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Transcript
Medicine in resource-limited
settings
October, 2009
HIV
2008 Malawi
HIV treatment
guideline
http://www.aidstar-one.com/sites/default/files/AIDSTAROne_Treatment_Summary_Table.pdf
Malaria
http://apps.who.int/malaria/docs/TreatmentGuidelines2006.pdf
Uncomplicated malaria in pregnant
woman
• Cochrane Review 2008
– Artesunate+atovaquone-proguanil vs. quinine
– Amodiaquine vs. chloroquine
– Amodiaquine+SP vs. chloroquine
– Artesunate+SP, azithromycin+SP vs SP alone
• Combination regimens may be more
effective?
Orton LC, Omari AAA. Cochrane Database Syst Rev. 2008 Oct 8;4
Ascites
• Transudate vs. exudate? (if you have laboratory
support)
• Ultrasound?
• Differential diagnoses
–
–
–
–
–
–
Portal hypertension due to hep B, C, alcohol, schisto
Right sided cardiac failure and pericardial effusion
Nephrotic syndrome
Severe hypoproteinemia 2/2 malnutrition, HIV/AIDS
Tuberculosis
Malignancy
Abdominal tuberculosis
• High index of suspicion
– Weight loss, abdominal pain, fever (1/2 of
cases)
• Peritoneal, ileal, or ileo-caecal
– CXR normal in a large % of cases*
In resource-limited settings:
• When
Median
age
38ascites
years and/or poor laboratory support
there
is no
• When
Diagnosis:
asciticis tap,
laparoscopy or
laparoscopy
unavailable
When
the patient is too ill for laparotomy
laparotomy
THERAPEUTIC TRIAL OF ANTI-TB TREATMENT!
*Ramesh J et al. Abdominal tuberculosis in a district general hospital. Q J Med
2008; 101:189-95
Acute Bacterial Meningitis
Threats:
• Dec-June
Penicillin-resistant and chloramphenicol-resistant bacteria
S. pneumoniae
reduced susceptibility to ceftriaxone
– 40,000
cases with
in 2006
• Serogroups B & C in N.
America and Europe
• Treatment:
• African epidemics: A & C
• X-pen + Chloramphenicol
The
• Asia:
A future rests with the provision of effective
• Ceftriaxone
conjugate
vaccines
against
S pneumoniae,
• Serogroup W135 in Saudi
• Vaccines
influenzae,
and N meningitides
to children
andHW.
Africa
in the poorest regions of the–world!
Polysaccharide
vaccines
– Monovalent against gp
C for
children/adolescent
Seizures
•
•
•
•
•
•
•
Not eclampsia-related
Alcohol, diabetes, infection, previous SZ?
Diazepam 10 mg IV
Phenobarbitone up to 600 mg IV over 6 minutes
Phenytoin 15 mg/kg IV
Paraldehyde 5 cc IM
Phenobarb 60-180 mg/d as outpatient
– Most are undertreated (20-40mg range)
Anemia prevalence and risk
factors
• Urban Pakistan
– 75% mild anemia (Hb <11); 15% moderate
(Hb 7-8.9); less than 1% severe (<7)
– Pica, tea consumption, and low intake of eggs
and red meat
• Urban and rural India
– 32% mild anemia; 14% moderate; 2% severe
– Protective factors: Muslim religion, high
socioeconomic status
Baig-Ansari N. Food Nutr Bull. 2008 Jun;29(2):132-9
Bentley ME. Eur J Clin Nutri. 2003;57(1):52-60
Anemia in developing countries
• Nutritional deficiencies
– Iron, B12, folate
• Chronic diseases
– TB, HIV
• Parasitic diseases
– Hookworm
– schistosomiasis
– Malaria
• Hemoglobinopathies
At QECH, of patients with Hb <7,
79% HIV+,
1/3 with TB,
21% bacteremic (NTS),
14% malaria
Hookworm common in HIV(-)
Lewis DK. Trans. Of the Royal
Soc. Of Trop. Med & Hyg 2005
Treatment for Anemia
• Improve diet
• Iron, multivitamin if available, B-complex
• Treat hookworm with
albendazole/mebendazole
• Treat schisto with praziquantel
• HIV, TB screen
Blood Transfusion
• A National Blood
Transfusion Service
– Time lost when relying
on family replacement
blood donors
– Paid donors and family
blood donors are
unsafe
– Voluntary unpaid
blood donation among
low risk population
groups
– Quality assurance
– Clinical guideline
Diarrhea
• Epidemiology
– Acute (< 3 weeks)
• Virus: rota
• Bacteria: E. coli, Shigella,
Campylobacter,
Fever
and blood:
Salmonella,
Giardia,
Entamoeba,
Shigella,
campylobacter,
Cryptosporidium,
Vibrio
–Salmonella,
Chronic EHEC
• Giardia, Campylobacter,
Salmonella, MAI,
Iso/micro, Stronglyloides,
IBD, malabsorption
• Treatment
– Resistance to
Bactrim, tetracycline
and ampicillin
– ORS and/or IVF
– Antibiotics
•
•
•
•
•
Cipro, Nalidixic acid
TMP/SMX
Metronidazole
Albendazole
Tetracycline, e-mycin or
doxy for cholera
– Public Health
INVESTIGATION?
