Ramesh Reddy Allam

Survival probability and predictors of mortality and retention in care among patients enrolled for first-line antiretroviral therapy, Andhra Pradesh, India, 2008–2011

BACKGROUND The national antiretroviral therapy (ART) initiative in India began in 2004. In order to better inform the national program, we estimated the mean cumulative survival probability and loss to follow-up (LFU) rate among patients initiated on ART. METHODS We identified a cohort of people living with HIV (PLHIV) aged ≥15 years initiated on ART in two ART centres in Hyderabad city, Andhra Pradesh state, India between January 2008 and December 2008. The cohort was followed-up until 31 December 2011 and death and/or LFU were the primary endpoints. Death from any cause during the study period was considered to be the result of HIV infection. We used the Kaplan-Meier estimation method for survival probability and Cox proportional hazard model to identify the predictors. RESULTS Of the 1690 patients initiated on ART, 259 (15.3%) were transferred out during the study period. Mortality rate was 7.6/100 person-years. Male gender, low CD4 count, history of tuberculosis before initiation of ART, and weight <48 kg were the predictors of mortality. Patients who were LFU were more likely to be males, unemployed, widowed, and had weight below 48 kg. CONCLUSION Survival rates on ART were higher compared to other resource-limited settings. Delayed diagnosis and initiation of ART and co-infection with TB were important predictors for both mortality and retention in care.

Predictors of immunological failure and determinants of suboptimal CD4 testing among adults with HIV on first-line antiretroviral therapy in Andhra Pradesh, India, 2008–2011

BACKGROUND Failure of first-line antiretroviral therapy (ART) results in high morbidity and mortality. We identified the predictors of immunological failure and suboptimal CD4 testing among adult people living with HIV (PLHIV) initiated on first-line ART. METHODS The cohort of PLHIV aged ≥ 15 years initiated on first-line ART in Hyderabad city, Andhra Pradesh state, in 2008 was followed-up until 31 December 2011 or until death and/or lost to follow-up (LFU). We estimated cumulative incidence of immunological failure. We explored socio-demographic, clinical, pharmacological and immunological factors to identify the predictors of immunological failure and determinants of suboptimal CD4 testing (<2 tests/year). RESULTS Among the 1431 PLHIV, 275 (19.2%) died and 263 (18.4%) were LFU. Of the remaining 893 (62.3%) patients on follow-up, 193 (21.6%) experienced immunological failure; these patients were more likely to be males, illiterate, with a history of pulmonary TB while on ART and taking stavudine-based regimen. Incidence of suboptimal testing ranged between 41 and 60% over 4 years of follow-up. Suboptimal CD4 testing among PLHIV was associated with history of TB prior to initiation of ART and stage 3 and 4 of HIV disease at enrollment. CONCLUSIONS There was low immunological failure rate but high incidence of suboptimal CD4 testing. The ART centre staff needs to be more vigilant about 6-monthly CD4 testing for timely detection of immunological failure and appropriate case management.

An outbreak of cholera in Medipally village, Andhra Pradesh, India, 2013

BackgroundCholera continues to remain endemic in over 50 countries and has caused large epidemics with around 3–5 million cases occurring every year in Asia alone. In India, cholera is endemic in many states. However, etiological information and age-specific incidence related to cholera outbreaks is limited. In November 2013, district authorities reported a cluster of diarrheal disease among residents of Medipally to the state surveillance unit. We investigated this cluster to confirm its etiology, describe its magnitude, identify potential risk factors, and make recommendations for control.FindingsA house-to-house active search was conducted to identify cases of acute diarrhea and collect information on drinking water source. Drinking water samples were collected from common water sources and sampled households to test for bacteriological quality. Ten stool samples were collected for culture. A matched case–control study was conducted to identify the risk factors. A total of 138 case-patients of diarrhea (Attack rate: 11.5/100; Population: 15 1,200) and 1 death (Case Fatality Ratio: 0.72/100) were identified. Five of the 10 stool samples were culture positive for V. cholerae, serogroup O1 El Tor. Drinking water from the overhead tank [Adjusted OR (AOR): 31.94, 95 % CI: 7.3-139.5] was associated with risk of developing illness.ConclusionsThis outbreak affected nearly 11% of the village population and was due to contamination of the main drinking water source. Outbreaks such as this can be prevented by constructing the drain away from the water pipelines and by monitoring regular chlorination of drinking water source and inspection of pipelines for damage.

