MALARIA AND ITS CONTROL IN PAKISTAN: Epidemiology, Progress and Challenges

Q Kakar, 2M A Khan, 1M K Bile

Abstract One priority for Pakistan is control of Malaria which is responsible for 6% of outpatient visits and 18% of hospital admissions. Widespread drug resistance has hampered control of P.falciparum which is less prevalent but more dangerous than P.vivax. Further, the confirmed mosquito vectors An. culicifacies and An. stephensi have shown resistance to organochlorine and organophosphate insecticides. Districts and agencies of Balochistan and FATA, bordering Afghanistan and Iran, share 37 % of the total national Malaria burden and have shown Annual Parasite Incidence greater than 4.5/1000 consistently over the past five years in spite of any control programme. Pakistans Roll Back Malaria Programme (RBM) from 2001 has introduced tested strategies and tools for Malaria Control such as partnership building, Artemisinin- based Combination Therapies, Long Lasting Insecticide-treated Nets, and Rapid Diagnostic Tests. However the technical and managerial challenges facing the Programme need to be addressed in order to achieve the set RBM and MDGs targets.

1 2

World Health Organization, Country Office, Islamabad, Pakistan Director-Directorate of Malaria Control Program, Islamabad, Pakistan

Words count= 2516

(excluding 986 words of tables, abstract and references)

INTRODUCTION Malaria is a deadly mosquito-borne disease, which takes almost one million lives per year and afflicts as many as a half a billion people in 109 countries in Africa, Asia and Latin America [1]. Pakistan is among the countries where malaria continues to be a major public health problem having extensive agricultural practices, vast irrigation network and monsoon rains that contribute to the malariogenic potential in many areas [2]. The Ministry of Health (MoH) reports that in 2006 malaria was the second most reported disease in the country [3] and the WHO reports a total of 4.5 million suspected cases of malaria in Pakistan, comprising 6% of all outpatient attendances and 18% admissions in hospital; while confirmed cases of malaria were 104,454 of which 30% were due to Plasmodium falciparum in 2008 [4]. Malaria is predominantly the disease of rural areas where more people live below the poverty line (38.65%) than in urban areas (22.39%) and, in highly endemic areas, income lost per year has been measured as 70% of per capita income [5]. Malaria control has been a priority programme in Pakistan since 1950s. Directorate of Malaria Control (DMC) in the MoH is currently implementing the Roll Back Malaria strategies to reduce the disease burden by 50% [6]. The proposed target and timeline are consistent with MDGs for improved maternal and child health, as children <5 years and pregnant women are the most vulnerable to malaria [7,8]. While DMC functions at both national and provincial level, the Programme achievements are still far from its set targets. Literature and Programme data review show that disease-specific epidemiological and entomological information is limited and scattered, while, at the Programme level, comprehensive information on

epidemiology, vector characteristics and bionomics, drug resistance, control strategies, resource allocation and intervention coverage is required on a regular basis. [8]

This paper attempts to provide an overview of the disease epidemiology, prevalent major vectors, current control strategies, the success achieved, challenges encountered, and the way forward to overcome any bottlenecks. METHODOLOGY An in-depth analysis of available surveillance data within the Malaria Control Programme and from the Health Management Information System (HMIS) was carried out along with a review of the findings of several research studies conducted in Pakistan. Other national and international reports generated on the Malaria situation in Pakistan, including demographic surveys and field situation analysis reports of national and international experts were also reviewed and major findings reported. RESULTS Table 1 and 2 illustrates the overall epidemiology of malaria parasite in Pakistan. The seroprevalence rate (parasite rate/1000 population) is highest in FATA (116) and lowest in Sindh (7.3). Similarly the annual parasite incidence (API) (cases/1000 population) in 2009 is highest in Balochistan (5.8) while lowest in Punjab (0.04) and decreasing API from Khyber Pakhtunkhwa (1.13) to Sindh (0.65) and AJK (0.07). There is no evidence of a reduction of API across the years 2004 to 2008 with consistently high APIs in both FATA and Balochistan as compared to the rest of the provinces/states. Similarly, from 2004 till 2009, the proportion of Falciparum malaria in total confirmed cases was highest in Sindh (range 31.0 44.6) followed by Balochistan (range 27.0 44.3) and remained high over the years as compared to other provinces. The proportion of F. malaria increased in 2009 as compared to 2008 inFATA, Balochistan, and Khyber Pakhtunkhwa. Provincial surveillance data 2004-2009 on the slide positivity rate (SPR) has increased in 2009 as compared to 2004 except in Sindh and AJK. The highest SPR has been recorded in FATA followed by Balochistan. The proportion of confirmed cases reported from Punjab (low endemic area) was more in patients greater than 15 years

