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1.  Complicated malaria and other severe febrile illness in a pediatric ward in Libreville, Gabon 
BMC Infectious Diseases  2012;12:216.
Although a substantial decline of Plasmodium falciparum infection is observed in Africa following implementation of new control strategies, malaria is still considered as the major cause of febrile illness in hospitalized African children. The present study was designed to assess the management of febrile illness and to determine the proportion of children with febrile illness hospitalized for primary diagnosis of malaria who had confirmed complicated malaria after implementation of new malaria control strategies in Libreville, Gabon.
Demographic, clinical and biological data from hospitalized children with fever or a history of fever, with a primary diagnosis of clinical malaria, aged less than 18 years old, who benefited from hematological measurements and microscopic malaria diagnosis, were recorded and analyzed during a prospective and observational study conducted in 2008 in the Centre Hospitalier de Libreville.
A total of 418 febrile children were admitted at hospital as malaria cases. Majority of them (79.4%) were aged below five years. After medical examination, 168 were diagnosed and treated as clinical malaria and, among them, only 56.7% (n = 95) had Plasmodium falciparum positive blood smears. Age above five years, pallor, Blantyre Coma Score ≤2 and thrombocytopenia were predictive of malaria infection. Respiratory tract infections were the first leading cause of hospitalization (41.1%), followed by malaria (22.7%); co-morbidities were frequent (22%). Less than 5% of suspected bacterial infections were confirmed by culture. Global case fatality rate was 2.1% and 1% for malaria. Almost half (46%) of the children who received antimalarial therapy had negative blood smears. Likewise, antibiotics were frequently prescribed without bacteriological confirmation.
The use of clinical symptoms for the management of children febrile illness is frequent in Gabon. Information, training of health workers and strengthening of diagnosis tools are necessary to improve febrile children care.
PMCID: PMC3520876  PMID: 22973831
2.  Illness-related practices for the management of childhood malaria among the Bwatiye people of north-eastern Nigeria 
Malaria Journal  2005;4:13.
A wide range of childhood illnesses are accompanied by fever,, including malaria. Child mortality due to malaria has been attributed to poor health service delivery system and ignorance. An assessment of a mother's ability to recognize malaria in children under-five was carried out among the Bwatiye, a poorly-served minority ethnic group in north-eastern Nigeria.
A three-stage research design involving interviews, participatory observation and laboratory tests was used to seek information from 186 Bwatiye mothers about their illness-related experiences with childhood fevers.
Mothers classified malaria into male (fever that persists for longer than three days) and female (fever that goes away within three days) and had a system of determining when febrile illness would not be regarded as malaria. Most often, malaria would be ignored in the first 2 days before seeking active treatment. Self-medication was the preferred option. Treatment practices and sources of help were influenced by local beliefs, the parity of the mother and previous experience with child mortality.
The need to educate mothers to suspect malaria in every case of febrile illness and take appropriate action in order to expose the underlying "evil" will be more acceptable than an insistence on replacing local knowledge with biological epidemiology of malaria. The challenge facing health workers is to identify and exploit local beliefs about aetiology in effecting management procedures among culturally different peoples, who may not accept the concept of biological epidemiology.
PMCID: PMC553996  PMID: 15723706
3.  Community Knowledge and Attitudes and Health Workers' Practices regarding Non-malaria Febrile Illnesses in Eastern Tanzania 
Although malaria has been the leading cause of fever for many years, with improved control regimes malaria transmission, morbidity and mortality have decreased. Recent studies have increasingly demonstrated the importance of non-malaria fevers, which have significantly improved our understanding of etiologies of febrile illnesses. A number of non-malaria febrile illnesses including Rift Valley Fever, dengue fever, Chikungunya virus infection, leptospirosis, tick-borne relapsing fever and Q-fever have been reported in Tanzania. This study aimed at assessing the awareness of communities and practices of health workers on non-malaria febrile illnesses.
Twelve focus group discussions with members of communities and 14 in-depth interviews with health workers were conducted in Kilosa district, Tanzania. Transcripts were coded into different groups using MaxQDA software and analyzed through thematic content analysis.
The study revealed that the awareness of the study participants on non-malaria febrile illnesses was low and many community members believed that most instances of fever are due to malaria. In addition, the majority had inappropriate beliefs about the possible causes of fever. In most cases, non-malaria febrile illnesses were considered following a negative Malaria Rapid Diagnostic Test (mRDT) result or persistent fevers after completion of anti-malaria dosage. Therefore, in the absence of mRDTs, there is over diagnosis of malaria and under diagnosis of non-malaria illnesses. Shortages of diagnostic facilities for febrile illnesses including mRDTs were repeatedly reported as a major barrier to proper diagnosis and treatment of febrile patients.
Our results emphasize the need for creating community awareness on other causes of fever apart from malaria. Based on our study, appropriate treatment of febrile patients will require inputs geared towards strengthening of diagnostic facilities, drugs availability and optimal staffing of health facilities.
Author Summary
Understanding the awareness of the community on non-malaria febrile illnesses is crucial, especially during the recent decline of malaria episodes of malaria. This study conducted focus group discussions with communities to assess their awareness of non-malaria febrile illnesses. In addition, in-depth interviews with health workers were conducted to explore their views and practices related to diagnosis and management of these illnesses. We identified that the awareness of the study participants on non-malaria febrile illnesses was low and the majority believed that most instances of fever are due to malaria. Moreover, the participants could not mention the right causes of fever and many had inappropriate beliefs about possible causes of fever. Health workers from our study looked for non-malaria febrile illnesses when a febrile patient had negative mRDT result or there was persistence of fever following completion of anti-malarial dosage. Shortages of diagnostic facilities were identified as one of the impediments to proper diagnosis of febrile illnesses. These findings indicate the need for creation of public awareness on causes of fever other than malaria. We recommend appropriate measures be taken by the government and other stake holders to improve health care services delivery particularly at primary health care facilities.
