Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Public health implication
- Kiran Toor (19 April 2007)
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Reply to rapid response given by Dr. Kiran Toor
- Harshpal Singh Sachdev, Anjana Gulani,Jitender Nagpal,Clive Osmond (24 April 2007)
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The worm will continue to cause blood loss if not killed, so must deworm!!
- Neeru Gupta, Kishan Kumar Jani (24 April 2007)
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Reply to rapid response given by Neeru Gupta et al
- Harshpal Singh Sachdev, Anjana Gulani, Jitender Nagpal, Clive Osmond (26 April 2007)
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Re: Reply to rapid response given by Neeru Gupta et al
- Kishan Kumar Jani, Neeru Gupta (30 April 2007)
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Reply to Rapid Response by Dr. Jani and Gupta
- Harshpal Singh Sachdev, Anjana Gulani, Jitender Nagpal, Clive Osmond (1 May 2007)
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Can we afford to ignore even small benefit when we have not much choice?
- Dr Sanjay Agarwal, Dr Rajiv Sharan, Specialist , Tata Motors Hospital ,India (28 May 2007)
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Mass Iron therapy: An alternative to Mass Anthelminthic therapy
- S Kapoor (29 May 2007)
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Anaemia in developing countries: mass iron or anthielmintic drugs. What is the best?
- Ariani I Souza (27 July 2007)
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Kiran Toor, Medical Resident UCSF Fresno , USA 93702
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The effort of Anjana Gulani et al in this systematic review [1]is commendable. In the abstract , the confidence interval for raised hemoglobin at 95% CI is 0.70 to 2.73. The range extends both sides of 1.Given the heterogenous studies , the implication of this is not clear. Would this not compromise the stastistical significance?. The accompanying figure 3 also gives same impression. There is no mention of the average study duration of the studies used for final analysis. If the raise in hemoglobin was only for a short duration , it would have less implications on a population basis. Iron deficiency anemia is the commonest cause of anemia in the world , and hookworm infection is the overall commonest etiology.Giving one time blanket treatment with Antihelminthic may not work in the long term , unless the transmission of helminths are addressed as well. This involves sanitation , clean water , drainage etc.We also need to recognice dietary iron deficiencies as contributing factor for anemia . The use of this strategy may be appropriate to immigrants of developed countries from developing countries[2]. [1]Effect of administration of intestinal anthelmintic drugs on haemoglobin: systematic review of randomised controlled trials BMJ, doi:10.1136/bmj.39150.510475.AE [2] The Cost Effectiveness of Strategies for the Treatment of Intestinal Parasites in Immigrants , NEJM Vol340:773-779 Competing interests: None declared |
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Harshpal Singh Sachdev, senior consultant Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Researc, Anjana Gulani,Jitender Nagpal,Clive Osmond
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We are pleased that Dr. Kiran Toor found our effort commendable. The confidence intervals refer to the pooled weighted mean difference (WMD) of the hemoglobin change and are above 0(0.70 to 2.73 g/l) which is in consonance with a p value of < 0.001 by random effects model, the appropriate technique to be adopted in presence of significant heterogeneity. The reported confidence interval should not be confused with the relative risk or odds ratio wherein an extension of interval on both sides of 1(rather than 0 for WMD) would indicate a lack of conventional statistical significance (p>0.05). Table A on the website of BMJ summarizes the baseline characteristics of included trials with information about number of courses and interval between the courses of anthelmintic drug. In all the trials hemoglobin was evaluated within 6 months of last anthelmintic dose. Relevant data is not available to comment on the long term impact of a single anthelmintic dose. In metaregression an increase in the number of doses of anthelmintic agent was not a significant predictor of haemoglobin response. As already stated in the discussion further trials could include information on the time sequence of helminthic re-infection and haemoglobin concentrations to gain better insight into this observation. We accept that sanitation, clean water and drainage may be important predictors of re-infection and thereby the duration of effect of a single dose. However, this was beyond the purview of the current systematic review. The use of this strategy could be appropriate for immigrants residing in developing countries. However, a detailed appraisal of various aspects influencing a public health decision would be required and some of the important points have already been highlighted in the last paragraph of the discussion. Competing interests: None declared |
