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https://doi.org/10.22214/ijraset.2021.39025

November 2021

Review on Infectious Diseases in India and their respective diagnostic platforms. PS Chandranand1, M. Harshitha2 1

NIB, New Delhi, India GITAM University, Visakhapatnam, India

Abstract: India is a lower-middle-income country with improved industrial output and expansion of innovative technologies (information, biopharmaceutical) with some notable health benefits in controlling very few infectious diseases due to an inadequate health system. It mainly focuses on providing medical care for urban population and lacks a common health framework that plays a critical role in illness prevention. However, these diseases are caused not only by a lack of sanitation and population density but also by environmental and behavioural changes. This study reviewed the literature on infectious diseases that cause deaths in India, such as tuberculosis, lower respiratory infections, and Transfusion Transmitted Infections (TTIs), diagnostic procedures for treatment and disease burden. Keywords: lower-middle-income country, Infectious diseases, Transfusion Transmitted Infections (TTIs), disease burden. I. INTRODUCTION Predicting the entry of a pathogenic agent is impossible but there is a continuous emergence of new pathogens or already known diseases which weakens significant numbers of people and also increases the risk of a bioterror attack. These infections depend on several factors such as the pathogen’s nature, environmental and human behavioral factors31. Generally, there are different modes of disease transmission in which the diseases that cause death are grouped as: - communicable (infectious and parasitic diseases and neonatal conditions), non-communicable (chronic), and injuries31. This study focuses mainly on infectious diseases which are due to existing harmful microorganisms, transmitted from person to person directly or indirectly. Further communicable diseases are led by faecally transmitted microorganisms15. Scope and burden of contagious diseases are high in India therefore predominant infections such as Malaria, Tuberculosis, and HIV infections are controlled through different vertical schemes where the Central Ministry of Health is behind in controlling the disease and its outbreaks15. There are different techniques to identify the disease-causing organisms but the recent advances include the use of Electrochemical Biosensor Technology which provides fast response, is highly selective and sensitive, and is portable. It involves the development of point-of-care (POC) devices22. A. Disease Burden in INDIA A series of recent studies have indicated that India saw an epidemic change in percentage of deaths and burden of disease i.e., from 1990 to 2016 with a steady rise in non-communicable diseases (NCDs) burden when compared to communicable diseases in which diarrhoeal, lower respiratory diseases, neonatal conditions, tuberculosis, and measles are the topmost exclusive causes of disease burden in 1990, India whereas diarrhea and lower respiratory infections are the top two disease burden infections that are still prevailing in 201627. Generally, disease prohibition can be obtained by altering or removing the risk components such as elevated glucose levels (fasting) and Body Mass Index (BMI), Air contamination - 9.8%, Dietary hazards - 8.9%, raise in systolic blood pressure - 8.5% or mainly child and maternal undernutrition which accounts for 14.6%10, 27. Studies in rural south Rajasthan suggest that the chief causes of burden of infection and deaths in children, youth, and senior group category are due to communicable-malnutrition- maternal-newborn diseases (CMNND), injuries, and non-infectious infections, independently27. B. Causes of Deaths over Age Group Distribution Particularly, the contribution of contagious and non-contagious infections is understood by differentiating the causes of death in India by age group where the elder population (40–69 years) experience and expire (73%) from non-infectious diseases while the younger population die (0–14 years- 81% deaths) from infectious diseases. However, the middle age group (15–40 years) die due to injuries which imparts nearly 1/3rd of total deaths while infectious and non-infectious diseases deliver uniformly to the remaining deaths27.

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International Journal for Research in Applied Science & Engineering Technology (IJRASET) ISSN: 2321-9653; IC Value: 45.98; SJ Impact Factor: 7.429 Volume 9 Issue XI Nov 2021- Available at www.ijraset.com C. Causes of Deaths by Demographic Distribution According to social and demographic profiles, a country comprises an expected burden for each disease. Thus, a country exceeds the expected burden due to failure in addressing the health facilities. Therefore, the greater the deviation, the greater is the failure. In India, the real burden of most of the infection conditions far exceeds the anticipated burden due to their social growth profiles, demography, and also slower decline in mortality rate though they include a vast web of primary health care services within a community, they lack resources and accountability27. II. INFECTIOUS DISEASES According to World Health Rankings, the following infections are in the order of top 50 causes of death in India33: Figure-1: Disease Burden of Infectious diseases, 20186,33. 700,000 616,531 600,000

