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This has contributed substantially to reductions in global morbidity and mortality from malaria.
Unfortunately, resistance to artemisinins has arisen recently in P. falciparum in South-East Asia, which threatens these gains.
The following core principles were used by the Guidelines Development Group that drew up the ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
1.
Early diagnosis and prompt, effective treatment of malaria Uncomplicated falciparum malaria can progress rapidly to severe forms of the disease, especially in people with no or low immunity, and severe falciparum malaria is almost always fatal without treatment.
Therefore, programmes should ensure access to early ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
2.
Rational use of antimalarial agents To reduce the spread of drug resistance, limit unnecessary use of antimalarial drugs and better identify other febrile illnesses in the context of changing malaria epidemiology, antimalarial medicines should be administered only to patients who truly have malaria.
Adherence to a... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Universal access to parasitological diagnosis of malaria is now possible with the use of quality-assured rapid diagnostic tests (RDTs), which are also appropriate for use in primary health care and community settings.
3.
Combination therapy Preventing or delaying resistance is essential for the success of both nation... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
To help protect current and future antimalarial medicines, all episodes of malaria should be treated with at least two effective antimalarial medicines with different mechanisms of action (combination therapy).
Core principles 4. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Core principles 4.
Appropriate weight-based dosing 138 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)To prolong their useful therapeutic life and ensure that all patients have an equal chance of being cured, the quality of antimalarial drugs must be ensured, and antimalarial drugs mu... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
To achieve this, dosage regimens should be based on the patient’s weight and should provide effective concentrations of antimalarial drugs for a sufficient time to eliminate the infection in all target populations.
Please refer to Malaria case management: operations manual [158].
5.1 Diagnosing malaria (2015) Suspect... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
There is no combination of signs or symptoms that reliably distinguishes malaria from other causes of fever; diagnosis based only on clinical features has very low specificity and results in overtreatment.
Other possible causes of fever and whether alternative or additional treatment is required must always be careful... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In malaria-endemic areas, malaria should be suspected in any patient presenting with a history of fever or temperature ≥ 37.5 °C and no other obvious cause.
In areas in which malaria transmission is stable (or during the high-transmission period of seasonal malaria), malaria should also be suspected in children with p... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In settings where the incidence of malaria is very low, parasitological diagnosis of all cases of fever may result in considerable expenditure to detect only a few patients with malaria.
In these settings, health workers should be trained to identify patients who may have been exposed to malaria (e.g.
recent travel t... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In all settings, suspected malaria should be confirmed with a parasitological test.
The results of parasitological diagnosis should be available within a short time (< 2 h) of the patient presenting.
In settings where parasitological diagnosis is not possible, a decision to provide antimalarial treatment must be base... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In children < 5 years, the practical algorithms for management of the sick child provided by the WHO–United Nations Children’s Fund (UNICEF) strategy for Integrated Management of Childhood Illness [159] should be used to ensure full assessment and appropriate case management at first-level health facilities and at the ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The two methods used routinely for parasitological diagnosis of malaria are light microscopy and immunochromatographic RDTs.
The latter detect parasite-specific antigens or enzymes that are either genus or species specific.
Both microscopy and RDTs must be supported by a quality assurance programme.
Antimalarial tre... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In nearly all cases of symptomatic malaria, examination of thick and thin blood films by a competent microscopist will reveal malaria parasites.
Malaria RDTs should be used if quality-assured malaria microscopy is not readily available.
RDTs for detecting PfHRP2 can be useful for patients who have received incomplete... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
If the initial blood film examination is negative in patients with manifestations compatible with severe malaria, a series of blood films should be examined at 6–12 h intervals, or an RDT (preferably one detecting PfHRP2) should be performed.
If both the slide examination and the RDT results are negative, malaria is e... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
For guidance, see the WHO manual Universal access to malaria diagnostic testing [160].
Diagnosis of malaria In patients with suspected severe malaria and in other high-risk groups, such as patients living with HIV/AIDS, absence or delay of parasitological diagnosis should not delay an immediate start of antimalarial t... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
loop-mediated isothermal amplification or PCR) do not have a role in the clinical management of malaria.
Where P. vivax malaria is common and microscopy is not available, it is recommended that a combination RDT be used that allows detection of P. vivax (pLDH antigen from P. vivax) or pan-malarial antigens (Pan-pLDH o... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Light microscopy Microscopy not only provides a highly sensitive, specific diagnosis of malaria when performed well but also allows quantification of malaria parasites and identification of the 139 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)infecting species.
