Indian J Med Res 125, January 2007, pp 65-72 Operational feasibility of rapid diagnostic kits & blister packs use for malaria control in high transmission areas of Orissa & Chhattisgarh A.M. Reetha, S.K. Sharma*, P.K. Tyagi*, Neena Valecha, B.N. Nagpal & A.P. Dash National Institute of Malaria Research (ICMR), Delhi & *Integrated Disease Vector Control Project, National Institute of Malaria Research, Field Station, Rourkela, India Received January 9, 2006 Background & objectives: Early diagnosis and prompt treatment of cases with malaria are two important components of malaria control strategy. The independent assessment of the operational feasibility of rapid diagnostic kits and blister packs for malaria in some selected high transmission areas of Orissa and Chhattisgarh was done with the objectives to assess the knowledge and skills of the paramedical personnel and their acceptability by the paramedical personnel and the community, and to assess improvement in patients health seeking behaviour. Methods: The basic information regarding malaria situation, epidemiological divisions, distribution data of rapid diagnostic kits and blister packs, etc., was collected from State and district headquarters. The subcentres from the primary health centres/community health centres were selected on the basis of supply of rapid diagnostic kits and blister packs. The subcentres were visited and health personnel interviewed about their knowledge and skills on the use of rapid diagnostic kits and blister packs. A cross-sectional survey was conducted to assess the public opinion about rapid diagnostic kits and blister packs. Results: We found that the paramedicals were well trained in the use of rapid diagnostic kits and blister pack administration and the acceptance was good by both paramedicals and general public. The compliance rate of radical treatment with blister packs was 100 per cent and no adverse events were reported. Interpretation & conclusion: Our findings showed that rapid diagnostic kits and blister packs under remote and inaccessible highly malarious areas can be introduced that will have significant impact in reducing malaria morbidity and mortality. Key words Blister packs - operational malaria control programme - rapid diagnostic kits 65
66 INDIAN J MED RES, JANUARY 2007 The early diagnosis and prompt treatment of cases of malaria has been a key component of the global malaria control strategy that aims at preventing mortality and reducing morbidity 1. In India, about 100 million blood smears from fever cases are examined annually to confirm the diagnosis of malaria. The time lag between collection of blood slide and onset of radical treatment is often delayed due to operational problems related to difficult terrain, poor public transportation and other communication facilities and shortage of trained laboratory technicians 2. As per drug policy of the National Vector Borne Disease Control Programme (NVBDCP, formerly known as National Anti Malaria Programme), Government of India, all fever cases without any other obvious causes should be presumed as malaria and chloroquine (CQ) be given as a presumptive treatment preferably after taking blood smear 3. In high-risk areas presumptive treatment with 25 mg/kg body weight of chloroquine base is to be given on 3 consecutive days with a single dose of primaquine (PQ 0.75 mg/kg body weight) on the first day. Conventional presumptive treatment (600 mg CQ) is though incomplete treatment but can act as an antipyretic and prevent complications. The full dose radical treatment (1500 mg CQ + 45 mg PQ) had advantage of complete treatment but majority of patients without Plasmodium falciparum (Pf) also get exposed to high dose of chloroquine and primaquine. A number of rapid diagnostic kits (RDK) based on P. falciparum histidine rich protein-2 (PfHRP-2) and lactate dehydrogenase (LDH) antigens have been field-tested and were found to be useful for prompt malaria diagnosis 4-6. Therefore, if rapid test for P. falciparum is conducted, only positive cases can be treated with full radical treatment while the rest can either be treated after microscopic diagnosis or can be given only 600 mg CQ since these will be either vivax cases or negative for malaria. Blister Packs containing 3 tablets of CQ (600+600+300mg) and one tablet of PQ (45 mg) in each pack, for the radical treatment of adult patients (15 yr and above) have been used in Maharashtra for about seven years and have been found to be effective and well accepted (Source: