Study Coordinator Dr Sajid Bashir Soofi Assistant Professor Department of Pediatrics &Child Health

Transcription

1 Community Case Management of Severe Pneumonia with Oral Amoxicillin in Children 2-59 months of age in rural Pakistan; a cluster randomized controlled trial Study Coordinator Dr Sajid Bashir Soofi Assistant Professor Department of Pediatrics &Child Health Principal Investigator Dr Zulfiqar A Bhutta Professor & Chair Women & Child Health Division Aga Khan University, Pakistan

2 A collaborative Project Aga Khan University, Pakistan Boston University School of Public Health, USA National Program for Family Planning and Primary Health Care, MOH, Pakistan

3 Background Acute respiratory tract infection (ARI) is one of the leading causes of morbidity and mortality in children under five. Pneumonia results in 1.6 million deaths in under 5 annually world wide. In Pakistan every year under 5 children die due to pneumonia. WHO/UNICEF recommend trained CHW treat non-severe pneumonia with oral antibiotics and refer severe pneumonia to health facility for injectable antibiotics (IMCI Guidelines)

4 Rationale In the rural communities treatment at health facility is not possible due to; Lack of resources and accessibility. Non-availability of doctors and trained health care providers. Lastly LHWs who are the primary health care providers are not trained to use injectable antibiotics; hence injectable treatment is not possible. Recent research in several parts of the world has shown that severe pneumonia can be treated with oral antibiotics at home when diagnosed at health facility by trained health workers.

5 What needs to be done? In order to address high burden of mortality due to pneumonia substantial evidence for the alternative management through oral therapy was needed, hence the group proposed management of severe pneumonia with oral antibiotics through CHW especially in resource constrained settings.

6 Primary Objective: To determine whether there is equivalency in treatment failure rates among children 2-59 months with WHO defined severe pneumonia in clusters receiving domiciliary oral amoxicillin versus children in the control clusters who received standard care.

7 Secondary Objectives To determine overall treatment failure rates between day 6 and day 14, in the intervention and control arms. To determine whether LHWs can adequately assess, classify, treat and refer treatment failure cases of severe pneumonia.

8 Brief description of methods Study Sites This study was conducted in Matiari district in Sindh Province of Pakistan. Study Design Two arm, prospective, unblinded cluster randomized controlled trial. Our study cluster was a Union Council. 18 clusters; 9 each in intervention and control arm. Almost 251 LHWs involved in the study in both arms.

9 Study site description Indicator Intervention Control Total Area 1417 Sq: Kilometer (547.1 sq mi) Population Children < Union Councils THQ Hospitals Rural Health Centers Basic Health Units LHWs

10 Matiari district map with clusters

11 Selection Criteria Inclusion Criteria: Age between 2 to 59 months who present to LHWs with severe pneumonia. Informed consent given by legal guardian. Exclusion Criteria: Very severe disease. Parental or caretaker refusal to participate in the study. Children currently being treated for non-severe pneumonia who advance to severe pneumonia. Children with severe malnutrition. Children with severe diarrhea with signs of dehydration.

12 Case Definitions for CHWs/LHWs Child having cough and/or difficult breathing: Non-severe pneumonia: Respiratory rate > 50 breaths per minute; No chest in-drawing; without danger signs (LHW National Program) Severe pneumonia: Chest in-drawing; and/or rapid breathing without any danger sign (WHO) Very Severe Disease: Any danger sign (persistent vomiting, convulsions, abnormally sleepy, unable to drink, difficult to wake).

13 Treatment Failure Criteria Day 3- after 48 hours of starting treatment Appearance of any danger sign* Or Persistent of fever (100 o F) or more and chest in-drawing Or Change of antibiotic Day 6- after completion of 5 days treatment Appearance of any danger sign* Or Persistent of fever (100 o F) or more Or Chest in-drawing Or Change of antibiotic Death- any time from day 1-14 * Unable to drink/ breast feed, abnormally sleepy/difficult to wake, persistent vomiting, convulsions

14 Relapse on Day 7-14 After child was cured at day 6, appearance of any of the following: Fever 100 o F or more Chest in-drawing Fast breathing > 50 breaths/minute Any danger sign

15 Study Framework Intervention Control Baseline Household Survey Household Survey LHW Training Treatment Enhanced training on pneumonia case management for recognition of severe pneumonia and its home management with oral amoxicillin. Community Management of non-severe pneumonia (NSP) and SP using oral amoxicillin Standard training for pneumonia case management. Community Management of NSP with oral cotrimoxazole and referral of SP after first dose of co-trimoxazole

16 Case Management Non-severe Pneumonia Severe Pneumonia Follow up visits Intervention Oral amoxicillin 25 mg/kg twice daily x 3 days Teach parents home care and when to return. Oral amoxicillin 50 mg/kg twice daily x 5 days Teach parents home care and when to return. Day 1, 2, 4, 6 and 14 Control Oral Co-trimoxazole twice daily x 5 days Teach parents home care and when to return Immediate referral after first dose Co-trimoxazole If referral not possible, continued treatment with oral co-trimoxazole at home Day 1, 6 and 14 in case of hospital admission and day 1,2, 4, 6 and 14 in refused referral cases/cases treated as outpatient.

