Category Archives: Infectious Diseases Tropical Medicine and Sexually Transmitted Diseases

Further Reading

.Adler M (1990) The ABC of Sexually Transmitted Diseases, 2nd edn. London: BMA Publications.

Adler M (1993) The ABC of AIDS, 3rd edn. London:
BMA Publications.
Arnold E (1990) Modern vaccines. London: Lancet Publications.
Bannister B (1983) Infectious Diseases. London: Bailliere Tindall.
raude AI (1985) Infectious Diseases and Medical Microbiology, 2nd edn. Philadelphia: WB Saunders.
Collier L & Oxford J (1993) Human Virology. Oxford:
Oxford University Press.
Cook GC (1988) Communicable and Tropical Diseases.
London: (Mainstream Medicine series). Heinemann Medical Books.
Department of Health Welsh Office, Scottish Office Home and Health Department, DHSS (Northern Ireland) (1992) lmmunisation against Infectious Disease.
London: HMSO.
Farthing MJG (1990) Balliere’s Clinical Gastroenterology.
Virus Infections of the gut and liver. London: Bailliere Tindall.
Farthing MJG & Keusch GT (1989) Enteric Infection:
Mechanisms, Manifestations and Management. London:
Chapman and Hall.
Fields Virology (1990) London: Raven Press.
Field M (1991) Diarrheal Diseases. New York: Elsevier.
Gracey M & lAD Bouchier (1993) Bailliere’s Clinical Gastroenterology.
Infectious diarrhoea. London: Bailliere Tindall.
Mandel GL, Douglas RG & Bennett JE (1985) Principles and Practice of Infectious Diseases, 2nd edn. London:
Bailliere Tindall.
Mimms C, Playfair J, Roitt I, Wakelin D, Williams R & Anderson R (1993) Medical Microbiology. London:
Mosby .
Peters W, Gilles HM (1989) A Colour Atlas of Tropical Medicine & Parasitology, 3rd edn. Netherlands: Wolfe Medical Publications Ltd.
Youmans GP, Paterson PY & Sommers HM (eds) (1985).
The Biologic and Clinical Basis of Infectious Diseases, 3rd edn. Philadelphia: WB Saunders.
Zuckerman AI, Banntvala JE & Pattison JR (1990) Clinical Virology. London: Wiley.

Diagnosis

Detection of IgG antibody to envelope components (gp120 and its subunits) is the most commonly used marker of infection with HIV. The routine tests are based on ELISA techniques which may be confirmed with Western blot assays. Up to 3 months may elapse from initial infection to antibody production (the window period). These antibodies have no protective function. As with all IgG antibodies they cross the placenta. All babies born to HIV -infected women will thus have the antibodyat birth. In this situation HN antibody is not a reliable marker of active infection and in uninfected babies will be lost gradually over the first 18 months of life.  HIV antibody testing should be carried out only after full discussion of the implications with the patient and with the patient’s express consent.Additional viral antigens and host antibodies can be detected in blood.

VIRAL p24 ANTIGEN is detectable shortly after infection but has usually disappeared by 8-10 weeks after exposure. It can be a useful marker in individuals who have recently been infected and have not yet had time to mount an antibody response. It may reappear at low levels intermittently during the asymptomatic phase and also as infection progresses in some people, in whom it can be used as a surrogate marker of viral activity.
IGG ANTIBODY TO  can be detected from the earliest weeks of infection and through the asymptomatic phase. It is often lost as disease progresses.
ISOLATION OF VIRUS IN CULTURE AND DETECTION BY POLYMERASE CHAIN REACTION are specialized techniques available in some laboratories which may aid diagnosis.

Investigation and management

Initial assessment

History and examination will provide a basis for the clinical staging of infection and give insight into the patient’s approach and particular circumstances. Baseline investigations will depend on the clinical setting but for an asymptomatic person are shown in Practical box l.l. The aims of management are to maintain health, avoid transmission of HIV and provide appropriate palliative support. Confidentiality must be strictly adhered to and psychological support must be readily available for the patient, family, friends and carers. Dietary assessment and advice should be freely accessible. Clear advice on reducing the risk of transmission must be provided and future sexual practices discussed. Informtion needs to be available for people to make informed choices about childbearing. The implications for existing family members should be considered. General health promotion advice on smoking, drug misuse and exercise is important.

Baseline investigations for HIV infection.

Baseline investigations for HIV infection.

Therapy

Treatment strategies for specific conditions are discussed in the appropriate sections above. Various events in the HIV life-cycle have been identified as potential targets for antiretroviral therapy. Antagonists of reverse transcriptase are so far the most developed.

ZIDOVUDINE (3-AZIDO-3-DEOXYTHYMIDINE, AZT)

is an analogue of thymidine which inhibits reverse transcriptase and also acts as a DNA chain terminator. It is now widely used in the developed world in patients with symptomatic HIV disease (CDC Group IV). Studies have shown a survival advantage in people with AIDS taking AZT and a reduction in opportunistic infections. Constitutional symptoms may be ameliorated. Neurological disease may improve. A transient rise in CD4 lymphocytes and a fall in P24 antigen levels are seen on treatment.Clinical and survival benefits of AZT in HIV-positive asymptomatic patients still have to be conclusively demonstrated. Side-effects include headache, nausea, abdominal  discomfort and insomnia, all of which may resolve after several weeks on AZT. The most common toxicity is bone marrow suppression, particularly megaloblasticchange and suppression of the red cell line. Neutropenia also occurs. Myopathy may occur after long-term use. Adverse reactions are more frequent and severe in patients with more advanced disease and are to some extent  dose dependent. In vitro resistance of HIV to AZT may be seen after 6 months on treatment but its clinical significance is not clear. Dose regimens range from 500 to 1000 mg daily in divided doses.

DIDEOXYINOSINE (DDI) AND DIDEOXYCYTIDINE

(DDC) are also inhibitors of reverse transcriptase. They are less well evaluated than AZT. Side-effects include acute pancreatitis and peripheral neuropathy, but bonemarrow toxicity is rare. As a result they may be used as second line therapy in patients who cannot tolerate AZT.

OTHER DRUGS include non-nucleoside reverse transcriptase inhibitors and agents that act at other sites in the HIV replication cycle, e.g. protease inhibitors. These compounds are currently undergoing therapeutic trialsbut are not yet commercially available. Drugs used in combinations are also being evaluated. Prevention and control The development of an effective vaccine against HIV is being pursued but is not a realistic prospect in the near future. Changing behaviour is notoriously difficult, especially in areas that carry as many taboos as HIV and AIDS. It is however the main tool available for prevention of infection. Education programmes providing factual knowledge and strategies to avoid infection are fundamental to the process. The use of condoms has been shown to reduce the spread of HIV infection in discordant couples and their use has been strongly promoted. Control of other STOs is crucial in view of their potential role in enhancing HIV transmission. Access to clean needles and syringes to prevent sharing amongst drug users is important, as are programmes to reduce injecting drug use. Screening of blood products has reduced iatrogenic infection in developed countries but is expensive and not globally available. The need for blood transfusion in developing countries could be reduced by improved control of conditions such as malaria and hookworm, which lead to anaemia. Partner notification schemes are in various stages of development worldwide but are controversial. Availability and accessibility of confidential HIV testing is important and provides an opportunity for individual health education and risk reduction to be discussed.

Microsporidiosis

This is a frequent cause of diarrhoea. Spores can be detected with great accuracy in the stools using a trichrome or a fluorescent stain that attaches to the chitin of the spore surface. Albendazole is effective in eradicating the organism.