NVBDCP; unpublished report). During 2003, NVBDCP has introduced rapid diagnostic kits and blister packs for the first time in the national programme in eight States (Orissa, Jharkhand, Madhya Pradesh, Chhattisgarh, Andhra Pradesh, Gujarat, Maharashtra and Rajasthan) under World Bank assisted Enhanced Malaria Control Project (EMCP) for early diagnosis and to improve acceptance of anti-malarial drugs and compliance of full course of radical treatment. Therefore, an independent assessment of the operational feasibility of rapid diagnostic kits and blister packs in some selected remote and inaccessible high transmission areas of Orissa and Chhattisgarh States was carried out during November 2003 to January 2004. The objectives were to assess the knowledge and skills of the paramedical personnel and the fever treatment depots (FTDs) on the use of rapid diagnostic kits and blister packs and their acceptability by the paramedical personnel and the community, and to assess improvement in patients health seeking behaviour. Material & Methods Study areas: The study was conducted in Mayurbhanj district of Orissa and Kanker district of Chhattisgarh States; these two being remote and inaccesible areas with inadequate microscopic facilities. Mayurbhanj district is located in the northeastern part of Orissa bordering West Bengal and Jharkhand. The district is characterized by Similipal National Reserve Forest that covers
REETHA et al: RAPID DIAGNOSTIC KITS & BLISTER PACKS IN OPERATIONAL MALARIA CONTROL PROGRAMME 67 44.9 per cent of the geographical area of the district. Malaria is a major public health problem in Mayurbhanj district. The high morbidity and mortality are mainly due to high prevalence of falciparum malaria and large pockets of tribals represented by about 50 ethnic tribal communities that constitute 57.9 per cent of the total population of the district (State Malaria Programme Officer, Chhattisgarh; personal communication). Chhattisgarh is a newly created State from eastern part of Madhya Pradesh with 16 revenue districts. The State is surrounded by Uttar Pradesh and Jharkhand in the north, Orissa in the east, Andhra Pradesh in south and Madhya Pradesh and Maharashtra in west. Kanker district is malaria endemic area of the State (State Malaria Programme Officer, Chhattisgarh; personal communication). The topography of the area with hilly tracts, banks of rivers and forests provide suitable ecological conditions for malaria transmission. The epidemiological data of two districts over a period of proceding five years are given in Tables I and II. Distribution of rapid diagnostic kits and blister packs: The Directorate of Health, Government of Orissa had received 30,000 rapid diagnostic kits (RDK) and 12,00,000 blister combi packs containing 3 tablets of CQ (600+600+300 mg) and 1 tablet of primaquine (45 mg) in each pack, in the first week of November, 2003. The distribution of rapid diagnostic kits and blister packs to 21 districts of Orissa under Enhanced Malaria Control Project was completed by the fourth week of November, 2003. Mayurbhanj district received 4950 test strips of rapid diagnostic kits and 69,600 blister packs in third week of November, 2003. The criteria for the distribution of the rapid diagnostic kits and blister packs in high risk areas were based on annual Table I. Epidemiological data of Mayurbhanj district, Orissa for the years 1998-2002 Year BSC/BSE +ve Pf Death ABER API SPR SFR Pf% 1998 305719 40709 36621 31 14.9 19.8 13.3 11.9 89.9 1999 252064 29794 26544 18 11.8 13.9 11.8 10.5 89 2000 296613 31161 27956 24 13.8 14.5 10.5 9.4 89 2001 311676 23536 21201 21 14 10.6 7.5 6.8 90 2002 407019 24163 21692 21 18.3 10.8 5.9 5.3 89.7 Source: District Malaria Officer, Mayurbhanj, Orissa BSE, blood slides examined; Pf, Plasmodium falciparum; ABER, annual blood examination rate; API, annual parasite index; SPR, slide positivity rate; SFR, slide falciparum rate Table II. Epidemiological data of Kanker district, Chhattisgarh for the years 1998-2002 Year BSC/BSE +ve Pf Death ABER API SPR SFR Pf% 1998 286558 53895 48293 0 43.24 81.33 18.80 16.85 89.60 1999 324390 68633 57565 0 47.76 96.63 20.23 17.75 87.70 2000 355823 69931 59344 7 51.11 100.45 19.65 16.68 84.86 2001 288993 37895 32262 1 40.50 53.11 13.11 11.16 85.14 2002 262007 28514 25499 0 35.91 39.08 10.88 9.73 89.43 Source: District Malaria Officer, Kanker, Chhattisgarh BSE, blood slides examined; Pf, Plasmodium falciparum; ABER, annual blood examination rate; API, annual parasite index; SPR, slide positivity rate; SFR, slide falciparum rate