PMCID: PMC4031176  PMID: 24852787
4.  Fever treatment in the absence of malaria transmission in an urban informal settlement in Nairobi, Kenya 
Malaria Journal  2009;8:160.
In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya.
In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour.
Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%–20.5%) and higher among children below five years (20.1%, 95%CI:13.8%–27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%–62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine.
The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria parasites to reduce the inappropriate exposure of poor communities to expensive anti-malarial drugs provided by clinical services and drug vendors, should be a priority for district planners.
PMCID: PMC2717114  PMID: 19604369
5.  Effectiveness of combined intermittent preventive treatment for children and timely home treatment for malaria control 
Malaria Journal  2009;8:292.
Whiles awaiting for the arrival of an effective and affordable malaria vaccine, there is a need to make use of the available control tools to reduce malaria risk, especially in children under five years and pregnant women. Intermittent preventive treatment (IPT) has recently been accepted as an important component of the malaria control strategy. This study explored the potential of a strategy of intermittent preventive treatment for children (IPTC) and timely treatment of malaria-related febrile illness in the home in reducing the parasite prevalence and malaria morbidity in young children in a coastal village in Ghana.
The study combined home-based delivery of IPTC among six to 60 months old and home treatment of suspected febrile malaria illness within 24 hours. All children between six and 60 months of age received intermittent preventive treatment using amodiaquine and artesunate, delivered by community assistants every four months (three times in 12 months). Malaria parasite prevalence surveys were conducted before the first and after the third dose of IPTC.
Parasite prevalence was reduced from 25% to 3% (p < 0.00, Mann-Whitney) one year after the inception of the two interventions. At baseline, 13.8% of the children were febrile (axillary temperature greater than or equal to 37.5 degree Celsius) compared to 2.2% at evaluation (post IPTC3 combined with timely home management of fever) (p < 0.00, Mann-Whitney).
The evaluation result indicates that IPTC given three times in a year combined with timely treatment of febrile malaria illness, impacts significantly on the parasite prevalence. The marked reduction in the parasite prevalence with this strategy points to the potential for reducing malaria-related childhood morbidity and mortality, and this should be explored by control programme managers.
PMCID: PMC2797018  PMID: 20003357
6.  Malaria morbidity and immunity among residents of villages with different Plasmodium falciparum transmission intensity in North-Eastern Tanzania 
Malaria Journal  2004;3:26.
The relationship between the burden of uncomplicated malaria and transmission intensity is unclear and a better understanding of this relationship is important for the implementation of intervention programmes.
A 6-month longitudinal study monitoring risk factors for anaemia and febrile malaria episodes was conducted among individuals aged below 20 years, residing in three villages of different altitude in areas of high, moderate and low malaria transmission intensity in North-Eastern Tanzania.
The burden of anaemia and malarial fever fell mainly on the youngest children and was highest in the village with high transmission intensity. Although a considerable percentage of individuals in all villages carried intestinal worms, logistic regression models indicated that Plasmodium falciparum was the only significant parasitic determinant of anaemia. Interestingly, children who carried low-density parasitaemia at the start of the study had a lower risk of contracting a febrile malaria episode but a higher risk of anaemia during the study period, than children who were slide negative at this point in time.
Young children living in the high transmission village carried a very high anaemia burden, which could be attributed to malaria. The overall incidence of febrile malaria was also highest in the high transmission village particularly among those under five years of age. These data suggest that in rolling back malaria, available resources in prevention programmes should primarily be focussed on young children, particularly those residing in areas of high malaria transmission.
PMCID: PMC514496  PMID: 15282030
7.  Antibiotic use among patients with febrile illness in a low malaria endemicity setting in Uganda 
Malaria Journal  2011;10:377.
Uganda embraced the World Health Organization guidelines that recommend a universal 'test and treat' strategy for malaria, mainly by use of rapid diagnostic test (RDT) and microscopy. However, little is known how increased parasitological diagnosis for malaria influences antibiotic treatment among patients with febrile illness.
Data collection was carried out within a feasibility trial of presumptive diagnosis of malaria (control) and two diagnostic interventions (microscopy or RDT) in a district of low transmission intensity. Five primary level health centres (HCs) were randomized to each diagnostic arm (diagnostic method in a defined group of patients). All 52,116 outpatients (presumptive 16,971; microscopy 17,508; and RDT 17,638) aged 5 months to ninety five years presenting with fever (by statement or measured) were included. Information from outpatients and laboratory registers was extracted weekly from March 2010 to July 2011. The proportion of patients who were prescribed antibiotics was calculated among those not tested for malaria, those who tested positive and in those who tested negative.
Seven thousand and forty (41.5%) patients in the presumptive arm were prescribed antibiotics. Of the patients not tested for malaria, 1,537 (23.9%) in microscopy arm and 810 (56.2%) in RDT arm were prescribed antibiotics. Among patients who tested positive for malaria, 845 (25.8%) were prescribed antibiotics in the RDT and 273(17.6%) in the microscopy arm. Among patients who tested negative for malaria, 7809 (61.4%) were prescribed antibiotics in the RDT and 3749 (39.3%) in the microscopy arm. Overall the prescription of antibiotics was more common for children less than five years of age 5,388 (63%) compared to those five years and above 16798 (38.6%).
