A handful of deadly infectious diseases, especially in low-income countries, claim millions of lives worldwide each year: lower respiratory tract infections, diarrheal diseases, HIV/AIDS, tuberculosis, and malaria. Together, they account for more than one in eight deaths globally. Several of these diseases have plagued humankind throughout history, often decimating populations with greater efficiency than wars. In an age of vaccines, antibiotics, and dramatic scientific progress, these diseases should have been brought under control. Yet they continue to kill at an alarming rate, particularly in the developing world. In low-income countries the dominant causes of death are infectious and parasitic diseases (including malaria) and poor medical care surrounding childbirth leading to maternal and neonatal deaths, although maternal deaths decreased by 30 percent between 2000 and 2013. By contrast, in high-income countries the leading causes of death are non-communicable diseases such as heart disease and cancer. Infectious and parasitic causes of mortality are farther down the list.

Lower respiratory tract infections (including pneumonia) account for more than 4 million deaths worldwide each year—the greatest global killer among infectious diseases. Pneumonia is also the leading cause of death of the very young, often striking children with low birth weight or those whose immune system is weakened by malnutrition or other diseases. Most of these deaths occur in developing countries.

 

Diarrheal diseases are among the top 10 leading causes of infectious disease deaths worldwide, accounting for 1.5 million deaths annually. Children under age 5 account for more than half of those deaths. Diarrheal disease is the second-leading cause of death in that age group. These infections are so widespread in developing countries that parents often fail to recognize when symptoms become critical. Children die simply because their bodies are weakened—often through rapid loss of fluids and undernourishment. The burden of diarrheal diseases is highest in deprived areas where there is poor sanitation, inadequate hygiene, and unsafe drinking water.

 

HIV stands for human immunodeficiency virus, the virus that causes acquired immunodeficiency syndrome (AIDS), the final stage of HIV infection. HIV appears to have jumped to humans early in the 20th century from a subspecies of chimpanzee in West Africa—most likely when humans hunted these animals for meat and came into contact with their infected blood. The virus slowly spread across Africa and later to other parts of the world.

At the end of 2015, more than 36 million people worldwide were infected with HIV. More than 2 million were newly infected in 2015 and an estimated 1.1 million died. Unlike most other viruses, HIV attacks the immune system, destroying a type of white blood cell (T cells or CD4 cells) that the immune system needs to fight disease. HIV is transmitted by having sex with someone infected with HIV, by sharing needles and syringes with an infected person, through blood or blood product transfusions, or by being exposed as a fetus or an infant to the virus before or during birth or through breastfeeding. HIV is not transmitted through casual contact such as shaking hands, hugging, modest kissing, or drinking from the same glass.

 

Someone in the world is newly infected with the tuberculosis (TB) bacterium every 5 seconds. In 2014, there were an estimated 6 million new cases of TB and 1.5 million deaths, even though the incidence of TB worldwide since 2000 has fallen by an average of 1.5 percent per year, a positive trend. The vast majority of TB deaths are in the developing world and more than half of all deaths occur in Asia. The United States is not risk free, however. While 9,421 U.S. TB cases were reported in 2014—which is a 2.2 percent decline from the number reported in 2013—outbreaks of TB occur in pockets across the country at rates even higher than in developing countries.

 

TB, which is caused by the bacterium Mycobacterium tuberculosis, is a contagious disease that spreads through the air when an infected person coughs or sneezes and people nearby breathe in the bacteria. TB bacteria can live in the body without making an individual sick, a condition known as latent TB infection. More than 2 billion people—about one-third of the world’s population—are infected, many asymptomatically, with TB bacilli. A person with active TB can be treated by taking several drugs for 6 to 12 months.

 

The problem of multidrug-resistant TB (MDR-TB) is grossly underestimated. There were about 310,000 MDR-TB patients in 2011. New data suggest that most new cases are the result of person-to-person contact and are not the result of inadequate treatment, inappropriate drugs, or lack of patient adherence to medication regimens. 

 

MDR-TB is difficult and expensive to treat and fails to respond to the standard first-line drugs that are most easily tolerated and have historically worked best against the disease. Extensively drug-resistant TB (XDR-TB) occurs when resistance to second-line drugs, which are typically more toxic and less effective, develops in addition to MDR-TB. Such infections are highly lethal.

On the global stage, HIV/AIDS and TB are tragically interconnected. Among HIV-infected people whose immune system is weakened by the effects of the virus, the risk of developing TB is much higher than for persons with a normal immune system. Indeed, TB is the leading cause of death worldwide among people infected with HIV. Likewise, among people with latent (inactive) TB infection, HIV infection is the strongest known risk factor for progressing to active TB disease.

 

Similar to the other global killers, malaria occurs mostly in poor, tropical, and subtropical areas of the world. In 2014, an estimated 214 million people were infected with malaria worldwide, leading to the death of about 438,000 people, most of whom were young children in sub-Saharan Africa. Malaria is a mosquito-borne disease caused by several different protozoan parasites. Humans infected with malaria parasites can, depending on the type, develop a wide range of illnesses—from mild infection that does not produce symptoms to the classic symptoms of malaria (fever, chills, sweating, headaches, muscle pains) to severe complications (anemia, kidney failure, coma) that can lead to death.

 

Malaria serves as a particularly dramatic example of infectious disease re-emergence and illustrates the challenges of controlling human vector-borne diseases. Following the enormous depopulation of Anopheles mosquitoes in the first half of the 20th century due to the liberal use of the pesticide DDT, malaria began its resurgence in Asia in the late 1960s. In Sri Lanka, where only 17 cases of malaria were reported in 1963, a major epidemic of more than 440,000 cases erupted 5 years later after preventive vector control was replaced with a strategy of identifying and treating new cases of the illness. Similarly, by the mid-1970s, millions of new cases had occurred in India after mosquito eradication efforts ceased. In Africa, where vector control programs were never initiated, a more recent upsurge in infections, including several explosive epidemics, erupted in endemic areas. Numerous factors drove this global resurgence, including the rapid spread of drug resistance among malarial parasites, changing rainfall patterns, and water development projects such as dams, which create new mosquito breeding sites.

 

Yet despite today’s dire headlines, progress is being made against the world’s modern infectious scourges. The scale-up of antiretroviral therapy has reduced the number of AIDS deaths and mother-to-child transmissions and it has improved survival and productivity. Wider access to antiretroviral treatments has also been accompanied by a dramatic reduction in prices. The prevalence of TB has declined since 2000, partly because the World Health Organization’s Directly Observed Treatment, Short-Course (DOTS) strategy brought treatment and a cure to tens of millions of patients. And malaria deaths have fallen with the development of artemisinin-based drugs, distribution of insecticide-treated bed nets, and indoor residual spraying of insecticides. Alongside these efforts there have been major investments in health care systems—bolstering infrastructure, laboratories, and human resources.