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Malaria in infants aged less than six months - is it an area of unmet medical need?
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PMID:  23198986     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Despite the protection provided by several factors, including maternal antibodies, the burden of malaria in young infants may be higher than previously thought. Infants with congenital or neonatal malaria may have a different clinical presentation than older children, and diagnosis may be confused with other neonatal diseases due to an overlap of clinical manifestations. In addition, there is little information on the use of artemisinin-based combination therapy in young infants. There is the need for a more accurate estimate of the parasite prevalence and the incidence of clinical malaria in infants under 6 months old, as well as a better characterization of risk factors, pharmacokinetic profiles, safety and efficacy of currently available anti-malarial treatments, in order to develop evidence-based treatment guidelines for this population.
Authors:
Umberto D'Alessandro; David Ubben; Kamal Hamed; Serign Jawo Ceesay; Joseph Okebe; Makie Taal; Eugene Kaman Lama; Moussa Keita; Lamine Koivogui; Alain Nahum; Kalifa Bojang; Aja Adam Jagne Sonko; Honorat Francis Lalya; Bernard Brabin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-12-02
Journal Detail:
Title:  Malaria journal     Volume:  11     ISSN:  1475-2875     ISO Abbreviation:  Malar. J.     Publication Date:  2012  
Date Detail:
Created Date:  2012-12-25     Completed Date:  2013-04-29     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101139802     Medline TA:  Malar J     Country:  England    
Other Details:
Languages:  eng     Pagination:  400     Citation Subset:  IM    
Affiliation:
Medical Research Council Unit, PO Box 273, Banjul, The Gambia. udalessandro@mrc.gm
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MeSH Terms
Descriptor/Qualifier:
Antimalarials / administration & dosage*,  pharmacokinetics
Humans
Incidence
Infant
Infant, Newborn
Malaria / epidemiology*,  pathology*
Prevalence
Chemical
Reg. No./Substance:
0/Antimalarials
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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Journal Information
Journal ID (nlm-ta): Malar J
Journal ID (iso-abbrev): Malar. J
ISSN: 1475-2875
Publisher: BioMed Central
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Copyright ©2012 D'Alessandro et al.; licensee BioMed Central Ltd.
open-access:
Received Day: 11 Month: 10 Year: 2012
Accepted Day: 28 Month: 11 Year: 2012
collection publication date: Year: 2012
Electronic publication date: Day: 2 Month: 12 Year: 2012
Volume: 11First Page: 400 Last Page: 400
PubMed Id: 23198986
ID: 3529680
Publisher Id: 1475-2875-11-400
DOI: 10.1186/1475-2875-11-400

Malaria in infants aged less than six months - is it an area of unmet medical need?
Umberto D’Alessandro12 Email: udalessandro@mrc.gm
David Ubben3 Email: ubbend@mmv.org
Kamal Hamed4 Email: kamal.hamed@novartis.com
Serign Jawo Ceesay1 Email: sjceesay@mrc.gm
Joseph Okebe1 Email: jokebe@mrc.gm
Makie Taal5 Email: makietaal@hotmail.com
Eugene Kaman Lama6 Email: eugenekokolylama@yahoo.fr
Moussa Keita6 Email: paluguinee@yahoo.fr
Lamine Koivogui6 Email: koivoguil@gmail.com
Alain Nahum7 Email: nahum_alain@yahoo.fr
Kalifa Bojang1 Email: kbojang@mrc.gm
Aja Adam Jagne Sonko5 Email: ajsonko@yahoo.com
Honorat Francis Lalya8 Email: lalyahf@hotmail.com
Bernard Brabin9 Email: B.J.Brabin@liverpool.ac.uk
1Medical Research Council Unit, PO Box 273, Banjul, The Gambia
2Institute of Tropical Medicine, Nationalestraat 155, 2000, Antwerp, Belgium
3Medicines for Malaria Venture (MMV), PO Box 1826, 20 rte de Pré-Bois, 1215, Geneva 15, Switzerland
4Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-01080, USA
5Ministry of Health and Social Welfare, The Quadrangle, Banjul, The Gambia
6Ministry of Health, BP 6623, Conakry, Guinea
7Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin
8Centre National Hospitalier Universitaire Hubert K. Maga, Cotonou, Benin
9Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L35QA, UK

Background

Although the burden of Plasmodium falciparum malaria in children aged under five years is well documented [1], there is limited and contradictory information about the impact of the disease in infants under six months of age. Early studies concluded that malaria was uncommon in young infants and that clinical disease was of little importance [2-4], despite several early reports of a uniform rise in parasite prevalence during the first few months of life [5]. Young infants with malaria may have different clinical manifestations [6,7] and lower parasite densities [5] than older children. Nevertheless, even low-density infections (1–500 parasites/μL) in infants can result in anaemia if left untreated [8], and may rapidly progress to become life-threatening [9].

