Search

Louse-borne relapsing fever (LBRF) is an epidemic disease with a fascinating history from Hippocrates’ times, through the 6th century ‘Yellow Plague’, to epidemics in Ireland, Scotland and England in the 19th century and two large Afro-Middle Eastern pandemics in the 20th century. An endemic focus persists in Ethiopia and adjacent territories in the Horn of Africa. Since 2015, awareness of LBRF in Europe, as a re-emerging disease, has been increased dramatically by the discovery of this infection in dozens of refugees arriving from Africa.The causative spirochaete,Borrelia recurrentis, has a genome so similar toB. duttoniiandB. crocidurae(causes of East and West African tick-borne relapsing fever), that they are now regarded as merely ecotypes of a single genomospecies. Transmission is confined to the human body lousePediculus humanus corporis, and, perhaps, the head louseP. humanus capitis, although the latter has not been proved. Infection is by inoculation of louse coelomic fluid or faeces by scratching. Nosocomial infections are possible from contamination by infected blood. Between blood meals, body lice live in clothing until the host's body temperature rises or falls, when they seek a new abode.The most distinctive feature of LBRF, the relapse phenomenon, is attributable to antigenic variation of borrelial outer-membrane lipoprotein. High fever, rigors, headache, pain and prostration start abruptly, 2–18 days after infection. Petechial rash, epistaxis, jaundice, hepatosplenomegaly and liver dysfunction are common. Severe features include hyperpyrexia, shock, myocarditis causing acute pulmonary oedema, acute respiratory distress syndrome, cerebral or gastrointestinal bleeding, ruptured spleen, hepatic failure, Jarisch–Herxheimer reactions (J-HR) and opportunistic typhoid or other complicating bacterial infections. Pregnant women are at high risk of aborting and perinatal mortality is high.Rapid diagnosis is by microscopy of blood films, but polymerase chain reaction is used increasingly for species diagnosis. Severe falciparum malaria and leptospirosis are urgent differential diagnoses in residents and travellers from appropriate geographical regions.High untreated case-fatality, exceeding 40% in some historic epidemics, can be reduced to less than 5% by antibiotic treatment, but elimination of spirochaetaemia is often accompanied by a severe J-HR.Epidemics are controlled by sterilising clothing to eliminate lice, using pediculicides and by improving personal hygiene.

Snakes of the families Viperidae and Elapidae are responsible for the high incidence of morbidity and mortality after snake bites in countries of West Africa, the Indian subcontinent, South-East Asia, New Guinea and Latin America. Envenoming can cause local effects, notably tissue necrosis; and systemic effects, including paralysis, haemostatic disturbances, shock, increased capillary permeability, myocardial damage, rhabdomyolysis and acute renal failure. Specific hyperimmune serum (antivenom) is the mainstay of medical treatment for severe envenoming. Ancillary treatments such as assisted ventilation, repletion of circulating volume, renal dialysis and surgical debridement of necrotic tissues are needed in some cases. Scorpion stings are a common medical problem in middle and southern America, North Africa and the Middle East. Vasodilator drugs are important to counter the effects of massive catecholamine release. Bites by spiders and stings by hymenoptera and marine animals are responsible for deaths and morbidity in some tropical countries.

Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Toxicon 32, 1045-1050, 1994.--A simple whole blood clotting test (WBCT20) was assessed for its efficacy in determination of severe defibrinogenation in patients envenomed by Bothrops snakes in Brazil. There was a close relationship between the results of the WBCT20 and plasma fibrinogen levels in 69 moderately envenomed patients. The advantage of the WBCT20 over estimation of plasma fibrinogen concentrations in patients is that it is a simpler, faster and more reliable test. It is also of use in assessing the effectiveness of antivenom therapy in relation to the restoration of blood coagulability.

The case fatality of WHO-defined 'severe falciparum malaria' remains unacceptably high, at 10-20%. However, a gradual decline in case fatality in adults and children treated in hospitals may reflect use of improved regimens of antimalarial chemotherapy and increased awareness of important complications of the disease. The development of severe, perhaps inevitably-fatal, malaria might be prevented by early appropriate chemotherapy of uncomplicated disease. At the most peripheral levels of the health service, suppository formulations of artemisinin derivatives can be administered even to patients who are vomiting or prostrated. At dispensaries, clinics or hospitals, where intramuscular or intravenous administration of antimalarial drugs is possible, quinine and artemisinin derivatives are the treatments of choice. There is growing evidence of the safety and efficacy of the quinine loading dose and of the use of artemether and artesunate, based on large, randomised, controlled clinical studies. No safe and effective form of prophylactic ancillary treatment has yet emerged. Results of studies of antipyretics, anticonvulsants (phenobarbitone), anticytokine/anti-inflammatory agents (anti-TNF antibodies, pentoxifylline, dexamethasone), iron chelators and hyperimmune sera have been disappointing. Only blood transfusion and treatment of respiratory, circulatory and renal failure are of obvious benefit. New ideas are needed, based on what is known of the pathophysiology of severe disease.

