The Hidden Epidemic: When Silent Malaria Meets HIV in Pregnancy

Uncovering the invisible threat to maternal and child health in Nigeria

The Invisible Danger Within

When 29-year-old Adekemi (name changed) arrived at a prenatal clinic in Sagamu, Nigeria, for her routine checkup, she appeared perfectly healthy. She reported no fever, chills, or body aches—none of the classic symptoms that would typically signal a malaria infection. Yet, hidden within her bloodstream and placenta, malaria parasites were silently multiplying. As an HIV-positive woman in her first pregnancy, Adekemi represented one of the most vulnerable patient populations in malaria-endemic regions—facing not one, but two intersecting health threats, with only one showing up on the standard radar 2 8 .

This is the silent crisis of asymptomatic malaria during pregnancy, a stealth infection that doesn't announce itself with obvious symptoms but can have devastating consequences for both mother and child.

When combined with HIV, the risks multiply in ways that scientists are only beginning to understand. In sub-Saharan Africa, where Nigeria bears one of the world's heaviest malaria burdens and has the second-largest HIV epidemic, this co-infection represents a critical public health challenge 2 .

13.3 Million

Pregnant women in sub-Saharan Africa infected with malaria in 2020 1

961,000

Newborns with low birth weight due to malaria infection 1

When Two Epidemics Collide: The Biology of Co-infection

The Stealthy Nature of Asymptomatic Malaria

Asymptomatic malaria represents a significant challenge to malaria control efforts. In these cases, individuals carry Plasmodium parasites in their bloodstream but, due to partial immunity developed from previous exposures, they don't experience the typical symptoms of malaria 6 .

For pregnant women, this silent infection is far from harmless—it can lead to severe maternal anaemia, stillbirth, miscarriage, and preterm delivery 1 .

The placenta becomes a particular target for certain malaria species, especially Plasmodium falciparum, which can accumulate in this vital organ, interfering with nutrient and oxygen transfer to the developing fetus 2 . This placental malaria contributes significantly to the risk of low birth weight, a major risk factor for infant death and long-term impacts including impaired growth and development 8 .

How HIV Changes the Game

HIV infection dramatically alters a pregnant woman's vulnerability to malaria through several biological mechanisms 2 :

  • Immune system compromise: HIV depletes CD4+ T lymphocytes, crucial cells for coordinating immune responses against malaria parasites.
  • Disrupted pregnancy immunity: In HIV-uninfected women, risk for malaria decreases with each subsequent pregnancy as they develop antibodies against placental malaria. HIV-infected women lose this protective effect, maintaining high vulnerability across all pregnancies.
  • Increased viral load: Malaria infection can cause temporary increases in HIV viral load, potentially accelerating HIV disease progression.
  • Higher parasite densities: HIV-positive women tend to have higher placental parasite densities compared to their HIV-negative counterparts.

How HIV and Malaria Interact in Pregnant Women

Interaction Type Biological Mechanism Impact on Pregnancy
Effect of HIV on malaria Depletion of CD4+ T cells More frequent symptomatic malaria
Effect of HIV on malaria Reduced antibody production Loss of pregnancy-specific immunity
Effect of malaria on HIV Increased viral load Potential acceleration of HIV progression
Dual infection consequences Combined immune activation Higher rates of maternal anaemia and low birth weight

The Sagamu Study: Investigating a Silent Co-epidemic

Research Methodology

A prospective study was designed with the objective of determining the prevalence of congenital malaria and identifying possible risk factors among newborns delivered at a tertiary care hospital in Sagamu, Ogun State, South-West Nigeria 3 . The innovative aspect of this research was its focus on asymptomatic infections that would typically go undetected in clinical settings.

Over a six-month period, researchers recruited 192 live newborns and their mothers, collecting data through a structured approach 3 :

Neonatal blood sampling

Within three days of life, peripheral blood samples were collected from newborns for malaria screening.

Diagnostic methods

Both traditional blood film microscopy and the OptiMAL Rapid Malaria Test kit (detecting plasmodium lactate dehydrogenase) were employed.

Maternal assessment

Simultaneous collection of maternal peripheral blood samples to check for malaria infestation.

Structured questionnaires

Administration of detailed questionnaires to mothers to identify potential factors associated with neonatal parasitaemia.

The study paid particular attention to possible risk factors for congenital malaria transmission, including prematurity, birth order, maternal HIV status, and history of febrile illness during pregnancy 3 .

Key Findings and Analysis

The study revealed a congenital malaria prevalence rate of 10.9% among the newborns, with 21 of the 192 infants testing positive for malaria parasites despite their mothers showing no symptoms 3 .

The research demonstrated that asymptomatic parasitaemia in pregnant women can and does lead to congenital malaria, with potentially serious consequences for the newborn. The findings strongly suggest that certain vulnerable groups—including preterm neonates, infants of primigravidae, and women with recent febrile illness or peripheral parasitaemia at delivery—would benefit from routine screening for malaria, regardless of symptom presentation 3 .

