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

The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17 th 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.

Skin and Mucocutaneous Manifestations: Useful Clinical Predictors of HIV/AIDS.

BACKGROUND AND AIMS: The HIV infection is associated with several dermatological conditions which may be the first pointer towards the existence of HIV. These may present with unusual and atypical manifestations in the course of the HIV infection. Keeping this in mind, the seroprevalence of HIV in these persons and the spectrum of the skin and the mucocutaneous lesions in the HIV positive patients was studied. METHODS: The current prospective study was conducted over a period of 3 years (2006-2008). A total of 604 persons who had any kind of skin and mucocutaneous infections were screened for the HIV infection as per the NACO guidelines after recording their clinical and epidemiological profiles. RESULTS: Out of the 604 patients who were screened, 90(14.90%) were seropositive for the HIV-I antibodies and none was positive for the HIV-2 antibodies. Seventy three point thirty three percent 73.33 of the seropositive patients were in the age group of 15-40 years, with a male-female ratio of 1:1.05. The heterosexual route was the most common mode of transmission (86.6%).A wide range of infectious and noninfectious lesions were observed. In the HIV seropositive patients, oral candidiasis (32.22%) was the most common infectious disease which was observed, followed by herpes zoster (13.33%), genital warts (7.77%) and genital herpes (6.66%). The most common noninfectious manifestation was seborrhoic dermatitis (8.88%), followed by pruritic papular eruptions (7.77%). CONCLUSION: As there is a high prevalence of the HIV infection in patients who have skin and mucocutaneous disorders, the doctors, during the investigation of these patients, must have a high level of suspicion for the HIV infection in their mind. An early detection of HIV optimizes the chemoprophylaxis for many opportunistic mucocutaneous disorders.

Prevalence of Sexually Transmitted Infections (HIV, Hepatitis B, Herpes Simplex Type 2 and Syphilis) Among Asymptomatic Pregnant Women.

OBJECTIVES: To determine the current prevalence of four major sexually transmitted infections (STIs: HIV, Hepatitis B, Herpes simplex virus 2, and Syphilis) in asymptomatic pregnant women. METHODS: This is a prospective study of 500 consecutive, apparently healthy asymptomatic pregnant women who were attending the antenatal clinic. The information regarding their socio-demographic and behavioral characteristics and obstetric performance was recorded. The blood samples was collected after obtaining their informed written consent from those who were tested for the HIV antibodies (NACO guidelines), HBsAg (ELISA test), HSV2-IgM (ELISA test), and Syphilis (VDRL and TPHA tests). RESULTS: The overall prevalence of one or the other four STIs studied was 4.8 % with the highest prevalence of HBV (2.4 %), followed by HSV-2 (2 %), and HIV (0.4 %). No woman tested positive for syphilis and multiple infections. All the infections were more common in illiterate, multigravida, monogamous women of low socio-economic status. High-risk sexual behavior of the husbands, history of STIs in husbands, and blood transfusions were the other factors associated with the prevalence of these infections. CONCLUSIONS: The relatively high prevalence of HBV and HSV-2 infections in asymptomatic pregnant women suggests that there is need of screening for HBV and HSV-2 infections along with the pre-existing screening for HIV and Syphilis and universal immunization of HBV high-risk infants.

Monitoring antimalarial drug resistance in India via sentinel sites: outcomes and risk factors for treatment failure, 2009-2010.

OBJECTIVE: To describe India's National Antimalarial Drug Resistance Monitoring System, measure the efficacy of first-line malaria treatments, and determine risk factors for treatment failure. METHODS: In 2009-2010, prospective studies with 28 days of follow-up were conducted at 25 sentinel sites. Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine (AS+SP); those infected with P. vivax were given chloroquine. Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure. Isolates of P. falciparum were checked for dhfr and dhps mutations. FINDINGS: Overall, 1664 patients were enrolled. Kaplan-Meier survival analysis showed an efficacy of 98.8% for AS+SP. Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation, but six, including four with treatment failure, remained parasitaemic after 72 hours. Double mutants in dhfr were found in 68.4% of the genotyped isolates. Triple or quadruple mutants in dhfr and mutations in dhps were rare. A daily dose of artesunate of < 3 mg per kg of body weight, age of less than 5 years, and fever at enrolment were associated with an increased risk of treatment failure. Chloroquine remained 100% efficacious and generally cleared P. vivax parasitaemias within 48 hours. Vomiting (seen in 47 patients) was the most common adverse event. CONCLUSION: India's National Antimalarial Drug Resistance Monitoring System provides wide coverage. The first-line antimalarials used in the country remain safe and efficacious. The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration.

Comparison of HIV antibody detection by conventional method and dried tube specimen: stability and validation study for HIV serology.

