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Euco-net.euThe Open Infectious Diseases Journal, 2011, 5, (Suppl 1-M5) 51-59
The Situation of HIV/M. tuberculosis Co-Infection in India
Seth Research Foundation, 1, Aradhana Colony, Sector 13, R.K. Puram, Ring Road, New Delhi-110066, India Abstract: In November 2008, European Commission initiated a collaborative research and information dissemination
project entitled "European Network for global cooperation in the field of AIDS and TB (EUCO-Net)" involving
Institutions in Europe (Germany, Belgium, Italy), Latin America (Brazil, Argentina, Colombia), Russia, South Africa, and
India with the following objectives: a) to provide an overview of the state of art in HIV and TB research and disease
management in different partner countries; b) to identify global research priorities; and c) to boost International
cooperation between leading HIV and TB experts from Europe and those countries mainly affected by these two diseases.
Therefore, in this report from India these objectives have been addressed under the following topics: i) Basic demographic
data; ii) Basic epidemiological Data of HIV and TB; iii) Medical treatment standards; iv) Diagnostic Standards.
Keywords: India, HIV/M. tuberculosis co-infection, revised national TB control programme (RNTCP).
causes of morbidity and one of the leading causes of mortality in people living with HIV/AIDS. The first HIV estimation in India was done in 1994 based on data from 52 sites. Since then, the process of estimation In recent years, India has witnessed rapid expansion of the of HIV infected persons in the country has evolved to a very DOTS strategy for TB control and scaling up of interventions to great extent. Since, the samples from which data were combat HIV/AIDS, including access for treatment with collected through sentinel surveillance were not exactly antiretroviral drugs. With the establishment of new mechanisms representative of the general population certain assumptions of funding like the Global Funds for AIDS, TB and Malaria, were used to generate estimates for the general population. financing of interventions against MTB/HIV is no longer an Over the years, these assumptions were gradually refined issue. Additionally, over the last few years, considerable with the help of other available data sources. The year 2006 experience has been gained on TB and HIV programme provided a unique opportunity when multiple data sources coordination, as well as individual patient care. Progress in such as a community based HIV prevalence study of improving HIV/MTB coordination and linkages in service National Family Health Survey-III, Integrated Bio- delivery will contribute greatly to achieving these goals. behavioural Assessment Survey, Endline Behavioural BASIC DEMOGRAPHIC DATA
Surveillance Survey could be utilized along with the data from the expanded sentinel surveillance system to arrive at The demographical information of India was obtained from more robust HIV estimates that are closer to reality. a website "Census of India" . The information collected Moreover, in 2006, the Workbook Model of WHO-UNAIDS during a countrywide census conducted in 2001. Census in was adopted that allowed international comparability. India is undertaken every ten years. Special statistical packages such as Random effects model India is a large country comprising 28 states and 7 union and Spectrum Projection Software are utilized to make more territories. These states and the union territories are divided into accurate and reliable estimates. districts. At the time of Census 2001 there were in all 593 The burden of MTB/TB and HIV/AIDS pose districts. Each district is further divided in to sub-districts, which unprecedented challenges on the public health system in are known differently in different parts in the country. India. Globally, India has the highest burden of TB and the As of 1st March, 2001 the population of India stood at number of HIV-infected people estimated in India is second 1,027,015,247 comprising 531,277,078 males and 495,738, 169 highest after South Africa. In addition to morbidity and females. Thus, India becomes the second country in the world mortality, the two diseases cause substantial economic and after China to cross the one billion mark. Life expectancy at social burden on the nation. TB and HIV are overlapping birth is 64 years. Urban population constitutes only 27.2% of epidemics. The HIV pandemic presents a massive challenge the total population. Meaning thereby, almost three-fourth's of to the control of TB at all levels. People living with HIV India's population lives in rural areas. One-third of India's have increased susceptibility to active tuberculosis, and HIV households are in urban areas, with two-thirds in rural areas. infection is the greatest risk factor worldwide for tuberculosis disease. TB is also one of the most common BASIC EPIDEMIOLOGIC DATA