17 e Field Procedures LHW visited child home or mother sought care from her. LHW identified children with severe pneumonia, enrolled and started treatment as per protocol. She informed study coordinating centre via phone about cases. Study physician and supervisor (study CHW) visited the child with in 48 hours of enrolment to review and validate diagnosis and treatment. Study physician reviewed & validated 10% of cases and 100 % in cases of discrepancy in diagnosis of CHW and LHW but CHW would validate each enrolled case. LHW and CHW followed up for 14 days for evaluation of the child condition and for treatment failure.

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19 Consort diagram

20 Participants baseline parameters Parameter Intervention Control All Subjects Male (%) 55.6% ( 1301/2341 ) 55.1% ( 1140/2069 ) 55.4% ( 2441/4410 ) Age of Subject Median Age in Months (IQR) 13.0 ( 6.00 to 29.00) 10.0 ( 5.00 to 24.00) 12.0 ( 6.00 to 24.00) Infant under 6 months 21.1% ( 495/2341 ) 28.5% ( 589/2069 ) 24.6% ( 1084/4410 ) Infant 6-11 months 24.9% ( 583/2341 ) 24.0% ( 497/2069 ) 24.5% ( 1080/4410 ) Child months 54.0% ( 1263/2341 ) 47.5% ( 983/2069 ) 50.9% ( 2246/4410 ) History of Current Illness reported by Caregiver S1 : Cough 99.5% ( 2320/2332 ) 99.3% ( 2042/2057 ) 99.4% ( 4362/4389 ) S2 : Difficult breathing 95.7% ( 2227/2326 ) 98.3% ( 2014/2049 ) 96.9% ( 4241/4375 ) S3: Fast Breathing 87.0% ( 2021/2323 ) 93.4% ( 1910/2046 ) 90.0% ( 3931/4369 ) S4: Fever 72.7% ( 1687/2322 ) 74.5% ( 1525/2048 ) 73.5% ( 3212/4370 ) Day 1 Examination/assessment by Lady Health Worker S5. Median Respiratory rate for full one minute 54.0 ( to 58.00) 57.0 ( to 61.00) 55.0 ( to 60.00) Fast Breathing 80.1% ( 1869/2333 ) 73.1% ( 1505/2058 ) 76.8% ( 3374/4391 ) S6. Lower chest in-drawing 100.0% ( 2333/2333 ) 100.0% ( 2058/2058 ) 100.0% ( 4391/4391 ) Median WHO Weight for Age Z-score (IQR) -1.5 ( to -0.71) -1.8 ( to -0.79) -1.6 ( to -0.75) Median Enrollment per Cluster (IQR) ( to ) ( to ) ( to )

21 Treatment Outcome Cluster Randomized Controlled Trial in Matiari, Pakistan Intervention clusters Control clusters Risk Difference (95% CI) Treatment Failure at day 6 8.0% (187/2341) 13.2% (273/2069) -5.21% (-7.03 to -3.38) Day % (28/2148) 1.2% (21/1782) 0.13 (-0.57 to 0.82) There were only two deaths in intervention arm of the study, both cases were referred by the LHW. Very few adverse events of which only 0.1% needed therapy change.

22 Accuracy of lady health worker diagnosis of severe pneumonia Severe pneumonia Intervention Control Total LHW Classification n (%) Study Physician Classification n (%) LHW Classification n (%) Study Physician Classification n (%) LHW Classification n (%) Study Physician Classification n (%) (93.5) (96.5) (95.4) No Pneumonia 10 (2.68) 21 (3.19) 31 (3.00) Pneumonia 12 (3.21) 2 (0.30) 14 (1.35) Very Severe Disease 2 (0.53) 0 (0) 2 (0.19) Total

23 Conclusions Oral amoxicillin is an effective antibiotic for treatment of severe pneumonia at domiciliary level in low HIV settings. CHWs can recognize and classify severe pneumonia with enhance training. Based on our findings, we recommend WHO to review their current guideline for management of severe pneumonia. We also recommend the Pakistan LHW National Program consider revision of current policy of referring cases with severe pneumonia to health facility for further management and allow LHWs to treat severe pneumonia cases without any danger signs with oral amoxicillin.