Tuberculosis

Basic facts

• Tuberculosis (TB) is a disease most commonly affecting the lungs, but also other organs.

• It is caused by the bacterium Mycobacterium tuberculosis. The M. tuberculosis complex includes M. tuberculosis and M. africanum, primarily from humans, and M. bovis, primarily from cattle.

• M. tuberculosis and M. africanum are transmitted by exposure to the bacilli in airborne droplet nuclei produced by people with pulmonary or laryngeal tuberculosis during expiratory efforts, such as coughing and sneezing.

• Bovine TB results from exposure to tuberculous cattle, usually by ingestion of unpasteurized milk or dairy products, and sometimes by airborne spread to farmers and animal handlers.

• The incubation period is about 2-10 weeks; latent infections may persist throughout a person's life.

• In the acute phase of an emergency, when mortality rates are high owing to acute respiratory infections, malnutrition, diarrhoeal diseases and malaria (where prevalent), TB control is not a priority. A TB control programme should not be implemented until crude mortality rates are below 1 per 10 000 population per day. It is crucial that there is some stability in the population, as all patients commencing TB treatment must complete the full 6- or 8-month treatment course. If there are high rates of treatment defaulters, there is a high risk of development of multidrug-resistant TB.

• Nevertheless, TB is a particularly important disease in long-term emergencies where refugees or internally displaced persons are in camps or overcrowded communities for long periods. In these conditions, people are at particularly high risk of developing TB owing to overcrowding, malnutrition and high HIV seroprevalence. In Kenya in 1993, the incidence of new infectious TB patients in camps was four times the rate in the local population. In two camps in Sudan in 1990, over one-third of all adult deaths were due to TB.

Diagnosis

The most important symptoms of TB are:

• productive cough of long duration ( > 3 weeks),

• significant weight loss.

TB patients may also have fever, night sweats, breathlessness, chest pain and loss of appetite.

The full case definitions for TB are given in Annex 5.

Patients with suspected TB should have three sputum samples examined by light microscopy for acid-fast bacilli, using the Ziehl-Neelsen stain.

Criteria for establishing a TB control programme in emergency situations

DOTS is the TB control strategy recommended by WHO. It is important that the TB programme implements the DOTS strategy and, where possible, coordinates this with the national TB programme of the host country. The same treatment protocols should be used, and data on case-finding and treatment outcome should be reported to the relevant district TB coordinator of the national TB programme. Implementation of a DOTS programme requires that the following criteria are met:

• case detection through sputum-smear microscopy; this implies the existence of a laboratory system capable of undertaking sputum-smear microscopy to an acceptable standard;

• standardized short-course chemotherapy available to at least all smear-positive patients under direct observation of treatment, at least during the initial phase of treatment;

• a secure and regular supply of appropriate anti-TB drugs;

• a monitoring system for programme supervision and evaluation;

• political willingness on the part of the relevant government(s) authorities to implement the programme.

The following criteria are essential before a TB programme is implemented:

• surveillance data indicate that TB is an important health problem;

• the acute emergency phase is over;

• the basic needs of water, adequate food, shelter and sanitation are met;

• essential clinical services and drugs are available;

• security in and stability of the affected population is envisaged for at least 6 months;

• sufficient funding is available to support the programme for at least 12 months;

• laboratory services for sputum-smear microscopy are available.

Once the decision to implement a DOTS programme is made, the following information should be collected:

• available funding and duration of support;

• annual TB incidence in the country of origin;

• TB control policies in the country of origin and the host country;

• expertise among the national TB programme or nongovernmental organizations in implementing TB control programmes.

Drug procurement, establishment of laboratory services and training may take up to 3 months, so the decision to implement a TB control programme should be made as soon as possible after the acute emergency phase is over. The key steps in setting up a TB control programme using the DOTS strategy are:

• lead agency identified, e.g. national TB programme, nongovernmental organization;

• funding identified;

• work plan, resource needs and budget prepared;

• TB coordinator(s) (if possible 1 per 50 000 population) appointed;

• agreement with national TB programme of host country on:

- integration of refugee/internally displaced person TB control programme with national TB programme,

- drug regimens to be used,

- coverage of the local population by the TB control programme,

- referral of seriously ill patients to local hospitals,

- laboratories suitable for quality control of smear examination,

- procurement of drug stocks and reagents,

- procedures for follow-up of cases in the repatriation phase,

- programme evaluation;

• staff needs assessed, job descriptions developed and staff recruited;

• secure storage facilities identified;

• production of local TB control protocol;

• reporting system established. Case management

The priority is the diagnosis and treatment of smear-positive infectious cases of TB. To ensure the appropriate treatment and cure of TB patients, strict implementation of the DOTS strategy is important. There are primarily three types of regimen:

• category 1 for new smear-positive (infectious) pulmonary cases,

• category 2 for re-treatment cases,

• category 3 for smear-negative pulmonary or extra-pulmonary cases.