Prescription of antibiotics in patients with febrile illness is high. Testing positive for malaria reduces antibiotic treatment but testing negative for malaria increases use of antibiotics.
Trial Registration NCT00565071
PMCID: PMC3258227  PMID: 22183039
Antibiotic treatment; febrile patients; malaria diagnosis
Fever is the most common sign of childhood illnesses and febrile children constitute a substantial proportion of the practice of pediatrics and family medicine.
To highlight the pattern of febrile illnesses in children attending pediatric ambulatory health-care settings.
A one-year prospective study was conducted on febrile children who were consecutively seen and managed at two walk-in primary-care clinics in Sulaimania Children's Hospital, Riyadh. Data collection and analysis were structured around the principal study objectives.
Among the 16,173 children seen, 4086 (25.3%) were identified as having a fever and evaluated to determine the aetiology of their febrile illness. Boys outnumbered girls and a significant increase in the frequency of febrile illnesses was noted in children 4 to 24 months of age. Upper respiratory tract infections were the commonest cause of fever (75%) and most of these infections were viral rhinopharyngitis. Viral gastroenteritis and pneumonia were prominent diagnoses, each accounting for 5% of febrile illnesses. Notably of low frequency were serious bacterial infections, such as meningitis (0.5%), cellulitis and bone or joint infection (1.8%) and urinary tract infection (0.7%). Only 9% of the febrile children required hospitalization. The ambulatory management of the other febrile children included the prescription of oral antibiotics to 64% of them.
The proper clinical assessment of these febrile children and the prudent use of laboratory tests and antimicrobials remain the most important management strategies in primary health-care practice.
PMCID: PMC3437113  PMID: 23008623
Bacteremia; Fever; Gastroenteritis; Meningitis; Otitis Media; Pneumonia; Upper respiratory tract infection; Urinary tract infection
9.  Confirmed malaria cases among children under five with fever and history of fever in rural western Tanzania 
BMC Research Notes  2011;4:359.
The World Health Organization recommends that malaria treatment should begin with parasitological diagnosis. This will help to control misuse of anti-malarial drugs in areas with low transmission. The present study was conducted to assess the prevalence of parasitologically confirmed malaria among children under five years of age presenting with fever or history of fever in rural western Tanzania. A finger prick blood sample was obtained from each child, and thin and thick blood smears were prepared, stained with 10% Giemsa and examined under the light microscope. A structured questionnaire was used to collect each patient's demographic information, reasons for coming to the health center; and a physical examination was carried out on all patients. Fever was defined as axillary temperature ≥ 37.5°C.
A total of 300 children with fever or a history of fever (1 or 2 weeks) were recruited, in which 54.3% (163/300, 95%CI, 48.7-59.9) were boys. A total of 76 (76/300, 25.3%, 95%CI, 22.8 - 27.8) of the children had fever. Based on a parasitological diagnosis of malaria, only 12% (36/300, 95%CI, 8.3-15.7) of the children had P. falciparum infection. Of the children with P. falciparum infection, 52.7% (19/36, 95%CI, 47.1-58.3) had fever and the remaining had no fever. The geometrical mean of the parasites was 708.62 (95%CI, 477.96-1050.62) parasites/μl and 25% (9/36, 95%CI, 10.9 -- 39.1) of the children with positive P. falciparum had ≥ 1001 parasites/μl. On Univariate (OR = 2.13, 95%CI, 1.02-4.43, P = 0.044) and multivariate (OR = 2.15, 95%CI, 1.03-4.49) analysis, only children above one year of age were associated with malaria infections.
Only a small proportion of the children under the age of five with fever had malaria, and with a proportion of children having non-malaria fever. Improvement of malaria diagnostic and other causes of febrile illness may provide effective measure in management of febrile illness in malaria endemic areas.
PMCID: PMC3180709  PMID: 21914203
Fever; history of fever; parasitological diagnosis; western Tanzania
10.  Use of drugs, perceived drug efficacy and preferred providers for febrile children: implications for home management of fever 
Malaria Journal  2009;8:131.
Community distribution of anti-malarials and antibiotics has been recommended as a strategy to reduce the under-five mortality due to febrile illnesses in sub-Saharan Africa. However, drugs distributed in these interventions have been considered weak by some caretakers and utilization of community medicine distributors has been low. The aim of the study was to explore caretakers' use of drugs, perceptions of drug efficacy and preferred providers for febrile children in order to make suggestions for community management of pneumonia and malaria.
The study was conducted in eastern Uganda using four focus group discussions with fathers and mothers of children under five; and eight key informant interviews with health workers in government and non-governmental organization facilities, community medicine distributors, and attendants in drug shops and private clinics. Caretakers were asked the drugs they use for treatment of fever, why they considered them efficacious, and the providers they go to and why they go there. Health providers were interviewed on their opinions of caretakers' perceptions of drugs and providers. Analysis was done using content analysis.
