Profiling the clinical presentation and bacterial causes of fever and hypothermia among neonates at a district hospital in rural Rwanda

doi:10.21203/rs.3.rs-3638992/v1

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Profiling the clinical presentation and bacterial causes of fever and hypothermia among neonates at a district hospital in rural Rwanda

https://doi.org/10.21203/rs.3.rs-3638992/v1

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Purpose

Neonatal sepsis remains a significant cause of morbidity and mortality worldwide, particularly in low-resource settings. We explored the clinical presentation and bacteria causing fever and hypothermia among neonates at a rural district hospital in Rwanda.

Methods

Between 29^th March to 7^th October 2022, a total of 126 children were enrolled in this cross-sectional study. Clinical data was obtained from children with fever or hypothermia at Butaro District Hospital. Blood culture was done using conventional methods. Positive cultures were sub-cultured onto MacConkey, blood agar, and chocolate, and incubated for 24 hours to confirm the pathogen. Mothers were followed for neonatal outcomes before and after discharge for two weeks.

Results

Among the neonates, 55.6% were males. The majority were aged 24 hrs and 6 days 99/126(78.6%). All children had fever or hypothermia, tachycardia (84.1%), tachypnea (87.3), poor perfusion (81%), abnormal breathing (70.6%), or abnormal cavities (50%), among others. Many mothers (46%) had at least four ANC visits, and none had a known HIV infection. In our sample of mothers, 7.9% reported a previous history of sepsis, 31.7% delivered by C-section, and 20.6% had a history of sepsis.

Blood cultures were positive in 67/126 (53.2%) neonates: 9 for Staphylococcus aureus (7.1%), 49 for coagulase-negative staphylococcus (CNS) (38.9%), 8 for gram-negative rods (6.4%), and 1 for Hemophilus species (0.8%). The mortality rate was reported at 7/126 (5.6%) among these children.

Conclusion

High positivity rates with CNS were reported among the neonates suggesting further approaches to minimize cross contamination in the neonatology unit.

neonates

bacteria

sepsis

outcome

Neonatal sepsis, a life-threatening condition characterized by systemic infection in newborn infants, is a global health problem. It remains a significant cause of morbidity and mortality worldwide, particularly in low-resource settings. Although there have been global initiatives to decrease neonatal mortality, World Health Organisation (WHO) evidence indicates that 47% of fatalities in children under 5 years of age were newborns, and among them, one-third didn't survive past birth, while nearly three-quarters succumbed within the first week of life (1).

The Sustainable Development Goals (SDGs) aim to reduce neonatal deaths to no more than 12 per 1000 live births by 2030 (UNICEF 2020), a target that remains challenging for many low- and middle-income countries (LMIC).

The diagnosis of neonatal sepsis requires a comprehensive evaluation that combines clinical assessment, laboratory tests, and microbiological investigations. Blood cultures remain the gold standard for identifying the causative pathogens. Unfortunately, the clinical signs and symptoms of sepsis are usually not straightforward as they mimic other conditions. Moreover, the heterogenicity in the definition of severe sepsis makes it difficult to ascertain children with the correct identification. A recent study named “Sepsis Prevalence, Outcomes, and Therapies (SPROUT)”, evaluated clinically diagnosed severe sepsis from children below 18 years and reported a high of up to 57% between physicians and the consensus definition (2).

Clinicians are urged to initiate prompt antimicrobial therapy for better outcomes in neonatal sepsis. This calls for empiric antibiotic therapy that is often observed, as recommended, based on local epidemiology data and risk factors. However, adjustments must be made based on the availability of culture and antimicrobial susceptibility results, although this is rarely possible in LMIC.

Epidemiological data from other countries indicate that early-onset neonatal sepsis is likely to involve pathogens such as Group B streptococcus, Escherichia coli, Coagulase-negative staphylococcus, Hemophilus influenzae, and Listeria monocytogenes (3). Late-onset neonatal sepsis also exhibits a similar trend but with both gram-positive and gram-negative organisms (4).

In Rwanda, there is a sparsity of data on the microbiology of neonatal sepsis as most hospitals rely on empirical treatment based on national guidelines (5).

Coincidentally, the most recent Rwanda Demographic Healthy Survey (DHS) report indicates a persistently high number of under-five child deaths. Between 2015 and 2020, the infant mortality rate was 33 deaths per 1000 live births, child mortality was 13 deaths per 1000 live births, and under-5 mortality was 45 deaths per 1000 live births (6). It has been previously reported that prematurity, asphyxia, and neonatal sepsis are the leading causes of neonatal death, contributing to 41%, 35%, and 10% of neonatal deaths, respectively (7). Most neonatal deaths occur in the early neonatal period, with 68% recorded at birth.

Although interventions to reduce under-five and maternal mortality rates have led to significant reduction from 152 deaths per 100,000 live births in 2005 to 50 deaths per 100,000 live births in 2015 (8), there is still room for further reduction.

