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. 2022 Apr 26;2(4):e0000284. doi: 10.1371/journal.pgph.0000284

Hypoxemia, hypoglycemia and IMCI danger signs in pediatric outpatients in Malawi

André Thunberg 1,2,*, Beatiwel Zadutsa 3, Everlisto Phiri 3, Carina King 1,4, Josephine Langton 5, Lumbani Banda 3, Charles Makwenda 3, Helena Hildenwall 1,2,6
Editor: Claire E von Mollendorf7
PMCID: PMC10021275  PMID: 36962312

Abstract

Hypoxemia and hypoglycemia are known risks for mortality in children in low-income settings. Routine screening with pulse oximetry and blood glucose assessments for outpatients could assist in early identification of high-risk children. We assessed the prevalence of hypoglycemia and hypoxemia, and the overlap with Integrated Management of Childhood Illness (IMCI) general danger signs, among children seeking outpatient care in Malawi. A cross-sectional study was conducted at 14 government primary care facilities, four rural hospitals and one district referral hospital in Mchinji district, Malawi from August 2019—April 2020. All children aged 0–12 years seeking care with an acute illness were assessed on one day per month in each facility. Study research assistants measured oxygen saturation using Lifebox LB-01 pulse oximeter and blood glucose was assessed with AccuCheck Aviva glucometers. World Health Organization definitions were used for severe hypoglycemia (<2.5mmol/l) and hypoxemia (SpO2 <90%). Moderate hypoglycemia (2.5–4.0mmol/l) and hypoxemia (SpO2 90–93%) were also calculated and prevalence levels compared between those with and without IMCI danger signs using chi2 tests. In total 2,943 children were enrolled, with a median age of 41 (range: 0–144) months. The prevalence of severe hypoxemia was 0.6% and moderate hypoxemia 5.4%. Severe hypoglycemia was present in 0.1% of children and moderate hypoglycemia in 11.1%. IMCI general danger signs were present in 29.3% of children. All severely hypoglycemic children presented with an IMCI danger sign (p <0.001), but only 23.5% of the severely hypoxemic and 31.7% of the moderately hypoxemic children. We conclude that while the prevalence of severe hypoxemia and hypoglycemia were low, moderate levels were not uncommon and could potentially be useful as an objective tool to determine referral needs. IMCI danger signs identified hypoglycemic children, but results highlight the challenge to detect hypoxemia. Future studies should explore case management strategies for moderate hypoxemia and hypoglycemia.

Introduction

Global child mortality has more than halved since 1990, but still 5.2 million children died before the age of five in 2019, with treatable infectious diseases remaining the leading post-neonatal cause of death [1]. The World Health Organization’s (WHO) Integrated Management of Childhood Illness (IMCI) was first introduced in the mid-1990’s and has since been implemented to some extent in over 100 countries [2]. This program aims to reduce child mortality through the timely identification of common infections, and increased access to antibiotics, antimalarial treatment and oral rehydration solution and zinc [3, 4]. Full implementation of IMCI has been linked with the achievement of the Millennium Development Goal 4 which aimed to reduce the under-five mortality rate by two thirds between 1990 and 2015 [5].

However, IMCI does not include any components of emergency case management, and primary healthcare facilities in low-income countries commonly lack the resources to treat severely ill children and instead refer these cases to hospitals [6]. Substantial challenges in the identification of severely ill children have been reported under IMCI, potentially leading to missed referrals [7]. In addition, completion of referrals are commonly complicated by family circumstances, costs and transportation issues [8], as well as gender norms [9], leading to delayed or incomplete referrals [10].

Early objective identification of children at higher risk of mortality could improve referral practices, both through emphasizing to caregivers the importance of attending the hospital, and by ensuring that children reach higher level facilities before they are critically ill. Hypoxemia and hypoglycemia are both known to be associated with poor outcomes [11, 12] but may go clinically undetected [13]. A study in Malawi reported that more than half of the hypoxemic pneumonia cases in children would not have been referred from primary care, using only the IMCI guidelines in the absence of a pulse oximeter [14]. Furthermore, the definitions of hypoxemia and hypoglycemia are topics of debate with studies demonstrating increased mortality also among children with moderately low saturation and blood glucose values [11, 15–19].

More frequent use of pulse oximetry and blood glucose assessments within higher mortality outpatient settings could improve outcomes through earlier identification and referral of those with moderately low oxygen saturation values and blood glucose concentrations. To inform referral strategies, the burden of severe illness needs to be determined alongside the utility of the current IMCI danger signs to identify children at risk. Therefore, we aimed to assess the prevalence of severe and moderate hypoxemia and hypoglycemia in children presenting to outpatient settings in Mchinji district, Malawi, and to explore the overlap between different levels of hypoxemia and hypoglycemia and IMCI danger signs.

Materials and methods

We conducted a cross sectional study of children aged 0 to 12 years presenting to outpatient facilities with an acute illness in Mchinji district, Malawi, from August 2019 to April 2020. The study was nested within a district wide cohort study (Emergency paediatric treatment and referral in Malawi in frontline healthcare settings–EREMISS study), which assessed the outcomes of children being referred from primary care health facilities. While the EREMISS study only enrolled children who were referred from primary care facilities to higher level care, the current study was run in parallel to provide data on the overall prevalence of hypoxemia and hypoglycemia among children seeking outpatient care in the district.

Setting

Mchinji district is located in Malawi’s central region and with an under-five population of approximately 90,000 in 2018 [20]. The under-five mortality rate was 123/1,000 livebirths in the 2015–16 Demographic Health Survey [21]. Data was collected at the 19 public health facilities, consisting of: 14 government health centers, four rural hospitals run by the Christian Health Association of Malawi (CHAM) and the district hospital. Health centers provide no pediatric inpatient care while hospitals both provide outpatient services and inpatient care. Patients were only enrolled from the outpatient department of the included hospitals. All care for children is provided free of charge at government facilities. Malawi implemented IMCI guidelines in 2000 [22].

Participant recruitment

Data was collected for one full working day per month at each of the study facilities. Study research assistants were present to collect data during ‘normal’ facility outpatient clinic times, usually between 8am– 3pm. Data collection days were randomly determined, using a simple random number generator with replacement in Microsoft Excel. This was done to ensure that any potential differences in patient load and/or type of diagnosis depending on the day of the week would be spread randomly across study facilities. Guardians of all children from 0 up to 12 years of age, inclusive, who sought care due to an acute illness (i.e., excluding children coming for immunization or growth control) were approached for recruitment.

Data collection

Children and their guardians were informed about the study when they were in the facility waiting area. Before seeing the clinician, guardians were approached by a study research assistant to ask for their consent, both to participate in the study and to have a blood glucose test done. Once consent was given, the research assistant assessed the child’s oxygen saturation using a Lifebox LB-01 pulse oximeter (Acare Technology Co. Ltd), with pediatric and universal clip probes. Research assistants were trained to use the child’s big toe for measurements and to wait for a stable waveform before collecting the saturation value. Blood glucose concentrations were measured after the oxygen saturation had been assessed. A capillary blood sample was collected after pricking the child’s finger and the glucose concentration was analyzed using a AccuCheck Aviva (Roche Diabetes Care, Inc) point of care device reporting results in mmol/l. The results were written in the child’s health passport, and clinical staff were immediately alerted if the blood glucose concentration was <2.5 mmol/l or if the oxygen saturation was <90%.

After these measurements, the child was assessed by routine clinic staff. Data on IMCI general danger signs i.e. being unable to eat/drink, vomits everything, unconscious, sleepy, lethargic and convulsions [3] were then extracted by the research assistant from the child’s health passport. While the IMCI danger signs are created for children below five years of age, there is a lack of validated assessments tools and routine guidelines for children aged 5–12 years, and therefore health workers in this setting commonly use IMCI for this age group. We therefor chose to extract the same clinical information for all children. Other variables collected were age and sex, and from the health passport any documented nutritional status, respiratory rate, temperature, presence of chest indrawing and the health worker diagnosis. The additional variables were chosen since commonly assessed by health workers and relevant for the potential relation with hypoxemia.