FUNGI

Cryptococcus

In the context of HIV with AIDS the commonest presentation is with meningitis, although it can cause pulmonary and disseminated infection. Clinical features of cryptococcal meningitis include headache, fever, impaired conscious level and abnormal affect. Neck stiffness and photophobia are rarely seen. The diagnosis is made on examination of the CSF (a CT scan must be performed first to exclude space-occupying lesions). India ink staining may show the organisms directly and cryptococcal antigen is positive at variabletitre. Cryptococci may be cultured from the CSF  and/or blood.
Signs associated with a poor prognosis include high organism count in the CSF, low white cell count in the CSF, and impaired conscious level at presentation. Treatment is with intravenous amphotericin B or fluconazole. Infection is not eradicated and lifelong maintenance therapy (usually with fluconazole) is needed to suppress infection.

Candida

Mucosal infection with C. albicans is extremely frequent in HIV-infected patients. Oropharyngeal involvement is common and oesophageal Candida causes dysphagia. HIV-infected women may have severe recurrent vulvovaginal Candida infection. Disseminated Candida is relatively uncommon in the context of HIV infection. Treatment is usually with systemic antifungal agents such as fluconazole and ketoconazole.

VIRUSES

Cytomegalovirus (CMV)

CMV is the cause of considerable morbidity in HIVinfected individuals, especially in the later stages of disease. The major problems encountered are retinitis, colitis, oesophagitis, encephalitis and pneumonitis. Polyradiculitis and adrenalitis may also be caused by CMV. The first two are the most common.
CMV RETINITIS. This occurs in up to 30% of AIDS cases and is the commonest cause of eye disease and blindness. Although usually unilateral to begin with the infection frequently progresses to involve both eyes. Presenting features depend on the area of the retina involved (loss of vision being most common with macular involvement) and include:
• Floaters
• Loss of visual acuity and scotoma
• Orbital pain and headache
Examination reveals haemorrhages and exudate which follow the vasculature of the retina (so-called pizza pie appearances). The features are highly characteristic and the diagnosis is made clinically. If untreated, retinitis spreads within the eye destroying the retina within its path. Routine fundoscopy should be carried out regularly on all HIV-infected patients to look for evidence of early infection. Treatment should be started as soon as possible with either ganciclovir or foscarnet. These agents halt disease but do not eradicate it. Reactivation occurs in a majority of cases and may lead to blindness in one or both eyes. Patients thus need long-term maintenance therapy but as these two agents are available only as intravenous preparations insertion of an indwelling line is necessary for long-term self-administered therapy.
CMV COLITIS. This is a cause of abdominal symptoms in AIDS. The usual presenting features include:
• Abdominal pain, often left iliac
• Diarrhoea which may be bloody
• Tenderness
• Low grade fever
Toxic dilatation of the colon may occur in severe cases. Sigmoidoscopy and biopsy may be performed safely if there is no evidence of toxic dilatation on the abdominal radiograph. Histology shows characteristic ‘owl’s eye’ cytoplasmic inclusion bodies. Treatment with ganciclovir or foscarnet is effective.
CMV may affect any site along the gastrointestinal tract giving rise to:
• Oesophageal ulcers, usually solitary in the lower third
• Small bowel ulceration
• An association with sclerosing cholangitis
• Hepatitis

Herpes

HSV types 1 and 2 cause frequent, severe, recurrent infections in people with HIV. There may be extensive ulceration and viral shedding may be prolonged in comparison to immunocompetent individuals. Genital, oral and occasionally disseminated infection are seen. Therapy with acyclovir is effective but frequent recurrences may need suppressive therapy. Acyclovir-resistant HSV (usually due to thymidine kinase-deficient mutations) in HIV-infected patients has become more common. Such strains may respond to foscarnet.

Papovavirus

Progressive multifocal leukencephalopathy (PML) is a demyelinating disease of cerebral white matter caused by papovavirus. The features are of progressive neurological and/or intellectual impairment. MRI scanning is the most sensitive and reveals characteristic multiple white matter lesions. Definitive diagnosis is made on histological and viral examination of brain tissue. There is no specifictreatment for the condition.

BACTERIAL INFECTIONS

Encapsulated bacteria such as Strep. pneumoniae, H. influenzae and Moraxella catarrhalis show an increased incidence in HIV infection and may result in pneumonia or disseminated disease. Recurrent episodes are common.The response to standard antibiotic therapy is usually  good, but long-term prophylaxis may be required if recurrent infection is frequent.

Non-typhoidal Salmonella spp. are frequent pathogens in HIV infection as intact cell-mediated immunity is a crucial part of host defence. Organisms are usually acquired orally and frequently result in disseminated infection. Gastrointestinal disturbance may be minimal, and once in the bloodstream any organ may be infected.
Response to standard antibiotic therapy, depending on laboratory sensitivities, is usually good in the acute phase but recurrent infection is common and long-term suppressive therapy may be necessary.

HN and AIDS 

Iiorating systemic symptoms but on the whole therapy is disappointing. Primary prophylaxis with rifabutin in profoundly immunosuppressed patients (CD counts < 100 mm “) may reduce the incidence of frank MAl infection.

TUMOURS

Kaposi’s sarcoma (KS)

This multifocal disease is caused by a proliferation of vascular endothelial cells, which form slit-like spaces similar to blood essels that trap red blood cells and cause the characteristic purple hue of the tumour. KS commonly involves:
• Skin
• Lymphatics and lymph nodes
• Lung
• Gut
Treatment depends on the site and extent of the lesions. Localized or cutaneous disease may respond to radiotherapy. Disseminated or visceral KS generally requires systemic chemotherapy. KS is particularly common in homosexual men and is rare in those who have acquired HIV via blood products or intravenous drug use. The possible existence of a sexually transmitted cofactor in the aetiology of the condition is being explored.

Lymphoma

Non-Hodgkin’s lymphoma (NHL) of B-cell origin occurs particularly in immunosuppressed individuals. In late stages of AIDS primary CNS NHL is common and responds poorly to therapy. However primary NHL outside the CNS (e.g. gastrointestinal tract or lung) may occur at earlier stages of immunosuppression and is more responsive to therapy.

Mycobacterial infections

An association between HIV infection and M. tuberculosis was recognized early in the epidemic. TB can cause disease when there is only minimal immunosuppression and thus often appears early in the course of HIV infection. In many countries where HIV is spreading and tuberculosis is endemic there is a substantial increase in the incidence of tuberculosis. Cases of HIV-related tuberculosis frequently represent reactivation of latent TB. There is also evidence for newly acquired infection and nosocomial spread in HIV-infected populations. The pattern of disease differs from that in the immunocompetent host in that extra pulmonary and disseminated infection is more common. The response to tuberculin testing is blunted in HIV -positive individuals and is unreliable. Sputum examination may be negative even in pulmonary infection and culture techniques are the best diagnostic tool.
TB usually responds well to standard treatment regimens, although there are increasing numbers of cases of multidrug resistance occurring in HIV-infected individuals, particularly in the USA. Increasing numbers of drugs are used in combination. Treatment is not curative and lifelong maintenance, usually with isoniazid, is required. HIV-infected individuals have shown a high frequency of severe adverse reactions to thioacetazone and this drug, although widely used for tuberculosis in developing countries, should be avoided in this group of patients if possible.
Atypical mycobacteria, particularly M. avium intracellulare complex (MAr) generally appear only in the later ages of AIDS when patients are profoundly immunosuppressed. It is a saprophytic organism of low pathogen- . ity that is ubiquitous in soil and water. Entry may be via the gastrointestinal tract or lungs with dissemination ill infected macrophages.
The major features are of fevers, weight loss and anoreria, Dissemination to the bone marrow causes anaemia. ointestinal symptoms may be prominent with diarand malabsorption. At this stage of disease patients . have other concurrent infections and differentiating AI on clinical grounds is difficult. Direct examination culture of bone marrow, liver, blood or lymph node the diagnosis most reliably.
Mai is  typically resistant to standard antituberculous pies. Newer drugs such as rifabutin in combination c1arithromycin and clofazirnine have shown some mise in reducing the burden of organisms and ameIiorating systemic symptoms but on the whole therapy is disappointing. Primary prophylaxis with rifabutin in profoundly immunosuppressed patients (CD counts < 100 mm “) may reduce the incidence of frank MAl infection.

