How a Peacekeeping Mission Imported Drug-Resistant Malaria
In 2010, a group of Guatemalan soldiers returned home from a peacekeeping mission in the Democratic Republic of the Congo (DRC) expecting a hero's welcome. Instead, they brought back an invisible stowaway that would trigger a public health investigation and highlight a growing threat to malaria elimination efforts worldwide. Within weeks of their return, one soldier was dead and several others were hospitalized, all infected with chloroquine-resistant Plasmodium falciparum—a deadly form of malaria that Central America hadn't faced before.
Chloroquine-resistant malaria was previously unknown in Central America before this incident.
This case illustrates how global travel can spread drug-resistant infections across continents.
This incident represents more than just a tragic case of imported disease; it illustrates the complex challenges of controlling malaria in an interconnected world. As military personnel, travelers, and migrants move between continents, they can unknowingly transport drug-resistant parasites across oceans, potentially undoing decades of progress in disease control. The story of these peacekeepers serves as a compelling case study of how global travel can facilitate the spread of drug-resistant infections, and why understanding this phenomenon is crucial for public health officials worldwide.
Malaria is a severe disease caused by parasites of the Plasmodium genus, which are transmitted to humans through the bites of infected female Anopheles mosquitoes. Once in the human bloodstream, these parasites travel to the liver, multiply, and then invade red blood cells, causing them to burst. This destruction leads to cyclical fevers, chills, flu-like symptoms, and in severe cases, organ failure and death. Among the five Plasmodium species that infect humans, P. falciparum is the most deadly, responsible for the vast majority of malaria-related fatalities globally 1 .
For decades, the inexpensive and widely available drug chloroquine was the gold standard for malaria treatment. This safe 4-aminoquinoline compound worked by accumulating inside the digestive vacuole of the malaria parasite, where it interfered with the detoxification of heme—a toxic byproduct created when the parasite digests hemoglobin from red blood cells. By preventing this essential process, chloroquine effectively killed the parasites and cleared infections 2 .
Sporozoites enter human bloodstream
Parasites multiply in liver cells
Parasites infect red blood cells
Mosquitoes pick up parasites from infected human
The first signs of chloroquine resistance appeared in Southeast Asia and South America in the late 1950s and subsequently spread across most malaria-endemic regions. This development proved catastrophic for global malaria control efforts. As resistance rendered chloroquine increasingly ineffective, malaria-related deaths surged, particularly in Africa where the disease burden was highest 3 .
Central America presents a unique case in this global story. While the region has seen a remarkable decline in malaria transmission—with five of seven Central American countries now designated as malaria-eliminating nations—they have largely retained chloroquine as a first-line treatment. This is because indigenous P. falciparum strains in Central America have remained chloroquine-susceptible, unlike their counterparts in Africa and Asia 4 . This created a perfect storm: as Central American peacekeepers deployed to UN missions in Africa, they encountered resistant malaria strains against which their region's standard treatment would prove useless.
For years, scientists suspected that chloroquine resistance involved multiple genes—a complex genetic basis that made the phenomenon difficult to study. The critical breakthrough came when researchers identified a specific gene, dubbed pfcrt (Plasmodium falciparum chloroquine resistance transporter), that showed a remarkable association with resistance 2 .
This gene produces a protein that sits in the membrane of the parasite's digestive vacuole—the very compartment where chloroquine accumulates to kill the parasite. Mutations in pfcrt, particularly a key change at position 76 (where the amino acid lysine is replaced by threonine, denoted as K76T), effectively reconfigure this transporter to pump chloroquine out of the vacuole, reducing the drug's concentration to sub-lethal levels. Think of it as the parasite evolving a specialized pump to remove the poison from its system 2 3 .
Normal chloroquine action: accumulates in digestive vacuole
With pfcrt mutation: chloroquine is pumped out of vacuole
Just when scientists thought they understood chloroquine resistance, a 2023 study revealed an unexpected twist. Researchers analyzing Gambian malaria parasites discovered strong signatures of selection on a second gene—a putative amino acid transporter they named AAT1 3 .