The interaction with HIV creates an especially dangerous scenario. Previous research has shown that HIV-coinfected women have higher placental parasite densities and altered immune responses to malaria, potentially explaining the increased transmission risk 2 .

Identified Risk Factors for Congenital Malaria Parasitaemia

Risk Factor Impact Level Statistical Significance
Maternal peripheral parasitaemia at delivery Strong association p < 0.001
History of fever within 3 months of delivery Significant association p < 0.05
First-order pregnancy (primigravidae) Higher risk p < 0.05
Premature birth Innate neonatal risk factor p < 0.05
HIV-positive maternal status Increased susceptibility Not specified in study

Research Toolkit: Essential Tools for Detection

Reagent/Technique Primary Function Advantages & Limitations
Giemsa-stained blood smear microscopy Identifies malaria species and determines parasite density Standard method, but has low sensitivity for low-density infections
Rapid Diagnostic Tests (RDTs) like Carestart TM Malaria Pf/Pv Detects parasite proteins (HRP2/PLDH) Fast and field-deployable, but less sensitive than molecular methods
Standard PCR (Polymerase Chain Reaction) Amplifies parasite DNA for detection Higher sensitivity than microscopy, but may still miss low-density infections
Ultra-sensitive PCR tests Detects very low parasitemia (as few as 22 parasites/mL) Highest sensitivity, reveals "submicroscopic" infections, but costly and technically demanding
Nested PCR targeting Glutamate-Rich Protein (GLURP) gene Confirms P. falciparum infection and determines complexity Useful for understanding infection diversity and transmission patterns
Laboratory Diagnostics

Advanced techniques like PCR enable detection of low-density infections that would otherwise go unnoticed.

Field Diagnostics

Rapid tests provide quick results in resource-limited settings but may miss submicroscopic infections.

Molecular Methods

Ultra-sensitive PCR can detect as few as 22 parasites/mL, revealing the true burden of infection.

Beyond Sagamu: The Broader Implications

The Challenge of Submicroscopic Infections

Recent research has revealed an even more hidden layer to this public health challenge: submicroscopic infections. These are malaria infections with parasite densities so low that they escape detection by standard microscopy or rapid diagnostic tests, yet still cause significant harm 8 .

A landmark study of over 4,000 pregnant women on the Thailand-Myanmar border found that submicroscopic infections were four times more prevalent than microscopically detectable infections. Most concerningly, these invisible infections were associated with substantially lower infant birth weight for both Plasmodium falciparum and Plasmodium vivax infections 8 .

This finding has profound implications for malaria screening protocols in pregnancy. If standard diagnostics miss most infections, and these "invisible" infections still cause harm, then our current approach to detecting and treating malaria in pregnant women requires significant reevaluation.

Current Prevention Strategies and Their Limitations

Several interventions currently exist to protect pregnant women from malaria's worst effects:

  • Insecticide-treated bed nets (ITNs): Research shows that not using ITNs increases the odds of asymptomatic malaria infection during pregnancy by 7.36 times 6 .
  • Intermittent preventive treatment in pregnancy (IPTp): The administration of antimalarial drugs at scheduled antenatal visits helps clear undetected infections and prevent new ones.
  • Indoor residual spraying (IRS): This vector control method has been shown to significantly reduce malaria transmission when properly implemented 1 .

However, these strategies face implementation challenges, and their effectiveness can be reduced in HIV-positive pregnant women. For instance, the gravidity-specific protection afforded by IPTp (where multigravidae women are better protected) is altered in HIV-infected women, who maintain the high vulnerability typical of first pregnancies 2 .

Promising Future Directions

Improved diagnostic tools

Developing affordable, highly sensitive point-of-care tests that can detect submicroscopic infections.

Integrated care models

Creating healthcare pathways that simultaneously address both HIV and malaria in antenatal care.

Novel prevention approaches

Investigating new vector control methods and preventive therapies tailored to co-infected patients.

Vaccine research

Developing malaria vaccines that are effective in pregnant women, including those living with HIV.

A Call to Action Against Silent Infections

The intersection of asymptomatic malaria and HIV in pregnancy represents a perfect storm of hidden risks and amplified dangers. The Sagamu study and subsequent research have illuminated a critical public health reality: what we don't see—or don't test for—can still cause profound harm to both mothers and their babies.

As Dr. James Beeson and Daniel Herbert Opi noted in their 2025 analysis, "submicroscopic infections were associated with substantially lower infant birth weight, and this negative association was observed for both P. falciparum and P. vivax infections" 8 .

This finding underscores the urgent need to rethink our approach to malaria detection and prevention in pregnant women, particularly those living with HIV.

The path forward requires a dual approach: strengthening existing prevention methods while investing in new technologies and integrated care models. Only by confronting both the visible and invisible threats of this co-epidemic can we hope to protect the most vulnerable among us—pregnant women and their newborns—from the devastating consequences of silent infections.

For women like Adekemi and the millions like her in malaria-endemic regions, the development of better diagnostic tools and prevention strategies can't come soon enough. Their health, and the health of their children, depends on our ability to see the invisible and confront the silent dangers that threaten their futures.

References

References will be listed here in the final version.

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