500,000 409,652

421,437

420967

400,000 300,000

200,000 106614 100,000

62851

62,104 24,079

III. PNEUMONIA Pneumonia, an acute respiratory infection caused by Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), 4,20,23 with a vast number of polymorphisms in several inflammatory genes have been found as candidates to explain genetic diversity in susceptibility to lung infections5. India is responsible for 20% of the pneumonia deaths when compared to other countries23. Between 2014 and 2015, Pneumonia cases and deaths were higher in men when compared to women (Figure-2,3)28. The total number of cases and deaths were 6,20,167 and 2,534, respectively in India, 2015 with highest number of cases in Rajasthan (1,08,427), least in Lakshadweep (28) and Delhi accounting a greater number of deaths (412) (Table-1)28. It holds for 15% of all the deaths of children younger than 5 years where 8,08, 694 children have died in 201731. For over a decade, diagnostic platforms for identifying the disease-causing respiratory agents are rapidly growing. Immunochromatographic-based urinary antigen tests are easily carried out, developed with quick response. Molecular diagnostic techniques are the recent advances in clinical microbiology laboratories which measure the Procalcitonin (PCT) quantity that differentiates between bacterial and viral pneumonia. Moreover, it helps in predicting the survival and severity of the disease12. Chest X-rays are been used efficiently to know the severity of infection. It can be treated with antibiotics such as amoxicillin dispersible tablets31.

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States & Union territories Andaman and Nicobar Andhra Pradesh Arunachal Pradesh Assam Bihar Chandigarh Chhattisgarh Dadra and Nagar Haveli Daman and Diu Delhi Goa Gujarat Haryana Himachal Pradesh Jammu and Kashmir Jharkhand Karnataka Kerala Lakshadweep Madhya Pradesh Maharashtra Manipur Meghalaya Mizoram Nagaland Orissa Puducherry Punjab Rajasthan Sikkim Tamil Nadu Tripura Uttar Pradesh Uttarakhand West Bengal TOTAL

Number of cases 98 21,606 477 16,840 36,642 18,524 9,153 164 73 24,599 424 2,360 8,020 22,157 40,592 6,278 18,496 5,913 28 70,028 8,820 2,102 2,216 2,175 745 29,134 1,009 11,039 1,08,427 145 4,191 2,247 84,428 17,989 43,028 6,20,167

Number of deaths 13 14 9 80 12 97 16 20 1 412 10 8 2 120 5 5 275 57 0 103 9 1 45 44 0 228 21 16 128 0 33 41 351 7 351 2,534

Table-1: Pneumonia- number of cases and deaths in India (State-wise and Union territories), 201528.

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2000

400000

1500

300000

1000

200000

500

100000

0 Male cases 2014

Female cases 2015

Figure-2: Pneumonia Cases in male and female in India, 2014-201528.

Male Deaths 2014

Female Deaths 2015

Figure-3: Pneumonia Deaths in male and female in India, 2014-201528.

IV. DIARRHOEA In India, Diarrhoea is the key cause of death in less than five years group of children that is accountable for 13% of deaths, killing about 3,00,000 children every year18. This infection can be prevented and treated with oral rehydration solution (ORS) and10–14day supporting care with 20mg zinc medicines which improved and lessened the duration of diarrhoea31. It is also caused due to genetic changes within the genome which develops a protein, GUCY2C where it acts a receptor for bacterial toxins whose activity becomes high in diarrhoea patients13. India is accountable for 20% of the global burden since 1.2 million children under the age of 5 years die in India34. According to 2017-India-State-Level-Disease-Burden-Initiative-Full-Report, Uttar Pradesh causes a 30% higher burden due to diarrheal infections10. There was a stable advancement in decreasing the children’s deaths from 2.5 million in 2001 to 1.5 million in 2012 due to novel development of a vaccine against rotavirus18 but still non-rotavirus diarrhoea is resuming which would be a prime cause for the increase in mortality rate. Prevalence rate of Diarrhoea is high in rural areas, about 15.30% followed by 60 years & above age group, 14.80% and the frequency of the infection is greater in men than women (Figure-4)21. Diagnostic platforms for Diarrhoea include the collection of stool samples or blood tests, performing sigmoidoscopy (different costings in various states in India) and colonoscopy (average costing is $128.10-$298.90)31. 16% 14% 12% 10% 8% 6% 4% 2% 0%

Figure-4: Prevalence of Diarrhoea in India (2017-18) in percentage (%)21. V. TUBERCULOSIS Tuberculosis, led by Mycobacterium tuberculosis, mainly attacks the lungs, which disperses through small droplets, whose incidence is elevated in rural areas than urban locality (Figure-4)21 which can be prevented by early diagnosis and proper management of Tuberculosis patients, awareness about cough etiquettes and residing in properly ventilated atmospheres31. It is a curable and treatable disease treated with antimicrobial drugs31. The epidemiological research showed that there are certain human genetic, environmental factors are responsible for social variableness over the years. Thus, molecular advancement has been made by detecting the major locus responsible for the resistance to infection with M. Tuberculosis and it is demonstrated that in-born mutations of interferon-γ immunity resulted in childhood tuberculosis1.