Data was collected electronically using Open Data Kit (ODK) on Android tablets and uploaded daily to an ODK database. Data queries were raised and resolved with regular communication between the Monitoring and Evaluation Officers, investigators and data manager. All patients were managed routinely by the facility staff according to needs and facility standards.

Prior to the study start, all participating healthcare providers underwent re-training in IMCI to ensure that minimum standard of care was being provided. A total of 20 research assistants were recruited locally and assigned different facilities within the study area. Research assistants had no formal clinical training but underwent one week training including: study procedures, conducting pulse oximetry and blood glucose testing and filling case report forms accurately. Following training, the study procedures were piloted for one week; continual mentorship and supervision was provided by the study Monitoring and Evaluation Officers and project manager in close communication with the study investigators, to correct any issues in protocol implementation.

Data management and analysis

Oxygen saturation was categorized into normal (SpO2 > = 94%), moderate hypoxemia (SpO2 90–93%) and severe hypoxemia (SpO2< 90%). Blood glucose concentration were classified as normal (4.1–11.0 mmol/l), moderate hypoglycemia (2.5–4.0 mmol/l) and severe hypoglycemia (<2.5mmol/l). Since nutritional assessment was not recorded for all children, we used the <2.5mmol/l as the primary hypoglycemia definition for the whole group but the prevalence of blood glucose concentrations <3 mmol/l was also calculated for those assessed to be malnourished. During data checks we noted that two research assistants reported unreasonably high proportions of hypoxemia, suggestive of measurement quality issues. We decided to exclude their SpO2 results (n = 306) from the primary analysis but conducted a sensitivity analysis which retained them (presented in S1 Table).

Patient characteristics were described by facility type, oxygen saturation and blood glucose level using proportions. Malnutrition was defined using weight-for-age Z-score (WAZ; moderately malnourished -3 to -2 SD; severely malnourished <-3 SD using WHO growth charts for children <5 years old and UK growth charts for children aged 5–12), or health worker’s clinical diagnosis. Differences in clinical characteristics between those with and without danger signs were compared using chi2 and Fishers exact tests.

As a quality control of the reported danger signs, we conducted a sensitivity analysis comparing the prevalence of danger signs between children with a positive malaria Rapid Diagnostic Test (danger signs expected) and children diagnosed with scabies only (danger signs not expected). Smoothed graphs were plotted to show the seasonal variation in clinical presentation, using a 2-week weighted moving averages. All data processing and analysis was done using Stata 12.

Ethical statement

The study was approved by the Malawi College of Medicine Research and Ethics Committee (reference: P11/18/25389). Guardians were informed about the study while in the waiting area and provided verbal consent for their minors to participate in the study prior to any data was collected. Due to literacy levels, study information was given verbally in Chichewa, and consent given verbally–the informed consent was subsequently recorded in the electronic data collection form. The consent covered both the collection of data from patient health passports and the assessment of blood glucose concentrations and oxygen saturation. Refusal to participate had no impact on the care provided to the patients and information sheets with study contact information were available for guardians to take with them.

Results

A total of 2,943 children aged 0–12 years were enrolled as they presented to health centers (2,343/2,943, 79.6%) and hospitals (601/2,943, 20.4%)–Table 1. There was a similar proportion of boys and girls (48.5% and 51.5%, respectively), and this was comparable at both hospital and health centers. The most common diagnosis was malaria (49.2%), followed by respiratory tract infections (24.2%).

Table 1. Baseline characteristics of recruited children.

Hospital Health center Total
N = 601 N = 2,342 N = 2,943
n (%) n (%) n (%)
Age
    <2 months 8 (1.3) 27 (1.2) 35 (1.2)
    2–11 months 102 (17.0) 371 (15.8) 473 (16.1)
    12–59 months 320 (53.2) 999 (42.7) 1,319 (44.8)
    5–12 years 171 (28.5) 945 (40.4) 1,116 (37.9)
Sex
    Male 292 (48.6) 1,136 (48.5) 1,428 (48.5)
    Female 309 (51.4) 1,206 (51.5) 1,515 (51.5)
Socio-economic factors
-   Education of mother
    No formal education 14 (2.3) 185 (7.9) 199 (6.8)
    Primary 357 (59.4) 1,752 (74.8) 2,109 (71.7)
    Secondary/further 226 (37.6) 400 (17.1) 626 (21.3)
    Missing 4 (0.7) 5 (0.2) 9 (0.3)
-   Mother’s marital status
    Married 541 (90.0) 2,076 (88.6) 2,617 (88.9)
    Never married 22 (3.7) 41 (1.8) 63 (2.1)
    Divorced/separated 28 (4.7) 206 (8.8) 234 (8.0)
    Widowed 10 (1.7) 17 (0.7) 27 (0.9)
    Missing 0 (0) 2 (0.1) 2 (0.1)
Nutritional status (WAZ and clinical)
    Well nourished 524 (87.2) 1,147 (49.0) 1.671 (56.8)
    Moderately malnourished 37 (6.2) 117 (5.0) 154 (5.2)
    Severely malnourished 24 (4.0) 145 (6.2) 169 (5.7)
    Missing 16 (2.7) 933 (40.0) 949 (32.3)
Diagnoses *
    Non-infectious 85 (14.1) 312 (13.3) 397 (13.5)
-   Infections
    Gastroenteritis 36 (6.0) 152 (6.5) 188 (6.4)
    Malaria 315 (52.4) 1,132 (48.3) 1,447 (49.2)
    Non-pneumonia respiratory tract infection 117 (19.5) 595 (25.4) 712 (24.2)
    Pneumonia 9 (1.5) 23 (1.0) 32 (1.1)
    Sepsis 60 (10.0) 185 (7.9) 245 (8.3)
    Other infection 33 (5.5) 325 (13.9) 358 (12.2)
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* Children may have more than one diagnosis and therefore the total number of diagnoses exceeds the total number of children.

Blood glucose assessment

Blood glucose was recorded in 99.1% of children (2,917/2,943; 1 child was too agitated, 3 caregivers refused assessment and in 22 cases there was a lack of test strips). The median blood glucose concentration was 5.3 mmol/l (IQR 4.5–6.0). Table 2 presents the characteristics of patients, depending on the level of the blood glucose concentration. The prevalence of severe hypoglycemia (<2.5 mmol/l) was 0.1% (95% CI 0.03–0.27) and moderate hypoglycemia (2.5–4.0 mmol/l) 11.1% (95% CI 9.9–12.2). All the children with severe hypoglycemia and 34.7% with moderate hypoglycemia (n = 112) presented with at least one IMCI danger sign with lethargy and inability to drink being more common among the severely/moderately hypoglycemic than in the normoglycemic group (p<0.01 for both). The most common diagnosis for both severely and moderately hypoglycemic children was malaria (75% and 51.4%, respectively). Of the children classified as severely malnourished, 1.8% (3/169) had a blood glucose concentration <3.0mmol/l and 11.2% (19/169) had a blood glucose of 3.0–4.0mmol/l.

Table 2. Prevalence of different blood glucose concentrations by background and clinical characteristics.

