Breaking the drug-resistant TB transmission cycle important


Nearly two months after the Health Ministry set a highly ambitious target of working towards elimination of tuberculosis by 2025, a study published in The Lancet Infectious Diseases indicates that India’s TB crisis is all set to snowball by 2040 when one in 10 cases could be drug-resistant. What is even more alarming is that the increased number of drug-resistant cases — both multidrug-resistant TB (resistant to more than one of the first-line drugs) and extensively drug-resistant TB (additionally resistant to fluoroquinolones and at least one of the second-line injectable drugs) — will come from direct transmission from infected people to others rather than by strains acquiring resistance to TB drugs during treatment due to inappropriate treatment or discontinuation of treatment midway. The study found that “most incident” MDR cases are “not caused” by acquired drug resistance, and that acquired drug resistance will become a “decreasing cause” of drug-resistant TB. The increased availability of drugs to fight drug-sensitive TB has led to the emergence of MDR-TB strains. With increasing number of MDR-TB cases, there has been a shift in the way people get infected with drug-resistant TB — from strains acquiring drug resistance during treatment to direct transmission of MDR-TB strains from an infected person. The same trend is seen in the case of XDR-TB too. As a result, in high MDR-TB burden countries such as India, improved treatment outcomes in people might only reduce and not eliminate drug-resistant TB. Till 2015, only about 93,000 people with MDR-TB have been diagnosed and put on treatment.

The study, based on a mathematical model to forecast how TB is likely to progress in the four most-affected countries (Russia, the Philippines and South Africa, India), suggests that the number of new MDR-TB cases in a year in India will touch 12.4% by 2040, up from 7.9% in 2000. In the case of XDR-TB, the incident cases will rise to 8.9%, up from 0.9% in 2000. In 2015, the four countries accounted for about 40% (more than 230,000) of all drug-resistant TB cases in the world. Besides increasing the number of people who are diagnosed early and successfully treated, India’s TB control programme has come up with enhanced interventions to break the transmission cycle of the bacteria in the community. One of the ways this can be achieved is by carrying out immediate screening of all family members of a patient who has been diagnosed with the disease. Contact screening of family members and preventive treatment of all children below the age of five years who have not developed TB disease are already a part of the Revised National Tuberculosis Control Program (RNTCP) but is rarely done. Another important strategy that has to be adopted is making drug susceptibility testing universal and mandatory. Developing more accurate, cheaper and effective diagnostic tests and improved treatment regimens that are less expensive and of shorter duration will also go a long way in winning the war against the disease.

Published in The Hindu on May 12, 2017

IGIB uses novel drug discovery approach to identify drug targets in TB bacteria


The researchers have already begun finding out novel lead compounds for 15 drug targets.

In a completely different approach to drug discovery, a team led by Dr. Samir K. Brahmachari at Delhi’s CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) has used a combination of approaches to predict potential drug targets in Mycobacterium tuberculosis, the TB causing bacteria. The novel method not only helps in speeding up drug discovery by finding potential, non-toxic drug targets but will also cost far less by reducing the chances of failure. The results were published in the journal Scientific Reports.

“Conventionally, drug discovery was never looked at from a Systems Biology point of view. The approach we used was rather unconventional. We looked at finding targets first based on evolutionary conservation principle in an organism,” says Dr. Divneet Kaur from IGIB and the first author of the paper. Evolutionary conservation is based on the premise that genes that are very critical for the bacteria do not undergo any mutation.

Based on a previous study that used the Systems Biology Spindle Map (SBSM) approach, the team was able to identify 890 non-toxic genes responsible for metabolism as drug targets. Using computational approaches, the potential drug targets were reduced to 116; these 116 genes are so vital that any inhibition would kill the bacteria.

In order to identify drug targets with the least likelihood of side effects, the 116 essential genes were compared with the human genome and human microbiome at the sequence level to identify genes that did not have any similarity (homology) with human genome sequences.