Neonatal malaria is considered a rare occurrence due to the protective effect of maternal immunity after birth. Maternal immunoglobulin G (IgG) antibodies are acquired by the fetus via the placenta in utero[10], although there is only limited evidence suggesting a protective role of these passively acquired antibodies against malaria parasites [11]. IgG levels are thought to decrease variably during the first year of life [12]. Neonates may also be protected through factors that inhibit parasite growth, such as lactoferrin (which binds iron) and secretory IgA, found in breast milk and in maternal and infant sera [13]. Parasite replication depends on the metabolic substrate para-aminobenzoic acid (pABA), which is present only in low levels in breast milk [10]. Haemoglobin F (HbF), present in high concentrations at birth [10], can inhibit parasite development [14] and can protect the infant in the first few months of life. The parasite antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) mediates cytoadherence of infected red blood cells to the endothelial cells lining the blood vessels. HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized erythrocytes in the first few months of life by altering PfEMP-1 display on HbF RBCs, and by binding PfEMP-1 and preventing sequestration of parasitized RBCs, respectively [15]. HbF levels decline after a peak at 6 weeks of age [10], and as both HbF and IgG disappear from circulation, infant susceptibility to P. falciparum malaria increases [15].

Iron-deficiency anaemia is common in sub-Saharan Africa and can cause impaired cognitive and motor development, growth impairment and anorexia. Consequently, in many areas, iron supplementation is recommended in children below two years of age. However, iron status has been shown to have an effect on the risk of malaria in young infants, with iron deficiency potentially causing a decrease in malaria morbidity and mortality [16].

In Mozambique and Benin, placental malaria has been associated with shorter time to first episode of infant malaria [17,18]. The mechanisms underlying this association are unclear but may relate to prenatal foetal priming [19]. Therefore, some reduction of malaria risk in infants can probably be achieved by improving malaria control in late pregnancy.


Burden of malaria in infants aged less than six months

Malaria in infants is classified according to the time of infection. Congenital malaria, defined as asexual parasites detected in the cord blood or in the peripheral blood during the first week of life [20], is due to transmission from the mother through the placenta just before or during delivery [21], while neonatal malaria, which can occur within the first 28 days of life, is due to an infective mosquito bite after birth [21]. Differentiating between congenital and acquired neonatal malaria can be difficult, especially in areas of intense malaria transmission [22]. Various studies across Africa have demonstrated that 7–10% of newborns may have malaria parasites in their cord blood [8], in some cases either without evidence of an active maternal infection or with parasite genotypes different to those found in the mother. This suggests transplacental passage of parasites followed by clearance from maternal and placental blood, with persistence in the foetus [8,23,24].

Recent reports suggest that malaria in infants under six months of age may not be uncommon, although data on prevalence and outcome are still contradictory [25]. Prevalence of infection can vary between 0% and 27% [9,25-33], while the percentage of deaths attributed to malaria (as determined by verbal autopsy) may be between 20.1% and 46.2% [34]. The occurrence of infection in utero is also reflected by the prevalence of splenomegaly at one month of age, which can be as high as 80%, indicating an early development of a splenic response to the infection [5,35].

In Mozambique, clinical malaria incidence in infants aged 1– < 6 months was substantial (320/1,000 child-years at risk in 2003–2004 and 146/1,000 child-years at risk in 2004–2005) [36]. Reports of congenital malaria have predominantly come from Nigeria; the prevalence of parasitaemia in infants in these studies as well as in those from other malaria-endemic regions varied widely – between 0.7% and 46.7% [20,33,37-51]. Parasite densities in neonatal blood were also varied, although most infections were of low density [20,40,42,48-50,52,53]. However, differences in transmission dynamics, small sample sizes and lack of details on quality control and sample selection procedures make the interpretation of these findings difficult [20,25].

Malaria infections (mean geometric parasite density = 533 parasites/μl of blood, as detected by PCR) were common in Ghanaian infants less than 6 months of age (13.6% in newborns; 1.5–9.7% in those aged from 2–26 weeks), although clinical malaria symptoms were rare or uncommon (fever, vomiting, diarrhoea and coughing occurred in 1.8%, 1.8%, 3.0% and 4.8% of infants aged 0–3 months, respectively, and in 4.5%, 3.0%, 8.0% and 10.6% of infants aged 3–6 months) [54]. In Mozambique, although malaria in infants aged under six months represented less than 20% of the total outpatient visits, infants with malaria were admitted in a significantly higher proportion than children aged 1–4 years [36]. The impact of malaria in this age group is also illustrated by a greater difference in mean haematocrit between malaria and non-malaria cases in infants aged from 2–12 months (4.9%) than in children aged 5 years or above (1.8%). Among infants aged under six months attending an urban hospital in Nigeria, 27.1% had a positive blood slide and a significantly lower haematocrit (33.0%) compared with those who were uninfected (35.1%)(p = 0.003). Indeed, a haematocrit of less than 33% was the most common clinical finding among infected infants, while the occurrence of fever was 4% [9].