Light microscopy invo... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Microscopy technicians may also contribute to the diagnosis of non-malarial diseases.
panel detection score against P. falciparum samples should be at least 75% at 200 parasites/µL.
• For detection of P. vivax in all transmission settings the panel detection score against P. vivax samples should be at least 75% at 20... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Although nucleic acid amplification-based tests are more sensitive, light microscopy is still considered the “field standard” against which the sensitivity and specificity of other methods must be assessed.
A skilled microscopist can detect asexual parasites at a density of < 10 per µL of blood, but under typical fiel... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Thus, microscopy provides good specificity for diagnosing malaria as the cause of a presenting febrile illness.
More sensitive methods allow detection of an increasing proportion of cases of incidental parasitaemia in endemic areas, thus reducing the specificity of a positive test. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Light microscopy has other important advantages: • low direct costs, if laboratory infrastructure to maintain the service is available; • high sensitivity, if the performance of microscopy is high; • differentiation of Plasmodia species; • determination of parasite densities – notably identification of hyperparasitaemi... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Good performance of microscopy can be difficult to maintain, because of the requirements for adequate training and supervision of laboratory staff to ensure competence in malaria diagnosis, electricity, good quality slides and stains, provision and maintenance of good microscopes and maintenance of quality assurance [1... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Numerous attempts have been made to improve malaria microscopy, but none has proven to be superior to the classical method of Giemsa staining and oil-immersion microscopy for performance in typical health care settings [163].
Rapid diagnostic tests Rapid diagnostic tests (RDTs) are immuno-chromatographic tests for det... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Some tests allow detection of only one species (P. falciparum); others allow detection of one or more of the other species of human malaria parasites (P. vivax, P. malariae and P. ovale) [164][165][166].
They are available commercially in various formats, e.g.
dipsticks, cassettes and cards.
Cassettes and cards are ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Since 2012, WHO has recommended that RDTs should be selected in accordance with the following criteria, based on the results of the assessments of the WHO Malaria RDT Product Testing programme [168]: • For detection of P. falciparum in all transmission settings, the • The false positive rate should be less than 10%.
•... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
• The invalid rate should be less than 5%.
Current tests are based on the detection of histidine-rich protein 2 (HRP2), which is specific for P. falciparum, pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH) or pan-specific aldolase.
The different characteristics of these antigens may affect the... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The tests have many potential advantages, including: • rapid provision of results and extension of diagnostic services to the lowest-level health facilities and communities; • fewer requirements for training and skilled personnel (for instance, a general health worker can be trained in 1 day); and • reinforcement of pa... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
They also have potential disadvantages, including: • inability, in the case of PfHRP2-based RDTs, to distinguish new infections from recently and effectively treated infections, due to the persistence of PfHRP2 in the blood for 1–5 weeks after effective treatment; • the presence in countries in the Amazon region of var... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In a systematic review [170], the sensitivity and specificity of RDTs in detecting P. falciparum in blood samples from patients in endemic areas attending ambulatory health facilities with symptoms suggestive of malaria were compared with the sensitivity and specificity of microscopy or polymerase chain reaction.
The ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
RDTs for detecting pLDH from P. falciparum are generally less sensitive and more specific than those for detecting HRP2, with an average sensitivity (95% CI) of 93.2% (88.0–96.2%) and a specificity of 98.5% (96.7–99.4%).
Several studies have shown that health workers, volunteers and private sector providers can, with ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Diagnosis with either microscopy or RDTs is expected to reduce overuse of antimalarial medicines by ensuring that treatment is 140 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)given only to patients with confirmed malaria infection, as opposed to treating all patients with fever [171... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
This is especially true when they are negative.
It is therefore important to ensure the accuracy of parasite- based diagnosis and also to demonstrate this to users and to provide them with the resources to manage both positive and negative results adequately [160].
reaction and loop-mediated isothermal amplification,... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
They are also useful for studies of drug resistance and other specialized epidemiological investigations [173]; however, they are not generally available for large-scale field use in malaria- endemic areas, nor are they appropriate for routine diagnosis in endemic areas where a large proportion of the population may ha... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Immunodiagnosis and nucleic acid amplification test methods Detection of antibodies to parasites, which may be useful for epidemiological studies, is neither sensitive nor specific enough to be of use in the management of patients suspected of having malaria [172].
