Malaria treatment during the first trimester of pregnancy in Nigeria is one of the most consequential prescribing decisions a clinician can face. Nigeria accounts for the highest number of malaria-related deaths in the world, and pregnant women are among the most at-risk population.(1) In the first trimester specifically, the stakes are even higher because organogenesis is ongoing and the wrong treatment choice (or worse, delayed treatment) can result in miscarriage, severe maternal anaemia, or even maternal death.
For many years, the standard recommendation was quinine plus clindamycin for uncomplicated malaria in the first trimester, based on concerns about the potential embryotoxicity of artemisinin derivatives. However, a landmark meta-analysis published in The Lancet in 2022, which reviewed data from over 34,000 pregnancies across 12 cohort studies, led the World Health Organization to significantly update its recommendations.(2)
Why This Guide Matters for Nigerian Clinicians
This guide explains the current WHO 2025 guidelines for malaria treatment in the first trimester of pregnancy, what is now recommended, what is contraindicated, and how to apply these guidelines practically in Nigerian clinical settings. For quick access to treatment guidelines and drug references at the point of care, visit Medituri Treatment Guidelines at medituri.com.
Drug Class: Antimalarial Agents
The parasite responsible for the vast majority of malaria cases in Nigeria is Plasmodium falciparum. Treatment in pregnancy is guided by the severity of illness, the trimester of pregnancy, and the safety profile of available drugs for the developing foetus. The main drug classes relevant to first trimester treatment include artemisinin-based combination therapies (ACTs), cinchona alkaloids (quinine), and clindamycin as a combination partner.(3)
Why Prompt Treatment Is Critical in the First Trimester
Malaria in the first trimester of pregnancy must never be managed with a watchful waiting approach. Untreated or delayed treatment of P. falciparum infection in early pregnancy is associated with:
- Spontaneous abortion and miscarriage
- Severe maternal anaemia leading to high-output cardiac failure
- Quinine therapy causes maternal hypoglycaemia, particularly in the first trimester
- Severe malaria with multi-organ failure
- Maternal death
The Cost of Delayed Treatment
The risk of withholding or delaying antimalarial treatment always outweighs the risk of the available treatments in the first trimester. Clinicians must begin treatment as soon as they confirm the diagnosis.(3)
The most current guidance is provided in the WHO Guidelines for Malaria, August 2025, which confirm and build on the 2022 update to first-trimester treatment recommendations. There are no new 2026 WHO malaria guidelines as of May 2026. The August 2025 guidelines remain the most current reference for clinical practice.(3,4)
Uncomplicated Malaria in the First Trimester: Artemether-Lumefantrine Now the Preferred Treatment
In 2022 the WHO updated its guidelines to recommend artemether-lumefantrine (AL) as the preferred first-line treatment for uncomplicated P. falciparum malaria in the first trimester of pregnancy.(4) This replaces the previous recommendation of quinine plus clindamycin for seven days.
The change was driven by a large meta-analysis that found AL was associated with 42 percent fewer adverse pregnancy outcomes (including pregnancy loss and major congenital malformations) compared to oral quinine in the first trimester.(2) AL has more human safety data in early pregnancy than any other ACT currently available.
Important: Other ACTs including artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine do not have sufficient safety data for routine use in the first trimester. WHO does not recommend them for first-trimester treatment. AL is the only ACT currently recommended for this indication.(3,4)
Artemether-Lumefantrine Dosing in First Trimester Pregnancy
The dosing of artemether-lumefantrine in first trimester pregnancy is the same as for non-pregnant adults. Treatment is given over three days as follows:(3)
| Time | Dose | Route | Notes |
| Hour 0 | 4 tablets (artemether 20 mg + lumefantrine 120 mg per tablet) | Oral | First dose |
| Hour 8 | 4 tablets | Oral | Second dose |
| Hour 24 | 4 tablets | Oral | Day 2 morning |
| Hour 36 | 4 tablets | Oral | Day 2 evening |
| Hour 48 | 4 tablets | Oral | Day 3 morning |
| Hour 60 | 4 tablets | Oral | Day 3 evening |
Always give artemether-lumefantrine with food or a fat-containing drink to ensure adequate absorption of lumefantrine. Taking AL on an empty stomach significantly reduces bioavailability and may result in treatment failure.
What If Quinine Is the Only Available Option?