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Neeru Gupta, Assistant Director General Indian Council of Medical Research, Ansari Nagar, New Delhi-110029, Kishan Kumar Jani
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This paper by Anjana Gulani et al is very interesting but programmatic inferences should have been interpreted with caution1. Authors have not precisely documented that how long after intervention the Hemoglobin measurements were done in the studies, they reviewed. In other words, over what period Hemoglobin rise occurred during Post intervention phase? The worms cause anemia by blood loss which nullifies or reverses the effect of nutrition and once this blood loss is eliminated the haemoglobin would rise and it will have a cumulative effect which will improve the levels of hemoglobin as the time will pass. One study in Uganda had aimed to assess the health impact of a national control programme targeting schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 20032. According to this study, there was a significant increase in haemoglobin concentration after one (0.135 g/dL (95% CI: 0.126-0.144)) and two years (0.303 g/dL (95% CI: 0.293-0.312)) of treatment2. There has to be prospective longitudinal surveys to know the effect of deworming on Hemoglobin status over a period of time because it is a cumulative gain. When comparisons are attempted between cost-effectiveness of administration of albendazole (single or multiple doses) and iron- supplementation for this much rise in hemoglobin then iron supplementation may appear cheaper on face value but as soon as the iron supplementation is withdrawn worm would do the harm again, so we have to treat the underlying cause. Besides worms not only cause bleeding in intestines and cause anemia but they also diminish other macro and micro-nutrients and cause cognitive impairments and stunting and malnutrition and could also cause intestinal obstruction, so value of antihelminthic treatment cannot be undermined just because statistical results are not favorable without taking pathology into consideration. The rise of hemoglobin by 1.7 gm/dl after deworming shows that worms were causing this much loss which would have continued had the drug not been given, decreasing hemoglobin further and depleting the iron stores too. But administration of albendazole as mass treatment may have certain other concerns in developing countries where neurocysticercosis is also endemic. According to a study in India neurocysticercosis is the cause of nearly one-third of all cases of active epilepsy in both the urban and rural regions in south India3. Extrapolating these results to the country as a whole leads to an estimated disease burden of 1 million patients in India with Active Epilepsy attributable to Neurocysticercosis3. Albendazole may cause inflammatory response due to dying Tenia solium cysts4,5. The latest recommendations on treatment of neurocysticercosis advocate to individualize therapeutic decisions, including whether to use antiparasitic drugs, based on the number, location, and viability of the parasites within the nervous system6. So in subjects with active epileptic disease this drug should be used with caution as this may interfere with the reputation of a National Programme involving mass treatment with Albendazole. References: 1. Anjana Gulani, Jitender Nagpal, Clive Osmond, H P S Sachdev, Effect of administration of intestinal anthelmintic drugs on haemoglobin: systematic review of randomised controlled trials. BMJ, doi:10.1136/bmj.39150.510475.AE (published 13 April 2007) 2. Kabatereine NB, Brooker S, Koukounari A, Kazibwe F, Tukahebwa EM, Fleming FM, Zhang Y, Webster JP, Stothard JR, Fenwick A. Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren. Bull World Health Organ. 2007 Feb;85(2):91-9 3. Rajshekhar V, Raghava MV, Prabhakaran V, Oommen A, Muliyil J. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurology. 2006 Dec 26;67(12):2135-9 4. Garcia HH, Gonzalez I, Mija L; Neurocysticercosis uncovered by single-dose albendazole. : N Engl J Med. 2007 Mar 22;356(12):1277-8. 5. Garg RK. Drug treatment of neurocysticercosis. Natl Med J India. 1997 Jul-Aug;10(4):173-7. 6. Garcia HH, Evans CA, Nash TE, Takayanagui OM, et al Current consensus guidelines for treatment of neurocysticercosis. : Clin Microbiol Rev. 2002 Oct;15(4):747-56. Competing interests: None declared |
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Harshpal Singh Sachdev, senior consultant Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Researc, Anjana Gulani, Jitender Nagpal, Clive Osmond
