A clinical algorithm for the diagnosis of malaria: results of an evaluation in an area of low endemicity

We conducted a study of 1945 children and 2885 adults who presented with fever to a hospital outpatients clinic in an urban area of India order to develop and evaluate a clinical algorithm for the diagnosis of malaria. Only 139 (7%) children and 349 (12%) adults had microscopically confirmed malaria. None of the symptoms or signs elicited from the respondents were good predictors of clinical malaria. Simple scores were derived through combining clinical features which were associated with slide positivity or were judged by clinicians to be important. The best-performing algorithms were a score of 4 clinical features in children (sensitivity 60.0% and specificity 61.2%) and a score of 5 in adults (sensitivity 54.6% and specificity 57.5%). The clinical features differed and algorithm performances were poorer than in previous studies in highly endemic areas. The conclusion is that malaria diagnosis in areas of low endemicity requires microscopy to be accurate.     

The diagnosis of Plasmodium falciparum infection in Gambian children, by field staff using the rapid, manual, ParaSight-F test

A rapid immunodiagnostic test for Plasmodium falciparum, the ParaSight-F test, was evaluated in the diagnosis of malaria in 139 children with uncomplicated malaria, who presented at the Medical Research Council's clinic at Basse in Upper River division, The Gambia. The aim was to evaluate the performance and usefulness of the test as a diagnostic method in a malaria-endemic area, when performed by a field worker. Compared with microscopy, the test had a sensitivity of 96.5%, a specificity of 90.5%, a negative predictive value of 94.2% and a positive predictive value of 94.3%. Because of its sensitivity, specificity and simplicity, the ParaSight-F test will be of value in situations where microscopy is not possible.     

Clinical diagnosis of Plasmodium falciparum among children with history of fever, Sindh, Pakistan.

OBJECTIVE: To identify clinical predictors for malaria and develop a clinical algorithm to more accurately identify malaria from non-malaria cases. METHODS: Four hundred thirty eight children aged 6-120 months attending the rural health center between August 15 and October 5, 1997, in Jhangara town of district Dadu, Sindh were recruited. A standard questionnaire was used to record symptoms and duration of child's illness. Each child was physically examined, had their axillary temperature measured, and blood samples were collected from which Giemsa stained thick and thin blood films were prepared and examined for presence of Plasmodium parasites. The sensitivity and specificity of several candidate algorithms for parasitemia were evaluated using various combinations of identified predictors. RESULTS: Twenty-six of 438 children (6%) were slide positive for malaria. An algorithm comprised of fever 3 days duration and (absence of cough or having rigors) had 100% sensitivity and 63% specificity for detecting P. falciparum. CONCLUSION: In this low malaria prevalence region, restricting the diagnosis of malaria to persons who had >3 days of fever and absence of cough or rigors, remained highly sensitive but was more specific than current practice. If validated prospectively, this algorithm could reduce misdiagnosis and mis-treatment.     

Clinical algorithms for malaria diagnosis lack utility among people of different age groups

We conducted a study to determine whether clinical algorithms would be useful in malaria diagnosis among people living in an area of moderate malaria transmission within Kilifi District in Kenya. A total of 1602 people of all age groups participated. We took smears and recorded clinical signs and symptoms (prompted or spontaneous) of all those presenting to the study clinic with a history of fever. A malaria case was defined as a person presenting to the clinic with a history of fever and concurrent parasitaemia. A set of clinical signs and symptoms (algorithms) with the highest sensitivity and specificity for diagnosing a malaria case was selected for the age groups /=15 years. These age-optimized derived algorithms were able to identify about 66% of the cases among those <15 years of age but only 23% of cases among adults. Were these algorithms to be used as a basis for a decision on treatment among those presenting to the clinic, 16% of children /=5000 parasites/microl of blood would be sent home without treatment. Clinical algorithms therefore appear to have little utility in malaria diagnosis, performing even worse in the older age groups, where avoiding unnecessary use of anti-malarials would make more drugs available to the really needy population of children under 5 years of age.     