Longitudinal genomic data showed that a specific mutation in this gene (S258L) increased from 0% to 97% frequency between 1984 and 2014, paralleling the rise of the pfcrt K76T mutation. Even more compelling was the discovery that these two genes showed significant linkage disequilibrium—a statistical association indicating they're co-evolving in response to the same selective pressure 3 .
| Gene | Chromosome | Mutation | Function | Significance |
|---|---|---|---|---|
| pfcrt | 7 | K76T | Digestive vacuole membrane transporter | Primary resistance mechanism; pumps chloroquine out of vacuole |
| AAT1 | 6 | S258L | Putative amino acid transporter | Potentiates resistance and compensates for fitness costs |
| AAT1 | 6 | F313S | Putative amino acid transporter | Common in Southeast Asia; reduces resistance but improves fitness |
This second transporter appears to play a dual role: it may help compensate for the fitness costs that resistant parasites incur, while also potentially influencing the balance between amino acid and drug transport. This discovery reveals that chloroquine resistance evolution is more complex than previously thought, involving multiple genetic players that work in concert to help parasites survive our chemical assaults 3 .
In January 2010, a contingent of 150 Guatemalan army special forces and support staff deployed to the Democratic Republic of the Congo (DRC) on a United Nations peacekeeping mission. For ten months, they operated in a region where chloroquine-resistant malaria was endemic—a stark contrast to their home country where such strains were nonexistent 1 4 .
Despite standard pre-deployment protocols that included provision of malaria prophylaxis (mefloquine) and recommended use of insecticide-treated bed nets (ITNs), investigations later revealed a troubling lack of adherence to these preventive measures. Not a single member of the contingent had consistently used ITNs or completed the full course of chemoprophylaxis while in the DRC, leaving them vulnerable to infection 4 .
The contingent returned to Guatemala City on October 17, 2010, and was granted leave five days later. Within weeks, disaster struck. Two soldiers were hospitalized with severe malaria, and one died after receiving chloroquine treatment—the standard first-line therapy in Guatemala at the time. The tragic outcome prompted an urgent investigation by the US Centers for Disease Control and Prevention (CDC) and the Center for Health Studies at Universidad del Valle de Guatemala (CES-UVG) 4 .
Deployment to DRC begins
Return to Guatemala
Leave granted to soldiers
First hospitalizations and death
Contingent recalled and screened
Authorities recalled the contingent to their base and conducted comprehensive screening. The results were alarming: investigators identified 12 confirmed cases of P. falciparum infection among the 150 returning peacekeepers—an 8% infection rate. Even more concerning was the discovery that seven of these cases showed no parasites on blood smears and were only detectable through more sensitive PCR testing, meaning they could have easily been missed by standard diagnostic approaches 4 .
| Parameter | Finding | Implication |
|---|---|---|
| Total contingent size | 150 personnel | Potential for widespread exposure |
| Confirmed cases | 12 (8% infection rate) | High transmission in deployment area |
| Diagnostic method | 5 by microscopy, 7 by PCR only | Standard diagnostics would miss majority of cases |
| Prophylaxis use | None adhered completely | Critical gap in prevention |
| Bed net usage | None used | Missed opportunity for vector control |
| Fatal case | 1 death | Demonstrates severity of imported resistant strains |
When the Guatemalan peacekeepers fell ill, scientists deployed an array of sophisticated tools to confirm the presence of chloroquine-resistant malaria. Understanding these methods provides insight into how modern disease detectives unravel such medical mysteries.
The initial diagnosis of malaria typically begins with light microscopy of Giemsa-stained blood films—the long-standing gold standard that can detect 10-100 parasites/μL of blood when performed by skilled technicians. In the field, Rapid Diagnostic Tests (RDTs) offer a practical alternative, detecting specific parasite antigens without requiring specialized equipment or training. However, these methods lack the sensitivity to detect low-level infections and cannot identify genetic markers of drug resistance 5 .
For the peacekeeper investigation, researchers turned to more advanced molecular techniques. They collected blood samples—including dried blood spots on filter paper, whole blood, and in the fatal case, post-mortem tissue specimens. DNA extracted from these samples underwent nested PCR targeting the 18S small subunit ribosomal RNA gene of P. falciparum, allowing confirmation of infection even in samples where parasites were undetectable by microscopy 4 .