*Address correspondence to this author at the Seth Research Foundation, 1, In India, countrywide control and prevention of Aradhana Colony, Sector 13, R.K. Puram, Ring Road, New Delhi-110066, HIV/AIDS and Tuberculosis is the responsibility of the India; Tel: +91-9810311407; Fax: +91-11-26876639; E-mail: email@example.com Government of India, Ministry of Health and Family
52 The Open Infectious Diseases Journal, 2011, Volume 5
Welfare (MOHFW). Two independent departments have regions. NACO utilizes this information for effective been created under the MOHFW to achieve the desired planning and implementation of its programs. Standardized effect. National AIDS Control Organization (NACO) is methods supported by WHO/UNAIDS are employed for responsible for control and prevention of HIV/AIDS; and estimating the burden of the epidemic overtime. Adult HIV Central TB Division of the Directorate General of Health prevalence has been estimated using WHO/UNAIDS Services, looks after tuberculosis prevention and control. Workbook restructured in 2006 for Indian epidemic Epidemiological data released by these sources were chosen situation. It included five subpopulations: intravenous drug because they were based on sound epidemiological methods users (IDU), men having sex with men (MSM), female sex accepted by the WHO and UNAIDS. The data were workers (FSW), long distance truckers and the general comprehensive and permitted comparison with global data population represented by the antenatal clinic attendees. released by the WHO and UNAIDS. Age-wise stratification of data was done by Spectrum Epidemiological data on HIV/AIDS were obtained from NACO report on HIV sentinel surveillance and HIV The total number of people living with HIV/AIDS estimation in India-2007  and Annual Report NACO (PLHA) in India in 2007 is estimated to be 2.31 million (1.8- 2008-09 . The data on Tuberculosis (TB) and multiple 2.9 million, Fig. 1). Females constitute around 39% of the
drug resistance tuberculosis MDR) were obtained from the burden (0.9 million). Children below 15 years constitute reports from Central TB Division [4, 5]. 3.5% of the estimated number of PLHA while elderly people HIV/AIDS epidemiologic data from NACO did not with age greater than 49 years constitute 7.8%. Adults aged stratify the estimated prevalence data as per EUCO-Net 15-49 years constitute 88.7% of the estimated number of questionnaire requirement particularly prevalence of HIV PLHA. The highest number of PLHA is in Andhra Pradesh infection in children (0 to 12 years). The cut-off age as per and Maharashtra, with nearly half-a-million PLHA each. NACO document is <15 years for children. Therefore in the Besides Tamil Nadu and Karnataka, West Bengal, Gujarat present report also we used <15 years cut-off age for and Uttar Pradesh are estimated to have higher burden of the disaggregation of data between children and adults. epidemic with greater than 0.1 million PLHA in each of these states. The four South Indian states contribute 60% of Epidemiological data on TB were obtained from Revised all PLHA in the country and along with West Bengal, National Tuberculosis Control Programme (RNTCP) Report Gujarat and Uttar Pradesh they contribute 80% of PLHA in -2009 . Here also, Central TB Division did not stratify the India. Though Manipur and Nagaland have the highest HIV estimated prevalence data age-wise. Indeed, it is only from prevalence in the country, due to small population size, the the year 2006 that the pediatric patients are being covered estimated number of PLHA in these two states is less than under RNTCP. In addition, other reports of the Central TB 25,000. The states of Kerala, Bihar and Rajasthan have more Division like Technical and operational Guidelines of TB than 50,000 PLHA each though the HIV prevalence in these control  Pediatric Guidelines, RNTCP Guidelines for states is low. Fig. (2) shows the distribution of PLHA among
diagnosis of TB , RNTCP DOTS plus guidelines  etc. the high burden states of India. Estimated Adult HIV prevalence in India in 2007 is 0.34% (0.25%-0.43%) (Fig. 1). Estimated HIV prevalence
among males (0.40%) continues to be higher than among
females (0.27%). Estimated Adult HIV prevalence remains The data generated through HIV sentinel surveillance is >1% in Manipur (1.57%) and Nagaland (1.20%) in 2007. used to estimate the level of infections in the country at Andhra Pradesh has an estimated adult HIV prevalence of regular intervals. The annual surveillance and estimation 0.97% while Karnataka and Maharashtra have estimated helps to understand the course of epidemic stage in different adult HIV prevalence <1%. Tamil Nadu, West Bengal, Fig. (1). Estimated Adult HIV Prevalence and total number of PLHA (million) in India 2002-07 (Adapted from HIV Sentinel Surveillance
The Situation of HIV/M. tuberculosis Co-Infection in India
The Open Infectious Diseases Journal, 2011, Volume 5 53
Fig. (2). Distribution of PLHA among High Burden States (2007) (Adapted from Annual Report NACO).