(82%) and lowest in 5-upto 10 years (3%) with major proportion occurring in males (61%) as compared to females. Three years hospital data from PHC Cell MoH show that the total reported deaths attributed to malaria declined from 341 in year 2006 to 201 in year 2007 while the case fatality rate remain steady in 2007 (0.4) as compared to 2004. Table 2 shows the stratification of malaria endemicity at district level with majority of highly endemic districts /agencies belong to Balochistan, FATA and Sindh provinces. Studies conducted on the vector fauna of Pakistan show that overall 24 species of anopheles mosquitoes have been identified so far including An. sergenti, An.s fluviatilis, An.dthali, An. turkhudi, An. annularis, An. subpictus, An. pulcherrimus, An. culicifacies, An. stephensi, An. pallidus, An. superpictus, An. moghulensis, An. multicolor, An. barianensis, An. splendidus, An. theobald, An. maculates, An. willmori, An. gigas, An. claviger, An. lindesayi, An. barbirostris, An. peditaeniatus, and An. nigerrimus. An. culicifacies and An. stephensi are the incriminated vector species with known resistance to previously used organochlorines (DDT, Dieldrin), carbamates (Propoxur) and organophosphates (malathion, fenitrothion). Table 3 illustrates the findings of Pakistan Demographic Health Survey (PDHS) 2006-07 on possession and use of mosquito nets and treatment of children with fever. This survey was conducted before the distribution of Long Lasting Insecticide-treated Nets (LLINs) in 2008 through Global Fund (in 19 districts); thus the depicted very low coverage of LLINs and effective treatment may have improved in the following year. Table 4 illustrates the antimalarial drug efficacy in treatment of Falciparum malaria. In 2004 the cure rate with chloroquine was 58% in Punjab and 17% in Sindh. That same year in Balochistan, the cure rate with chloroquine was 17%, with sulfadoxin pyrimethamine was 44%, and with amodiaquine was 47%. The cure rate with artesunate + SP in FATA in 2004 was 97% while in 2008 in Sindh, Balochistan and FATA was 100%. Similarly in 2009, the cure rate with Artemether and Lumifantrine in FATA, Balochistan, NWFP and Sindh was 100%. 4

Discussion
Malaria is a major public health problem in Pakistan and, along with other Category 3 countries (Somalia, Sudan, Yemen, Afghanistan, Djibouti and Pakistan) of the Eastern Mediterranean Region (EMR) account for more than 95% of the regional burden [9]. Malaria endemicity in Pakistan has been categorized on the basis of average API of the last 5 years. The districts falling in the highly endemic category belong to Balochistan, FATA and Sindh. All of the districts of Punjab fall in the hypo-endemic category with reported API of <0.1/1000, however the API is as high as 5.46 in Balochistan followed by FATA 3.90. Low endemicity in Punjab may have resulted from low densities of Pakistans primary vector An.culicifacies as a result of large-scale ecological changes in this Province, where water logging of soil with related salinization has created an environment not favoured for its breeding while favouring the abundance of more salt-tolerant and less efficient vector An. stephensi [10]. There has been a visible shift in spatial pattern of malaria endemicity from the eastern agriculture plains (Punjab) to the north-western mountainous regions (Balochistan and FATA) bordering with Iran and Afghanistan, linked with refugees influx in 1980s [11]. The results of recent parasite sero-prevalence survey conducted in 19 highly endemic districts shows the highest parasite prevalence rate in FATA (116 per 1000 population) followed by Balochistan (47.9 per 1000 population) [12]. Information on age and sex for confirmed clinical malaria cases is very scarce, but a situation analysis report of the low endemic province of Punjab in 2008 revealed that males of age >14 are more affected by malaria infections as compared to females of the same age [13]. While information on severe and complicated malaria cases and on mortality is not routinely collected by the programme, thethree years hospital data from PHC Cell MoH indicate case fatality rate is unchanged. 5

