Iron supplementation in prevention of severe anaemia and malaria
Authors: Clara Menendez, Pedro Alonso
Journal: The Lancet (1997)

Authors' replySir—On the basis of the results of a study in transmigrant Javanese men in Irian Jaya, Kevin Baird and Stephen Hoffman propose two alternative explanations to the increased post-prophylaxis risk to malaria and anaemia seen in Tanzanian infants living in an area of intense and perennial malaria transmission. As we state in our discussion, we have documented a possible overestimation of the attack rates after completing chemoprophylaxis because of a loss of comparability of the two cohorts at the outset of the post-prophylaxis period. However, we also report the results of an analysis including all previously withdrawn children, and this still yields a significant difference in risk. The emergence of accumulated subpatent parasitaemias suppressed by the drug is an interesting hypothesis that may account for the findings in Irian Jaya, but we find this an unlikely explanation of our findings because the increased attack rate in the post-chemoprophylaxis group extends well beyond a 4-week period, and we suspect is the result of a difference in the level and efficacy of naturally acquired clinical immunity to malaria between the two cohorts.We essentially agree with Umberto D'Alessandro's comments. Indeed our findings suggest that there is no increased severity of the clinical episodes in previously chemosuppressed infants, but we must remain cautious. The Tanzanian study has documented a shift in the age frequency of disease, but was not designed to assess the impact of such a shift on the frequency of different clinical presentations or survival by age 5. The cohorts are still being followed, but the question still remains as to what is the effect of age at the time of first encounter with P falciparum in determining the risk, severity, and case fatality of that encounter? A clear answer to this question will be important in guiding the rational development, planning, and implementation of malaria-control tools, including vaccines, in different endemic settings. Authors' reply Sir—On the basis of the results of a study in transmigrant Javanese men in Irian Jaya, Kevin Baird and Stephen Hoffman propose two alternative explanations to the increased post-prophylaxis risk to malaria and anaemia seen in Tanzanian infants living in an area of intense and perennial malaria transmission. As we state in our discussion, we have documented a possible overestimation of the attack rates after completing chemoprophylaxis because of a loss of comparability of the two cohorts at the outset of the post-prophylaxis period. However, we also report the results of an analysis including all previously withdrawn children, and this still yields a significant difference in risk. The emergence of accumulated subpatent parasitaemias suppressed by the drug is an interesting hypothesis that may account for the findings in Irian Jaya, but we find this an unlikely explanation of our findings because the increased attack rate in the post-chemoprophylaxis group extends well beyond a 4-week period, and we suspect is the result of a difference in the level and efficacy of naturally acquired clinical immunity to malaria between the two cohorts. We essentially agree with Umberto D'Alessandro's comments. Indeed our findings suggest that there is no increased severity of the clinical episodes in previously chemosuppressed infants, but we must remain cautious. The Tanzanian study has documented a shift in the age frequency of disease, but was not designed to assess the impact of such a shift on the frequency of different clinical presentations or survival by age 5. The cohorts are still being followed, but the question still remains as to what is the effect of age at the time of first encounter with P falciparum in determining the risk, severity, and case fatality of that encounter? A clear answer to this question will be important in guiding the rational development, planning, and implementation of malaria-control tools, including vaccines, in different endemic settings. Iron supplementation in prevention of severe anaemia and malariaClara Menendez and colleagues (Sept 20, p 844)1 show the protective effect of Deltaprim (3·125 mg pyrimethamine plus 25 mg dapsone) in infants exposed to intense transmission of Plasmodium falciparum. On the basis of post-treatment attack rates, they state, “The study shows that partly effective malaria control has modified the rate at which naturally acquired immunity develops”. We offer two alternative explanations. Full-Text PDF Iron supplementation in prevention of severe anaemia and malariaDoes severity of malaria decrease with age? Is there a vulnerable period for children living in endemic areas where they are more susceptible to severe disease? Is the length of it dependent on the intensity of transmission? These are some of the questions that can be asked after reading Clara Menendez and colleagues' report.1 The main findings of this trial are: iron supplementation decreases the frequency of severe anaemia (packed-cell volume <25%) but had no effect on the frequency of clinical malaria; weekly chemoprohylaxis with dapsone and pyrimethamine decreases both the frequency of clinical malaria and severe anaemia; and after stopping chemoprophylaxis, children who had received it had higher rates of severe anaemia and clinical malaria, although the rates of all-cause and malaria-specific hospital admissions were similar to the other treatment groups. Full-Text PDF