Techniques to detect parasite nucleic acid, e.g.
pol... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
At present, nucleic acid-based amplification techniques have no role in the clinical management of malaria or in routine surveillance systems [174].
Good practice statement All cases of suspected malaria should have a parasitological test (microscopy or RDT) to confirm the diagnosis.
Both microscopy and RDTs should b... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
All patients with suspected malaria should be treated on the basis of a confirmed diagnosis by microscopy examination or RDT testing of a blood sample.
Correct diagnosis in malaria-endemic areas is particularly important for the most vulnerable population groups, such as young children and non-immune populations, in w... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
WHO strongly advocates a policy of “test, treat and track” to improve the quality of care and surveillance.
5.2 Treating uncomplicated malaria Definition of uncomplicated malaria A patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) but with no features of severe malar... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Therapeutic objectives The clinical objectives of treating uncomplicated malaria are to cure the infection as rapidly as possible and to prevent progression to severe disease.
“Cure” is defined as elimination of all parasites from the body.
The public health objectives of treatment are to prevent onward transmission ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Incorrect approaches to treatment Use of monotherapy The continued use of artemisinins or any of the partner medicines alone will compromise the value of ACT by selecting for drug resistance. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
As certain patient groups, such as pregnant women, may need specifically tailored combination regimens, single artemisinin derivatives will still be used in selected referral facilities in the public sector, but they should be withdrawn entirely from the private and informal sectors and from peripheral public health ca... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Similarly, continued availability of amodiaquine, mefloquine and SP as monotherapies in many countries is expected to shorten their useful therapeutic life as partner drugs of ACT, and they should be withdrawn wherever possible.
Incomplete dosing In endemic regions, some semi-immune malaria patients are cured by an in... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In the past, this led to different recommendations for patients considered semi-immune and those considered non-immune.
As individual immunity can vary considerably, even in areas of moderate-to-high transmission intensity, this practice is 141 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organizatio... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
other childhood fevers, but, like aspirin and other non-steroidal anti-inflammatory drugs, it is no longer recommended because of the risks of gastrointestinal bleeding, renal impairment and Reye’s syndrome.
Another potentially dangerous practice is to give only the first dose of a treatment course to patients with su... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Additional considerations for clinical management Can the patient take oral medication?
Some patients cannot tolerate oral treatment and will require parenteral or rectal administration for 1–2 days, until they can swallow and retain oral medication reliably.
Although such patients do not show other signs of severity... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Use of antipyretics In young children, high fevers are often associated with vomiting, regurgitation of medication and seizures.
They are thus treated with antipyretics and, if necessary, fanning and tepid sponging.
Antipyretics should be used if the core temperature is > 38.5 ºC.
Paracetamol (acetaminophen) at a do... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Ibuprofen (5 mg/kg bw) has been used successfully as an alternative in the treatment of malaria and Use of anti-emetics Vomiting is common in acute malaria and may be severe.
Parenteral antimalarial treatment may therefore be required until oral administration is tolerated.
Then a full 3-day course of ACT should be g... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
They should therefore be used with caution.
Management of seizures Generalized seizures are more common in children with P. falciparum malaria than in those with malaria due to other species.
This suggests an overlap between the cerebral pathology resulting from falciparum malaria and febrile convulsions.
As seizure... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
If the seizures continue, the airways should be maintained and anticonvulsants given (parenteral or rectal benzodiazepines or intramuscular paraldehyde).
When the seizure has stopped, the child should be treated as indicated in section 7.10.5, if his or her core temperature is > 38.5 ºC.
There is no evidence that pro... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
5.2.1 Artemisinin-based combination therapy Strong recommendation for , High certainty evidence Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following ACTs: • artemether + lumefantrine • artesunate + amodiaquine • artesunate + mefloq... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The drug has also received a positive scientific opinion from the European Medicines Agency and undergone a positive review by the WHO Advisory Committee on Safety of Medicinal Products. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Countries can consider including this medicine in their national treatment guidelines for the treatment of malaria based on WHO’s position on the use of this drug pending the formal recommendation anticipated in 2021. WHO's position was published in the information note The use of artesunate-pyronaridine for the treatm... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Practical Info The pipeline for new antimalarial drugs is healthier than ever before, and several new compounds are in various stages of 142 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)development.