P.falciparum and P.vivax are the only prevalent species of malaria parasite in the country; P.vivax is the predominant one (>74%) throughout Pakistan, with maximum number being reported from Khyber Pakhtunkhwa (26%) and FATA regions [4]. Studies conducted on genetic characterization of P. vivax populations have shown multiplicity of infections andmarked polymorphism with extensive allelic variation, which has been linked with cross border movements of populations living in frontier regions of the country [14]. However, molecular characterization of P. falciparum field isolates in Pakistan show that majority of patients had monoclonal infections with genetic diversity and allelic distribution similar to previous reports from India and other Southeast Asian countries having low malaria endemicity [15]. Resistance of P. falciparum to antimalarial drug Chloroquine was first detected in 1981 in district Sheikhupura, Punjab. The consolidated analysis of 20 years (1977-1995) of susceptibility studies conducted by the former National Institute of Malaria Research and Training (NIMRT) Lahore, published in 1997, revealed that RI level Chloroquine resistance is widespread in Pakistan (frequency ranging from 30-84%)[19]. Programme surveys on the efficacy of antimalarial drugs since 2004 to 2009 show that resistance to Chloroquine is common in falciparum malaria in all parts of the country with rising trend of resistance to SP. ACT, on the other hand, has been found to be 100% effective in treating uncomplicated falciparum malaria.

Information on prevalent vectors and their bionomics show that overall twenty-four species of Anopheles are known to occur in Pakistan An. culicifacies is the primary vector active in rural areas [16]. An. stephensi is incriminated to be responsible for urban transmission, but its role as a major vector needs to be further evaluated. Both are endophilic in resting habits and usually bite from midnight till 2:30 a.m., and their density peak in August, September and October is linked with the peak seasonality of the disease. Out of the five known sibling species A, B, C, D 6

and E of An. culicifacies A and B have been reported from the neighbouring countries of Iran, India, Afghanistan and China, but information on these sibling species and their role in malaria transmission in Pakistan need to be explored[17]. Resistance to previously used organochlorines (DDT, Dieldrin), carbamates (Propoxur) and organophosphates (Malathion, fenitrothion) has been well documented [18]. Malaria Control activities are on ground since 1950s through succession of different approaches. The most ambitious program was the Malaria Education Campaign, spearheaded by USAID and WHO since 1961. In 1977, Malaria control activities were integrated with the other Communicable Disease Control programmes in the provinces. Subsequently in 1978, it was integrated with the PHC services. Following some major failures in other endemic countries, the Roll Back Malaria (RBM) initiative was coordinated and started by WHO, UNICEF, UNDP and the World Bank in 1998. Being a signatory to the initiative, Pakistan commenced the implementation of RBM interventions in a phased manner since 2001, backed up by a National Strategic Plan based on the following six key elements: Appropriate strategies and processes including monitoring, supervision etc. Early Diagnosis and Rapid Treatment at general health facilities and, when appropriate, in the community. Multiple prevention measures including promotion of insecticide treated materials, targeted use of residual spraying, health education, and introduction of biological and environmental management approaches. Improved detection and response to epidemics. Developing viable partnerships with international and in country government and nongovernment partners. Operational research.

 Elimination of residual foci of malaria transmission in areas in the Province of Punjab, AJK, FANA and ICT with very low endemicity through the implementation of Preelimination strategy. In spite of the efforts of the Malaria Control Programme and partners, the desired coverage of the effective interventions was not achieved by 2007, as is evident from PDHS that year; the overall ownership of one LLIN per household was only 0.8%, and the overall net use by pregnant women and children <5 years was 4.2 % [20]. However distribution of 1 million LLINs through Global Fund R-7 grant support in 19 highly endemic districts is changing the scenario. Programme is keen to enhance the coverage of LLINs and diagnostic services through the forthcoming Global Fund rounds to achieve universal coverage. Ever since the inception of RBM project in 2001, Malaria Control Programme has made tangible progress in partnership building, policy guidelines for new interventions such as LLINs, RDTs and ACTs, and imposing bans on the production of oral artemisinin montherapies, injection chloroquine and halofantrine, which were injudiciously prescribed by private care providers. WHO has been the major agency providing technical assistance and supporting the Programme in its initiatives [20]. Low technical and managerial capacities of the Programme at national and provincial levels and low coverage of interventions of the population at risk are the major challenges faced by the Programme. CONCLUSION Malaria is a major cause of morbidity in districts and agencies located in FATA, Balochistan, Sindh and Khyber Pakhtunkhwa provinces. Weak health systems incapable of providing quality-assured early diagnosis and prompt treatment services, low coverage of prevention tools (LLINs, IRS) and deteriorating security situation has increased the transmission potential of 8

these districts. Although technical support from WHO is available to the Programme and substantial progress has been achieved in resource mobilization from Global Fund, introduction of new interventions as LLINs, combination therapies (ACT), rapid diagnostic tests (RDTs) and partnership building with international and national development partners, still the challenges of low technical and managerial capacities of the Programme at all levels, low coverage of available interventions, weak health systems, paucity of domestic and external funding sources persist. Resistance to antimalarial drugs in the parasite and resistance to insecticides in the vectors pose a potential threat of losing these effective control tools. Strategic and policy review, establishment of technically sound and managerially strong provincial Programme teams entrenched in strong political support of policy makers appear to delineate the way forward.