TUMOURS

Kaposi’s sarcoma (KS)

This multifocal disease is caused by a proliferation of vascular endothelial cells, which form slit-like spaces similar to blood vessels that trap red blood cells and cause the characteristic purple hue of the tumour. KS commonly involves:
• Skin
• Lymphatics and lymph nodes
• Lung
• Gut
Treatment depends on the site and extent of the lesions. Localized or cutaneous disease may respond to radiotherapy. Disseminated or visceral KS generally requires systemic chemotherapy.
KS is particularly common in homosexual men and is rare in those who have acquired HIV via blood products or intravenous drug use. The possible existence of a sexually transmitted cofactor in the aetiology of the condition is being explored.

Lymphoma

Non-Hodgkin’s lymphoma (NHL) of B-cell origin occurs particularly in immunosuppressed individuals. In late stages of AIDS primary CNS NHL is common and responds poorly to therapy. However primary NHL outside the CNS (e.g. gastrointestinal tract or lung) may occur at earlier stages of immunosuppression and is more responsive to therapy.

Persistent generalized lymphadenopathy (PGL) (eDe Group III)

A subgroup of patients with asymptomatic HIV infection have PGL, defined as lymphadenopathy (>1 ern) at two or more extra-inguinal sites for more than 3 months in the absence of causes other than HIV infection. The nodes are usually symmetrical, firm, mobile and non-tender. There may be associated splenomegaly. The architecture of the nodes shows hyperplasia of the follicles and proliferation of the capillary endothelium. Biopsy is rarely indicated. Similar disease progression has been noted in asymptomatic patients with or without PGL. Nodes may  isappear with disease progression. The same laboratory markers as above are used to monitor patients. ‘USA definition also includes those with a CD4 count <200/mm3.

Symptomatic HIV infection (one Group IV)

Clinical evidence of progression of HIV infection is manifested by an array of symptoms and signs and CD4 cell counts decrease. Susceptibility to a range of opportunistic and conventional pathogens and tumours is increased as immunosuppression becomes more profound. Immunodeficiency leads to the following problems in clinical practice:
• Susceptibility to opportunistic infections and tumours
• Presence of multiple infections at one time
• Lack of typical signs and symptoms due to failure of the inflammatory response, e.g. cryptococcal meningitis commonly presents without signs of meningism and there may be no white cells present in the CSF These features mean that tissue or body fluid is required to directly identify infecting organisms.

CONSTITUTIONAL SYMPTOMS

Include general lassitude, weight loss, night sweats (often soaking the sheets) and diarrhoea. Such symptoms may be the earliest signs of major infections or malignancies or can be a direct result of HIV infection.
SKIN AND MUCOUS MEMBRANES are frequently the site of bacterial, fungal and viral infections. An intensely pruritic, papular eruption favouring the extremities may be found, particularly in patients from sub-Saharan Africa. Generalized dry, itchy, flaky skin is typical and hair may become thin and dry. Seborrhoeic dermatitis occurs on the face and trunk. Folliculitis, usually bacterial and often generalized, is common. Stomatitis, recurrent aphthous ulcers and gum disease may impair the patient’s ability to eat. Oral candidiasis is frequently extensive with associated angular cheilitis. In female patients recurrent severe vulvovaginal candidiasis may occur. Oral hairy leucoplakia is a sign of imrnuno-suppression first noted in HIV but now also recognized in other conditions. It appears intermittently on the lateral borders of the tongue or the buccal mucosa as a pale, ridged lesion. It is usually asymptomatic although patients may find it unsightly and occasionally painful. It shows a variable response to acyclovir. Aetiology is not clear but Epstein Barr virus (EBV) particles can be identified histologically. Labial and genital Herpes simplex virus (HSV) occur with increasing frequency and severity. Herpes zoster may occur in an atypical pattern, affecting more than one dermatome or becoming disseminated. Human papillomavirus (HPV) infection produces genital, planar and occasionally oral warts which may be slow to respond to therapy and recur repeatedly. The association of HPV with cervical and anal intraepithelial neoplasia in HIV -infected patients is still subject to scrutiny; however female patients should have cervical cytology on at least an annual basis. Molluscum contagiosum is very common appearing in atypical sites particularly on the face and around the eyes.

NEUROLOGICAL DISEASE (CDC Group IVB).

The mechanism for the causation of neurological dysfunction is not well understood but may result from direct infection of the glial cells and/or the effects of viral products on neurones. Loss of neurones and vacuolization occur in advanced nfection. Direct HIV pathology must be differentiated from opportunistic infections and tumours as the management strategies differ.
There may be a sensory polyneuropathy, ranging from mild paraesthesia to severe pain usually in the lower limbs. A progressive myelopathy can occur producing motor signs in the legs and sphincter disturbance. Autonomic neuropathy may be seen. Intellectual and cognitive impairment can occur, usually in the later stages of disease. The onset is usually insidious, with decrease in memory, poor concentration and personality change. Changes in affect are common and depressive or psychotic features can be present. Functional psychiatric disorders must be differentiated from organic disease. CT scan reveals varying degrees of atrophic change and EEG may give an encephalopathic picture.

GASTROINTESTINAL MANIFESTATIONS.

Weight loss, diarrhoea and malabsorption are all common problems in chronic HIV infection. Anorexia, nausea and vomiting frequently complicate acute episodes of opportunistic infection and their therapy. An HIV enteropathy has been described but the exact role of HIV in the pathogenesis of diarrhoea and malabsorption is not clear.The major conditions affecting the gastrointestinal tract in HIV infection.

HAEMATOLOGICAL COMPLICATIONS OF HIV

INFECTION. Anaemia, neutropenia and thrombocytopenia are all common in advanced HIV infection and may indicate underlying opportunistic infection or tumour, particularly if the patient is pancytopenic. All may be exacerbated iatrogenically.
1 Anaemia of chronic HIV infection is usually mild, normocytic and normochromic.
2 Neutropenia is common and usually mild.
3 Thrombocytopenia may be the only manifestation of HIV infection. Platelet counts are often moderately reduced, but may fall dramatically (10-20 x 109/litre) producing easy bruising and bleeding. The aetiology is unclear. Megakaryocytes are increased in the bone marrow but function may be impaired. Circulating antiplatelet antibodies may lead to peripheral destruction. Opportunistic disease in H IV infection As immunosuppression increases patients are susceptible to a wide range of infections and tumours. In an individual patient the clinical consequences of HIV -related immune dysfunction will depend on:
THE MICROBIAL EXPOSURE OF THE PATIENT

THROUGHOUT LIFE. Many of the clinical episodes represent reactivation of previously acquired infection which has been latent. Geographical factors are important in determining the microbial repertoire of an individual patient. Those organisms requiring intact cell-mediated immunity for their control are most likely to cause clinical problems.

Mucocutaneous manifestations of HIV infection.

Mucocutaneous manifestations of HIV infection.

THE PATHOGENICITY OF ORGANISMS ENCOUNTERED.

High-grade pathogens such as M. tuberculosis, Candida and herpes viruses are clinically relevant even when immunosuppression is mild and will thus occur earlier in the course of disease. Susceptiblity to infections such as Pneumocystis carinii occur at later stages of immunodeficiency (usually when the CD4 cell count is less than 200/mm3)

THE DEGREE OF IMMUNOSUPPRESSION OF THE HOST

When patients are severely imrnunocompromised (CD4 cell count <100/mm3), disseminated infections with organisms of very low pathogenicity, such as atypical mycobacteria and cryptosporidia occur. These infections are very resistant to treatment, not only because there are no good antimicrobial treatments available, but also because there is no functioning immune response. This hierarchy of infection allows for appropriate intervention with prophylactic drugs.
A summary of the infections in AIDS is given. The most important are described below.

