Anemia

From : Williams Hematology

Pathophysiology and Manifestations

Effect on Oxygen Transport

The clinical manifestations of anemia are a function of the degree of tissue hypoxia and the etiology and pathogenesis of the specific anemia (e.g., splenomegaly characteristic of hereditary spherocytosis, mucosal tongue atrophy of pernicious anemia). Reduced oxygen-carrying capacity mobilizes compensatory mechanisms designed to prevent or ameliorate tissue anoxia. The red cells also carry carbon dioxide from the tissues to the lungs and help distribute nitric oxide throughout the body, but transport of these gases does not appear to be dependent on the number of red cells available and remains normal in anemic patients. Tissue hypoxia occurs when the pressure of oxygen in the capillaries is too low to provide cells with enough oxygen for the cells' metabolic needs. In an average person, the red cell mass must provide the total body tissues with about 250 ml/min of oxygen to support life. Because the oxygen-carrying capacity of normal blood is 1.34 ml per gram of hemoglobin (approximately 200 ml per liter of normal blood) and cardiac output is approximately 5000 ml/min, 1000 ml/min of oxygen is available at the tissue level. Extraction of one fourth of this amount reduces the oxygen tension of 100 torr in the arterial end of the capillary to 40 torr in the venous end. This partial extraction ensures the presence of sufficient diffusion pressure throughout the capillaries to provide all cells with enough oxygen for the cells' metabolic needs (Fig. 32-1). In anemia, extraction of the same amount of oxygen leads to greater hemoglobin desaturation and lower oxygen tension at the venous end of the capillary. The resulting anoxia in the immediate vicinity initiates a number of compensatory and frequently symptomatic adjustments in the supply of blood and oxygen.

Hypoxia-Inducible Transcription Factor 1

Hypoxia-inducible transcription factor 1 (HIF-1) plays a central role in the body's response to hypoxia (see Chaps. 30 and 56). HIF-1 was first identified as a factor regulating the transcriptional activity of erythropoietin gene¹ (see Chap. 30). The essential role of this transcriptional factor in global regulation of protection against hypoxia soon became clear. Its actions include respiratory control, transcriptional regulation of glycolytic enzyme genes, angiogenesis, and energy metabolism.^2,3,4 The prediction that hypoxia-regulated subunit of HIF-1 (HIF-1) degradation is controlled by an enzyme sensitive to the presence or absence of oxygen⁵ proved to be prescient. The current knowledge of hypoxia sensing is described in greater detail in Chap. 30. Tissue-specific and known and unknown factors are responsible for tissue-specific mobilization of the compensatory mechanisms listed below that permit survival under hypoxic conditions. Figure 32-2 outlines the regulation of some physiologic processes by hypoxia.

Decreased Oxygen Consumption

Energy metabolism at the optimal oxygen supply is generated by efficient oxidative phosphorylation. In hypoxia, energy is produced by less efficient glycolysis accomplished by up-regulation of transcription of glycolytic enzyme genes⁴ and increased glucose transport, a process known as the Pasteur effect. Pasteur and its cancer exception, i.e., the Warburg effect, are explained at the molecular level by changes in HIF-1 levels.^4,6,7,8

Decreased Oxygen Affinity

Efficient increase of tissue oxygen delivery is accomplished by decreasing the affinity of hemoglobin for oxygen (right-shifted hemoglobin oxygen dissociation curve). This action permits increased oxygen extraction from the same amount of hemoglobin⁹ (see Chap. 47). Acutely, a very small shift in pH produces a large effect on the dissociation curve because of the Bohr effect. In chronic anemia, increased oxygen tissue delivery is accomplished by increased amounts of 2,3-bisphosphoglycerate⁹ (see Chap. 45). The increased synthesis of 2,3-bisphosphoglycerate in anemia is accomplished by increasing the intracellular pH of red cells (see Chap. 45) by respiratory alkalosis resulting from increased respiration. This effect is clearly demonstrated in individuals with high-altitude hypoxemia.¹⁰