Of the 116 genes, 104 genes were found to have no similarity with the human genome sequences, meaning any drug developed targeting these 104 genes will only target the TB bacteria and not cause any harm to human cells.

“There is a need for drug discovery to move from Wright brothers’ era of trial and error method. The trial and error approach is slow and too expensive.”The potential drug targets were further shortlisted to 33 genes. The 33 genes play an essential role in bacteria metabolism and have not undergone any mutation in any of the 1,623 TB strains, including the 1,084 multidrug-resistant TB strains, isolated from people with TB. The presence or absence of mutations in any of the 33 genes was evaluated using the Genome-wide Mycobacterium tuberculosis variation (GMTV) database. The genes which are essential for bacteria never undergo any mutations as that would be lethal for their survival.

Potential targets

The crystal structure, which is essential for carrying out drug discovery process, was available for 15 of the 33 targets. “For the 15 genes which have a crystal structure, work has already begun in finding out novel lead compounds for the targets,” says Dr. Mukta Sharma, who is presently involved in the study but is not an author of the paper.

“Once we have the targets and have structures of these targets then can tailor-make molecules to inhibit even MDR-TB and XDR-TB,” says Dr. Kaur. Dr. Debasis Dash from IGIB and one of the authors of the paper helped identify the amino acid changes and mapped them onto the proteins.

The team has already carried out druggability assessment (to find out if the targets have certain properties for a drug to bind to receptors) for all the 33 gene targets. “Most of the 33 genes were found to be highly druggable and none was found to be non-druggable,” says Dr. Sharma. “This validates the approach adopted by this study.”

“There is a need for drug discovery to move from Wright brothers’ era of trial and error method. The trial and error approach is slow and too expensive,” says Dr. Brahmachari. “Through computational approach we first make sure that the target is the Achilles’ heel of M. Tuberculosis and is absent in human cells. Using our new approach, we can work on all organisms.”

According to Dr. Brahmachari, all the genes, targets and even ligands will be in open source so anyone can develop new drug molecules.

Drug resistance

In order to understand the drug resistance seen in many TB drugs, the researchers evaluated the gene targets of known drugs — isoniazid, pyrazinamide, ethambutol for any mutations. “The current drug targets show a high degree of mutations,” says the paper. While isoniazid showed relatively lower variation compared with other drugs, the target of bedaquiline (for MDR-TB) drug showed no mutation. According to the paper, this “supports the hypothesis of the importance of completely invariant genes as potential targets for the successful development of novel antibiotics”.

Metformin, a drug used for diabetes care, was found to have minimum number of mutations, so can be repurposed as an adjunct therapy for MDR-TB.

Published in The Hindu on April 29, 2017

TB vaccine trial on adults begins in June in India

VPM 1002 TB vaccine

The candidate vaccine VPM1002 will be tested in India.

In June this year, the Pune-based Serum Institute of India Pvt Limited will begin a Phase II/III vaccine trial for tuberculosis using a novel, recombinant BCG (bacillus Calmette-Guérin) vaccine. The double-blind, placebo-controlled, randomised trial will be carried out on 2,000 adults who have been successfully treated (and cured) for TB. While 1,000 adults will receive the vaccine, the remaining volunteers will receive a placebo. A single dose of the vaccine will be administered and the volunteers will be followed-up for a year. The trial will be conducted in 15-17 centres across India.

The new TB vaccine (VPM1002) that will be tested is based on the BCG vaccine that is currently being used but is more powerful and efficacious as it contains a gene that is better recognised by the immune system.

“Adults who have completed TB treatment will be first screened and enrolled if found eligible 2-4 weeks after completion of TB treatment,” says Dr. Prasad S. Kulkarni, Medical Director at Serum Institute. “Traces of the drugs may be present in the body for two weeks after completion of the treatment. Since the vaccine contains live, weakened bacteria, the drugs can kill them if given earlier than two weeks after completing the treatment.”

