care health care facilities, the essence lies in recognition of severe malaria and its complications in order to ensure timely referral of these cases. An acronym that encompasses the clinical and laboratory spectrum of severe malaria could prove to be helpful in this setting - COMPLICATED MALARIA (where COM stands for coma, P for pulmonary edema, L for Low BP, I for increased bilirubin, C for convulsions, A for anemia, T for thrombocytopenia, ED for elevated lactate, MA for massive parasitemia, L for low blood sugar, AR for acute renal failure, I for intravascular hemolysis and A for acidosis). This acronym again is not a substitute, only an aid to good clinical judgment because one must remember that one sees only what one is looking for! References: 1. Maitland K, Nadel S, Pollard AJ, Williams TN, Newton CR, Levin M. Management of severe malaria in children: proposed guidelines for the United Kingdom. BMJ 2005; 331: 337-343. 2.Taylor WRJ and White NJ. Malaria and the lung. Clin Chest Med 2002; 23: 457– 468. 3.World Health Organization. Severe falciparum malaria. Trans R Soc Trop Med Hyg 2000; 94(Suppl 1): S1– S90. 4.South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 2005; 366: 717–725. Competing interests: None declared |
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jeewan rawal, consultant paediatrician old church hospital romford essex rm7 obe, Dr G. Subramanian ,Dr Bikash Bhojanagarwala, Dr Ashwani Peshen
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Dear Sir or Madam, We refer to the clinical review’ Management of severe malaria in children”: proposed guidelines for the United Kingdom by Maitland et al published in BMJ (2005:331:337-43) dated 6th august 2005. In this article use of oral quinine is not recommended for treating malaria. Our experience has been otherwise. We would like to share our small experience in the management of children with malaria, who presented to A&E at Old Church Hospital, Romford, Essex, U.K. we have treated 12 patients in last 6 months, all of whom were from West Africa with confirmed M.falciparum infection. We managed these children with intravenous or oral quinine, as appropriate depending on the severity. Oral quinine was tolerated very well. Follow up of these cases confirmed complete clinical resolution of symptoms. In terms of cost effectiveness the treatment recommended by authors, costs 12 times more than oral quinine e.g. (20Kg child recommended treatment malaron costs £ 12,while oral quinine <£1 (BNF49 March 2005) .we believe oral quinine is a cheaper and effective medication where severity does not warrant intravenous treatment Dr Bikash Bhojanagarwala, Dr Ashwani Peshen (Middle Grade Paediatricians) Dr J Rawal, Dr G. Subramanian (Consultant Paediatricians) Competing interests: None declared |
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