Increased Tissue Perfusion

The effect of decreased oxygen-carrying capacity on the tissue tension of oxygen can be compensated by increasing tissue perfusion by changing vasomotor activity and angiogenesis.² Because in most anemias the blood volume is not changed (Fig. 32-3),¹¹ increased tissue perfusion is organ selective, accomplished by shunting the blood from nonvital donor areas to oxygen-sensitive essential recipient organs. In acute anemia, the major donor areas for redistribution of blood are the mesenteric and iliac beds.¹² In chronic anemia in humans, the donor areas are the cutaneous tissue¹³ and the kidneys.¹⁴ Vasoconstriction and oxygen deprivation in the skin causes characteristic pallor of anemia. In the kidneys, the oxygen supply under normal conditions exceeds oxygen demands. The arteriovenous oxygen difference in the kidney is as low as 1.4 ml/dl (compared with the myocardium, where the difference can be as high as 20 ml/dl), indicating that even a severe reduction in kidney perfusion can be tolerated. Nevertheless, enough renal hypoxia must be present to activate HIF-1 and stimulate increased erythropoietin production and erythropoiesis (see Chap. 30). The effect on renal excretory mechanisms is slight because the reduction in renal blood flow is offset by high plasmacrit. Even in severe anemia where renal blood flow reduced by almost 50 percent, the total renal plasma flow is only moderately reduced. Severe anemia can cause retinal hemorrhages.¹⁵ Thus, organs with the most pressing need for oxygen, such as myocardium, brain, and muscles, are largely unimpeded by a moderate reduction in oxygen-carrying capacity.

Increased Cardiac Output

Increased cardiac output is an excellent but metabolically expensive compensatory device.¹⁶ It decreases the fraction of oxygen that must be extracted during each circulation, thereby maintaining high oxygen pressure. Because the viscosity of blood in anemia is decreased and selective vascular dilatation decreases peripheral resistance, high cardiac output can be maintained without any increase in blood pressure.¹⁷ In an otherwise healthy person, a measurable increase in resting cardiac output does not occur until hemoglobin concentration is less than 7 g/dl, and clinical signs of cardiac hyperactivity usually are not present until hemoglobin concentration reaches even lower levels.¹⁸

Signs of cardiac hyperactivity include tachycardia, increased arterial and capillary pulsation, and hemodynamic "flow" murmurs.¹⁹ The murmurs usually are heard during systole at the apex, over the pulmonary valve area, or at the pulmonary valve area. Murmurs and bruits have been described in many regions, such as over the jugular vein, the closed eye, and the parietal region of the skull, and may be sensed by the patient as roaring in the ears (tinnitus), especially at night. They disappear promptly after the hemoglobin concentration is restored to normal.¹⁹ The myocardium tolerates a prolonged period of sustained hyperactivity. However, angina pectoris and high-output failure may supervene if anemia is so extreme that it exceeds myocardial oxygen demands or if the patient has coronary artery disease. Cardiomegaly, pulmonary congestion, ascites, and edema have been observed, and they require prompt treatment with oxygen and transfusion of packed red cells.

Increased Pulmonary Function

Significant anemia leads to compensatory increase in respiratory rate that decreases the oxygen gradient from ambient air to alveolar air and increases the amount of oxygen available to oxygenate a greater than normal cardiac output. Consequently, exertional dyspnea and orthopnea are characteristic clinical manifestations of severe anemia.^18,19,20,21

Increased Red Cell Production

The most appropriate response to anemia is a compensatory increase of red cell production, which may increase about twofold to threefold acutely and fourfold to sixfold chronically, and occasionally as much as 10-fold in the latter case. The increase is mediated by increased production of erythropoietin. The rate of erythropoietin synthesis is inversely and logarithmically related to hemoglobin concentration (see Chap. 30). Erythropoietin concentration can increase from approximately 10 mU/ml at normal hemoglobin concentrations to 10,000 mU/ml in severe anemia (Fig. 32-4).^22,23 The change in erythropoietin levels ensures red cell production fully balances red cell destruction (compensated hemolysis) or chronic moderate blood loss. Augmented erythroid activity expands marrow space, which can cause sternal tenderness and diffuse bone pains. The number and proportion of reticulocytes increase. Because erythroid transit time through the marrow is shortened, "stress reticulocytes" having increased cell volume and surface area appear. Nucleated red cells may be observed in severe anemia.