Season, fever prevalence and pyrogenic threshold for malaria disease definition in an endemic area of Mali

BACKGROUND: Modelling malaria parasitaemia as function of fever has been proposed as best alternative to estimate the attributable fraction of malaria fever and the sensitivity and specificity of different case definitions of malaria disease. OBJECTIVES: To determine the prevalence of fever and its relation to malaria parasitaemia and to establish a pyrogenic threshold for malaria disease in the area. METHODS: We conducted two cross-sectional surveys in children of 6 months to 9 years of age (2434 during the rainy season of 1993 and 2353 during the dry season of 1994) randomly selected from 21 areas of Bandiagara district, Mali. RESULTS: The relationship between fever and Plasmodium falciparum parasitaemia depends strongly on the season, thus affecting the malaria-attributable fraction of fever cases and the sensitivity and specificity of malaria case definitions. The overall proportion of fever attributable to malaria parasitaemia was 33.6% during the rainy season and 23.3% during the dry season, with the highest proportion occurring among the youngest children. The cut-off value, where the sensitivity curve crosses the specificity curve, was around 3200 pf/microl for all age categories during the rainy season and 200 pf/microl during the dry season. CONCLUSIONS: Malaria remains a main cause of fever in this area of Mali. The pyrogenic threshold of parasitaemia depends strongly on the season, and different cut-off levels of parasitaemia should be used during the two seasons to define malaria cases in this area.     

Usefulness of clinical algorithm as screening process to detected malaria in low-to-moderate transmission areas of scarce health related resources

Introduction: In areas of low-to-moderate risk of malaria transmission, the World Health Organization recommends parasitic confirmation before treatment. Such areas have usually low budget for health care and malaria diagnosis is mostly based on clinical assumption. Algorithms have been developed to improve health care providers’ identification of clinical malaria and could be used as screening to reduce the number of individuals requiring parasitic confirmation before treating. Methods: Prospective clinical and parasitological data were collected from inhabitants of four villages from March 1984 through March 1985. Symptoms and signs recorded by physicians were used in multivariate models to test the best predictors of malaria. Sensitivity and specificity were calculated for various cut-offs of scores and compared to clinical diagnosis. Results: A total of 8.941 individuals were evaluated during the 1-year period of data collection. The overall prevalence of malaria parasitemia was 19.7% (n = 1762). Of the 4280 people evaluated during the high season period, 24% (n = 1024) presented any parasitemia, 55.3% (566/1024) due to Plasmodium falciparum. The final clinical algorithm included history of fever, rigors, headache, absence of myalgia, backache or cough, nausea or vomiting, and splenomegaly on examination as predictable variables. At a cut-off score of 2.0, the sensitivity of the algorithm was higher for the entire sample (57% vs. 43%), for high season period (70% vs. 53%), for children less than 6 years of age (59% vs. 40%), for individuals with parasitemia due to P. falciparum (65% vs. 48%), and for high P. falciparum parasitemic individuals at high season (84% vs. 68%). However, specificity was usually lower unless a higher cut off was used, in which case the gain in sensitivity by using the algorithm was reduced. Conclusion: In low-to-moderate transmission areas in which health related resources are scarce, a clinical algorithm increases the identification of real cases of malaria and could be used as screening for further parasitic identification.     

Assessing diarrhoea-induced dehydration at the community level

A community based study of children under 5 years of age in Nampula, Mozambique, assessed children with diarrhoea for the 12 signs and symptoms of dehydration listed in the World Health Organization's Diarrhoea Treatment Chart and for the additional indicators of observed thirst and reported fever. The point prevalence of diarrhoea was 13.1%. The signs and symptoms of dehydration reported by carers were compared with signs detected on physical examination at the time of the interview. The presence of four or more stools, a history of drinking either more or less than usual, and reported fever in the preceding 24 h had the highest sensitivities. Individual symptoms with the highest specificity were decreased urine output, vomiting, and the passing of 10 or more stools during the 24 h preceding the interview. The combination of fever or vomiting had a sensitivity of 68.3% and a specificity of 55.9%, whereas a combination of vomiting or drinking more than usual or fever had a sensitivity of 87.8% and a specificity of 34.1%. These findings are compared with the results of similar studies conducted in different clinical and cultural settings.     