• Safe drinking water,
latrines, hygiene
Sepsis syndrome
• Fever, jaundice, oliguria, breathlessness,
prostration, shock, encephalopathic
• Blood film, CBC, glucose, CSF?
• Diff: bacteremia, malaria, hepatitis,
meningitis, encephalitis, pneumonia
• HIV+ at higher risk for bacteremia
• Empiric treatment: IVF, IV PCN and
gentamicin+/- chloramphenicol or
Ceftriaxone, ?IV Quinine
Causes of sepsis variable
• Northeast Thailand
– S. aureus, pneumococci, other streptococci,
E. coli, other Enterobacteriaceae,
Pseudomonas spp., B. pseudomallei,
leptospirosis, scrub typhus, dengue
• Vientiane, Laos
– Salmonella enterica, S. aureus, E. coli
Cheng A C. PLoS Medicine August 2008.
Syndromic management
• Upper respiratory infection
• Gastroenteritis
• STD/STI
– Genital ulcers
– Lower abdominal pain/PID
– Vaginal discharge
• Fever, sepsis?
Hypertension
• ¾ of the world’s hypertensives (639
million) live in developing countries
• Prevalence of HTN in females 15-49 in
Jordan: 19%
– 7.5% in the very young
– 58% 45-49 years
– Associated variables: education, marital
status, parity, obesity, and dietary patterns
Shakhatreh et al. Health Care for Women International 2008;29:3953
Managing hypertension
• Low levels of awareness and inadequacy of
treatment!
• WHO criteria: >140/90 on at least 3 occasions
• Urine dipstick, U&E?
• Lifestyle modifications
• High-risk patients benefit from antihypertensives
even at lower BP readings
• Meds: HCT, propanolol, methyldopa, ?captopril,
nifedipine, hydralazine, furosemide
– Polypill: thiazide diuretic, ACE inhibitor, beta blocker,
statin, aspirin and folic acid
Which of the following statements are true
regarding hypertensive disorders in
developing countries?
a. Calcium supplementation is recommended for
women at high risk for hypertension in
pregnancy
b. The proportion of premature death due to
hypertension is much greater in high-income
countries compared to low, middle-income
countries
c. Hypertension prevalence is highest in women in
the "former socialist countries" of Europe
d. It is more difficult to control BP in resourcelimited settings
The silent epidemic: diabetes
• WHO predicts that developing countries will bear
the brunt of this epidemic in the 21st century,
with 80% of all new cases of diabetes expected
to appear in the developing countries by 2025
• A person requiring insulin for survival in Zambia
will live an average of 11 years; a person in Mali
can expect to live for 30 months; in Mozambique
a person requiring insulin will be dead within 12
months
www.worlddiabetesfoundation.org
Diabetes management
• Think DKA in any patients with mental status
change or septic appearance whether or not
they are known to have diabetes!
• DKA: IVF, soluble insulin, ?2-hourly monitoring,
urine dip for ketones/glucose; glucometers are
usually not available in the hospital
• Outpatient management:
– Oral agents: glibenclamide/glipizide, ?metformin
– Soluble (2-3X a day) and lente insulin (1-2X a day)
– When in doubt: 10 units
• No self monitoring/home glucometer!
• No refrigeration; reusing insulin syringes
common!
What are cost-effective strategies in
improving pregnancy (and neonatal)
outcomes in diabetic women?
a.
b.
c.
d.
Better screening and antenatal booking
Specialized diabetes care center
Scheduled cesarean section
Provision of self-monitoring of glucose
(finger sticks or urine dip)
e. Improve availability of insulin and
syringes
f. Effective diabetes education by
community health workers
Heart disease in Soweto
• 1593 new cases of CV disease in 2006 at a
tertiary care centre
– 85% black Africans
– 59% were women
• Mean age was 53 years
– Heart failure was the most common primary Dx
• Dilated cardiomyopathy or hypertensive heart
disease
– 56% dx’d with hypertension
– ¼ had valvular heart disease
– Black Africans – more likely to have heart failure and
less likely to have coronary disease
Sliwa K et al. Spectrum of heart disease and risk factors in a black urban
population in South Africa: a cohort study. Lancet 2008;371-:915-22
Heart Failure
• Peripartum - 1 in 100-1 in 1000 deliveries
• Pericardial effusion (TB, KS, bacterial,
malignancy)
• BP (hypertensive cardiomyopathy)
• HIV (viral cardiomyopathy)
• Murmur (rheumatic heart disease)
• Endomyocardial fibrosis (tropical regions of
East, Central, and West Africa)
• Treatment limited:
– oxygen, morphine, aminophylline
– furosemide, digoxin, captopril, B-blocker
– isosorbide dinitrate/hydralazine combination?