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International Journal for Research in Applied Science & Engineering Technology (IJRASET) ISSN: 2321-9653; IC Value: 45.98; SJ Impact Factor: 7.429 Volume 9 Issue XI Nov 2021- Available at www.ijraset.com It is the foremost disease burden in India with a 21% frequency rate and 27% of the patients do not acquire proper medical therapy due to lack of uniform health care systems15. As per World Health Organization, it is the second prime worldwide killer as a single infectious agent with 30 Tuberculosis highly burden countries rated for about 87% of latest instances and India directing as the top in the count in 201931. Prevalence rate of Tuberculosis is high in men, about 1.30% followed by 60 years & above age group, 1.10% (Figure-5) 21. In the 1950s, tuberculosis prevalence was proved by surveys using the tuberculin test and miniature chest radiographs15. The rapid molecular diagnostic analysis is done as a formal test for patients with signs due to high diagnostic accuracy which will aid in the early detection of the disease. These tests include Xpert MTB/RIF (Mycobacterium tuberculosis (MTB) and Resistance to rifampicin (RIF) but diagnosing multidrug-resistant can be complex and expensive. Truenat is a new molecular assay which is a battery-powered testing platform and cost-effective that quickly identifies the infection and rifampicin-resistance which is a batterypowered testing platform and cost-effective. Sensitivity for Tuberculosis detection is done using a microsimulation model along with their costing mentioned in the below table2: 1) Truenat for point-of-care testing in primary healthcare facilities (Truenat POC)- 95%. 2) Xpert MTB/RIF in DMCs (Xpert)- 89% 3) Truenat in DMCs (Truenat DMC)- 86% 4) Sputum smear microscopy in designated microscopy centres (DMCs) (SSM)- 84%19. Monthly expenditures for treating Tuberculosis for first-line therapy is $28.13, $104.23 for second-line therapy and for retreating it is $32.25, which consists of regular visits, price of medication, observing test reports, clinical visits and hospitalizations throughout the treatment procedures19. Diagnostic tests

Base case per test

Truenat

$30.93

Xpert

$12.63

Sputum smear microscopy

$0.86

Range per test $27.23 – $34.63 $11.47 – $14.84 $0.24–1.58

Table-2: Approximate costing for the above diagnostic platforms per test (USD 2017)19.

1.40% 1.20% 1.00% 0.80% 0.60% 0.40% 0.20% 0.00% 45-59 60 Male Female Rural years years & above

Urban Total

Figure-5: Prevalence of Tuberculosis (2017-18) in percentage (%)21.

VI. CORONA VIRUS DISEASE 2019 (COVID-19) Coronavirus (COVID-19), an epidemic caused due to Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-CoV-2), there are certain Indian vaccines administered to the patients as a layer of protection such as Covaxin and Covishield. Countries also set up a plan to decrease virus proliferation by lessening the social interaction31. In Covid-19 infected patients, it was identified that there was an accepted loss of X-chromosomal TLR7 activity which were related to the disability of type I and II Interferon responses30. Number of cases and deaths increased gradually from 14th March,2020 till 16th September, 2020 and decreased. Later on, it slowly peaked on 8th may 2021 and gently started lowering in India (Figure-6,7)7. As per World Health Organization, 39, 361new cases were registered with 3, 14, 11, 262 confirmed cases and 4, 20, 967 confirmed deaths in India on 26th July 2021. It also led to an economic loss of affected countries including high mortality rate31. Virus containing RNA as genetic material is diagnosed using Real-Time- Polymerase Chain Reaction (RT-PCR) by taking swab samples of nose and throat. There is also another way of detecting the virus which is done using rapid kits31. Usually, in suspected patients, molecular assays are used as a standard way for detecting the viral genome within a sample35 and Serology-based immunoassays are used to find the antibodies such as anti-N and anti-S proteins, IgA, IgM, and IgG for SARS-CoV-2 in the infected patient’s serum/plasma. Their estimated costing depends on the rules given by the respective states in India8.

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4500 4000 3500 3000 2500 2000 1500 1000 500 0

Figure-6: Incidence of Covid-19 cases7.

Figure-7: Covid-19 Deaths7.