Malaria diagnosis and treatment under the strategy of the integrated management of childhood illness (IMCI): relevance of laboratory support from the rapid immunochromatographic tests of ICT Malaria P.f/P.v and OptiMal

The algorithm developed for the integrated management of childhood illness (IMCI) provides guidelines for the treatment of paediatric malaria. In areas where malaria is endemic, for example, the IMCI strategy may indicate that children who present with fever, a recent history of fever and/or pallor should receive antimalarial chemotherapy. In many holo-endemic areas, it is unclear whether laboratory tests to confirm that such signs are the result of malaria would be very relevant or useful. Children from a holo-endemic region of Tanzania were therefore checked for malarial parasites by microscopy and by using two rapid immunochromatographic tests (RIT) for the diagnosis of malaria (ICT Malaria P.f/P.v and OptiMal. At the time they were tested, each of these children had been targeted for antimalarial treatment (following the IMCI strategy) because of fever and/or pallor. Only 70% of the 395 children classified to receive antimalarial drugs by the IMCI algorithm had malarial parasitaemias (68.4% had Plasmodium falciparum trophozoites, 1.3% only P. falciparum gametocytes, 0.3% P. ovale and 0.3% P. malariae). As indicators of P. falciparum trophozoites in the peripheral blood, fever had a sensitivity of 93.0% and a specificity of 15.5% whereas pallor had a sensitivity of 72.2% and a specificity of 50.8%. The RIT both had very high corresponding sensitivities (of 100.0% for the ICT and 94.0% for OptiMal) but the specificity of the ICT (74.0%) was significantly lower than that for OptiMal (100.0%). Fever and pallor were significantly associated with the P. falciparum asexual parasitaemias that equalled or exceeded the threshold intensity (2000/microl) that has the optimum sensitivity and specificity for the definition of a malarial episode. Diagnostic likelihood ratios (DLR) showed that a positive result in the OptiMal test (DLR = infinity) was a better indication of malaria than a positive result in the ICT (DLR = 3.85). In fact, OptiMal had diagnostic reliability (0.93) which approached that of an ideal test and, since it only detects live parasites, OptiMal is superior to the ICT in monitoring therapeutic responses. Although the RIT may seem attractive for use in primary health facilities because relatively inexperienced staff can perform them, the high cost of these tests is prohibitive. In holo-endemic areas, use of RIT or microscopical examination of bloodsmears may only be relevant when malaria needs to be excluded as a cause of illness (e.g. prior to treatment with toxic or expensive drugs, or during malaria epidemics). Wherever the effective drugs for the first-line treatment of malaria are cheap (e.g. chloroquine and Fansidar), treatment based on clinical diagnosis alone should prove cost-saving in health facilities without microscopy.     

Clinical predictors of malaria and other febrile illnesses in children under five on Pemba Island, Tanzania

Under the current guidelines of presumptive treatment of all children with reported fever, the risk of over-prescribing antimalarial drugs and missing other important causes of fever, like acute respiratory tract infection (ARI), is substantial. Clinical algorithms have been shown to be useful in diagnosing malaria, but often with differing results, due to regional variations. We set out to explore the clinical features associated with malaria compared with other febrile illnesses and specifically severe malaria with ARI in children under five in Pemba. Two hundred and seven children aged six months to five years presenting to a hospital clinic with fever were studied in Pemba. Clinical findings were related to the presence of malaria parasitaemia. Malaria accounted for 67.7% of the febrile episodes investigated. Five symptoms and signs, including pallor, drowsiness, splenomegaly, fever duration and no chest crackles, could accurately predict a case of malaria with a sensitivity of 91.3% and specificity of 53% and positive predictive value of 80.3%. Several clinical features were found to differentiate severe malaria from ARI. These results confirm that clinical algorithms can increase the diagnostic accuracy of malaria, although not sufficiently to replace microscopy, and by promoting the use of clinical skills other treatable causes of febrile illnesses may be identified.These findings could have implications in optimizing treatment and malaria control in children on Pemba.     

