Monday, June 4, 2012

Malaria Life Cycle

Malaria Life Cycle
Follow the Plasmodium parasite's intricate and, occasionally bizarre, 13 steps to transmitting malaria:

Step 1
With her recent blood meal, the female Anopheles mosquito consumed dozens of stowaways: gametocytes male and female forms of the parasite Plasmodium falciparum.

Step 2
In the mosquito’s midgut, male gametocytes produce sperm-like microgametes. The female macrogametes soon are fertilized by the males, transform into zygotes and lengthen into sausage-shaped ookinetes.

Step 3
A few ookinetes pass through the midgut wall and form oocysts.

Step 4
For 8 to 15 days, the oocysts produce thousands of thread-like sporozoites. Perhaps 20 percent of them reach the mosquito’s salivary glands.

Step 5
As the mosquito bites another person, about 100 sporozoites swim with the saliva into the victim.

Step 6
The sporozoites ride the bloodstream. Only one or two reach their target: the liver. The human victim isn’t yet aware of the enemy within.

Step 7
After infiltrating a liver cell, each sporozoite transforms into a schizont that produces thousands of merozoites, which will invade red blood cells.

Step 8
After 5 to 7 days, the merozoites burst from the infected liver cell, enter the bloodstream and invade red blood cells. The infected person still doesn’t feel any symptoms.

Step 9
The parasite first takes on a signet-ring shape inside the red blood cell and later makes knobs on the red blood cell's surface, causing it to adhere to blood vessel lining and impede blood flow.

Step 10
The rings and the later form—trophozoites—feast on the red blood cell’s cytoplasm and hemoglobin. This stage ends with the formation of a schizont that produces up to 32 new merozoites. These exit and in a burst, invade still more red blood cells.

Step 11
The parasite’s numbers increase tenfold every 48 hours. From the one or two sporozoites that entered the liver, trillions of parasites may teem in the body. Two weeks after the mosquito’s bite, the patient experiences fever, headache, malaise and nausea.

Step 12
The knobby red blood cells stick like Velcro to the endothelial cells lining the blood vessels of the brain, heart and lung—and, in pregnant women, the placenta—which often leads to death.

Step 13
During the blood stage, some merozoites develop into yet another form of the parasite: the infective male and female gametocytes—seeds of destruction for malaria’s next victims.

Malaria: The Forever War

Malaria—the disease that for millennia has filled cemeteries, killed kings, wrecked empires and thwarted human attempts to quash it—begins modestly enough. About 100 parasites swim in the saliva of a female mosquito.

That humble start spawns personal and global misery. The few parasites that invade a person can quickly expand to trillions, overwhelming the human body. The effect manifests in the dulled eyes of blinded children, the paroxysms of fever and chills racking the victim, the deaths of children and pregnant women, and the hobbled productivity of entire nations. Each year, malaria causes nearly 800,000 deaths and 225 million clinical cases.

Were it not such a horror, the Plasmodium parasite would be one of the wonders of the world. The resilient shape-shifter constantly adapts to its surroundings, masters sexual and asexual reproduction, slips past the immunological defenses of the Anopheles mosquito and human beings, rides in the belly of its arthropod ally to new victims…. A testament to evolutionary engineering, the parasite has a solution to every barrier it meets.

And so, Plasmodium has been virtually unstoppable. Humanity’s last global attempt at malaria’s eradication in the 1950s ended in shambles. Bright hopes were extinguished by the parasite’s resilience (and the mosquito’s growing resistance to insecticides).

However, the malaria story does not end there.

We Homo sapiens have our own brand of resilience, innovation and tricks for survival. Breakthroughs in genetics, parasitology, entomology, drug development, satellite technology and other areas have summoned new hopes against our old enemy.

Analyzing Disease Transmission at the Community Level

Researchers at the Johns Hopkins Bloomberg School of Public Health have found evidence of a role for neighborhood immunity in determining risk of dengue infection. While it is established that immunity can be an important factor in the large-scale distribution of disease, this study demonstrates that local variation at spatial scales of just a few hundred meters can significantly alter the risk of infection, even in a highly mobile and dense urban population with significant immunity. The study is published in May 28 edition of the journal PNAS.

Dengue is a mosquito-borne disease that infects nearly 50 million people worldwide each year, resulting in more than 19,000 deaths. There are four serotypes of dengue virus (DENV1–4) circulating in Bangkok, Thailand, where the study was conducted. Infection with dengue provides lifelong immunity to the infecting serotype and there is evidence infection temporarily protects from infection by other serotypes. When susceptibility to other serotypes returns there is an increased risk for severe disease. For the study, the research team used the household location of 1,912 confirmed dengue cases in Bangkok that were admitted to a local children’s hospital between 1995 and 2000. The available data enabled the researchers to pair dengue serotype infections with specific households.

Observations indicated that immunological memory of dengue serotypes occurs at the neighborhood level in this large urban setting. The researchers developed methods that have broad application to studying the spatiotemporal structure of disease risk where pathogen serotype or genetic information is known.

“We observe patterns of spatiotemporal dependence consistent with the expected impacts of lifelong and short-term immunity, and immune enhancement of disease at distances of under one kilometer,” said Henrik Salje, lead author of the study and doctoral candidate in the Bloomberg School’s Department of Epidemiology.

“By providing insight into the potential spatial scales that immunity in a population is correlated and distances over which the disease is dispersed, these findings can help us further understand how dengue is being maintained in endemic populations,” said the study’s senior author, Derek Cummings, PhD, assistant professor with the Bloomberg School’s departments of Epidemiology and International Health.

The authors of “Revealing the microscale spatial signature of dengue transmission and immunity in an urban population” are Henrik Salje, Justin Lessler, Timothy P. Endy, Frank Curriero, Robert V. Gibbons, Ananda Nisalak, Suchitira Nimmannitya, Siripen Kalayanarooj, Richard G. Jarman, Stephen J. Thomas, Donald S. Burke and Derek A. T. Cummings.

The research was funded by grants from the Gates Foundation Vaccine Modeling Initiative, the National Institutes of Health, the Burroughs Wellcome Fund Career Award, and the Research and Policy for Infectious Disease Dynamics initiative of the NIH and Department of Homeland Security.