Gujarat and Delhi have estimated adult HIV prevalence of Maharashtra state: Pune, Mumbai and Thane have shown 0.4%. Fig. (2) shows the year-wise estimated adult HIV
>30% HIV prevalence among FSW. prevalence from 2002 to 2007 derived from Spectrum However, there is a decline in HIV prevalence among Package. Fig. (3) shows the state-wise estimated adult HIV
FSW in South Indian States reflecting the impact of prevalence in selected groups for the years 2006 and 2007 interventions, while rising trends are evident in the North derived from Workbook model as well as Spectrum Package. East suggesting a dual nature of the epidemic. In the low However, there are considerable differences in the prevalence states, the trends are stable. prevalence rates across different geographical regions. HIV Men who have Sex with Men Prevalence amongst ANC clinic attendees has been around 1% in the states of Andhra Pradesh, Karnataka in South Expansion of surveillance among MSM has revealed new India and in Manipur, Nagaland and Mizoram in North- pockets of epidemic. Among MSM, high HIV prevalence is eastern region of India. Tamil Nadu and Maharashtra have recorded in the states of Karnataka (17.6%) followed by recorded less than 1% HIV prevalence in ANC clinic Andhra Pradesh (17.04%), Manipur (16.4%), Maharashtra attendees. The epidemic is greater in urban areas than rural (11.80%) and Delhi (11.73%), Goa (7.93%) and Gujarat areas, greater among males than females, decreases with (8.40%) (Fig. 3). In total, 10 states have shown greater than
increasing education level, and is found to be highest among 5% HIV prevalence among MSM. Thirty out of forty women whose spouses work in transport industry. districts with MSM sites show HIV prevalence greater than 5%. Among MSM, HIV trends are rising in south Indian HIV Epidemic Among High Risk Groups states. Rising trends are also noted Delhi while trends are Female Sex Workers stable at the single MSM site in Manipur. At the state level, HIV prevalence among FSWs is very STD Clinic Attendees high in Maharashtra (17.91%), followed by Manipur Among the STD clinic attendees, Andhra Pradesh (13.07%), Andhra Pradesh (9.74%), Nagaland (8.91%) and continues to show the highest prevalence (19.72% (7.60%- Mizoram (7.2%). Among the other states, Gujarat, 39.20%) followed by Maharashtra (16.18% (7.20%-32.20%), Karnataka, and West Bengal have HIV prevalence greater Karnataka (7.15% (1.60%-10.80%)) and Tamil Nadu than 5% among FSW. Fig. (3) shows state-wise HIV
(12.04% (1.60%-38.40%)). Mizoram (7.13%) and Goa prevalence among high risk groups. Pockets in three cities of Fig. (3). States with high prevalence among different groups, 2007; IVD, injecting drug users; MSM, men who have sex with men; FSW,
female sex workers (Adapted from HIV Sentinel Surveillance Report).