A systematic review of age-patterns of malaria revealed that as transmission increased, there was a shift of clinical malaria towards younger age groups, regardless of seasonality [55]. As transmission intensity increased and seasonality decreased, severe cases became more frequent in the younger ages. Nevertheless, wherever a comparison between age groups was possible, malaria mortality was higher in younger children, with the peak age shifting towards infants as transmission became more intense [55].


Clinical signs and symptoms and malaria diagnosis in infants aged under six months

Signs and symptoms of congenital malaria include fever, anaemia, splenomegaly, hepatomegaly, jaundice, vomiting, diarrhoea, poor feeding, restlessness, drowsiness, pallor, respiratory distress, cyanosis, and possibly convulsions [39,56].

Malaria in young infants may be asymptomatic [6,7], or it may be difficult to diagnose because the clinical presentation may mimic other diseases, such as sepsis [33]. Indeed, congenital malaria may be more common in newborns with suspected or confirmed sepsis (28.6%) [38,47]. It is unclear what influence infant HIV infection has on these risks.

In areas with limited resources, the capacity to diagnose malaria in young infants may be limited [57,58], and any issues with quality or accuracy of the diagnostic technique may result in the diagnosis of malaria being missed [59]. In many malaria-endemic countries, infants and children frequently die at home [60] and the cause of death remains undetermined and unrecorded [17,34,61]. Therefore, the overall malaria mortality in infants aged under six months is highly uncertain. As approximately 40% of all child deaths occur in the neonatal period, and many deliveries occur outside health facilities, the proportion of these deaths that is malaria-related is unclear [60].


Pharmacokinetics of anti-malarials in young infants

Due to the dynamic developmental changes experienced by infants aged under 6 months, the pharmacokinetic profiles of anti-malarials may be different than in older children, and age-dependent dose adjustments may be necessary [62]. For example, gastric emptying is slower in neonates and young infants, and is only comparable with adults after six months of age. Absorption of drugs is also affected by intestinal motor activity and villous formation, both of which mature by week 20 [62]. Drug metabolism may be altered as enzyme systems, such as the hepatic enzymes, are immature (anti-malarials are typically metabolized in the liver) [63], possibly resulting in an enhancement of bioavailability [62]. Activity of such metabolizing enzymes is typically low at birth and rapidly develops over the first 1–2 years of life [64].


Current national recommendations for treating infants aged under 6 months

As the burden of disease in infants under 6 months of age is not well defined, this age group has been excluded from previous clinical trials and national treatment guidelines on uncomplicated P. falciparum malaria. Thus, oral anti-malarials recommended as first- and second-line therapies are frequently used off-label, based on the recommended mg/kg dosing schedule for older children [28].


Issues with currently available anti-malarials

There is little information on the use of artemisinin-based combination therapy (ACT) in young infants, to the extent that many of them carry label restrictions for this age group [63]. Accurate dosing is particularly important, but this is difficult when paediatric formulations are unavailable. Nevertheless, young infants with malaria should receive appropriate treatment. Among the recommended ACT, excluding the combination containing sulphadoxine-pyrimethamine that is not recommended during the first 6 weeks of life [65], there is no evidence of specific serious toxicity [63]. However, additional efforts should be made to establish their safety profile, the correct dosage and formulation, so that young infants with malaria can be managed adequately.

With these issues in mind, it must be considered how ACT could be used to treat malaria in infants aged under six months. There are no official data on how to use ACT in this age group, despite the fact that malaria can occur at a very young age and that ACT offers greater efficacy and tolerability compared with quinine, which is often used in infants with clinical malaria. Furthermore, the use of a unified first-line therapy could offer benefits for healthcare providers with similar anti-malarial use for the whole population, as well as logistical benefits in terms of procurement and distribution. The safety profile of these combination therapies in young infants should be established.


Preventive treatment

Previous studies have shown that chemoprophylaxis in infants has the potential to reduce malaria-related morbidity and mortality [66]. In The Gambia, infants receiving weekly chloroquine from birth until the age of two years had fewer episodes of malaria, grew better, and had higher haemoglobin levels than the control group [67].

Some studies of intermittent preventive treatment (IPT) in infants (IPTi) have timed the doses of anti-malarial to coincide with routine vaccinations delivered by WHO’s Expanded Programme on Immunization (EPI) at 2, 3 and 9 months. In a pooled analysis of six randomized, placebo-controlled trials of IPTi using sulphadoxine-pyrimethamine delivered at the same time as EPI immunizations, a protective efficacy against clinical malaria of 30.3% was reported [68].

Seasonal malaria chemoprevention (SMC), previously referred to as IPT in children (IPTc), involves the administration of full anti-malarial treatment courses during the malaria season to children aged 3–59 months [69]. The WHO recommends that SMC be used in areas of high seasonal malaria transmission across sub-Saharan Africa, and that treatment with amodiaquine plus sulphadoxine-pyrimethamine should be given at monthly intervals from the start of the transmission season, up to a maximum of four doses [69]. The main potential risks associated with SMC are safety and drug resistance [70]. However, SMC may provide a substantial protective effect against malaria [70], and is a potentially valuable tool that could contribute to reducing the malaria burden in infants aged over three months in areas with seasonal transmission.