68 INDIAN J MED RES, JANUARY 2007 parasite index (API), remoteness and inaccessibility of the areas and inadequate blood examination facilities. Training about the use of rapid diagnostic kits and blister packs was given to the multipurpose health workers (MPHW) and Anganwadi workers (AWW) in a phased manner during early December 2003. In Chhattisgarh, 48000 rapid diagnostic kits and 646,000 blister packs were received during September, 2003. The Directorate of Health conducted training for all District Malaria Officers (DMO) at the State headquarter. Subsequently DMOs had arranged training for Block Medical Officers, Malaria Inspectors and laboratory technicians during November and rapid diagnostic kits and blister packs were distributed at the same time. Field staff training was arranged at primary health centre level. Methodology: Before starting the assessment of the feasibility of rapid diagnostic kits and blister packs in the periphery, the basic information regarding malaria situation, epidemiological divisions, distribution data of rapid diagnostic kits and blister packs, etc., was collected from the State headquarter as well as from DMOs. Thereafter, on the basis of available parasitological data at least three high risk primary health centres/community health centres were selected where both rapid diagnostic kits and blister packs were supplied in some subcentres and only blister packs in other subcentres. At Kanker district there was no centre where only blister packs were supplied. The subcentres were visited and health personnel were interviewed regarding their knowledge and skills on the use of rapid diagnostic kits and blister packs. Health workers such as surveillance workers, lady health visitors, mitanin and auxiliary nurse midwives were interviewed regarding test procedure as well as spot demonstration of test performance and regarding drug administration. The health workers supplied with blister pack and rapid diagnostic kits were interviewed regarding feasibility of blister pack, drug dose, treatment, contraindication and difficulty in use, if any. The patients and medical officers were also interviewed regarding any adverse drug reaction. This was followed by an assessment at both the places by an independent assessment team consisting of medical experts from Ispat General Hospital, Rourkela and from Malaria Research Centre, Delhi. The independent team held discussions with the officials at the Directorate of Health Services, State programme officer, and district malaria officer. They also visited the primary health centres, community health centres, and subcentres and supervised some of the health personnel demonstrating the rapid diagnostic tests and administering the blister packs. Some selected persons considered to be opinion leaders representing cross-section of communities in the villages were interviewed through a structured questionnaire specifically prepared pretested and validated by National Institute of Malaria Research, field station, Rourkela, for this study. The persons interviewed were village head, ward member, Mahila Mandal group leader, teacher, traditional birth attendants (TBA) and some persons from different socio-economic groups. The questionnaire contained multi-choice questions relating to general health awareness with particular reference to malaria. The general awareness about the introduction of new methods such as rapid diagnostic kits, blister packs and the opinion about the usefulness of such methods were assessed. Results In Mayurbhanj district, nine subcentres under four primary health centres were visited and 17 female health workers and malaria link volunteers were interviewed. At Kanker, six subcentres from
REETHA et al: RAPID DIAGNOSTIC KITS & BLISTER PACKS IN OPERATIONAL MALARIA CONTROL PROGRAMME 69 three PHCs were visited and a total of 16 paramedical workers were interviewed. The team assessed the performance of health personnel in conducting the rapid diagnostic tests and administering blister packs. It was observed that all the paramedicals interviewed were well trained in the use of rapid diagnostic kits and blister pack administration. It was also observed that they are giving full radical treatment even to those patients who were negative for malaria by rapid test. Visit to the subcentres and community health centres, which are located inside the Simlipal Tiger and Biosphere Reserve, revealed that the rapid diagnostic kits and blister packs were in use