Some novel antimalarial agents are already registered in some countries.
The decisi... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In general, when there are no satisfactory alternatives, newly registered drugs may be recommended; however, for global or unrestricted recommendations, considerably more evidence than that submitted for registration is usually required, to provide sufficient confidence for their safety, efficacy and relative merits as... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Some are still in the pre-registration phase and are not discussed here.
Arterolane + piperaquine, artemisinin + piperaquine base and artemisinin + napththoquine are new ACTs, which are registered and used in some countries.
In addition, there are several new generic formulations of existing drugs.
None of these yet... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
unrestricted use).
Artesunate + pyronaridine A systematic review of artesunate + pyronaridine included six trials with a total of 3718 patients.
Artesunate + pyronaridine showed good efficacy as compared with artemether + lumefantrine and artesunate + mefloquine in adults and older children with P. falciparum malaria... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In addition, regulatory authorities noted slightly higher hepatic transaminase concentrations in artesunate + pyronaridine recipients than in comparison groups and recommended further studies to characterize the risk for hepatotoxicity.
Preliminary data from repeat-dosing studies are reassuring. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In 2012, artesunate-pyronaridine was granted a positive scientific opinion under the European Medicines Agency (EMA) Article 58 procedure, but with a restricted label, mainly due to concerns over potential hepatotoxicity of the pyronaridine component, efficacy in children under 5 years of age, and safety, especially wi... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In 2015, an EMA Scientific Advisory Group concluded that cumulative safety data on hepatic events had provided sufficient evidence to alleviate concerns over hepatotoxicity and thus to allow recommendation of the use of artesunate pyronaridine for the treatment and re-treatment of uncomplicated malaria in patients with... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The EMA therefore modified the product label to remove all restrictions on repeat dosing, on use only in areas of high antimalarial drug resistance and low malaria transmission, and on requirements to monitor liver function.
In addition, it granted a positive scientific opinion for artesunate-pyronaridine granules for... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Artesunate-pyronaridine was included in WHO’s list of prequalified medicines for malaria in April 2012, based on the EMA’s positive scientific opinion of this product in accordance with Article 58.
Since labelling provisions are based on EMA conclusions, these provisions were updated as a result of the EMA’s 2015 revi... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Products included in the WHO prequalification list are those that have been assessed through the various mechanisms and found to comply with WHO-recommended regulatory standards and requirements for quality, safety and efficacy.
In June 2017, artesunate-pyronaridine was also added to the WHO Model List of Essential Me... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Due to the hepatotoxicity concerns identified in 2012, the WHO Guidelines for the treatment of malaria (2015) did not recommend the use of artesunate-pyronaridine for general use.
A further meeting in December 2017 resulted in the need for GMP to request, in 2018, the support of the WHO Advisory Committee on Safety of... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Having completed its review, the committee considered that the current safety restrictions on the use of artesunate-pyronaridine (Pyramax®) for the treatment of uncomplicated malaria, as stated in the Guidelines for the treatment of malaria, are no longer justified [176].
The Global Malaria Programme will revise the G... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
There are currently insufficient data to make general recommendations.
Artemisinin + piperaquine base combines two well-established, well-tolerated compounds.
It differs from previous treatments in that the piperaquine is in the base form, the artemisinin dose is relatively low, and the current recommendation is for ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
There are insufficient data from clinical trials for a general recommendation, and there is concern that the artemisinin dose regimen provides insufficient protection against resistance to the piperaquine component.
Artemisinin + naphthoquine is also a combination of two relatively old compounds that is currently bein... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
There are currently insufficient data from rigorously conducted randomized controlled trials to make general recommendations.
143 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)Many ACTs are generics.
The bioavailability of generics of currently recommended drugs must be comparable t... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Please refer to Good procurement practices for artemisinin-based antimalaria medicines [178].
Evidence To Decision Benefits and harms Recommendation: Treat adults and children with uncomplicated P. falciparum malaria (including infants, pregnant women in their second and third trimesters and breastfeeding women) with ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Desirable effects • Studies have consistently demonstrated that the five WHO-recommended ACTs result in < 5% PCR-adjusted treatment failures in settings with no resistance to the partner drug (high- quality evidence).
Undesirable effects Increased cost.
• Recommendation: Dihydroartemisinin + piperaquine is recommende... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
• Dihydroartemisinin + piperaquine has a longer half-life than artemether + lumefantrine, and fewer new infections occur within 9 weeks of treatment with dihydroartemisinin + piperaquine (high-quality evidence).