The candidate malaria vaccine RTS,S/AS01 administered to infants aged 6–12 weeks at the time of the first vaccination provided modest protection against both uncomplicated and severe malaria [71], casting doubts on whether this vaccine could be included in the routine panel of infants’ immunization [72]. However, additional analyses are needed to understand the reasons of the observed lower efficacy in young infants as compared with older infants and children (aged 5–17 months) [73].


Future clinical studies

There are several ongoing or planned clinical studies aiming to obtain more accurate estimates of the malaria burden and parasite prevalence in infants aged less than 6 months living under different endemic conditions, as well as the safety and efficacy of currently available ACT in this population. Future longitudinal studies should also characterize infant iron status in relation to subsequent malaria risk, and relate findings to the occurrence of placental malaria.

A multicentre descriptive study is underway, aiming to assess malaria morbidity (prevalence and incidence) and corresponding risk factors in young infants, compared with their siblings, in areas of seasonal low (The Gambia) and high (Guinea) malaria transmission, and in an area with intense, perennial transmission (Benin).

A multicentre trial will evaluate the safety, pharmacokinetics and efficacy of dispersible artemether-lumefantrine tablets in infants weighing under 5 kg with uncomplicated P. falciparum malaria. This trial, sponsored by Novartis and in association with MMV, commenced in 2012 and involves sites in Benin, Burkina Faso, the Democratic Republic of the Congo, Nigeria and Togo.

Another study planned at the College of Medicine at the University of Malawi will assess the population pharmacokinetics and the safety and efficacy of ACT in infants weighing under 5 kg or aged less than 6 months.

Knowledge gained from such studies will assist in guiding the development of evidence-based treatment guidelines for this population.


Conclusions

The perception that malaria is uncommon in young infants has resulted in the paucity of information currently available and the lack of evidence-based treatment guidelines in this population. Many children are dying before malaria is diagnosed. In resource-constrained settings, diagnostic techniques may not be available, or malaria may not be recognized due to overlapping symptoms with other neonatal illnesses such as sepsis [33]. Malaria in infants aged under six months is not a rare occurrence in endemic areas and its burden may be underestimated. Therefore, it is necessary to collect reliable data on the malaria burden in this population. Awareness by health professionals should increase so that any infant aged under 6 months brought to a health facility in a malaria-endemic area with unexplained fever or suspected sepsis should be systematically screened for malaria. Current policy for malaria diagnosis dictates that all fevers in all age groups and settings should be tested for malaria before treatment is initiated.

ACT is being used off-label in this vulnerable patient group, with physicians using a pragmatic approach to guide dosing. At this time, a clear recommendation on the use of ACT could be difficult, due to a lack of data in infants with a body weight of less than 5 kg (less than 4.5 kg for artesunate plus amodiaquine). A more accurate estimate of the disease burden and parasite prevalence, risk factors for infection including iron status, as well as the pharmacokinetic profiles, safety and efficacy of currently available ACT in early infancy from data provided by clinical trials that are planned or underway will contribute to the development of evidence-based treatment guidelines for this population, as well as aid the research and development of new drugs. It is definitely worth providing malaria control strategies that are aimed directly at this vulnerable age group, in a bid to reduce infant mortality.


Abbreviations

ACT: Artemisinin-based combination therapy; EPI: Expanded Programme on Immunization; HbF: Haemoglobin F; HIV: Human Immunodeficiency Virus; IgA: Immunoglobulin A; IgG: Immunoglobulin G; IPT: Intermittent preventive treatment; IPTc: Intermittent preventive treatment in children; IPTi: Intermittent preventive treatment in infants; MMV: Medicines for Malaria Venture; pABA: Para-aminobenzoic acid; PCR: Polymerase Chain Reaction; PfEMP-1: Plasmodium falciparum erythrocyte membrane protein-1; SMC: Seasonal malaria chemoprevention; WHO: World Health Organization.


Competing interests

UD has been invited as speaker at symposia organized by Sigma Tau and Novartis Pharma, and has received a research grant from Sigma Tau. KH is an employee of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. This declaration is made in the interest of full disclosure and not because the author considers this to be a competing interest. The other authors have no competing interest to declare.


Authors’ contributions

All authors met International Committee of Medical Journal Editors criteria for authorship. All authors contributed to the development of the outline, revised the manuscript critically, and read and approved the final manuscript.


Acknowledgements

Editorial assistance was provided by Caroline Sharp (PreScript Communications), with funding from MMV.