The vaccine will be first administered in 200 volunteers and safety of the vaccine will be tested. “If there are no safety concerns then the trial will continue in the remaining 1,800 volunteers,” he says.

The safety of the vaccine has already been tested in two Phase I trials — 80 adults in Germany (2009) and 24 adults in South Africa (2010) — and one Phase 2a trial in South Africa in 2012 in 48 newborn infants who have not been exposed to HIV. “These trials have confirmed the safety of the vaccine and sufficient strengthening of the immune system,” says Umesh Shaligram, Director-R&D, Serum Institute.

The results of the Phase 2a trial in newborns in South Africa published in February this year in the journal Clinical and Vaccine Immunology has confirmed the safety of the vaccine. “The VPM1002 is a safe, well-tolerated, and immunogenic vaccine in newborn infants, confirming results from previous trials in adults,” the paper says.


The currently used BCG vaccine causes problems in HIV positive babies.

A Phase 2b trial on 416 newborns who have either been exposed or not exposed to HIV is currently under way in South Africa. “Results of the Phase 2b trial will be known in August-September this year. So far there have been no safety concerns,” Dr. Kulkarni says.

While the currently used BCG vaccine causes BCG-related disease in HIV-positive babies (due to reduced immunity), the recombinant version is expected to be safe in babies exposed to HIV.

Serum Institute is also planning to start next year a Phase III trial in newborns in India.

The recombinant vaccine was developed by a team led by Stefan H.E. Kaufmann, the founding director of the Max Planck Institute for Infection Biology, Berlin. The Max Planck Institute holds the patent and has licensed the vaccine to VPM; VPM, in turn, has out licensed it to Serum Institute.

In February last year Prof. Kaufmann told me: “The vaccine being tested is intended to replace the current BCG vaccine and will be administered to young children to protect them against tuberculosis. Adults may also be able to benefit from it later.”

Published in The Hindu on March 29, 2017

In a breakthrough, a blood test can diagnose TB disease

TB photo-Optimized

This is an animation depicting an active TB infection targeting the lungs. — Jason Drees, Biodesign Institute at Arizona State University

In a marked departure, researchers have used a rapid blood test that relies on two Mycobacterium tuberculosis-specific peptide fragments for diagnosis of TB disease and monitoring treatment. Currently, sputum samples are used for diagnosing TB disease in the case of pulmonary TB and tissue samples in the case of extra-pulmonary TB. The blood test accurately detects minute levels of two biomarkers — CFP-10 and ESAT-6 — that are “actively secreted” by the bacteria when it causes TB disease. Currently, the assay costs less than $10.

In a pilot study, the new blood test was able to diagnose active TB cases with “high sensitivity and specificity”. It was able to diagnose active TB even in people who were coinfected with HIV. The results were published in a paper published today (March 28) in the Proceedings of the National Academy of Sciences (PNAS) by Chang Liu from Houston Methodist Research Institute. Dr. Liu is currently at Arizona State University.

The blood-based assay was able to provide quantitative results that will help in knowing the severity of active TB and in monitoring treatment outcomes. Unlike Xpert, it cannot detect rifampicin resistance.

The blood-based assay was able to diagnose both pulmonary and extra-pulmonary TB cases with high sensitivity — over 91% in the case of culture-positive pulmonary TB (PTB) and above 92% extra-pulmonary TB (EPTB), and 82% in culture-negative PTB and 75% in EPTB in HIV-positive patients. In the case of HIV coinfected cases, the sensitivity was 87.5% for PTB and 85.7% for EPTB cases. It also had high specificity (87-100%) in both healthy and high-risk groups.

“We want to detect only active TB, but not latent TB, so we selected CFP-10 and ESAT-6. However, we believe these two biomarkers are capable of detecting early activation of latent TB, but we are conducting more experiments to confirm that,” says Dr. Liu in response to a question on the choice of the two peptide fragments.

