Erratum: Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains.

[This corrects the article DOI: 10.1093/ve/vey027.][This corrects the article DOI: 10.1093/ve/vey027.].

Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains.

The respiratory syncytial virus (RSV) group A variant with the 72-nucleotide duplication in the G gene, genotype ON1, was first detected in Kilifi in 2012 and has almost completely replaced circulating genotype GA2 strains. This replacement suggests some fitness advantage of ON1 over the GA2 viruses in Kilifi, and might be accompanied by important genomic substitutions in ON1 viruses. Close observation of such a new virus genotype introduction over time provides an opportunity to better understand the transmission and evolutionary dynamics of the pathogen. We have generated and analysed 184 RSV-A whole-genome sequences (WGSs) from Kilifi (Kenya) collected between 2011 and 2016, the first ON1 genomes from Africa and the largest collection globally from a single location. Phylogenetic analysis indicates that RSV-A circulation in this coastal Kenya location is characterized by multiple introductions of viral lineages from diverse origins but with varied success in local transmission. We identified signature amino acid substitutions between ON1 and GA2 viruses' surface proteins (G and F), polymerase (L), and matrix M2-1 proteins, some of which were positively selected, and thereby provide an enhanced picture of RSV-A diversity. Furthermore, five of the eleven RSV open reading frames (ORFs) (G, F, L, N, and P) formed distinct phylogenetic clusters for the two genotypes. This might suggest that coding regions outside of the most frequently studied G ORF also play a role in the adaptation of RSV to host populations, with the alternative possibility that some of the substitutions are neutral and provide no selective advantage. Our analysis provides insight into the epidemiological processes that define RSV spread, highlights the genetic substitutions that characterize emerging strains, and demonstrates the utility of large-scale WGS in molecular epidemiological studies.

Impact of a Rapid Results Initiative Approach on Improving Male Partner Involvement in Prevention of Mother to Child Transmission of HIV in Western Kenya.

A rapid results initiative (RRI) aimed at increasing male involvement in prevention of mother-to-child transmission (PMTCT) and service uptake among pregnant women at 116 antenatal clinics in Western Kenya was compared at baseline, during the RRI, and 3-months post-RRI. Male involvement increased from 7.4 to 54.2% during RRI (risk difference [RD] 0.47, CI 0.45-0.48) then 43.4% post-RRI (RD 0.36, CI 0.35-0.37). Among HIV-infected women, facility delivery increased from 40.0 to 49.9% (RD 0.10, 95% CI 0.06-0.13) and 65.0% post-RRI (RD 0.25, 95% CI 0.22-0.28). HIV-infected pregnant women linkage to HIV care increased from 58.6 to 85.9% (RD 0.27, CI 0.24-0.30) and 97.3% post-RRI (RD 0.39, CI 0.36-0.41). Time to ART initiation reduced from 29 days (interquartile range [IQR] 6-56) to 14 days (IQR 0-28) to 7 days (IQR 0-20). A male-centered RRI can significantly increase men's engagement in antenatal care leading to improved partner utilization of PMTCT and antenatal services.

Surveillance for respiratory health care-associated infections among inpatients in 3 Kenyan hospitals, 2010-2012.

BACKGROUND: Although health care-associated infections are an important cause of morbidity and mortality worldwide, the epidemiology and etiology of respiratory health care-associated infections (rHAIs) have not been documented in Kenya. In 2010, the Ministry of Health, Kenya Medical Research Institute, and Centers for Disease Control and Prevention initiated surveillance for rHAIs at 3 hospitals. METHODS: At each hospital, we surveyed intensive care units (ICUs), pediatric wards, and medical wards to identify patients with rHAIs, defined as any hospital-onset (≥3 days after admission) fever (≥38°C) or hypothermia (<35°C) with concurrent signs or symptoms of acute respiratory infection. Nasopharyngeal and oropharyngeal specimens were collected from these patients and tested by real-time reverse transcription polymerase chain reaction for influenza and 7 other viruses. RESULTS: From April 2010-September 2012, of the 379 rHAI cases, 60.7% were men and 57.3% were children <18 years old. The overall incidence of rHAIs was 9.2 per 10,000 patient days, with the highest incidence in the ICUs. Of all specimens analyzed, 45.7% had at least 1 respiratory virus detected; 92.2% of all positive viral specimens were identified in patients <18 years old. CONCLUSION: We identified rHAIs in all ward types under surveillance in Kenyan hospitals. Viruses may have a substantial role in these infections, particularly among pediatric populations. Further research is needed to refine case definitions and understand rHAIs in ICUs.