References
WHOWorld malaria reportYear: 2011World Health Organization, Geneva
Macdonald G,The analysis of malaria parasite rates in infantsTrop Dis BullYear: 19504791593814798657
Foll CV,Application of malariometric data obtained from longitudinal studies on infants in northern NigeriaBull World Health OrganYear: 1968382552655302301
Thomson JG,Malaria in nyasaland: (section of tropical diseases and parasitology)Proc R Soc MedYear: 19352839140419990138
Brabin B,An analysis of malaria parasite rates in infants: 40 years after MacdonaldTrop Dis BullYear: 199087121
Biggar RJ,Collins WE,Campbell CC,The serological response to primary malaria infection in urban Ghanaian infantsAmJTrop Med HygYear: 198029720724
Sehgal VM,Siddjiqui WA,Alpers MP,A seroepidemiological study to evaluate the role of passive maternal immunity to malaria in infantsTrans R Soc Trop Med HygYear: 198983Suppl1051062696154
Fischer PR,Malaria and newbornsJ Trop PediatrYear: 20034913213410.1093/tropej/49.3.13212848200
Afolabi BM,Salako LA,Mafe AG,Ovwigho UB,Rabiu KA,Sanyaolu NO,Ibrahim MM,Malaria in the first 6 months of life in urban African infants with anemiaAmJTrop Med HygYear: 200165822827
Riley EM,Wagner GE,Akanmori BD,Koram KA,Do maternally acquired antibodies protect infants from malaria infection?Parasite ImmunolYear: 200123515910.1046/j.1365-3024.2001.00364.x11240896
Riley EM,Wagner GE,Ofori MF,Wheeler JG,Akanmori BD,Tetteh K,McGuinness D,Bennett S,Nkrumah FK,Anders RF,Koram KA,Lack of association between maternal antibody and protection of African infants from malaria infectionInfect ImmunYear: 2000685856586310.1128/IAI.68.10.5856-5863.200010992495
Doolan DL,Dobano C,Baird JK,Acquired immunity to malariaClin Microbiol RevYear: 2009221336 Table. 10.1128/CMR.00025-0819136431
Kassim OO,Ako-Anai KA,Torimiro SE,Hollowell GP,Okoye VC,Martin SK,Inhibitory factors in breastmilk, maternal and infant sera against in vitro growth of Plasmodium falciparum malaria parasiteJ Trop PediatrYear: 200046929610.1093/tropej/46.2.9210822935
Gitau GM,Eldred JM,Malaria in pregnancy: clinical, therapeutic and prophylactic considerationsObstet GynaecolYear: 2005751110.1576/toag.7.1.005.27036
Amaratunga C,Lopera-Mesa TM,Brittain NJ,Cholera R,Arie T,Fujioka H,Keefer JR,Fairhurst RM,A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malariaPLoS OneYear: 20116e1479810.1371/journal.pone.001479821532754
Gwamaka M,Kurtis JD,Sorensen BE,Holte S,Morrison R,Mutabingwa TK,Fried M,Duffy PE,Iron deficiency protects against severe Plasmodium falciparum malaria and death in young childrenClin Infect DisYear: 2012541137114410.1093/cid/cis01022354919
Bardaji A,Sigauque B,Sanz S,Maixenchs M,Ordi J,Aponte JJ,Mabunda S,Alonso PL,Menéndez C,Impact of malaria at the end of pregnancy on infant mortality and morbidityJ Infect DisYear: 201120369169910.1093/infdis/jiq04921199881
Schwarz NG,Adegnika AA,Breitling LP,Gabor J,Agnandji ST,Newman RD,Lell B,Issifou S,Yazdanbakhsh M,Luty AJ,Kremsner PG,Grobusch MP,Placental malaria increases malaria risk in the first 30 months of lifeClin Infect DisYear: 2008471017102510.1086/59196818781874
Malhotra I,Dent A,Mungai P,Wamachi A,Ouma JH,Narum DL,Muchiri E,Tisch DJ,King CL,Can prenatal malaria exposure produce an immune tolerant phenotype? A prospective birth cohort study in KenyaPLoS MedYear: 20096e100011610.1371/journal.pmed.100011619636353
Falade C,Mokuolu O,Okafor H,Orogade A,Falade A,Adedoyin O,Oguonu T,Aisha M,Hamer DH,Callahan MV,Epidemiology of congenital malaria in Nigeria: a multi-centre studyTrop Med Int HealthYear: 2007121279128710.1111/j.1365-3156.2007.01931.x17956542
Mukhtar M,The growing incidence of neonatal malaria–a situational review in developing countriesNiger J MedYear: 200716253017563964
Fischer PR,Nyirjesy P,Toko RM,Congenital malaria in twinsWest J MedYear: 19951633953967483614
Fischer PR,Congenital malaria: an African surveyClin Pediatr (Phila)Year: 19973641141310.1177/0009922897036007069241479