According to a 2014 WHO report, there is a need for a “rapid biomarker based non-sputum-based diagnostic test that uses an easily accessible sample and is able to accurately diagnose pulmonary TB (and ideally also extrapulmonary TB)”.

Obtaining sputum samples is not always easy and is particularly difficult in the case of little children and people who are HIV positive. About 15-25% of all TB cases are extrapulmonary and biopsy samples are needed in such cases. Even Gene Xpert, introduced a few years ago to improve sensitivity and specificity, relies on sputum samples, and as per a 2014 WHO update, Xpert has “very low quality evidence” for EPTB diagnosis. Also, cerebrospinal fluid or other samples are needed for diagnosing EPTB using Xpert.

The blood-based TB diagnostic assay will be go a long way in the war against TB, particularly in diagnosing TB in little children, people with HIV and extra-pulmonary TB cases.

The blood sample is first microwave irradiated for about 20 minutes, and the target peptides are enriched using a nanoparticle enrichment platform and a high-throughput mass spectroscopy for enhancing the detection of Mycobacterium-specific biomarkers. It take some about four hours to prepare a serum sample and 10 minutes to know if the two peptides are present in the blood.

“CFP-10 and ESAT-6 are also expressed by some other mycobacteria, they cause NTM infection, not TB. We discovered peptides in CFP-10 and ESAT-6 that are specific to TB. So we digest the two proteins [using microwave irradiation] before diagnosis,” Dr. Liu, who is the first author of the paper, says in an email. “NanoDisk is functionalized with antibody. Their capture and isolate the peptide targets from patient serum sample. In addition, due to their special material and nanostructure, they can enhance the signal of mass spectrometry during detection.”

“We are particularly excited about the ability of our high-throughput assay to provide rapid quantitative results that can be used to monitor treatment effects, which will give physicians the ability to better treat worldwide TB infections,” said Prof. Ye Hu from the Houston Methodist Research Institute and the Corresponding author of the paper said in a release. Prof. Hu  is currently at Arizona State University. “Furthermore, our technology can be used with standard clinical instruments found in hospitals worldwide.”

According to the authors, the NanoDisk-MS assay meets several of the WHO criteria for a noninvasive TB assay — “it uses a small, non-invasive specimen; does not require bacterial isolation; has high sensitivity and specificity for active TB cases in extrapulmonary, culture-negative, and HIV-infected TB patients; and directly quantifies Mtb antigens for rapid monitoring of anti-TB therapy effects”.

The assay was able to detect marked reduction in the peptides levels in both HIV-positive and HIV-negative TB cases that were started on TB treatment. But more studies need to be carried out to evaluate the performance of NanoDisk-MS assay in treatment monitoring as the pilot study was not designed to measure the rate of decline of TB bacteria with treatment.

“We have tested 21 patients (HIV- and HIV+) with multiple longitudinal samples, and were able to see biomarker decrease correlated to treatment in 19 of them. Larger clinical validation is underway [to know treatment resistance and therapeutic efficacy],” he says.

The researchers note that larger, randomised studies are needed to confirm the results of the pilot study.

“Any blood-based, rapid TB diagnostic assay is ideal and has huge potential as it does not depend on sputum samples [for pulmonary TB], and tissue samples in the case of extra-pulmonary TB. But many studies based on blood-based assays have not been successful earlier,” says Dr. Soumya Swaminathan, Director-General of ICMR, Delhi. “High specificity [correctly identify those with the disease] is very important and so large-scale tests have to be carried out in countries like India where a large population has latent TB infection.”

Published in The Hindu on March 28, 2017

Without a magic wand, India cannot eliminate TB by 2025


Only 93,000 MDR-TB cases have been diagnosed till 2015 in India.

At the end of 50 years of tuberculosis control activities, the disease remains a major health challenge in India. As per new estimates, the number of new cases every year has risen to 2.8 million and mortality is put at 4,80,000 each year. These figures may go up when the national TB prevalence survey is undertaken in 2017-18. Against this backdrop, the Ministry of Health and Family Welfare, in its national strategic plan for tuberculosis elimination (2017-2025), has set a highly ambitious goal of “achieving a rapid decline in burden of TB, morbidity and mortality while working towards elimination of TB by 2025.”