Asthma
• Nebulised salbutamol and/or salbutamol
inhaler
• Prednisone 40 mg
• Aminophylline 250mg IV
• Inhaled corticosteroid usually not available
• Oxygen if available
• Environmental triggers?
Mental Health
• Low-income countries have an average of
only five psychiatrists and one-and-a-half
psychiatric nurses per million people.
• Chad, Eritrea and Liberia have just one
psychiatrist each*
• Rule out organic causes of acute
psychotic presentation (delirium)
• Somatoform disorders
– Conversion disorder
– depression
*http://allafrica.com/stories/200801250553.html?page=3
Question
•
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
Which of the following are considered priorities in
improving healthcare delivery in resource-limited
setting? Which one can improve health/mortality?
Increasing the number of nurses, clinicians, and/or labrad technicians
Improved distribution of medications and supply
(formulary and inventory)
CTs, MRIs, and advanced diagnostic testings
Improve training for health professionals
Technical support/consultants and volunteers
Informational management system
Operational research/quality improvement/EBM
Advocacy/change health policy
Strengthen public health infrastructure
Improve the socio-economic status of women
Case 1: “worse on ART”
• A 31 yo male presented with 2 weeks of mental
status change, neck and backache, not talking, no
bowel movements
• Started on T30 (d4T/3TC/NVP) and CPT 2 weeks
ago
• A year ago, he was diagnosed with sputum negative
PTB but only took 3 months of treatment
• Exam: somnolent male, GCS 11/15; CN’s intact; no
thrush; +neck stiffness; no focal spinal tenderness;
no cLN; decreased BS at both bases with crepitus on
the left; abdomen is distended with tympanic sounds
throughout. Rectal tone is diminished with little stool.
Both legs were very weak (1/5) with slt hyperreflexia.
Bladder was full prior to catherization.
Case 1 (continued)
• WBC 8.0; Hb 12; CSF OP 35, glu 6; crypto Ag positive,
Indian Ink neg; WBC 35 with lymphocyte predominance,
+RBC; CXR ?bilateral diffuse interstitial infiltrates; abd
flat film with large bowel distension
• He was started on Diflucan 1200 mg/d and 3 days later,
Decadron 8 mg IV (when his condition deteriorated)
• 5 days into treatment, he became more alert with
increased strength in his legs but left leg is much weaker
than right.
• Dx? Further management?
AIDS 2008
Case 2: “creepy crypto”
• 38 yo male admitted for recurrent headache
• Enrolled in the UNC crypto study 2 months
ago when he was treated with Diflucan
1200mg->400mg/d, was improving until a
week prior to admission
• Started on T40 and CPT last month; CD4?
• Indian Ink positive this adm; repeated LP
every 2 days with high OP
• Ampho B started this admission with clinical
improvement
Case 2 (continued)
• Culture by UNC: CFU 450 (compared to
30K on initial dx)
• Keep on Diflucan maintenance vs. Ampho
B?
• Duration of Ampho B?
• Patient “absconded” when it was
recommended that he stayed for at least 2
weeks
UNC Project Malawi CM study, IAS 2009.
Case 3 : another crypto
• Lucious is a 39 yo male who was diagnosed
with cryptococcal meningitis 4 weeks ago
when he presented with headache and oral
thrush. HIV was newly dx’d with CD4 12. He
was started on fluconazole/flucytosine and
CPT. He had repeated LPs for high OP and
was discharged 2 weeks ago.
• He returned with worsening headache and
neckache, OP 45 on fluconazole 800 mg qd.
U & E was normal except for sodium of 131
and he was started on amphotericin B.
Case 3 (continued)
• Logistics of Ampho B administration in
resource-limited settings:
– Central line
– Prolonged hospitalization
• Guardian, work
– Nursing care
– Availability of Ampho B
– Laboratory monitoring
Case 4: “pus around my heart”
• 21 yo male admitted for severe dyspnea
• Treated for sputum + PTB 6 months ago,
improving until couple weeks prior to adm
• ART started 2 months ago, CD4 212
• CXR with bilateral infiltrates and enlarged
cardiac shadow
• Large pericardial effusion noted with
thickened fibrinous pericardium
• 1.5L of dark yellowish fluid drained with
symptomatic relief
• Fluid sent for culture and sensitivity
Case 4 (continued)
• He was treated initially with X-pen +
chloramphenicol, switched to Ceftriaxone
• Concern for resistant TB?