Kamwendo DD,Dzinjalamala FK,Snounou G,Kanjala MC,Mhango CG,Molyneux ME,Rogerson SJ,Plasmodium falciparum: PCR detection and genotyping of isolates from peripheral, placental, and cord blood of pregnant Malawian women and their infantsTrans R Soc Trop Med HygYear: 20029614514910.1016/S0035-9203(02)90284-112055802
Mwaniki MK,Talbert AW,Mturi FN,Berkley JA,Kager P,Marsh K,Newton CR,Congenital and neonatal malaria in a rural Kenyan district hospital: an eight-year analysisMalar JYear: 2010931310.1186/1475-2875-9-31321054891
Dicko-Traoré F,Syla M,Djimde AA,Diakité AA,Diawara M,Togo B,Togo P,Dara A,Dama S,Traoré K,Traoré S,Sissoko S,Poudiougo B,Sidibé T,Keita MM,Doumbo O,[Congenital and neonatal malaria in sub-sahara Africa, a scarce event?]J Pediatr PuericYear: 2011245761
Klein Klouwenberg PM,Oyakhirome S,Schwarz NG,Glaser B,Issifou S,Kiessling G,Klöpfer A,Kremsner PG,Längin M,Lassmann B,Necek M,Pötschke M,Ritz A,Grobusch MP,Malaria and asymptomatic parasitaemia in Gabonese infants under the age of 3 monthsActa TropYear: 200595818510.1016/j.actatropica.2005.05.00315950165
Larru B,Molyneux E,ter Kuile FO,Taylor T,Molyneux M,Terlouw DJ,Malaria in infants below six months of age: retrospective surveillance of hospital admission records in Blantyre. MalawiMalar JYear: 2009831010.1186/1475-2875-8-31020038299
Nankabirwa V,Tylleskar T,Nankunda J,Engebretsen IM,Sommerfelt H,Tumwine JK,Malaria parasitaemia among infants and its association with breastfeeding peer counselling and vitamin A supplementation: a secondary analysis of a cluster randomized trialPLoS OneYear: 20116e2186210.1371/journal.pone.002186221760916
Pedro R,Akech S,Fegan G,Maitland K,Changing trends in blood transfusion in children and neonates admitted in Kilifi District Hospital. KenyaMalar JYear: 2010930710.1186/1475-2875-9-30721034494
Runsewe-Abiodun IT,Ogunfowora OB,Fetuga BM,Neonatal malaria in Nigeria–a 2 year reviewBMC PediatrYear: 200661910.1186/1471-2431-6-1916768801
van Eijk AM,Ayisi JG,ter Kuile FO,Slutsker L,Shi YP,Udhayakumar V,Otieno JA,Kager PA,Lal RB,Steketee RW,Nahlen BL,HIV, malaria, and infant anemia as risk factors for postneonatal infant mortality among HIV-seropositive women in Kisumu. KenyaJ Infect DisYear: 2007196303710.1086/51844117538880
Ojukwu JU,Ezeonu CT,Ogbu CN,Severe malaria in neonates masquerading as septicaemiaNigerian J PaediatrYear: 2004314855
Abdullah S,Adazu K,Masanja H,Diallo D,Hodgson A,Ilboudo-Sanogo E,Nhacolo A,Owusu-Agyei S,Thompson R,Smith T,Binka FN,Patterns of age-specific mortality in children in endemic areas of sub-Saharan AfricaAmJTrop Med HygYear: 20077799105
Corkill JA,Brabin BJ,MacGregor DF,Alpers MP,Milner RD,Newborn splenic volumes vary under different malaria endemic conditionsArch Dis ChildYear: 19896454154510.1136/adc.64.4.5412665658
Guinovart C,Bassat Q,Sigauque B,Aide P,Sacarlal J,Nhampossa T,Bardají A,Nhacolo A,Macete E,Mandomando I,Aponte JJ,Menéndez C,Alonso PL,Malaria in rural Mozambique. Part I: children attending the outpatient clinicMalar JYear: 200873610.1186/1475-2875-7-3618302770
Adja EA,Dick FA,N’guessan R,[Epidemiological study of the malaria at the neonatal period in the teaching hospital of Yopougon–Republic of Cote d’Ivoire] (in French)Mali MedYear: 200924363920093219
Ekanem AD,Anah MU,Udo JJ,The prevalence of congenital malaria among neonates with suspected sepsis in Calabar. NigeriaTrop DoctYear: 200838737610.1258/td.2007.00527418453488
Ibhanesebhor SE,Clinical characteristics of neonatal malariaJ Trop PediatrYear: 19954133033310.1093/tropej/41.6.3308606438
Lesi FE,Mukhtar MY,Iroha EU,Egri-Okwaji MT,Clinical presentation of congenital malaria at the Lagos university teaching hospitalNiger J Clin PractYear: 20101313413820499743
Mosha TCE,Ntarukimana D,John M,Prevalence of congenital malaria among neonates at morogoro regional hospital, morogoro. TanzaniaTanzania J Health ResYear: 201012110