Descriptive epidemiology of novel influenza A (H1N1), Andhra Pradesh 2009-2010

BACKGROUND The first case of pandemic Influenza A (H1N1) in India was reported from Hyderabad, Andhra Pradesh on 16 th May 2009. Subsequently, all suspected cases seeking treatment from A (H1N1) treatment centers and their contacts were tested. Laboratory confirmed cases were hospitalized and treated with antivirals according to national guidelines. We reviewed the surveillance data to assess the morbidity and mortality due to A (H1N1) in the state of Andhra Pradesh (population-76,210,007) during the period from May 2009 to December 2010. MATERIALS AND METHODS We obtained the line-list of suspected (influenza like illness as per World Health Organization case definition) and laboratory confirmed cases of A (H1N1) from the state unit of integrated disease surveillance project. We analyzed the data to describe the distribution of case-patients by time, place and person. RESULTS During May 2009 to December 2010, a total of 6527 suspected (attack rate: 8.6/100,000) and 1480 (attack rate: 1.9/100,000) laboratory confirmed cases were reported from the State. Nearly 90% of the suspected and 93% of the confirmed cases was from nine districts of Telangana region, which includes Hyderabad. Nearly 65% of total confirmed cases were reported from Hyderabad. The attack rate was maximum (2.6/100,000) in the age group of 25-49 years. The cases peaked during August-October. 109 case-patients died (Case fatality ratio: 7%) and most (80%) of these patients had comorbid conditions such as diabetes (24%), chronic obstructive pulmonary disease (20%), hypertension (11%) and pregnancy (11%). Case fatality was higher (16%) among patients who were older than 60 years of age compared with other age groups. CONCLUSIONS In Andhra Pradesh, H1N1 transmission peaked during August-October months and predominately affected adults. Case fatality was higher in patients older than 60 years with comorbid conditions.

A Case-control Study of Diphtheria in the High Incidence City of Hyderabad, India.

Background: India accounts for approximately 72% of reported diphtheria cases globally, the majority of which occur in the state of Andhra Pradesh. The aim of this study is to better understand lack of knowledge on diphtheria vaccination and to determine factors associated with diphtheria and low knowledge and negative attitudes. Methods: We performed a 1:1 case–control study of hospitalized diphtheria cases in Hyderabad. Eligible case patients were 10 years of age or older, resided within the city of Hyderabad and were diagnosed with diphtheria per the case definition. Patients admitted to the hospital for nonrespiratory communicable diseases and residing in the same geographic region as that of cases were eligible for enrolment as controls Results: There were no statistical differences in disease outcome by gender, education, economic status and mean room per person sleeping in the house in case and control subjects. Not having heard of diphtheria (adjusted odds ratio: 3.56; 95% confidence intervals: 1.58–8.04] and not believing that vaccines can prevent people from getting diseases (adjusted odds ratio: 3.99; 95% confidence intervals: 1.18–13.45) remained significantly associated with diphtheria on multivariate analysis. Conclusion: To reduce the burden of diphtheria in India, further efforts to educate the public about diphtheria should be considered.

Prescription practices & use of essential medicines in the primary health care system, Shimoga district, Karnataka, India

