Dr. John Bartlett’s presentation last week was a great introduction to Dr. Carol Hamilton’s TB lecture today, emphasizing challenges of TB/HIV co-infections and growing drug-resistance, both causing individual and structural (e.g. systemic) barriers to global TB control. Although TB is a major challenge in India and China (accounting for 35% of the global burden in just those two countries alone), a lot of Dr. Hamilton’s lecture focused on the concentration of TB/HIV co-infection in sub-Saharan Africa as well as drug-resistant TB. Brittney just returned from five weeks working in multi-drug resistant tuberculosis (MDR-TB) hospitals in South Africa (in the KwaZulu-Natal and Eastern Cape provinces) where 70% of MDR-TB patients are co-infected with HIV. We think Dr. Hamilton’s points about current TB treatment being problematic were well stated and cannot be under scored enough – especially within certain populations such as children or those co-infected with HIV. The treatment burden can be immense; for those infected with MDR-TB daily treatment consists of approximately 15-20 pills per day along with a daily injection for up to six months during the intensive phase of treatment.
For individuals co-infected with HIV, pill burden and drug interactions may be increased. Despite this, initiation of antiretroviral therapy (ART) is recommended in all patients co-infected. Attached is a recent meta-analysis measuring “The Effect of Early Initiation of Antiretroviral Therapy in TB/HIV Coinfected Patients: A Systematic Review and Meta-Analysis” which assessed 2,272 study participants from 6 trials where early ART initiation (2-4 weeks versus 8-12 weeks) was conclusively found to reduce all-cause mortality in TB/HIV co-infected patients (Abay, et al. 2015). This evidence strengthens many national TB control program guidelines, although implementation of recommendations surely will be a challenge. In settings where lack of reliable supply chains exist, access to care and poverty are daily concerns, and poor diagnostics and/or lack of provider awareness of proper protocols is common; dual therapy for TB and HIV is, and will continue to be, challenging. Translating this dilemma to the pediatric population only adds complexity. The photo (from the TB Alliance) below illustrates just how demanding of a regimen we ask patients to accept.
As a final thought, story telling is another
way in which to raise awareness to global health challenges in a unique
way. In order to get grants funded or
manuscripts published we need decent data.
We all know that. However; the
human connection and the stories behind the numbers are what call most of us
into this field, and what bring us satisfaction after arduous days in the
field, or sleepless nights writing, reading, and interpreting our data. These are a few more stories worth
highlighting the impact and burden of TB in addition to Thembi Jakiwe’s story
of strength we shared earlier.
- Dalene von Delft – a physician from South Africa tells her battle with MDR-TB
- Dr. Lucica Ditiu (Executive Secretary of the Stop TB Partnership) talks about the stigmatizing language surrounding TB.
- Phumeza Tisile: HearNo Evil – a South African woman who survived XDR yet suffers from permanent hearing loss due to kanamycin (causing severe ototoxicity) discusses her journey through treatment and life after TB.
- Thato Mosidi - a physician in South Africa tells her story of being diagnosed with XDR and the isolation it caused her from her husband and 3-year-old daughter.
CHILDHOOD TB AND GROWING PAINS; NOTES FROM THE FIELD (Part 1)
ReplyDeleteBy Emily Esmaili
We in pediatrics like to stage our patients using developmental milestones. Those of us working in the “developing” world find children developing in those worlds faced with persistent challenges: an array of neglected, outdated diseases; severely limited resources; and unstable families. In Rwanda, the terrible act of genocide has left families fragmented, still struggling to recover. In addition to high prevalence of HIV, malnutrition, and poverty, they also must live in very close proximity; these factors, then, increase and exacerbate those diseases characteristic of the developing world, such as tuberculosis -- which in turn make a compromised people even weaker. To make matters worse, a disease as common as TB challenges bright physicians worldwide. For example, in my referral teaching hospital in Rwanda, although national protocols clearly guide diagnosis, and treatment is easy to access, TB still remains a diagnosis of exclusion. My Rwandan colleagues and postgraduate students grow tired of my reminders to add TB to their differentials. TB patients often have poor prognoses: They present in late stages; have many co-infections; suffer many comorbidities; and have many poor outcomes. However, I would like to share one clinical experience with childhood tuberculosis-- one with a happier ending.
ES was an 8 year-old male who presented with severe respiratory distress and inability to walk. He weighed 17 kg, heaving against his non-rebreather mask with 7L of oxygen and still desaturating. His right hip was flexed and guarded; his left foot and ankle were doubled in size by exquisitely tender swelling. X-ray films showed extensive bilateral infiltrates with multifocal opacities and a right-sided empyema. The surgeons placed a chest tube; they incised the dorsal surface of his foot; and drained copious amounts of purulent fluid, milking it down his entire leg. The next day he was taken to the operating room for his septic right hip to be drained; and his femoral head osteomyelitis to be debrided. He had a microcytic anemia, along with leukocytosis and neutrophil predominance. Having obtained cultures from gastric aspirates, we began broad-spectrum antibiotics. We guessed that he had a disseminated stapholococcal infection -- on top of active TB.