The chemotherapeutic regimens are based on standardized combinations of five essential drugs: rifampicin (R), isoniazid (H), pyrazinamide (P), ethambutol (E) and streptomycin (S).

Each of the standardized chemotherapeutic regimens consist of two phases:

• the initial (intensive) phase: 2-3 months, with 3-5 drugs given daily under direct observation;

• the continuation phase: 4-6 months, with 2-3 drugs given three times a week under direct observation, or in some cases (e.g. during repatriation of refugees) two drugs for 6 months given daily unsupervised, but in fixed-dose combination form.

All doses of rifampicin-containing regimens should be observed by staff. Actual swallowing of medication should be supervised.

Multidrug-resistant TB

• MDR-TB is a specific form of drug-resistant TB due to a bacillus resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs.

• DOTS-Plus is designed to cure MDR-TB using second-line anti-TB drugs.

• DOTS-Plus is needed in areas where MDR-TB has emerged due to previous inadequate TB control programmes.

• DOTS-Plus pilot projects are recommended only in settings where the DOTS strategy is fully in place to protect against the creation of further drug resistance.

• It is vital that WHO is consulted before DOTS-Plus pilot projects are launched in order to minimize the risk of creating drug resistance to second-line anti-TB drugs.

Further reading

Harries AD, Maher D. TB/HIV: a clinical manual. Geneva, World Health Organization,

1996 (document WHO/TB/96.200).

Treatment of tuberculosis: guidelines for national programmes, 2nd ed. Geneva,

World Health Organization, 1997 (document WHO/TB/97.220).

Tuberculosis control in refugee situations: an inter-agency field manual. Geneva,

World Health Organization, 1997 (document WHO/TB/97.221).

5.20 Typhoid fever

Basic facts

• Typhoid fever is caused by Salmonella Typhi, a Gram-negative bacterium. A very similar but often less severe disease is caused by the Salmonella serotype Paratyphi A. In most countries in which these diseases have been studied, the ratio of disease caused by S. Typhi to that caused by S. Paratyphi is about 10:1.

• Typhoid fever remains a global health problem. It is difficult to estimate the real burden of typhoid fever in the world because the clinical picture is confused with many other febrile infections because of the lack of appropriate laboratory resources in most areas in developing countries. Many cases remain under-diagnosed. In both endemic areas and in large outbreaks, most cases of typhoid fever are seen in those aged 3-19 years.

• Humans are the only natural host and reservoir. The infection is transmitted by ingestion of faecally contaminated food or water. The highest incidence occurs where water supplies serving a large population are faecally contaminated.

• The incubation period is usually 8-14 days, but may extend from 3 days up to 2 months.

• Some 2-5% of infected people become chronic carriers who harbour S. Typhi in the gall bladder. Chronic carriers are greatly involved in the spread of the disease.

• Patients infected with HIV are at a significantly increased risk of severe disease due to S. Typhi and S. Paratyphi.

Clinical features

The clinical presentation of typhoid fever varies from a mild illness with low-grade fever, malaise and dry cough to a severe clinical picture with abdominal discomfort, altered mental status and multiple complications. Clinical diagnosis is difficult. In the absence of laboratory confirmation, any case of fever of at least 38 °C for 3 or more days is considered suspect if the epidemiological context is conducive.

Depending on the clinical setting and quality of available medical care, some 5-10% of typhoid patients may develop serious complications, the most frequent being intestinal haemorrhage or peritonitis due to intestinal perforation. Clinical case definitions are given in Table 5.16.

Table 5.16 Clinical case definitions

Confirmed case of typhoid fever

A patient with fever (38 °C or more) lasting 3 or more days, with laboratory-confirmed S. Typhi organisms (blood, bone marrow, bowel fluid)

Probable case of typhoid fever

A patient with fever (38 °C or more) lasting 3 or more days, with a positive serodiagnosis or antigen detection test but no S. Typhi isolation

Chronic carrier

An individual excreting S. Typhi in the stool or urine for longer than one year after the onset of acute typhoid fever; short-term carriers also exist, but their epidemiological role is not as important as that of chronic carriers

Diagnosis

✓ The definitive diagnosis of typhoid fever depends on the isolation of S. Typhi organisms from the blood or bone marrow or bowed fluid. Blood culture bottles should be transported to the referral laboratory at ambient temperature.

