COMMENTARY

July 15, 2003

John Bartlett, MD

July 23, 2003

Malaria Outcome: Effect of Age

Muhlberger N, Jelinek T, Behrens RH, et al. Age as a risk factor for severe manifestations and fatal outcome of Falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data. Clin Infect Dis. 2003;36:990-995. Abstract The authors report the results of a European network, TropNetEurop, and its sister organization in Germany, SIMPID, which are designed to detect emerging infections. The present report deals with Falciparum malaria reported to the networks for the period 1999 to 2002. The results are based on analysis of 3028 patients with imported Falciparum malaria with ages ranging from 10 to 81 years. There were 113 cases (9.6%) of severe malaria, including 37 (3.1%) with cerebral malaria. There were 17 (1.4%) deaths. The probability of developing severe disease increased by about 30% per decade of life. The authors conclude that Falciparum malaria is more serious in older patients, and their study also shows that networks with clinical surveillance are capable of generating high-quality data. The results of the study are summarized in Table 6 .

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Cite this: July 15, 2003 - Medscape - Jul 24, 2003.

Table 1. Clinical Observations in 144 SARS Cases
Symptoms	Percentage of Cases
Fever	99
Dry cough	69
Myalgias	49
Diarrhea	24
Nausea/vomiting	19
Cough + sputum	5
Rhinorrhea	1
Signs
Fever	100
Fever > 4 days in hospital	28
Chest x-ray
Admission - normal	25
Unilateral infiltrates	46
Bilateral infiltrates	29
Course - never had infiltrate	15
Lab (median values)
White blood count	5200/mm³
Total lymphocyte count	900/mm³
Lactic dehydrogenase	396
Outcome/course
ICU admission	20
Mechanical ventilation	14
Died	7

Table 2. SARS Classification Criteria
Classification Criteria	Probable	Suspected
Clinical	Severe respiratory illness	Moderate respiratory illness
Epidemiologic	Exposure	Exposure
Lab	Confirmed, negative, or undetermined	Confirmed, negative, or undetermined

Table 4. Epidemiology of Early SARS Cases
Hotel Guest	Destination
A	Index case in Hotel M; index case in Hong Kong Hospital #2 -- 6 cases including 4 healthcare workers (HCWs)
B	Index case for Hanoi -- 59 cases including 37 HCWs and 1 Thailand case
C, D, and E	Index cases in Singapore -- 70 cases including 34 HCWs and 3 cases in Germany
F	Index case in Toronto -- 16 cases including 10 HCWs
H	Index case in Hong Kong Hospital #1 -- 116 cases including 99 HCWs
J	Index case in Hong Kong Hospital #3 -- 3 cases including 3 HCWs

Table 5. Bacteriology of Bacteremia in Patients With Hematologic and Solid Organ Malignancies
Organism	Total, n (%)
Gram-positive	1639 (61)
Coag-negative staph	818 (30)
Staphylococcus aureus	311 (12)
Enterococcus faecalis	125 (5)
Enterococcus faecium	140 (5)
Streptococci	163 (6)
Gram-negative bacilli	720 (27)
Escherichia coli	206 (8)
Klebsiella spp	173 (6)
Pseudomonas aeruginosa	117 (4)
Other	136 (5)
Anaerobes	93 (3)
Fungi	259 (10)

	1995, %	2000, %
Gram-positive	62	76
Gram-negative	22	14

Table 6. Age-Specific Outcomes of Falciparum Malaria Among European Patients
		Patients, %
Age (yrs)	n	Fatal	Cerebral malaria	Other complications	Hospital
10-19	50	0	0	4	70
20-29	290	0.7	1.0	6.2	79
30-39	369	0.5	1.9	7.3	79.7
40-49	225	2.2	6.2	13.8	81.8
50-59	162	2.4	4.7	14.2	85.2
60-69	56	3.6	5.4	8.9	73.2
70-79	20	10	10.0	30.0	95.0

Table 7. Resistance Rates for 27,828 Isolates of Streptococcus pneumoniae for 1998-2002
Antimicrobial Agent	1998-9, %	2001-2, %
Penicillin	14.7	18.4
Ceftriaxone	1.2	1.7
Azithromycin	22.7	27.5
Trimethoprim/sulfamethoxazole (TMP-SMX)	27.3	26
Levofloxacin	0.6	0.9

Table 8. Molecular Diagnostic Techniques for Pathogens Associated With Pneumonia
Pathogen	Comment
Streptococcus pneumoniae	Can't distinguish colonization vs infection
Mycoplasma pneumoniae	More sensitive than culture
Legionella	As sensitive as culture
Chlamydia pneumoniae	More sensitive than culture
Pneumocystis carinii	More sensitive than cytology but specificity is uncertain
Viruses	Most useful in compromised patients