Sir As per the estimates of the World Health Organization (WHO) worldwide more than half of all the medicines are prescribed, dispensed or sold inappropriately and about one-third of the worlds population lack access to essential medicines1,2. Irrational use of medicines has several severe consequences including adverse drug reactions, drug resistance, protracted illness and even death. Inappropriate use and over-use of medicines waste resources, resulting in increased out-of-pocket expenditure by patients1,2. The Government of Karnataka in 2005 published essential medicines list (EML) and standard treatment guidelines (STG) for use in the primary health care facilities in the State3,4. Since the implementation of these guidelines there was no formal assessment of the prescription practices and availability of essential medicines in the State. Hence, a study was conducted to describe the medicine prescription practices of the medical officers, and medicine dispensing practices of the pharmacists in primary health centres (PHCs) of Shimoga district, Karnataka, following the WHO guidelines for investigation of drug use in health facilities5. Twenty of the 65 PHCs in Shimoga district were randomly selected. From each PHC, 30 consecutive patients were contacted on each Monday during the study period (December 2011-April 2012). The prescriptions of these patients were reviewed to abstract the details of medicines prescribed using the standardized data collection form to calculate five prescription indicators, i.e. (i) average number of medicines per prescription, (ii) percentage of medicines prescribed by generic name, (iii) percentage of prescriptions with antibiotic, (iv) percentage of medicines prescribed as per the essential medicines list, and (v) percentage of prescriptions with injections. For calculating the patient care indicators, ten consecutive patients exiting from dispensing room on each Monday during the study period were observed from each PHC to calculate the dispensing time, and were interviewed to know their knowledge about the dosage of medicines prescribed. From the prescriptions of these patients, the information about the number of medicines prescribed, number of medicines actually dispensed, and number of medicines adequately labelled with respect to their strength, dosage and frequency was abstracted. To calculate the facility based indicators [availability of essential medicine list (EML) and STG, percentage availability of key indicator medicines], we physically verified the availability of 20 key essential medicines in the PHC and interviewed the medical officers and pharmacists to assess their awareness about EML and STG. Averages and proportions were calculated for the medicine use indicators. To assess the degree of rational prescribing, the Index of Rational Drug Prescribing (IRDP) was calculated6. This index system has been validated for use in medical and health research6,7,8. The index of individual prescribing indicator was calculated by dividing the optimal level recommended for that indicator with the observed level in the survey. IRDP was calculated by adding up all the five indices described above. The study was approved by the institutional ethics committee of National Institute of Epidemiology (NIE), Chennai. For describing the prescription indicators, information was abstracted from 600 prescriptions from the 20 sampled primary health centres. A total of 2059 medicines were prescribed in these prescriptions (average: 3.43, SD=1.53, range: 1-9). Most of the medicines prescribed were from EML (94%) and were prescribed by generic name (84%). About a quarter of the prescriptions were poly-pharmacy prescriptions (defined as prescriptions with 5 or more drugs). Antibiotics and injections were prescribed in 49 and 61 per cent of the prescriptions respectively (Table I). Table I Indicators of rational drug use, Shimoga, Karnataka, India, 2012. The 200 prescriptions surveyed for patient care indicators contained 673 medicines, of which 93 per cent medicines were dispensed in the PHC. Only 25 per cent of the medicines dispensed were adequately labelled with a mention of strength, dosage and duration. All prescriptions had a pictogram indicating the frequency of medicine use. Majority (75%, 149/200) of patients interviewed knew the correct dosage schedule for all the medicines prescribed. The average dispensing time was 86 ± 32.36 sec. Overall, 82 per cent of the essential medicines were available in the PHCs. The EML and STG were available in three (15%) and 11 (55%) PHCs, respectively. Seventeen of the 20 (85%) medical officers and 15 of the 20 pharmacists (75%) interviewed were aware of essential medicines list. Twelve doctors (60%) were aware of standard treatment guidelines. The overall IRDP of the Shimoga district was 3.42 compared to the optimal level of 5. The indices of rational antibiotic prescribing and injection use were low at 0.68 and 0.19, respectively (Table II). The findings of our study indicated that majority of the health facilities in Shimoga district had the key essential medicines. However, the index of rational drug prescribing was below the optimal level with high proportion of prescriptions containing injections and antibiotics. The findings of our study were comparable with the findings of studies conducted in 35 low-income countries which reported 45 per cent (range: 22-77%) of prescriptions had antibiotics2. It is a well established fact that overuse of antibiotics leads to bacterial drug resistance, which is an important public health problem in many developing countries9,10. Table II Index of rational drug prescribing (IRDP) in primary health centres of Shimoga, Karnataka, India, 2012. Overuse of injection was the most prominent manifestation of irrational prescribing in Shimoga with more than 60 per cent prescriptions containing at least one injection as compared to the optimal level of 10 per cent. High proportion of prescriptions with at least one injection was reported from several studies in India11,12. Our study had certain limitations. First, the prescribers were aware about the study, which could have biased the prescribing indicators in a socially desirable direction. Second, determining the quality of diagnosis and evaluating the appropriateness of choice of medicine was beyond the scope of our study. Third, the study was conducted in only one district of Karnataka and hence it would not be possible to generalize the findings in other districts. In conclusion, prescription and dispensing practices of health care providers in Shimoga district were found to be below the optimal level, especially with respect to prescribing injection and antibiotics. It is, therefore, necessary to train the health care providers in the district about the rational use of injections and antibiotics. Interventions such as interactional group discussion on safety of injection to doctors working in the primary health centres have shown to reduce injection prescribing13. It is also necessary to ensure that the EML and STG for antibiotic use are made available in every primary health centre. Shimoga is one of the better performing districts in the State with respect to health indicators14. The prescribing indicators observed in the district are, therefore, likely to reflect the best case scenario in the State and are likely to be better compared with other districts.