VII. HEPATITIS B Hepatitis B, affects the liver, transmitted through contaminated blood, sexual transmission or sharing needles or syringes which increases the risk of cirrhosis and liver carcinoma24. WHO suggests to include oral therapy to lessen the duplication of the virus using tenofovir or entecavir as the effective drugs31. Acute hepatitis B cannot be treated but a proper nutritional diet is mandatory whereas chronic hepatitis B can be treated with the help of oral antiviral agents which reduces the process of cirrhosis and thereby, enhances the survival rate. Overall, it can be prevented by a vaccine that is 98-100% safe and effective31. It also involves HBV-HIV coinfection and the carrier rate of HBV is 3.0% in India with a high-frequency rate within the tribal community24. Each year, around 2.6 crore infants are born in India of which about 1 million show the risk of causing chronic HBV infection 24. India presents a vast part with greater than 37 million HBV carriers24. The number of HBV deaths have been increased gradually between 1990 and 2019 (Figure-8)5. Various blood tests are there to diagnose and evaluate the conditions of the patients which distinguishes acute and chronic infections by identifying the presence of surface antigen HBsAg31. 140000 120000

DEATHS

100000 80000 60000 40000 20000 0 1985 1990 1995 2000 2005 2010 2015 2020 2025

Year Figure-8: HBV related Deaths6. VIII. HEPATITIS C Hepatitis C, a liver disease caused due to hepatitis C virus (HCV), a bloodborne virus, transfusion-transmitted infection (TTI) through exposure to small quantities of blood i.e., unscreened blood due to unsafe injection practices before transfusion which causes acute and chronic hepatitis that results in liver cancer3,26,31. It is marked by high levels of genetic differences which include inaccurate viral RNA polymerase rate and also due to pressure of the infected host’s immune system. This led to development of HCV into 7 various genotypes and greater than 67 subtypes11,14.

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International Journal for Research in Applied Science & Engineering Technology (IJRASET) ISSN: 2321-9653; IC Value: 45.98; SJ Impact Factor: 7.429 Volume 9 Issue XI Nov 2021- Available at www.ijraset.com Presently, early diagnosis of HCV infection can only be treated with antiviral drugs, greater than 95% of the infection which depends on the genotype3. The severity of liver damage should be evaluated with the aid of non-invasive tests in chronic HCV infected patients31. 12-18 million patients are carrying this disease in India with an average prevalence percentage due to the vast population size. Around 30% of the infected patients usually can clear the virus within 6 months of infection in devoid of any treatment whereas the remaining 70% of the patients lead to chronic HCV infection 31. The number of HCV deaths have been increased rapidly between 1990 and 2019 for over a period of 29years (Figure-9)5. Earlier, the serological activity of HCV infection, ELISA is done using Recombinant Immunoblot Assay (RIBA) but at present, the standard method for confirming active HCV infection is achieved by using Nucleic Acid Testing (NAT), a molecular technique that involves amplification and detection of HCV genome within a sample. Rapid assays are also been used as point-of-care testing diagnostic platforms and serological assays help in the identification of anti-HCV antibodies either in the serum or plasma containing samples3,26, 31. 80000 70000 60000

DEATHS

50000 40000 30000 20000 10000 0 1980

1990

2000

2010

2020

2030

YEAR Figure-9: HCV related deaths5. Hepatitis virus type

Source of Infection

Hepatitis A Hepatitis B

Contaminated water or food. Exposure through body fluids (Infected blood) or contaminated injection practices. Exposure through body fluids (Infected blood) or contaminated injection practices. Infected body fluids. Contaminated water or food.

Hepatitis C

Hepatitis D Hepatitis E

Table-3: Types of Hepatitis virus and their source of infection31. IX. ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) Human immunodeficiency virus (HIV) attacks the immune system of the body whose treatment is complex, mutations in human genetic content result in HIV infection where 40% imbalance is found in the env gene, and 8–10% difference in the pol/gag genes29. HIV disease treatment involves antiretroviral therapy (ART) which only suppresses the viral replication within a person's body16,17,25,31.