PROTOZOA

Pneumocystis carinii

This organism most commonly causes pneumonia (PCP) ut can cause disseminated infection. The characteristic presenting features are persistent, non-productive cough, increasing shortness of breath, hypoxia and fever. The clinical features and investigation are discussed on Typically the chest X-ray shows a diffuse interstitial shadowing extending through the mid-zones bilaterally. In mild cases both the clinical examination and the chest X-ray may be within normal limits.

Major pathogens in HIV infection.

Major pathogens in HIV infection.

Treatment should be instituted as early as possible. The first line therapy is with high doses of co-trimoxazole orintravenous pentamidine for 21 days. In severe cases the addition of systemic corticosteroids has been shown to reduce mortality.
Recurrence is frequent but can be largely prevented by the use of low-dose co-trimoxazole (960 mg thrice weekly) or nebulized pentamidine (300 mg monthly). Prevention of PCP with the use of primary prophylaxis in HIV -infected patients known to be at risk of PCP (those with CD4 cell counts <200/mm3) has led to a marked reduction in incidence from around 50% to 5% in the UK. Although systemic prophylaxis is associated with a greater incidence of side-effects, nebulized pentamidine only protects the lungs and extrapulmonary pneumocystosis may occur in patients on this therapy.

Toxoplasmosis

Toxoplasma gondii most commonly causes encephalitis and cerebral abscesses in the context of AIDS, due usually to reactivation of previously acquired infection. Up to 45% of AIDS patients who have antibodies to T. gondii may still develop cerebral toxoplasmosis. Features of cerebral toxoplasmosis include focal neurological signs, convulsions, headache, multiple ring-enhancing lesions on CT scan, and positive IgG anti- Toxoplasma serology. The diagnosis is usually made on the basis of the CT or MRI brain scan. If there is doubt stereotactic brain biopsy can be performed.
Treatment is with pyrimethamine in combination with sulphonamide. Clindamycin and pyrimethamine may be used in sulphonarnide-sensitive patients. These regimens will control but not eradicate infection and thus lifelong maintenance is required to prevent relapse. Newer drugs are undergoing evaluation to eradicate the cysts of toxoplasmosis and potentially cure the infection.

Cryptosporidiosis

Cryptosporidium parvum can cause a self-limiting acute diarrhoea in an immunocompetent individual. In HIV infection it can cause a severe and progressive watery diarrhoea which may be associated with anorexia, abdominal pain, nausea and vomiting. Cysts attach to the epithelium of the wall of small bowel causing secretion of fluid into the gut lumen and leading to failure of absorption. It is associated with sclerosing cholangitis. The cysts may be seen on stool specimens stained with Kinyoun acid fast stain. The organism can be easily seen on small bowel biopsy specimens.
Treatment is largely supportive as there are no effective antimicrobial agents available other than a nonabsorbable aminoglycoside, paromamycin, which may have a limited effect on diarrhoea.

HIV and AIDS

Introduction

HIV was identified as the causative organism of AlDS in 1983. Current WHO estimates are of 13 million adults infected worldwide, of whom 2.5 million have died. By the year 2000 WH 0 estimates that there will be up to 80 million infections worldwide. In the UK, women currently account for 15% of known HIV infections and 6%
of AIDS cases reported.

Epidemiology

Despite the fact that HIV can be isolated from a wide range of body fluids and tissues the majority of infections are transmitted via semen, cervical secretions and blood. Transmission is via the following routes. Sexual intercourse (vaginal and anal) Worldwide, heterosexual intercourse accounts for the vast majority of infections, and coexistent STDs, especially those causing genital ulceration, enhance transmission. Passage of HIV appears to be more efficient from men to women than vice versa. There is a geographical variation in the epidemiology. In Europe, USA and Australasia the initial wave of infection was amongst homosexual men with a second wave developing amongst intravenous drug users and their sexual partners. The incidence of HIV in heterosexuals is rising and is likely to form a further epidemic wave over the next 20-30 years.
In central and sub-Saharan Africa the ratio of women to men is at least 1 : 1, the predominant mode of spread being heterosexual intercourse. Similar patterns are seen in South-East Asia, the Indian subcontinent and Latin America.
Mother to child (prenatally, perina tally, breastfeeding) As more women in their reproductive years are infected the numbers of babies acquiring HIV vertically will increase. European studies suggest that 14% of babies born to HIV-infected women are likely to be infected although rates of up to 40% have been reported from Africa and USA. Transmission can occur in utero, during childbirth or via breast milk. Contaminated blood, blood products and organ donations Screening of blood and blood products was introduced in 1985 in Europe and North America. Prior to this HIV infection was associated with the use of clotting factors (for haemophilia) and with blood transfusions. Clotting factors are now heat treated and the risk of transfusionrelated HIV infection in developed countries is tiny. In some countries where this is not possible or in areas of the world where the rate of new HIV infections is very high the risk of transfusion-associated transmission remains significant.
Contaminated needles (intravenous drug misuse, injections, needlestick injuries) The practice of sharing needles and syringes for intravenous drug use continues to be a major route of transmiSSIOn of HIV. Iatrogenic transmission from needles and syringes in developing countries is reported. Health care workers have a risk of approximately 0.3% following a single needlestick injury with known HIV-infected blood. There is no evidence that HIV is spread by social or household contact nor by blood-sucking insects such as mosquitoes and bed bugs. The virus HIV belongs to the lentivirus group of the retrovirus family. There are at least two types, HIV-1 and HIV-2. HIV- 2 is almost entirely confined to West Africa where it is associated with an AIDS-type illness. Retroviruses are characterized by the possession of the enzyme reverse transcriptase, which allows viral RNA to be transcribed into DNA, and thence incorporated into the host cell genome.
The structure of the virus is illustrated. Glycoproteins on the surface of the virus bind to target cells. Multiple regulatory proteins are encoded by the virus which controls the life-cycle and viral expression. shows the sequence of events in the reproductive  cycle of the virus within infected cells.

IMMUNOPATHOGENESIS 

The cellular receptor for HIV is the CD4 molecule, which defines the cells that are susceptible to infection. Many cells within the immune system bear this molecule and include CD4+ T lymphocytes (which are most affected). A number of pathogenic mechanisms have been described to account for the profound cellular immunodeficiency. There is a progressive and severe depletion of CD4 ‘helper’ lymphocytes and it is this that leads to the clinical manifestation of HIV infection.

Structure of HIV.

Structure of HIV.

HIV entry and replication in CD4 T lymphocytes. The virus replicates by making a DNA copy (provirus) of its diploid RNA (using reverse transcriptase) which then becomes inserted into the host cell chromosomal DNA. This then provides RNA genomes for a progeny of new viruses.

HIV entry and replication in CD4 T lymphocytes. The
virus replicates by making a DNA copy (provirus) of its diploid
RNA (using reverse transcriptase) which then becomes inserted
into the host cell chromosomal DNA. This then provides RNA
genomes for a progeny of new viruses.

Clinical features

The spectrum of illness associated with HIV infection is broad. Several classification systems exist, the most widely used being the Centers for Disease Control (cnc) classification (Information box 1.5). As immunosuppression progresses the patient is susceptible to an increasing range of opportunistic infections and tumours, certain of which meet the criteria for a diagnosis of AIDS (Information box 1.6). Since 1993 the definition of AIDS has differed between the USA and Europe. The USA definition includes individuals with CD4 cell counts of less than 200 mm ” in addition to the clinical classification based on the presence of specific indicator diagnoses shown in Information box 1.6. In Europe the definition remains based on the diagnosis of specific clinical conditions with no inclusion of CD4 lymphocyte counts.