Prevalence of Vitamin D Deficiency, Metabolic Syndrome and Association Between the Two in a South Asian Population

Background: The etiological role of vitamin D in the metabolic syndrome among Asian Indians with good exposure to sunlight is not well understood. The objective of this was to estimate the prevalence of metabolic syndrome and vitamin D deficiency and to determine the association between vitamin D status and metabolic syndrome in an Asian Indian population from Hyderabad, India.Methods: 299 normal individuals were randomly selected, for this cross sectional study, from individuals who voluntarily participated in a health camp. Anthropometric measures were taken along with 25-hydroxyvitamin D, fasting blood glucose, complete lipid profiles were also assessed. Socio-demographic data such as sex, age, smoking status, physical activity and diet were also collected. Data was analyzed using t-tests and chi-square test of association.Results: 81.6% had 25 (OH) D deficiencies, 13.4% had insufficiency and 44% had metabolic syndrome. Females had lower levels of mean 25 (OH)D 18.33 ± 12.9 nmol/l as compared to males. 34.4% had 25 (OH)D deficiency as well as metabolic syndrome. A significant (p=0.02) association was observed between serum 25(OH)D and metabolic syndrome. Participants with 25(OH)D insufficiency had 4.6 (p-value=0.023) times higher odds of metabolic syndrome versus those with 25(OH)D >100 nmol/l, whereas those with deficiency had approximately 2 times higher odds.Conclusion: Vitamin D deficiency has become a pervasive problem with implications for cardiovascular health across age and gender groups. Our research indicates that women are at a higher risk of having metabolic syndrome than men if they have deficiency or insufficiency of vitamin D. Timely translational research needs to develop the appropriate interventions to stem this.

Assessment of quality of antiretroviral therapy services in India 2014-2015.

Background Following a decade of provision of free antiretroviral therapy (ART) in India, a nationwide assessment of ART services was conducted to review quality of care at ART centers. This paper presents the methods and defines replicable model of undertaking large scale assessments. Methods During the period January 2014-March 2015, 357 ART centers were reviewed under four domains, namely, operations, technical, monitoring and evaluation (M&E), and logistics. Mixed methods, comprising of desk review and on-site facility assessment; random sample of records, interviews with both health-care staff and people living with HIV (PLHIV) were used. Grading for each of the domain was done on a scale of 5, with 1 (Very poor) being the lowest and 5 (Excellent) as highest. Results 1720 health-care staff and 1762 beneficiaries were interviewed; 34 600 patient cards were reviewed. Of the 357 centers assessed 60, 169 and 128 scored Excellent, Average and Poor, respectively, in operations domain; 147, 176, 34 in Technical domain; 215, 115, 27 in M&E domain; 263, 71, 23 centers in logistics domain scored Excellent, Average and Poor, respectively. About 95% (1698/1785) of PLHIV were satisfied with the care provided at ART centers. Conclusion The methodology used for the assessment of ART centers in India yielded insights on the different domains that impact implementation and quality of service delivery. The design of this exercise may inform other researchers and managers planning similar large-scale assessments.