This study was carried out to compare HIV antibody detection by conventional method and serum dried in test tube and to check the stability of dried tube specimen (DTS) at ambient temperature. A total of 50 serum samples were tested for HIV antibodies, which were sent for testing in the state reference laboratory, by conventional method according to NACO guidelines. The same serum samples were dried in test tubes and then after elution with PBS again tested for HIV antibodies by same method and kits at 0 day and after 30 days. DTS eluted by PBS showed linear correlation to the serum samples. The antibodies in DTS were found to be stable at 37 degrees c up to 30 days. This method is simple, sensitive and specific and can be used in resource limited settings embarking on scaling up of HIV testing.

Antimalarial drug resistance of Plasmodium falciparum in India: changes over time and space.

After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965. However, the initial success could not be maintained and a resurgence of malaria began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was first reported in 1973 and increases in antimalarial resistance, along with rapid urbanisation and labour migration, complicated the challenge that India's large geographical area and population size already pose for malaria control. Although several institutions have done drug-resistance monitoring in India, a complete analysis of countrywide data across institutions does not exist. We did a systematic review of P falciparum malaria drug-efficacy studies in India to summarise drug-resistance data and describe changes over the past 30 years to inform future policy. Continued use of chloroquine for treatment of P falciparum malaria in India will likely be ineffective. Resistance to sulfa-pyrimethamine should be closely monitored to protect the effectiveness of treatment with artesunate plus sulfadoxine-pyrimethamine, which is the new first-line treatment for P falciparum malaria. Strategies to reduce the emergence and spread of future drug resistance need to be proactive and supported by intensive monitoring.

Seroprevalence of HIV infection among the patients attending various emergency departments in a tertiary care hospital.

Emergency departments (EDs) receive patients from every background, socioeconomic group and health status. Hence, EDs can play a critical role in offering human immunodeficiency virus (HIV) testing and help in the national strategy of early HIV detection. The present study was conducted on 400 patients attending various EDs after taking Institutional Review Board approval. They were screened for HIV antibodies by three rapid/simple assay tests having different principles/antigens as per the NACO guidelines. Twenty-three (5.75%) of the 400 patients were HIV reactive. Fifteen (65.22%) of the 23 HIV-reactive patients were unaware of their reactive status. Majority of the HIV-reactive (65.22%) patients were from the Medicine emergency followed by Orthopaedics and Surgery (13.04%). Seven (30.43%) had history of fever of more than 1 month duration. Eight (34.78%) of them were later on clinically diagnosed as having various opportunistic infections. Thus, the study emphasizes the need for expansion of routine voluntary HIV counseling and testing to all the patients who come to the ED and practicing universal work precautions by health care workers.

Prevalence of Methicillin-resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Hospital in Northern India.

AIM: The emergence of Methicillin-resistant Staphylococcus aureus (MRSA) has posed a serious therapeutic challenge. We report the prevalence and antibiotic susceptibility pattern of MRSA in the hospitals attached to GMC, Amritsar, Punjab. MATERIALS AND METHODS: The study comprised of 250 coagulase-positive staphylococci (COPS) isolated from a total of 6743 clinical specimens (like pus, blood, urine, high vaginal swab, sputum, etc.) of patients admitted in hospitals attached to Government Medical College, Amritsar from January 2008-February 2009. Routine antibiotic susceptibility testing was performed and interpreted as per standard guidelines. Methicillin resistance was detected using oxacillin and cefoxitin disc diffusion method, oxacillin screen agar method, and minimum inhibitory concentration using broth macrodilution method. RESULTS: A total of 115 (46%) strains were found to be methicillin resistant. Multidrug resistance was observed in 73% MRSA strains. However, no strain was resistant to vancomycin. CONCLUSION: Regular surveillance of hospital-associated infection and monitoring of antibiotic sensitivity pattern is required to reduce MRSA prevalence.

Prevalence of human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus in three groups of populations at high risk of HIV infection in Amritsar (Punjab), Northern India.

Three groups of populations at high risk of human immunodeficiency virus (HIV) infection, i.e., injecting drug users (IDUs), truckers, and attendees of sexually transmitted disease (STD) clinic of Amritsar (Punjab), Northern India, were studied in order to determine the prevalence of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections. Of the 157 IDUs, 16.6, 17.8, and 33.7% were found to be positive for HIV, HBV, and HCV infections, respectively. HCV showed significant difference (P<0.01) and very high rate (8.3%) of co-infection with HIV. In truckers, maximum seropositivity was associated with HIV (19%), i.e., significantly higher than that of HBV (6%, P<0.01) and HCV (3%, P<0.01). In STD clinic attendees, the highest rate of seroprevalence was that of HIV (4.3%), followed closely by that of HBV (3.7%), and HCV (2.6%). The present study emphasizes the need for early screening for HBV and HCV infections of all those also at high risk for HIV infection, and the results highlight the importance of relevant targeted interventions in these populations.

Emergence of drug resistance in India.