Most of the infectious diseases to which travellers are exposed can now be prevented by immunization, chemoprophytaxis protection against insect bites, strict food and water hygiene and avoidance of unprotected sexual activity. Some basic childhood immunizations (tetanus, diphtheria, poliomyelitis) may need to be boosted. Special vaccines are available for regional disease problems such as Japanese encephalitis in Asia and tick- borne encephalitis in Central Europe. Yellow Fever vaccination is statutory in endemic areas of Africa and Latin America. Pre-exposure immunization against rabies is increasingly advocated for travellers. When advising travellers it is important to obtain up-to-date information about recent epidemics. This is provided by Morbidity and Mortality Weekly Report (MMWR) and WHO epidemiological reports. Annual epidemics of meningococcal meningitis are predictable in some areas such as the 'meningitis' belt of Africa. Traveller's diarrhea remains the commonest of diseases of travellers, with an incidence of >50% in some countries, while malaria is the most likely to prove fatal. However, most deaths in travellers are caused by trauma, including road traffic accidents, and chronic conditions not directly related to travel (for example, cardiovascular disease).

Three monospecific antivenoms for Malayan pit viper (MPV) (Calloselasma rhodostoma) were compared in Southern Thailand, where this species is the most common cause of snake bite morbidity. Forty-six patients with proved MPV bites and incoagulable blood, indicating systemic envenoming, were randomly allocated for treatment with Thai Red Cross (TRC), Thai Government Pharmaceutical Organization (GPO), or Twyford Pharmaceutical monospecific antivenoms. Both GPO and Twyford antivenoms produced rapid and permanent restoration of blood coagulability, but TRC antivenom failed in 2/15 cases. Patients in the GPO group showed the greatest increase in plasma fibrinogen concentration during the first 24 hr and had fewer early anaphylactic reactions (6/15) compared with Twyford 8/16 and with TRC 13/15. Pyrogenic reactions occurred more frequently after TRC antivenom (8/15) than GPO (1/15) or Twyford (0/16). Patients requiring more than one dose of antivenom were identifiably more severely envenomed on admission. In an accompanying laboratory study the antivenoms were assessed in rodents using five WHO standard tests of neutralizing activity. Compared with the other two antivenoms TRC was significantly inferior in anti-lethal potency, GPO was superior in anti-hemorrhagic and anti-necrotic potency and Twyford was superior in anti-procoagulant and anti-defibrinogenating potency. The clinical efficacy of these antivenoms against local necrosis remains equivocal. GPO and Twyford antivenoms are recommended for the treatment of systemic envenoming by MPV in an initial dose of 5 ampoules.

One hundred and six asthma patients were studied in Zaria in the Nigerian savanna region. This group resembled hospital attenders in general in containing a disproportionately large number of immigrants from southern Nigeria and students undergoing higher education. Childhood asthma was rare. Asthma started after the age of 19 years in 69 per cent of patients. Twenty-seven per cent gave a history of rhinitis but none had had eczema. Twenty-two per cent gave a family history of asthma. Cutaneous hypersensitivity to house dust supported by a history of attacks being precipitated by dust was found in 41 per cent of patients. Asthma was worst in the rainy season in 45 per cent of patients. Mites were found in mattress dust samples; the mean count was 243 mites per g dust; Dermatophagoides farinae formed 86-6 per cent of the total mite population. The variability of airways obstruction averaged 50 per cent of maximum values for forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF). The median severity of airways obstruction measured as FEV1/VC per cent was four standard deviations below predicted normal. Eighty-seven per cent of patients were positive to prick skin tests with one or more allergens. The commonest reactions were to house dust (58 per cent), house dust mite (45 per cent) and Dermatophagoides farinae (44 per cent). Fifty-one per cent of a group of controls were also positive on skin testing but the pattern of responses was different from the asthmatic patients. This high proportion of reactors is explained by high allergen load. Serum IgE levels were lower in the asthmatics than in a group of healthy controls who showed the very high levels characteristic of some African populations. We suggest that the controls were protected from atopic disease by developing high blocking levels of non-specific IgE, perhaps in response to gut helminths. The clinical pattern of asthma in Zaria is compared with other countries in the tropical and temperate zones. The particular problems of treating asthma in developing tropical countries are discussed.

Antigen-stimulated lymphocyte transformation was studied in recipients of intradermal human diploid cell rabies vaccine (HDCV). HDCV was administered intradermally at 8 different anatomical sites, 0.1 ml each, on day 0; followed by another 4-site injection on day 7. Rabies antigen-stimulated in vitro proliferative response was evident as early as 7 days after starting immunization. It reached a peak on day 14 and had declined by day 28. The cellular proliferative response preceded and roughly correlated with the antirabies antibody response. Simultaneous administration of inosiplex, an antiviral and immunopotentiating drug, during the first 10 days of intradermal HDCV immunization did not result in heightened antibody titres or cell-mediated immune response to the vaccine. The number of T cells and the lymphocyte proliferative response to phytohaemagglutinin in inosiplex-treated vaccinees were similarly not significantly different from untreated controls. Our results confirm other previous findings that a specific cell-mediated immune response can be consistently and rapidly induced by an intradermal regimen of HDCV immunization. The addition of inosiplex to this regimen did not enhance the humoral or cell-mediated immune responses to the vaccine. The apparent lack of immunostimulating effect of inosiplex in this setting may be the result of several factors such as the immunization schedule and the immunologic parameters examined.