Drugs that have been phased out as first-line treatment for malaria, such as chloroquine and sulphadoxine/pyrimethamine, are still perceived as efficacious. Use of drugs depended on perception of the disease, cost and drug availability. There were divergent views about drug efficacy concerning drug combinations, side effects, packaging, or using drugs over time. Bitter taste and high cost signified high efficacy for anti-malarials. Government facilities were preferred for conducting diagnostic investigations and attending to serious illnesses, but often lacked drugs and did not treat people fast. Drug shops were preferred for having a variety of drugs, attending to clients promptly and offering treatment on credit. However, drug shops were considered disadvantageous since they lacked diagnostic capability and had unqualified providers.
Community views about drug efficacy are divergent and some may divert caretakers from obtaining efficacious drugs for febrile illness. Interventions should address these perceptions, equip community medicine distributors with capacity to do diagnostic investigations and provide a constant supply of drugs. Subsidized efficacious drugs could be made available in the private sector.
PMCID: PMC2702349  PMID: 19523220
11.  No asymptomatic malaria parasitaemia found among 108 young children at one health facility in Dar es Salaam, Tanzania 
Malaria Journal  2013;12:417.
Asymptomatic malaria parasitaemia has been reported in areas with high malaria transmission. It may serve as a reservoir for continued transmission, and furthermore complicates diagnostics, as not all individuals with a positive malaria test are necessarily ill due to malaria, although they may present with malaria-like symptoms. Asymptomatic malaria increases with age as immunity to malaria gradually develops. As mortality and morbidity of malaria is higher among younger children it is important to know the prevalence of asymptomatic malaria parasitaemia in this population in order to interpret laboratory results for malaria correctly.
A total of 108 children that had neither been treated for malaria nor had a fever the previous four weeks were recruited consecutively at a maternal and child health clinic (MCHC) in Dar es Salaam, Tanzania. A rapid diagnostic test (RDT) for malaria and dried blood spot (DBS) on filter paper were taken from each child. Social and clinical data were recorded. DNA was extracted from the DBS of study participants by a method using InstaGene™ matrix. PCR targeting the Plasmodium mitochondrial genome was performed on all samples.
Median age was 4.6 months (range 0.5-38). All the RDTs were negative. PCR was negative for all study subjects.
The study suggests that asymptomatic malaria may not be present in apparently healthy children up to the age of three years in Dar es Salaam, Tanzania. However, because of the small sample size and low median age of the study population, the findings cannot be generalized. Larger studies, including higher age groups, need to be done to clarify whether asymptomatic malaria parasitaemia is present in the general population in the Dar es Salaam area.
PMCID: PMC3830543  PMID: 24228811
Malaria; Asymptomatic infection; Dried blood spots
12.  The relationship between reported fever and Plasmodium falciparum infection in African children 
Malaria Journal  2010;9:99.
Fever has traditionally served as the entry point for presumptive treatment of malaria in African children. However, recent changes in the epidemiology of malaria across many places in Africa would suggest that the predictive accuracy of a fever history as a marker of disease has changed prompting calls for the change to diagnosis-based treatment strategies.
Using data from six national malaria indicator surveys undertaken between 2007 and 2009, the relationship between childhood (6-59 months) reported fever on the day of survey and the likelihood of coincidental Plasmodium falciparum infection recorded using a rapid diagnostic test was evaluated across a range of endemicities characteristic of Africa today.
Of 16,903 children surveyed, 3% were febrile and infected, 9% were febrile without infection, 12% were infected but were not febrile and 76% were uninfected and not febrile. Children with fever on the day of the survey had a 1.98 times greater chance of being infected with P. falciparum compared to children without a history of fever on the day of the survey after adjusting for age and location (OR 1.98; 95% CI 1.74-2.34). There was a strong linear relationship between the percentage of febrile children with infection and infection prevalence (R2 = 0.9147). The prevalence of infection in reported fevers was consistently greater than would be expected solely by chance and this increased with increasing transmission intensity. The data suggest that in areas where community-based infection prevalence in childhood is above 34-37%, 50% or more of fevers are likely to be associated with infection.
The potential benefits of diagnosis will depend on the prevalence of infection among children who report fever. The study has demonstrated a predictable relationship between parasite prevalence in the community and risks of infection among febrile children suggesting that current maps of parasite prevalence could be used to guide diagnostic strategies in Africa.
PMCID: PMC2867992  PMID: 20398428
13.  Estimating the Number of Paediatric Fevers Associated with Malaria Infection Presenting to Africa's Public Health Sector in 2007 
PLoS Medicine  2010;7(7):e1000301.
Peter Gething and colleagues compute the number of fevers likely to present to public health facilities in Africa and the estimated number of these fevers likely to be infected with Plasmodium falciparum malaria parasites.
As international efforts to increase the coverage of artemisinin-based combination therapy in public health sectors gather pace, concerns have been raised regarding their continued indiscriminate presumptive use for treating all childhood fevers. The availability of rapid-diagnostic tests to support practical and reliable parasitological diagnosis provides an opportunity to improve the rational treatment of febrile children across Africa. However, the cost effectiveness of diagnosis-based treatment polices will depend on the presumed numbers of fevers harbouring infection. Here we compute the number of fevers likely to present to public health facilities in Africa and the estimated number of these fevers likely to be infected with Plasmodium falciparum malaria parasites.
Methods and Findings
We assembled first administrative-unit level data on paediatric fever prevalence, treatment-seeking rates, and child populations. These data were combined in a geographical information system model that also incorporated an adjustment procedure for urban versus rural areas to produce spatially distributed estimates of fever burden amongst African children and the subset likely to present to public sector clinics. A second data assembly was used to estimate plausible ranges for the proportion of paediatric fevers seen at clinics positive for P. falciparum in different endemicity settings. We estimated that, of the 656 million fevers in African 0–4 y olds in 2007, 182 million (28%) were likely to have sought treatment in a public sector clinic of which 78 million (43%) were likely to have been infected with P. falciparum (range 60–103 million).