Table 9. Pneumonia in the Elderly: Observations in 1474 Hospitalized Patients
	< 80 years, n = 1169	> 80 years, n = 305
Microbiology
Streptococcus pneumoniae	273 (23%)	70 (23%)
Legionella	96 (8%)	4 (1%)*
Gram-negative	13 (1%)	8 (3%)
Viruses	22/328 (7%)	6/72 (8%)
Aspiration	59 (5%)	30 (10%)*
Atypicals	78 (7%)	3 (1%)*
Pneumococcal pneumonia	273	70
Acute onset	206 (76%)	53 (76%)
Chills	171 (63%)	42 (6%)
Purulent sputum	209 (77%)	49 (70%)
Treatment/outcome
Length IV treatment (mean)	5 days	4.7 days
Length of stay (mean)	11.4 days	10.2 days
30-day mortality	75 (6%)	46 (15%)*

Table 10. Percentage of *S pneumoniae* Resistant to Antibiotics
Antimicrobial Agent	2000-1 Age 18-64 Years	2001-2 Age 18-64 Years	2001-2 Age < 2 Years
Penicillin	15.4%	15.6%	34%
Amoxicillin CA	2.3%	3.4%	9.9%
Ceftriaxone	1.1%	1.9%	4.5%
Azithromycin	25.1%	25.1%	43.5%
TMP-SMX	26.1%	22.7%	44.8%
Levofloxacin	0.7%	1.1%	0

Table 11. FUO Cause in 190 Patients
Cause of Fever	Number of Patients
Infection	57 (30%)
Endocarditis	11
Tuberculosis	8
Urinary tract infection	6
Abdominal abscess	5
Cytomegalovirus	6
Other	21
Neoplasm	29 (15%)
Hematologic	22
Solid organ	7
Connective tissue disease	68 (34%)
Still's disease	18
Systemic lupus erythematosus	8
Other	9
Vasculitis	19
Giant cell arthritis	11
Granulomatous disease	14 (20%)
Sarcoid	10
Miscellaneous	38 (20%)
Thyroiditis	6
Habitual hyperthermia	11
Factitious	1

Table 12. Comparison of Major Publications on FUO
Source	Petersdorf^[49]	Larson^[50]	Barbado^[51]	Knockaert^[52]	Iikuni^[53]	DeKleijn^[54]	Present
Publication	1961	1982	1984	1992	1994	1997	2003
Period of review	52-57	70-80	68-81	80-89	82-92	92-94	91-99
Location	US	US	Spain	Belgium	Japan	The Netherlands	Belgium
Number	100	105	133	197	153	167	189
Diagnosis (%)
Infection (%)	40	36	39	30	33	37	23
Neoplasm (%)	21	38	25	10	16	18	21
Inflammatory Disease (%)	19	15	19	13	35	33	39
Miscellaneous (%)	21	11	16	29	16	11	17
No diagnosis (%)	9	16	22	26	12	31	53

Table 13. Regional Estimates of HIV and TB Incidence, Prevalence, and Mortality in 2000
	Africa	Americas	Europe	Southeast Asia	West Pacific	Globe
Population (x 1 million)	640	832	874	1536	1688	6053
New TB (/100,000)	290	46	54	194	120	137
HIV prevalence in new TB cases (%)	38	5.9	2.8	3.2	1.3	11
HIV-TB coinfection (%)	2.7	0.1	0	0.3	0	0.4
TB deaths (/100,000)	75	6.6	8.3	47	22	30
Adult AIDS deaths in TB cases (%)	12	4.1	10	8.1	17	11
TB deaths in HIV cases (%)	39	6.5	2.1	3.7	1.4	12

Table 14. Estimates of HIV and TB Incidence, Prevalence, and Mortality in 2000, by Country
Country	Population x million	TB incidence /100,000	HIV prevalence in new TB cases, %	HIV/TB co-infect adults, %	TB deaths /100,000	AIDS deaths due to TB, %
Afghanistan	22	319	0	0	92	0
Bangladesh	137	237	0.1	0	57	13
Brazil	170	67	3.3	0.1	8.8	3.2
Cambodia	13	573	20	3.1	121	30
China	1,275	113	0.4	0	21	8.6
Congo	51	294	24	1.8	70	15
Ethiopia	63	294	22	1.8	74	10
India	1,009	180	4	0.3	45	10
Indonesia	212	274	0.3	0	69	18
Kenya	31	449	49	0.1	24	12
Pakistan	141	173	0.6	0	46	8
Philippines	76	304	0.4	0	58	23
Russia	145	126	1.0	0	23	35
Tanzania	35	335	35	2.7	77	11
Thailand	63	137	12	0	21	3
Uganda	23	323	35	1.3	82	8.1
Vietnam	78	183	1.4	0.1	24	12
Zimbabwe	13	604	67	5.0	130	7.5

Table 15. Incidence of Major Adverse Drug Reactions*
Major Adverse Reaction	All Drugs 8488 person-months	INH 2747 person-months	RIF 2972 person-months	PZA 1336 person-months
Total	0.55	0.49	0.43	1.48
Hepatitis	0.14	0.18	0	0.52
Rash	0.25	0.15	0.30	0.60
GI	0.13	0.16	0.13	0.21

Table 16. Hazard Ratios (HR) for Major Adverse Reactions
Variable	HR (% CI)
Drug
PZA	1.48 (1.31-1.61)
INH	0.49 (0.42-0.55)
RIF	0.13 (0.37-0.49)
ETH	0.07 (0.04-0.10)
Age
35-59 vs < 35	1.7 (0.8-3.8)
> 60 years	2.9 (1.3-3.8)
Female vs male	2.5 (1.3-4.7)
HIV-positive	3.8 (1.05-13.4)
Birth in Asia	2.5 (0.9-6.6)

Table 17. Medical vs Surgical Treatment in Prosthetic Valve Endocarditis
Mortality and Disease-free Survival	Medical (n = 28)	Surgical (n = 38)
Inpatient mortality	13 (46%)	9 (24%)
Mortality with elimination of 7 patients not considered surgical candidates	6/21 (29%)
Endocarditis-free at 5 years	65%	60%

Table 18. Use of Neuraminidase Inhibitors in the Treatment of Influenza A and B
	Reduction in Symptoms in Days (mean ± 1 SE)
Treatment	Zanamivir 8 reports	Oseltamivir 9 reports
Children	1.0 (0.4-1.6)	1.5 (0.8-2.2)
Adults	1.3 (0.6-1.9)	1.4 (0.8-2.0)
High-risk adults	2.0 (0.9-3.1)	1.4 (1.0-1.9)

Table 19. Use of Neuraminidase Inhibitors in the Prevention of Influenza A and B
Prevention	Zanamivir 3 reports	Oseltamivir 4 reports
Seasonal prophylaxis	69% (36% to 86%)	74% (16% to 92%)
Postexposure	81% (62% to 91%)	90% (71% to 96%)
Residential care	-	92% (39% to 99%)

Table 20. Activity of Antibiotics vs Multiple Drug-Resistant Strains
Antimicrobial Agent	Penicillin-resistant S pneumoniae (n = 187)	MRSA (n = 305)	VRE (n = 219)
Amoxicillin /clavulanate	46%*	-	-
Ceftriaxone	82%	-	-
Clindamycin	74%	36%	-
Levofloxacin/cipro	98%	12%	1%
Vancomycin	100%	100%	0
Linezolid	100%	100%	99%
Synercid	100%	100%	97%
Daptomycin	0.12	0.5	4

Table 21. Fluoroquinolone Resistance in *Neisseria gonorrhoeae* Isolates From UK*
Agent	2000 (n = 2351)	2001 (n = 2369)	2002 (n = 2204*)
Ciprofloxacin % resistant	2.1	3.1	9.8

Table 22. New Antimicrobial Drugs and New Formulations - 2001
Date	Drug	Indication
1/19/01	Peginterferon alfa 2b (PEGINTRON)	Chronic hepatitis C, age > 18, compensated liver disease
1/26/01	Caspofungin (Candidas)	Invasive aspergillosis refractory or intolerant to other treatment
3/29/01	Valganciclovir (Valcyte)	CMV retinitis in AIDS patients
8/3/01	Clarithromycin (Biaxin XL)	CAP- Haemophilus influenzae, Streptococcus pneumoniae, M catarrhalis Mycoplasma, Chlamydia pneumoniae
8/16/01	Lamivudine (Epivir-HBV)	Hepatitis B in patients aged 2-17 years
8/29/01	Cefditoren (Spectracef)	Pharyngitis, AECB, skin & soft tissue
10/26/01	Tenofovir (Viread)	HIV infection
10/31/01	Ribavirin (Rebetol)	Separately available for use with interferon for HCV
11/9/01	Ertapenem (Invanz)	Adults with IAS, skin and soft tissue infections, CAP, UTI, gynecologic infections
11/30/01	Moxifloxacin (Avelox IV)	Sinusitis, AECB, CAP, skin and soft-tissue infections

Table 23. New Antimicrobial Drugs and New Formulations - 2002
Date	Drug	Indication
6/3/02	Voriconazole (Vfend)	Invasive aspergillosis and serious infections due to Scedosporium apiospermum and Fusarium
6/18/02	Doxycycline	Inhalation anthrax
8/21/02	Cefditoren (Spectracef)	CAP
9/9/02	Valacyclovir (Valtrex)	Herpes labialis
9/20/02	Caspofungin (Cancidas)	Esophageal candidiasis
9/20/02	Adefovir (Hepsera)	Chronic hepatitis B
9/22/02	Amoxicillin - CA (Augmentin XR)	CAP, AECB
10/2/02	Peginterferon alfa 2a (Pegasys)	Chronic hepatitis C
11/22/02	Nitazoxanide (Alinia)	Diarrhea due to cryptosporidium or Giardia lamblia in children aged 1-11 years
12/3/02	Ribavirin (Copegus)	Chronic hepatitis C
12/13/02	Ciprofloxacin (Cipro XR)	Uncomplicated UTIs
12/31/02	Stavudine (Zerit XR)	HIV infection

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July 15, 2003

Malaria Outcome: Effect of Age

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