a leading non-profit for global tuberculosis research and development of new tb vaccines. to advance tb development, tb alliance creates partnerships with private, public, academic, and philanthropic sectors to develop products in underserved communities. in 2019, tb alliance became the first not-for-profit organization to develop and register an anti-tb drug. tb alliance also works closely alongside the world health organization (who), u.s fda, and the european medicine agency (ema) to endorse regulative policies and treatments that are affordable. fhi 360 is an international tuberculosis non-profit organization funded by usaid to treat and support patients in myanmar, china, and thailand. the organization developed an app called dotsync for healthcare staff to administer antibiotics and monitor the side effects of patients. this is incredibly imperative to eliminating tuberculosis because it allows healthcare workers to have follow-up checkups with patients to ensure that tuberculosis treatments are effective. operation asha is a tb nonprofit organization that was founded in 2006. located in india and cambodia, operation asha focuses on the development of "e-compliance," which is a verification and sms text messaging system where patients can use their fingerprints to access their medical records and be reminded daily via text when to take their medication. according to operation asha, the e-compliance treatment successive rate is 85%. treatment failure patients who fail treatment must be distinguished from patients who relapse. patients who responded to treatment and appeared to be cured after completing a course of tb treatment are not classed as treatment failures, but as relapses and are discussed in a separate section below. patients are said to have failed treatment if they fail to respond to treatment (cough and sputum production persisting throughout the whole of treatment), or only experience a transient response to treatment (the patient gets better at first, but then get worse again, all the while on treatment). it is very uncommon for patients not to respond to tb treatment at all (even transiently), because this implies resistance at base-line to all of the drugs in the regimen. patients who fail to get any response at all while on treatment should first of all be questioned very closely about whether or not they have been taking their medicines, and perhaps even be admitted to hospital to be observed taking their treatment. blood or urine samples may be taken to check for malabsorption of tb drugs. if it can be shown that they are fully compliant with their medication, then the probability that they have another diagnosis (perhaps in addition to the diagnosis of tb) is very high. these patients should have their diagnosis carefully reviewed and specimens obtained for tb culture and sensitivity testing. patients who get better and then get worse again should likewise be questioned very closely about adherence to treatment. if adherence is confirmed then they should be investigated for resistant tb (including mdr-tb), even if a specimen has already been obtained for microbiology before commencing treatment. prescription or dispensing errors will account for a proportion of patients who fail to respond to treatment. immune defects are a rare cause of non-response. in a tiny proportion of patients, treatment failure is a reflection of extreme biological variation and no cause is found. treatment relapse patients are said to relapse if they improve while on treatment, but become ill again after stopping treatment. patients who experience only a transient improvement while on treatment, or who never respond to treatment are said to have failed treatment and are discussed above. there is a small relapse rate associated with all treatment regimens, even if the treatment has been taken religiously with 100% compliance (the standard regimen 2hrez/4hr has a relapse rate of 2 to 3% under trial conditions). the majority of relapses occur within 6 months of finishing treatment. patients who are more likely to relapse are those who took their medication in an unreliable and irregular fashion. the probability of resistance is higher in those patients who relapse and every effort must be made to obtain a specimen that can be cultured for sensitivities. that said, most patients who relapse do so with a fully sensitive strain and it is possible that these patients have not relapsed, but have instead been re-infected; these patients can be re-treated with the same regimen as before (no drugs need to be added to the regimen and the duration need not be any longer). the who recommends a regimen of 2shrez/6hre when microbiology is not available (the majority of countries where tb is highly endemic). this regimen was designed to provide optimal treatment for fully sensitive tb (the most common finding in patients who have relapsed) as well as to cover the possibility of inh-resistant tb (the most common form of resistance found). because of the lifelong risk of relapse, all patients should be warned of the symptoms of tb relapse upon finishing treatment and given strict instructions to return to their doctor if symptoms recur. public health and health policy as of 2010, india has more reported cases of tb than any other country. this is in part due to severe mismanagement of diagnosis and treatment of tb within the private health care sector of india that serves about 50% of the population. there are therefore calls for the private sector to engage in the public revised national tuberculosis control program that has proved effective in reducing tb amongst the patients receiving health care through the government. additionally, a study by maurya et al. conducted in 2013 shows evidence that there is a burden of multidrug-resistant tuberculosis in india and change is needed for testing, surveillance, monitoring and management. during the covid-19 pandemic, 80% fewer tb cases were reported daily in april 2020 in india, reducing the diagnosis and treatment of tb. trial of therapy in areas where tb is highly endemic, it is not unusual to encounter patient with a fever, but in whom no source of infection is found. the physician may then, after extensive investigation has excluded all other diseases, resort to a trial of tb treatment. the regimen used is hez for a minimum of three weeks; rmp and stm are omitted from the regimen because they are broad spectrum antibiotics, whereas the other three first-line drugs treat only