Mukhtar MY,Lesi FE,Iroha EU,Egri-Okwaji MT,Mafe AG,Congenital malaria among inborn babies at a tertiary centre in Lagos. NigeriaJ Trop PediatrYear: 200652192310.1093/tropej/fmi04415927946
Mwangoka GW,Kimera SI,Mboera LE,Congenital Plasmodium falciparum infection in neonates in Muheza District. TanzaniaMalar JYear: 2008711710.1186/1475-2875-7-11718598342
Obiajunwa PO,Owa JA,Adeodu OO,Prevalence of congenital malaria in Ile-ife. NigeriaJ Trop PediatrYear: 20055121922210.1093/tropej/fmi00315980030
Oduwole OA,Ejezie GC,Odey FA,Oringanje CM,Nwakanma D,Bello S,Oriero E,Okebe J,Alaribe AA,Etuk S,Meremikwu M,Congenital malaria in Calabar, Nigeria: the molecular perspectiveAmJTrop Med HygYear: 20118438638910.4269/ajtmh.2011.10-0253
Okafor UH,Oguonu T,Onah HE,Risk factors associated with congenital malaria in Enugu. South eastern NigeriaJ Obstet GynaecolYear: 20062661261610.1080/0963828060090289317071423
Okechukwu AA,Olateju EK,Olutunde EO,Congenital malaria among newborns admitted for suspected neonatal sepsis in AbujaNigerian J PaediatrYear: 2011388289
Omalu IC,Mgbemena C,Mgbemena A,Ayanwale V,Olayemi IK,Lateef A,Chukwuemeka VI,Prevalence of congenital malaria in Minna, north central NigeriaJ Trop MedYear: 2012201227414221876706
Orogade AA,Falade CO,Okafor HU,Mokuolu OA,Mamman AI,Ogbonu TA,Ogunkunle OO,Ernest KS,Callahan MV,Hamer DH,Clinical and laboratory features of congenital malaria in NigeriaJ Pediatr Infect DisYear: 20083181187
Pineros-Jimenez JG,Alvarez G,Tobon A,Arboleda M,Carrero S,Blair S,Congenital malaria in Uraba. ColombiaMalar JYear: 20111023910.1186/1475-2875-10-23921846373
Sule-Odu AO,Ogunledun A,Olatunji AO,Impact of asymptomatic maternal malaria parasitaemia at parturition on perinatal outcomeJ Obstet GynaecolYear: 200222252810.1080/0144361012010166412521723
Larkin GL,Thuma PE,Congenital malaria in a hyperendemic areaAmJTrop Med HygYear: 199145587592
Akindele JA,Sowunmi A,Abohweyere AE,Congenital malaria in a hyperendemic area: a preliminary studyAnn Trop PaediatrYear: 1993132732767505553
Wagner G,Koram K,McGuinness D,Bennett S,Nkrumah F,Riley E,High incidence of asymptomatic malara infections in a birth cohort of children less than one year of age in Ghana, detected by multicopy gene polymerase chain reactionAmJTrop Med HygYear: 199859115123
Carneiro I,Roca-Feltrer A,Griffin JT,Smith L,Tanner M,Schellenberg JA,Greenwood B,Schellenberg D,Age-patterns of malaria vary with severity, transmission intensity and seasonality in sub-Saharan Africa: a systematic review and pooled analysisPLoS OneYear: 20105e898810.1371/journal.pone.000898820126547
Hashemzadeh A,Heydarian F,Congenital malaria in a neonateArch Iranian MedYear: 20058226228
Hailegiorgis B,Girma S,Melaku Z,Teshi T,Demeke L,Gebresellasie S,Yadeta D,Tibesso G,Whitehurst N,Yamo E,Carter J,Reithinger R,Laboratory malaria diagnostic capacity in health facilities in five administrative zones of oromia regional state. EthiopiaTrop Med Int HealthYear: 2010151449145710.1111/j.1365-3156.2010.02646.x21040254
Ishengoma DR,Derua YA,Rwegoshora RT,Tenu F,Massaga JJ,Mboera LE,Magesa SM,The performance of health laboratories and the quality of malaria diagnosis in six districts of TanzaniaAnn Trop Med ParasitolYear: 201010412313510.1179/136485910X1260701237399320406579
Uneke CJ,Congenital Plasmodium falciparum malaria in sub-Saharan Africa: a rarity or frequent occurrence?Parasitol ResYear: 200710183584210.1007/s00436-007-0577-917549517
Lawn JE,Cousens S,Zupan J,4 million neonatal deaths: when? Where? Why?LancetYear: 200536589190010.1016/S0140-6736(05)71048-515752534
Sacarlal J,Nhacolo AQ,Sigauque B,Nhalungo DA,Abacassamo F,Sacoor CN,Aide P,Machevo S,Nhampossa T,Macete EV,Bassat Q,David C,Bardají A,Letang E,Saúte F,Aponte JJ,Thompson R,Alonso PL,A 10 year study of the cause of death in children under 15 years in Manhica. MozambiqueBMC Publ HealthYear: 200996710.1186/1471-2458-9-67