Severe Hypoglycemia <2.5 mmol/l Moderate hypoglycemia 2.5–4.0 mmol/l Normoglycemia 4.1–11.0 mmol/l Hyperglycemia >11 mmol/l Total
N = 4 N = 323 N = 2,579 N = 11 N = 2,917
n (%) n (%) n (%) n (%) n (%)
Age
    <2 month 1 (25.0) 3 (0.9) 29 (1.1) 1 (9.1) 34 (1.2)
    2–11 months 0 (0.0) 29 (9.0) 439 (17.0) 0 (0.0) 468 (16.0)
    12–59 months 2 (50.0) 143 (44.3) 1,150 (44.6) 9 (81.8) 1,304 (44.7)
    5–12 years 1 (25.0) 148 (45.8) 961 (37.3) 1 (9.1) 1,111 (38.1)
Sex
    Male 2 (50.0) 140 (43.3) 1,276 (49.5) 3 (27.3) 1,421 (48.7)
    Female 2 (50.0) 183 (56.7) 1,303 (50.5) 8 (72.7) 1,496 (51.3)
Facility type
    Hospital 0 (0.0) 44 (13.6) 555 (21.5) 2 (18.2) 601 (20.6)
    Health center 4 (100.0) 279 (86.4) 2,024 (78.5) 9 (81.8) 2,316 (79.4)
Nutritional status (WAZ and clinical)
    Well nourished 2 (50.0) 179 (55.4) 1,481 (57.4) 7 (63.6) 1,669 (57.2)
    Moderate malnourished 0 (0.0) 24 (7.4) 130 (5.0) 0 (0.0) 154 (5.3)
    Severely malnourished 0 (0.0) 22 (6.8) 144 (5.6) 3 (27.3) 169 (5.7)
    Missing 2 (50.0) 98 (30.3) 824 (32.0) 1 (9.1) 925 (31.7)
Any IMCI danger sign * 4 (100.0) 112 (34.7) 725 (28.1) 5 (45.5) 846 (29.0)
    Unable to drink/feed 2 (50.0) 59 (18.3) 317 (12.3) 0 (0.0) 378 (13.0)
    Vomits everything 1 (25.0) 39 (12.1) 381 (14.8) 1 (9.1) 422 (14.5)
    Convulsions 0 (0.0) 1 (0.3) 16 (0.6) 0 (0.0) 17 (0.6)
    Unconscious 0 (0.0) 5 (1.6) 36 (1.4) 0 (0.0) 41 (1.4)
    Sleepy/lethargic 2 (50.0) 61 (18.9) 331 (12.8) 4 (36.4) 398 (13.6)
Clinical signs/test
    Chest indrawing 0 (0.0) 2 (0.7) 32 (1.2) 1 (9.1) 35 (1.2)
    Temperature = >37.5°C ** 1 (25.0) 98 (30.3) 784 (30.4) 7 (63.6) 890 (30.5)
    Malaria RDT positive 3 (75.0) 175 (54.2) 1,245 (48.3) 6 (54.6) 1,429 (49.0)
Diagnoses by clinician ***
    Non-infectious 0 (0.0) 35 (10.8) 356 (13.8) 1 (9.1) 392 (13.4)
-   Infections
    Gastroenteritis 0 (0.0) 25 (7.7) 162 (6.3) 0 (0.0) 187 (6.4)
    Malaria 3 (75.0) 166 (51.4) 1,260 (48.8) 4 (36.4) 1,433 (49.1)
    Non-pneumonia respiratory tract infection 0 (0.0) 86 (26.6) 619 (24.0) 4 (36.4) 709 (24.3)
    Pneumonia 0 (0.0) 3 (0.9) 27 (1.1) 0 (0.0) 30 (1.0)
    Sepsis 0 (0.0) 19 (5.9) 223 (8.7) 1 (9.1) 243 (8.3)
    Other infections**** 1 (25.0) 64 (19.8) 290 (11.2) 3 (27.3) 358 (12.2)
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* The same child could have more than one danger sign.

** 2,298 children had a temperature taken. 2,295 had temperature and glucose result.

*** The same child could have more than one diagnosis.

**** 1 child with hypoglycemia was diagnosed with fever of unknown cause and included in “other infections”.

Oxygen saturation measurement

Table 3 demonstrates the patient characteristics depending on their oxygen saturation. Three patients lacked SpO2-results due to caregiver refusal, and 306 suspected error measurements were excluded, giving a total of 2,634 (89.5%) children with a SpO2-result. Of these, a stable SpO2 curve was not achieved in 4.7% (n = 124) cases, and these are reported separately. An unstable curve was more common in children <12 months compared to older children (8.4% vs 4.0%, p<0.01).

Table 3. Prevalence of oxygen saturation levels depending on background and clinical characteristics.

Unstable curve Severe Hypoxemia <90% Moderate hypoxemia 90–93% Normal 94–100% Total
N = 124 N = 17 N = 142 N = 2,351 N = 2,634
n (%) n (%) n (%) n (%) n (%)
Age
    <2month 4 (3.2) 0 (0.0) 7 (4.9) 16 (0.7) 27 (1.0)
    2–11 months 32 (25.8) 1 (5.9) 41 (28.9) 334 (14.2) 408 (15.5)
    12–59 months 71 (57.3) 10 (58.8) 70 (49.3) 1,029 (43.8) 1,180 (44.8)
    5–12 years 17 (13.7) 6 (35.3) 24 (16.9) 972 (41.3) 1,019 (38.7)
Sex
    Male 64 (51.6) 10 (58.8) 75 (52.8) 1,138 (48.4) 1,287 (48.9)
    Female 60 (48.4) 7 (41.2) 67 (47.2) 1,213 (51.6) 1,347 (51.1)
Facility type
    Hospital 10 (8.1) 4 (23.5) 65 (45.8) 522 (22.2) 601 (22.8)
    Health center 114 (91.9) 13 (76.5) 77 (54.2) 1,829 (77.8) 2,033 (77.2)
Nutritional status (WAZ and clinical)
    Well nourished 38 (30.7) 11 (64.7) 107 (75.4) 1,316 (56.0) 1,472 (55.9)
    Moderate malnourished 4 (3.2) 2 (11.8) 6 (4.2) 118 (5.0) 130 (4.9)
    Severely malnourished 1 (0.8) 0 (0.0) 7 (4.9) 132 (5.6) 140 (5.3)
    Missing 81 (65.3) 4 (23.5) 22 (15.5) 785 (33.4) 892 (34.9)
Any IMCI danger sign 20 (16.1) 4 (23.5) 45 (31.7) 685 (29.1) 754 (28.6)
    Unable to drink/breastfeed 10 (8.1) 1 (5.9) 23 (16.2) 272 (11.6) 306 (11.6)
    Vomits everything 14 (11.3) 2 (11.8) 21 (14.8) 340 (14.5) 377 (14.3)
    Convulsions 0 (0.0) 0 (0.0) 3 (2.1) 14 (0.6) 17 (0.7)
    Unconscious 3 (2.4) 1 (5.9) 3 (2.1) 22 (0.9) 29 (1.1)
    Sleepy/lethargic 10 (8.1) 1 (5.9) 26 (18.3) 354 (15.1) 391 (14.8)
Clinical signs/test
    Chest indrawing 2 (1.6) 0 (0.0) 5 (3.5) 22 (0.9) 29 (1.1)
    Tachypnea for age (IMCI)* 1 (0.8) 1 (5.9) 1 (0.7) 47 (2.0) 50 (1.9)
    Temperature = >37.5°C ** 30 (24.2) 5 (29.4) 65 (45.8) 718 (30.5) 818 (31.1)
    Malaria RDT positive 46 (37.1) 10 (58.8) 62 (43.7) 1,218 (51.8) 1,336 (50.7)
Diagnoses by clinician ***
    Non-infectious 13 (10.5) 2 (11.8) 16 (11.3) 290 (12.3) 321 (12.2)
-   Infections
    Gastroenteritis 10 (8.1) 3 (17.7) 9 (6.3) 133 (5.7) 155 (5.9)
    Malaria 47 (37.9) 10 (58.8) 61 (43.0) 1,240 (52.7) 1,358 (51.6)
    Non-pneumonia respiratory tract infection 48 (38.7) 4 (23.5) 40 (28.2) 549 (23.4) 641 (24.3)
    Pneumonia 3 (2.4) 0 (0.0) 5 (3.5) 24 (1.0) 32 (1.2)
    Sepsis 11 (8.9) 0 (0.0) 16 (11.3) 214 (9.1) 241 (9.2)
    Other infections 11 (8.9) 2 (11.8) 9 (6.3) 248 (10.6) 270 (10.3)
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* Tachypnea defined as RR >60 for children <2 month, >50 2–12 months, >40 12–60 months, <30 >60 months according to IMCI guidelines. RR assessed in 263 out of the 2,634 children included in SpO2 measurement.