54 The Open Infectious Diseases Journal, 2011, Volume 5
(5.60%) have also shown HIV prevalence greater than 5% estimated at 3.8 million bacillary cases for the year 2000, by among STD clinic attendees. Trends among STD clinic the expert group of Govt. of India. In addition, an estimated attendees are declining at all India level and in high 40% of the Indian population is latently infected with M. prevalence states, while rising trends are noted in tuberculosis. Chhattisgarh, Mizoram and Gujarat. Stable trends are noted By any measure the burden of TB in India is staggering. in other low prevalence states. More than 80% of the burden of tuberculosis is due to Injecting Drug Users premature death, as measured in terms of disability-adjusted High HIV prevalence among IDUs has been noted in life years (DALYs) lost. Every day, more than 5,000 people Maharashtra (24.4%), Manipur (17.90%), Tamil Nadu develop TB disease, and nearly 1,000 people die of TB, i.e. 2 (16.80%), Punjab (13.79%), Delhi (10.10%), Orissa (7.3%) deaths every 3 minutes. As per WHO estimates in 2006, and Kerala & West Bengal (7.8%). Trends among IDUs are nearly 322,000 persons in India died of tuberculosis on a decline in Manipur, Nagaland and Chennai reflecting (mortality rate 28 per 100,000 persons), which was estimated impact of interventions while rising trends are noted in at over 500,000 annually at the beginning of the RNTCP. Meghalaya, Mizoram, West Bengal, Mumbai, Kerala and Data from specific surveys, however, suggest that case fatality rates prior to RNTCP were generally greater than 25%. In the RNTCP era, case fatality has remained below The overall HIV prevalence among different population 5% for new cases registered for treatment under the groups in 2007 continues to portray the concentrated programme. Deaths due to TB exceed the combined deaths epidemic in India, with a very high prevalence among High from all other communicable diseases and account for 26% Risk Groups - IDU (7.2%), MSM (7.4%), FSW (5.1%) & of all avoidable adult deaths. TB is also the leading killer of STD clinic attendees (3.6%) (Fig. 4) and low prevalence
women, causing more orphans than those produced by all among ANC clinic attendees (age adjusted - 0.48%). causes of maternal mortality combined. Though heterosexual mode of transmission is still the MDR/XDR Tuberculosis predominant mode of HIV transmission in India, HIV epidemic in India appears to be dual epidemic driven by The emergence of resistance to drugs used to treat TB, sexual and IDU routes of transmission, concentrated in and particularly MDR-TB, has become a significant public nature with high HIV prevalence among high risk groups health problem in a number of countries and an obstacle to and heterogeneous in spread with pockets of infection found effective TB control. Several small surveys conducted across in various districts of the country. the country have shown the prevalence rates of MDR-TB in the country at around 1%- 3% among new cases, and 12% Tuberculosis Epidemiology
among retreatment cases. A retrospective analysis of various India is the highest TB burden country globally (29.9 randomized clinical trials conducted by the Tuberculosis million patients), accounting for one fifth of the global Research Centre (Chennai, India) with various rifampicin incidence and 2/3rd of the cases in South East Asia (Fig. 5).
containing regimens in the initial intensive phase, and with Nearly 40% of the Indian population is infected with the or without rifampicin in the continuation phase, revealed an MTB bacillus. Each year, 1.9 million new cases of TB occur overall emergence of resistance to rifampicin in only 2% in the country, of which about 0.8 million are infectious new patients despite a high level (18%) of initial resistance to smear positive pulmonary TB cases. The estimate of TB isoniazid either alone or in combination with other anti-TB incidence in India is based on findings of the nationwide drugs. A large scale population based survey in the states of Annual Risk of MTB Infection (ARTI) study conducted in Gujarat and Maharashtra has also indicated similar resistance 2000-03. The national ARTI was estimated at 1.5% i.e. 75 levels (new-3% and retreatment-12-17%). Available new smear positive pulmonary TB cases are expected per information suggests that the proportion of MDR-TB is 100,000 population annually. The prevalence of TB has been relatively low in India. However, this translates into a large absolute number of cases, with an estimated annual Fig. (4). HIV prevalence among different population groups (Adapted from Annual Report NACO).
The Situation of HIV/M. tuberculosis Co-Infection in India
The Open Infectious Diseases Journal, 2011, Volume 5 55
Fig. (5). Global Incidence of TB Burden (Adapted from RNTCP Status Report).