Spatial estimates of childhood fevers and care-seeking rates can be combined with a relational risk model of infection prevalence in the community to estimate the degree of parasitemia in those fevers reaching public health facilities. This quantification provides an important baseline comparison of malarial and nonmalarial fevers in different endemicity settings that can contribute to ongoing scientific and policy debates about optimum clinical and financial strategies for the introduction of new diagnostics. These models are made publicly available with the publication of this paper.
Please see later in the article for the Editors' Summary
Editors' Summary
Malaria —an infectious parasitic disease transmitted to people through the bite of an infected mosquito —kills about one million people (mainly children living in sub-Saharan Africa) every year. Although several parasites cause malaria, Plasmodium falciparum is responsible for most of these deaths. For the past 50 years, the main treatments for P. falciparum malaria have been chloroquine and sulfadoxine/pyrimethamine. Unfortunately, parasitic resistance to these “monotherapies” is now widespread and there has been a global upsurge in the illness and deaths caused by P. falciparum. To combat this increase, the World Health Organization recommends artemisinin combination therapy (ACT) for P. falciparum malaria in all regions with drug-resistant malaria. In ACT, artemisinin derivatives (new, fast-acting antimalarial drugs) are used in combination with another antimalarial to reduce the chances of P. falciparum becoming resistant to either drug.
Why Was This Study Done?
All African countries at risk of P. falciparum have now adopted ACT as first-line therapy for malaria in their public clinics. However, experts are concerned that ACT is often given to children who don't actually have malaria because, in many parts of Africa, health care workers assume that all childhood fevers are malaria. This practice, which became established when diagnostic facilities for malaria were very limited, increases the chances of P. falciparum becoming resistant to ACT, wastes limited drug stocks, and means that many ill children are treated inappropriately. Recently, however, rapid diagnostic tests for malaria have been developed and there have been calls to expand their use to improve the rational treatment of African children with fever. Before such an expansion is initiated, it is important to know how many African children develop fever each year, how many of these ill children attend public clinics, and what proportion of them is likely to have malaria. Unfortunately, this type of information is incompletely or unreliably collected in many parts of Africa. In this study, therefore, the researchers use a mathematical model to estimate the number of childhood fevers associated with malaria infection that presented to Africa's public clinics in 2007 from survey data.
What Did the Researchers Do and Find?
The researchers used survey data on the prevalence (the proportion of a population with a specific disease) of childhood fever and on treatment-seeking behavior and data on child populations to map the distribution of fever among African children and the likelihood of these children attending public clinics for treatment. They then used a recent map of the distribution of P. falciparum infection risk to estimate what proportion of children with fever who attended clinics were likely to have had malaria in different parts of Africa. In 2007, the researchers estimate, 656 million cases of fever occurred in 0–4-year-old African children, 182 million were likely to have sought treatment in a public clinic, and 78 million (just under half of the cases that attended a clinic with fever) were likely to have been infected with P. falciparum. Importantly, there were marked geographical differences in the likelihood of children with fever presenting at public clinics being infected with P. falciparum. So, for example, whereas nearly 60% of the children attending public clinics with fever in Burkino Faso were likely to have had malaria, only 15% of similar children in Kenya were likely to have had this disease.
What Do These Findings Mean?
As with all mathematical models, the accuracy of these findings depends on the assumptions included in the model and on the data fed into it. Nevertheless, these findings provide a map of the prevalence of malarial and nonmalarial childhood fevers across sub-Saharan Africa and an indication of how many of the children with fever reaching public clinics are likely to have malaria and would therefore benefit from ACT. The finding that in some countries more than 80% of children attending public clinics with fever probably don't have malaria highlights the potential benefits of introducing rapid diagnostic testing for malaria. Furthermore, these findings can now be used to quantify the resources needed for and the potential clinical benefits of different policies for the introduction of rapid diagnostic testing for malaria across Africa.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the World Health Organization on malaria (in several languages) and on rapid diagnostic tests for malaria
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish)
MedlinePlus provides links to additional information on malaria (in English and Spanish)
Information on the global mapping of malaria is available at the Malaria Atlas Project
Information is available from the Roll Back Malaria Partnership on the global control of malaria (in English and French) and on artemisinin combination therapy
PMCID: PMC2897768  PMID: 20625548
14.  Outcome of Presumptive Versus Rapid Diagnostic Tests-Based Management of Childhood Malaria - Pneumonia Overlap in Urban Nigeria: A Pilot Quasi-Experimental Study 
Symptoms of malaria and pneumonia overlap in African under-five children and the integrated management of childhood illness strategy require that such children be managed presumptively with both antibiotics and antimalarials. A 2003 WHO expert meeting recommended the evaluation of malaria rapid diagnostic test in the management of children with this overlap, but this has not been evaluated. Therefore, the objective of this study was to compare the clinical outcome of presumptive versus malaria rapid diagnostic test-based management of childhood malaria-pneumonia overlap in Nigeria.
