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Immunization Dialogue Indian Pediatrics 1999;36: 1061-1065 |
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Polio Virus Isolates from AFP Cases |
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The monthly newsletter of the National Polio Surveillance Project publishes data on different aspects of AFP and Polio Surveillance. The tables number 5 in the newsletters of November, 1998 (Volume 2 no. 8) and May 1999, Volume 3 No. 2 show Intra Typic Differentiation (ITD) of polio isolates for AFP cases. An abridged form of data from the three tables for the years 1977, 1998 and upto 5th June 1999 is depicted in Table I. Table I__Intra Typic Differentiation (ITD) of Polio Isolates from AFP Cases.
W_Wild; V_Vaccine For polio virus type 2, vaccine virus has been higher; more during 1997 but for types 1 and 3, there is a subsequent rise during 1998 and 1999. There is yearly increase in vaccine virus detected. What is the interpretation or clinical significance of this increase in the vaccine virus in AFP cases? Yash Paul, Reply Dr. Yash Paul has raised an important question about the clinical significance and interpretation of the numbers of wild and vaccine polioviruses isolated from children with acute flaccid paralysis (AFP) in India. The data of 1998 and 1999 (as of July, 1999) have been revised by the National Polio Surveillance Project (NPSP) (Hlady G, Personal commu-nication). Thus, in 1998 the numbers of wild virus types 1, 2 and 3 were, 1731, 73 and 187, respectively. In 1999 the numbers are 86, 6 and 72 wild virus types 1, 2 and 3, respectively. In other words, the total numbers of wild poliovirus isolations in the recent past have been 706 in 1997, 2001 in 1998 and so far 164 in 1999. The detection of 2001 wild virus isolates in 1998 after three years of annual 2-dose OPV pulse immunizations (in December-January of 1995-96, 1996-97 and 1997-98) has made the policy makers realize their error in conducting the 2-dose pulses. Even after the fourth year of pulse immunization (December-January of 1998-99), we have had 164 wild virus isolations in the first half of the year. We expect a larger number in the second half. In Vellore, we had earlier shown that the field level efficacy of three doses of pulsed OPV was 100%, with marked herd effect eliminating disease from a community for 9 months(1,2). As one case represents about 160 or more infected children, absence of cases meant less than 160 children infected over the 9 months; in other words, transmission was most probably interrupted(1,2). A second three-dose pulse one year later kept the population polio-free for nine months in the second year also(2). Pulse immunization rapidly reduces the size of the susceptible pool of children. When the reduction is sufficiently sharp and steep, transmission of wild viruses ceases. If the reduction is insufficient, transmission will slow down, but not cease. This is my interpretation as to why three-dose pulses seemed to immediately interrupt transmission in Vellore, whereas in Brazil it took 9 years of two-dose pulses (named National Immunization Days) to interrupt transmission(2). The policy makers have now decided to give four-dose pulses in most of India and six-dose pulses in some States. I suspect that this decision is partly a `panic reaction' and partly a way to avoid facing the issue of three-dose pulses. If they used a four-dose pulse and succeeded, then it can always be argued that the performance of OPV was unexpectedly poor in India and extraordinary measures were necessary. If they used three-dose pulse and succeeded they could be asked to explain why this was not accepted in the first place. Dr. Yash Paul also raises the question of vaccine virus isolations from children with AFP. The revised data show that the numbers of vaccine virus type 1, 2 and 3 were 58, 83 and 88 in 1998 and 63, 34 and 44 in 1999. What he has failed to notice in the data sets are the numbers of children from whom mixtures of vaccine viruses were isolated. There were 51 and 33 such children in 1998 and 1999, respectively. In short, there were 280 children with AFP in 1998 from whom only vaccine polioviruses were isolated and 174 such children in the first half of 1999. In the case definitions recommended by the World Health Organization, a child with AFP and wild virus isolation is accepted as confirmed polio, but if only vaccine virus was isolated, that case is `discarded' as not polio. This case definition is only for the public health purposes of polio eradication, which is defined by WHO as the total absence of AFP due to wild polioviruses even after high quality AFP surveillance and virus studies. In clinical practice, a child with AFP and vaccine virus isolation (and no wild virus) has vaccine induced (or associated) paralytic poliomyelitis (VAPP). The rule of thumb is to expect one child with VAPP for every 400,000 given the first dose of OPV(3). Since we have annual cohorts of about 25 million children getting their first OPV experience, I had earlier predicted that we might see some 60 caes of VAPP each year(4). The numbers of children with