Analysis of different clinical criteria in malaria patients in Papua New Gwinea

To assess the validity of different clinical criteria in malaria patients, a small study including 92 children presented with fever or history of fever were examined in a highly endemic area of Papua New Gwinea. In 21 children parasitaemia was confirmed by microscopy examination of thick and thin smear stained with Giemsa method (9 cases of Plasmodium falciparum, 8 cases of Plasmodium vivax and 4 cases of mixed invasion Plasmodium falciparum and Plasmodium vivax). Only 4 from different 39 criteria analyzed in children with history of fever or hot skin showed significant association with parasitaemia (conscious disturbances, severe wasting, enlarged spleen and diarrhoea), however none of the criteria presented high sensitivity and could serve as good predictors for parasitaemia accept two (first and second one). These findings help to realize the importance of laboratory examination in diagnosis of malaria and explain difficulties in confirming or exclusion of malaria where microscopy is not available.     

Predictive Symptoms and Signs of Laboratory-confirmed Influenza: A Prospective Surveillance Study of Two Metropolitan Areas in Taiwan

Influenza infection poses annual threats and leads to significant morbidity and mortality. Early diagnosis is the key to successful treatment. Laboratory-based diagnosis has various limitations. Diagnosis based on symptoms or signs is still indispensable in clinical practice. We investigated the symptoms or signs associated with laboratory-confirmed influenza.A prospective study across 2 influenza seasons was performed from June 2010 to June 2012 at 2 branches (Taipei and Lin-Kou) of Chang Gung Memorial Hospital. Patients who visited outpatient clinics with suspected acute respiratory tract infection were sampled by throat swab or nasopharyngeal swab. RT-PCR and/or virus culture were used as a reference standard. We used logistic regression to identify the symptoms or signs associated with laboratory-confirmed influenza infection. We also evaluated the performance metrics of different influenza-like illness used in Taiwan, the USA, and WHO.A total of 158 patients were included in the study. The prevalence of influenza infection was 45% (71/158). Fever, cough, rhinorrhea, sneezing, and nasal congestion were significant predictors for influenza infection. Whereas fever + cough had a best sensitivity (86%; confidence interval [CI] 76%–93%), fever + cough and sneezing had a best specificity (77%; CI 62%–88%). Different case definitions of influenza-like illness had comparable accuracy in sensitivity and specificity.Clinical diagnosis based on symptoms and signs is useful for allocating resources, identifying those who may benefit from early antiviral therapy and providing valuable information for surveillance purpose.     

Renal involvement in Gambian children with cerebral or mild malaria

Kidney function was studied in 80 Gambian children with cerebral malaria, 73 children with mild malaria, and in 19 children with other febrile illnesses. Serum creatinine was measured, and the excretion in urine of immunoglobulin G, transferrin, albumin and alpha 1 microglobulin was determined. Twenty-five percent of children with cerebral malaria, and 4% of children with mild malaria had an elevated serum creatinine above 62 mumol/l. Increased urinary protein excretion was frequent: 53% of children with cerebral malaria had a glomerulo-tubular pattern of protein excretion, and 46% a tubular pattern. Median albuminuria was 68 mg/l in children with cerebral malaria, 18 mg/l in children with mild malaria, and 9 mg/l in febrile children with other diseases (P < 0.0001). There was no significant association between the proteinuria and height of fever or the degree of parasitaemia, and there was no significant association between death and signs of renal impairment. Renal involvement is common in children with malaria in The Gambia, with prerenal, glomerular, and tubulo-interstitial factors contributing. It is more pronounced in children with cerebral malaria than in those with mild malaria. However, renal dysfunction is relatively mild and does not indicate a worse prognosis.     