Administration of human recombinant erythropoietin augments or replaces endogenous synthesis. At pharmacologic amounts, the effect on hemoglobin concentration is most noticeable if endogenous production is subnormal as a result of renal failure or systemic illnesses (see Chaps. 35 and 43). In severe anemia where endogenous erythropoietin production (providing production is not impaired) has already increased red cell production maximally, administration of erythropoietin generally does not help, and the patients require transfusion.²³

Uncorrected Tissue Hypoxia

A certain residual degree of tissue hypoxia remains despite mobilization of compensatory mechanisms. Hypoxia is essential for initiation of adequate cardiovascular and erythropoietic compensation mechanisms, but severe tissue hypoxia can cause the following symptoms: dyspnea on exertion or even at rest, angina, intermittent claudication, muscle cramps typically at night, headache, light-headedness, and fatigue. A number of diffuse gastrointestinal and genitourinary symptoms are associated with anemia (e.g., abdominal cramps, nausea), but whether the symptoms should be attributed to tissue hypoxia, compensatory redistribution of blood, or the underlying cause of anemia is uncertain.

Classification

Based on determination of the red cell mass, anemia and polycythemia can be classified as (1) relative or (2) absolute. Relative anemia and relative polycythemia are characterized by a normal total red cell mass. The conditions usually are not thought of as hematologic disorders but rather as disturbances in plasma volume regulation. However, dilution anemia and dehydration polycythemia are of clinical and differential diagnostic importance for the hematologist.

Classification of the absolute anemias with decreased red cell mass is difficult because the classification has to consider kinetic, morphologic, and pathophysiologic interacting criteria. Initially, all anemias should be divided into anemias caused by decreased production and anemias caused by increased destruction of red cells. The differentiation is based largely on the reticulocyte count. Subsequent diagnostic breakdown can be based on either morphologic or pathophysiologic criteria.

Morphologic classification subdivides anemia into (1) macrocytic anemia, (2) normocytic anemia, and (3) microcytic hypochromic anemia. The main advantages of this classification are that the classification is simple, is based on readily available red cell indices (MCV and MCHC), and forces the physician to consider the most important types of curable anemia: vitamin B12 , folic acid, and iron-deficiency anemias. Such practical considerations have led to wide acceptance of this classification. Pathophysiologic classification (Table 32-1) is best suited for relating disease processes to potential treatment. In addition, anemia resulting from deficiency states occurs in a significant proportion of patients with normal indices.

Kejang Demam

Source : Konsensus Kejang Demam 2005

Kejang demam adalah bangkitan kejang yang terjadi karena kenaikan suhu tubuh (suhu rektal di atas 38 ^OC) yang disebabkan oleh suatu proses ekstrakranium. Biasanya terjadi pada anak umur 6 bulan-5 tahun.

Bila anak berumur kurang dari 6 bulan atau lebih dari 5 tahun mengalami kejang didahului demam, pikirkan kemungkinan lain misalnya infeksi SSP maupun infeksi yang kebetulan terjadi bersama demam.

Klasifikasi kejang demam menurut Fukuyama:

1. Kejang Demam Sederhana (Simple Febrile Seizure)

2. Kejang Demam Kompleks (Complex Febrile Seizure)

1. Kejang Demam Sederhana

Kejang demam yang berlangsung singkat, kurang dari 15 menit, umum tonik dan atau klonik, umumnya akan berhenti sendiri, tanpa gerakan fokal atau berulang dalam 24 jam.

2. Kejang Demam Kompleks

Kejang demam dengan ciri (salah satu di bawah ini):

a. Kejang lama > 15 menit

b. Kejang fokal atau parsial satu sisi, atau kejang umum didahului kejang parsial.

c. Berulang atau lebih dari 1 kali dalam 24 jam.