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International Journal for Research in Applied Science & Engineering Technology (IJRASET) ISSN: 2321-9653; IC Value: 45.98; SJ Impact Factor: 7.429 Volume 9 Issue XI Nov 2021- Available at www.ijraset.com Of the estimated Human Immunodeficiency Virus burden in India, women and girls are responsible for about 40% whereas children are about only 4%. The proportion of HIV infected patients has elevated in the states such as Andhra Pradesh about 21% and 20% Maharashtra with 1%, 0·7% prevalence rate in adults, respectively15. Rate of adult HIV prevalence has been reduced from 0.45% to 0.35% and also a slight decrease in number of HIV cases between 2002 and 2007 (Figure-11)5. A progressive decline of HIVpositive persons (in both children and adults) has been observed from 2003–2005 to the years 2010–2015 (Figure-10)25 and even a decrease in its prevalence in female sex workers (5.06% in 2007 to 2.67% in 2011) due to HIV prevention programme2. HIV trends were recorded which did not show any change between drug-injecting users (7.23–7.14%)25. HIV can be diagnosed through different Immunoassays such as rapid, ELISA (Enzyme-Linked Immunosorbent Assay), Western blot and NAA testing. For children less than 18 months of age, along with serological testing, virological testing is also required to identify HIV. Limiting antigen (LAg)-avidity assay and BioRad avidity assay helps in identifying the recent HIV infection in HIV seropositive patients which estimates the bond strength of HIV- specific antibodies and HIV proteins16. 3 2.64

2.51

2.5

2.27

1.78

1.56

1.5

1.41

1.29

1.17

1.06

1 0.5

0.21

0.23

0.24

0.25

0.26

0.25

0.24

0.23

0.21

0.96 0.2

0.88 0.18

0.85 0.17

0.82 0.17

0.8

0.79

0.16

0.15

0.77

0.76

0.12

0.1

0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 New HIV Infections in adults (15+ years) in lakhs

New HIV Infections in children (0-14 years) in lakhs

Figure-10: New HIV infections in India 1998–2015 (2 different age groups)25.

Figure-11: HIV Burden estimation and adult prevalence in India (National AIDS Control Organization)15. X. MALARIA Malaria, a lethal disease transmitted by Plasmodium parasites that spread through the bites of malarial vectors31. It can be prevented by using antimalarial drugs such as sulfadoxine-pyrimethamine31. It is resulted due to gene selective pressure within the genome and is associated as a transformative force for genetic diseases, such as sickle cell disease (SCD), thalassemia9. The primary vector for malaria in India is Anopheles culicifacies which is resistant to numerous insecticides and the secondary vector is Anopheles fluviatilis which proliferates during monsoon season and increases the disease burden15,31. Malaria treatment is not sustained because the malarial vectors are becoming resistant to the old drugs which were developed in 1950-1960s such as chloroquine and sulfadoxine-pyrimethamine (SP). Malaria caused by Plasmodium falciparum can be cured using Artemisinin-based combination therapy (ACT)31. In future, proteomics technologies will play an important role in eradicating the spread of malaria26. Malaria mainly affects the rural and poor urban communities in India with 1,144 deaths in the year 2009 and the number of cases (P. vivax and P. falciparum cases), deaths has been decreased from 2000 to 2020 till October with few fluctuations (Figure-12)32. In 1973, P. falciparum showed stability towards chloroquine and sulfadoxine-pyrimethamine which was raised from 12% in 1984–92 to 24% in 1997–200715,31. Prevalence rate of malaria is high in rural, about 10% followed by 60 years & above age group, 8.60% and the frequency is higher in men than women (Figure-13)21.

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International Journal for Research in Applied Science & Engineering Technology (IJRASET) ISSN: 2321-9653; IC Value: 45.98; SJ Impact Factor: 7.429 Volume 9 Issue XI Nov 2021- Available at www.ijraset.com Suspected cases of malaria can be confirmed within 30 minutes with the aid of parasite-based diagnostic testing either microscopy or rapid diagnostic test prior starting the treatment31. 2,500,000

2000

2,000,000

1500

1,500,000

1000

1,000,000

500

500,000

Cases

P. vivax cases

P. falciparum cases

Deaths

6.00% 4.00% 2.00% 0.00%

0 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018

12.00% 10.00% 8.00%

Figure-12: Epidemiological shift of Malaria in India (2000-2019) P. vivax and P. falciparum cases32.

Figure-13: Prevalence of Malaria (2017-18) in percentage (%)21.

XI. CONCLUSION Improvements in diagnostic platforms, vaccination schemes against various illnesses, identification and knowledge of genetic origins, and pharmacological treatment are all strategies to reduce the death rate associated with infectious diseases. Children can be protected from diarrhoeal infections if prevention techniques are implemented, which include social factors such as appropriate sanitation. Similarly, preventive and control efforts, as well as education about vaccine timings, must be effectively aimed for each infectious disease. It is suggestive that government’s need to be prepared for any type of disease by researching cures and medications that can be stockpiled or manufactured quickly. Therefore, in India, communicable diseases, which include infectious diseases, cause significant disease burden and mortality as a result of inadequate nutrition, sanitation, human genetic variations, behavioural and environmental changes, and limited access to health care systems. REFERENCES [1]

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