In settings where AL is unavailable, oral quinine plus clindamycin remains an acceptable alternative for uncomplicated malaria in the first trimester.(3) The dosing is as follows:
- Quinine: 10 mg/kg (salt) three times daily for 7 days
- Clindamycin: 10 mg/kg twice daily for 7 days
If clindamycin is unavailable, quinine monotherapy may be used for 7 days, though it is less effective and associated with higher rates of recrudescence. Clinicians should make every effort to source clindamycin where possible.(3)
Severe Malaria in First Trimester: Parenteral Treatment
Severe malaria in any trimester of pregnancy is a medical emergency. Treatment must not be delayed for any reason. The current WHO 2025 recommendation for severe malaria in the first trimester is parenteral artesunate as the preferred option, consistent with treatment in the second and third trimesters.(3,4)
In the first trimester specifically, both injectable artesunate and intravenous quinine are considered acceptable options where artesunate is unavailable, as safety data for artesunate in the first trimester is more limited than in later pregnancy.(4) However, treatment must not be withheld while debating drug choice. If only one option is available, it must be used immediately.
| Severity | Preferred Treatment | Alternative If Unavailable |
| Uncomplicated malaria | Artemether-lumefantrine oral 6 doses over 3 days | Quinine + clindamycin oral for 7 days |
| Severe malaria | Injectable artesunate IV or IM | IV quinine (if artesunate unavailable) |
Antimalarial Drugs Contraindicated in First Trimester Pregnancy
The following antimalarial drugs must not be used in the first trimester of pregnancy:
- Primaquine: Causes haemolysis and is contraindicated throughout pregnancy. Do not use for radical cure of P. vivax or P. ovale in pregnant women.
- Tafenoquine: Contraindicated in pregnancy. Same mechanism as primaquine and carries the same haemolytic risk.
- Tetracyclines (doxycycline): Contraindicated in pregnancy due to effects on foetal bone and tooth development.
- Sulfadoxine-pyrimethamine (SP): SP is used for Intermittent Preventive Treatment in Pregnancy (IPTp) but only from week 13 of pregnancy onwards (second trimester). It must not be given in the first trimester.
- Artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-mefloquine: Insufficient safety data for first trimester use. Not recommended by WHO for this indication.(3,4)
Important Drug Interactions in First Trimester Malaria Treatment
Clinicians treating malaria in pregnant women must also be aware of the following interactions:
- AL and rifampicin: Rifampicin significantly reduces lumefantrine plasma levels through CYP3A4 induction. Avoid co-administration in TB-malaria co-infected patients where possible.(5)
- Quinine and mefloquine: Additive risk of QT prolongation and seizures. Do not co-administer.
- Quinine and beta-blockers or digoxin: Risk of cardiac conduction abnormalities. Monitor ECG if co-prescribing.
- Quinine and antacids containing aluminium or magnesium: Reduce quinine absorption. Separate administration by at least 2 hours.
Adverse Effects of First Trimester Antimalarial Treatment
Artemether-Lumefantrine
- Nausea, vomiting, and abdominal discomfort: common, particularly when taken without food
- Headache, dizziness, and sleep disturbance: usually mild and self-limiting
- QT prolongation: rare at standard doses but avoid in patients with cardiac arrhythmias
- No significant increase in congenital malformations or pregnancy loss has been demonstrated in available human data.(2,4)
Quinine
- Hypoglycaemia: particularly dangerous in pregnant women. Monitor blood glucose closely during IV quinine administration.
- Cinchonism: tinnitus, headache, nausea, and visual disturbances at therapeutic doses
- QT prolongation at high doses: monitor ECG during IV administration
- Uterine contractions at high doses: use with caution and at correct doses only
Monitoring and Prescribing Tips
- Confirm the diagnosis with a malaria rapid diagnostic test (RDT) or blood film microscopy before treating. Do not treat empirically without diagnostic confirmation where testing is available.
- Always take a drug history before prescribing. Ask specifically about herbal preparations, which are widely used in Nigerian antenatal care and may interact with antimalarial drugs.
- Monitor blood glucose closely in all pregnant women receiving antimalarial treatment, particularly those on quinine. Pregnant women are at significantly higher risk of hypoglycaemia.
Follow-Up and Special Considerations
- Assess for anaemia at presentation and after treatment. Malaria in pregnancy worsens anaemia and may require iron supplementation or transfusion.
- Always follow up after treatment to confirm parasite clearance. Repeat RDT or blood film at day 3 and day 28 where possible.
- If the patient is on antiretroviral therapy for HIV, check for interactions with the selected antimalarial drug before prescribing.