Faktor risiko berulangnya kejang demam

Kejang demam akan terjadi kembali pada sebagian kasus. Faktor resiko berulangnya kejang demam adalah :

1. Riwayat kejang demam dalam keluarga

2. Usia kurang dari 15 bulan

3. Temperatur yang rendah saat kejang

4. Cepatnya kejang setelah demam

Bila seluruh faktor di atas ada, kemungkinan berulang 80%, sedangkan bila tidak terdapat faktor tersebut hanya 10%-15% kemungkinan berulang. Kemungkinan berulang paling besar pada tahun pertama.

Faktor risiko terjadinya epilepsi

Faktor risiko lain adalah terjadinya epilepsi di kemudian hari.

Faktor risiko menjadi epilepsi adalah :

1. Kelainan neurologis atau perkembangan yang jelas sebelum kejang demam pertama.

2. Kejang demam kompleks

3. Riwayat epilepsi pada orang tua atau saudara kandung

Masing-masing faktor resiko meningkatkan kemungkinan kejadian epilepsi sampai 4%-6%, kombinasi dari faktor risiko tersebut meningkatkan kemungkinan epilepsi menjadi 10%-49%. Kemungkinan menjadi epilepsi tidak dapat dicegah dengan pemberian obat rumat pada kejang demam.

Penatalaksanaan Kejang Demam

Biasanya kejang demam berlangsung singkat dan datang kejang sudah berhenti. Apabila datang dalam keadaan kejang obat yang paling cepat untuk menghentikan kejang adalah diazepam yang diberikan secara intravena. Dosis diazepam intravena adalah 0,3-0,5 mg/kg perlahan-lahan dengan kecepatan 1-2 mg/menit atau dalam waktu lebih dari 2 menit, dengan dosis maksimal 20 mg.

Obat praktis dan dapat diberikan oleh orang tua atau di rumah adalah diazepam rektal. Dosis diazepam rektal adalah 0,5-0,75 mg/kg atau diazepam rektal 5 mg untuk anak dengan berat badan kurang dari 10 kg dan 10 mg untuk berat badan lebih dari 10 kg atau diazepam rektal dengan dosis 5 mg untuk anak dibawah usia 3 tahun atau dosis 7,5 mg untuk anak di atas usia 3 tahun.

Kejang yang belum berhenti dengan diazepam rektal dapat diulang lagi dengan cara dan dosis yang sama dengan interval waktu 5 menit.

Bila 2 kali dengan diazepam rektal masih kejang, dianjurkan ke rumah sakit.

Bila kejang tetap belum berhenti diberikan fenitoin secara intravena dengan dosis awal 10-20 mg/kg/kali dengan kecepatan 1 mg/kg/menit atau kurang dari 50 mg/menit. Bila kejang berhenti dosis selanjutnya adalah 4-8 mg/kg/hari, yaitu 12 jam setelah dosis awal.

Bila dengan fenitoin kejang belum berhenti maka pasien harus dirawat di ruang rawat intensif.

Bila kejang telah berhenti, pemberian obat selanjutnya tergantung dari jenis kejang demamnya dan faktor risikonya, apakah kejang demam sederhana atau kompleks.

Pemberian obat rumat

Pemberian obat fenobarbital atau asam valproat setiap hari efektif dalam menurunkan risiko berulangnya kejang.

Dosis asam valproat 15-40 mg/kg/hari dalam 2-3 dosis, fenobarbital 3-4 mg/kg/hari dalam 1-2 dosis.

Manajemen Asfiksia Bayi Baru Lahir

By : Vincent

Asfiksia merupakan suatu gangguan bernafas neonatus pada saat setelah kelahiran. Keadaan tersebut merupakan suatu keadaan gawat darurat, sehingga manajemen penatalaksanaannya menjadi suatu hal yang penting untuk diketahui, dengan menajemen yang baik maka prognosisnya (perkiraan perjalanan penyakit) bisa menjadi lebih baik.