Kearns GL,Abdel-Rahman SM,Alander SW,Blowey DL,Leeder JS,Kauffman RE,Developmental pharmacology–drug disposition, action, and therapy in infants and childrenN Engl J MedYear: 20033491157116710.1056/NEJMra03509213679531
WHOGuidelines for the treatment of MalariaYear: 2010SecondWorld Health Organization, Geneva, Switzerland
Milsap RL,Jusko WJ,Pharmacokinetics in the infantEnviron Health PerspectYear: 1994102Suppl 1110711010.1289/ehp.94102s111077737034
Menendez C,Mayor A,Congenital malaria: the least known consequence of malaria in pregnancySemin Fetal Neonatal MedYear: 20071220721310.1016/j.siny.2007.01.01817483042
Geerligs PD,Brabin BJ,Eggelte TA,Analysis of the effects of malaria chemoprophylaxis in children on haematological responses, morbidity and mortalityBull World Health OrganYear: 20038120521612764517
McGregor IA,Gilles HM,Walters JH,Davies AH,Pearson FA,Effects of heavy and repeated malarial infections on Gambian infants and children; effects of erythrocytic parasitizationBMJYear: 1956268669210.1136/bmj.2.4994.68613356045
Aponte JJ,Schellenberg D,Egan A,Breckenridge A,Carneiro I,Critchley J,Danquah I,Dodoo A,Kobbe R,Lell B,May J,Premji Z,Sanz S,Sevene E,Soulaymani-Becheikh R,Winstanley P,Adjei S,Anemana S,Chandramohan D,Issifou S,Mockenhaupt F,Owusu-Agyei S,Greenwood B,Grobusch MP,Kremsner PG,Macete E,Mshinda H,Newman RD,Slutsker L,Tanner M,Alonso P,Menendez C,Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trialsLancetYear: 20093741533154210.1016/S0140-6736(09)61258-719765816
WHO Global Malaria ProgrammeWHO Policy Recommendation: Seasonal Malaria Chemoprevention (SMC) for Plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in AfricaYear: 2012 http://www.who.int/malaria/publications/atoz/smc_policy_recommendation_en_032012.pdf.
Gosling RD,Okell L,Mosha J,Chandramohan D,The role of antimalarial treatment in the elimination of malariaClin Microbiol InfectYear: 2011171617162310.1111/j.1469-0691.2011.03660.x21951597
The RTS,S Clinical Trials PartnershipA phase 3 trial of RTS,S/AS01 malaria vaccine in African infantsN Engl J MedYear: 201210.1056/NEJMoa1208394
Daily JP,Malaria vaccine trials - beyond efficacy end pointsN Engl J MedYear: 201210.1056/NEJMe1213392
Agnandji ST,Lell B,Soulanoudjingar SS,Fernandes JF,Abossolo BP,Conzelmann C,Methogo BG,Doucka Y,Flamen A,Mordmüller B,Issifou S,Kremsner PG,Sacarlal J,Aide P,Lanaspa M,Aponte JJ,Nhamuave A,Quelhas D,Bassat Q,Mandjate S,Macete E,Alonso P,Abdulla S,Salim N,Juma O,Shomari M,Shubis K,Machera F,Hamad AS,Minja R,Mtoro A,Sykes A,Ahmed S,Urassa AM,Ali AM,Mwangoka G,Tanner M,Tinto H,D’Alessandro U,Sorgho H,Valea I,Tahita MC,Kaboré W,Ouédraogo S,Sandrine Y,Guiguemdé RT,Ouédraogo JB,Hamel MJ,Kariuki S,Odero C,Oneko M,Otieno K,Awino N,Omoto J,Williamson J,Muturi-Kioi V,Laserson KF,Slutsker L,Otieno W,Otieno L,Nekoye O,Gondi S,Otieno A,Ogutu B,Wasuna R,Owira V,Jones D,Onyango AA,Njuguna P,Chilengi R,Akoo P,Kerubo C,Gitaka J,Maingi C,Lang T,Olotu A,Tsofa B,Bejon P,Peshu N,Marsh K,Owusu-Agyei S,Asante KP,Osei-Kwakye K,Boahen O,Ayamba S,Kayan K,Owusu-Ofori R,Dosoo D,Asante I,Adjei G,Adjei G,Chandramohan D,Greenwood B,Lusingu J,Gesase S,Malabeja A,Abdul O,Kilavo H,Mahende C,Liheluka E,Lemnge M,Theander T,Drakeley C,Ansong D,Agbenyega T,Adjei S,Boateng HO,Rettig T,Bawa J,Sylverken J,Sambian D,Agyekum A,Owusu L,Martinson F,Hoffman I,Mvalo T,Kamthunzi P,Nkomo R,Msika A,Jumbe A,Chome N,Nyakuipa D,Chintedza J,Ballou WR,Bruls M,Cohen J,Guerra Y,Jongert E,Lapierre D,Leach A,Lievens M,Ofori-Anyinam O,Vekemans J,Carter T,Leboulleux D,Loucq C,Radford A,Savarese B,Schellenberg D,Sillman M,Vansadia P,RTS,S Clinical Trials Partnership: First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African childrenN Engl J MedYear: 20113651863187522007715

Article Categories:
  • Opinion

Keywords: Malaria, Neonate, Congenital, Prevalence, Parasitaemia, Artemisinin-based combination therapy.

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