Clinical Tips for Nigerian Practice
- The most common clinical error in Nigerian antenatal care is using sulfadoxine-pyrimethamine for IPTp before week 13 of pregnancy. SP must not be given in the first trimester. Confirm gestational age before administering any IPTp dose.
- Many Nigerian clinicians are still prescribing quinine plus clindamycin as first-line for uncomplicated first-trimester malaria. This is now outdated. Artemether-lumefantrine is the WHO 2025 preferred first-line treatment for this indication.
When First-Line Drugs Are Unavailable
Where AL is unavailable at a health facility, refer urgently or facilitate emergency dispensing rather than defaulting to monotherapy.
Severe malaria in any pregnant woman is an obstetric emergency. Involve obstetric care, manage in a facility with IV access and blood glucose monitoring, and do not delay parenteral treatment.
Document gestational age clearly in all prescription records for pregnant patients. Treatment choice and safety guidance depends on trimester.
Nigeria and West Africa Context
Nigeria carries the world’s highest malaria burden, accounting for approximately 25.9 percent of global malaria cases and 31 percent of global malaria deaths.(1) The Nigeria National Malaria Elimination Programme (NMEP) guidelines are largely aligned with WHO recommendations, though the transition from quinine-based to AL-based first-trimester treatment may not yet be uniformly reflected in all Nigerian health facility protocols. Clinicians should follow WHO 2025 guidance as the current evidence-based standard.
A 2026 study published in the Nigerian Health Journal analyzed prescribing patterns at a Nigerian tertiary hospital and found that while overall adherence to malaria-in-pregnancy guidelines was high at 99.4 percent, first-trimester prescriptions showed the highest rates of deviation from guidelines.(6) This highlights a specific knowledge gap that this post aims to address.
Availability Challenges in Nigerian Primary Care
Furthermore, a significant challenge in Nigerian primary care is the inconsistent availability of artemether-lumefantrine and clindamycin at the primary health centre level. Clinicians in rural settings should be aware of referral pathways when first-line drugs are unavailable for a pregnant patient in the first trimester.
Traditional herbal preparations for malaria remain widely used in Nigeria and West Africa, including in pregnant women. Clinicians should ask specifically about herbal medicine use at every antenatal visit, as some preparations may cause uterine contractions or interact with prescribed antimalarials.
Conclusion
Malaria treatment in pregnancy during the first trimester in Nigeria has changed significantly following the WHO 2022 guideline update, confirmed in the August 2025 guidelines. Artemether-lumefantrine is now the preferred first-line treatment for uncomplicated P. falciparum malaria in the first trimester, replacing the previous quinine plus clindamycin regimen.
In conclusion, the key principles for every clinician managing malaria in the first trimester of pregnancy in Nigeria are: treat promptly without delay, use AL as first-line for uncomplicated malaria, use parenteral artesunate or quinine for severe malaria, avoid contraindicated drugs including SP, primaquine, and tetracyclines, and monitor closely for hypoglycaemia and anaemia throughout treatment.
Getting this right protects two patients at once: the mother and the unborn child. That is a responsibility every clinician in Nigeria must take seriously.
Access Malaria Treatment Guidelines on Medituri
For quick access to malaria treatment protocols, drug interaction checks, and evidence-based clinical guidelines at the point of care, visit the Medituri Treatment Guidelines and Drug Database at medituri.com. Medituri gives healthcare professionals in Nigeria and West Africa instant access to reliable clinical drug information on any device, any time.
References
- World Health Organization. World Malaria Report 2024. Geneva: WHO; 2024. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2024
- Saito M, McGready R, Tinto H, et al. Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: an individual patient data meta-analysis. Lancet. 2023;401(10371):118-130. doi:10.1016/S0140-6736(22)01881-5.
- World Health Organization. WHO Guidelines for Malaria. Geneva: WHO; 13 August 2025. Available from: https://www.who.int/publications/i/item/guidelines-for-malaria
- World Health Organization. Evidence re
- view for the treatment of uncomplicated malaria in the first trimester of pregnancy. Geneva: WHO; 2022. Available from: https://www.who.int/publications/i/item/9789240069404
- Byakika-Kibwika P, Lamorde M, Mayito J, et al. Significant pharmacokinetic interactions between artemether-lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults. J Antimicrob Chemother. 2012;67(9):2213-2221.
- Okwori JM, Itodo MO, Abatur SC, Eze SC, Okoye SC. Antimalarial prescription patterns and adherence to the WHO 2024 guidelines among pregnant women: a case study from a Nigerian tertiary hospital. Niger Health J. 2026;25(4):1543-1554.