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In response to Dr. Gupta and Dr. Jani’s comments we would like to state the following: The stated objective of this systematic review was to aid public health decision by evaluating the effect of routine administration of intestinal anthelmintic agents on haemoglobin and to identify any effect predictors. This is precisely what the review has done without making any recommendations. However, we have pointed out other important aspects, including growth and cognitive performance, which should be considered for making public health decision. We do not debate the need to prescribe deworming agents in subjects with documented intestinal helminthiasis. In contrast, this review relates to routine administration of intestinal anthelmintic drugs in a population wherein the infestation status of a particular individual is unknown. As pointed out in the last paragraph of discussion, ethical aspects and adverse effects would assume importance for prescribing a drug in individuals who do not have helminthiasis. Table A on the website summarizes the baseline characteristics of included trials with information about number of courses and interval between the courses of anthelmintic drug. In all the trials hemoglobin was evaluated within 6 months of last anthelmintic dose. Unfortunately, relevant data is not available to comment on the long term impact of a single anthelmintic dose. On metaregression an increase in the number of doses of anthelmintic agent was not a significant predictor of haemoglobin response. We had already stated in the discussion that further trials should be done including information on the time sequence of helminthic re-infection and haemoglobin concentrations to gain better insight into this observation. The average estimated rise of haemoglobin was 1.7 g/L and not 1.7 g/dl as stated by Dr. Gupta and Dr. Jani. On the basis of included trials, we cannot provide evidence to corroborate or refute the interesting theoretical possibility of precipitating seizures after consumption of albendazole. Competing interests: None declared |
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Kishan Kumar Jani, Chief Medical Officer Civil Hospital, Shahdra, Delhi-110032, Neeru Gupta
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Even a rise of Hemoglobin by 1.7gm/l in six months after the last dose of antihelminthic without hematinics is appreciable and towards the positive side. When authors themselves are time and again emphasizing that the helminthiasis is present in 2 billion of world's population and Indian population is also having it, are the authors in their response suggesting that stool examination should be done in every case before deworming and what will be financial implications of this manoeuvre in resource poor settings. Competing interests: None declared |
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Harshpal Singh Sachdev, senior consultant Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Researc, Anjana Gulani, Jitender Nagpal, Clive Osmond
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Classifying a haemoglobin increment of 1.7 g/L as “appreciable” is a matter of subjective judgment, which will vary amongst individuals and policy makers in different settings. In order to aid interpretation, the systematic review had also quantified the expected reductions in baseline anaemia prevalence with this magnitude of rise in haemoglobin. We have never suggested that for an envisaged public health programme, stool examination should be mandatory prior to deworming. Competing interests: None declared |
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Dr Sanjay Agarwal, Specialist, Tata Motors Hospital , Jamshedpur , India , 831004, Dr Rajiv Sharan, Specialist , Tata Motors Hospital ,India
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Dear editor Result of review on effect of antihelminthic drugs on hemoglobin level (1) although exploratory can be of paramount importance in public health especially in third world countries like India where 74 percent of population live in villages and 90 percent of them defecate in open due to lack of adequate sanitation (2). Situation is no better in urban area where only 15 percent population have amenity of sewerage system. To add to this only 80 % has access to improved water(3). This is the current situation even after almost two decade of launch of international drinking water supply and sanitation decade in 80s. Worldwide prevalence of hookworm infection (an important cause of iron deficiency anemia in developing countries) is estimated to be151 million, out of which a significant number is from India (4). Only way to eradicate worm infestation and related morbidity and mortality is to improve sanitation, but this need enormous resources and strong political will; so in the mean time incorporation of routine administration of antihelmenthic drugs to children and women of child bearing age through ongoing different health programmes viz National Rural Health Mission, Child Survival Safe Motherhood , Anganwadi etc may help in some improvement in aneamia without a significant increase in cost as existing services and manpower could be utilized. Even 5 to 10 percent reduction in prevalence of aneamia in population as suggested by current study is significant if we consider the high prevalence of worm infestation and anemia and its clinical consequences. Thus addition of antihelminthic can improve to some extent haemoglobuline level by reducing an important cause of iron loss till adequate sanitation is available to all. Reference: 1.Gulati A ,Nagpal G,Osmond C,Sachdev HPS.Effect of administration of intestional antihelminthic drugs on hemoglobin: Systemic review of randomized controlled trials.BMJ 2007;334;1095,doi: 10.1136/bmj.39150.510475.AE (published 13 April 2007) 2. K Park .Park’s text book of preventive and social medicine. 17th edition.Jabalpur:Banarsidas Bhanot Publication,2002: 532. 3.The world Health Report 2004. changing history; Anexure: India. 4.WHO (2002),Weekly Epidemiological Record, No6,8th feb.2002. Competing interests: None declared |