A pilot quasi-experimental study was conducted November 2009 through February 2010 in an urban comprehensive health centre in Ogun, South-Western Nigeria. First, 50 children with malaria-pneumonia symptom overlap were consecutively enrolled and treated presumptively with antibiotics and antimalarials irrespective of malaria test result (control arm).Then, another 50 eligible children were enrolled and treated with antibiotics with/out antimalarials based on rapid diagnostic test result (intervention arm). Primary endpoint: clinical cure at day-5. The data were analyzed using Epi Info version 3.4.1.
The intervention and control arms did not differ significantly regarding patient demographic and clinical characteristics. Clinical cure rate was slightly higher in children managed presumptively 49 (98%) than those managed rapid diagnostic test -based 47 (94%) (P = 0.31). However, rapid diagnostic test -based treated children had lower risk of receiving antimalarials compared to those treated presumptively (48% vs. 100%), (P = <0.001; relative risk 2.08, CI 1.56 to 2.78). No death or severe complications were recorded in either group at day-5 follow-up.
Outcome of rapid diagnostic test-based treatment is not inferior to presumptive management in children with malaria-pneumonia symptom overlap. More extensive studies with larger sample sizes are needed.
PMCID: PMC3275847  PMID: 22434977
Malaria management; malaria- pneumonia overlap; rapid diagnostic tests; safety; Nigeria
15.  Impact of training in clinical and microscopy diagnosis of childhood malaria on antimalarial drug prescription and health outcome at primary health care level in Tanzania: A randomized controlled trial 
Malaria Journal  2008;7:199.
Prescribing antimalarial medicines based on parasite confirmed diagnosis of malaria is critical to rational drug use and optimal outcome of febrile illness. The impact of microscopy-based versus clinical-based diagnosis of childhood malaria was assessed at primary health care (PHC) facilities using a cluster randomized controlled training intervention trial.
Sixteen PHC facilities in rural Tanzania were randomly allocated to training of health staff in clinical algorithm plus microscopy (Arm-I, n = 5) or clinical algorithm only (Arm-II, n = 5) or no training (Arm-III, n = 6). Febrile under-five children presenting at these facilities were assessed, treated and scheduled for follow up visit after 7 days. Blood smears on day 0 were only done in Arm-I but on Day 7 in all arms. Primary outcome was antimalarial drug prescription. Other outcomes included antibiotic prescription and health outcome. Multilevel regression models were applied with PHC as level of clustering to compare outcomes in the three study arms.
A total of 973, 1,058 and 1,100 children were enrolled in arms I, II and III, respectively, during the study period. Antimalarial prescriptions were significantly reduced in Arm-I (61.3%) compared to Arms-II (95.3%) and III (99.5%) (both P < 0.001), whereas antibiotic prescriptions did not vary significantly between the arms (49.9%, 54.8% and 34.2%, respectively). In Arm-I, 99.1% of children with positive blood smear readings received antimalarial prescriptions and so did 11.3% of children with negative readings. Those with positive readings were less likely to be prescribed antibiotics than those with negative (relative risk = 0.66, 95% confidence interval: 0.55, 0.72). On day 7 follow-up, more children reported symptoms in Arm-I compared to Arm-III, but fewer children had malaria parasitaemia (p = 0.049). The overall sensitivity of microscopy reading at PHC compared to reference level was 74.5% and the specificity was 59.0% but both varied widely between PHCs.
Microscopy based diagnosis of malaria at PHC facilities reduces prescription of antimalarial drugs, and appears to improve appropriate management of non-malaria fevers, but major variation in accuracy of the microscopy readings was found. Lack of qualified laboratory technicians at PHC facilities and the relatively short training period may have contributed to the shortcomings.
Trial registration
This study is registered at with the identifier NCT00687895.
PMCID: PMC2566575  PMID: 18831737
16.  Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers’ practices in Zanzibar 
Malaria Journal  2013;12:37.
In Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers’ practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients.
Semi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children.
The following themes were identified: 1) health workers use caregivers’ history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers’ resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making.
This pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria.
PMCID: PMC3626688  PMID: 23356837
Malaria elimination; Diagnostic decision-making; Non-malarial fevers
17.  Falciparum Malaria as an Emerging Cause of Fever in Adults Living in Gabon, Central Africa 
BioMed Research International  2014;2014:351281.
Following the observed increase of malaria prevalence among older children in Gabon, a descriptive observational study was carried out in 2012 to determine the prevalence of malaria in adults presenting with fever in two health centres of Libreville, the capital city of Gabon. Thick- and thin-blood smears for malaria diagnosis were performed in febrile individuals aged more than 15 years old. Age, use of bed nets, previous antimalarial drug treatment, clinical symptoms, chest radiography results, and available haemoglobin data were also recorded. Among the 304 patients screened, the global malaria frequency was of 42.1% (n = 128/34). Plasmodium (P). falciparum was the only species identified. The proportion of patients with a clinical malaria requiring parenteral treatment was 38.5%, whereas 47.5% of outpatients had uncomplicated malaria. According to WHO classification, 14 (19.7%) infected patients had severe malaria; neurological and respiratory symptoms tended to be more frequent in case of P. falciparum infection. Anaemia was found in 51.5% adults and none had severe anaemia. Almost half of adults consulting for fever in two health centres of the urban city of Libreville have malaria. The use of insecticide-treated bed nets, the screening, and the treatment of individuals with P. falciparum microscopic and submicroscopic asymptomatic infection or clinical malaria should be emphasized to reduce the transmission.
PMCID: PMC4022109  PMID: 24982865
18.  Severe falciparum malaria in Gabonese children: clinical and laboratory features 
Malaria Journal  2005;4:1.