AFP and vaccine viruses found in stools in 1998 and 1999 far exceed the prediction and we do need some explanations. Children with AFP may have wild poliovirus etiology, vaccine virus etiology or non-poliovirus etiology. Since we are offering many doses of OPV to children, it is possible that vaccine polioviruses may be found both in genuine VAPP cases (as etiology), as well as in the other two categories (as mere `passenger' or `bystander' viruses). In order to define more precisely the role of vaccine viruses in causing paralysis, each child with vaccine virus isolation must be reviewed carefully. The NPSP would not do this because it has already `discarded' such cases as not polio. The clinicians responsi-ble for the clinical diagnosis and treatment of these children must bear this responsibility also. They should insist on receiving the virus isolation and intratypic differentiation data for each and every child with AFP they have reported. It is very important to document the history of any recent feeding of OPV to such children. In children given OPV and paralysis developing within one month, the diagnosis by definition is VAPP, unless wild virus was detected in the stool. The presence of vaccine virus strengthens the diagnosis of VAPP. If a child with AFP and vaccine virus in the stools had not been given OPV in the very recent past, then that child had presumably got infected with the vaccine virus from some other child given OPV, in the vicinity. Although this may not be a common occurrence, it is probable that the neuroviru-lence of vaccine viruses may increase with passage in children. If a child with AFP is diagnosed clinically to have acute anterior poliomyelitis and if the stool tests were negative, there are two possibilities: the child could have non-poliovirus etiology or, the isolation of wild or vaccine poliovirus was missed due to sampling inadequacy, delay in transportation, etc. If vaccine virus alone was detected in such a child, it would look like VAPP, but in reality it could have been wild virus induced polio with false negative laboratory results. Thus, when we see larger than expected numbers of children with AFP and vaccine viruses in their stools, we have to provisionally interpret the data to consider that they include: (a) some children with true VAPP, (b) some with true wild virus induced polio but with false negative wild virus isolation, and (c) non-polio AFP, but with intercurrent and innocent vaccine virus infection. Unless all the cases are reviewed we will not know if we have in India a higher frequency of VAPP than one per 400,000 first OPV dose responders. The occurrence of VAPP cases is an important issue in medical ethics, but outside the purview of the NPSP as I have already indicated. This is an issue of the moral responsibility of the Ministry of Health and Family Welfare under whose aegis India is immunizing children with OPV and endeavoring to eliminate wild poliovirus circulation. Parents are accepting repeated doses of OPV for the sake of the national program for polio eradication. Therefore any adverse effects that occur due to compliance is personal injury for no fault of theirs. The official view of the Committee on Immunization of the IAP is that all children with AFP must be given free treatment and free rehabilitation services and those with VAPP ought be given some compensation in addition to the treatment and rehabilitation. I must add here that these issues must in no way reduce our enthusiasm or efforts to eliminate wild polioviruses from our country and we have our role to play both as individuals and as the Academy. Eradication of wild viruses (earlier defined as phase w) must be followed by elimination of VAPP (defined as phase v), which can be achieved only when we discontinue the use of OPV for primary immunization(4). This approach is being adopted by several countries where they use Inactivated Poliovaccine (IPV) instead of OPV. Soon the policy makers in India will be forced to face this option (of using IPV) in the immediate post-phase w period. Eventually, perhaps 5 years after the whole world has been certified to have eradicated wild polioviruses, we may be able to discontinue polio immunization altogether, but in the interim between the last reported case of AFP due to wild poliovirus in India and the global certification of eradication, which vaccine should we use? If we continue to use OPV, then we will continue to have many children with VAPP, which in the absence of wild virus-induced polio in the community, is an ethically untenable situation. While there is still wild virus circulation, the government can justify the use of OPV for greater common good. On the other hand, if we use IPV, then we will graduate to eradication phase v forthwith. If India had used IPV even for polio eradication, we could have achieved eradication phases w and v simultaneously. Had we used IPV for eradica-tion we could also have avoided pulse immunization (which is needed only for OPV), and thus avoided the adverse effects of inten-sive pulse campaigns on routine immunization. On the contrary, we would have strengthened the routine immunization by using a combi-nation vaccine of DPT and IPV. While we cannot go backwards with IPV, we still can opt for it from the time we document the absence of wild polioviruses in the country, hopefully from the beginning of the year 2001. Planning must start now if this option is seriously taken. T. Jacob John, References 1. John TJ, Pandian R, Gadomski A. Control of poliomyelitis by pulse immunization in Vellore, India. Brit Med J 1983; 286: 31-32. 