A recent retrospective study reported a proportion of neonatal infection of 23.6% between 2013 and 2014 in Rwinkwavu and Kirehe district hospitals (9). Other Rwandan studies have reported neonatal deaths without providing detailed information on the cause (10). Routine national data from 2016 shows a similar trend, with neonatal illnesses accounting for 22.6% of inpatient hospitalizations and 49.5% of mortality among under-5-year-olds (11).

We explored the clinical presentation of neonates and mothers and documented the bacteria causing fever and hypothermia at a district hospital in Rwanda.

Aim of the study

The primary aim of the study was to determine the clinical presentation of neonates suspected of sepsis and profile the bacteria associated with sepsis among children under 5 years at Butaro District Hospital in the northern province of Rwanda. The clinical and demographic data of mothers were also collected to explain the cause of fever in neonates.

Study design

A quantitative cross-sectional study design was used. Participants were children under 5 years presenting at Butaro District Hospital with fever or hypothermia and other symptoms suggestive of sepsis.

Study location

The study was conducted at Butaro District Hospital which also serves as the district hospital for Burera and its neighboring communities. Located in the northern province, it is situated approximately 96 kilometers north of Kigali, the national capital of Rwanda. The hospital comprises general and maternity wards with a combined bed capacity of 156, and it receives around 210 deliveries each month with 65 (30%) of them being cesarean sections (12).

Characteristics of participants

Neonates were screened in neonatology based on the classification as guided by the Rwanda pediatric treatment protocol (13). The children were comprehensively screened for fever with or without obvious indication of infection, presence of a negative blood film for malaria, stiffness of the neck or other specific signs of meningitis (or if a lumbar puncture for meningitis was negative), signs of systemic upset (e.g., inability to drink or breastfeed, convulsions, lethargy or vomiting everything), any signs of local infection (infected wound, joints swollen, abscess), any signs of respiratory distress (details: chest recession, grunting, tachypnea RR: >20, flari), any signs of meningeal irritation (details: irritability, DTR increased, LOC, active convulsion, focal signs), any signs of shock and severe dehydration (details: LOC using AVPU score, cold extremities, poor perfusion, tachycardia HR >100, hypotension, skin signs of dehydration like sunken eyes, dry lips, poor urine output), increased or decreased WBC (<4,000 mm3> 12,000 mm3), and presence or absence of purpura.

Clinical and Laboratory investigations

Clinical investigations: Nurses obtained consent from all guardians or parents on the ethical principles related to this study, after the pediatrician completed their ward rounds. Clinical and demographic information were collected. In addition, blood for culture was ascetically collected in the BD BACTEC bottles and immediately transported to the UGHE microbiology laboratory for culture. All study participants were followed for one week for outcomes that included survival or death.

Blood culture: On arrival at the UGHE microbiology laboratory, the laboratory techs incubated the blood culture bottles at 37^oC and checked them visually every 24 hours until day seven. Growth was considered if the cultures exhibited hemolysis or turbidity. For positive cultures and those without any of the two appearances after seven days, we sub-cultured them on blood agar, chocolate, and MacConkey agar and incubated them at 37^oC for 24 hours to look for possible bacterial causes.

Identification of bacterial species was done based on colony morphology, Gram stain appearance, and standard biochemical tests. All isolates were stored in 20% glycerol in Brain Heart Infusion broth at -80°C for subsequent antimicrobial susceptibility testing and molecular assays.

Statistical analysis

Data was entered into epi-info software and analyzed using Stata 15.0 software (College Station, Texas, USA). The descriptive analysis comprises frequency tables to capture demographics, clinical presentation, and pathogen profile.

Between 29^th March to 7^th October 2022, a total of 126 children were enrolled at Butaro District Hospital, Burera District, Northern Rwanda. Among the neonates, 70/126 (55.6%) were males and the majority (99 out of 126) were aged between 24 hrs and 6 days (78.6%) [Table 1].

Table 1: Demographic characteristics of the neonates

Characteristics

Number

Age

<2 days

2-6days

7-11 days

12-16 days

17-21 days

>21 days

37(29.4)

62(49.2)

11(8.7)

5(4)

2(1.6)

9(7.1)

Gender

Male

Female

70(55.6)

56(44.4)

All children had fever or hypothermia, tachycardia 106/126 (84.1%), tachypnea 110/126 (87.3%), poor perfusion 102/126 (81%), abnormal breathing 89/126 (70.6%), abnormal color 55/126 (43.7%) abnormal cavity 63/63 (50%), resuscitation at birth 107/126 (84.9%) among others [Table 2].

