[Impact of Streptococcus pneumoniae on pneumonia in Latin American children. SIREVA-Vigía Group]. / Impacto de Streptococcus pneumoniae en las neumonías del niño latinoamericano. Grupo SIREVA-Vigía.

Community-acquired pneumonia is one of the leading causes of infant morbidity and mortality. Studies conducted in developing countries indicate that the most serious symptoms of pneumonia are associated with bacterial causes, mainly Streptococcus pneumoniae, followed by Haemophilus influenzae type b. Managing those infections in children under two years of age is hindered by the lack of appropriate vaccines and by the decreased susceptibility of S. pneumoniae to penicillin and other antibiotics. In 1993, at the initiative of the Regional System for Vaccines of the Pan American Health Organization, and with funding from the Canadian International Development Agency, a study was designed to identify the S. pneumoniae capsular types that cause invasive disease in Latin American children under 5 years of age. The objective of the study was to determine the ideal composition of a conjugate vaccine that could be used in Latin America, and the penicillin susceptibility of the S. pneumoniae isolates. The initiative was undertaken in Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. This report analyzes the information that the participating countries generated on pneumococcal pneumonia. A total of 3,393 children were found with systemic S. pneumoniae infections, of which 1,578 corresponded to pneumonias. The analysis focused on 1,409 cases of pneumonia in Argentina, Brazil, Colombia, Mexico, and Uruguay. Of the children, 63.8% of them were under two years of age. Twelve prevalent capsular types were identified, of which serotypes 14, 5, and 1 were the three most common in the majority of the countries. At the beginning of the study the highest level of penicillin resistance was found in Mexico (47.0%), and the lowest in Colombia (12.1%). Over the 1993-1998 period, resistance to penicillin increased in the five countries. Penicillin resistance was associated with a small number of capsular serotypes, mainly 14 and 23F. The first of those serotypes was resistant to penicillin and to trimethoprim-sulfamethoxazole, and the second was multiresistant. The frequency of resistance to trimethoprim-sulfamethoxazole was high in all of the countries; Argentina had the highest level, 58.0%. A decrease in susceptibility to chloramphenicol was uncommon, except in Colombia, where there was a resistance level of 23.4%. Resistance to erythromycin was low in all the countries, and all the isolates were susceptible to vancomycin.

Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial.

BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. METHODS: Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). FINDINGS: About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. INTERPRETATION: Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

Improving the monitoring of immunization services in Kyrgyzstan.

Following the disbanding of the Soviet Union in 1991, the government of Kyrgyzstan was unable to maintain the previous level of health services. To revitalize the health services, the Ministry of Health (MOH) first focused on improving their immunization services, including the immunization component of the Health Management Information System (HMIS). Secondly, to increase immunization coverage, the MOH set as a priority the elimination of prescribing false contraindications to immunization. To accomplish both goals, the MOH updated the national immunization policies and established a more effective structure for managing immunization services. To support the MOH, the US Agency for International Development (USAID) Resources for Child Health (REACH) and Basic Support for Institutionalizing Child Survival (BASICS) projects provided technical assistance through a resident coordinator and consultants, and by organizing an international seminar. The improvements extended beyond systems and forms, but, instead, emphasized monitoring by the frontline health worker and supervising the quality of health information. To accomplish their objectives, the MOH appointed a Working Group to define the problems, revise record-keeping procedures, and develop monitoring tools. This group, representing both national and local levels, was composed of MOH epidemiologists, paediatricians and a management information specialist. To reduce the burden of excessive record-keeping and reporting requirements, the Working Group identified four key indicators for the service delivery level: (1) DPT3 immunization coverage rates for children less than 1 year of age; (2) contraindication rates for DPT; (3) usage of DPT vaccine; and (4) daily refrigerator temperatures. Additional indicators were included at district and provincial levels. After a successful 1-year trial, the MOH implemented the revised HMIS nationally. Not only did the quality of the information system improve, but the new approach provided visible evidence, from facility to national levels, that the MOH was approaching their objective of reducing contraindication rates for DPT immunizations to 5% or less, and that vaccine wastage could be substantially reduced. The project demonstrated that giving health workers the basic epidemiologic skills to monitor their own work measurably improved the quality of the data, and by acquiring the new skills, the workers developed a sense of pride in their work.