1. Penilaian = Bayi menangis, tidak bernafas spontan atau megap-megap

• Langkah awal (Dilakukan dalam 30 detik)

Jaga Bayi agar tetap hangat
Atur posisi bayi
Isap lendir
Keringkan dan rangsang taktil
Reposisi

2. Penilaian = Apakah bayi menangis atau bernafas spontan dan teratur

• Jika Ya ---> Lanjut No. 5
  
• Jika Tidak ---> Lanjut No. 2a

2a. Ventilasi

Pasang sungkup, perhatikan lekatan
Ventilasi 2x dengan tekanan 30 cm air, amati gerak dada bayi
Bila dada bayi mengembang, lakukan ventilasi 20x dengan tekanan 20 cm air dalam 30 detik

3. Penilaian = Apakah bayi menangis atau bernafas spontan

• Jika Ya ---> Lanjut No. 5
  
• Jika Tidak ---> Lanjut No. 3a

3a. Lanjutkan Ventilasi, Hentikan tiap 30 detik

4. Penilaian = Apakah bayi manangis atau bernafas spontan

• Jika Ya ---> Lanjut No. 5
  
• Jikat Tidak ---> Lanjut No. 4a

4a. Lanjutkan Ventilasi selama 2 menit, Jika tidak berhasil ---> Siapkan rujukan
4b. Bila bayi tidak bisa dirujuk dan tidak bisa bernafas, hentikan Ventilasi setelah 20 menit
4c. Konseling dukungan emosional
4d. Pencatatan Bayi Meninggal

5. Asuhan Pasca Resusitasi

Jaga bayi agar tetap hangat
Lakukan Pemantauan
Konseling
Pencatatan

Febrile Seizures

Linda D. Leary

Douglas R. Nordli Jr.

Timothy A. Pedley

A febrile seizure is an event in infancy or childhood, usually occurring between 3 months and 5 years of age, associated with fever, but without evidence of an intracranial infection or defined cause (National Institutes of Health Consensus Conference, 1980). This definition excludes children who have had previous afebrile seizures.

Febrile seizures are the most common cause of convulsions in children: Between 2% and 5% of all children in the United States and Europe and 6% to 9% of children in Japan have at least one febrile seizure before age 5 years. Hauser (1994) estimated that in 1990, there were 100,000 cases of newly diagnosed febrile seizures in the United States. Genetic predisposition is an important factor. Overall, siblings and offspring of affected probands have a twofold to threefold increased risk of seizures with fever. Based on studies of large families with simple febrile seizures, four genetic loci have been mapped. These loci are referred to as FEB1 (8q13-q21), FEB2 (19p), FEB3 (2q23-q24), and FEB4 (5q14-q15). Some families have a susceptibility to febrile seizures and later epilepsy, and these traits are inherited in an autosomal-dominant fashion. This has been termed generalized epilepsy febrile seizures plus (GEFS+). Mutations in the voltage-gated sodium channel ²-1 subunit gene (SCN1B; OMIM 600235) on chromosome 19q13 cause GEFS+ type 1; mutations in the SCN1A gene (OMIM 182389) on 2q24 cause GEFS+ type 2; and mutations in the GABRG2 gene (OMIM 137164) on 5q31.1-q33.1 cause GEFS+ type 3. Mutations in the SCN2A (OMIM 182390) gene cause febrile seizures associated with afebrile seizures. Owing to the overlap between the loci for FEB 3 and GEFS+ type 2, it is uncertain if FEB3 is a unique genetic locus for simple febrile seizures. The role of identified genes in sporadic febrile seizures remains to be determined.

CLINICAL MANIFESTATIONS

About two-thirds of febrile seizures occur early in the febrile illness (that is, within the first 24 hours). In some children, the seizure is the first indication of illness. Febrile seizures are subdivided into simple and complex types. Simple febrile seizures are most common, representing 80% to 90% of all febrile seizures. Simple febrile seizures are isolated, brief generalized convulsions. Complex febrile seizures are those that are focal or followed by a postictal deficit (Todd paresis), last more than 10 to 15 minutes, or occur more than once within 24 hours.