Table 2: Clinical presentation of neonates

Characteristics

Number (%)

Child fever or hypothermia

Yes

126(100)

0(0)

Tachycardia

Yes

106(84.1)

20(20)

Tachypnea

Yes

110(87.3)

16(12.7)

Poor perfusion

Yes

102(81)

24(19)

Abnormal breathing

Yes

89(70.6)

37(29.4)

Abnormal color

Yes

55(43.7)

71(56.3)

Scherera

Yes

15(11.9)

111(88.1)

Abnormal cavity

Yes

63(50)

Abnormal feeding

Yes

80(63.5)

46(36.5)

Unexplained hypothermia

Yes

14(11.1)

112(88.9)

Bulging fontal

Yes

5(4)

121(96)

In addition, there were cases of malfunctions in the mothers at delivery, including uterine tenderness 36/126 (28.6%) and meconium-stained fluid 103/126 (81.7%).

Most of the mothers were married 119/126 (94.4%), with a primary level of education 92/126 (73%), practicing farming 117/126 (92.6%), with an average income level of 10,000-50,000 Rwf monthly. Many mothers 58/126 (46%) had at least four ANC visits and the first parity 45/125 (35.7%) [Table 3].

Table 3: Maternal demographics

Status

Number (%)

Marital status

Married

Single

Separated

Widowed

119 (94.4)

6 (4.8)

1 (0.8)

0 (0)

Education level

None

Primary

Secondary

Post-secondary

10 (7.9)

92 (73.0)

21 (16.7)

3 (2.4)

Occupation

Housewife

Business

Professional

Farmer

0(0)

1(0.8)

8(6.3)

117(92.9)

Household income

none

10-50k

50-100k

>100k

26(20.6)

94(74.6)

1(0.8)

5(4.0)

ANC visits

none

2(1.6)

10(7.9)

21(16.7)

33(26.2)

58(46.0)

2(1.6)

Parity

45(35.7)

38(30.2)

17(13.5)

10(7.9)

16(12.7)

None of the mothers reported having an HIV infection, while 10/126 (7.9%) reported a previous history of sepsis, 40/126 (31.7%) delivered by C-section, 25/126 (19.8%) had a UTI infection at delivery, and 10/126 (7.9%) had a history of sepsis [Table 4].

Table 4: Maternal Health conditions

Status

number (%)

HIV Status

Negative

Positive

Don’t know

126(100)

0(0)

History of sepsis

Yes

10(7.9)

116(92.1)

0(0)

Complaints at delivery

No complaint

UTI complaint

Other complaints

99(78.6)

25(19.8)

2(1.6)

Smoking during pregnancy

Smoked in pregnancy

Never smoked

1(0.8)

125(99.2)

Alcohol intake in pregnancy

Drunk in pregnancy

Never drunk

15(11.9)

111(88.1)

History of UTI

Yes

None

26(20.6)

100(79.4)

Mode of delivery

Vaginally

C- Section

86(68.3)

40(31.7)

Maternal fever

Yes

7(5.6)

119(94.4)

Maternal UTI

Yes

35(27.8)

91(72.2)

Membrane rapture duration >18 hrs

Yes

59(46.8)

67(53.2)

Uterine tenderness

Yes

36(28.6)

90(71.4)

Obstetric diagnosis of chorioamnionitis

Yes

3(2.4)

123(97.6)

Maternal Group B strep

Yes

1(0.8)

125(99.2)

Resuscitation at birth

Yes

107(84.9)

19(15.1)

Meconium-stained fluid

Yes

103(81.7)

23(18.3)

Home delivery

Yes

11(8.7)

115(91.3)

Blood cultures were positive in 67/126 (53.2%) with the following bacteria: Staphylococcus aureus 9 (7.1%), coagulase-negative staphylococcus (CNS) 49 (38.9%), gram-negative rods 8 (6.4%), and Hemophilus species 1 (0.8%) [Table 5].

Table 5: Characteristics of bacteria isolated from blood culture of neonates

Isolate	N, (%)
No growth	59(46.8)
Staphylococcus aureus	9 (7.1)
Coagulase negative staphylococcus	49(38.9)
Gram-negative rods	8(6.4)
Haemophilus species	1(0.8)
Total	126

The mortality rate was reported at 7/126 (5.6%) among these children.

Most of the neonates were males born less than six days prior to the presentation of clinical signs of sepsis. This trend seems to be commonly observed in the Rwandan context where a majority of neonatal sepsis studies report a higher proportion of males (9, 14–16).

Most of the mothers in this study had attended at least 3–4 antenatal care visits. The quality and number of ANCs have been previously documented in amplifying sepsis among neonates (17). In this study, despite the high ANC turnout, the outcome of bacterial sepsis was high. Perhaps this could be associated with the quality of ANC at the facilities. This can be further explained by the high prevalence of urinary tract infections (19.8%) observed at the time of delivery. During ANC visits, it is expected that screening for urinary tract infections and sexually transmitted infections should be routinely practiced. We recently reported high rates of congenital syphilis in Uganda mostly related to poor screening practices for sexually transmitted infections (18). Moreover, a high proportion of mothers already reported a previous history of sepsis (7.9%), indicating ongoing infections among mothers and children. This implies that the focus of intervention aimed at reducing sepsis should be extended to the communities and other health centers where primary health care is offered.