PIP: Following the disbanding of the Soviet Union in 1991, the government of Kyrgyzstan was unable to maintain the previous level of health services. To revitalize the health services, the Ministry of Health (MOH) first focused on improving their immunization services, including the immunization component of the Health Management Information System (HMIS). Secondly, to increase immunization coverage, the MOH set as a priority the elimination of prescribing false contraindications to immunization. To accomplish their objectives, the MOH appointed a Working Group to define the problems, revise record-keeping procedures, and develop monitoring tools. To reduce the burden of excessive record-keeping and reporting requirements, the working group identified four key indicators for the services delivery level: 1) diphtheria, pertussis, tetanus (DPT) immunization coverage rates for children less than 1 year of age; 2) contraindication rates for DPT; 3) usage of DPT vaccine; and 4) daily refrigerator temperature. After a successful 1-year trial, the MOH implemented the revised HMIS nationally. Not only did the quality of the information system improve, but also the new approach provided visible evidence that the MOH was approaching its objectives. The project demonstrated that giving health workers the basic epidemiological skills to monitor their own work measurably improved the quality of the data, and by acquiring the new skills, the workers developed a sense of pride in their work.

Vaginal infections in pregnant women in Jamaica: prevalence and risk factors.

Trichomoniasis, bacterial vaginosis (BV) and candidiasis are reproductive tract infections (RTIs) of the vagina. We conducted a cross-sectional study in 4 prenatal clinics in Kingston, Jamaica, to estimate the prevalence of these infections and the risk factors that may facilitate their transmission among pregnant women. Of the 269 women studied, 18.0% had culture-positive trichomoniasis, 44.1% had BV (Nugent score > or = 7) and 30.7% were positive for candidiasis by wet mount. A multiple logistic regression analysis showed that having a malodorous discharge was associated with trichomoniasis (odd ratios [OR]=3.9, confidence intervals [CI]=1.04-14.7) and BV (OR=3.4, CI=1.3-8.7). Women who took action to prevent HIV infection had lower BV prevalence (OR=0.34, CI=0.12-0.98). Women who were employed were less likely to have any of the infections (OR=0.61, CI=0.36-1.03). The strong association of a symptomatic presentation with trichomoniasis and BV suggests the merit of considering syndromic management of vaginitis in this population.

Geographical patterns of cholera in Mexico, 1991-1996.

BACKGROUND: The seventh cholera pandemic has been ongoing in Mexico since 1991 and threatens to become endemic. This paper aims to determine the geographical pattern of cholera in Mexico to define areas at high risk of endemic cholera. METHODS: Ecologic research was conducted based upon the cartography of disease incidence. The 32 Mexican states were grouped into five strata according to the value of the 1991-1996 cumulative incidence rate of cholera. Rate ratios were computed for strata of states classified by geographical situation, urbanization, and poverty level. RESULTS: Cholera incidence was 2.47 times higher in coastal states than in the interior (95% CI : 2.42-2.52). The disease was negatively associated with urbanization. Incidence in the least urbanized stratum was four times as high as in the most urban stratum (95% CI : 3.9-4.12). The poorest stratum showed the most remarkable incidence, i.e. 5.9 times higher than the rate in the least poor stratum (95% CI : 5.73-6.04). CONCLUSIONS: This ecologic research suggests that high poverty level, low urbanization, and southern location are the most important predictors of endemic cholera in Mexican states. It is hypothesized that the natural environment of the coastal plains in southern states may also play a significant role in cholera incidence. Poor communities residing in the southern, predominantly rural, coastal states should be prioritized when it comes to investing in safe water supply facilities, adequate excreta disposal systems and cholera surveillance.

23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial.

