In vitro sensitivity pattern of chloroquine and artemisinin in Plasmodium falciparum.

Artemisinin (ART) and its derivatives form the mainstay of antimalarial therapy. Emergence of resistance to them poses a potential threat to future malaria control and elimination on a global level. It is important to know the mechanism of action of drug and development of drug resistance. We put forwards probable correlation between the mode of action of chloroquine (CQ) and ART. Modified trophozoite maturation inhibition assay, WHO Mark III assay and molecular marker study for CQ resistance at K76T codon in Plasmodium falciparum CQ-resistant transporter gene were carried out on cultured P. falciparum. On comparing trophozoite and schizont growth for both CQ-sensitive (MRC-2) and CQ-resistant (RKL-9) culture isolates, it was observed that the clearance of trophozoites and schizonts was similar with both drugs. The experiment supports that CQ interferes with heme detoxification pathway in food vacuoles of parasite, and this may be correlated as one of the plausible mechanisms of ART.

Antimalarial drug policy in India: Past, present & future.

The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17th century. Since the formal establishment of a malaria control programme in 1953, shortly after independence, treatments provided by the public sector ranged from chloroquine, the mainstay drug for many decades, to the newer, recently introduced artemisinin based combination therapy. The complexity of considerations in antimalarial treatment led to the formulation of a National Antimalarial Drug Policy to guide procurement as well as communicate best practices to both public and private healthcare providers. Challenges addressed in the policy include the use of presumptive treatment, the introduction of alternate treatments for drug-resistant malaria, the duration of primaquine therapy to prevent relapses of vivax malaria, the treatment of malaria in pregnancy, and the choice of drugs for chemoprophylaxis. While data on antimalarial drug resistance and both public and private sector treatment practices have been recently reviewed, the policy process of setting national standards has not. In this perspective on antimalarial drug policy, this review highlights its relevant history, analyzes the current policy, and examines future directions.

The National Academy of Vectors and Vector Borne Diseases in India: two decades of progress.

The National Academy of Vector Borne Diseases (NAVBD) was founded at Bhubaneswar in 1994, by Dr AP Dash, along with 15 like-minded scientists from all over India. NAVBD is a non-profit academic organization in India, dedicated to advancing and promoting knowledge on vectors and vector-borne diseases, and encouraging scientists and members of the academy to conduct research on vectors and vector-borne diseases. NAVBD convenes national and international seminars, symposia and workshops to exchange knowledge on recent advances in the field of vectors and vector-borne diseases and raise public awareness. Plans are under way to expand the Academy’s activities to the rest of the South- East Asia Region.

In vitro assessment of drug resistance in Plasmodium falciparum in five States of India.

Background & objectives: In vitro assays are an important tool to assess baseline sensitivity and monitor the drug response of Plasmodium falciparum over time and place and, therefore, can provide background information for the development and evaluation of drug policies. This study was aimed at determining the in vitro sensitivity of P. falciparum isolates to antimalarials. Methods: The in vitro activity of 108 P. falciparum isolates obtained from five States of India was evaluated using WHO microtest (Mark III) to chloroquine, monodesethylamodiaquine, dihydroartesunate and mefloquine. Samples were collected from the States of Orissa, Jharkhand, Karnataka, Goa and Chhattisgarh from September 2007 to August 2009. In addition, representative samples from different States of India cryopreserved and culture adapted in the Malaria Parasite Bank of National Institute of Malaria Research, New Delhi, were also evaluated. Results: The proportion of isolates resistant to chloroquine and monodesethylamodiaquine was 44.4 and 25 per cent, respectively. Of the 27 isolates resistant to monodesethylamodiaquine, 16 (59.3%) were cross-resistant to chloroquine. No isolate showed resistance to dihydroartesunate and mefloquine. Isolates from Orissa showed the highest degree of resistance to chloroquine and amodiaquine followed by Jharkhand. Forty two isolates were genotyped for pfcrt T76K chloroquine resistant mutation; mutations were seen in 38 (90.47%) isolates. Interpretation & conclusions: The Indian P. falciparum isolates showed a high degree of resistance to chloroquine followed by monodesethylamodiaquine. No resistance was recorded to mefloquine and dihydroartesunate.

Plasmodium vivax merozoite surface protein-3a: A high-resolution marker for genetic diversity studies.