References
1. World Malaria Day - April 25, 2010. Countdown to save a million lives. Geneva, World Health Organization, 2010 [Website] (http://www.rbm.who.int/worldmalariaday/background.html, accessed on 4 May 2010). 2. 3. World Malaria Report 2005. Geneva, World Health Organization, 2005. Murtaza G et al. Malaria morbidity in Sind and the plasmodium species distribution. Pakistan journal of medical science, 2009, 25(4): 646-9. 4. 5. World Malaria Report 2009. Geneva, World health Organization, 2009. Mukhtar EM, ed. Economic analysis for a national study on malaria control in Pakistan. Islamabad, Pakistan, Malaria control programme, Ministry of health, 2004. 6. National strategic plan Directorate of Malaria Control 2006-2010. Islamabad, Pakistan, Malaria control programme, Ministry of health, 2006. 7. Teklehaimanot A et al. Coming to grips with malaria in the new millennium. London, United Kingdom, UN Millennium Project, 2005. 8. Bhatti MA et al. Malaria and Pregnancy: the perspective in Pakistan. Journal of Pakistan Med Association, 2007,57( 1):15-18. 9. Huda A, Zamani G. The progress of roll back malaria in Eastern Mediterranean region over the past decade. Eastern Mediterranean health journal, 2009, 14:S82-9. 10. Herrel N. et al, Adult anopheline ecology and malaria transmission in irrigated areas of South Punjab, Pakistan. Medical and veterinary entomology, 2004, 18:141-52. 11. Jamil HK, Kavita P. Disease and dislocation: the impact of refugee movements on the geography of malaria in NWFP, Pakistan. Social science & medicine, 2001, 52: 1043-55. 12. Malariometric Survey 19 districts Pakistan (Draft final report) 2009. Islamabad, SoSec Consulting services, 2009. 13. Kondrachine A. Situation analysis of malaria in the province of Punjab 1-21st September 2008. Islamabad, Pakistan, Country office, World Health Organization, 2008.

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Zakeri et al. Molecular characterization of plasmodium vivax clinical isolates in Pakistan and Iran using pvmsp-1, pvmsp-3 and pvcsp genes as molecular markers. Parasitology international, 2010, 59: 15-21.

15. Ghanchi NK et al. Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2. Malaria Journal 2010, 9:1 doi:10.1186/1475-2875-9-1 16. Khan MA. The Mosquitoes of Pakistan: a checklist. Mosq.syst, 1971, 3(4). 17. Barik,TK, Sahu B, Swain V. A review on An.culicifacies : from Bionomics to control with special reference to Indian subcontinent. Actatropica, 2008.

18. Rathore HR et al. Insecticide resistance in anopheline mosquitoes of Punjab province Pakistan.Pakistan journal of zoology, 1985, 17(1): 35.
19. Shah et al. Chloroquine resistance in Pakistan and the upsurge of falciparum malaria in Pakistan and Afghan refugee population. Annals of tropical medicine and parasitology,1997,91(6):pages 59102. 20. Pakistan Demographic and Health Survey 2006-07: preliminary report. Islamabad, Pakistan, National Institute of Population Studies, 2007. 21. Minutes of the 207th Meeting of the Central Licensing Board held on 20-21st July 2007. Islamabad, Pakistan, Ministry of health, 2007.

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Table 1: Epidemiology of Malaria Parasite in Pakistan Variable/Indicator

Sero Prevalence Rate (Parasite rate/1000 population) in 19 highly endemic districts of the country (2009)

Area
FATA Balochistan Khyber Pakhtunkhwa Sindh Total Year FATA Balochistan Khyber Pakhtunkhwa Sindh Punjab AJK Total FATA Balochistan Khyber Pakhtunkhwa Sindh Punjab AJK Total Pakistan 0-upto 5 years 5-upto 10 years 10-upto15 years Greater than 15 years Male Female Year Hospital admissions due to all communicable diseases 2004 322970 2006 198574 2007 197490