BACKGROUND: Infection with Streptococcus pneumoniae is a frequent and serious problem for HIV-immunosuppressed adults. Vaccination is recommended in the USA and Europe, but there are no prospective data that show vaccine efficacy. METHODS: 1392 (937 female) HIV-1-infected adults in Entebbe, Uganda, were enrolled. 697 received 23-valent pneumococcal polysaccharide vaccine and 695 received placebo. The primary endpoint was first event invasive pneumococcal disease. Secondary endpoints included vaccine serogroup-specific invasive disease, all (probable and definite) pneumococcal events, all-cause pneumonia, and death. FINDINGS: First invasive events occurred in 25 individuals (24 bacteraemias, one pyomyositis), 15 in the vaccine arm and ten in the placebo arm (hazard ratio [HR] 1.47; 95% CI 0.7-3.3). 22 isolates (88%) were of vaccine-specific serogroups with 15 events in the vaccine arm compared with seven in the placebo arm (HR 2.10; 0.9-5.2). All pneumococcal events had a similar distribution (20 vs 14; HR 1.41; 0.7-2.8) though all-cause pneumonia was significantly more frequent in the vaccine arm (40 vs 21; HR 1.89; 1.1-3.2). Mortality was unaffected by vaccination. INTERPRETATION: 23-valent pneumococcal polysaccharide vaccination is ineffective in HIV-1-infected Ugandan adults and probably has little, or no, public health value elsewhere in sub-Saharan Africa. Increased rates of pneumococcal disease in vaccine recipients may necessitate a reappraisal of this intervention in other settings.

John Snow: the first hired gun?

The 1854 English cholera outbreak led to reform of Victorian public health legislation, including the Nuisances Removal and Diseases Prevention Act. The reforms threatened the closure of many factories whose fumes were considered hazardous to the public's health. The second witness to appear before the Parliamentary committee considering the reforms was Dr. John Snow. Snow testified on behalf of the manufacturers threatened by the reforms. He stated that the fumes from such establishments were not hazardous. He contended that the workers in these factories did not become ill as a result of their exposures, and therefore these fumes could not be a hazard to the general public's health. Snow also presented data from the 1854 cholera outbreak as the basis for his belief that epidemic diseases were transmitted by water, not air. Although the data concerned cholera, Snow extended the inference to all epidemic diseases. When the committee's report was published, The Lancet chastised Snow in a stinging editorial. Parliament subsequently revised the bill in favor of the manufacturers and passed it into law. The implications of this particular episode in the history of epidemiology are discussed.

Invited commentary: the testimony of Dr. Snow.

PIP: This paper presents a commentary on the testimony delivered by Dr. John Snow before the British Parliamentary Committee in 1855. It is noted that in Snow's testimony was highlighted his extremely strong belief in germ theory and contagion and his consequent contempt for anything close to the rivaling theory that miasmatic emanations cause disease. Snow's unreasonableness may have been because he already held his germ theory and drinking water convictions before he made his observations. In addition, based on his published books it has become apparent that even his data analysis was guided by such preconceptions. Although Snow's opinion on germ theory created contemporaries, it is noted however, that Snow did not truly sway contemporary opinion, and his theories were not agreed as a complete breakthrough in the way that they are often presented as being in epidemiological textbooks. Overall, the fundamental problem with the miasma and contagion theories at the time was that both failed to answer certain questions, including transmission of diseases, development of diseases, and the issue of temporary carriers of causative germs.^ieng

Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine.

Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to a Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diphtheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titres (> 1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups > 98% of infants attained anti-PRP antibody titres > or = 0.15 microgram/ml. The geometric mean anti-PRP antibody titres were 5.41 micrograms/ml and 2.1 micrograms/ml for infants immunized with three doses of PRP-T versus two doses of PedVax HIB vaccines, respectively (P < 0.005). Similarly, the proportion of infants who achieved titres > or = 1 microgram/ml was higher in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A subgroup analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either < 1 IU of anti-tetanus antibody per millilitre or > or = 1 IU/ml at baseline. These finding indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T antibody levels after immunization.

PIP: Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diptheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titers (1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups, 98% of infants attained anti-PRP antibody titers of 0.15 mcg/ml or higher. The geometric mean anti-PRP antibody titers were 5.41 mcg/ml and 2.1 mcg/ml for infants immunized with 3 doses of PRP-T vs. 2 doses of PedVax HIB vaccines, respectively (P 0.005). Similarly, the proportion of infants who achieved titers of 1 mcg/ml or higher was greater in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A group analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either less than 1 IU/ml of anti-tetanus antibody or 1 or more IU/ml at baseline. These findings indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T levels after immunization.

Determination of drug susceptibility and DNA fingerprint patterns of clinical isolates of Mycobacterium tuberculosis from Kampala, Uganda.