Background & objectives: Malaria, an ancient human infectious disease caused by five species of Plasmodium, among them Plasmodium vivax is the most widespread human malaria species and causes huge morbidity to its host. Identification of genetic marker to resolve higher genetic diversity for an ancient origin organism is a crucial task. We have analyzed genetic diversity of P. vivax field isolates using highly polymorphic antigen gene merozoite surface protein-3alpha (msp-3α) and assessed its suitability as high-resolution genetic marker for population genetic studies. Methods: 27 P. vivax field isolates collected during chloroquine therapeutic efficacy study at Chennai were analyzed for genetic diversity. PCR-RFLP was employed to assess the genetic variations using highly polymorphic antigen gene msp-3α. Results: We observed three distinct PCR alleles at msp-3α, and among them allele A showed significantly high frequency (53%, χ2 = 8.22, p = 0.001). PCR-RFLP analysis revealed 14 and 17 distinct RFLP patterns for Hha1 and Alu1 enzymes respectively. Further, RFLP analysis revealed that allele A at msp-3α is more diverse in the population compared with allele B and C. Combining Hha1 and Alu1 RFLP patterns revealed 21 distinct genotypes among 22 isolates reflects higher diversity resolution power of msp-3α in the field isolates. Interpretation & conclusion: P. vivax isolates from Chennai region revealed substantial amount of genetic diversity and comparison of allelic diversity with other antigen genes and microsatellites suggesting that msp-3α could be a high-resolution marker for genetic diversity studies among P. vivax field isolates.

Malaria in India: challenges and opportunities.

India contributes about 70% of malaria in the South East Asian Region of WHO. Although annually India reports about two million cases and 1000 deaths attributable to malaria,there is an increasing trend in the proportion of Plasmodium falciparum as the agent. There exists heterogeneity and variability in the risk of malaria transmission between and within the states of the country as many ecotypes/paradigms of malaria have been recognized. The pattern of clinical presentation of severe malaria has also changed and while multi-organ failure is more frequently observed in falciparum malaria, there are reports of vivax malaria presenting with severe manifestations. The high burden populations are ethnic tribes living in the forested pockets of the states like Orissa, Jharkhand, Madhya Pradesh, Chhattisgarh and the North Eastern states which contribute bulk of morbidity and mortality due to malaria in the country. Drug resistance,insecticide resistance,lack of knowledge of actual disease burden along with new paradigms of malaria pose a challenge for malaria control in the country. Considering the existing gaps in reported and estimated morbidity and mortality, need for estimation of true burden of malaria has been stressed. Administrative, financial,technical and operational challenges faced by the national programme have been elucidated. Approaches and priorities that may be helpful in tackling serious issues confronting malaria programme have been outlined.

Operational feasibility of rapid diagnostic kits & blister packs use for malaria control in high transmission areas of Orissa & Chhattisgarh.

BACKGROUND & OBJECTIVE: 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.

Assessment of therapeutic efficacy of chloroquine and sulphadoxine-pyrimethamine in uncomplicated falciparum malaria.

A standardised protocol has been developed by World Health Organization (CDS/RBM/2002) to assess the efficacy of common antimalarials in the treatment of clinically manifested infection with uncomplicated P. falciparum malaria for areas with low to moderate transmission. The therapeutic efficacy protocol is based on clinical and parasitological responses of the patients and it has the purpose of determining the practical efficacy of the drug regimen in study areas with the ultimate objective of ascertaining its continued usefulness or the necessity for replacing it in the routine treatment. Present study has been conducted at seven sites--Kathiatali and Simonabasti of District Nowgaon, Assam; Sonapur and Boko of District Kamrup, Assam; Keonjhar Town, Padampur and Basudebpur of District Keonjhar, Orissa. In order to reduce the patient recruitment time, health centre close to well-defined community was identified to conduct the activities at peak malaria season by selecting local pockets and organising mobile clinics. Microscopically confirmed cases of P. falciparum were enrolled according to the criteria for inclusion and exclusion. Treatment with recommended drug was given under supervision and a follow-up schedule at various intervals for 28 days was maintained. In chloroquine (CQ) study areas, wherever patients showed treatment failure, they were treated with second line drug--sulphadoxine-pyrimethamine (SP) combination and then followed-up as per study protocol. It was observed that 30% cases showed treatment failure to CQ in District Nowgaon, where revised drug policy has already been introduced. In Kamrup district, treatment failure with CQ was found to be less than 25%, which denotes the said regimen is still effective. Almost all the patients from Padampur and Basudebpur of District Keonjhar responded to CQ, treatment failure was noticed only in two patients (3%). The antifolate combination found to be fully effective as second line and also as first line wherever revised drug policy has been introduced.