Malaria continues to claim one to two million lives a year, mainly those of children in sub-Saharan Africa. Reduction in mortality depends, in part, on improving the quality of hospital care, the training of healthcare workers and improvements in public health. This study examined the prognostic indicators of severe falciparum malaria in Gabonese children.
An observational study examining the clinical presentations and laboratory features of severe malaria was conducted at the Centre Hospitalier de Libreville, Gabon over two years. Febrile children aged from 0 to 10 years with Plasmodium falciparum infection and one or more features of severe malaria were enrolled.
Most children presenting with severe falciparum malaria were less than 5 years (92.3% of 583 cases). Anaemia was the most frequent feature of severe malaria (67.8% of cases), followed by respiratory distress (31%), cerebral malaria (24%) hyperlactataemia (16%) and then hypoglycaemia (10%). Anaemia was more common in children under 18 months old, while cerebral malaria usually occurred in those over 18 months. The overall case fatality rate was 9%. The prognostic indicators with the highest case fatality rates were coma/seizures, hyperlactataemia and hypoglycaemia, and the highest case fatality rate was in children with all three of these features.
Prompt and appropriate, classification and treatment of malaria helps identify the most severely ill children and aids early and appropriate management of the severely ill child.
PMCID: PMC546207  PMID: 15638948
19.  Diagnostic Workup of Febrile Children Under 24 Months of Age: A Clinical Review 
Western Journal of Medicine  1982;137(1):1-12.
One of the most challenging situations encountered by primary care physicians is the diagnostic workup of a febrile child. Several studies have shown the surprisingly high incidence of clinically unsuspected, potentially major illness in febrile children. Bacteremia, pneumonia and urinary tract infection are particularly likely to present in an occult manner, while meningitis is more likely to be clinically suspected.
An examination of the literature regarding febrile children under two years of age is necessary in order to synthesize the relevant information. Although there are large gaps in our knowledge, it is possible to make specific recommendations for a treatment plan, keeping in mind that areas of controversy and other reasonable approaches exist.
PMCID: PMC1273976  PMID: 6753341
20.  Prevalence and determinants of Campylobacter infection among under five children with acute watery diarrhea in Mwanza, North Tanzania 
Archives of Public Health  2014;72(1):17.
Campylobacteriosis, a zoonotic bacterial disease observed world-wide, is becoming the most commonly recognized cause of bacterial gastroenteritis in humans. This study was done to determine the prevalence and determinants of Campylobacter infection among under-fives with acute watery diarrhea in Mwanza City, Tanzania.
This cross-sectional hospital-based study was conducted at Bugando Medical Centre (BMC) and Sekou Toure Hospital in Mwanza City. All inpatients and outpatients under-fives who met the inclusion criteria from October 2012 to April 2013 were enrolled in the study. Demographic and clinical data were obtained using standardized data collection tools. Stool samples were collected for gram staining and culture for Campylobacter spp. on Preston selective agar media. In addition, blood slides for malaria and HIV tests were done to all patients.
A total of 300 children were enrolled with a median age of 12 [interquartile range, 8–19] months. Of these, 169 (56.5%) were from BMC and 131 (43.7%) from Sekou-Toure hospital. One hundred and seventy (56.7%) of the participating children were male. Of 300 under-fives with acute watery diarrhea, 29 patients (9.7%) were found to have Campylobacter infection. A significant higher number of children with Campylobacter infection were found in Sekou Toure hospital compared to BMC [16.0% (21/29) versus 4.7% (8/29), p = 0.002)]. Age above 2 years was independently found to predict campylobacter infection (OR: 2.9, 95% CI 1.1-7.7, p = 0.0037). Of 30 patients with a positive blood slide for Plasmodium falciparum, 20.0% were also positive for Campylobacter infection (OR: 3.9, 95% CI 1.2-10.1, p = 0.021).
Campylobacter infection shows a comparatively low prevalence in under-fives with acute watery diarrhea in Mwanza city and is independently associated with positive slides for malaria and an age above 2 years. Further studies are needed to type the most prevalent Campylobacter species and to determine their antibiotic susceptibility pattern.
PMCID: PMC4057571  PMID: 24932408
Acute watery diarrhea; Campylobacteriosis; Under five children
21.  Using community-owned resource persons to provide early diagnosis and treatment and estimate malaria burden at community level in north-eastern Tanzania 
Malaria Journal  2012;11:152.
Although early diagnosis and prompt treatment is an important strategy for control of malaria, using fever to initiate presumptive treatment with expensive artemisinin combination therapy is a major challenge; particularly in areas with declining burden of malaria. This study was conducted using community-owned resource persons (CORPs) to provide early diagnosis and treatment of malaria, and collect data for estimation of malaria burden in four villages of Korogwe district, north-eastern Tanzania.
In 2006, individuals with history of fever within 24 hours or fever (axillary temperature ≥37.5°C) at presentation were presumptively treated using sulphadoxine/pyrimethamine. Between 2007 and 2010, individuals aged five years and above, with positive rapid diagnostic tests (RDTs) were treated with artemether/lumefantrine (AL) while under-fives were treated irrespective of RDT results. Reduction in anti-malarial consumption was determined by comparing the number of cases that would have been presumptively treated and those that were actually treated based on RDTs results. Trends of malaria incidence and slide positivity rates were compared between lowlands and highlands.