External built residential environment characteristics that affect mental health of adults.

External built residential environment characteristics include aspects of building design such as types of walls, doors and windows, green spaces, density of houses per unit area, and waste disposal facilities. Neighborhoods that are characterized by poor quality external built environment can contribute to psychosocial stress and increase the likelihood of mental health disorders. This study investigated the relationship between characteristics of external built residential environment and mental health disorders in selected residences of Nakuru Municipality, Kenya. External built residential environment characteristics were investigated for 544 residents living in different residential areas that were categorized by their socioeconomic status. Medically validated interview schedules were used to determine mental health of residents in the respective neighborhoods. The relationship between characteristics of the external built residential environment and mental health of residents was determined by multivariable logistic regression analyses and chi-square tests. The results show that walling materials used on buildings, density of dwelling units, state of street lighting, types of doors, states of roofs, and states of windows are some built external residential environment characteristics that affect mental health of adult males and females. Urban residential areas that are characterized by poor quality external built environment substantially expose the population to daily stressors and inconveniences that increase the likelihood of developing mental health disorders.

Impact of expanded antiretroviral use on incidence and prevalence of tuberculosis in children with HIV in Kenya.

SETTING: Antiretroviral therapy (ART) reduces pulmonary tuberculosis (PTB) in human immunodeficiency virus (HIV) infected children. Recent ART recommendations have increased the number of children on ART. OBJECTIVE: To determine the prevalence and incidence of TB in HIV-infected children after the implementation of expanded ART guidelines. DESIGN: A prospective cohort study including HIV-infected children aged 6 weeks to 14 years was conducted in Kenya. The primary outcome measure was clinically diagnosed TB. Study participants were screened for prevalent TB at enrollment using Kenya's national guidelines and followed at monthly intervals to detect incident TB. Predictors of TB were assessed using logistic regression and Cox proportional hazards regression. RESULTS: Of 689 participants (median age 6.4 years), 509 (73.9%) were on ART at baseline. There were 51 cases of prevalent TB (7.4%) and 10 incident cases, with over 720.3 child-years of observation (incidence 1.4 per 100 child-years). Months on ART (adjusted hazard ratio [aHR] 0.91, P = 0.003; aOR 0.91, P< 0.001) and months in care before ART (aHR 0.87, P= 0.001; aOR 0.92, P < 0.001) were protective against incident and prevalent TB. CONCLUSIONS: ART was protective against TB in this cohort of HIV-infected children with high levels of ART use. Optimal TB prevention strategies should emphasize early ART in children.

The Effect of a Local Mineral Kadosero Towards the Antimicrobial Activity of Medicinal Plant's Extract : Case of Lake Victoria Basin; Tarime; Tanzania

The effect of kadosero; a crude mineral used by traditional healers as a supplement to plant extracts against microbial infections was evaluated. A sample of kadosero from a local market was both analyzed for its basic composition and its role on bioactivity of plant extract. Titrimetric; Gravimetric and Atomic Absorption Spectrometric analyses were used to determine contents of the mineral kadosero. Disc Diffusion Assay was used for bioactivity screening in-vitro. Chemical analysis of kadosero revealed the presence of (0.0038mg/g); Fe2 (0.0027mg/g); Cl- (232.683mg/g) and Na+ (151.25mg/g). In-vitro tests revealed that supplementing extract of Balanites aegyptiaca with a mineral kadosero by using untreated well water reduced number of bacterial from 100 colony forming units to nil at a mass of a mineral between 60-100 mg. On the other hand; a mineral kadosero did not increase bioactivity of the extract of B. aegyptiaca against the test microbes in agar disc diffusion assay. This was attributed by interaction between the mineral kadosero and nutrient agar medium. The crude mineral kadosero can be supplemented to other plant extracts used locally for treatment of general bacterial infections for increased bioactivity. Further study is recommended to determine mechanisms for bacterial vulnerability to this mineral supplement

The effect of Local Mineral Kadosero Towards the Antimicrobial Activity of Medical Plant's Extract: Case of Lake Victoria Basin; Tarime Tanzania