To specifically probe for chloroquine resistance, the research team amplified and sequenced a critical region of the pfcrt gene using semi-nested PCR. This technique allows million-fold amplification of specific DNA sequences, enabling researchers to obtain detailed genetic information even from minimal parasite material. The resulting DNA sequences were then aligned with reference strains to identify characteristic polymorphisms associated with resistance 4 .
The laboratory work confirmed the worst fears: the parasites carried mutant pfcrt genotypes identical to those found in the DRC, explaining why chloroquine treatment had failed for the deceased soldier. This genetic evidence provided incontrovertible proof that fully chloroquine-resistant malaria had been imported into Central America—a finding with significant implications for regional malaria control strategies 1 4 .
| Research Reagent | Function | Application in Guatemala Case |
|---|---|---|
| Giemsa stain | Stains parasite nuclei and cytoplasm | Initial blood smear microscopy |
| OptiMAL-IT RDT | Detects parasite lactate dehydrogenase (pLDH) | Rapid field screening for active infection |
| QIAamp DNA Mini Kit | Extracts DNA from clinical samples | Obtained genetic material from blood and tissue |
| PCR primers for 18S rRNA | Amplifies Plasmodium-specific gene region | Confirmed P. falciparum species |
| pfcrt-specific primers | Amplifies chloroquine resistance gene region | Identified K76T resistance mutation |
| ExoSap reaction | Purifies PCR products | Prepared samples for sequencing |
The Guatemala peacekeeper incident serves as a cautionary tale with relevance extending far beyond this single case. It highlights several critical vulnerabilities in our global defense against infectious diseases.
As Central American countries progress toward malaria elimination, imported drug-resistant cases represent a significant threat to these achievements. A single imported case can potentially reignite local transmission if competent mosquito vectors are present, especially if the infection goes undetected or is improperly treated 4 .
The peacekeeper case also exposed gaps in current prevention approaches. The complete non-adherence to both chemoprophylaxis and ITN use among the contingent points to the challenges of maintaining consistent malaria prevention measures during military deployments, particularly long-term missions where vigilance may wane over time 4 .
In response to these challenges, public health experts have called for enhanced screening protocols for military personnel, travelers, and immigrants returning from regions with known drug-resistant malaria. They also recommend that all malaria cases in individuals with recent travel to areas with chloroquine resistance should be presumed to carry resistant parasites and receive appropriate alternative therapies, such as artemisinin-based combination treatments (ACTs) 1 4 .
Beyond clinical management, the incident underscores the need for better education on malaria prevention for deploying personnel and the importance of developing more tolerable prophylactic regimens that encourage adherence. It also highlights the value of molecular surveillance systems that can quickly detect and characterize imported resistance alleles before they have a chance to establish local transmission 4 .
"The battle against malaria has always been an arms race between drug development and parasite evolution; now, that race has taken on a new dimension as resistant parasites hitch rides across continents with unwitting human hosts."
Implement rigorous screening for personnel returning from endemic areas
Develop better training on prophylaxis adherence and prevention measures
Establish systems to detect resistance alleles before local transmission occurs
The story of the Guatemalan peacekeepers serves as a powerful reminder that in our interconnected world, geographical boundaries offer little protection against the movement of drug-resistant infections.
The incident represents a collision of two worlds—the chloroquine-sensitive malaria ecology of Central America meeting the drug-resistant strains of Africa through human mobility.
While the single death was tragic, it could have been far worse had the imported parasites sparked local transmission. Thanks to a rapid public health response and sophisticated molecular detective work, a broader outbreak was averted. Nevertheless, the case stands as a sentinel event, warning of the ongoing threat that drug-resistant malaria poses to elimination efforts in Central America and beyond.
As research continues to unravel the complex genetics of drug resistance—from the well-characterized pfcrt mutations to the newly discovered role of AAT1—the global health community must strengthen systems to prevent, detect, and respond to such importation events. The battle against malaria has always been an arms race between drug development and parasite evolution; now, that race has taken on a new dimension as resistant parasites hitch rides across continents with unwitting human hosts.