Clinical case definition of malaria at a secondary level hospital in northern India

Malaria has re-emerged as a major public health problem in India. At present, under the National guidelines; all fevers are presumed to be due to malaria and chloroquine is given as presumptive treatment. This results in overtreatment. We did a pilot study to see whether some clinical predictors of malaria could be identified in the Indian setting. This case control study was done in a secondary level hospital. All those with fever who were smear positive for malaria were enrolled as cases and other patients fever who were smear negative for malaria served as the controls. All the factors under study were ascertained by a history or detailed clinical examination. A total of 41 cases and 95 controls were enrolled. Of the 41 cases, 35 were positive for P. vivax and six were positive for P. falciparum. After multivariate analysis, only splenomegaly (OR = 2.11; 95% CI = 1.27-3.50) and pallor (OR = 2.01; 95% CI = 1.16-3.48) were significantly associated with malaria. It appears that history of fever along with one or both of these two signs can be a useful predictor of malaria in a secondary level hospital in India. The utility and feasibility of a similar approach in a field setting needs to be studied further.     

National early warning score on admission as risk factor for invasive mechanical ventilation in COVID-19 patients: A STROBE-compliant study

The coronavirus disease (COVID-19) has become a global pandemic. Invasive mechanical ventilation is recommended for the management of patients with COVID-19 who have severe respiratory symptoms. However, various complications can develop after its use. The efficient and appropriate management of patients requires the identification of factors associated with an aggravation of COVID-19 respiratory symptoms to a degree where invasive mechanical ventilation becomes necessary, thereby enabling clinicians to prevent such ventilation. This retrospective study included 138 inpatients with COVID-19 at a tertiary hospital. We evaluated the differences in the demographic and clinical data between 27 patients who required invasive mechanical ventilation and 111 patients who did not. Multivariate logistic regression analysis indicated that the duration of fever, national early warning score (NEWS), and lactate dehydrogenase (LDH) levels on admission were significantly associated with invasive mechanical ventilation in this cohort. The optimal cut-off values were: fever duration ≥1 day (sensitivity 100.0%, specificity 54.95%), NEWS ≥7 (sensitivity 72.73%, specificity 92.52%), and LDH >810 mg/dL (sensitivity 56.0%, specificity 90.29%). These findings can assist in the early identification of patients who will require invasive mechanical ventilation. Further studies in larger patient populations are recommended to validate our findings.     

Child malaria treatment practices among mothers in the district of Yanfolila, Sikasso region, Mali

We studied child malaria treatment practices among mothers living in the District of Yanfolila in southern Mali. For sampling, we first chose five of 13 health areas with probability proportional to size. Then villages, compounds and mothers with at least one child aged 1-5 years were randomly chosen. We assessed the spleen size of one 1-5 year-old child of each mother, collected a thick blood film and recorded the body temperature of every child whose mother thought he/she was sick. 399 mothers in 28 villages were interviewed with a structured questionnaire divided into two parts. If the child had had soumaya (a term previously associated with uncomplicated malaria) during the past rainy season, we asked about signs and symptoms, health-seeking behaviour (who the mother consulted first) and treatment. If not, information about knowledge of the disease and treatment to be given was collected. 86% of the mothers interviewed stated that their child had been sick and almost half of them had had soumaya. All mothers named at least one sign by which they recognized the disease. Vomiting, fever and dark urine/yellow eyes/jaundice were the three most common signs mentioned. 75.8% managed their child's disease at home and used both traditional and modern treatment. The most common anti-malarial drug was chloroquine, often given at inappropriate dosage. The sensitivity and specificity of the mothers' diagnosis was poor, although this might be explained by the large percentage of children who had already been treated at the time of the interview. The results of our survey call for prompt educational action for the correct treatment of uncomplicated malaria/soumaya, particularly for mothers and possibly for shopkeepers. The high spleen rate (58.1%) among randomly selected children confirms that malaria is a common disease in this area. Improved case-management at home could only be beneficial.     