DIAGNOSIS

Diagnosis is made by excluding other possible causes of the convulsion, such as meningitis, metabolic abnormalities, or structural brain lesions. Depending on the manifestations and the clinician’s experience, laboratory tests are not always necessary. Usually, a clinically identifiable illness such as otitis media, upper respiratory infection, or gastroenteritis is present. Fever after immunization may also trigger a febrile seizure. Any suspicion of meningitis, however, mandates lumbar puncture. The typical indicators of meningeal irritation, such as nuchal rigidity and the Brudzinski sign, are not reliable in young infants. Practice guidelines of the American Academy of Pediatrics (1996) recommend that lumbar puncture be strongly considered if the child is younger than 12 months of age or if the child has already been treated with antibiotics regardless of age. Lumbar puncture may be indicated in children between 12 and 18 months. If the seizure has focal features, or if the examination elicits focal neurologic abnormalities, brain imaging is necessary. EEG is not useful, because it does not provide information regarding either the risk for recurrence of febrile seizures or later development of epilepsy.

PROGNOSIS AND TREATMENT

About one-third of children with febrile seizures have more than one attack. Recurrence is highest in infants whose first febrile seizure occurred before the age of 1 year and in children with a family history of febrile seizures. Febrile seizures represent acute symptomatic or reactive seizures, and even when recurrent do not warrant the designation of epilepsy.

Children who have an isolated febrile seizure have a risk of developing epilepsy that is similar to that of the general population. This risk increases if simple febrile seizures recur (2%-3%), and if the febrile seizures are complex, there is a family history of afebrile seizures, or neurological abnormalities were detected before the first febrile convulsion (10%-13%). When all three features of complex febrile seizures are present (prolonged, focal, repeated), the risk of subsequent epilepsy may be as high as 49%. Mortality is not increased in children with febrile seizures who are neurologically normal.

Simple febrile seizures have not been associated with, nor do they lead to, mental retardation, low IQ, poor school achievement, or behavioral problems. Most studies have also failed to demonstrate any cognitive or behavioral consequences of complex febrile seizures, although some differences have been reported. In children with prolonged febrile convulsions, nonverbal intelligence measures may be slightly lower compared with children with simple febrile seizures and normal controls. Children with complex febrile seizures are also more likely to require special schooling than those with simple febrile seizures.

Whether prolonged febrile seizures cause mesial temporal sclerosis and refractory partial seizures is controversial. Large prospective studies have failed to find an association, but experience in adult epilepsy surgical centers suggests otherwise, because many adults with mesial temporal sclerosis have had a prolonged febrile convulsion as a child. Furthermore, MRI in some children with prolonged febrile seizures has shown acute changes in the mesial temporal region that progress over time to mesial temporal sclerosis.

Because most children with febrile seizures have no long-term consequences, prophylactic treatment using antiepileptic drugs should be avoided, even after two or three isolated convulsions. Although both phenobarbital and valproate are effective in reducing recurrence, evidence does not show that treatment alters the risk of later epilepsy. In addition, adverse drug effects occur in as many as 40% of infants and children treated with phenobarbital, and valproate carries a risk of idiosyncratic fatal hepatotoxicity and pancreatitis. Phenytoin and carbamazepine are ineffective.

If treatment is considered at all, it should be reserved for children with a high risk of developing epilepsy or a history of prolonged febrile seizures. A reasonable alternative to chronic drug therapy is intermittent treatment using rectal diazepam. Several studies have shown that rectal administration of diazepam during febrile illnesses is safe and as effective as phenobarbital in reducing seizure recurrence. Although oral diazepam has also been shown to be effective, as many as 30% of children experience adverse effects, including ataxia, lethargy, or irritability. Antipyretics may improve the child’s comfort during the febrile illness, but they have not been shown to be effective in preventing the recurrence of febrile convulsions.