OBJECTIVE: To ascertain the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis in Kampala, Uganda. SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital, Kampala, Uganda and Case Western Reserve University, Cleveland, Ohio, USA and McClellan Memorial Veterans Hospital, Little Rock, Arkansas, USA. METHODS: Using a radiometric BACTEC 460 TB system, susceptibility of 215 M. tuberculosis isolates from previously untreated patients from Kampala, Uganda (age range, 17-48 years, mean, 28 years; 56% males and 69% human immunodeficiency virus (HIV)-seropositive) was determined for isoniazid, rifampin, streptomycin and ethambutol. Isolates from 73 patients, selected on the basis of geographical location, were tested for strain diversity or relatedness using the IS6110 DNA fingerprinting technique. RESULTS: Resistance rates were as follows: isoniazid, 7.9% streptomycin, 6.1% rifampin, 1.4% and ethambutol 0.9%. Twelve per cent of the strains were resistant to at least one of the first line drugs tested and 4.7% were multiply resistant. There were no significant differences in resistance rates between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical RFLP patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates. Three (4.1%) isolates had less than seven copies of IS6110. CONCLUSION: This study shows that in Uganda initial drug resistance rates to anti-tuberculosis agents are low and similar to other sub-Saharan African countries and that multiple strains of M. tuberculosis have been transmitted within the community.

PIP: This study was undertaken to determine the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis (TB) in Kampala, Uganda. Using a radiometric BACTEC 460 TB system, 215 M. tuberculosis isolates from previously untreated patients (aged 17-48 years, mean age = 28 years; 56% males and 69% HIV-seropositive) were analyzed for susceptibility to isoniazid, rifampin, streptomycin, and ethambutol. Isolates from 73 patients were examined for strain diversity or relatedness using the insertional sequence 6110 (IS6110) DNA fingerprinting technique. The study revealed the following drug resistance rates: isoniazid, 7.9%; streptomycin, 6.1%; rifampin, 1.4%; and ethambutol, 0.9%. Resistance to at least one of the first line drugs tested were developed by 12% of the strains, while 4.7% showed multiple resistance. However, no significant differences in resistance rates were found between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates, and three isolates had less than 7 copies of IS6110. These findings suggest that initial drug resistance to anti-tuberculosis agents in this region is low and similar to other countries in sub-Saharan Africa and that multiple strains of M. tuberculosis have been transmitted within the community.

Amylase-resistant starch plus oral rehydration solution for cholera.

BACKGROUND: Although standard glucose-based oral rehydration therapy corrects the dehydration caused by cholera, it does not reduce the diarrhea. Short-chain fatty acids, which are produced in the colon from nonabsorbed carbohydrates, enhance sodium absorption. We conducted a study to determine the effects of an orally administered, nonabsorbed starch (i.e., one resistant to digestion by amylase) on fecal fluid loss and the duration of diarrhea in patients with cholera. METHODS: We randomly assigned 48 adolescents and adults with cholera to treatment with standard oral rehydration therapy (16 patients), standard therapy and 50 g of rice flour per liter of oral rehydration solution (16 patients), or standard therapy and 50 g of high-amylose maize starch, an amylase-resistant starch, per liter of oral rehydration solution (16 patients). The primary end points were fecal weight (for every 12-hour period during the first 48 hours after enrollment) and the length of time to the first formed stool. RESULTS: The mean (+/-SD) fecal weights in the periods 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours after enrollment were significantly lower in the resistant-starch group (2206+/-1158 g, 1810+/-1018 g, and 985+/-668 g) than in the standard-therapy group (3251+/-766 g, 2621+/-1149 g, and 2498+/-1080 g; P=0.01, P= 0.04, and P=0.001, respectively). From 36 to 48 hours after enrollment, fecal weight was also significantly lower with the resistant-starch therapy than with the rice-flour therapy (985+/-668 g vs. 1790+/-866 g, P=0.01). The mean duration of diarrhea was significantly shorter with the resistant-starch therapy (56.7+/-18.6 hours) than with standard therapy alone (90.9+/-29.8 hours, P=0.001) or the rice-flour therapy (70.8+/-20.2 hours, P=0.05). Fecal excretion of starch was higher with the resistant-starch therapy (32.6+/-30.4) than with the standard therapy (11.7+/-4.1 g, P=0.002) or the rice-flour therapy (15.1+/-8.4 g, P=0.01). CONCLUSIONS: The addition of a resistant starch to oral rehydration solution reduces fecal fluid loss and shortens the duration of diarrhea in adolescents and adults with cholera.