The effect of Kadosero; a crude mineral used by traditional healers as a supplement to plant extracts against microbial infections was evaluated. A sample of kadosero from a local market was both analyzed for its basic composition and its role on bioactivity of plant extract. Titrimetric; Gravimetric and Atomic Absorption Spectrometric analyses were used to determine contents of the mineral kadosero. Disc Diffusion Assay was used for bioactivity screening in-vitro. Chemical analysis of kadosero revealed the presence of SO4-2(0.0038mg/g); Fe2 (0.0027mg/g); Cl- (232.683mg/g) and Na+ (151.25mg/g). In-vitro tests revealed that supplementing extract of Balanites aegyptiaca with a mineral kadosero by using untreated well water reduced number of bacterial from 100 colony forming units to nil at a mass of a mineral between 60-100 mg. On the other hand; a mineral kadosero did not increase bioactivity of the extract of B. aegyptiaca against the test microbes in agar disc diffusion assay. This was attributed by interaction between the mineral kadosero and nutrient agar medium. The crude mineral kadosero can be supplemented to other plant extracts used locally for treatment of general bacterial infections for increased bioactivity. Further study is recommended to determine mechanisms for bacterial vulnerability to this mineral supplement

Seroprevalence of hepatitis B markers in pregnant women in Kenya.

OBJECTIVE: To evaluate hepatitis B serological markers in pregnant women from various geographical sites in Kenya. DESIGN: A cross-sectional observational study of women attending antenatal clinics. SETTING: The Kenyatta National Hospital and eight hospitals from five provinces in Kenya. SUBJECTS: All women in their third trimester of pregnancy attending the antenatal clinic over the period June 2001 to June 2002. MAIN OUTCOME MEASURES: For each pregnant woman age and gestation were documented. Hepatitis serological markers were evaluated. RESULTS: A total of 2241 pregnant women were enrolled. Among them 205 women (9.3%) were positive for HbsAg and from these 18 (8.8%) were found to have HbeAg. Protective antibodies (anti-HbsAg) were detected in 669 (30.2%) of the women. There were notable significant regional differences for HbsAg rates. CONCLUSIONS: These results confirm the presence of high disease carrier rate and the corresponding previously reported low level of HbeAg suggesting questionable low rate of perinatal transmission but high rate of horizontal transmission.

Effectiveness of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study.

OBJECTIVE: To monitor the effectiveness of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) for the control of malaria in pregnancy at delivery in the Provincial Hospital in Kisumu, Kenya, and to assess the effect of IPT in participants in a cohort study. METHODS: Between June 1999 and June 2000, information on IPT and birth outcome was collected in 2302 consecutive deliveries. A group of 889 women, who were enrolled in a cohort to assess the interaction between malaria and HIV, were analysed separately because of the enrollment criteria and different access to health care. RESULTS: The prevalence of placental malaria was 13.8% and of low birthweight (LBW) was 12.2%. In multivariable analysis, IPT (> or =1 dose of SP) was associated with a reduction in placental malaria and LBW [adjusted odds ratio (OR) 0.56, 95% confidence interval (CI) 0.39-0.83 and OR 0.65, 95% CI 0.45-0.95, respectively]. An adjusted mean increase in birthweight of 61 g was seen (95% CI 22-101 g) for each increment in number of SP doses (> or =2 doses grouped together). IPT was associated with a reduction in placental malaria in HIV-seronegative women (OR 0.49, 95% CI 0.28-0.86) but this was not significant among HIV-seropositive women (OR 0.45, 95% CI 0.20-1.05). A significant effect on birthweight could not be detected among participants in the HIV-cohort. CONCLUSIONS: This evaluation confirms that IPT with SP is effective in reducing placental malaria and LBW. It will be important to increase coverage of IPT and to extend IPT to antenatal clinics in peri-urban and rural areas.

Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya.