Watching their child have a convulsion is a frightening experience for parents. The physician therefore must provide reassurance to dispel any myths the family may have, emphasizing in particular that febrile seizures are neither life threatening nor damaging to the brain. The American Academy of Pediatrics offers copies of its Guidelines and an information sheet for parents through its website (http://www.aap.org), and the Epilepsy Foundation website (http://www.epilepsyfoundation.org) provides information about febrile seizures.

Source : Merritt's Neurology, 11th Edition

Water-related Diseases (Leptospirosis)

Leptospirosis

The disease and how it affects people

Leptospirosis is a bacterial disease that affects both humans and animals. The early stages of the disease may include high fever, severe headache, muscle pain, chills, redness in the eyes, abdominal pain, jaundice, haemorrhages in skin and mucous membranes (including pulmonary bleeding), vomiting, diarrhoea and a rash.

The cause

Pathogenic Leptospira spp. cause leptospirosis. Human infection occurs through direct contact with the urine of infected animals or by contact with a urine-contaminated environment, such as surface water, soil and plants. The causative organisms have been found in a variety of both wild and domestic animals, including rodents, insectivores, dogs, cattle, pigs and horses. Leptospires can gain entry through cuts and abrasions in the skin and through mucous membranes of the eyes, nose and mouth. Human-to-human transmission occurs only rarely.

Distribution

Leptospirosis occurs worldwide, in both rural and urban areas and in temperate and tropical climates. It is an occupational hazard for people who work outdoors or with animals, such as rice and sugar-cane field workers, farmers, sewer workers, veterinarians, dairy workers and military personnel. It is also a recreational hazard to those who swim or wade in contaminated waters. In endemic areas the number of leptospirosis cases may peak during the rainy season and even may reach epidemic proportions in case of flooding.

Scope of the Problem

The number of human cases worldwide is not well-documented. It probably ranges from 0.1 to 1 per 100 000 per year in temperate climates to 10 or more per 100 000 per year in the humid tropics. During outbreaks and in high-risk groups, 100 or more per 100 000 may be infected. For several reasons leptospirosis is overlooked and consequently underreported in many areas of the world. In the wake of hurricane Mitch in 1995, an outbreak of leptospirosis with pulmonary haemorrhages was reported in Nicaragua. In 1998, there was an outbreak in the continental United States. 1998 also saw an outbreak in Peru and Ecuador following heavy flooding. A post-cyclone outbreak was reported in Orissa, India in 1999.

Interventions

The disease is often difficult to diagnose clinically; laboratory support is indispensable. Treatment with appropriate antibiotics should be initiated as early as possible. Untreated cases can progress to a more severe and potentially fatal stage. Preventive measures must be based on a knowledge of the groups at particular risk of infection and the relevant local epidemiological factors. For intervention one may:

• aim at control at the level of the infection source (e.g. rodent control, animal vaccination);
• interrupt the transmission route (e.g. wearing protective clothing, refrain from contact with infected animals and from swimming in contaminated water, provide clean drinking-water); or
• prevent infection or disease in the human host (e.g. vaccination, antibiotic prophylaxis, information to doctors, veterinarians, risk groups and the general population).

Prepared for World Water Day 2001. Reviewed by staff and experts from the cluster on Communicable Diseases (CDS) and Water, Sanitation and Health unit (WSH), World Health Organization (WHO).

The Unexplored Story of HIV and ageing

George P Schmid ^a, Brian G Williams ^b, Jesus Maria Garcia-Calleja ^a, Chris Miller ^c, Emily Segar ^c, Monica Southworth ^c, David Tonyan ^c, Jocelyn Wacloff ^c & James Scott ^c

a. Department of HIV/AIDS, World Health Organization, 20 avenue Appia, 1211 Geneva 27, Switzerland.
b. Independent Consultant, Geneva, Switzerland.
c. St Olaf College, Northfield, MN, United States of America.

Correspondence to George Schmid (e-mail: schmidg@who.int).

Bulletin of the World Health Organization 2009;87:162-162. doi: 10.2471/BLT.09.064030

As people in developing and industrialized countries increasingly live longer, healthier lives, why do the scant data that exist suggest a surprisingly high prevalence and incidence of HIV among individuals 50 years of age and over (“older individuals”)?