Though the Revised National Tuberculosis Control Programme (RNTCP) has treated 10 million patients, the rate of decline has been slow. Providing universal access to early diagnosis and treatment and improving case detection were the main goals of the national strategic plan 2012-17. But the RNTCP failed on both counts, as the Joint Monitoring Mission report of 2015 pointed out. Going by the current rate of decline, India is far from reaching the 2030 Sustainable Development Goals — reducing the number of deaths by 90% and TB incidence by 80% compared with 2015. Yet, the latest report for TB elimination calls for reducing TB incidence from 217 per 1,00,000 in 2015 to 142 by 2020 and 44 by 2025 and reduce mortality from 32 to 15 by 2020 and 3 per 1,00,000 by 2025.

Incidentally, nearly 50% of people in India are latently infected with TB. According to CDC, 5-10% of infected people will develop TB disease at some time in their lives. “About half of those people who develop TB will do so within the first two years of infection,” the CDC says. With the latently infected people acting as a reservoir, it will be nearly impossible to eliminate TB in India by 2025.

Radical approaches are needed to come anywhere close to reaching these ambitious targets. Most importantly, the TB control programme plans to do away with the strategy of waiting for patients to walk in to get tested and instead engage in detecting more cases, both drug-sensitive and drug-resistant. The emphasis will be on using highly sensitive diagnostic tests, undertaking universal testing for drug-resistant TB, reaching out to TB patients seeking care from private doctors and targeting people belonging to high-risk populations.

The other priority is to provide anti-TB treatment — irrespective of where patients seek care from, public or private — and ensure that they complete the treatment. For the first time, the TB control programme talks of having in place patient-friendly systems to provide treatment and social support. It seeks to make the daily regimen universal; currently, the thrice weekly regimen is followed by RNTCP, and the daily regimen has been introduced only in five States. There will be a rapid scale-up of short-course regimens for drug-resistant TB and drug sensitivity testing-guided treatment. In 2013, India “achieved complete geographical coverage” for MDR-TB (multi-drug-resistant tuberculosis) diagnosis and treatment.  Yet, only 93,000 people with MDR-TB had been diagnosed and put on treatment till 2015; several MDR-TB cases are simply not diagnosed.

What next?

Though Bedaquiline, the drug for people who do not respond to any anti-TB medicine, is provided in six sites in the country, the number of beneficiaries is very small. It has been a battle to get the drug for treatment, as in the case of an 18-year-old who had to approach the Supreme Court for help. Yet, the report envisages a countrywide scale-up of Bedaquiline and Delamanid.

In a marked departure, the report underscores the need to prevent the emergence of TB in susceptible populations. One such segment is those in contact with a recently diagnosed pulmonary TB. Incidentally, active-case finding is already a part of the RNTCP programme but rarely implemented. It wants to increase active case finding to 100% by 2020. Since RNTCP expenditure has increased by 27% since 2012 and is inadequately funded, the Ministry proposes to increase funding to ₹16,500 crore.

Acknowledging that the business-as-usual approach will not get the Health Ministry anywhere close to the goals, it has earmarked critical components that will be addressed on priority. These include sending customised SMSes to improve drug compliance, incentivising private doctors to notify cases and providing free medicines to patients approaching the private sector, facilitating nutritional support to TB patients, including financial support, rewarding States performing well in controlling TB, and using management information systems to monitor all aspects of TB control. “The ultimate impact of this national strategic plan will be transformational improvements in the end TB efforts of India,” the report says. It plans to take a “detect-treat-prevent-build approach” in its war against TB.

Published in The Hindu on March 19, 2017

Can health spending of 2.5% of GDP only by 2025 help achieve the goals set by India’s National Health Policy?