Evaluation of an algorithm for integrated management of childhood illness in an area of Vietnam with dengue transmission

OBJECTIVES: To determine whether nurses, using the WHO/UNICEF algorithm for integrated management of childhood illness (IMCI), modified to include dengue infection, satisfactorily classified children in an area endemic for dengue haemorrhagic fever (DHF). METHODS: Nurses assessed and classified, using the modified IMCI algorithm, a systematic sample of 1250 children aged 2 months to 10 years (n = 1250) presenting to a paediatric hospital in Dong Nai Province, Vietnam. Their classification was compared with that of a paediatrician, blind to the result of the nurses' assessment, which could be modified in the light of simple investigations, e.g. dengue serology. RESULTS: In children aged 2-59 months (n = 859), the nurses were able to classify, using the modified chart, the presenting illness in >99% of children and found more than one classification in 70%. For the children with pneumonia, diarrhoea, dengue shock syndrome, severe DHF and severe disease requiring urgent admission, the nurse's classification was >60% sensitive and >85% specific compared with that of the paediatrician. For the nurse's classification of DHF the specificity was 50-55% for the children <5 years and in children with definitive dengue serology. Alterations in the DHF algorithm improved specificity at the expense of sensitivity. CONCLUSION: Using the IMCI chart, nurses classified appropriately many of the major clinical problems in sick children <5 years in southern Vietnam. However, further modifications will be required in the fever section, particularly for dengue. The impact of using the IMCI chart in peripheral health stations remains to be evaluated.     

Interpreteation of immunochromatographic tests with HRP-2 antigen in children under 5 years in an area of high risk of malaria transmission in Papua New Guinea

The immunochromatographic tests with HRP-2 antigen (histidine-rich protein) Vision Biotech Pf Rapid Malaria Test was performed in 291 children under 5 years presenting fever or history of fever (malaria presumptive cases) admitted to Children Out-Patient Department of the Modilon Hospital in Madang, in a high malaria risk area of Papua New Guinea. The results of the tests were compared to the results of the parasitic examination of the peripheral blood with light microscopy (thick and thin smears). The HRP-2 test showed very high sensitivity (95.4%) and specificity (94.1%) for Plasmodiumfalciparum parasitaemia and none or very low sensitivity and specificity for other malaria species. The HRP-2 test detected both asexual and sexual stages of the Plasmodium falciparum parasites. The test did not show significant changes in detection of different levels of parasitaemia. These findings enable to conclude that the HRP-2 immunochromatographic assay can be very helpful to diagnose Plasmodium falciparum malaria when microscopy examination is not available, but as qualitative tests can be difficult for interpretation especially in high malaria risk areas. Therefore it can require re-examination of blood with microscopy to confirm species and development stages of Plasmodium spp. and to assess parasite load.     

Ocular lesions associated with malaria in children in Mali

This study sought to estimate the frequency of ocular complications in malaria and its prognostic value in Mali. A total of 140 children (aged 6 months to 9 years) with severe malaria (105 with cerebral malaria, 35 without neurological complications) were compared with 34 children with mild malaria and 82 children with nonmalarial fever. Ocular lesions were rare in the mild malaria group (5.8%). Retinal hemorrhages occurred in 11.8% of the children in the severe noncerebral malaria group. Cerebral malaria was associated with retinal hemorrhages (22.9%) and retinal edema (10.5%). No association was found between ocular signs such as retinal hemorrhages or retinal edema and mortality. Exudates, papilledema, and the presence of cottonwool spots were associated with an increased risk of death. Coma score and convulsions were significantly associated with death but not with ocular signs. The presence of retinal signs in a child in a malaria-endemic area may signal a case of severe malaria.     

Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high-transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria.