Medicine in resource-limited settings

October, 2009

HIV

2008 Malawi HIV treatment guideline

http://www.aidstar-one.com/sites/default/files/AIDSTAR-One_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*• Median age 38 years• Diagnosis: ascitic tap, laparoscopy or

laparotomy

In resource-limited settings:When there is no ascites and/or poor laboratory supportWhen laparoscopy is unavailableWhen the patient is too ill for laparotomyTHERAPEUTIC 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

• Dec-June– 40,000 cases in 2006

• Serogroups B & C in N. America and Europe

• African epidemics: A & C• Asia: A• Serogroup W135 in Saudi

and W. Africa

• Treatment:

• X-pen + Chloramphenicol

• Ceftriaxone

• Vaccines

– Polysaccharide vaccines

– Monovalent against gp C for children/adolescent

The future rests with the provision of effectiveconjugate vaccines against S pneumoniae, H influenzae, and N meningitides to children in the poorest regions of the world!

Threats:Penicillin-resistant and chloramphenicol-resistant bacteriaS. pneumoniae with reduced susceptibility to ceftriaxone

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% malariaHookworm 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, Salmonella, Giardia, Entamoeba, Cryptosporidium, Vibrio

– Chronic• 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• Safe drinking water,

latrines, hygiene

Fever and blood:Shigella, campylobacter,

Salmonella, EHEC

INVESTIGATION?

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;29:39-53

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 resource-limited 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. Better screening and antenatal booking

b. Specialized diabetes care center

c. Scheduled cesarean section

d. 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• Which of the following are considered priorities in

improving healthcare delivery in resource-limited setting? Which one can improve health/mortality?

a. Increasing the number of nurses, clinicians, and/or lab-rad technicians

b. Improved distribution of medications and supply (formulary and inventory)

c. CTs, MRIs, and advanced diagnostic testingsd. Improve training for health professionalse. Technical support/consultants and volunteersf. Informational management systemg. Operational research/quality improvement/EBMh. Advocacy/change health policyi. Strengthen public health infrastructurej. 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 ARTScaling 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