2. John TJ. Immunization against polioviruses in developing countries. Rev Med Virol 1993; 3: 149-160. 3. Bottiger M. The elimination of polio in the Scandinavian countries. Pub Health Rev 1993/94; 21: 27-33. 4. John TJ. Can we eradicate poliomyelitis? In: Frontiers in Pediatrics. Eds. Sachdev HPS, Choudhury P. New Delhi, Jaypee Brothers, 1996; pp 76-90. In the IAP publication entitled "Key Communication Messages. Pulse Polio Immu-nization and Field Guide on the Surveillance of Acute Flaccid Paralysis", Dr. Hathi has stated on pages 1 and 2 under point no. 6: "What about routine and regular polio vaccination during pulse polio days? Routine and regular polio vaccinations must be continued without fail even if the pulse polio days fall on the next day of the routine days. This does not in any way interfere with regular polio vaccination but provides an additional protection against the dreaded disease." 1. If the Pulse Polio Day Falls on the next day of the routine day: (i) Why should the routine polio adminis-tration not be postponed for a day? (ii) Why should the routine polio dose administered a day before the pulse polio day not be considered as pulse polio dose? The vaccine used in both is same. Does it make any differences in eradication of polio if it is given on 6th December and not on 7th December? 2. This (pulse polio dose) does not in any way interfere with regular polio vaccinations, but provides an additional protection against the dreaded disease: (i) If two doses are given on two consecutive days, i.e., 6th and 7th December or 17th and 18th January, effect of replication of vaccine virus will not be there because of 24 hours interval only in the administration of the second dose. How will the next day's polio vaccine administration provide additional protection? Should we give two doses of polio vaccine on consecutive days for routine vaccination also for better effect? (ii) In case where routine polio vaccine has been given about 3 weeks earlier and the polio vaccine has been administered again during pulse polio campaign, will replication of vaccine virus of routine vaccination in the intestine affect the uptake of polio vaccine administered 3 weeks later? Yash Paul, Reply The spirit of the statement that `routine and pulse doses of OPV must be given as per schedule' is to simplify instructions rather than to answer the many questions that would arise if conditionalities are raised. I am surprised that these issues are still unsettled among ourselves. Let me ask if both the routine dose of OPV and the pulse dose fell on one and the same day what would you do? Will you give only one dose or will you give two doses of OPV? I would given only one dose, but I would count it against the routine dose that was due and put it in the child's record. We need not keep an account of the pulse doses for individual children. If a routine dose was due several days or weeks prior to the pulse campaign day, I would tend to give that dose since there is no guarantee that the child will take the subsequent pulse dose. There could be some reason (illness of the child or of some one in the family, for example) why a child might not be taken to the pulse immunization booth inspite of the family wanting (earlier) to do so. If the child was actually taken to the booth on the appointed day and given the pulse dose also, there is no harm at all. If the earlier dose resulted in infection by all 3 serotypes, the next dose would be ineffective. But if one or more serotype had not infected the child, another chance is now given. Theoretically, this argument applies to any interval, even a day, between doses, except that no one has tested such a sequence. If the routine dose was due within just a few days of the pulse, I would tend to postpone that dose until the day of the pulse campaign. Again I would record that dose as one routine dose. If on the other hand a routine dose was due within 4 weeks after the pulse dose, what I would do is to postpone it until 4 weeks and then give it. Since every dose of OPV is not a predictably immunogenic dose, and since some 7-9 doses are required for about 99% probability of protection, I would not worry too much about the number of excess doses or the shortness of intervals between doses of OPV. Rules are made to guide as and when situation warrants we must take judgements, even if contrary to rules, in specific cases, with clear reasons for any deviation from the stipulated rule. As far as the effectiveness of pulse immunization is concerned, it would not make a difference if a dose was given one day before or after the due date of pulse, in a given child, or in a given group, or in a community. T. Jacob John, |