incidence of 110,000 cases of MDR-TB. XDR-TB has been However, BCG vaccination has no effect on the transmission reported in India by isolated studies with non-representative of the disease. The most effective step in the prevention of and highly selected clinical samples. The magnitude of the TB is to cure infectious cases in order to break the chain of problem remains to be determined due to the absence of transmission. The BCG Vaccination is given at birth under laboratories capable of conducting quality assured second UIP to all children including HIV infected child if the child line Drug Susceptibility Testing (DST). However, what is is asymptomatic or mildly symptomatic. The guidelines frightening is the potential threat of XDR-TB in India, with issued by the NACO, recommend withholding all live unregulated availability and injudicious use of the second vaccines for symptomatic and severely immune- line drugs along with non-existence of systems to ensure compromised HIV infected children. standardized regimens and treatment adherence for MDR-TB outside the national programme. The problem of MDR and MEDICAL TREATMENT STANDARDS
XDR-TB in India and across the world raises the possibility HIV Medical Treatment Standards
that the current TB epidemic of mostly drug susceptible TB will be replaced with a form of TB with severely restricted The free ART programme was launched on 1 April 2004 treatment options. If this happens it would jeopardize the by the Government of India. The technical guidelines were progress made in recent years to control TB globally as well initially modified from "WHO guidelines for ART in as in India and would also put at risk the plans to progress resource constraint settings". As the global experience towards a world where TB ceases to be a public health increased a need was felt to revise the 2004 guidelines. The final guidelines were developed which were again modified in view of revised WHO 2006 ART guidelines . As A major limiting factor in making State wise recommended in these guidelines any person who has a representative data on MDR/XDR-TB is the lack of quality confirmed HIV infection is subjected to further evaluation assured culture and drug sensitivity testing (DST) laboratory for determining whether he requires ART or not by facilities. It is important to note that the diagnosis of performing CD4 count and other baseline investigations. All MDR/XDR-TB is laboratory based. RNTCP is in the process those eligible as per technical guidelines are started on ART. of establishing in a phased manner a nationwide network of Initially eight tertiary-level government hospitals in the six quality assured culture and DST laboratory facilities. high-prevalence states of Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu, Manipur and Nagaland, as well as the NCT of Delhi were included in this programme. In Phase In India BCG vaccination is a part of Universal I of the implementation of this programme, the subgroups of Immunization Programme (UIP) under which vaccines for the people living with HIV/AIDS (PLHA) targeted on a six preventable diseases (tuberculosis, diphtheria. Pertusis, priority basis were: i) sero-positive mothers who have tetanus, poliomyelitis and measles) are available to all participated in the prevention of parent-to-child transmission eligible children free of cost. This programme was launched (PPTCT) programme; ii) sero-positive children below the in 1985 with the aim to cover all districts by 1990 and to age of 15 years; and iii) people with AIDS who seek immunize 85% of all infants against six vaccine preventable treatment in government hospitals. The ART centres were diseases. BCG vaccination has a complementary role in TB scaled up in a phased manner and to provide treatment to control, with particular impact in the prevention of severe 100,000 patients by the end of 2007 and 300,000 patients by forms of TB in children . The vaccination has a non- 2011 in 250 centres across the country. specific beneficial effect on infant survival and a BCG scar is a marker of better survival among children in areas with The free ART programme has adopted the public health high child mortality. Important contributing factors for the approach to administration and distribution of ART all of variable efficacy observed for the present BCG vaccine are which are manufactured in India. This implies a said to include background immunity induced by non- comprehensive prevention, care and treatment programme, tuberculous environmental mycobacteria, diversity of BCG with a standardized, simplified combination of ART strains, and over- attenuation of presently used strains. regimens, a regular secure supply of good-quality ARV 56 The Open Infectious Diseases Journal, 2011, Volume 5
drugs, and a robust monitoring and evaluation system. Since NACO. Nonetheless, NACO has developed guidelines in all first line and second line ART drugs are being 2008 on roll out of second line ART . According to these manufactured in India the Government of India has been able guidelines failure of first line ART should be suspected to scale up ART under NACO with the aim to provide care among the patients who having received first line ART for at and treatment to as many people as possible, while working least six months either show clinical deterioration after initial towards universal access to care and treatment. The selection improvement or no improvement despite good adherence to of first-line regimens is determined on the basis of a number therapy. The guidelines further define ART failure as of considerations, such as potency, profile of side-effects, clinical, immunological (fall in CD4 count to pre-therapy ability to keep future treatment options open, ease of level or persistent CD4 levels below 100 cells/ul), and adherence, cost, risk during pregnancy and potential of the virological (plasma viral load >10,000 copies/mL). development of resistant viral strains. The current global After the failure of first line therapy the second-line ART recommendation in all circumstances is a triple drug is the next regimen immediately used in sequence. Second line ART was initiated in January 2008 at only two site The national ART programme aims at i) providing long- (Tamil Nadu and Mumbai). During following 12 months it term ART to eligible patients, ii) monitoring and reporting was expanded to 10 more centres. Though provision was treatment outcomes on a quarterly basis; iii) attaining made to provide second line drugs to 3000 patients during individual drug adherence rates of 95% or more; iv) 2008-09, only 344 patients were receiving second line drugs. increaseing life span so that 50% of patients on ART are The NACO standard second line regimen comprise alive 3 years after starting the treatment; and v) ensuring that Tenofovir DF+ Lamivudine+ Zidovudine+ 50% of patients on ART are engaged in or can return to their Lopinavir/Ritonavir (TDF + 3TC + ZDV + LPV/r) aims to previous employment. achieve viral suppression for as long as possible, so that Eligibility for ART survival can be prolonged. Current NACO treatment guidelines recommend that the protease inhibitor (PI) class is The national programme offers ART to the following reserved for, and therefore characterizes second-line ART. groups of persons: i) All persons with HIV infection who are clinically eligible to receive ART; and ii) those who are Transmission of Drug Resistant HIV Strains
already on ART (outside the national programme) and want There is no study from NACO on this subject. Studies to enrol with the national programme for the available ART from academic institutions on small sample size suggest regimens, after written informed consent. about 10% primary infections may be due to resistant strains Antiretroviral Therapy Regimens (Seth P. unpublished). Nevertheless, there is low prevalence of primary drug resistant infections. This scenario offers an Currently, the national programme provides the opportunity to maintain low levels of drug resistant HIV following combinations for first-line regimens strains by provision of better treatment monitoring. Stavudine (30 mg) + Lamivudine (150 mg) However, compliance is an issue in patients undergoing ARV treatment even though it is free. Therefore, there is Zidovudine (300 mg) + Lamivudine (150 mg) likelihood of rise in drug resistant HIV strains and their (iii) Stavudine (30 mg) + Lamivudine (150 mg) + subsequent transmission. Nevirapine (200 mg) Tuberculosis Medical Treatment Records
(iv) Zidovudine (300 mg) + Lamivudine (150 mg) + RNTCP launched in 1997 is based on DOTS strategy. Nevirapine (200 mg) RNTCP uses intermittent short-course chemotherapy (SCC) regimens to facilitate direct observation of treatment. This is consistent with the World Health Organization guidelines. RNTCP ensures that there is no interruption in drugs and Current NACO treatment guidelines for first-line ART treatment once a person is diagnosed with TB. Sufficient recommends two classes of drugs for initial treatment ie 2 anti-TB drugs in patient-wise boxes are made available at all NRTI + 1 NNRTI. Fixed-dose combinations (FDCs) are the appropriate levels (Peripheral Health Institution/TB preferred because they are easy to use, have distribution unit/District/ State/National) ensuring that the treatment does advantages (procurement and stock management), improve not stop mid-way due to lack of drugs. adherence to treatment and thus reduce the chances of development of drug resistance. The current national The uninterrupted supply of drugs to each patient is made experience shows that bid (twice a day) regimens of FDCs possible through the "patient-wise box." Patient-wise drug are well tolerated and complied with. boxes (both adult and pediatric) are an innovation of RNTCP wherein a box of medications for the entire duration of the Initiative to provide free ART to pediatric patients was treatment is earmarked for every patient registered. This launched on Nov 30, 2006 by NACO. So far 47,784 children ensures the availability of the full course of medication to the living with HIV/AIDS (CLHA) have registered at ART patient the moment s/he is registered for treatment. Patient- centres and 14,383 CLHA have been receiving free ART as wise drug boxes have helped to improve patient care, adherence, drug supply and drug stock management. Since monitoring of patients on first line ART is done by Under RNTCP, all sub-centres, primary health centres, periodic peripheral blood CD4 T cell count at ART centres, community health centres, and other health facilities provide data on emerging ART resistant strains are not available with DOTS services to patients. Since TB patients may also seek The Situation of HIV/M. tuberculosis Co-Infection in India