mycobacterial infection. resolution of the fever after three weeks of treatment is good evidence for occult tb and the patient should then be changed to conventional tb treatment (2hrez/4hr). if the fever does not resolve after three weeks of treatment then it is reasonable to conclude that the patient has another cause for his fever. this approach is not recommended by the who and most national guidelines. surgical treatment surgery has played an important part in the management of tuberculosis since the 1930s. historical surgical management the first successful treatments for tuberculosis were all surgical. they were based on the observation that healed tuberculous cavities were all closed. surgical management was therefore directed at closing open cavities to encourage healing. these procedures were all used in the pre-antibiotic era. there exists a myth that surgeons believed that the purpose was to deprive the organism of oxygen: it was however well known that the organism survives anaerobic conditions. although these procedures may be considered barbaric by 21st century's standards, it must be remembered that these treatments represented a potential cure for a disease that at the time had a mortality at least as bad as lung cancer in 2000s. recurrent or persistent pneumothorax the simplest and earliest procedure was to introduce air into the pleural space so as to collapse the affected lung and therefore the open cavity. there was always spontaneous resolution of the pneumothorax and the procedure had to be repeated every few weeks. phrenic nerve crush the phrenic nerve (which supplies the diaphragm) was cut or crushed so as to permanently paralyse the diaphragm on that side. the paralysed diaphragm would then rise up and the lung on that side would collapse, thus closing the cavity. thoracoplasty when the cavity was located in the apex of the lung, thoracoplasty could be performed. six to eight ribs were broken and pushed into the thoracic cavity to collapse the lung beneath. this was a disfiguring operation, but it avoided the need for repeated procedures. in the novosibirsk tb research institute (russia), osteoplastic thoracoplasty (a variant of extrapleural thoracoplasty) has been used for the last 50 years for patients with complicated cavitary forms of tb for whom lung resection is contraindicated. plombage plombage reduced the need for a disfiguring operation. it involved inserting porcelain balls into the thoracic cavity to collapse the lung underneath. surgical resections of infected lungs were rarely attempted during the 1930s and 1940s, due to the extremely high perioperative mortality rate. modern surgical management in modern times, the surgical treatment of tuberculosis is confined to the management of multi-drug resistant tb. a patient with mdr-tb who remains culture positive after many months of treatment may be referred for lobectomy or pneumonectomy with the aim of cutting out the infected tissue. the optimal timing for surgery has not been defined, and surgery still confers significant morbidity. the centre with the largest experience in the us is the national jewish medical and research center in denver, colorado. from 1983 to 2000, they performed 180 operations in 172 patients; of these, 98 were lobectomies, and 82 were pneumonectomies. they report a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (particularly extreme breathlessness). of 91 patients who were culture positive before surgery, only 4 were culture positive after surgery. some complications of treated tuberculosis like recurrent hemoptysis, destroyed or bronchiectasic lungs and empyema (a collection of pus in the pleural cavity) are also amenable to surgical therapy. in extrapulmonary tb, surgery is often needed to make a diagnosis (rather than to effect a cure): surgical excision of lymph nodes, drainage of abscesses, tissue biopsy, etc. are all examples of this. samples taken for tb culture should be sent to the laboratory in a sterile pot with no additive (not even water or saline) and must arrive in the laboratory as soon as possible. where facilities for liquid culture are available, specimens from sterile sites may be inoculated directly following the procedure: this may improve the yield. in spinal tb, surgery is indicated for spinal instability (when there is extensive bony destruction) or when the spinal cord is threatened. therapeutic drainage of tuberculous abscesses or collections is not routinely indicated and will resolve with adequate treatment. in tb meningitis, hydrocephalus is a potential complication and may necessitate the insertion of a ventricular shunt or drain. nutrition it is well known that malnutrition is a strong risk factor for becoming unwell with tb, that tb is itself a risk factor for malnutrition, and that malnourished patients with tb (bmi less than 18.5) are at an increased risk of death even with appropriate antibiotic therapy. knowledge about the association between malnutrition and tb is prevalent in some cultures, and may reduce diagnostic delay and improve adherence to treatment. although blood levels of some micronutrients may be low in people starting treatment for active tuberculosis, a cochrane review of thirty-five included trials concluded that there is insufficient research to know whether the routine provision of free food or energy supplements improves tuberculosis treatment outcomes. however, nutritional supplementation probably improves weight gain in some settings. vitamin d and tuberculosis epidemiology tuberculosis phototherapy treatment on 3 march 1934 in kuopio, finland vitamin d deficiency is a risk factor for tuberculosis, and vitamin d deficiency appears to impair the body's ability to fight tuberculosis, but there is no clinical evidence to show that treating vitamin d deficiency prevents tuberculosis, although the available evidence is that it ought to. reduced levels of vitamin d may explain the increased susceptibility of african-americans to tuberculosis, and may also explain why phototherapy is effective for lupus vulgaris (tuberculosis of the skin) (a finding which won niels finsen the nobel prize in 1903), because skin exposed to sunlight naturally produces more vitamin d. concerns that tuberculosis treatment itself decreases vitamin d levels appear not to be an issue in clinical practice. genetic differences in the vitamin d receptor in west african, gujarati and chinese populations have been noted to affect susceptibility to tuberculosis, but there