More than 99% of all human rabies deaths in the world occur in tropical developing countries. In India alone, 30,000 to 50,000 people may die of rabies each year. The Lyssaviruses (Family Rhabdoviridae) include rabies and rabies-related viruses, 3 of which have caused human disease. Rabies is a zoonosis, principally affecting domestic and stray dogs in most parts of Africa, Asia and Latin America. In North America, southern Africa, parts of the Caribbean and Europe, the principal mammalian reservoir species are wild carnivores. The pathogenesis, clinical features and differential diagnosis of rabies are discussed. The planning of rabies control strategies requires background information on the distribution and incidence of rabies in animals and the species involved. In some parts of the world, such as Latin American cities, most domestic dogs, even apparent strays, have an owner and can be immunized with conventional canine vaccines during well publicized campaigns. However, in areas such as India, where there may be a high proportion of stray domestic dogs without owners, and in those areas where wild mammals are the principal reservoir species, immunization may be possible using live attenuated or recombinant oral vaccines distributed in baits. In the poor tropical developing countries, unsatisfactory nervous tissue vaccines are still widely used. However, economical multisite intradermal regimens using tissue culture vaccines have proved effective and have begun to replace nervous tissue vaccines in some countries.

Local synthesis of immunoglobulin within the central nervous system has been evaluated in 37 patients with acute cerebral malaria; seven patients were also studied in the convalescent phase. There was evidence in the cerebrospinal fluid (CSF) of 21 patients that intrathecal IgG synthesis occurs in the acute phase. There were raised IgG: albumin ratios in 43% of acute patients. Oligoclonal IgG bands or cathodal IgG was seen in the CSF of 43% of patients tested by polyacrylamide electrophoresis. Only eight out of 37 acute patients (22%) had no evidence of intrathecal IgG synthesis by either method. The serial studies showed that most patients had IgG-CSF abnormalities when tested in convalescence. These studies suggest that an immune stimulus (perhaps malarial antigens or mitogens) may be present in the brain in acute cerebral malaria.

Uncoagulable blood and life-threatening bleeding can result from the action of some snake venom toxins on haemostatic components of blood and vessel walls. Although envenoming by Micropechis ikaheka primarily affects neurones and muscle cells causing post-synaptic neuromuscular blockade and rhabdomyolysis, disturbances of haemostasis also occur. Therefore, the present study explored the effects of M. ikaheka venom on platelets and endothelium, which are important components of the haemostatic mechanism. The venom inhibited platelet aggregation in response to ADP and collagen, and also delayed clotting dependent on platelet activation or endothelial cell tissue factor expression. Some of these effects were reduced by the incubation of venom with a phospholipase A2 (PLA2) inhibitor and could be reproduced by a 17 kDa venom fraction containing a PLA2. In addition, an 11 kDa fraction containing a long-chain neurotoxin reduced ADP-induced aggregation. The venom was also found to reduce endothelial cell adherence to vitronectin-, fibronectin- and collagen-coated surfaces. These results suggest that, by inhibiting procoagulant activities of platelets and endothelial cells, a 17 kDa PLA2 plays an important role in the anticoagulant action of M. ikaheka venom.

Herbert Gilles played an important role in the establishment of the Wellcome-Mahidol University, Oxford Tropical Medicine Research Programme in Thailand in 1979. The randomized, placebo-controlled trial of dexamethasone in cerebral malaria that was carried out in Chantaburi in 1980 yielded results which led to the abandonment of ancillary corticosteroid therapy in this disease and contributed to a rejection of the 'permeability hypothesis'. The clinical manifestations of strictly defined cerebral malaria have not been described both in non-immune adults in Thailand and Vietnam and in African children. Clinical and histopathological studies in human patients, together with laboratory studies of cyto-adherence, malaria 'toxin' and cytokine production have provided some evidence for both the 'mechanical' and 'toxin-cytokine' hypotheses to explain the pathophysiology of this condition. Chemotherapy is challenged by the continuing evolution of antimalarial resistance. Recently, the most powerful studies ever carried out with antimalarial drugs have demonstrated that artemether and quinine achieve similar case fatalities, in the range 11%-21%, and that both drugs have some advantages and disadvantages. Further studies are needed to define the efficacy and safety of prophylactic anticonvulsants and exchange transfusion in cerebral malaria. Cerebral malaria remains a major cause of mortality and, in African children, morbidity.