Older individuals are rarely included in Demographic Health Surveys (DHS). In the last 5 years, only 13 of 30 surveys included older males and none included older females. The National Health and Nutrition Examination Survey in the United States of America (USA) does not collect data from people older than 49. There is a dearth of prevalence data; what about incidence?

Incidence could be determined via case reporting, serologic incidence assays or modelling. Developing countries have limited case-reporting systems, but industrialized countries do better. In the USA, case reporting from 2003 to 2006 shows the proportion of older HIV-positive individuals has climbed from 20% to 25% and numbers of cases have risen in all 5-year age bands from 45 years to 65 years and older;¹ using serology, 11% of 2006 incident cases are in older individuals.² In WHO’s European Region, 8% of reported cases in 2005 are older.³ Similar data from the developing world are unavailable, and modelled incidence data are not publicly available.

We have calculated prevalence by age, using UNAIDS’ estimated numbers of cases of HIV and United Nations population estimates, by country. One finds a consistent pattern that prevalence in older individuals is one-quarter to one-third that of the 15–49-year age group. We have debated with our colleagues whether these findings are surprising. Most of us think “yes”.

This is particularly so because prevalences for this age group are deceptively low. There is little appreciation that the older the individual, the faster the progression from HIV infection to AIDS.^1,4,5 The effect is considerable, linear and remains after adjusting for all-cause mortality.^4,5 For example, there is a life expectancy of more than 13 years in people infected at age 5–14. This declines to 4 years in those infected at age 65 or older.⁵ Waning immunity with age may be the reason. Since incidence is indirectly related to duration of disease, prevalence in those aged 50 and above should be approximately doubled to be compared with those in the 15-24 year age group. While long-available antiretroviral therapy (ART) could increase prevalence among older individuals in industrialized countries, this is not true of the developing world, where ART was introduced later.

Is the epidemiology of HIV in older individuals of purely academic interest? No, because understanding risk factors leads to interventions. Intriguingly, the Alpha Network in Africa has shown that in many sites, secondary peaks of HIV incidence appear at older ages.⁶ Why might older individuals be becoming infected? We can only conjecture. In a systematic literature search, we found only one, limited, epidemiological study exploring HIV acquisition in older individuals, from urban USA.

Sexual activity of older individuals in the developing world is barely researched. Many older individuals everywhere are sexually active, although interest in sex and frequency of vaginal intercourse decline with age.⁷ Since 1998, erectile-dysfunction drugs have been extending the sex life of many older individuals and, at the same time, may be extending the HIV epidemic into older age groups. Many studies show that older individuals are less likely than their younger counterparts to practise safer sex. While erectile dysfunction is common and erectile-dysfunction drugs are widely distributed in developing countries,⁸ no study has been done of their possible impact on the HIV epidemic, although their use in industrialized countries has been associated with risky sexual practices.⁹ Whether HIV-positive men should be prescribed these drugs has been debated.¹⁰

If sex is the main cause of HIV infection in older individuals and many older individuals are not having penetrative intercourse, then the risk of acquiring HIV per sexual act in these individuals must be high. We can only speculate what the reasons may be. The thinning of vaginal mucosa with age may play a role; for both sexes, the prevalence of antibodies against herpes simplex virus 2 increases with age,¹¹ indicating continual risky sexual behaviour and enhanced risk of HIV transmission.

While sexual activity is the most likely mode of transmission, research is required to establish the relative contribution of different risk factors and modes of transmission.

One consistent finding is the failure to consider HIV as a cause of illness in older individuals. These individuals have a shorter time from diagnosis to onset of AIDS,¹ reflecting both age-related faster progression to AIDS and doctors’ failure to consider HIV as a diagnosis. Screening is less common for older adults, who are assumed not to be at risk.

HIV prevalence and incidence in the over-50-year-olds seem surprisingly high and the risk factors are totally unexplored. Understanding the epidemiology of HIV infection in older individuals can lead to interventions to make these years safer and more enjoyable. ■

References

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