Diphtheria in urban slums in north India.

We recorded a reappearance of cases of microbiologically confirmed diphtheria in a tertiary care hospital in north India. Poor immunisation coverage, population migrations, and overcrowded urban slums may be contributory factors.

PIP: This article highlights the prevalence of diphtheria in urban slums in north India. In 1997, diphtheria cases reached 1326, and in a study conducted in September 1999, 4 diphtheria cases were reported in a tertiary care hospital. These cases occurred despite the vaccination programs against diphtheria. Clinical manifestation included fever, sore throat, dysphagia, and swelling in the neck of 2-10 days duration. Immunization records of these children revealed that 2 were nonimmunized and the other 2 received only 2 doses of diphtheria-pertussis-tetanus vaccine in their first year of life. Using electrocardiography, 3 of the cases were suggestive of myocarditis. Laboratory examinations, such as Albert's staining and Loeffler's serum slope, were used to confirm the diagnosis. This epidemic was found to be caused by a large population of susceptible children and adults, decline in childhood immunization, poor socioeconomic conditions, and large-scale population movements. In conclusion, the 44% dropout rate between the third dose of primary immunization and the first booster could be one factor in the emergence of diphtheria.

Emergency or routine vaccination against meningococcal disease in Africa?

PIP: The spread of meningococcal disease in sub-Saharan Africa, which extends from Senegal to Ethiopia, has already affected thousands of people in the region and is urgently in need of an intervention. The meningococcal epidemic in Africa is usually caused by serogroup A and sweeps over the region within several weeks; it then disappears and reappears 5-10 years later. Although vaccination against serogroup A and C meningococci may have its limitations, it is still capable of eliminating the disease. In Ghana, the Ministry of Health launched a vaccination campaign which covered 72% of the population and prevented 23% of cases and 18% of deaths. A simple method of identifying an impending epidemic followed by the development of various vaccination strategies is necessary among less developed countries. WHO recommends that emergency vaccination be implemented, while continuous and improved surveillance systems must be used to confront the epidemic. In conclusion, this paper suggests that the meningococcal disease in sub-Saharan Africa would be better dealt with by well organized campaigns rather than by repeated vaccinations of the entire population.^ieng

Emergency vaccination against epidemic meningitis in Ghana: implications for the control of meningococcal disease in West Africa.

BACKGROUND: Recurrent epidemics of meningococcal disease have been reported throughout the African meningitis belt since description of the disease in 1912. Meningooccal polysaccharide vaccines can effectively prevent disease but the optimum strategy for their use in this setting has been controversial. We used data from an outbreak of meningococcal disease in northern Ghana in 1997 to assess the potential effect of different vaccination strategies. METHODS: We identified all reported cases of meningococcal meningitis and estimated the number of cases and deaths that could have been prevented by vaccination through use of a simple mathematical model. We then assessed the potential effect of different vaccination strategies and the burden of these strategies on the public-health system. FINDINGS: In the three affected regions in northern Ghana there were 18703 cases and 1356 deaths reported between November, 1996, and May, 1997. Vaccination began in the third week of February and continued to April, reaching 72% of the at-risk population and preventing an estimated 23% of cases and 18% of deaths. A strategy of routine childhood and adult immunisation would have prevented 61% of cases had this same rate of vaccine coverage been achieved and maintained before the epidemic. If vaccination had started after the onset of the epidemic in January, as currently advocated by WHO guidelines, a similar proportion (61%) of cases could have been prevented. INTERPRETATION: Prevention of epidemics of meningococal disease in west Africa will be difficult until long-lasting conjugate vaccines capable of interrupting transmission of Neisseria meningitidis can be incorporated into routine infant-immunisation schedules. Until then, the strategy of surveillance and response advocated by WHO is as effective and more practical than a strategy of routine childhood and adult vaccination with currently available polysaccharide vaccines.