** Temperature was measured in 2,024 out of the 2634 tested for blood glucose.

*** The same child could have more than one diagnosis.

The median SpO2 was 97% (IQR 96–98%). The prevalence of severe hypoxemia (SpO2 <90%) was 0.6% (95% CI 0.3–0.9) and moderate hypoxemia was present in 5.4% (95% CI 4.6–6.3) of children. None of the children with hypoxemia had recorded chest indrawing, and only one had been assessed with tachypnea. Malaria was the most common diagnosis among severely hypoxemic children (58.8%), while no child with hypoxemia had been diagnosed by the routine healthcare worker as having pneumonia. The sensitivity analysis with the excluded SpO2 results did not show any difference in the presence of danger sign among the severely and moderately hypoxemic patients (S1 Table).

General danger signs

Table 4 presents the clinical characteristics of the children, according to the presence of IMCI danger signs. There was no significant difference between children aged <5 years and children aged 5–12 years in terms of presence of any IMCI danger sign (p = 0.072). Of all children presenting with a danger sign, 512 children had only one danger sign and 336 had two or more. At least one of the IMCI danger signs was present in 28.8% (95%CI 27.2–30.5) of children. If including chest indrawing as an indicator for referral, the proportion increased to 29.3% (n = 861), with chest indrawing documented in only 35/2,943 children. The prevalence of high temperature and chest indrawing was more common in the group with danger signs than in those without any danger sign (p<0.001 for both).

Table 4. Clinical characteristics by presence of any IMCI danger sign.

IMCI general danger sign present IMCI general danger sign not present P-value
N = 848 N = 2,095
n (%) n (%)
Age
    <2month 4 (0.5) 31 (1.5) p<0.001
    2–11 months 93 (11.0) 380 (18.1)
    12–59 months 408 (48.1) 911 (43.5)
    5–12 years 343 (40.5) 773 (36.9)
Temperature *
    Low <36.5°C 180 (21.2) 460 (22.0) p<0.001
    Normal 36.5°C– 37.4°C 215 (25.4) 551 (26.3)
    High = >37.5°C 360 (42.5) 532 (25.4)
    Missing 93 (11.0) 552 (26.4)
Respiratory signs
    Tachypnea for age** 38 (4.5) 63 (3.0) p = 0.088
    RR not done/error 718 (84.7) 1,826 (87.2)
    Chest indrawing 22 (2.6) 13 (0.6) p <0.001
Oxygen saturation (%)
    Normal SpO2 (94–100) 685 (80.8) 1,666 (79.5) p = 0.018
    Moderate hypoxemia (90–93) 45 (5.3) 97 (4.6)
    Severe Hypoxemia (<90) 4 (0.5) 13 (0.6)
    Unable to obtain stable SpO2 wave 20 (2.4) 104 (5.0)
    Excluded SpO2-results*** 94 (11.1) 215 (10.3)
Blood glucose concentration (mmol/l)
    Severe Hypoglycemia (<2.5) 4 (0.5) 0 (0.0) p<0.001
    Moderate hypoglycemia (2.5–4.0) 112 (13.2) 211 (10.1)
    Normal b-glucose (4.1–11) 725 (85.5) 1,854 (88.5)
    Hyperglycemia (>11) 5 (0.6) 6 (0.3)
    No blood glucose result**** 2 (0.2) 24 (1.2)
Nutritional status
    Well nourished 459 (54.1) 1,212 (57.9) p<0.001
    Moderately malnourished 60 (7.1) 94 (4.5)
    Severely malnourished 70 (8.3) 99 (4.7)
    Missing 259 (30.1) 690 (32.9)
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*Temperature was assessed in 2,298.

** Respiratory rate was assessed in 399 children.

*** 306 excluded (every assessment from two research assistants with frequent unexpected results). 3 missing due to refusal by caregiver.

**** No result due to refusal by caregiver (3), lack of test strips (22) and 1 child too agitated.

The group of children presenting with at least one danger sign included all severely hypoglycemic children and 34.7% with moderate hypoglycemia. Only 23.5% of children with severe hypoxemia and 31.7% of children with moderate hypoxemia had a danger sign. Of all children with severe or moderate hypoxemia (n = 159), there was no significant difference in the presence of a danger sign between children below 5 years of age (29.5%) and children aged 5–12 years (36.7%, p = 0.441). Similarly, there was no significant difference between age groups in the presence of danger signs among children with severe or moderate hypoglycemia (n = 327), 33.2% for 0–5 years vs 38.3% for 5–12 years, p = 0.0336). The prevalence of danger signs was significantly higher among mRDT positive children (40.6%) compared to children diagnosed with scabies (2.9%) (p<0.001). Notably, we observed a huge variation in the proportions of children with severe hypoxemia and IMCI danger signs between facilities. The proportions of children with danger signs ranged between facilities from 4.1–66.0% (median 18.8%). Severe hypoxemia was reported in 0–3.7% of patients (median 0.3%)–excluding the two research assistants with suspected invalid results (reporting 15.2% and 32.5% hypoxemia, respectively) and moderate hypoxemia 0–26.9% (median 2.5%) (S1 Fig).

Temporal trends

Fig 1 demonstrates the seasonality of reported infectious diagnoses over the study period, and Fig 2 presents the seasonality of reported infectious versus non-infectious illness along with the prevalence of IMCI danger signs, low oxygen saturation and low blood glucose concentrations. While there is a clear seasonality in infectious disease presentations, with one peak almost exclusively caused by malaria, the prevalence of danger signs, hypoglycemia and hypoxemia are relatively stable throughout the year.

Fig 1. Seasonality of different infections by week.

Fig 1

Open in a new tab

Fig 2. Seasonality of infectious disease, non-infectious disease, IMCI danger signs, SpO2 <94% and blood glucose <4.0mmol/l.

Fig 2

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Discussion

This study assessed the prevalence of low oxygen saturation and low blood glucose concentrations among children seeking outpatient care in Malawi. Our results demonstrate an overall low prevalence of WHO defined hypoglycemia and hypoxemia amongst a general pediatric outpatient population. Yet, moderate hypoglycemia and hypoxemia were more common (11.1% and 5.4%, respectively). More than a quarter of the included children presented with any IMCI danger sign. The presence of a danger sign identified all children with severe hypoglycemia, but only 23.5% of children with severe hypoxemia. The variance in proportions of hypoxemia and IMCI danger signs between facilities suggests issues in the accuracy of assessments.

There is a lack of data on the prevalence of hypoxemia in undifferentiated populations of sick children presenting to primary health care facilities in low-income countries, with earlier studies focusing on hypoxemia prevalence in children admitted to hospital, or in children diagnosed with pneumonia [23]. A minority of children in our study were diagnosed with pneumonia, despite acute respiratory tract infections being commonly diagnosed. Notably, none of the children diagnosed with pneumonia were severely hypoxemic and only 15.6% had moderate hypoxemia. When combined, the hypoxemia prevalence among pneumonia and non-pneumonia respiratory tract infection did not differ from the overall study population. Unsurprisingly, the hypoxemia prevalence was much lower in this outpatient population than in studies on hypoxemia in children in hospital settings, where prevalences of 5.3–14.1% have been reported [23–25].

WHO defined hypoglycemia (<2.5mmol/l) was rare in this population, with only four patients affected. Nonetheless, a substantially higher prevalence of moderate hypoglycemia (11.1%) was found. The WHO definition of hypoglycemia as a blood glucose concentration of <2.5mmol/l is a topic of debate, following a number of studies showing that sick children with blood glucose concentrations above 2.5mmol/l and with a variable upper limit of as high as 5.0mmol/l, also suffer an increased risk of mortality compared to children with higher blood glucose concentrations [11, 15, 16]. While there is an absence of comparable data from primary care facilities, severely sick children with moderate hypoglycemia are likely to benefit from a higher level of monitoring [26] and it can be hypothesized that referral of children with moderate hypoglycemia could contribute to reduced mortality.