In the weeks that followed, ES continued to spike high fevers. The hemoculture, pus culture, and sputum culture all resulted negative -- none of which were surprising given our laboratory’s integrity. Continuing to search for some clear confirmation of our clinical diagnosis, we repeated chest X-rays, repeated sputum cultures, and sent samples for a GeneXpert test. He was not getting better. Along with his ongoing fevers, he continuously required oxygen. He was anorexic. He shrieked in pain each time we assessed him. Even our brazen surgeons predicted he would not survive. Over those challenging weeks, his mother was very patient; as well she was an excellent nurse.
(...to be continued!)
CHILDHOOD TB AND GROWING PAINS; NOTES FROM THE FIELD (Part 2)
ReplyDeleteBy Emily Esmaili
Finally one day, a postgraduate came to me with a perplexed look: the GeneXpert test was positive! Although his diagnosis was frustratingly delayed, ES tolerated treatment well. We all were relieved when his fever resolved. Soon after, he slowly gained weight, and he even broke free a smile.
By starting treatment sooner, could we have reduced his suffering? Could we have prevented his resulting disability? Could we have helped his mother save her precious francs? We could have trusted his presentation that was so typical of childhood TB: persistent fevers, osteomyelitis, septic arthritis, empyema, anemia, lymphadenopathy, all along with severe acute malnutrition. We did not truly need the positive test result and his clinical improvement to validate our clinical judgment. Too often, we doubt our thoughtful diagnoses. We blame limited resources for our failures. However, especially in the developing world, this fatalistic attitude is unacceptable. It is true that in our settings, we have certain limitations: we may not be equipped to perform cardiac surgery; we may not be able to offer mechanical ventilation; our patients may not be able to afford their daily medications, or food. Nevertheless, we can confidently treat debilitating conditions, such as TB. By diagnosing and treating early, we can reduce the global burden of childhood TB. In the “developmental milestones” of the developing world, this would be a tremendous achievement.
Thanks, Emily, for sharing your story, and to Laura and Brittney for facilitating. For any of us who have known or treated someone with TB, it can be a very difficult thing to deal with, especially when children are involved. But as I think about Emily's story, the videos, and the discussion from class, I come back to a central question with all of these global health challenges. Given that we have fixed resources of time, money, staff, etc, how to we make the biggest health impact and use our resources responsibly? As a critical care physician, my natural bias is to say that we want resources for the sickest people. We need more hospitals, with ventilators and advanced life support to help people who are really suffering from disease. But if I think from a public health and cost effectiveness standpoint, the resources we expend on advanced treatments can't have the same benefit as prevention measures. The mantra "an ounce of prevention is worth a pound of cure" comes to mind as I think about these things. To give an example, we had a very rich conversation on the sidelines about a government program in Kenya, where they offer anyone who is interested the opportunity to receive free treatment for latent TB (meaning you have the bacteria in your body, but it is not causing disease at this point, though you are at risk in the future of developing disease). The thought behind it is similar to what we discussed about malaria; that if you can stamp out the reservoir of disease, you can have a huge impact on disease incidence, and potentially even move towards erradication, or at least control in your local context.
ReplyDeleteGoing back to our central question, obviously in an ideal situation there are enough resources to pour into every facet of these complex health issues. This just isn't reality. We do not live in a world of unlimited resources. So how do we balance our good, altruistic nature to want to pour money into saving those who are deathly sick (aka the reason I became a doctor) with the less attractive, less immediate gratification public health programs where the best story is no story - no child gets sick, no one has to make the miraculous recovery, no one makes the big save. I don't know how to strike that balance, but as we dive into more global health challenges, I think it is a central question we are going to have to deal with if we want to move from being consumers of data to informers of policy. I welcome others' thoughts on this.
Devon, I think resources should be allocated equally for both prevention and cure of TB.
ReplyDeleteAs Emily suggested diagnosing and treating early is important for patients who have suspected or confirmed TB disease. Every person who is at high risk for exposure to TB should be diagnosed. Every person who is confirmed TB disease should receive treatment immediately.
However, not only is TB treatment crucial but also TB prevention (e.g. TB education) is important. Since the treatment for TB lasts at least 6 months, patients need to be well educated about the danger of not taking antibiotics on schedule. In addition, patients’ relatives or caretakers should be well informed about TB to help prevent the spread of TB. In 2013, two-year-old girl was diagnosed with TB at our clinic at Thai-Myanmar border. She received drugs from the clinic for several months. We thought her family took care of her well and gave her medicines regularly. I was shocked when others told me that the family split the tablets in half and only gave half of the drugs to children everyday. The family said they were concerned about the side effects of TB drugs on their child. Even worse, they stopped the medication after three months and didn’t come to the clinic. Perhaps it is time to think about child friendly TB drugs? In the same year, I visited my friend who was hospitalized in a small town in Myanmar. She was placed in the same room with a patient who has TB meningitis. To my surprise, TB meningitis relatives and nurses didn’t wear protective masks. People looked at me strangely as I was the only one who wore a protective mask. Therefore, I think that educating patients, relatives, and health workers is equally important to treating TB patients.