To assess risk factors for anemia in late pregnancy, we studied healthy pregnant women with a singleton uncomplicated pregnancy of > or = 32 weeks attending the prenatal clinic in the Provincial Hospital in Kisumu, Kenya. Between June 1996 and December 1998, 4,608 pregnant women had a blood sample collected for hemoglobin (Hb) measurement, malaria smear, and testing for human immunodeficiency virus (HIV). The mean +/- standard deviation of Hb was 9.58 +/- 1.8 g/dL; 21% had malaria in their blood; and 25% of the women were HIV seropositive. Plasmodium falciparum parasitemia was more common among HIV-seropositive women in all gravidities compared with HIV-seronegative women (risk ratio, 1.71; 95% confidence interval, 1.53-1.92). In a multivariate analysis, for primi- and secundigravidae women, the factors malaria, belonging to the Luo tribe, and HIV seropositivity were significantly associated with any anemia (Hb < 11 g/dL), and HIV seropositivity and documented fever were associated with severe anemia (Hb < 7 g/dL). In women of higher gravidities, HIV seropositivity was the only statistically significant factor associated with any anemia or with severe anemia. Asymptomatic HIV seropositivity is an important risk factor to be considered in the differential diagnosis of maternal anemia, independent of P. falciparum parasitemia.

Risk factors for HIV infection among asymptomatic pregnant women attending an antenatal clinic in western Kenya.

Our objective was to evaluate HIV prevalence and identify risk factors for HIV infection among women attending the antenatal clinic (ANC) at a large public hospital in Kisumu town, western Kenya. Between June 1996 and November 1997, in the context of a study to determine the effect of placental malaria on mother-to-child transmission of HIV in western Kenya, HIV-1 antibody testing was offered to women with a singleton uncomplicated pregnancy of > or =32 weeks' gestation attending the ANC. Women were interviewed using a structured questionnaire and had a fingerstick blood sample collected for haemoglobin (Hb), malaria smears, and HIV antibody testing. Overall HIV seroprevalence was 26.1% (743/2844) (95% confidence interval (CI): 24.5-27.7) and in bivariate evaluation was significantly associated with anaemia (Hb <11 g/dl) (risk ratio (RR) 1.8), malarial parasitaemia (RR 1.6), fever (axillary temperature > or =37.5 degrees C at screening) (RR 1.6), a history of being treated for either vaginal discharge (RR 1.5) or tuberculosis (RR 1.6), reported alcohol consumption (RR 1.6), being an unmarried multigravida (RR 2.2) or a history of the most recent child having died (RR 2.0). Poisson regression analysis for all women identified 5 significant factors independently associated with HIV seropositivity: anaemia (adjusted RR 1.7; 95% CI 1.3-2.0), malarial parasitaemia (adjusted RR 1.7; 95% CI 1.4-2.0), a history of being treated for vaginal discharge (adjusted RR 1.5; 95% CI 1.1-2.0), fever (adjusted RR 2.0; 95% CI 1.3-3.2) and reported alcohol consumption (adjusted RR 1.6; 95% CI 1.1-2.5). Multigravidae women whose most recent child had died were also more likely to be HIV seropositive (adjusted RR 1.9; 95% CI 1.7-2.8). Only 5.5% (156/2844) of the women had none of these risk factors, of whom 12% (18/156) were HIV(+). Even though the model containing the 5 identified factors fitted the data well (goodness-of-fit chi2=18.41, P=0.10), its collective capacity to predict HIV infection was poor; while 74% of the truly positive women were correctly predicted positive by the model, 52% of the truly negative women were misclassified. Among pregnant women attending the ANC in western Kenya, we were unable to identify a subgroup at risk of HIV infection using non-serological information, indicating that wherever possible universal access to voluntary HIV counselling and testing would be preferable to targeted screening.

PIP: This study evaluated the HIV prevalence and identified the risk factors for HIV infection among women attending the antenatal clinic at a public hospital in Kisumu, western Kenya. Also, the effect of placental malaria on vertical HIV transmission were determined using structured interviews and HIV-1 antibody testing and hemoglobin malaria smears were offered to the respondents. Overall, HIV seroprevalence was 26.1% (743/2844) (95% confidence interval [CI]: 24.5-27.7) and in bivariate evaluation was significantly associated with anemia (risk ratio [RR] 1.8), malarial parasitemia (RR 1.6), fever (RR 1.6), a history of being treated for either vaginal discharge (RR 1.5) or tuberculosis (RR 1.6), alcohol consumption (RR 1.6), being an unmarried multigravida (RR 2.2), or a history of the most recent child having died (RR 2.0). Using the Poisson regression analysis, 5 significant factors associated with HIV seropositivity were identified: anemia, malarial parasitemia, and history of being treated for vaginal discharge, fever, and reported alcohol consumption. Among the pregnant women, the researchers were unable to identify a subgroup at risk of HIV infection using nonserological information, indicating that universal access to voluntary HIV counseling and testing would be preferable to targeted screening.

Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission.

In 1993, the World Health Organization completed the development of a draft algorithm for the integrated management of childhood illness (IMCI), which deals with acute respiratory infections, diarrhoea, malaria, measles, ear infections, malnutrition, and immunization status. The present study compares the performance of a minimally trained health worker to make a correct diagnosis using the draft IMCI algorithm with that of a fully trained paediatrician who had laboratory and radiological support. During the 14-month study period, 1795 children aged between 2 months and 5 years were enrolled from the outpatient paediatric clinic of Siaya District Hospital in western Kenya; 48% were female and the median age was 13 months. Fever, cough and diarrhoea were the most common chief complaints presented by 907 (51%), 395 (22%), and 199 (11%) of the children, respectively; 86% of the chief complaints were directly addressed by the IMCI algorithm. A total of 1210 children (67%) had Plasmodium falciparum infection and 1432 (80%) met the WHO definition for anaemia (haemoglobin < 11 g/dl). The sensitivities and specificities for classification of illness by the health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia (97% sensitivity, 49% specificity); dehydration in children with diarrhoea (51%, 98%); malaria (100%, 0%); ear problem (98%, 2%); nutritional status (96%, 66%); and need for referral (42%, 94%). Detection of fever by laying a hand on the forehead was both sensitive and specific (91%, 77%). There was substantial clinical overlap between pneumonia and malaria (n = 895), and between malaria and malnutrition (n = 811). Based on the initial analysis of these data, some changes were made in the IMCI algorithm. This study provides important technical validation of the IMCI algorithm, but the performance of health workers should be monitored during the early part of their IMCI training.

PIP: The World Health Organization (WHO) in 1993 developed the integrated management of childhood illness (IMCI) draft algorithm which offers guidelines upon the diagnosis and treatment of acute respiratory infections, diarrhea, malaria, measles, ear infections, and malnutrition, as well as immunization status. During a 14-month study period, 1795 children aged 2 months to 5 years were enrolled in the study from the outpatient pediatric clinic of Siaya District Hospital in western Kenya, of whom 52% were male and the median age was 13 months. 51% of the children complained of having fever, 22% of having a cough, and 11% of having diarrhea. 86% of the main complaints were directly addressed by the IMCI algorithm. 1210 children had Plasmodium falciparum infection and 1432 met the WHO definition for anemia. The sensitivities and specificities for classification of illness by a minimally trained health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia, 97% sensitivity and 49% specificity; dehydration in children with diarrhea, 51% and 98%, respectively; malaria, 100% and 0%; ear problem, 98% and 2%; nutritional status, 96% and 66%; and need for referral, 42% and 94%. Detection of fever by placing a hand upon the forehead was 91% sensitive and 77% specific. Considerable clinical overlap was observed between pneumonia and malaria, and between malaria and malnutrition. Study findings led to some changes in the IMCI algorithm.

Assessment of potential indicators for protein-energy malnutrition in the algorithm for integrated management of childhood illness.

Potential indicators were assessed for the two classifications of protein-energy malnutrition in the guidelines for integrated management of childhood illness: severe malnutrition, which requires immediate referral to hospital, and very low weight, which calls for feeding assessment, nutritional counselling and follow-up. Children aged < 2 years require feeding assessment and counselling as a preventive intervention. For severe malnutrition, we examined 1202 children admitted to a Kenyan hospital for any association of the indicators with mortality within one month. Bipedal oedema indicating kwashiorkor, and two marasmus indicators (visible severe wasting and weight-for-height (WFH) Z-score of < -3) were associated with a significantly increased mortality risk (odds ratios, 3.1-3.9). Very low weight-for-age (WFA) (Z-score of < -4.4) was not associated with an increased risk of mortality. Because first-level health facilities generally lack length-boards, bipedal oedema and visible severe wasting were chosen as indicators of severe malnutrition. To assess potential WFA thresholds for the very low weight classification, our primary source of data came from 1785 Kenyan outpatient children, but we also examined data from surveys in Nepal, Bolivia, and Togo. We examined the performance of WFA at various thresholds to identify children with low WFH and, for children aged < or = 2 years, low height-for-age (HFA). Use of a WFA threshold Z-score of < -2 identified a considerable proportion of children (from 13% in Bolivia to 68% in Nepal) which, in most settings, would pose an enormous burden on the health facility. Among ill children in Kenya, a threshold WFA Z-score of < -3 had a sensitivity of 89-100% to detect children with WFH Z-scores of < -3, and, with an identification rate of 9%, would avoid overburdening the clinics. Potential modifications include use of a more restrictive cut-off in countries with high rates of stunting, or the elimination of the WFA screen in order to concentrate efforts on intervention for all children below the 2-year age cut-off. Key issues in every country include the capacity to provide counselling for many children and linkage to nutritional improvement programmes in the community.