Of 15,729 cases attended, slide positivity rate was 20.4% and declined by >72.0% from 2008, reaching <10.0% from 2009 onwards; and the slide positivity rates were similar in lowlands and highlands from 2009 onwards. Cases with fever at presentation declined slightly, but remained at >40.0% in under-fives and >20.0% among individuals aged five years and above. With use of RDTs, cases treated with AL decreased from <58.0% in 2007 to <11.0% in 2010 and the numbers of adult courses saved were 3,284 and 1,591 in lowlands and highlands respectively. Malaria incidence declined consistently from 2008 onwards; and the highest incidence of malaria shifted from children aged <10 years to individuals aged 10–19 years from 2009.
With basic training, supervision and RDTs, CORPs successfully provided early diagnosis and treatment and reduced consumption of anti-malarials. Progressively declining malaria incidence and slide positivity rates suggest that all fever cases should be tested with RDTs before treatment. Data collected by CORPs was used to plan phase 1b MSP3 malaria vaccine trial and will be used for monitoring and evaluation of different health interventions. The current situation indicates that there is a remarkable changing pattern of malaria and these areas might be moving from control to pre-elimination levels.
PMCID: PMC3517357  PMID: 22554149
22.  Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study 
The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.
Methods and Findings
We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.
Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.
Author Summary
The syndrome of fever is caused by a large number of infectious diseases. Malaria is thought to have been declining in the tropics since 2004. Increasing use of malaria diagnostic tests reveal a growing proportion of patients with fever who do not have malaria. While malaria diagnostic tests may be available, healthcare workers have few tools to diagnose causes of fever other than malaria. In order to identify major causes of fever other than malaria in northern Tanzania, we studied 870 patients with fever who were sufficiently ill to require admission to hospital. Malaria was uncommon and over-diagnosed, whereas invasive infections, including bloodstream infections, were underappreciated. Infections associated with animals such as brucellosis, leptospirosis, Q fever, and spotted fever group rickettsioses as well as viral infections transmitted by mosquitoes were common yet overlooked. We recommend that research on the syndrome of fever in resource-limited areas should focus on a wide range of potential causes. Animal-associated infections should be prioritized in patient management and disease control.
PMCID: PMC3715424  PMID: 23875053
23.  Impact of home-based management of malaria on health outcomes in Africa: a systematic review of the evidence 
Malaria Journal  2007;6:134.
Home-based management of malaria (HMM) is promoted as a major strategy to improve prompt delivery of effective malaria treatment in Africa. HMM involves presumptively treating febrile children with pre-packaged antimalarial drugs distributed by members of the community. HMM has been implemented in several African countries, and artemisinin-based combination therapies (ACTs) will likely be introduced into these programmes on a wide scale.
Case presentations
The published literature was searched for studies that evaluated the health impact of community- and home-based treatment for malaria in Africa. Criteria for inclusion were: 1) the intervention consisted of antimalarial treatment administered presumptively for febrile illness; 2) the treatment was administered by local community members who had no formal education in health care; 3) measured outcomes included specific health indicators such as malaria morbidity (incidence, severity, parasite rates) and/or mortality; and 4) the study was conducted in Africa. Of 1,069 potentially relevant publications identified, only six studies, carried out over 18 years, were identified as meeting inclusion criteria. Heterogeneity of the evaluations, including variability in study design, precluded meta-analysis.
Discussion and evaluation
All trials evaluated presumptive treatment with chloroquine and were conducted in rural areas, and most were done in settings with seasonal malaria transmission. Conclusions regarding the impact of HMM on morbidity and mortality endpoints were mixed. Two studies showed no health impact, while another showed a decrease in malaria prevalence and incidence, but no impact on mortality. One study in Burkina Faso suggested that HMM decreased the proportion of severe malaria cases, while another study from the same country showed a decrease in the risk of progression to severe malaria. Of the four studies with mortality endpoints only one from Ethiopia showed a positive impact, with a reduction in the under-5 mortality rate of 40.6% (95% CI 29.2 – 50.6).
Currently the evidence base for HMM in Africa, particularly regarding use of ACTs, is narrow and priorities for further research are discussed. To optimize treatment and maximize health benefits, drug regimens and delivery strategies in HMM programmes may need to be tailored to local conditions. Additional research could help guide programme development, policy decision-making, and implementation.
PMCID: PMC2170444  PMID: 17922916
24.  Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study 
Malaria Journal  2011;10:64.
Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home.
An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with, number NCT00454961.
A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046).
Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.
PMCID: PMC3065443  PMID: 21410954
25.  Diagnosis of Malaria Infection with or without Disease 
The revised W.H.O. guidelines for malaria management in endemic countries recommend that treatment should be reserved to laboratory confirmed cases, both for adults and children. Currently the most widely used tools are rapid diagnostic tests (RDTs), that are accurate and reliable in diagnosing malaria infection. However, an infection is not necessarily a clinical malaria, and RDTs may give positive results in febrile patients who have another cause of fever. Excessive reliance on RDTs may cause overlooking potentially severe non malarial febrile illnesses (NMFI) in these cases. In countries or areas where transmission intensity remains very high, fever management in children (especially in the rainy season) should probably remain presumptive, as a test-based management may not be safe, nor cost effective. In contrast, in countries with low transmission, including those targeted for malaria elimination, RDTs are a key resource to limit unnecessary antimalarial prescription and to identify pockets of infected individuals. Research should focus on very sensitive tools for infection on one side, and on improved tools for clinical management on the other, including biomarkers of clinical malaria and/or of alternative causes of fever.
PMCID: PMC3375766  PMID: 22708051

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