• Dihydroartemisinin + piperaquine and artesunate + mefloquine have similar half-lives, and a similar frequ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Undesirable effects: • A few more patients receiving dihydroartemisinin + piperaquine than those given artesunate + mefloquine had a prolonged QT interval (low-quality evidence) • A few more patients receiving dihydroartemisinin + piperaquine than those given artesunate + mefloquine or artemether + lumefantrine had bor... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Justification High GRADE In the absence of resistance to the partner drug, the five recommended ACTs have all been shown to achieve a PCR- adjusted treatment failure rate of 5% in many trials in several settings in both adults and children (high-quality evidence) [179][180].
Other considerations The guideline developm... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Remarks Recommendation: Treat adults and children with uncomplicated P. falciparum malaria (including infants, pregnant women in their second and third trimesters and breastfeeding women) with ACT.
The WHO-approved first-line ACT options are: artemether + lumefantrine, artesunate + amodiaquine, artesunate + mefloquine... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
These options are recommended for adults and children, including infants, lactating women and pregnant women in their 144 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)second and third trimester. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In deciding which ACTs to adopt in national treatment policies, national policy- makers should take into account: the pattern of resistance to antimalarial drugs in the country, the relative efficacy and safety of the combinations, their cost, the availability of paediatric formulations and the availability of co-formu... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The Guideline Development Group decided to recommend a “menu” of approved combinations from which countries can select first- and second- line therapies.
Modelling studies suggest that having multiple first-line ACTs available for use may help to prevent or delay the development of resistance.
Recommendation: Dihydro... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
A systematic review showed that the dosing regimen of dihydroartemisinin + piperaquine currently recommended by the manufacturers leads to sub-optimal dosing in young children.
The group plans to recommend a revised dosing regimen based on models of pharmacokinetics.
Further studies of the risk for QT interval prolon... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The artemisinin component rapidly clears parasites from the blood (reducing parasite numbers by a factor of approximately 10 000 in each 48 h asexual cycle) and is also active against the sexual stages of the gametocytes that mediate onward transmission to mosquitos.
The longer- acting partner drug clears the remainin... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Partner drugs with longer elimination half-lives also provide a period of post-treatment prophylaxis.
The GDG recommended dihydroartemisinin + piperaquine for use in 2009 but re-evaluated the evidence in 2013 because additional data on its safety had become available. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The group noted the small absolute prolongation of the QT interval with dihydroartemisinin + piperaquine but was satisfied that the increase was of comparable magnitude to that observed with chloroquine and was not important clinically [178][181]. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
5.2.2 Duration of treatment A 3-day course of the artemisinin component of ACTs covers two asexual cycles, ensuring that only a small fraction of parasites remain for clearance by the partner drug, thus reducing the potential development of resistance to the partner drug.
Shorter courses (1–2 days) are therefore not r... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Treating uncomplicated P. falciparum malaria (2015) Strong recommendation for , High certainty evidence Duration of ACT treatment: ACT regimens should provide 3 days’ treatment with an artemisinin derivative.
Evidence To Decision Benefits and harms Desirable effects • Fewer patients taking ACTs containing 3 days of an... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
• Fewer participants taking ACTs containing 3 days of an artemisinin derivative have gametocytaemia at day 7 (high-quality evidence).
145 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)Certainty of the Evidence For all critical outcomes: High. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Justification High GRADE In four randomized controlled trials in which the addition of 3 days of artesunate to SP was compared directly with 1 day of artesunate with SP: • Three days of artesunate reduced the PCR-adjusted treatment failure rate within the first 28 days from that with 1 day of artesunate (RR, 0.45; 95% ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
• Three days of artesunate reduced the number of participants who had gametocytaemia at day 7 from that with 1 day of artesunate (RR, 0.74; 95% CI, 0.58–0.93, four trials, 1260 participants, high-quality evidence).
Other considerations The guideline development group considered that 3 days of artemisinin derivative ar... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Remarks Longer ACT treatment may be required to achieve > 90% cure rate in areas with artemisinin-resistant P. falciparum, but there are insufficient trials to make definitive recommendations.
A 3-day course of the artemisinin component of ACTs covers two asexual cycles, ensuring that only a small fraction of parasite... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Shorter courses (1–2 days) are therefore not recommended, as they are less effective, have less effect on gametocytes and provide less protection for the slowly eliminated partner drug.