PIP: This study assessed the potential effects of different vaccination strategies using data from the 1997 meningococcal outbreak in northern Ghana. Since the description of the disease in 1912, recurrent epidemics of meningococcal disease have been reported throughout the African meningitis belt. The use of meningococcal polysaccharide vaccines has been proven to effectively prevent the disease, although the method of vaccine distribution was disputable. Using a simple mathematical model, meningococcal meningitis cases and deaths, which could have been forestalled by vaccination, were identified, and the effect of developed vaccination strategies on the public health system was analyzed. About 18,703 cases and 1356 deaths were reported in 3 regions of northern Ghana between November 1996 and May 1997. Vaccination was conducted between February and April, which covered 72% of the high-risk population and prevented approximately 23% of cases and 18% of deaths. Routine childhood and adult immunization would have prevented 61% of cases had this same rate of vaccine coverage been achieved and maintained before the epidemic. This study suggests that the prevention of the meningococcal disease epidemic in West Africa would be difficult unless long-lasting conjugate vaccines are incorporated into routine infant immunization schedules. For now, the surveillance and response strategies advocated by the WHO serve as an effective and practical intervention.

Mass vaccination with a two-dose oral cholera vaccine in a refugee camp.

In refugee settings, the use of cholera vaccines is controversial since a mass vaccination campaign might disrupt other priority interventions. We therefore conducted a study to assess the feasibility of such a campaign using a two-dose oral cholera vaccine in a refugee camp. The campaign, using killed whole-cell/recombinant B-subunit cholera vaccine, was carried out in October 1997 among 44,000 south Sudanese refugees in Uganda. Outcome variables included the number of doses administered, the drop-out rate between the two rounds, the proportion of vaccine wasted, the speed of administration, the cost of the campaign, and the vaccine coverage. Overall, 63,220 doses of vaccine were administered. At best, 200 vaccine doses were administered per vaccination site and per hour. The direct cost of the campaign amounted to US$ 14,655, not including the vaccine itself. Vaccine coverage, based on vaccination cards, was 83.0% and 75.9% for the first and second rounds, respectively. Mass vaccination of a large refugee population with an oral cholera vaccine therefore proved to be feasible. A pre-emptive vaccination strategy could be considered in stable refugee settings and in urban slums in high-risk areas. However, the potential cost of the vaccine and the absence of quickly accessible stockpiles are major drawbacks for its large-scale use.

PIP: This study was undertaken to assess the feasibility of mass vaccination using a two-dose oral cholera vaccine in a refugee setting in Uganda. A total of 44,000 south Sudanese refugees were involved in the study. The campaign was conducted using killed whole-cell/recombinant B-subunit cholera vaccine. Measured outcomes include the total number of doses administered, the dropout rate between the two rounds, the amount of vaccine wasted, the cost of the campaign, and the vaccine coverage. Given the results of the study, the mass vaccination of a refugee population with a two-dose oral cholera vaccine proved to be feasible. A total of 63,220 vaccines were administered, with 200 vaccine doses given per vaccination area per hour. The campaign cost was US$14,655, excluding the cost of the vaccine. Vaccine coverage was 83% for the first round and 75.9% for the second round. A presumptive vaccination strategy could be taken into account in stable refugee settings and in urban slums in high-risk sites. However, the potential amount of the vaccine and the absence of immediately accessible stockpiles are major constraints for its large-scale implementation.

Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.

PIP: This article presents a review of the literature published between 1966 and 1997 on Shigella infection. The purpose of the review is to provide data on the global morbidity and mortality caused by the infection and to plan strategies of prevention and treatment. The data obtained from this literature were used to calculate the number of Shigella infection cases and the associated mortality occurring worldwide each year, by age and by clinical category. The burden of Shigella infection was also estimated by serogroup and serotype. A sensitivity analysis was performed to estimate the high and the low range of morbid and fatal cases in each category (mild cases remaining at home, moderate cases requiring outpatient care and severe cases demanding hospitalization). The result of the calculations and analysis revealed that the annual number of Shigella infections throughout the world was estimated to be 164.7 million. 163.2 million occurred in developing countries, with 1.1 million deaths, and 1.5 million occurred in industrialized countries. More than half of the episodes and death affects children under 5 years of age. In comparing developing countries against industrialized countries, the median of isolates are S. flexneri (60% vs. 16%), S. sonnei (15% vs. 77%), S. dysenteriae (6% vs. 1%), and S. boydii (6% vs. 2%). The predominant serotype of S. flexneri in developing countries is 2a, followed by 1b, 3a, 4a, and 6, while in industrialized countries most isolates are S. flexneri 2a and unspecified type 2 strains.