The National Health Policy wants to reduce infant mortality rate to 28 per 1,000 live births by 2019.

The long awaited National Health Policy announced a few days ago proposes to raise public health expenditure as a percentage of GDP from the current 1.15% to 2.5% by 2025. The resource allocation to individual States will be linked with their development indicators, absorptive capacity and financial indicators. “There will be higher weightage given to States with poor health indicators and they will receive more resources. The Policy aims to end inequity between States. But at the same time, States will be incentivised to increase public health expenditure,” says Manoj Jhalani, Joint Secretary — Policy, Ministry of Health and Family Welfare.

The catch

While public health expenditure as a percentage of GDP will reach 2.5% only by 2025, many of the goals listed in the Policy have a deadline of 2025 and some of them even earlier.

The Policy stresses on preventive healthcare by engaging with the private sector to offer healthcare services and drugs that are affordable by all. It wants to reduce out-of-pocket “catastrophic” health expenditure by households by 25% from current levels by 2025.

The focus is on providing free, comprehensive care in primary care for the most prevalent communicable and non-communicable diseases, and increased affordability of care at secondary and tertiary care services by a combination of public and not-for-profit private providers wherever necessary. It wants to increase the utilisation of public health facilities by 50% from the current levels by 2025.

Health card roll out

The Centre is working on introducing a health card — an electronic health record of individuals. “The health card will be for retrieving and sharing health data by lower [PHC] and higher [secondary and tertiary] healthcare facilities. It will be helpful when patients move from primary to secondary or tertiary healthcare facilities,” says Mr. Jhalani. “It will be launched in six months to one year’s time. It will be launched in those States that show interest to roll it out in certain districts or across the State.”

Disease control and elimination

Like the Health Ministry’s National strategic plan for tuberculosis elimination 2017-2025 report, the Policy wants to reduce incidence of new TB cases to reach elimination by 2025. In a similar vein, the policy has set 2017 as the deadline to eliminate kala-azar and lymphatic filariasis in endemic pockets, and 2018 in the case of leprosy. In the case of chronic diseases such as diabetes, cancer, cardiovascular diseases, it envisages a 25% reduction in premature mortality by 2025.

The Policy “aspires” to provide secondary care right at the district level and reduce the number of patients reaching tertiary hospitals. For the first time, there is any mention of public hospitals and facilities being periodically measured and certified for quality.

Pipe dream

The Policy has sharpened its war on tobacco by indicating a 15% relative reduction in tobacco use prevalence by 2020 and 30% by 2025. But the most ambitious target is providing access to safe water and sanitation by all by 2020. As per January 2016 Ministry of Drinking Water and Sanitation country paper, sanitation coverage was only 48%.

Reducing IMR and MMR

Other challenging targets set by the Policy include reducing infant mortality rate to 28 per 1,000 live births by 2019 and under five mortality to 23 per 1,000 live births by 2025. According to the National family Health Survey 4, IMR was 41 in 2015-16; it took 10 years to reduce IMR from 57 to 41. Similarly, under five mortality was 50 in 2015-16 and it took 10 years to reduce it from 74. Over 38% children under five years were stunted according to the NFHS-4 report. The Health Policy wants to reduce this by 40% by 2025.

Increasing immunisation coverage

As against 62% children 12-23 months old who were fully immunised in 2015-16 according to the NFHS-4 data, the Policy has set a target of 90% by 2025. “Going up to 70% coverage is hugely a challenge of reaching the community. But beyond 70% coverage, other factors come in and it becomes a very big challenge,” says Dr. Pradeep Haldar, Deputy Commissioner — Immunisation, Ministry of Health. According to J.P. Nadda, the Union Health Minister, the Mission Indradhanush has increased the annual increase in full immunisation from 1% to 5-7%.