All children with severe hypoglycemia presented with an IMCI danger sign, in line with a study from Laos in which 93.3% of admitted children with hypoglycemia also presented with any IMCI general danger sign [27]. The danger signs lethargy and inability to drink/feed were more common among children with low blood glucose concentrations. However, the specificity of any general danger sign for detecting hypoglycemia was low since severe hypoglycemia affected only four children but a general danger sign was present in almost 29% (n = 848). Two thirds of the moderately hypoglycemic children had no danger sign, so consequently were not likely to be referred. Glucose testing at frontline facilities has the potential to identify the children with moderate hypoglycemia without danger signs, who may still benefit from referral for observation and/or treatment.

In contrast to hypoglycemia, our findings correspond with previous research showing that IMCI danger signs inadequately identify severely hypoxemic children in outpatient settings [14, 28].Chest indrawing has been suggested as the single best predictor of hypoxemia in children with pneumonia but still with only 69% sensitivity and 82% specificity [29]. In this real-world context, the presence of chest indrawing was not commonly reported by health workers and did not improve the identification of hypoxemic children. This likely reflects sub-optimal guidelines implementation and poor quality of respiratory clinical examination [30], but is reflective of routine care and subsequent case management. These data reinforce the need for pulse oximetry for the detection of hypoxemia, in a general population of acutely sick children [31]. A recently published data-linkage study found that pulse oximetry at outpatient facilities identified fatal pneumonia cases that would not have been referred using WHO referral guidelines only [32].

Considering the increased mortality risk among children with moderate hypoxemia and hypoglycemia it is possible that early identification and hospital referral of these children could prevent progression to severe hypoglycemia/hypoxemia and reduce mortality. However, the potential benefits need to be weighed against the risk of adding patients to already over-burdened hospitals and the costs for individual families implied by potential unnecessary referrals. Therefore, issues related to the quality of assessment are of high relevance for future guideline considerations. Despite training and close supervision, we chose to exclude results from two out of 20 research assistants due to unrealistically high proportions of hypoxemia. Known challenges in achieving reliable measurements with pulse oximetry include motion artifacts, poor perfusion, irregular heart rhythm, skin pigmentation, probe positioning and presence of abnormal hemoglobin molecules [33–36]. We also noted a higher proportion of unstable curves among younger children in this study. Considering that it may be more challenging to achieve a stable curve in a severely sick child, a failed SpO2 measurement has been suggested as a referral criteria [14]; but it is also important to consider the potential for false positives leading to unnecessary referrals if quality cannot be maintained.

The prevalence of IMCI danger signs was similar between age groups, and no difference was seen between children under 5 and children aged 5–12 in the presence hypoxemia or hypoglycemia, suggesting that IMCI danger signs may be applied even in older children. The overall prevalence of danger signs was high and raised concerns for over-classifications by health workers. However, the significant difference in IMCI danger signs prevalence among children with scabies and those with a positive malaria RDT indicates that danger signs are assigned to “the right patients”, which is also supported by previous findings [37]. There was a clear seasonality in cause of presentation, with a defined malaria peak during the rainy season (January–March), as would be expected. The peak of mixed infections seen during the southern hemisphere winter is also in line with expected respiratory pathogen transmission, although suggestive of misdiagnosis of pneumonia as malaria [38, 39]. However, the prevalence of danger signs, as well as hypoxemia and hypoglycemia were relatively stable throughout the year, and is surprising given the wide variation in patient loads observed in the hospital during the year.

Adherence to other aspects of the IMCI assessment however showed poor performance, such as the lack of respiratory rate recorded for children with reported cough and almost a third lacking recorded nutritional status. This is in line with previous studies from Sub-Saharan Africa, in which a correct classification/diagnosis was achieved by health workers’ assessments in around 40% of the children [30, 40, 41].

We had four key limitations, first that this district wide study relied primarily on capturing data from standard assessments of sick children, which may result in inter-center variability due to differences in staff performance. We chose to use this approach to get a picture of routine rather than optimized guideline use, but data quality concerns were seen. Secondly, in the absence of validated danger signs for children aged 5–12 years we applied the same danger signs as for children under 5 years. Thirdly, the lack of outcome and follow-up data is a limitation since no conclusion can be drawn on the risks of different levels of oxygen saturation or glucose concentration. Finally, the research assistants were non-clinical staff and while they received training, supervision and follow-up, it was apparent that there were still issues in some of the oximetry assessments. This raises an important point when designing programs for oximetry scale-up in primary care, and the need for on-going mentorship.

Conclusion

The prevalence of hypoxemia and hypoglycemia at primary care level are low, but moderate levels are not uncommon and could potentially be useful as an added tool to determine referral needs. IMCI danger signs were present in children with hypoglycemia, but not in the majority with severe or moderate hypoxemia. This highlights the difficulties in diagnosing hypoxemia through clinical presentation only, especially in a setting where lack of training, equipment and time is common. Future studies should focus on the role of moderate hypoxemia and hypoglycemia in subsequent outcomes, and optimized case management for these children.

Supporting information

S1 Table. IMCI general danger signs (unconscious, sleepy/lethargic, convulsing, vomits everything, unable to eat/drink) depending on clinical characteristics.

SpO2 results excluded from manuscript included. * Respiratory rate was assessed in 399 children. ** 3 caregiver refused SpO2-meassurment. *** No result due to refusal by caregiver (3), lack of test strips (22) and child too agitated (1).

(DOCX)

Click here for additional data file. (15KB, docx)
S1 Fig. Prevalence of low SpO2-results (<90%, 91–93%) and IMCI danger signs depending on health center (HC) and hospitals (H).

*The results of SpO2 from HC 2 and HC 9 were excluded from the analysis.

(TIF)

Click here for additional data file. (384.2KB, tif)

Acknowledgments

We would like to thank all the children and their parents who participated in this study, and the healthcare workers who supported our research assistant teams in their work. We are also grateful to the research assistants for their hard work, and the Mchinji District Health Management Team for their input and support.

Data Availability

Unidentified data has been uploaded to the public repository Dataverse and can be accessed here: https://doi.org/10.7910/DVN/0YWX8J.

Funding Statement

The study was funded by grants from the Vetenskapsrådet SE (2017-05579) HH, Laerdal Foundation (40348) HH and the Einhorn Family Foundation HH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