Findings
Sample PF PV Total Parasite Pop Rate/1000 116.0 003 081 084 0724 47.9 119 198 317 6613 35.0 019 049 068 1944 7.3 009 010 019 2595 41.1 150 338 488 11876 2004 2005 2006 2007 2008 2009 3.95 4.50 5.44 6.19 4.64 3.9 4.23 7.41 6.23 6.33 4.56 5.8 1.13 0.92 0.83 0.80 0.68 1.15 1.01 0.81 0.89 0.71 0.62 0.65 0.05 0.03 0.02 0.02 0.04 0.04 0.16 0.16 0.07 0.21 0.05 0.07 1.75 2.30 2.25 2.38 1.77 1.93 17.0 14.9 17.4 16.0 15.6 31.0 34.0 44.3 33.9 43.0 27.0 32.0 9.0 10.5 09.2 10.0 7.0 10.0 33.0 36.7 44.6 33.0 32.3 31.0 11.0 02.6 05.4 02.0 01.8 05.0 19.0 23.4 21.5 19.0 29.9 13.0 20.5 22.06 22.0 20.5 18.9 20.3 113 (6.0 %) 056 (3.0 %) 163 (9.0 %) 1571 (82.0%) 1162 (61%) 0740 (39%) Admissions Deaths CFR% due to malaria 58389 60162 50409 250 341 201 0.4 0.5 0.4

Annual Parasite Incidence (Cases/1000 population)

Proportion of Falciparum Malaria in total confirmed cases

Proportion of confirmed cases of Punjab by age group in 2007. Proportion of confirmed cases of Punjab by gender in 2007 Disease attributed mortality

Table-2. Categorization of districts based on the reported case burden 2008

Endemicity Hyper endemic districts Average 5 years API >5 Mesoendemic districts Average 5 years API >1 <5 Hypo endemic Punjab Sindh Kashmore,T.Allahyar Balochistan Zhob, Punjgur, Kharan, Noushki, Gawadar, Kech, Ziarat, J.Mangsi, Jaffarabad, Sibi, Kohlu K.Saiful,Bolan, Nasiabad, Loralai, Mustang, Chagi, Washuk Khuzdar Pishin, Musakhel, Barkhan Awarn, Lasbella, Kalat K.Abudla Quetta D.Bugti, Sherani, Harnahi NWFP FATA Kurum, Khyber AJK

Average API <1

All the districts of Punjab

Mithi, N.Feroz, Mirpurkhas, Umerkot,Khairpur,B adin,Nawabshah, Sanghar Thatta Shkarpur Gotki Dadu Sukkr Tando M.Khan Larkana Hyderabad Jamshoro Jacoabad Shahdadkot ,Matiari Karachi

Buner,L.Marawat.Bann u, Tank, Hangu,Karak, Mardan,Malakand Swat D.I.Khan Charsada,Batagram , Kohat , Naushera, Dir Up Chitral Dir lower ,Swabi Haripur Menshera,Abbotabad Peshawar. Kohistan Shangla

Bajor, Orakzai, Mohmnd, S.Waziristan Poonch Mirpur Kotli Muzafara bad

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Table 3. Coverage of interventions (treatment and LLINs) DHS Pakistan 2006-07

Variable/Indicator Households possession of nets (treated or untreated) Households with at least one insecticide-treated net (ITN) Children under 5 sleeping under a mosquito net the night before the survey Children under 5 who slept under an ITN the night before the interview Pregnant women who slept under a mosquito net the night before the interview pregnant women age who slept under an ITN the night before the interview children under age 5 with fever in the two weeks preceding the survey who took antimalarial drugs children under age 5 with fever in the two weeks preceding the survey, who took antimalarial drugs the same day/next day n 3159 3159 2636 2636 364 364 791 791 Urban % 3.5 0.7 1.2 0.2 0.7 0.0 2.5 2.0 Rural n 6096 6096 6142 6142 829 829 1777 1777 % 7.8 0.8 1.8 0.2 2.0 0.0 3.7 2.8 n 9255 9255 8778 8778 1193 1193 2569 2569 Total % 6.3 0.8 1.6 0.2 1.6 0.0 3.3 2.6

Table-4
District Khurram

Antimalarial Drug Efficacy Monitoring Surveys 2004-2009

Province FATA Punjab Sindh Sindh Balochistan Survey Year 2004 2008 2009 2004 2004 2008 2009 2008 2009 2004 Drugs tested SP-AS Artesunate+SP Artemether+Lumifantrine CQ CQ Artesunate+SP Artemether+Lumifantrine Artesunate+SP Artemether+Lumifantrine AQ SP CQ Artesunate+SP Artemether+Lumifantrine Cure Rate % 97 100 100 58 17 100 100 100 100 47 44 17 100 100

Muzaffargarh Mirpurkhas Thatta Zhob

Kech/Turbat

Balochistan 2008 2009

Figure-1

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