even in remote villages where there are no transports, electricity or communication facilities. The rapid diagnostic kits and blister packs were well accepted by the paramedical personnel and the community as observed from the interest they had shown in both the new tools in operational malaria control programme. The compliance rate of radical treatment with blister pack was found to be 100 per cent and no adverse effects were reported either by the patients or clinicians. In areas where both the rapid diagnostic kits and blister packs were introduced, there was no time lag as the radical treatment started immediately after confirming malaria by rapid diagnostic test. In areas where only blister packs were introduced, the treatment with blister packs was started immediately after collecting the blood smear. In areas without rapid diagnostic kits and blister packs, the malaria link volunteer (MLV) prepared the blood slide and gave only presumptive treatment because radical treatment for fever was given only by health workers at fever treatment depots. In such situations there was a time lag of 18-20 days before the start of radical treatment. Comparison of consumption of drugs in two different areas with and without rapid diagnostic kits showed no reduction in usage of drugs because in the absence of new guidelines the health workers were still giving full radical treatment to those patients who had tested negative by the rapid diagnostic kits. Cross-sectional opinion on a structured questionnaire was recorded from 66 (37 males, 29 females, age 17-70) and 113 (70 males, 43 females, Table III. Results of cross-sectional opinion survey regarding rapid diagnostic kits and blister combi pack in Mayurbhanj (Orissa) and Kanker (Chhattisgarh) Parameters Mayurbhanj Kanker (Orissa) (Chhattisgarh) (n=66) (n=113) No. of respondents suffered from malaria 46 (69.7) 74 (65.5) Average time lag between collection of blood smear and availability of report 20 days 18 days Knowledge about malaria diagnosis by RDK 7 (10.6) 45 (39.8) No. of respondent examined through RDK 6 (9.1) 13 (11.5) No. of respondent in favour of RDK over microscopic examination 66 (100.0) 113 (100.0) Knowledge about blister combi packs 8 (12.1) 35 (30.9) No. of respondent who have taken blister packs for treatment of malaria 6 (9.1) 13 (11.5) No. of respondents in favour of blister packs than taking loose tablets 64 (97.0) 113 (100.0) Figures in the parenthesis represent percentages RDK: Rapid diagnostic kit
70 INDIAN J MED RES, JANUARY 2007 Fig. Results of cross-sectional surveys to assess the knowledge of respondents regarding malaria in Orissa and Chhattisgarh. age 17-60) respondents from Mayurbhanj and Kanker districts respectively. The average age of respondents in both the areas was 37-38 yr (range 17-70 yr). In Orissa, 65 per cent respondents were either high school pass or graduates whereas in Chhattisgarh, only 35 per cent respondents were in this educational status category. In Orissa, 12 per cent respondents were illiterate while in Chhattisgarh illiterate respondents were 21 per cent. The respondents at both the places had fairly good knowledge about malaria transmission, mosquito breeding sites and how malaria is diagnosed (Fig.). Of the total respondents, 69.7 and 65.5 per cent had suffered from malaria in Mayurbhanj and Kanker districts, respectively. The average time lag between collection of blood smear and availability of blood examination report was between 18-20 days. In Mayurbhanj district, only 10.6 and 12.1 per cent of the respondents had knowledge about rapid diagnostic kit and blister packs respectively, whereas in Kanker (Chhattisgarh) 39.8 and 30.9 per cent respondents had knowledge about RDK and blister pack. It was because RDK and blister packs were introduced 2-3 months earlier in Kanker than in Mayurbhanj district. However, only 9-11 per cent respondents had been examined by RDK and had taken blister packs for radical treatment at both the places. All respondents at both the areas, except two female respondents in Mayurbhanj district gave their opinion in favour of RDK and blister packs as convenient methods of malaria diagnosis and treatment (Table III). Discussion Introduction of rapid diagnostic test kits and blister packs in the operational malaria control programme was a beneficial step in reducing malaria morbidity and mortality especially in the hard-core remote and inaccessible areas. However, so far the blister packs are available only for adults, while in