PIP: Severe malnutrition and very low weight were assessed as potential indicators for the classification of protein-energy malnutrition in the guidelines for the integrated management of childhood illness. For severe malnutrition, the authors examined 1202 children under age 5 years admitted to a Kenyan hospital for any association of the indicators with mortality within 1 month. Bipedal oedema indicating kwashiorkor, and the marasmus indicators of visible severe wasting and a weight-for-height (WFH) Z score of less than -3 were associated with a significantly increased risk of mortality. Very low weight-for-age (WFA) was not associated with an increased risk of mortality. Bipedal edema and visible severe wasting were chosen as indicators of severe malnutrition since first-level health facilities typically lack length-boards. Data for 1785 Kenyan outpatient children as well as survey data from Nepal, Bolivia, and Togo were used in assessing potential WFA thresholds for the very low weight classification. Use of a WFA threshold Z-score of less than -2 identified from 13% of children in Bolivia to 68% in Nepal who would in most settings burden health facilities. Among sick children in Kenya, a threshold WFA Z-score of less than -3 was 89-100% sensitive in detecting children with WFH Z-scores of less than -3 and, with an identification rate of 9%, would not overburden health clinics. Potential modifications include the use of a more restrictive cutoff in countries with high rates of stunting or the elimination of the WFA screen in order to focus efforts upon intervention for all children under the 2-year age cutoff.

Clinical signs for the recognition of children with moderate or severe anaemia in western Kenya.

Optimal treatment of Plasmodium falciparum-related paediatric anaemia can result in improved haematological recovery and survival. Clinical predictors are needed to identify children with anaemia in settings where laboratory measurements are not available. The use of conjunctival (eyelid), palmar, nailbed, and tongue pallor to detect children with moderate anaemia (haemoglobin, 5.0-7.9 g/dl) or severe anaemia (haemoglobin, < 5.0 g/dl) was evaluated among children seen at an outpatient and inpatient setting in a hospital in western Kenya. Severe nailbed or severe palmar pallor had the highest sensitivity (62% and 60%, resp.), compared with severe conjunctival pallor (sensitivity = 31%), to detect children with severe anaemia in the outpatient setting. Children with moderate anaemia were best identified by the presence of nailbed or palmar pallor (sensitivity = 90% for both signs), compared with conjunctival pallor (sensitivity = 81%). Clinical signs of respiratory distress, in addition to the presence of severe pallor, did not increase the recognition of children requiring hospitalization for severe anaemia. Among inpatients, the sensitivity of severe nailbed pallor (59%) was highest for detecting children with severe anaemia, although the sensitivity of severe conjunctival pallor and severe palmar pallor was the same (53% for both signs). Presence of conjunctival pallor (sensitivity = 74%) was similar in sensitivity to both nailbed and palmar pallor (70% for both signs) among children with moderate anaemia. The sensitivity of tongue pallor was low among all children evaluated. Low haemoglobin levels were significantly associated with the likelihood of being smear-positive for P. falciparum. This study demonstrates that clinical criteria can be used to identify children with moderate and severe anaemia, thus enabling implementation of treatment algorithms. Children aged < 36 months who live in an area with P. falciparum malaria should receive treatment with an effective antimalarial drug if they have pallor.