We detected a high proportion of bacteria associated with sepsis (53.2%). This is not a finding unique to our study as it has been previously reported. A retrospective study at one of the referral hospitals in Kigali, Rwanda reported a much higher bacterial (94%) among neonates with suggestive signs of sepsis (14). In the neighboring district hospital within the Northern Province, a more similar level of positive culture (30%) was recently reported (19). However, this positivity is much higher than what was reported in Uganda (12.6%) at a national referral hospital (20). The disparity in positivity could be attributed to the hospital levels as the national referral hospital is geographically located in the capital city of Uganda and by its health system level, is likely to have more improved infection control systems.

This is supported by the much higher positivity rate observed in a regional hospital in Uganda, closer to Rwanda geographically, where a 32.5% positivity rate was reported in a similar population in 2013 (21). On the other hand, Ethiopia reported a much higher prevalence (77.9%) (16). Again, contextual differences are clearly observed.

This could also be further supported by the observed mode and place of delivery in our study. A high proportion of mothers delivered by cesarian section (31.7%), while 8.7% delivered at home. Cesarian deliveries may be prone to contamination with skin flora as observed in our study. We found that most of the infections (38.9%) were caused by coagulase negative staphylococcus, which are predominantly found on the skin. Whereas we cannot rule out the possibility of contamination during sample collection, the treatment outcome reported after adjusting the drug regimen based on laboratory findings indicates a relationship with the cause of fever.

Other bacterial types reported in this study include Gram-negative bacilli (6.4%), Staphylococcus aureus (7.1%), and Hemophilus species (0.8%). Few studies have documented the microbiological culture outcomes of neonates with sepsis in Rwanda. In a retrospective study at a referral hospital in Kigali City, Rwanda, Gram-negative bacilli were predominant (54%), followed by Klebsiella (14), with a majority of these organisms resistant to Ampicillin and gentamicin. In neighboring Uganda, most of the infections were caused by Staphylococcus aureus (63%), Escherichia coli (15.2%), and Klebsiella pneumoniae (10.9%) (20). Our findings differ possibly due to diversity in practices at different levels of hospitals but also context.

Finally, the mortality rate among the neonates was reported at 5.6%. sepsis is usually associated with a high mortality rate especially when detected very late. Our mortality rate is lower than what was reported previously (13.3%) in rural Rwanda (9).

We observed a high presence of bacteria associated with fever among neonates at Butaro District Hospital, Northern Rwanda. As most infections isolated are CNS, the possibility of inadequate infection control measures in the neonatology facility cannot be ignored.

We propose further studies and interventions in the infection control system in neonatology.

Limitations

We were unable to confirm gram-negative bacilli up to the species level.
We could not rule out possible contaminating organisms at sampling that may have caused, high positivity, for example, skin flora.
We were unable to perform antimicrobial susceptibility on all the isolates, but isolates were stored to be done once the microbiology facility gets adequate capacity.

ANC Antenatal clinic, DHS Demographic Health Survey, LMIC Low- Middle-Income Countries, MOH Ministry of Health, SDG Sustainable Development Goals, RBC Rwanda Biomedical Centre, SPROUT Sepsis Prevalence, Outcomes, and Therapies, UGHE University of Global Health Equity, UNICEF United Nations Child’s Fund, WHO World Health Organization

Ethics Approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki.

Approval was granted by the Institutional Research Board of University of Global Health Equity (UGHE-IRB/2021/010).

Consent to participate

Written informed consent was obtained from the parents.

Availability of data and material

The dataset used and/or analyzed during this study is available from the corresponding author on reasonable request.

Funding

There was no funding for this study.

Acknowledgment

We thank University of Global Health Equity for allowing us to use their equipment in the laboratory. We are strongly indebted to Butaro District Hospital staff and Director General, for helping in sample collection. We are grateful to Mr. Jean Marie Vianney Bigirimana, Ms. Valentine Nyirabagabe, for helping in patient screening and data collection. Finally, appreciate the extensive review provided by Ms. Emmanuelle Rosenthal.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

PO and AB conceived the idea, designed the study, and collected data with support from DS. In addition, PO, DS, DR, LM, JBN, EB, and IN processed samples, interpretated results, performed analysis and wrote the manuscript. All authors read and approved the final manuscript.

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No competing interests reported.

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Profiling the clinical presentation and bacterial causes of fever and hypothermia among neonates at a district hospital in rural Rwanda

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Abstract

Background

Methods

Aim of the study

Study location

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

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