Clinical profile, complications and outcome of scrub typhus in children: A hospital based observational study in central Nepal.

BACKGROUND: Scrub typhus, an important cause of unexplained fever, is grossly neglected and often misdiagnosed in low and middle income countries like Nepal. The main aim of this study was to report on the clinical profile and complications of scrub typhus and its outcome in Nepalese children. METHODS: A prospective observational study was carried out in children aged 1-16 years, admitted to a tertiary care hospital of central Nepal in between July 2016- Aug 2017. Scrub typhus was diagnosed with IgM ELISA. RESULTS: All cases of scrub typhus (n = 76) presented with fever and commonly had other symptoms such as headache (75%), myalgia (68.4%), vomiting (64.5%), nausea (59.2%), abdominal pain (57.9%), cough (35.5%), shortness of breath (22.4%), altered sensorium (14.5%), rashes (13.2%) and seizures (11.8%). Important clinical signs noticed were lymphadenopathy (60.5%), hepatomegaly (47.4%), edema (26.3%), jaundice (26.3%), and splenomegaly (15.8%). About 12% (n = 9) had necrotic eschar. Similarly, thrombocytopenia, raised liver enzymes and raised creatinine values were seen in 36.9%, 34.2% and 65.8% respectively. The most common complications were myocarditis (72.4%), hypoalbuminemia (71.1%), severe thrombocytopenia (22.4%), renal impairment (65.8%), hyponatremia (48.7%) and hepatitis (34.2%). Over two-thirds (69.70%) of the cases were treated with doxycycline followed by combination with azithromycin in the remaining 18.4%. Overall, mortality rate in this group was 3.9%. CONCLUSIONS: Scrub typhus should be considered as a differential in any community acquired acute undifferentiated febrile illness regardless of the presence of an eschar. Myocarditis and acute kidney injury are important complications which when addressed early can prevent mortality. Use of doxycycline showed a favorable outcome.

Streptococcus pneumoniae carriage prevalence in Nepal: evaluation of a method for delayed transport of samples from remote regions and implications for vaccine implementation.

BACKGROUND: Pneumococcal disease is a significant cause of morbidity and mortality in young children in Nepal, and currently available pneumococcal conjugate vaccines offer moderate coverage of invasive disease isolates. METHODS: A prevalence study of children aged 1.5 to 24 months in urban and rural Nepal was conducted. In the urban group, nasopharyngeal swabs (NPS) were transported using silica desiccant packages (SDP) with delayed processing (2 weeks), or skim-milk-tryptone-glucose-glycerin (STGG) with immediate processing (within 8 hours). Pneumococcal nasopharyngeal carriage prevalence, serogroup/type distribution and isolate genotypes (as defined by multilocus sequence typing) were determined. RESULTS: 1101 children were enrolled into the study: 574 in the urban group and 527 in the rural group. Overall carriage prevalence based on culture from specimens transported and stored in STGG was 58.7% (337/574), compared to 40.9% (235/574) in SDP. There was concordance of detection of pneumococcus in 67% of samples. Using the SDP method, pneumococcal carriage prevalence was higher in the rural population (69.2%; 364/526) compared to the urban population (40.9%; 235/574). Serogroup/type distribution varied with geographical location. Over half of the genotypes identified in both the urban and rural pneumococcal populations were novel. CONCLUSION: The combination of delayed culture and transport using SDP underestimates the prevalence of pneumococcal carriage; however, in remote areas, this method could still provide a useful estimate of carriage prevalence and serogroup/type distribution. Vaccine impact is unpredictable in a setting with novel genotypes and limited serotype coverage as described here. Consequently, continued surveillance of pneumococcal isolates from carriage and disease in Nepali children following the planned introduction of pneumococcal conjugate vaccines introduction will be essential.

Evaluation of haemophilus influenzae type b vaccine for routine immunization in Nepali infants.

BACKGROUND: Haemophilus influenzae type b (Hib) carriage and disease studies in Nepali children suggest a significant burden of infection. Hib conjugate vaccines (HibCV) do not have uniform immunogenicity between populations. We determined the immunogenicity of HibCV in Nepali infants, before its introduction into the routine immunization schedule. METHODS: Ninety infants recruited at Patan Hospital, Kathmandu, received 3 doses of the HibCV with routine immunizations (diphtheria, tetanus, whole cell pertussis-hepatitis B vaccine + oral polio vaccine) at 6, 10 and 14 weeks of age, and a HibCV booster at 52 weeks. Anti-polyribosylribitol phosphate (PRP) concentrations were measured at 18, 52 and 56 weeks, and the antibody persistence at 52 weeks was compared with antibody values in unimmunized controls (n = 30). RESULTS: After 3 doses of primary immunizations, at 18 weeks of age (n = 74), all infants had anti-PRP concentrations above the accepted thresholds for short- and long-term protection (0.15 and 1.0 µg/mL, respectively). At 1 year of age, before administration of the booster of HibCV, the anti-PRP geometric mean antibody concentration was 2.76 µg/mL (confidence interval: 1.88-4.07) in sera from the immunized children compared with 0.11 µg/mL (95% confidence interval: 0.08-0.17) in the nonimmunized control group (n = 30). Twenty-seven percent (20/74) of participants, however, had anti-PRP concentrations <1.0 µg/mL. Four weeks after the booster dose of HibCV, 98.5% of infants had anti-PRP concentrations above 1.0 µg/mL. CONCLUSION: Immunization with HibCV given as part of the Expanded Program on Immunization schedule in Nepal elicits robust antibody responses. Though the antibody wanes during the first year of life, most 1-year-old infants remain protected and respond robustly to a booster dose of the vaccine.