Acute primary infection (CDC Group I)

The majority of HIV seroconversions are asymptomatic. In a small proportion, a self-limiting non-specific illness occurs 4-8 weeks after exposure. Symptoms include fever, arthralgia, myalgia, lethargy, lymphadenopathy, sore throat and occasionally a transient, faint, pink maculopapular rash. Neurological symptoms are common including headache, photophobia, myelopathy, neuropathy and in rare cases encephalopathy. The illness lasts up to 3 weeks and recovery is usually complete.
Laboratory abnormalities include lymphopenia with atypical reactive lymphocytes noted on the blood film, thrombocytopenia and raised liver transaminases CD4 .lymphocytes may be markedly depleted and the CD4 : CDS ratio reversed. Antibodies to HIV may be absent during this early stage of infection although the viral core protein antigen may be present. There is evidence to suggest that patients experiencing a severe seroconversion illness may progress more quickly to AIDS.

Summary of classification system for HIV infection.

Summary of classification system for HIV
infection.

AIDS-defining diagnoses (1993 classification, Europe').

AIDS-defining diagnoses (1993
classification, Europe’).

Asymptomatic infection (eDe Group II)

The majority of people with HIV infection are asymptoatic, but the  irus continues to replicate and the person remains infectious. The  uration of an asymptomatic carrier state is variable but studies  uggest a mean of 10 years – om infection to development of AIDS. The natural history of HIV infection has yet to be studied for long enough to know whether all those with asymptomatic ection progress to AIDS.
Various laboratory markers of progression are used to onitor asymptomatic patients and to guide therapeutic intervention. The most commonly used are:
• Depletion of CD4 lymphocyte counts and percentages
• Raised CDS lymphocyte counts and percentages
• Reversed CD4 : CDS ratios
• Raised serum 132-microglobulin
• Raised serum and urinary neopterin
• Raised p24 antigen titre
• Falling p24 antibody titre

CLINICAL FEATURES

Vaginal discharge and odour are the commonest complaints although a proportion of women are asymptomatic. A homogeneous, greyish white, adherent discharge is present in the vagina, the pH of which is raised (greater than 5). Associated complications are ill-defined but may include chorioamnionitis and an increased incidence of premature labour in pregnant women. Whether BV disposes non-pregnant women to upper genital tract infection is unclear.

DIAGNOSIS

Different authors have differing criteria for making the diagnosis of BV. In general it is accepted that three of the following should be present for the diagnosis to be made:

1 Characteristic vaginal discharge.
2 A raised vaginal pH using narrow range indicator paper (>4.7).
3 A fishy odour on mixing a drop of discharge with 10% potassium hydroxide.
4 The presence of clue cells on microscopic examination of the vaginal fluid. Clue cells are squamous epithelial cells from the vagina which have bacteria adherent to their surface giving a granular appearance to the cell. A Gram stain gives a typical mixed reaction. Additional laboratory tests include cultures for G. vaginalis but this is non-specific as the organism can be recovered in over 50% of women who do not meet the clinical diagnostic criteria for BV. Metabolic by-products of the altered vaginal flora may be detected using gas or thin layer chromatography.

MANAGEMENT

Metronidazole given orally in doses of 800-1200 mg daily for 5-7 days is usually recommended. A single dose of 2 g metronidazole is less effective. Penicillins and other J3-lactam antibiotics are much less useful presumably because of J3-lactamase production by anaerobes. Topical clindamycin is being evaluated in the UK and is available in the USA where it seems efficacious. Topical acetic acid gel has been used with mixed results.
The rate of recurrence is high with some studies giving a recurrence rate of 80% within 9 months of completing metronidazole therapy. There is debate over the treatment of asymptomatic women who fulfil the diagnostic criteria for BV. The diagnosis should be fully discussed and treatment offered if the woman wishes. Until the relevance of BV to other pelvic infections is elucidated the routine treatment of all women with BV is not to be recommended. There is no convincing evidence that simultaneous treatment of the male partner influences the rate of recurrence of BV and routine treatment of male partners is not indicated.

INFESTATIONS

Pediculosis pubis

The pubic louse (Phthirius pubis) is a blood-sucking insect which attaches tightly to the pubic hair. It is rela-tively host specific and is transferred only by close bodily contact. Eggs (nits) are laid at hair bases and hatch within a week. Although infestation may be asymptomatic the commonest complaint is of itch.

DIAGNOSIS

Lice may be seen on the skin at the base of pubic hairs. They may resemble small scabs or freckles but if they are picked up with forceps and placed on a microscope slide will move and walk away. Nits are usually closely adherent to hairs. Both are highly characteristic under the low power microscope. As with all sexually transmitted infections the patient must be screened for coexisting pathogens.

TREATMENT

It is important that both lice and eggs are killed. This is achieved with 1% y-benzene hexachloride or 0.5% malathion. The preparation should be applied to all areas of the body from the neck down and washed off after 24 hours. In a few cases a further application at 1 week may be necessary. In severe infestations antipruritics may be indicated for the first 48 hours. All sexual partners should be seen and screened.

Warts

Anogenital warts are amongst the commonest sexually acquired infections with ever growing numbers of people seeking treatment. The causative agent is human papillomavirus (HPV) especially types 6 and 11. HPV is acquired by direct sexual contact with a person with either clinical or subclinical infection. Neonates may acquire HPV from an infected birth canal which may result either in anogenital warts or in laryngeal papillomas. The incubation period may range from 2 weeks to 8 months or even longer.

CLINICAL FEATURES

Warts may develop around the external genitalia in women, usually starting at the fourchette and may involve the perianal region. The vagina may be infected. Flat warts may develop on the cervix that may not be easily visible on routine examination. Such lesions may have an association with cervical intraepithelial neoplasia and may be diagnosed on cervical cytology or at colposcopy. In men the penile shaft and sub preputial space are the commonest sites although warts may involve the urethra and meatus. Perianal lesions are more common in men who practise anoreceptive intercourse but may be found in any patient. The rectum may become involved. Warts may become more florid during pregnancy or in immunosuppressed patients.

DIAGNOSIS

The diagnosis is essentially clinical. It is important to differentiate condylomata lata of secondary syphilis.Unusual lesions should be biopsied if the diagnosis is in doubt. Up to 30% of patients may have coexisting infections with other STDs and a full screen is important.

TREATMENT

Local agents include podophyllin extract 10-25%, podophyllotoxin and trichloroacetic acid. In extensive or recalcitrant infection cryotherapy, electrocautery or laser ablation is indicated. Podophyllin is contraindicated in pregnancy. Sexual contacts should be examined and treated if necessary. In view of the difficulties of diagnosing subclinical HPV, condoms should be used for up to 8 months after treatment. Because of the association of HPV with cervical intraepithelial neoplasia women with warts and female partners of men with warts are advisedto have cervical cytology carried out annually. Some clinics advocate colposcopy for all women with HPV infection.

Hepatitis B

Sexual contacts should be screened and offered vaccine if they are not immune.

Trichomoniasis

Trichomonas vaginalis (TV) is a flagellated protozoon which is predominantly sexually transmitted. It is able to attach to squamous epithelium and can infect the vagina and urethra. Infected women may, unusually, be asymptomatic. Commonly the major complaints are of vaginal discharge which may be offensive and of local irritation. Examination often reveals a frothy yellowish vaginal discharge and erythematous vaginal walls. The cervix may have multiple small haemorrhagic areas which lead to the description ‘strawberry cervix’. In men the infection is usually asymptomatic but may be a cause of NGU.

DIAGNOSIS

Phase-contrast microscopy of a drop of vaginal discharge shows TV swimming with a characteristic motion. Many polymorphonuclearleucocytes are also seen. Culture techniques are good and confirm the diagnosis.

TREATMENT

Metronidazole 400 mg twice daily for 7 days is the treatment of choice. There is some evidence of resistance although a single dose of 2 g can be given. Nimorazole may be effective in these cases. Topical therapy with clotrimazole may be effective but if extra-vaginal infection exists this may not be eradicated and vaginal infection reoccurs. It is important that male partners are followed up especially as they are likely to be asymptomatic.