✓ The classical Widal test measuring agglutinating antibody titres against S. Typhi in serum has only moderate sensitivity and specificity. It can be negative in up to 30% of culture-proven cases of typhoid fever and can be falsely positive in many circumstances. Newer diagnostic tests based on detection of serum antibodies highly specific to S. Typhi are currently being developed and some have already been marketed. They are rapid, very accurate and easy to perform. Although they have not yet been evaluated extensively in the field, they are likely to become standard point-of-care tests for the diagnosis of typhoid fever, particularly in emergencies where access to blood culture facilities is compromised.

Case management

• More than 90% of patients can be managed at home with oral antimicrobial, minimal nursing care, and close medical follow-up for complications or failure to respond to therapy. However, the emergence of multidrug-resistant strains in many parts of the world has reduced the choice of effective antimicrobial available in many areas. When feasible, antimicrobial susceptibility testing is crucial as a guide to clinical management.

• The available evidence suggests that the fluoroquinolones7 are the optimal choice for the treatment of typhoid fever at all ages. However, in areas of the world where the bacterium is still fully sensitive to traditional first-line drugs (chloramphenicol, ampicillin, amoxicillin or trimethoprim-sulfamethoxazole) and fluoroquinolones are not available or affordable, these drugs do remain appropriate for the treatment of typhoid fever. Chloramphenicol, despite the risk of agranulocytosis (1 per 10 000 patients), is still widely prescribed in developing countries to treat typhoid fever. S. Typhi strains from many areas of the world, such as Indonesia and most countries in Africa, remain sensitive to this drug.

• Supportive measures are important in the management of typhoid fever, such as oral or intravenous hydration, antipyretics, and appropriate nutrition and blood transfusions, if indicated.

• Typhoid fever patients with changes in mental status characterized by delirium, obtundation or stupor should be immediately evaluated for meningitis by examination of the cerebrospinal fluid. If the findings are normal and typhoid fever is suspected, adults and children should immediately be treated with high-dose intravenous dexamethasone in addition to antimicrobials. Dexamethasone, given in an initial dose of 3 mg/kg body weight by slow intravenous infusion over 30 minutes, followed 6 hours later by 1 mg per kg body weight every 6 hours for a total of eight times, can reduce mortality by approximately 80-90% in these high-risk patients. Dexamethasone, given in a lower dose, is not effective. High-dose steroid treatment need not await the results of typhoid blood cultures if other causes of severe disease are unlikely.

Prevention and control measures

• Health education, clean water, food inspection, proper food handling and proper sewage disposal are essential in preventing typhoid fever outbreaks.

• Early detection and containment of the cases are paramount in reducing dissemination. The health authorities must be informed if one or more

7 Of the available fluoroquinolones, ofloxacin, ciprofloxacin, fleroxacin and perfloxacin are all highly active and equivalent in efficacy. Nalidixic acid and norfloxacin do not achieve adequate blood concentrations and should not be used in typhoid fever.

suspected cases are identified. The outbreak should be confirmed following WHO guidelines, and a referral laboratory should be consulted whenever possible to quickly obtain an antimicrobial sensitivity pattern of the outbreak strain.

Vaccination

• The old parenteral, killed, whole-cell vaccine was effective but produced an unacceptable rate of side-effects. Nowadays, a parenteral vaccine containing the polysaccharide Vi antigen is the vaccine of choice in displaced populations. A live oral vaccine using S. Typhi strain Ty21a is also available. Neither the polysaccharide vaccine nor the Ty21a vaccine is licensed for children under 2 years of age. The Ty21a vaccine should not be used in patients receiving antimicrobials.

• Mass vaccination may be an adjunct for the control of typhoid fever during a sustained, high-incidence epidemic. This is especially true when access to well functioning medical services is not possible or in the case of a multidrug-resistant strain. If the involved community cannot be fully vaccinated, children aged 2-19 years should be given priority.

5.21 Typhus (epidemic louse-borne)

Basic facts

• Typhus is a rickettsial disease caused by the pathogen Rickettsia prowazeki.

• It is transmitted by the human body louse, which is infected by feeding on the blood of a patient with acute typhus. Infected lice excrete rickettsiae in their faeces, and humans are infected by rubbing faeces or crushed lice into the bite.

• The disease is endemic in the highlands and cold areas of Africa, Asia and South America. Cases occurred in the past in the Balkans and parts of the former Soviet Union, and cases of Brill-Zinsser disease (recrudescent typhus) are still reported from these regions.

• Refugees and displaced persons in affected areas are at a high risk of epidemics if there are overcrowding, poor washing facilities and body lice.

• Large outbreaks have been reported among refugees in Burundi, Ethiopia and Rwanda.

• The crude mortality rate ranges from 10% to 40% without treatment, and can rise to 50% in the elderly.

• The crude mortality rate is around 70% among those who develop complications.

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