Rapid assessment of facilitators and barriers related to the acceptance, challenges and community perception of daily regimen for treating tuberculosis in India

ABSTRACT Introduction: The Revised National Tuberculosis Control Program (RNTCP) is the largest tuberculosis (TB) control program in the world based on Directly Observed Treatment Short-Course (DOTS) strategy. Globally, most countries have been using a daily regimen and in India a shift towards a daily regimen for TB treatment has already begun. The daily strategy is known to improve program coverage along with compliance. Such strategic shifts have both management and operational implications. We undertook a rapid assessment to understand the facilitators and barriers in adopting the daily regimen for TB treatment in three Indian states. Methods: In-depth interviews were planned across six districts of three purposively selected states of Maharashtra, Bihar and Sikkim, among health system personnel at various levels to identify their perspectives on adoption of a daily regimen for TB. These districts were sampled on the basis of TB notification rates. Thematic analysis of the qualitative data was undertaken. Results: 62 respondents were interviewed from these 6 districts. During the analysis, it was observed that an easily accessible, patient-centred and personalized outreach is an enabling factor for adherence to treatment. Lack of transportation facilities, out-of-pocket expenses and loss of wages for accessing DOTS at institutions are major identified barriers for treatment adherence at individual level. At program level, lack of trained service providers, poor administration of treatment protocols and inadequate supervision by health care providers and program managers are key factors that influence program outcomes. Conclusion: A major observation that emerged from the interviews is that the key to achieve a relapse-free cure is ensuring that a patient receives all doses of the prescribed treatment regimen. However, switching to a daily regimen makes adherence difficult and thus new strategies are needed for its implementation at patient and health provider levels. Most stakeholders appreciate the reasons for switching to a daily regimen. The stakeholders recognised the efforts of the Ministry of Health & Family Welfare (MoHFW) in spearheading the program. Strategies like the 99 DOTS call-centre approach may also further ensure treatment adherence.