Candidiasis

‘ulvovaginal infection with Candida albicans is extremely common. The organism is also responsible for balanitis in men. Candida may be isolated from the vagina in a high proportion of women of childbearing age, many of whom will have no symptoms. The role of Candida as pathogen or commensal is difficult to disentangle and it may be changes in host environment which allow the organism to produce pathological effects. Predisposing factors include pregnancy, the oral contraceptive pill, diabetes and broadspectrum antibiotics. Immunosuppression can produce more florid infection.

CLINICAL FEATURES

In women pruritus vulvae is the dominant symptom. Vaginal discharge is present in varying degree. Many women have only one or occasional isolated episodes but in a minority of patients the symptoms may be recurrent or chronic. Examination reveals erythema and swelling of the vulva with broken skin in severe cases. The vagina may contain adherent curdy discharge. Men may have a florid balanoposthitis. More commonly self-limiting burning penile irritation immediately after sexual intercourse with an infected partner is described. Diabetes must be excluded in men with balanoposthitis.

DIAGNOSIS

Microscopic examination of a smear from the vaginal wall reveals the presence of spores and mycelia. Culture of swabs should be undertaken but may be positive in women with no symptoms. It is important to exclude Trichomonas and bacterial vaginosis in women with itch and discharge.

TREATMENT

Pessaries or creams containing one of the imidazole antifungals such as clotrimazole used intravaginally are usually effective. Nystatin is also useful. The triazole drugs such as fluconazole 150 mg single dose or itraconazole 200 mg twice in 1 day may be used systemically in circumstances where topical therapy has failed or is inappropriate. Although the evidence for sexual transmission of Candida is slight, male partners of women with frequent recurrent episodes should be reviewed and possibly treated.

Bacterial vaginosis

Bacterial vaginosis (BV) or non-specific vaginosis is a disorder characterized by an offensive vaginal discharge. The aetiologyand pathogenesis is unclear but the normal lactobacilli of the vagina are replaced by a mixed flora of Gardnerella vaginalis, anaerobes including Bacteroides, and Mycoplasma hominis. Amines and their breakdown products from the abnormal vaginal flora are thought to be responsible for the characteristic odour associated with the condition. As vaginal inflammation is not part of the syndrome the term vaginosis is used rather than vaginitis. It is not clear to what extent BY is a sexually transmitted condition

Lymphogranuloma venereum (lGV)

Chlamydia trachomatis types 1, 2 and 3 is responsible for this sexually transmitted infection. It is endemic in the tropics, with the highest incidences in Africa, India and South East Asia.

CLINICAL FEATURES

The primary lesion is a painless ulcerating papule on the genitalia and only occurs in one-quarter of the patients. A few days after this heals, regional lymphadenopathy develops. The lymph nodes are painful and fixed and the overlying skin develops a dusky erythematous appearance. Finally, nodes may become fluctuant (buboes) and may rupture. Acute LGV may present as proctitis with perirectal abscesses, the appearances sometimes resembling anorectal Crohn’s disease.

DIAGNOSIS

The diagnosis is made on the basis of:
• The characteristic clinical picture
• Isolation of an LGV strain of C. trachomatis (only possible in specialized laboratories)
• Immunofluorescence using specific monoclonal antibodies for identifying organisms in pus from a bubo
• A rising titre in a complement-fixation test

The intradermal Frei test is non-specific and unreliable.
Great care must be taken to exclude syphilis and genital herpes.

TREATMENT

Early treatment with oxytetracycline 500 mg four times daily for at least 2 weeks is generally necessary. Chronic infection may result in extensive scarring and abscess and sinus formation. Surgical drainage may be required. Sexual partners should also be treated.

Granuloma inguinale

Granuloma inguinale is the least common of all STDs in North America and Europe, but is endemic in the tropics and subtropics, particularly the Caribbean, South-East Asia and South India. Infection is caused by Calymmatobacterium granulomatis, a short, encapsulated Gramnegative bacillus. The infection was also known as Donovanosis, the organism originally being known as Donovan’s body. Although sexual contact appears to be the most important mode of transmission, the infection rates are low, even between sexual partners of many years’ standing.

CLINICAL FEATURES

In the vast majority of patients, the characteristic, heapedup ulcerating lesion with prolific red granulation tissue appears on the external genitalia, perianal skin or the inguinal region within 1-4 weeks of exposure. However, almost any cutaneous or mucous membrane site can be involved, including the mouth and anorectal regions. Extension of the primary infection from the external genitalia to the inguinal regions produces the characteristic lesion, the ‘pseudo-bubo’.

DIAGNOSIS

The clinical appearance usually strongly suggests the diagnosis but C. granulomatis (Donovan bodies) may be identified intracellularly in scrapings or biopsies of an ulcer. Culture or serological methods of diagnosis are not available.

TREATMENT

Antibiotic treatment should be given for at least 10-14 days. Tetracycline 500 mg four times daily, streptomycin 1 g twice daily i.m. or ampicillin 500 mg four times daily are the three most commonly used drugs. Alternatives include erythromycin and chloramphenicol.

Herpes simplex

Genital herpes is one of the commonest STDs worldwide – in 1990 in the UK 20 000 new cases were seen in GUM clinics. Transmission occurs during close contact with a person who is shedding virus. Genital contact with oral lesions caused by HSV-1 can produce genital infection. HSV can be divided into types 1 and 2. Both can cause genital infection although type 1 is typically associated with sores on the lips. Susceptible mucous membranes include the genital tract, rectum, mouth and oropharynx. The virus has the ability to establish latency in the dorsal root ganglia by ascending peripheral sensory nerves from the area of inoculation. It is this ability which allows for recurrent attacks.

CLINICAL FEATURES

Asymptomatic infection has been reported but is rare. Primary genital herpes is usually accompanied by systemic symptoms of varying severity including fever, myalgia and headache. Multiple painful shallow ulcers develop which may coalesce. Tender inguinal lymphadenopathy is usual. Over a period of 10-14 days the lesions develop crusts and dry. In women with vulval lesions the cervix is almost always involved. Rectal infection may lead to a florid proctitis. Neurological complications can include aseptic meningitis and/or involvement of the sacral autonomic plexus leading to retention of urine. Recurrent attacks may be expected in a significant proportion of people following the initial episode. Precipitating factors vary amongst individuals as does the frequency of recurrence. Recurrent attacks are usually less severe. A symptom prodrome may be present in some people prior to the appearance of lesions. Systemic symptoms are rare in recurrent attacks.
The clinical manifestations in immunosuppressed patients (including those with HIV) may be more severe and recurrences may occur with greater frequency. Systemic spread has been documented.

DIAGNOSIS

Although the history and examination may be highly suggestive of HSV infection a firm diagnosis can only be made on the basis of isolation of virus from lesions. Swabs should be taken and placed in viral transport medium. Virus is most easily isolated from new lesions.

MANAGEMENT

Primary

Salt water bathing or sitting in a warm bath is soothing and may allow the patient to pass urine with some degree of comfort. Oral acyclovir (200 mg five times daily initially for 5 days) is useful if patients are seen whilst lesions are still moist. If lesions are already crusting acyclovir will do little to change the clinical course. Secondary bacterial infection may occasionally be present and should be treated. Rest, analgesia and antipyretics should be advised. In rare instances patients may need to be admitted to hospital and acyclovir given intravenously, particularly if HSV encephalitis is suspected.

Recurrence

Recurrent attacks tend to be much less severe and can be managed with simple measures such as salt water bathing. Psychological morbidity may be associated with recurrent genital herpes and frequent recurrences impose strains on relationships; patients need considerable support. Longterm suppressive acyclovir therapy can be given in patients with frequent recurrences. An initial course of 200 mg three to four times daily for 6 months usually reduces the frequency of attacks although there may still be some breakthrough.