Rationale for the recommendation: The Guideline Development Group considers that 3 days of an artemisinin derivative are necessary to... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
5.2.3 Dosing of ACTS ACT regimens must ensure optimal dosing to prolong their useful therapeutic life, i.e.
to maximize the likelihood of rapid clinical and parasitological cure, minimize transmission and retard drug resistance.
It is essential to achieve effective antimalarial drug concentrations for a sufficient ti... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
The dosage recommendations below are derived from understanding the relationship between dose and the profiles of exposure to the drug (pharmacokinetics) and the resulting therapeutic efficacy (pharmacodynamics) and safety.
Some patient groups, notably younger children, are not dosed optimally with the “dosage regimen... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
In these guidelines when there was pharmacological evidence that certain patient groups are not receiving optimal doses, dose regimens were adjusted to ensure similar exposure across all patient groups.
Weight-based dosage recommendations are summarized below.
While age-based dosing may be more practical in children,... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Age-based dosing can therefore result in under- dosing or over-dosing of some patients, unless large, region-specific weight-for-age databases are available to guide dosing in that region.
Factors other than dosage regimen may also affect exposure to a drug and thus treatment efficacy.
The drug exposure of an individ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Poor adherence is a major cause of treatment failure and drives the emergence and spread of drug resistance.
Fixed-dose combinations encourage adherence and are preferred to loose (individual) tablets.
Prescribers should take the time necessary to explain to patients why they should complete antimalarial course. | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Artemether + lumefantrine Formulations currently available: Dispersible or standard tablets containing 20 mg artemether and 120 mg lumefantrine, and standard tablets containing 40 mg artemether and 240 mg lumefantrine in a fixed-dose combination formulation.
The flavoured dispersible tablet paediatric formulation faci... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Target dose range: A total dose of 5–24 mg/kg bw of artemether and 29–144 mg/ kg bw of lumefantrine 146 of 396 WHO Guidelines for malaria - 3 June 2022 - World Health Organization (WHO)Recommended dosage regimen: Artemether + lumefantrine is given twice a day for 3 days (total, six doses).
The first two doses should, ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Body weight (kg) Artesunate + amodiaquine dose (mg) given daily for 3 days Body weight (kg) Dose (mg) of artemether + lumefantrine given twice daily for 3 days 5 to < 15 20 + 120 15 to < 25 40 + 240 25 to < 35 60 + 360 ≥ 35 80 + 480 Factors associated with altered drug exposure and treatment response: • Decreased expos... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
As these target populations may be at increased risk for treatment failure, their responses to treatment should be monitored more closely and their full adherence ensured.
Increased exposure to lumefantrine has been observed in patients concomitantly taking lopinavir- lopinavir/ritonavir-based antiretroviral agents bu... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
• Additional comments: • An advantage of this ACT is that lumefantrine is not available as a monotherapy and has never been used alone for the treatment of malaria.
• Absorption of lumefantrine is enhanced by co-administration with fat.
Patients or caregivers should be informed that this ACT should be taken immediate... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
Artesunate + amodiaquine Formulations currently available: A fixed-dose combination in tablets containing 25 + 67.5 mg, 50 + 135 mg or 100 + 270 mg of artesunate and amodiaquine, respectively Target dose and range: The target dose (and range) are 4 (2–10) mg/kg bw per day artesunate and 10 (7.5–15) mg/kg bw per day amo... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
4.5 to < 9 25 + 67.5 9 to < 18 50 + 135 18 to < 36 100 + 270 ≥ 36 200 + 540 Factors associated with altered drug exposure and treatment response: • Treatment failure after amodiaquine monotherapy was more frequent among children who were underweight for their age.
Therefore, their response to artesunate + amodiaquine ... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
• Artesunate + amodiaquine is associated with severe neutropenia, particularly in patients co-infected with HIV and especially in those on zidovudine and/or cotrimoxazole.
Concomitant use of efavirenz increases exposure to amodiaquine and hepatotoxicity.
Thus, concomitant use of artesunate + amodiaquine by patients t... | https://docs-lawep.s3.us-east-2.amazonaws.com/1710246783294.pdf | https://www.healthynewbornnetwork.org/hnn-content/uploads/WHO-UCN-GMP-2022.01-Rev.2-eng.pdf | Nigeria |
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