PIP: The ability of pallor of the conjunctiva, palms, nailbed, and tongue to identify children with Plasmodium falciparum-related anemia in developing country settings, where laboratory measurements are not available, was investigated in children attending Siaya District Hospital in western Kenya. Enrolled were all children 2 months to 5 years of age admitted to the hospital's inpatient unit in 1993-94 (n = 1048), and every fifth child presenting to the outpatient clinic (n = 1666). Severe nailbed or severe palmar pallor had the highest sensitivities (62% and 60%, respectively) in the detection of severe anemia in outpatients, while those with moderate anemia were best identified by nailbed or palmar pallor (90% sensitivity for both signs). The addition of clinical signs of respiratory distress to pallor did not increase the identification of children requiring hospitalization for severe anemia. Among inpatients, severe nailbed, conjunctival, and palmar pallor had sensitivities of 59%, 53%, and 53%, respectively, for detecting severe anemia. In the detection of moderate anemia, the sensitivities were 74%, 70%, and 70%, respectively, for conjunctival, nailbed, and palmar pallor. Tongue pallor had a low sensitivity among all children examined. Low hemoglobin levels were significantly associated with P. falciparum infection. It is recommended that all children under 36 months of age, in areas with P. falciparum malaria, should receive antimalarial treatment if they present with pallor.

An evaluation of clinical indicators for severe paediatric illness.

To help reduce paediatric morbidity and mortality in the developing world, WHO has developed a diagnostic and treatment algorithm that targets the principal causes of death in children, which include acute respiratory infection, malaria, measles, diarrhoeal disease, and malnutrition. With this algorithm, known as the Sick Child Charts, severely ill children are rapidly identified, through the presence of any one of 13 signs indicative of severe illness, and referred for more intensive health care. These signs are the inability to drink, abnormal mental status (abnormally sleepy), convulsions, wasting, oedema, chest wall retraction, stridor, abnormal skin turgor, repeated vomiting, stiff neck, tender swelling behind the ear, pallor of the conjunctiva, and corneal ulceration. The usefulness of these signs, both in current clinical practice and within the optimized context of the Sick Child Chart algorithm in a rural district of western Kenya, was evaluated. We found that 27% of children seen in outpatient clinics had one or more of these signs and that pallor and chest wall retraction were the signs most likely to be associated with hospital admission (odds ratio (OR) = 8.6 and 5.3, respectively). Presentation with any of these signs led to a 3.2 times increased likelihood of admission, although 54% of hospitalized children had no such signs and 21% of children sent home from the outpatient clinic had at least one sign. Among inpatients, 58% of all children and 89% of children who died had been admitted with a sign. Abnormal mental status was the sign most highly associated with death (OR = 59.6), followed by poor skin turgor (OR = 5.6), pallor (OR = 4.3), repeated vomiting (OR = 3.6), chest wall retraction (OR = 2.7), and oedema (OR = 2.4). Overall, the mortality risk associated with having at least one sign was 6.5 times higher than that for children without any sign. While these signs are useful in identifying a subset of children at high risk of death, their validation in other settings is needed. The training and supervision of health workers to identify severely ill children should continue to be given high priority because of the benefits, such as reduction of childhood mortality.

PIP: The World Health Organization (WHO) has developed a diagnostic and treatment algorithm to facilitate the rapid identification and management of severely ill children in developing countries. 13 indicators are listed on Sick Child Charts: inability to drink, abnormal mental status (e.g., sleepiness), convulsions, wasting, edema, chest wall retraction, stridor, abnormal skin turgor, repeated vomiting, stiff neck, tender swelling behind the ear, pallor of the conjunctiva, and corneal ulceration. These indicators target the principal causes of child mortality: acute respiratory infection, malaria, measles, diarrheal disease, and malnutrition. The usefulness of the WHO algorithm was evaluated in 4 clinics in western Kenya's Siaya district and in the pediatric outpatient and inpatient departments of Siaya District Hospital. 770 (28%) of the 2799 children (mean age, 13 months) seen in these rural outpatient clinics had 1 or more of the 13 signs, most frequently repeated vomiting (13%). Children with any of these signs had a 2.3 times higher odds of hospitalization than those without such signs; however, 424 admitted children (54%) had none of the 13 signs. Pallor and chest wall retraction were most highly associated with hospital admission (odds ratio [OR], 8.6 and 5.3, respectively). Among the 1139 inpatients, 666 (58%) presented with at least 1 sign and 75 (7%) died, 67 (89%) of whom had at least 1 clinical sign at admission. Overall, the mortality risk associated with having at least 1 sign was 6.5 times higher than that for children with none of the signs. The signs most associated with mortality were abnormal mental status (OR, 59.6), poor skin turgor (OR, 5.6), pallor (OR, 4.3), repeated vomiting (OR, 3.6), chest wall retraction (OR, 2.7), and edema (OR, 2.4). Although studies in other settings are required to validate the WHO logarithm, this schema appears to be a feasible means for identifying high-risk children in developing countries.