Pregnancy

If HSV is acquired for the first time during pregnancy transplacental infection of the fetus may occur. For women with previous infection or primary infection at the time of labour concern focuses on the baby acquiring HSV from the birth canal. The risk is very low in recurrent attacks but rather greater in a primary episode.
Obstetric opinion is divided but if the woman has an attack around the time of labour Caesarian section may be performed. Acyclovir is not licensed for use in pregnancy but studies are being carried out to evaluate its use in the last few weeks of pregnancy in women with recurrent HSV.

PREVENTION AND CONTROL

Patients must be advised that they are infectious when lesions are present; sexual intercourse should be avoided during this time or during prodromal stages. Condoms may not be effective as lesions may occur outside the areas covered. Sexual partners should be examined and may need information on avoiding infection.

DIAGNOSIS

TP is not amenable to in vitro culture-the most sensitive and specific method is identification by dark-ground microscopy. Organisms may be found in variable numbers from primary chancres and the mucous patches of secondary lesions. Individuals with either primary or secondary disease are highly infectious. Serological tests used in diagnosis are either treponemal specific or non-specific. Three main tests are used routinely:
1 The VDRL (Venereal Disease Reference Laboratory) is non-specific but is a useful screening test, becoming positive within 3-4 weeks of the primary infection. It generally becomes negative by 6 months after treatment. It is a quantifiable test which can be used to monitor treatment efficacy and is helpful in assessing disease activity. The VDRL may also become negative in untreated patients (50% of patients with late stage syphilis). False-positive results may occur in other conditions particularly: infectious mononucleosis, hepatitis, Mycoplasma infections, some protozoal infections, cirrhosis, malignancy, autoimmune disease and chronic infections.
2 T. pallidum haemagglutination assay (TPHA) and fluorescent treponema antibodies absorbed (FTA-ABS) test are both highly specific for treponemal disease but will not differentiate between syphilis and other conditions such as yaws.
3 The FTA-ABS test is positive in more than 90% of patients with primary infection and in all patients with latent and late syphilis. It remains positive for life, even after treatment.
All serological investigations may be negative in early primary syphilis. The diagnosis will then hinge on positive dark-ground microscopy and treatment should not be delayed if serological tests are negative in such situations. In certain cases examination of the CSF for evidence of neurosyphilis and a chest X-ray to determine the extent of cardiovascular disease will be indicated.

Syphilis serology.

Syphilis serology.

TREATMENT

Early syphilis (primary or secondary) should be treated with long-acting procaine penicillin 1.2 g daily by intramuscular injection for 10 days. When compliance is in doubt, a single injection of benzathine penicillin 2.4 g will maintain adequate levels of drug for approximately 2 weeks. For late stage syphilis, particularly when there is cardiovascular or neurological involvement, the treatment course should be extended to 4 weeks. For patients sensitive to penicillin, either tetracycline or erythromycin may be given. Tetracycline is contraindicated in pregnancy. The Jarisch-Herxheimer reaction, which is due to release of endotoxin when large numbers of organisms are killed by antibiotics, is seen in 50% of patients with  primary syphilis and up to 90% of patients with secondary syphilis. It occurs about 8 hours after the first injection and usually consists of mild fever, malaise and headache lasting several hours. In cardiovascular or neurosyphilis the reaction, although rare, may be severe and exacerbate the clinical manifestations. Prednisolone given for 24 hours prior to therapy ameliorates the reaction. Penicillin should not be withheld because of the Jarisch-Herxheimer reaction; since it is not a dose-related phenomenon, there is no value in giving a smaller dose.
The prognosis depends on the stage at which the infection is treated. Early and early latent syphilis have an excellent outlook but once extensive tissue damage has occurred in the later stages the damage will not be reversed although the process may be halted. Symptoms in cardiovascular and neurosyphilis may therefore persist. The sexual partners of all patients with early syphilis must be contacted and screened.

Chancroid

Chancroid or soft chancre is an acute STD caused by Haemophilus ducreyi. It is common in tropical areas of the world and is endemic in parts of Africa and Asia. Epidemiological studies in Africa have shown an association between genital ulcer disease, frequently chancroid, and the acquisition of HIV infection. A new urgency to control chancroid has resulted from these observations.

CLINICAL FEATURES

The incubation period is 4-7 days. An initial erythematous papular lesion forms which then breaks down into an ulcer. Several ulcers may merge to form giant serpiginous lesions. Ulcers appear most commonly on the prepuce and frenulum in men and may erode through tissues. In women the most commonly affected site is the vaginal entrance and the perineum. The lesions in women may go unnoticed. At the same time inguinal lymphadenopathy develops (usually unilateral) and may progress to form large buboes which can suppurate.

DIAGNOSIS

Chancroid must be differentiated from other genital ulcer diseases (see Table 1.36). Isolation of H. ducreyi in specialized culture media is definitive but difficult. Swabs hould be taken from the ulcer and material aspirated from the local lymph nodes for culture.

TREATMENT

Increasing evidence is appearing of clinically significant plasmid-mediated antibiotic resistance of H. ducreyi. Cotrimoxazole and tetracyclines are the most commonly used agents but newer cephalosporins and quinolones are effective. All sexual partners should be seen and treated.

CLINICAL SYNDROMES

Gonorrhoea

The incidence of gonorrhoea (GC) in developing countries has fallen dramatically since the early 1970s but in Asia and Africa it still remains high. In 1990 WHO estimated 35 million cases worldwide, second to Chlamydia trachomatis amongst STDs. The causative organism, Neisseria gonorrhoeae (gonococcus), is a Gram-negative intracellular diplococcus which infects epithelium particularly of the urogenital tract, rectum, pharynx and conjunctivae. Humans are the only host and the organism is spread by intimate physical contact. It is very intolerant to drying and although occasional reports of spread by fomites exist this route of infection is extremely rare.

CLINICAL FEATURES

Forty per cent of women and some men are asymptomatic. The incubation period ranges from 2 to 14 days with most symptoms occurring between days 2 and 5. In men the commonest syndrome is one of anterior urethritiscausing dysuria and/or urethral discharge. Complications include ascending infection involving the epididymis, testes or prostate leading to acute or chronic infection. In homosex ual men rectal infection may produce proctitis with pain, discharge and itch. In women the primary site of infection is usually the endocervical canal and symptoms consist of a vaginal discharge,dysuria and intermenstrual bleeding. Complications  include ascending infection leading to salpingitis with associated pelvic pain and fever. In rare cases a perihepatitis may develop (Fitz-Hugh-Curtis syndrome).
Bartholin’s abscesses may develop. On a global basis GC is one of the commonest causes of female infertility. Rectal infection, due to local spread, may occur in women and is usually asymptomatic as in pharyngeal infection. Conjunctival infection is seen in neonates born to infected mothers and is one cause of ophthalmia neonatorum.Disseminated GC leads to arthritis (usually rnonoarticular or pauciarticular)and a characteristic purplish macular rash in association with fever and malaise.

DIAGNOSIS

The organism is identified from infected areas by Gram stain and culture on special media. Blood culture and synovial fluid investigations should be performed in cases of disseminated GC. Coexisting pathogens such as Chlamydia, Trichomonas and syphilis must be sought.

TREATMENT

The gonococcus is sensitive to a wide range of antimicrobial agents but an increase in antibiotic resistance has been seen over the past two decades. Therapy initiated in the clinic on the basis of Gram-stained slides prior to culture results is influenced by travel history or details known from contacts.
Therapy with single-dose amoxycillin 3 g with probenecid 1 g is given in uncomplicated cases. Spectinomycin 2 g i.m. or ciprofloxacin 250 mg are used in penicillinresistant or allergic cases. Longer courses of antibiotics are required for complicated infections. Patients must be followed up to ensure that the organism has been eradicated and all sexual contacts should be examined and treated as necessary.