References

  • 1.United Nations Inter-agency Group for Child Mortality Estimation (UNIGME). Levels & Trends in Child Mortality: Report 2020, Estimates developed by the United Nations Inter-agency Group for Child Mortality Estimation. New York: United Nations Children’s Fund, 2020. [Google Scholar]
  • 2.Jacobs M, Merson M. Introductory commentary: a strategic review of options for building on lessons learnt from IMCI and iCCM. Bmj. 2018:bmj.k3013. doi: 10.1136/bmj.k3013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.World Health Organisation. Integrated Management of Childhood Illness. Chart Booklet. Geneva: 2014.
  • 4.World Health Organisation. Integrated Management of Childhood Illness Global Survey Report. Geneva: 2017 978-92-4-151298-5.
  • 5.Boschi-Pinto C, Labadie G, Dilip TR, Oliphant N, Dalglish SL, Aboubaker S, et al. Global implementation survey of Integrated Management of Childhood Illness (IMCI): 20 years on. BMJ Open. 2018;8(7):e019079. doi: 10.1136/bmjopen-2017-019079 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Johansson EW, Lindsjö C, Weiss DJ, Nsona H, Selling KE, Lufesi N, et al. Accessibility of basic paediatric emergency care in Malawi: analysis of a national facility census. BMC Public Health. 2020;20(1):992. Epub 2020/06/26. doi: 10.1186/s12889-020-09043-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Krüger C, Heinzel-Gutenbrunner M, Ali M. Adherence to the integrated management of childhood illness guidelines in Namibia, Kenya, Tanzania and Uganda: evidence from the national service provision assessment surveys. BMC Health Services Research. 2017;17(1):822. doi: 10.1186/s12913-017-2781-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Rahimi A, Kassam R, Dang Z, Sekiwunga R. Challenges with accessing health care for young children presumed to have malaria in the rural district of Butaleja, Uganda: a qualitative study. Pharmacy Practice. 2019;17(4):1622. doi: 10.18549/PharmPract.2019.4.1622 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Peterson S, Nsungwa-Sabiiti J, Were W, Nsabagasani X, Magumba G, Nambooze J, et al. Coping with paediatric referral—Ugandan parents’ experience. The Lancet. 2004;363(9425):1955–6. doi: 10.1016/S0140-6736(04)16411-8 [DOI] [PubMed] [Google Scholar]
  • 10.King C, Banda M, Bar-Zeev N, Beard J, French N, Makwenda C, et al. Care-seeking patterns amongst suspected paediatric pneumonia deaths in rural Malawi. Gates Open Research. 2020;4:178. doi: 10.12688/gatesopenres.13208.2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Ngwalangwa F, Phiri CHA, Dube Q, Langton J, Hildenwall H, Baker T. Risk Factors for Mortality in Severely Ill Children Admitted to a Tertiary Referral Hospital in Malawi. The American Journal of Tropical Medicine and Hygiene. 2019;101(3):670–5. doi: 10.4269/ajtmh.19-0127 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Bhutta ZA, Lazzerini M, Sonego M, Pellegrin MC. Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis. Plos One. 2015;10(9):e0136166. doi: 10.1371/journal.pone.0136166 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Madrid L, Sitoe A, Varo R, Nhampossa T, Lanaspa M, Nhama A, et al. Continuous determination of blood glucose in children admitted with malaria in a rural hospital in Mozambique. Malaria Journal. 2017;16(1):184. doi: 10.1186/s12936-017-1840-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.McCollum ED, King C, Deula R, Zadutsa B, Mankhambo L, Nambiar B, et al. Pulse oximetry for children with pneumonia treated as outpatients in rural Malawi. Bulletin of the World Health Organization. 2016;94(12):893–902. doi: 10.2471/BLT.16.173401 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Nadjm B, Mtove G, Amos B, Hildenwall H, Najjuka A, Mtei F, et al. Blood Glucose as a Predictor of Mortality in Children Admitted to the Hospital with Febrile Illness in Tanzania. The American Journal of Tropical Medicine and Hygiene. 2013;89(2):232–7. doi: 10.4269/ajtmh.13-0016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Achoki R, Opiyo N, English M. Mini-review: Management of hypoglycaemia in children aged 0–59 months. J Trop Pediatr. 2010;56(4):227–34. Epub doi: 10.1093/tropej/fmp109 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Faustino EV, Bogue CW. Relationship between hypoglycemia and mortality in critically ill children. Pediatr Crit Care Med. 2010;11(6):690–8. doi: 10.1097/PCC.0b013e3181e8f502 [DOI] [PubMed] [Google Scholar]
  • 18.Hooli S, King C, Zadutsa B, Nambiar B, Makwenda C, Masache G, et al. The Epidemiology of Hypoxemic Pneumonia among Young Infants in Malawi. The American Journal of Tropical Medicine and Hygiene. 2020;102(3):676–83. doi: 10.4269/ajtmh.19-0516 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Ammann RA, Blanc J, Locatelli I, Rarau P, Mueller I, Genton B, et al. Retrospective study on the usefulness of pulse oximetry for the identification of young children with severe illnesses and severe pneumonia in a rural outpatient clinic of Papua New Guinea. Plos One. 2019;14(4):e0213937. doi: 10.1371/journal.pone.0213937 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.National Statistical Office. 2018 Malawi Population and Housing Census Main Report. In: National Statistical Office, editor.: Government of Malawi; 2019. [Google Scholar]
  • 21.National Statistical Office/Malawi ICF. Malawi Demographic and Health Survey 2015–16. Zomba, Malawi: National Statistical Office and ICF, 2017. [Google Scholar]
  • 22.Kanyuka M, Ndawala J, Mleme T, Chisesa L, Makwemba M, Amouzou A, et al. Malawi and Millennium Development Goal 4: a Countdown to 2015 country case study. The Lancet Global Health. 2016;4(3):e201–e14. doi: 10.1016/S2214-109X(15)00294-6 [DOI] [PubMed] [Google Scholar]
  • 23.Graham H, Bakare AA, Ayede AI, Oyewole OB, Gray A, Peel D, et al. Hypoxaemia in hospitalised children and neonates: A prospective cohort study in Nigerian secondary-level hospitals. EClinicalMedicine. 2019;16:51–63. doi: 10.1016/j.eclinm.2019.10.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.McCollum ED, Bjornstad E, Preidis GA, Hosseinipour MC, Lufesi N. Multicenter study of hypoxemia prevalence and quality of oxygen treatment for hospitalized Malawian children. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2013;107(5):285–92. doi: 10.1093/trstmh/trt017 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Mwaniki M. Emergency triage assessment for hypoxaemia in neonates and young children in a Kenyan hospital: an observational study. Bulletin of the World Health Organization. 2009;87(4):263–70. doi: 10.2471/blt.07.049148 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Oxner A, Vellanki M, Myers A, Bangura F, Bangura S, Koroma AM, et al. Reducing mortality from severe malaria in Sierra Leonean children by applying the World Health Organization’s standard malarial protocol with additional sublingual glucose: A continuous quality improvement report. International Journal of Infectious Diseases. 2020;96:61–7. doi: 10.1016/j.ijid.2020.04.046 [DOI] [PubMed] [Google Scholar]
  • 27.Folli F, Barennes H, Sayavong E, Pussard E. High Mortality Risk in Hypoglycemic and Dysglycemic Children Admitted at a Referral Hospital in a Non Malaria Tropical Setting of a Low Income Country. Plos One. 2016;11(2):e0150076. doi: 10.1371/journal.pone.0150076 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Zhang L, Mendoza-Sassi R, Santos JC, Lau J. Accuracy of symptoms and signs in predicting hypoxaemia among young children with acute respiratory infection: a meta-analysis. Int J Tuberc Lung Dis. 2011;15(3):317–25. [PubMed] [Google Scholar]
  • 29.Basnet S, Adhikari Kant R, Gurung Kumar C. Hypoxemia in children with pneumonia and its clinical predictors. Indian Journal of Pediatrics. 2006;73(9):777–81. doi: 10.1007/BF02790384 [DOI] [PubMed] [Google Scholar]
  • 30.Ho J, Horwood C, Vermaak K, Rollins N, Haskins L, Nkosi P, et al. An Evaluation of the Quality of IMCI Assessments among IMCI Trained Health Workers in South Africa. PLoS ONE. 2009;4(6):e5937. doi: 10.1371/journal.pone.0005937 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Ayieko P. In Children Aged 2–59 months with Pneumonia, Which Clinical Signs Best Predict Hypoxaemia? Journal of Tropical Pediatrics. 2006;52(5):307–10. doi: 10.1093/tropej/fml036 [DOI] [PubMed] [Google Scholar]
  • 32.Bassat Q, Colbourn T, King C, Beard J, Phiri T, Mdala M, et al. Predictive value of pulse oximetry for mortality in infants and children presenting to primary care with clinical pneumonia in rural Malawi: A data linkage study. PLOS Medicine. 2020;17(10):e1003300. doi: 10.1371/journal.pmed.1003300 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Fouzas S, Priftis KN, Anthracopoulos MB. Pulse Oximetry in Pediatric Practice. Pediatrics. 2011;128(4):740–52. doi: 10.1542/peds.2011-0271 [DOI] [PubMed] [Google Scholar]
  • 34.Sjoding MW, Dickson RP, Iwashyna TJ, Gay SE, Valley TS. Racial Bias in Pulse Oximetry Measurement. New England Journal of Medicine. 2020;383(25):2477–8. doi: 10.1056/NEJMc2029240 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Baker K, Ward C, Maurel A, de Cola MA, Smith H, Getachew D, et al. Usability and acceptability of a multimodal respiratory rate and pulse oximeter device in case management of children with symptoms of pneumonia: A cross‐sectional study in Ethiopia. Acta Paediatrica. 2020;110(5):1620–32. doi: 10.1111/apa.15682 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.King C, Boyd N, Walker I, Zadutsa B, Baqui AH, Ahmed S, et al. Opportunities and barriers in paediatric pulse oximetry for pneumonia in low-resource clinical settings: a qualitative evaluation from Malawi and Bangladesh. BMJ Open. 2018;8(1):e019177. doi: 10.1136/bmjopen-2017-019177 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Warburton D, Kalu N, Lufesi N, Havens D, Mortimer K. Implementation of World Health Organization Integrated Management of Childhood Illnesses (IMCI) Guidelines for the Assessment of Pneumonia in the Under 5s in Rural Malawi. Plos One. 2016;11(5):e0155830. doi: 10.1371/journal.pone.0155830 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Graham H, Bakare AA, Ayede AI, Oyewole OB, Gray A, Neal E, et al. Diagnosis of pneumonia and malaria in Nigerian hospitals: A prospective cohort study. Pediatric Pulmonology. 2020;55(S1). doi: 10.1002/ppul.24691 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Källander K, Nsungwa-Sabiiti J, Peterson S. Symptom overlap for malaria and pneumonia—policy implications for home management strategies. Acta Tropica. 2004;90(2):211–4. doi: 10.1016/j.actatropica.2003.11.013 [DOI] [PubMed] [Google Scholar]
  • 40.Pariyo GW, Gouws E, Bryce J, Burnham G. Improving facility-based care for sick children in Uganda: training is not enough. Health Policy and Planning. 2005;20(suppl_1):i58–i68. doi: 10.1093/heapol/czi051 [DOI] [PubMed] [Google Scholar]
  • 41.Bjornstad E, Preidis GA, Lufesi N, Olson D, Kamthunzi P, Hosseinipour MC, et al. Determining the quality of IMCI pneumonia care in Malawian children. Paediatrics and International Child Health. 2013;34(1):29–36. doi: 10.1179/2046905513Y.0000000070 [DOI] [PMC free article] [PubMed] [Google Scholar]
PLOS Glob Public Health. doi: 10.1371/journal.pgph.0000284.r001