Chikungunya outbreak in Atmakur village, Medak district, Telangana State, India

Sir, Chikungunya is an acute febrile illness caused by chikungunya virus (CHIKV), transmitted by Aedes aegypti and Ae. albopictus mosquitoes which predominantly breed in fresh water1,2. After an incubation period of 3-7 days (range: 1-12 days), the infected person develops high grade fever (typically >39°C) and poly-arthralgia. Joint involvement is usually bilateral and symmetric, and can be severe and debilitating. Other symptoms may include headache, myalgia, arthritis, conjunctivitis, nausea/vomiting, or maculo-papular rash3,4,5. The articular symptoms usually resolve within days to a few weeks, but in some cases, these may last for months or even years6. Even though, the disease is rarely life-threatening, the widespread occurrence of disease causes substantial morbidity and economic loss7. In 2006, chikungunya re-emerged in India with widespread outbreaks in Andhra Pradesh, Karnataka, Tamil Nadu and Maharashtra8,9,10. According to the National Vector Borne Disease Control Programme, more than 2.7 lakh cases were reported from almost all the States of the country11. Although the disease incidence has shown a decline in India12, outbreaks continue to occur in areas that were not previously affected. On November 12, 2013, the District Medical and Health Officer of Medak district in Andhra Pradesh (this district is now in Telangana State) informed the State Disease Surveillance Unit about unusually high number of cases of febrile illness from Atmakur village (n=1045). On further enquiry, it was found that all the cases presented with joint pain. The State Disease Surveillance Unit, SHARE India and trainee of the field Epidemiology Training Programme of National Institute of Epidemiology, Chennai began investigations during November 15 to December 16, 2013 with the objectives of (i) confirming the aetiology, (ii) estimating the magnitude, (iii) identifying the risk factors, and (iv) proposing recommendations to control. A suspected case of chikungunya was defined as an acute occurrence of fever with joint pain in a resident of Atmakur since November 1, 201313. Trained community health workers searched for suspected cases of chikungunya by house-to-house visits and collected information about age, sex, location, symptoms, date of onset, information about hospitalization, and duration of illness. A total of 20 serum samples were collected from suspected patients admitted in the district hospital, Medak; and were transported to Institute of Preventive Medicine, Hyderabad, for testing IgM antibodies against CHIKV using IgM-capture ELISA developed by the National Institute of Virology (NIV), Pune, India. The age and sex specific attack rates were calculated by dividing the number of cases by using projected, 2012 population estimates14. The epidemic curve was plotted to describe the distribution of cases by time. Spot map was prepared to understand the distribution of cases. For the mosquito larval survey, Atmakur village was stratified into two areas (area-1 and area-2) by geographic location of houses and 85 households from each of the areas were systematically sampled and surveyed. The household surroundings were searched for the presence of mosquito breeding places like water storage containers, water containers for animals, flower pots, earthen pots, coconut shells, stagnant pits and tyres, etc. House index (HI) was calculated as the proportion of houses having containers with larvae and the Breteau index (BI) as the number of containers positive for mosquito larvae per 100 houses. A total of 114 suspected chikungunya case-patients were identified from a population of 954 (attack rate: 11.9%; no deaths). All age groups were affected; with higher attack rates among individuals aged 15-45 yr (13.78%) and males (12.3%, Table I). The patients started coming from November 12, 2013, peaked during 15 to 20 November, and subsequently continued to occur for about four weeks. Besides fever (100%) and arthralgia (100%), common symptoms included headache (76%), myalgia (72%), back pain (23%), oedema (20%), nausea (20%), vomiting (18%), and rash (10%). The median number of joints affected was three. The most common joints involved were ankle, knee, wrist, and small joints of hands. Forty three (37.7%) of the 114 suspected patients were hospitalized in the district hospital (n=29) or primary health centre (n=14) for a median duration of eight days. Most of these patients on admission had high-grade fever, severe joint pain, dehydration and headache. At the district hospital, patients were investigated for malaria (peripheral smear), typhoid (Widal test, Span Diagnostics Ltd, Surat, India), and dengue infection (NS1 card test, J. Mitra & Co. Pvt. Ltd, New Delhi, India). All these tests were negative. Ten of the 20 serum samples from the admitted patients were positive for IgM antibodies against CHIKV. Although the sensitivity and specificity for the laboratory assay is high (95 and 97.2%, respectively), the sensitivity of the test in the first week of illness is low. This could be a possible reason for only 50 per cent positivity among the samples tested13,15. Table I Distribution of suspected chikungunya patients by age-group, gender and locality, Atmakur village, Medak, Andhra Pradesh (now Telangana), India (December 2013) The cases were clustered in area-1 compared to area-2 of the village. Area-2, where houses were made of clay or dried bamboos with no water storage facility had lower attack rate (attack rate: 7%, 27/381). In contrast, the attack rate in area-1 where majority of the houses were pucca houses made with brick and mortar and had plenty of water storage containers was 15 per cent (87/573) (Table I). The mean numbers of containers per household in area-1 and area-2 were six and 11, respectively. The entomological indices were higher in area-1 as compared to area-2 (Table II). Table II Entomological indices in areas 1 and 2, Atmakur, Medak, Andhra Pradesh (now Telangana), December 2013 Although only 50 per cent of the samples tested were positive for IgM antibodies against CHIKV, but negative test results for other likely aetiologies (dengue, typhoid, malaria), clinical presentation of cases and entomological findings supported chikungunya as the aetiology of outbreak in Atmakur village. In conclusion, an outbreak of chikungunya occurred in Atmakur village, Medak district in November-December 2013 affecting about 12 per cent of the village population. High entomological indices and the water storage practices in the village were favourable for the transmission of the infection. As per the guidelines of the National Vector borne Disease Control Programme, the health authorities applied temephos in domestic water storage containers and sprayed indoors with pyrethrum extract spray16. The number of cases declined following these control measures. However, the transmission continued for about one month, as the anti-larval and anti-adult measures were conducted only for one week on alternate days. This finding underscores the need for continuation of vector control activities till the outbreak subsides. The State of Andhra Pradesh (now Andhra Pradesh and Telangana) experienced large-scale outbreaks during 2005-20068,9,12. The occurrence of this outbreak also indicates that chikungunya remains a risk in previously unaffected areas. Health authorities, therefore, need to institute surveillance for chikungunya outbreaks for detecting and responding early so as to interrupt the transmission to other unaffected areas.