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S Kapoor, M.D. University of Illinois at Chicago, Chicago, IL
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The article by Gulani et al is highly interesting and suggests that routine administration of intestinal anthelmintic agents results in a marginal increase in haemoglobin (1.71 g/l). (1) What needs to be considered is whether this approach of mass anthelminthic therapy is actually economically feasible, especially in third world countries where iron deficiency anemia is a major health issue.(2)This needs special consideration given the fact that the primary cause of anemia in third world countries is dietary malnutrition rather than intestinal infestation with helminths. (3) A better and more economically feasible approach to thwart the “epidemic” of anemia might be mass supplementation of iron supplements such as oral ferrous sulphate. (4)The average cost of mebendazole treatment (100 mg three times a day for three days) is 15 GBP. According to Gulani et al this regimen increases the hemoglobin level by 1.7 grams/liter. On the other hand ferrous sulphate at a dose of 325 mg three times a day will increase the hemoglobin level by the same value in about two weeks. The comparative cost of two weeks of ferrous sulphate therapy is only 1GBP. Clearly there is a wide gap here. This wide financial disparity and the fact that decreased dietary intake is a more common cause of anemia, lends more support to mass iron supplementation rather than mass anthelminthic therapy. 1. Gulani A, Nagpal J, Osmond C, Sachdev HP. Effect of administration of intestinal anthelmintic drugs on haemoglobin: systematic review of randomised controlled trials. BMJ 2007; May 26;334(7603):1095. 2. Cook JD, Reusser ME. Iron fortification: an update. Am J Clin Nutr 1983; Oct;38(4):648-59. 3. Tatala S, Svanberg U, Mduma B. Low dietary iron availability is a major cause of anemia: a nutrition survey in the Lindi District of Tanzania. Am J Clin Nutr 1998; Jul;68(1):171-8. 4. Mitra AK, Akramuzzaman SM, Fuchs GJ, Rahman MM, Mahalanabis D. Long-term oral supplementation with iron is not harmful for young children in a poor community of Bangladesh. J Nutr 1997; Aug;127(8):1451-5. Competing interests: None declared |
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Ariani I Souza, Research Physician Instituto Materno Infantil Professor Fernando Figueira (IMIP) - Recife - PE - Brazil (50.000-000)
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Concerning the Gulani A et al. paper (BMJ 2007; 334:1095) and the Kapoor S letter (BMJ 2007; 334:1180), I would like to considere that despite of the primary cause of anaemia in the third world countries to be dietary malnutrition rather than helminths´s intestinal infestation, like says Kapoor; the treatment suggested (ferrous sulphate at a dose of 325 mg three times a day) has a big problem: the side effects of this iron salt. These effects frequently induce a low treatment adherence and consequently a low effectivness. There are many studies about the use of intermitent schedule for iron anemia treatment.(1,2,3,4,5) I believe that the intermitent schedule can minimize the low adherence problem. Finnally, althougt the intermitent iron treatment as well the routine antihemintc drugs are good procedures, I expect that changes in the population socioeconomics conditions could be the definitive solution for this public health´s problem in the third world coutries . Ariani Impieri de Souza, Research Physician
1 - Schultink W, Gross R, Gliwitzki M, Karyadi D, Matulessi P. Effect of daily vs weekly iron supplementation in Indonesian preschool children with low iron status Am J clin Nutr 1995; 61:111-115. 2 - Ridwan E, Schultink W, Dillon D, Gross R. Effect of weekly iron supplementation on pregnant Indonesian women are similar to those of daily supplementation. Am j Clin Nutr 1996 63:884-890 3 - Berger J, Aguayo VM, Tellez W, Lujan C, TrISSAC p, San Muguel JL. Weekly iron supplementation is as effective as 5 days per week iron supplementation in Bilivia school children living at high altitude. Eur J Clin Nutrit 1997 51(6):381-286 4 - Viteri FE, Ali F, Tujague J. Long term weekly iron supplementation improves and susteins nonpregnant women,s iron status as well or better than currently recommended short-term daily supplementation. J Nutr 1999; 129:2013-2020 5 - Souza AI, Batista Filho M, Ferreira LOC, Figueiroa JN. [The effectiveness of three regimens using ferrous sulfate to treat anemia in pregnant women]. Rev Panam Salud Publ/Pan Am J Public Health 2004 15(5):313-319. Competing interests: None declared |
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