• KCH micro lab grew strep pneumo from
pericardial fluid; pus drained on day 2
• Purulent drainage continued
• Options: pericardial window, ?irrigation
with streptokinase, ?antibiotics
Case 5: TB Rx and ART option
• GP is a 39 yo male presented in August 2008 with
on/off headache for couple months, intermittent
nausea/vomiting, weakness
• Started on ART 3 years ago, initially on T40 and CPT
then switch to AZT/3TC and Nevirapine due to
?n/v/?pancreatitis
• CD4 76 in ’05; repeated=25 in 3/08; unclear
adherence history
• Had sputum negative for TB recently
• Had headache 3 months ago, LP was negative X 2,
also transient left sided weakness
• Repeated CXR showed moderate right pleural
effusion and infiltrate
http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.379_eng.pdf
Public Health Approach to ART
Scaling up controversies
• Risks
– Clinical eligibility criteria: patients in st 1,2 with immune
dysfunction or pts in st 3,4 with high CD4
– Clinical outcome measures: viral resistance identified at
later stage
• Facilities to monitor CD4 and viral load?
–
–
–
–
–
COST!
Poor laboratory services
Health worker shortage
Treatment adherence
Medical errors from managing a more complex protocol
Case 6: RIP
• MK is a 40 yo female who presented with
weakness, body pain, difficulty swallowing
and puffy face. She was started on T30 last
year with completion of PTB (sputum neg)
treatment. She was noted to gain weight.
Last CD4 was 358
• She was found to be semi-conscious, febrile,
dyspneic with decreased BS at the bases and
slightly distended abdomen; no meningismus.
CXR showed small right pleural effusion
Case 6 (continued)
• She was started on Quinine + Ceftriaxone.
Abdominal u/s revealed adenopathy,
hepatomegaly and peripancreatic fluid; NPS
on thick film; sodium 129, bicarb 17, urea 28,
crea 1.3; AST 116, ALT 26, albumin 0.6;
WBC 6; Hb 5.9 and Plt 15K
• Her condition deteriorated 3 days into
hospitalization. She was found pulseless by
the nurse during the night
• Stigmata of NG feeding and oxygen therapy
• Many deaths occur at night and on weekends
Case 7 : drug reaction?
• KM is a 39 yo male dx with HIV in 2005, with
CD4=4, started on T30 and CPT
• He developed neuropathy around the same
time and was changed to Duovir and NVP 2
years later
• Course is complicated by intermittent nausea,
elevated amylase and lipase and worsening
leg weakness and numbness. He had no
relief on amitriptyline 75 mg daily.
• Has had neg AFBs, never been treated for TB
• Repeat CD4 in 2008 was 105
Case 7 (continued)
• Since May’08, he developed worsening LE
weakness, balance problem, & difficulty
ambulating. Clinicians queried cerebellar
disorder and toxo. He was started on
empiric toxo with SP 3 weeks prior to
admission in August 2008
• He subsequently presented with epistaxis
with plt of 6, WBC 800 and Hb 9.1
• Central blood bank and transfusion
logistics
Case 8: another admission soon after ART initiation
• 38 yo male with recent dx of HIV, unknown
CD4. He was started on T30 a week prior to
admission (history of chronic cough, weight
loss, weakness, AFB neg)
• He developed ?acute confusion, fever,
abdominal pain and dry cough.
• He is from a small village 80 km away, seen
originally by a mission hospital; self-referred
to KCH
• LP is completely negative
• CXR is c/w miliary pattern
• Diarrhea improved
Case 8 (continued)
• He was started in Rifampin/INH/PZA/EMB
• He developed hearing loss; confusion was
better prior to discharge to home
• Follow-up issues
– Health records
– Referral from/to health center, district hospital,
mission hospital, private clinic, etc.
– No discharge summary or verbal communication
Case 9 : liver dysfunction
• SC is a 28 yo HIV+ female, dx’d in 2007. She was
treated for TB peritonitis with abdominal pain, weight
loss from 11/07 to 5/08. AFBs were neg. She did not
improve on TB treatment
• She was started on T30 in 2/08, unknown CD4
• She continued to have episodic abd pain, n/v/d,
fever, backache, headache. She was admitted for
septicemia in 3/08. TB treatment was restarted in
July ‘08.
• She was then admitted 8/08 for abdominal pain,
nausea, vomiting, fever. U/S revealed
hepatosplenomegaly and adenopathy. She had
cervical adenopathy.
• She subsequently developed jaundice and confusion.
Alk Phos is 1067, AST 84, T bili 14; Hb 6.5; WBC is
41K (lab error?) and Plt 307
Case 9 (continued)
• MAC treatment?
• Lymphoma?
• She was married, 2 healthy children.
Mother was the guardian
• She developed worsening somnolence
and seizure activities