Published in The Hindu on March 19, 2017

Top health stories of 2016

On the health front, the year 2016 witnessed a few setbacks and but also a few positive developments. Here are the most important health developments of 2016

1. Trial results confirm Ebola vaccine provides high protection

who-ebola-optimizedThe Ebola virus that killed more than 11,300 people in three West African countries — Guinea, Liberia and Sierra Leone has finally met its match.

In December, an Ebola vaccine trial carried out in 2015 in nearly 12,000 people in Guinea was found to be safe and highly protective against the deadly virus.

No Ebola cases were recorded in nearly 6,000 people who received the vaccine, while there were 23 cases in the arm that received the vaccine after a 3-week delay. The trial used an innovative design called a “ring vaccination” approach — the same method that was used to eradicate small pox. In the ring vaccination strategy, whenever a new Ebola case was diagnosed, all the people who may have been in contact with that person were traced and included in the trial.

The vaccine was found to have high efficacy even when the interim results were announced. So everyone included in the trial was offered the vaccine immediately, including children older than 6 years.

A total of 28,616 Ebola cases and 11,310 deaths have been reported in three countries, as on June 2016.

Oraquick2. HIV self-testing gets a shot in the arm

Access to and uptake of HIV diagnosis got a shot in the arm when the WHO in November released new guidelines on HIV self-testing. Lack of an HIV diagnosis has been a major obstacle in the war against HIV.

Today, 40 per cent of all people with HIV (over 14 million) are simply unaware of their status. While more than 18 million people with HIV are currently taking anti-retroviral treatment (ART), and a similar number is still unable to access treatment as many are not aware of their HIV positive status.

Only 30 per cent of men have tested for HIV. As a result, men with HIV are less likely to be diagnosed and more likely to die of HIV-related causes than women.

Testing also remains low among high-risk population such as men who have sex with men, sex workers, transgender people, injection drug users, and people in prisons.  These people comprise nearly 44 per cent of the 1.9 million new adult HIV infections that occur each year.

People can use oral fluid or blood- finger-pricks to discover their status in the comfort of their house with no fear of being subjected to stigma and discrimination. This is bound to encourage more people to get tested.

Results are ready within 20 minutes or less. Those with positive results are advised to seek confirmatory tests at health clinics. Twenty three countries currently have national policies that support HIV self-testing. India is yet to approve HIV self-testing.

zika-microcephaly - Photo WHO3. Zika virus and public health emergency of international concern

On November 18, the World Health Organisation declared that Zika virus is no longer a public health emergency of international concern. It was in February that the WHO declared the Zika outbreak and congenital malformations and neurological disorders in newborns believed to be caused by the virus as a global public health emergency. Brazil has been the worst affected by the virus.

A distinct pattern of birth defects caused by Zika infection during pregnancy is now officially known as congenital Zika syndrome.

In November, a study showed that a small group of Zika-infected babies in Brazil who were born with normal-size heads had developed microcephaly five months to a year after birth.

The virus that has caused about 2,300 confirmed cases of microcephaly (a congenital disorder where babies are born with a small head) since May 2015. The link between Zika virus and microcephaly was established in May this year. After the initial spread to 67 countries, including countries in Southeast Asia, the spread has since slowed down.

While Aedes species of mosquitoes is the primary vector that transmits the virus, it can also be transmitted though semen, blood, tears and other blood fluids. Unlike in the case Ebola, scientists are yet to find an efficacious vaccine against Zika virus. And we are yet to fully understand the entire spectrum of neurological problems that may show up in children born with microcephaly. Meanwhile, the WHO has advised that pregnant women refrain from travelling to countries where local transmission of Zika virus is still prevalent.

GeneXpert4. Incidence of TB in India increases sharply

Although global TB deaths dropped by 22 per cent between 2000 and 2015, TB is still one of the top 10 causes of death worldwide. It kills more people than HIV and malaria.