REETHA et al: RAPID DIAGNOSTIC KITS & BLISTER PACKS IN OPERATIONAL MALARIA CONTROL PROGRAMME 71 such malaria endemic areas children suffer more from malaria. Therefore, blister packs should also be made available for younger age groups. The clinicians at the health centres reported patient s satisfaction with rapid diagnostic kits and blister packs. They also felt that continuous supply of rapid diagnostic kits and blister packs was necessary for compliance. Although there was no perceptible improvement in the patients health seeking behaviour because rapid diagnostic kits and blister packs have been introduced very recently, but it will be worthwhile to study this at a later date. Further, the health workers opined that the instructions for the use of rapid diagnostic kit and blister packs should be in local languages also. The routine identification of infections with Plasmodium species currently depends upon microscopic examination of blood smears. However, microscopy is time consuming, labourintensive and largely depends on the expertise and diligence of the microscopist 7. Moreover, microscopic examination is rather impractical in remote inaccessible tribal areas such as in Orissa and Chhattisgarh, which constitute a distinct malaria paradigm and are badly affected by perennial malaria transmission 8. In this context, introduction of rapid diagnostic kits and blister packs in the operational malaria control programme in remote and inaccessible highly malarious areas have special significance in reducing morbidity and mortality due to malaria. Presently, the rapid test kits are being used for early and easy diagnosis of P. falciparum malaria but it may assume special significance in highly endemic tribal areas for mass screening of asymptomatic carriers, which are commonly prevalent in such areas due to development of natural immunity because of repeated exposures 9. The only disadvantage of rapid diagnostic test based on PfHRP antigen is the false positivity up to three weeks even after clearance of parasitaemia. This problem may be solved if rapid test kits detecting only viable parasites are used. In conclusion, keeping in view all the advantages, both these new tools will help in reducing parasite load in high transmission areas for achieving a sustainable malaria control. Acknowledgment Authors thank the Director, National Vector Borne Disease Control Programme, Government of India, for funding the study, Dr S. Pattanayak, Prof. R.C. Mahajan and Late Dr M.A. Ansari for guidance, and Dr B.S. Das, Former Advisor, Department of Biotechnology, Government of India for associating with the independent assessment team and providing useful suggestions. The technical support provided in the field by Shriyuts P. Pradhan and D.M. Padhi, Health Educators, and other field staff from NIMR field station, Rourkela, is acknowledged. References 1. World Health Organization. Global malaria control strategy. World Health Organ Bull 1993; 71 : 281-4. 2. Sharma VP. Fighting malaria in India. Curr Sci 1998; 75 : 1127-40. 3. Sharma RS, Sharma GK, Dhillon GPS. Epidemiology and control of malaria in India. Delhi: National Malaria Eradication Programme; 1996. 4. Singh N, Valecha N, Sharma VP. Malaria diagnosis by field workers using immunochromatographic test. Trans R Soc Trop Med Hyg 1997; 91 : 396-7. 5. Valecha N, Sharma VP, Usha Devi C. A rapid immunochromatographic test (ICT) for diagnosis of Plasmodium falciparum. Diagn Microbiol Infect Dis 1998; 30 : 257-60. 6. Sharma SK, Tyagi PK, Haque MA, Padhan K. Field studies on the sensitivity and specificity of an immunochromatographic test for the detection of Plasmodium falciparum malaria in tribal areas of Orissa. Indian J Malariol 1999; 36 : 65-9. 7. Molineaux L, Gramiccia G. The Garki Project: Research on the epidemiology and control of malaria in the Sudan
72 INDIAN J MED RES, JANUARY 2007 Savanna of West Africa. Geneva: World Health Organization; 1980 p. 109-15. 8. Pattanayak S, Sharma VP, Kalra NL, Orlov VS, Sharma RS. Malaria paradigms in India and control strategies. Indian J Malariol 1994; 31 : 141-99. 9. Sharma SK, Chattopadhyay R, Chakrabarti K, Pati SS, Srivastava VK, Tyagi PK, et al. Epidemiology of malaria transmission and development of natural immunity in a malaria-endemic village, San Dolakudar, in Orissa state, India. Am J Trop Med Hyg 2004; 71 : 457-65. Reprint requests: Dr A.M. Reetha, Deputy Director, National Institute of Malaria Research (ICMR) 22 Sham Nath Marg, Delhi 110054, India e-mail: reethavijayan@rediffmail.com