Chloroquine resistance in Plasmodium malaria is an emerging problem globally. In India resistance of Plasmodium falciparum to choloroquine, the cheapest and the most used drug was first reported in the year 1973 from Diphu of Karbi-Anglong district in Assam state. Systematic monitoring of drug resistance is being undertaken in the country from 1978 by the Directorate of National Vector Borne Disease Control Programme (NVBDCP) through its 13 Pf monitoring teams. The findings of these drug resistance studies has helped the programme for the revision of the drug policy and update it from time to time thereby facilitating appropriate measures for not only individual cases but also to contain and prevent further spread of resistant foci. This article summarises therapeutic efficacy studies conducted by the Pf monitoring teams in the country between 2001 and 2007 related to efficacy of chloroquine and other antimalarials drugs. As per the results available, the efficacy of chloroquine for treating uncomplicated falciparum at most of the study sites is much lower than the desired cut off levels of 10% (83% studies have shown treatment failure more than 10%). Total of 4273, 168 and 137 P. falciparum cases have been tested against chloroquine, sulphadoxine/pyrimethamine and ACT(AS+SP) combination. During the period under report, 85 new chloroquine resistant PHCs/foci from 64 districts were qualified warranting change of drug policy as per the national guidelines. These studies show that chloroquine resistance in P. falciparum is widespread in the country. To combat the drug resistant in malaria, the use of combination therapy ie, artesunate plus sulfadoxine/pyrimethamine has been recommended for treatment of all confirmed P. falciparum cases in all the qualified areas as per the criteria laid down in National Drug Policy on malaria.

Extended spectrum beta lactamase--mediated resistance among isolates of family Enterobacteriaceae.

The emergence and spread of extended spectrum beta lactamase (ESBL) producing strains have led to questions regarding optimal therapy for infections especially empirical treatment of suspected gram negative infection. A total of400 isolates belonging to family enterobacteriaceae were isolated from various clinical samples and were studied for ESBL production by NCCLS (National Committee for Clinical Laboratory Standards) confirmatory test (using disc diffusion technique) and MIC brott dilution test. ESBL production was found in 61.72% of hospital isolates and 30.90% of outdoor isolates. The susceptibility of ESBL producers to imipenem and amikacin was found to be 100% and 63.38% respectively. A high degree of associated resistance to other antimicrobial was found in ESBL producers. Tests for detection of ESBLs and continuous monitoring of antimicrobial sensitivity pattern in individual setting is emphasized to minimise the emergence of drug resistant bacteria.

Seroprevalence of human immunodeficiency virus-2 in and around Amritsar.

A total of 14555 serum samples collected between January, 2001 to April, 2006 were screened for HIV infection. Antibodies to HIV-1/ HIV-2 were present in 985 (6.76%) of which 964 (97.86%) and 2 (0.22%) were positive for HIV-1 and HIV-2 alone respectively and 19 (1.92 %) for both HIV-1 and HIV-2. Of the 21 in whom HIV-2 infection was detected (alone and dual), 19 (90.5%) were in the age group of 21-40 years and 2 were children below the age of 11 years. Predominantly mode of transmission in them was heterosexual (85.71%) while the 2 children (9.53%) had most probably got the infection through perinatal route. Nine (42.85%) were asymptomatic and 12 (57.15%) clinically presented with chronic diarrhoea (5), prolonged fever (4) and symptoms related to sexually transmitted diseases (3). Opportunistic infections like Oral candidiasis was observed in 3 and pulmonary tuberculosis in 2.

Characterisation, biotyping, antibiogram and klebocin typing of Klebsiella with special reference to Klebsiella oxytoca.

400 strains of Klebsiellae identified by culture characteristics and biochemical reactions were subjected to biotyping, antibiogram and klebocin typing. Based on indole production, pectin and gelatin liquefaction 16.0% of all the isolates were Klebsiella oxytoca. Maximum sensitivity was shown to Amikacin (72%) and maximum resistance to Ampicillin (87.5%). Klebocin typability was 73.5%. So by combining biotyping, antibiogram and Klebocin typing, Klebsiella could be differentiated better than based on any single marker.

Non-fermenters in human infections.

One thousand and one hundred thirty non-fermenting gram negative bacteria were isolated from various samples. Of these, Pseudomonas aeruginosa was the commonest isolate (72.83%) followed by Acinetobacter anitratus (8.4%), Alcaligenes faecalis (7.6%), Acinetobacter lwoffi (4.4%), Pseudomonas flourescens (2.4%), Schwanella putrefaciens (1.6%), Stenotrophomonas maltophilia (1.6%), Pseudomonas putida (0.4%), Bravundimonas vesicularis (0.4%) and Flavobacterium meningosepticum (0.4%). Antibiotic sensitivity pattern showed multiple drug resistance pattern with majority of the isolates being resistance to two or more drugs.