Unless something is soon done to curb multidrug-resistant tuberculosis, experts warn that the world may be headed for a medical version of the perfect storm.
Making reference to the 1997 Sebastian Junger novel The Perfect Storm, in which three weather fronts come together to create a storm of singular fury, researchers at the Centers for Disease Control in Atlanta and at several institutions in Africa argue in a supplement to the November 15th edition of the Journal of Infectious Diseases that the global epidemics of HIV and TB may soon coalesce into a perfect storm with deadly consequences.
These warnings, put forward by Charles Wells of the CDC and colleagues in Mozambique, Kenya and South Africa, are based on their review of published data and global surveillance studies. Their report summarises our current knowledge of the epidemics of HIV and multi-drug resistant TB (MDR-TB) and identifies steps to thwart their convergence.
MDR-TB is TB caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin, two key first-line drugs used to treat the infection. MDR-TB is increasingly seen as a global epidemic with approximately 425,000 new cases each year, about 5% of the world’s annual TB burden.
While worldwide surveillance data of HIV and MDR-TB are limited, the researchers conclude that the two infections have the potential to converge in several countries, notably those of sub-Saharan Africa, the former Soviet Union, and in India and China.
Sub-Saharan Africa, which has born the brunt of the AIDS epidemic, also has some of the highest incidences of TB. A 2002 South Africa survey found that 40% of all patients with MDR-TB were co-infected with HIV, leading to an estimated 4,000 new cases of HIV each year. Surveys in Latvia and India report HIV–MDR-TB co-infection rates around 5%.
While acknowledging reports of MDR-TB outbreaks among HIV-positive patients in the hospital setting, the researchers conclude there is little current data supporting a disproportionate association between HIV and MDR-TB. They note that clinical trial data reveal that HIV infection is associated with resistance to rifampin and with poorer absorption of TB drugs overall.
What is certain is that HIV-positive people infected with MDR-TB have a poorer prognosis than their HIV-negative counterparts. The researchers point to studies from Argentina, Latvia, South Africa, and the US that have shown mortality rates among co-infected individuals of 40-50%, about twice that of people with MDR-TB alone. These studies also reported shorter median survival times for co-infected individuals.
This deadly mix of HIV and MDR-TB has the potential to explode, according to the researchers. They go on to identify tinder points between the two epidemics.
First, clinical management of MDR-TB, which requires at least four drugs, is complicated by the presence of HIV and anti-HIV treatments. Since one of the TB drugs is injected, safe injection practices are key to avoiding spread of HIV. Treatment of both infections can involve up to ten different drugs. This large drug burden complicates care due to overlapping toxicities and TB drug–HIV drug interactions.
Second, the researchers call attention to the high potential for spread of MDR-TB and extensively drug-resistant TB (XDR-TB) in many settings where HIV is prevalent, such as hospitals and prisons. The concern is bolstered by reports of high levels of drug susceptible TB transmission among healthcare workers, patients and inmates in sub-Saharan Africa, where HIV prevalence among these groups is also high. The lack of infection control measures in many countries where the two infections are prevalent, according the authors, creates an ideal environment for the rapid spread of MDR-TB among vulnerable groups.
Finally, current TB programs are threatened by the crushing impact of HIV, the researchers warn. In sub-Saharan Africa, TB control programs are struggling under the combined weight of increased caseload and the toll of HIV on the region’s healthcare workers. The inability to provide proper care may lead to treatment default and an increase in MDR-TB. As well, the impact of HIV and its treatment on TB treatments increases the risk of developing MDR-TB.
And in countries of Asia and the former Soviet Union where MDR-TB is well established, the growing prevalence of HIV could devastate TB programs.
Based on their analysis, the researchers outline several actions urgently needed in order to avoid a perfect storm of HIV and TB infections. They underscore the need to control infection, starting with proper surveillance of MDR-TB. They also call for the implementation of infection control procedures especially in facilities providing HIV treatment. Rapid detection of cases will be key to success, they say, and requires increased laboratory capacity and better screening of close contacts of TB-infected patients. Finally, effective treatment of the two infections will be improved by building the capacity of facilities to co-manage MDR-TB and HIV, strengthening partnerships between HIV and TB programs and by increasing research into the co-infection.
Wells CD et al. HIV Infection and multidrug-resistant tuberculosis—the perfect storm. J Infect Dis 196: S86 – S107, 2007.