The Open Infectious Diseases Journal, 2011, Volume 5 57
treatment from private physicians, the government has taken initiatives to provide DOTS services through the private sector and through community volunteers. India has well developed laboratory approaches for ensuring blood safety and donation safety (including tissue By March 2006, 1114 million populations have been and organ); surveillance of high risk groups; sentinel covered in a nationwide programme for tuberculosis surveillance; diagnosis and research. Most HIV antibody detection. So far 10 million patients have been treated with a screening and supplemental testing is performed at various success rate of 86%, reducing the death rate due to testing centres under NACO whereas Reference centres tuberculosis from 29% in 1990 to 4% in 2006. provide reference diagnostic services for problematic sera Direct Observed Treatment (DOTS and DOTS-Plus)
and perform assays like Western Blots, PCR and viral load assays etc. Directly observed treatment (DOT) is one of the key elements of the DOTS strategy. Under DOTS programme Primary screening is done at Integrated Counselling and RNTCP uses four oral anti-TB drugs (Isoniazid, Rifampicin, Testing (ICTC) by rapid tests. Rapid tests approved by the Ethambutol and Pyrazinamide). In DOTS, an observer NACO for use as primary screening tests are based on the (health worker or trained community volunteer who is not a principle of EIA or particle agglutination. These are provided family member) watches and supports the patient in taking free of cost to all ICTCs and other testing centres under drugs. It is this DOTS provider who ensures that the patient NACO. Samples found positive in primary screening are takes the right drugs, in the right doses, at the right intervals, further tested by two different EIAs/ELISAs or by Western for the right duration. 30000 DOTS providers have been Blot assay for validation of results. This service is provided recruited nationwide to provide treatment to the patients. free of cost to all individuals reporting at ICTCs. Under optimal programme conditions, treatment without Since HIV infection in infants (<18 months) born to observation achieves a success rate of 30-60%, whereas, HIV–infected mothers cannot be established on the basis of direct observation results in a much higher success rate of serological tests because of transplacentally transmitted 85-95%. DOTS helps to reduce development of drug maternal antibodies HIV specific DNA PCR is resistance, because direct observation ensures adherence and recommended. Facility for such a test is provided at all the hence reduces the probability of emergence of drug-resistant Reference centres by the NACO. These tests are also organisms. Further, following a correct treatment regimen provided free of cost only in these centres. reduces the spread of infection in the community and helps Although NACO recommends CD4+ T-cell enumeration in controlling development of new cases. and HIV plasma viral load by real time PCR assay for To address the MDR-TB problem through appropriate monitoring patients on ART, it has been providing only management of patients and strategies to prevent the CD4+ T-cell enumeration to all patients free of costs. propagation and dissemination of MDR-TB, the Indian Tuberculosis Diagnosis
Government introduced DOTS-Plus programe under RNTCP in 2009 and issued DOTS-Plus guidelines promoting full Sputum microscopy continues to be the primary tool for integration of DOTS and DOTS-Plus activities so that detection of infectious TB, as it provides information on the patients with MDR-TB are both correctly identified and extent of infection of the patient, helps in categorization of properly managed under this programme. the patient for treatment and is an objective method to monitor the patient's progress. Moreover, the result is Under DOTS-plus programme RNTCP uses oral second available within two days and the correct treatment can be line six anti TB drugs (Kanamycin, Ofloxacin, Ethionamide, started immediately. Apart from sputum microscopy, Pyrazinamide, Ethambutol and Cycloserine) during 6-9 RNTCP also uses standardized diagnostic algorithms to months of the Intensive Phase and 4 drugs (Ofloxacin, diagnose and treat all forms of TB wherein X-ray plays a Ethionamide, Ethambutol and Cycloserine) during the 18 supporting role (Fig. 6).