Decision Letter 0

Claire E von Mollendorf, Julia Robinson

18 Nov 2021

PGPH-D-21-00696

Hypoxemia, hypoglycemia and IMCI danger signs in pediatric outpatients in Malawi

PLOS Global Public Health

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Reviewer #1: REVIEWER COMMENTS

Abstract

1. Line 26: include the word “of” after “prevalence”

2. Line 32: may be you can call them research assistants instead of data collectors

3. Line 33 and 34: include in brackets the manufacturers of the respective equipment that was used ie Lifebox LB-01 pulse oximeter and AccuCheck Aviva glucometers

4. Line 35 and 36: the author mentions severe and moderate hypoxemia and hypoglycaemia and then gives respective ranges. It is best to dissociate the moderate from severe hypoxemia or hypoglycaemia to make more clarity in the sentence

5. Conclusions: I am not sure whether the analysis is robust enough to draw these conclusions.

6. The authors say that they run a chi2 test… but the outcome(s) of the study are not clear.

Introduction: main text

7. Line 60 – 62: It would be better to link the success of the IMCI program to most recent targets like the SDGs instead of the long gone MDGs

8. The objective of the study is not quite clear.

9. It would have been great to classify the IMCI in terms of the illnesses

10. Materials and methods: it would be great to describe the Emergency paediatric treatment and referral in Malawi in frontline healthcare settings – EREMISS study)study in which the current research study is nested. If the paper for this study is published then give reference to the paper. When was the EREMISS study conducted? Was the EREMISS study conducted concurrently with the study under review? What kind of participants were recruited? What was the eligibility criteria? How long was the parent study?

11. Study setting: It is important to describe the different types of study sites involved in the study.. do the patients pay for the services provided? What is the structure of the healthcare setting in Malawi? How do the different study sites fit in with in the health system structure of Malawi? What kinds of patients seek health care at the different study sites in general? Do these patients pay for the services offered? What is the difference between “health centre” and “hospital”? this distinction can be described earlier on in the text so that the reader can understand the results table 1 much better.

12. Include a separate section on sample size estimation in which the authors can state that all children seen in a certain time period were included.

13. What was the rationale for only including only participants that had an acute illness? Why were those classified as having moderate, severe illness not recruited yet they could be having characteristics that may be of interest to science and policy

14. Participant recruitment: line 111 – you can refer to the data collectors as research assistants.

15. Line 116 – 118: It is not possible that it is the children that were approached for recruitment. Actually the parents or care givers of these children are the ones who should have been approached to obtain consent for the recruitment of their children. What do the ethical guidelines say in Malawi about the assenting of children? Some of these children should have been able to assent. These procedures should be discussed in detail.

16. Data collection procedures: line 124: please include the manufacturer of the Lifebox LB-01 pulse oximeter and the machine for blood glucose, the AccuCheck Aviva point of care device.

17. How was observer bias handled while the measurements of variables was being done? This can be clarified in data collection procedures.

18. What was the qualification of the “data collectors” (research assistants)? Were they trained in handling children? Were they nurses? Midwives? Or doctors? Were they trained in research? Were the research assistants employees of the different health facilities at which the study was conducted?

19. Was consent sought for the collection of blood from the child (it is a separate consent process from the participation in the study)

20. For those children that were hypoxemic and those that were hypoglycemic, what further steps did the study team under take to ensure that these participants received the medical care that they required? This should be highlighted for purposes of equipoise

21. Line 138: where was the data being uploaded? Was it on a server?

22. It would be very informative to include a section entitled variables under which the authors describe all the key / important variables that they have measured in the study ie outcome variables and exposures.

23. Line 169 – 170: the IMCI guidelines recommend the evaluation of a number of danger signs ie bacterial infection, dehydration, jaundice, diarrhoea, low blood sugar, difficulty in breathing etc. It is important for the authors to specify exactly which danger signs they included in their study and how this differed from the exposures that they objectively measured.

24. Ethical statement: line 179 – 183: this study involved paediatric participants. The authors must show an effort to convince the readership that the participation of these participants was not coerced. If the data collectors were employees of the different study sites and at the same time research assistants, how did this double role play prevent coercion of participation? How was confidentiality of the information collected from the participants observed? Was the information collected by the ODK uploaded to a server? If so, how was this uploaded data handled? Was assenting for children aged 10 years or more done? What if this child declined assenting? How did the authors handle care givers or parents of children / infants that were minors (less than 18 years)? In this section the authors can also endeavour to make mention of what was done for oh how the study handled participants that needed medical attention. In the results the authors say that some parents / care givers declined participation. How were these participants handled?

25. Results: was data about the father of the child collected? It would be informative to include this in the analysis as well. What reference was used to classify the disease diagnosis? Was it the ICD? The authors can mention this.

26. The authors should calculate or estimate the 95%CI for the major proportions / prevalence. This can be done in stata using the exact method.

27. The results can be presented in a more coherent manner. This section can be improved after the section of the variables is constructed.

28. Discussion: this is too long and can be shortened.

29. The study must be having some limitations. The authors can look into including this section in the manuscript. For example this is a purely descriptive study and it’s very difficult to make inferences to the general population.

30. THE AUTHORS SHOULD CONSIDER TO USE THE STROBE GUIDELINES WHILE REVISING THIS MANUSCRIPT

Reviewer #2: GENERAL

This is an interesting and valuable topic.

The data is original but there are numerous errors in the tables and the analysis is incomplete.

IMCI was developed specifically for the assessment of children below five years of age but in this study the danger signs have been applied to children up to 12 years of age without any justification or comment on the appropriateness or applicability of the danger signs to the older child. The analysis of danger signs and the relationship of these to both hypoxemia and hypoglycaemia needs to be disaggregated by age to differentiate between those under and over five years of age.

The English is fair although there is the occasional typographical error.

TITLE

The title is an appropriate reflection of the content of the paper.

ABSTRACT

The abstract is a fair summary of the full content of the article.

However it may need to be revised if further analysis reveals any differences between younger and older children.

There are a few errors in the text:

Line 32 - needs to be corrected to “one day per month in each facility”

Line 34 – WHO needs to be presented in full before the abbreviation can be used

Line 42 – need to add severely ie “23.5% of the severely hypoxemic and..”