Of the estimated 10.4 million new cases worldwide, the estimated number of new cases in India alone has increased sharply from 2.2 in 2014 to 2.8 million in 2015. The true incidence in India will be known once the national TB prevalence survey scheduled to begin next year is completed. Besides the uptick in incidence, the number of estimated deaths caused by TB has also more than doubled from 220,000 in 2014 to 483,000 in 2015.

The sudden increase in TB incidence in India is due to 34 per cent increase in case notification between 2013 and 2015 by doctors in the private sector. Yet, in 2015, notification by private-sector doctors was only 16 per cent of the total case notification. Of the 2.8 million estimated cases each year in India, only 1.7 million cases both in the public and private sector were notified in 2015. So the remaining 1.1 million cases are simply not known.

anopheles-gambiae-mosquito-james-gathany-cdc5. Sri Lanka becomes malaria-free

In September, Sri Lanka achieved a huge public health success when the WHO declared it as malaria-free. There has been no local transmission nation-wide in Sri Lanka since October 2012. The WHO certifies a country as malaria-free when the chain of local transmission has been interrupted nationwide for at least three years. With this, Sri Lanka joins the ranks of 34 countries that have been certified as malaria-free since 1960s.

With no local transmission currently, Sri Lanka’s focus is on preventing the re-introduction of malaria from outside, particularly countries such as India, which are malaria-endemic. There were 95 re-introduced cased in 2013, 49 cases in 2014 and 36 cases in 2015.

Sri Lanka was able to win the war against malaria by targeting both the vector and the parasite. This was achieved by active detection of cases and targeting parasite carriers by screening people whether they had malaria symptoms or not.

It came to eliminating malaria in 1963 when it reported just 17 cases including six that were due to local transmission.

Zika - antenatal-care. Photo WHO6. Thailand ends vertical transmission of HIV

In June, Thailand became the first country in the Asia-Pacific region to end vertical transmission of HIV from mother to child.

In 2000, an estimated 1,000 children in Thailand were infected with HIV due to vertical transmission. But in 2015, the numbers dropped dramatically to just 85, a decline of more than 90 per cent. The rate of mother-to-child transmission of HIV has been reduced to less than 2 per cent.

Thailand achieved this feat by ensuring that 98 per cent of all pregnant women with HIV had access to antiretroviral therapy. Women with HIV have a 15-45 per cent chance of transmitting the virus to their children during pregnancy, labour, delivery or breastfeeding if they are not on treatment during pregnancy. But the risk drops to just over 1 per cent if antiretroviral medicines are given to both mothers and children throughout the stages when infection can occur.

Treatment to prevent vertical transmission is not 100 per cent certain.  So vertical transmission is considered to be eliminated when a country successfully achieves a reduction in transmission to such a low level that it no longer constitutes a public health problem.

Besides treating pregnant women with HIV with antiretroviral medicines, Thailand witnessed a sharp drop in the number of women in the child-bearing age becoming infected with HIV. Between 2000 and 2014, the annual number of women newly infected with HIV fell from 15,000 to 1,900 — an 87 per cent reduction.

polio7. Polio end game starts across the world

In April, 155 countries including India switch from using a trivalent oral polio vaccine that contains type 1, type 2 and type 3 strains to a bivalent oral polio vaccine that contains only type 1 and type 3 strains. The global vaccine switch took place between April 17 and May 1.

The reason for removing the type 2 strain from the vaccine was to confer better protection against polio. The oral polio vaccine contains live, weakened virus, which on rare occasions can turn virulent and cause vaccine-derived poliovirus. Though wild poliovirus type 2 was eradicated in 1999, all type 2 polio cases have been caused only by vaccine-derived polioviruses.  The type 2 strain in the trivalent OPV had caused over 90 per cent of vaccine-derived poliovirus cases in the world in the last 10 years.

Polio, including vaccine-derived polio, can be eradicated only when oral polio vaccine is eventually withdrawn after wild polio transmission has been stopped. Removing type 2 strain from the vaccine and switching over to a bivalent vaccine is the “first major step” of this withdrawal process.

Published in The Hindu on December 28, 2016