Mycobacterium ulcerans infection.

After tuberculosis and leprosy, Buruli-ulcer disease (caused by infection with Mycobacterium ulcerans) is the third most common mycobacterial disease in immunocompetent people. Countries in which the disease is endemic have been identified, predominantly in areas of tropical rain forest; the emergence of Buruli-ulcer disease in West African countries over the past decade has been dramatic. Current evidence suggests that the infection is transmitted through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation; there is one unconfirmed preliminary report on possible transmission by insects. The clinical picture ranges from a painless nodule to large, undermined ulcerative lesions that heal spontaneously but slowly. Most patients are children. The disease is accompanied by remarkably few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. Extensive scarring can lead to contractures of the limbs, blindness, and other adverse sequelae, which impose a substantial health and economic burden. Treatment is still primarily surgical, and includes excision, skin grafting, or both. Although BCG has a mild but significant protective effect, new vaccine developments directed at the toxins produced by M. ulcerans are warranted. In West Africa, affected populations are underprivileged, and the economic burden imposed by Buruli-ulcer disease is daunting. Combined efforts to improve treatment, prevention, control, and research strategies (overseen by the WHO and funded by international relief agencies) are urgently needed.

PIP: This paper focuses on Buruli-ulcer disease, the third most common mycobacterial disease among immunocompetent people. Buruli-ulcer disease is caused by an infection with Mycobacterium ulcerans, which belongs to the large group of environmental mycobacteria. It is endemic in many countries, usually in areas of tropical rain forest. Transmission of infection is through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation. This disease mostly affects children which manifest from painless nodules to large, undermined ulcerative lesions that heals spontaneously but slowly. Buruli-ulcer disease is accompanied by few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. However, extensive scarring can lead to contractures of the limbs, blindness, and other adverse complications. Management of the disease is still primarily surgical, and includes excision, skin grafting, or both. Although Bacillus Calmette-Guerin vaccine has mild but a significant protective effect, vaccine developments directed at the toxin produced by M. ulcerans are needed.

Typhoid fever and childhood vaccine strategies.

PIP: This article reports findings on the true incidence of typhoid fever in a poor area of Delhi, India. Anju Sinha and colleagues did a prospective study among 8172 patients over a 1-year period. The study detected 63 cases of typhoid fever, 44% of which were in children under 5 years old. The analysis revealed that children under age 5 had a three-fold increase in culture-positive typhoid fever compared with 5-19 year olds. These findings--prospectively acquired clinical and microbiological data correlated with carefully controlled epidemiological data--confound the common view that typhoid fever occurs principally in schoolchildren and young adults. The researchers noted that their findings have relevance to the urban area they studied and may not be generally applicable. On the other hand, the idea that typhoid vaccine might be introduced into the pediatric vaccination schedule raises concerns on the route and efficacy of available vaccines and the difficulty of introducing a vaccine into pediatric schedules.^ieng

Typhoid fever in children aged less than 5 years.

BACKGROUND: Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. METHODS: A baseline census was undertaken in 1995. Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. FINDINGS: 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. INTERPRETATION: Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed.

PIP: This study was conducted to measure the incidence of typhoid fever among preschoolers. It was suggested that children aged 5 years do not need vaccination against typhoid fever. However, it is important to re-examine this view, particularly in infants and young children in the low-income urban area of Delhi, India, through active surveillance. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. Findings revealed 63 culture-positive typhoid fever cases, about 44% of which were in children under 5 years of age. Morbidity in children under age 5 and in older people was similar in terms of duration of fever, signs and symptoms, and the need for hospital admission. The incidence of typhoid fever and the age distribution of the case varied between developing countries. Thus, the age patterns of typhoid fever observed in the urban study area may differ in rural areas within India or in other developing countries. A reevaluation of the optimum age and vaccine of choice is needed.