INTRODUCTION

The introduction is clear and succinct.

It sets the scene, highlights common challenges in identifying and referring critically ill children from the primary care level and suggests a possible response to identifying these children.

This study was undertaken to assess the validity of this suggestion.

METHODOLOGY

Although the description of the methodology is clear it requires some expansion or additions:

1. Justification is required for the use of IMCI danger signs out of their intended purpose ie in the assessment of children over 5 years of age. They need to provide some evidence to show that this is an appropriate tool to use in older children.

2. Some explanation is required as to why the authors chose to supplement the 5 IMCI danger signs with temperature, respiratory rate and chest indrawing and what evidence supports the choice of these specific signs as “danger” signs

Line 106 – “hospitals” is the incorrect term as participants were enrolled from hospitals and health centres. Better to refer to “health facilities”.

RESULTS

The results are presented in a series of 4 tables.

Tables 1, 2, and 3 all contain data errors and only table 4 has any statistical analysis.

Comments on individual tables are very limited and are restricted to the prevalence of the focus area of each table (hypoxemia, hypoglycaemia or danger sings) without any commentary on possible associations with or variations between subgroups ie age, gender, diagnosis or nutritional stuats.

Table 1 – Baseline characteristics

A note should be added to indicated that children may have more than 1 diagnosis – there were 2,943 children in the study but 3,379 diagnoses.

There are 2 data errors - The number of mothers with secondary education who presented at a health centre should be 400 not 340 and the total number of children with a diagnosis of other infection should be 268 not 358 and the % needs to be adjusted from 12.2% to 9.1%

A superficial analysis suggests that children who presented to the hospital were younger, had mothers with more education, a known nutritional status and more sepsis but fewer respiratory infections. Some statistical analysis is required to determine whether any of these are significant.

Table 2 - Hypoglycemia

This table has 5 errors all in the final column for total numbers – I’m assuming this is the error as the numbers in the other columns do not match the totals.

Total number of well nourished children should be 1669 not 1671

Total number of children with missing nutritional status should be 925 not 949

Total number of children with a temperature ≥37.5oC should be 890 not 892

Total number of children with gastroenteritis is 187 not 188

Total number of children with a diagnosis of “other infections” is the correct sum of previous columns but is inconsistent with the number in Table 1 which was 268

Again there is no commentary on patterns with subgroups – children with moderate hypoglycaemia appear to be older, female, and to be sleepy and unable to drink

Table 3 - Hypoxemia

This table has 7 errors all in the final column for total numbers – again I’m assuming this is the error as the numbers in the other columns do not match the totals.

Total number of well nourished children should be 1472 not 1671;

Total number of children with moderate malnutrition should be 130 not 154

Total number of children with severe malnutrition should be 140 not 169

Total number of children with missing nutritional status should be 893 not 949

Total number of children with a temperature ≥37.5oC should be 818 not 892

Total number of children with gastroenteritis is 155 not 188

Total number of children with a diagnosis of “other infections” is 270 not 358 and this is also inconsistent with the number in Table 1 which was 268

Again there is no commentary on patterns with subgroups – children with moderate hypoxemia appear to be younger males with convulsions or loss of consciousness

Table 4 – Danger signs

There are no obvious errors in this table however a bit more information is needed – there were 848 children with danger sings which is 28.8% but how many had more than one danger sign, what were the number of children with danger signs in each age group.

Whilst interesting I don’t believe that the temporal trends and Figures 1a and 1b add any value.

Figure S1 needs a title and correction of the legend – IMCI refers to danger sings so relabel either as “IMCI danger signs” or just “”danger signs” rather than “IMCI”

DISCUSSION

The discussion is reasonable however the sequence should ideally mirror the order in which data is presented in the results section ie hypoglycaemia then hypoxemia and then IMCI danger signs.

The local findings are compared to a few studies of either in- or outpatient settings from LMIC however there is no comment on the age groups in these studies compared to the age group in this study. Presumably the outpatient studies using IMCI focus on the under-5 age group which is not the case in this study. So some comment is required on the age groups and how this may have affected the findings.

There are a few “typos”

Lines 307, 309 and 323 refer to severe hypoglycaemia

Line 323 sign not sig

Line 344 in a general population

LIMITATIONS

This is adequately covered apart from the issue of using an assessment tool designed for children under 5 years of age on children aged 5 – 12 years.

CONCLUSIONS

The conclusion is appropriate.

REFERENCES

There is an extensive, comprehensive and up to date list of 44 references.

There are however inconsistencies in the structure of the references with some giving the first page number only and others the first and last pages.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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PLOS Glob Public Health. doi: 10.1371/journal.pgph.0000284.r003

Decision Letter 1

Claire E von Mollendorf

25 Jan 2022

PGPH-D-21-00696R1

Hypoxemia, hypoglycemia and IMCI danger signs in pediatric outpatients in Malawi

PLOS Global Public Health

Dear Dr. Thunberg,

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 11 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Claire E. von Mollendorf

Academic Editor

PLOS Global Public Health

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

There are a few spelling and grammatical errors in the manuscript. Please proofread prior to resubmission.

Consider adding a comment in the manuscript regarding the missing nutritional status data and the differences between the healthcare center and hospital sites.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: GENERAL COMMENT

The data errors have been corrected and the inconsistencies explained.

Comment has been added on the use of IMCI danger signs in the older, 5 – 12 year, age group and a comparison of findings between young and older age groups is now included.

I believe that the principle of presenting words in full before using acronyms or abbreviations holds and applies to WHO which needs to be spelt out in full at the start of the document.

The English is fair.

METHODOLOGY

The authors have now provided a rationale for the use of IMCI danger signs in older children.

However they still need to provide an explanation as to why they chose to supplement the 5 IMCI danger signs with temperature, respiratory rate and chest indrawing. They have provided this in their response to the reviewers but did not include this in the article. It needs to be included in the article.

RESULTS

The data has been cleaned and inconsistencies explained.

Line 246 close the brackets (49.2%)

Line 321 “health worker” should be “research assistants”

DISCUSSION

This is reasonable and now includes comment on the different age groups.

LIMITATIONS

This has been expanded to include a comment on the use of an assessment tool designed for children under 5 years of age on children aged 5 – 12 years.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLOS Glob Public Health. doi: 10.1371/journal.pgph.0000284.r005

Decision Letter 2

Claire E von Mollendorf, Julia Robinson

2 Mar 2022

Hypoxemia, hypoglycemia and IMCI danger signs in pediatric outpatients in Malawi

PGPH-D-21-00696R2

Dear Thunberg,

We are pleased to inform you that your manuscript 'Hypoxemia, hypoglycemia and IMCI danger signs in pediatric outpatients in Malawi' has been provisionally accepted for publication in PLOS Global Public Health.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact globalpubhealth@plos.org.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.

Best regards,

Claire E. von Mollendorf

Academic Editor

PLOS Global Public Health

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Reviewer Comments (if any, and for reference):

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. IMCI general danger signs (unconscious, sleepy/lethargic, convulsing, vomits everything, unable to eat/drink) depending on clinical characteristics.

    SpO2 results excluded from manuscript included. * Respiratory rate was assessed in 399 children. ** 3 caregiver refused SpO2-meassurment. *** No result due to refusal by caregiver (3), lack of test strips (22) and child too agitated (1).

    (DOCX)

    Click here for additional data file. (15KB, docx)
    S1 Fig. Prevalence of low SpO2-results (<90%, 91–93%) and IMCI danger signs depending on health center (HC) and hospitals (H).

    *The results of SpO2 from HC 2 and HC 9 were excluded from the analysis.

    (TIF)

    Click here for additional data file. (384.2KB, tif)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (53.6KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (24.6KB, docx)

    Data Availability Statement

    Unidentified data has been uploaded to the public repository Dataverse and can be accessed here: https://doi.org/10.7910/DVN/0YWX8J.

    Articles from PLOS Global Public Health are provided here courtesy of PLOS

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