months of the Continuation Phase. p-aminosalicylic acid (PAS) is included in the regimen as a substitute drug if any MDR/XDR-TB Diagnosis
bactericidal drug (Kanamycin, Ofloxacin, Z Pyrazinamide A major limiting factor in making State wise and Ethionamide) or 2 bacteriostatic (Ethambutol and representative data on MDR/XDR-TB is the lack of quality Cycloserine) drugs are not tolerated. All the drugs used in assured culture and drug susceptibility testing (DST) DOTS and DOTS-plus strategies of RNTCP are laboratory facilities. It is important to note that the diagnosis manufactured in India. of MDR/XDR-TB is laboratory based. The programme is in DIAGNOSTIC STANDARDS AND AVAILABILITY
the process of establishing a network of 27 accredited DIAGNOSTIC TESTS
Culture and Drug Susceptibility testing Intermediate Reference Laboratories (IRLs) across the country in a phased HIV Diagnosis
manner for diagnosis and follow up of MDR-TB patients. Six culture and DST Labs including 6 IRLs (Andhra Pradesh, Delhi, Gujarat, Kerala, Maharashtra and Tamil All laboratories including those in the private sector Nadu) and 2 private sector labs (BPRC Andhra Pradesh and undertaking HIV testing activities follow guidelines issued CMC Vellore) have been accredited in 2008. Another 8 IRLs by the National AIDS Control Organization . These (Chattisgarh, Haryana, Jharkhand, Orissa, Rajasthan, guidelines provide all information regarding the diagnosis of Uttarakhand, Uttar Pradesh, West Bengal) and 5 medical HIV infection, monitoring of patients on ART etc. college laboratories were under accreditation process and
58 The Open Infectious Diseases Journal, 2011, Volume 5
Fig. (6). Tuberculosis Diagnosis Algorithm (Adapted from RNTCP Status Report).
expected to be accredited in 2010. The remaining IRLs will Prevalence States. Three other states namely Goa, Gujarat be accredited in 2011. and Pondicherry, have been classified as Moderate HIV prevalence states. Even within the high prevalence states, HIV/MTB CO-INFECTION
there are districts which have ante-natal HIV levels below The emergence and spread of HIV and drug-resistant tuberculosis further threaten to complicate the tuberculosis Tuberculosis is one of the earliest opportunistic diseases situation in the country. India, the third highest HIV to develop amongst persons infected with HIV. HIV burdened country, had an estimated 2.47 million people infection is the most powerful risk factor for the progression living with HIV/AIDS (PLHAs) in 2006 (that is, 0.36% of of latent MTB infection to TB disease. An HIV positive adult population in the country), emphasizing the enormous person co-infected with MTB has 50-60% life time risk of challenge ahead. All States and Union Territories of the developing TB disease, as compared to an HIV negative country have reported HIV/AIDS patients. However, the person who has a 10% life-time risk of developing TB HIV epidemic pattern shows great variance across the disease. Thus TB mortality could well be influenced by the country. The worst affected states are Andhra Pradesh, MTB/HIV co-infection al least in certain districts in the Karnataka, Maharashtra, Manipur, Nagaland and Tamil country particularly in districts in India with high prevalence Nadu. These six states have reported more than 75% of all of HIV in TB patients. the AIDS cases in India and are classified as High The Situation of HIV/M. tuberculosis Co-Infection in India
The Open Infectious Diseases Journal, 2011, Volume 5 59
In India, the TB epidemic is pre-dominantly driven by Programme of the European Commission. Author of this the non-HIV positive TB cases. It is estimated that nearly report was Core group expert on HIV and Tuberculosis from 5% of all TB patients are infected with HIV. The periodic India in this project. He was very ably assisted by additional HIV survey in TB patients, which was carried out in 4 experts (Dr. Naveet Wig, Dr. Kamini Walia and Dr. Akash districts in 2005-06, was scaled up to 15 districts in 2006-07. Gulalia) in collection of information used for preparation of The 2007 survey represents the most detailed evaluation to the Country report and this manuscript. Collation of date of HIV epidemiology among TB patients in India. The information and assistance in writing the manuscript by survey demonstrated that the prevalence of HIV among TB Kartik Yadav is greatly appreciated. patients varied substantially across the geographic regions between 1% and 13.8% across the 15 surveyed districts . REFERENCES
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Mayo Clinic Proceedings Access this article on Remission of Disseminated Cancer After Systemic Oncolytic Published Online: May 13, 2014 Publication stage: In Press Corrected Proof No data is available Need help playing this video? Supplemental Video AbstractMV-NIS is an engineered measles virus that is selectively destructive to myeloma plasma cells and can be monitored bynoninvasive radioiodine imaging of NIS gene expression. Two measles-seronegative patients with relapsing drug-refractory myeloma and multiple glucose-avid plasmacytomas were treated by intravenous infusion of 10 TCID