Chlamydia

Chlamydia trachomatis  is an obligate intracellular bacterial parasite which cannot be grown on artificial culture media. Cell culture systems are not universally available and indirect diagnostic methods are still being perfected. The organism has a worldwide distribution and silent infection is common. In men 30-40% of non-gonococcal and postgonococcal urethritis is due to Chlamydia. It is frequently found in association with other pathogens: 20% of men and 40% of women with gonorrhoea have been found to have coexisting chlarnydial infections.

CLINICAL FEATURES

In men Chlamydia gives rise to an anterior urethritis with dysuria and discharge; infection is often asymptomatic and detected by contact tracing. Ascending infection leadsto epididymitis. Rectal infection leading to proctitis may occur in men practising anoreceptive intercourse. In  women the commonest site of infection is the endocervix where it may go unnoticed; ascending infection causes acute salpingitis. In women sub fertility may be the first problem encountered. Reiter’s syndrome  has been related to infection with C. trachomatis. Neonatal infection, acquired from the birth canal, can result in mucopurulent conjunctivitis and pneumonia.

DIAGNOSIS

Cell culture systems are still considered the definitive method of diagnosis but are costly and not suitable for routine use. Antigen detection systems depending on either direct fluorescent antibody or enzyme immunoassay are increasingly available. In view of the intracellular nature of the organism care must be taken to obtain adequate specimens and it is essential that cells are collected. Wooden swabs may interfere with assay techniques. Special transport media are required.

MANAGEMENT

Tetracyclines or macrolide antibiotics are most commonly used to treat Chlamydia. Oxytetracycline 500 mg 6-hourly or doxycycline 100 mg 12-hourly for 7 days areeffective. Tetracyclines are contraindicated in pregnancy and erythromycin 500 mg 6-hourly for 7-14 days can be given. Contacts must be traced and treated.

Urethritis

Urethritis is usually characterized in men by a discharge from the urethra, dysuria and varying degrees of discomfort within the penis. In 10-15% of cases there may be no symptoms. A wide array of aetiologies can give rise to the clinical picture, but may be divided into two broad bands: gonococcal or non-gonococcal urethritis (NGU). NGU occurring shortly after infection with gonorrhoea is known as postgonococcal urethritis (PGU). Gonococcal urethritis and chlamydial urethritis (a major cause of NGU) are discussed above.
In Chlamydia-negative NGU, Ureaplasma urealyticum is the next most frequent organism. Bacteroides sp. and Mycoplasma are responsible for a minority of cases. HSV can cause urethritis in about 30% of cases of primary infection, considerably fewer in recurrent episodes. Other causes include syphilitic chancres and warts within the urethra. Non-sexually transmitted NGU may be due to urinary tract infections, prostatic infection, foreign bodies and strictures.

CLINICAL FEATURES

The urethral discharge is often mucoid and worse in the mornings. It may be noted as crusting at the meatus or stains on underwear. Dysuria is common but not universal. Discomfort or itch within the penis may be present. The incubation is from 1 to 5 weeks with a mean of 2- 3 weeks. The importance of asymptomatic urethritis must be recognized as a major reservoir of infection. Associated features of conjunctivitis and/or arthritis may occur, particularly in HLA B27-positive individuals.

DIAGNOSIS

Smears should be taken from the urethra when the patient has not voided urine for at least 4 hours and should be Gram stained and examined under a high power (x 1000) oil immersion lens. The presence of five or morepolymorphonucleocytes per high power field is diagnos tic. Men who are  symptomatic but have no objective evidence of urethritis should be re-examined and tested after holding urine overnight. Cultures for gonorrhoea must be taken together with swabs for Chlamydia testing.

MANAGEMENT

Therapy is with tetracyclines initially, using either oxytetracycline 500 mg 6-hourly or doxycycline 100 mg 12- hourly for 7 days. Sexual intercourse should be avoided. The vast majority of patients will show partial or total response. For those left with objective evidence of urethritis, erythromycin 500 mg 6-hourly for 1-2 weeks should be prescribed. Sexual partners must be traced and treated; C. trachomatis can be isolated from the cervix in 50-60% of the female partners of men with gonorrhoea or N GU, many of whom are asymptomatic. This causes long-term morbidity in such women, acts as a reservoir of infection for the community and may lead to reinfection in the index case if not treated.

RECURRENT/PERSISTENT NGU

This is a common and difficult clinical problem. The usual time for patients to re-present is 2-3 weeks following treatment. Tests for Chlamydia and Ureaplasma are usually negative. It is important to document objective evidence of urethritis, check compliance and establish any possible contact with untreated sexual partners. Investigations should include wet preparation and culture of a urethral smear for Trichomonas vaginalis and fungi. Cultures should be taken for HSV. A mid-stream urine sample should be examined and cultured. A further 2 weeks’ treatment with erythromycin may be given and any specific additional infection treated appropriately. If symptoms are mild and all partners have been treated patients should be reassured and further antibiotic therapy avoided. In cases of frequent recurrence and/or florid unresponsive urethritis the prostate should be investigated and urethroscopy or cystoscopy performed to investigate possible strictures, periurethral fistulae or foreign bodies.

Syphilis

The causative organism, Treponema pal/idum (TP), is a motile spirochaete that is generally acquired by close sexual contact and transplacentally from mother to fetus. The organism enters the new host through breaches in squamous or columnar epithelium. Primary infection of non-genital sites may occasionally occur but is rare. Syphilis is a chronic systemic disease which can be quiescent or show protean manifestations. Both congenital and acquired syphilis have early and late stages, each of which has classical clinical features.

Primary

Between 10 and 90 days (mean 21 days) after exposure to the pathogen a papule develops at the site of inoculation. This ulcerates to become a painless, firm chancre. There is usually painless regional lymphadenopathy in association. The primary lesion may go unnoticed especially if it is on the cervix or within the rectum. Healing occurs spontaneously within 2-3 weeks.

Classification and clinical features of syphilis.

Classification and clinical features of syphilis.

Secondary

Between 4 and 10 weeks after the appearance of the primary lesion constitutional symptoms with fever, sore throat, malaise and arthralgia appear. Signs include:

GENERALIZED LYMPHADENOPATHY (50%)
GENERALIZED SKIN RASHES involving the whole body including the palms and soles but excluding the face (75%)
CONDYLOMATA LATA-warty, plaque-like lesions found in the perianal area and other moist body sites
SUPERFICIAL CONFLUENT ULCERATION OF MUCOSAL SURFACEs-found in the mouth and on the genitalia
ACUTE NEUROLOGICAL SIGNS (less than 10%) Without treatment, symptoms and signs abate over 3-12 weeks, but in up to 20% of individuals may recur during a period known as early latency, a 2-year period in the UK (I year in USA). Late latency is based on reactive syphilis serology with no clinical manifestations for at least 2 years. This may continue for many years before the late stages of syphilis become apparent.

Tertiary

Late benign syphilis, so called because of its response to therapy rather than its clinical manifestations, generally involves the skin and the bones. The characteristic lesion, the gumma (granulomatous, sometimes ulcerating, lesions), can occur anywhere in the skin, frequently at sites of trauma. Gummas are commonly found in the skull, tibia, fibula and clavicle, although any bone may be involved. Visceral gummas occur mainly in the liver (hepar lobatum) and the testes. Cardiovascular and neurosyphilis.

Congenital syphilis

Congenital syphilis usually becomes apparent between the second and sixth week after birth, early signs being nasal discharge, skin and mucous membrane lesions, and failure to thrive. Signs of late syphilis generally do not appear until after 2 years of age and take the form of ‘stigmata’ relating to early damage to developing structures, particularly teeth and long bones. Other late manifestations parallel those of adult tertiary syphilis.